Aquatic metabolism response to the hydrologic alteration in the Yellow River estuary, China

NASA Astrophysics Data System (ADS)

Shen, Xiaomei; Sun, Tao; Liu, Fangfang; Xu, Jing; Pang, Aiping

2015-06-01

Successful artificial hydrologic regulation and environmental flow assessments for the ecosystem protection require an accurate understanding of the linkages between flow events and biotic responses. To explore an ecosystem's functional responses to hydrologic alterations, we analysed spatial and temporal variations in aquatic metabolism and the main factors influenced by artificial hydrologic alterations based on the data collected from 2009 to 2012 in the Yellow River estuary, China. Gross primary production (GPP) ranged from 0.002 to 8.488 mg O2 L-1 d-1. Ecosystem respiration (ER) ranged from 0.382 to 8.968 mg O2 L-1 d-1. Net ecosystem production (NEP) ranged from -5.792 to 7.293 mg O2 L-1 d-1 and the mean of NEP was -0.506 mg O2 L-1 d-1, which means that the trophic status of entire estuary was near to balance. The results showed that seasonal variations in the aquatic metabolism are influenced by the hydrologic alteration in the estuary. High water temperature and solar radiation in summer are associated with low turbidity and consequently high rates of GPP and ER, making the estuary net autotrophic in summer, and that also occurred after water-sediment regulation in August. Turbidity and water temperature were identified as two particularly important factors that influenced the variation in the metabolic balance. As a result, metabolism rate did not decrease but increased after the regulation. ER increased significantly in summer and autumn and reached a maximum after the water-sediment regulation in September. GPP and NEP reached a maximum value after the water-sediment regulation in August, and then decreased in autumn. Estuarine ecosystem shifted from net heterotrophy in spring to net autotrophy in summer, and then to net heterotrophy in autumn. Our study indicated that estuarine metabolism may recover to a high level faster in summer than that in other seasons after the short-term water-sediment regulation due to higher water temperature and nutrients.

Ultra-Sensitive Transition-Edge Sensors for the Background Limited Infrared/Sub-mm Spectrograph (BLISS)

NASA Technical Reports Server (NTRS)

Beyer, A. D.; Kenyon, M. E.; Echternach, P. M.; Chui, T.; Eom, B.-H.; Day, P. K.; Bock, J. J.; Holmes, W.A.; Bradford, C. M.

2011-01-01

We report progress in fabricating ultra-sensitive superconducting transition-edge sensors (TESs) for BLISS. BLISS is a suite of grating spectrometers covering 35-433 micron with R approx. 700 cooled to 50 mK that is proposed to fly on the Japanese space telescope SPICA. The detector arrays for BLISS are TES bolometers readout with a time domain SQUID multiplexer. The required noise equivalent power (NEP) for BLISS is NEP = 10(exp -19) W/Hz(exp 1/2) with an ultimate goal of NEP= 5 x 10(exp -20) W/Hz(exp 1/2) to achieve background limited noise performance. The required and goal response times are tau = 150 ms and tau = 50ms respectively to achieve the NEP at the required and goal optical chop frequency 1-5 Hz. We measured prototype BLISS arrays and have achieved NEP = 6 x 10(exp -18) W/Hz(exp 1/2) and tau = 1.4 ms with a Ti TES (T(sub C) = 565 mK) and NEP approx. 2.5 x 10(exp -19) W/Hz(exp 1/2) and tau approximates 4.5 ms with an Ir TES (T(sub C) = 130 mK). Dark power for these tests is estimated at 1-5 fW.

Neprilysin, obesity and the metabolic syndrome

PubMed Central

Standeven, Kristina F.; Hess, Katharina; Carter, Angela M.; Rice, Gillian I.; Cordell, Paul A.; Balmforth, Anthony J.; Lu, Bao; Scott, D. Julian; Turner, Anthony J.; Hooper, Nigel M.; Grant, Peter J.

2010-01-01

Objective Neprilysin (NEP), a zinc metallo-endopeptidase, has a role in blood pressure control and lipid metabolism. The present study tested the hypothesis that NEP is associated with insulin resistance and features of the metabolic syndrome (MetS) in a study of 318 healthy human subjects and in murine obesity and investigated NEP production by adipocytes in-vitro. Methods and Results In 318 white European males, plasma NEP was elevated in the MetS and increased progressively with increasing MetS components. Plasma NEP activity correlated with insulin, homeostasis model assessment and body mass index in all subjects (p<0.01). Quantitative RT-PCR and Western blotting showed that in human pre-adipocytes NEP expression is upregulated 25-30 fold during differentiation into adipocytes. Microarray analysis of mRNA from differentiated human adipocytes confirmed high NEP expression comparable to adiponectin and plasminogen activator inhibitor-1. In a murine model of diet-induced insulin resistance, plasma NEP levels were significantly higher in high fat diet (HFD)-fed compared with normal chow diet (NCD)-fed animals (1642±529 and 820±487 pg/μl, respectively; p<0.01). Tissue NEP was increased in mesenteric fat in HFD compared with NCD-fed mice (p<0.05). NEP knock out mice did not display any changes in insulin resistance, glucose tolerance or body and epididymal fat pad weight compared to wild type mice. Conclusions In humans, NEP activity correlated with body mass index and measures of insulin resistance with increasing levels in subjects with multiple cardiovascular risk factors. NEP protein production in human adipocytes increased during cell differentiation and plasma and adipose tissue levels of NEP were increased in obese insulin resistant mice. Our results indicate that NEP associates with cardio-metabolic risk in the presence of insulin resistance and increases in obesity. PMID:21042321

Neutral endopeptidase modulates substance P-induced activation of human neutrophils.

PubMed

Iwamoto, I; Kimura, A; Yamazaki, H; Nakagawa, N; Tomioka, H; Yoshida, S

1990-01-01

Neutral endopeptidase (NEP; EC 3.4.24.11) is well recognized as a regulatory peptidase for substance P (SP)-induced responses in various tissues. To determine whether NEP regulates SP-induced activation of human neutrophils, we examined the effect of the NEP inhibitor phosphoramidon on SP-induced superoxide generation and chemotaxis in human blood neutrophils. SP (10(-6)-10(-4) M) induced superoxide generation and chemotaxis in the neutrophils dose dependently. The NEP inhibitor enhanced the SP-induced responses. Thus, phosphoramidon (10(-6) M) shifted the dose-response curves of SP-induced superoxide generation and chemotaxis of the neutrophils to the left by 0.5-0.6 log. Phosphoramidon prevented the hydrolysis of SP by the neutrophils, the NEP activity of the neutrophils being assessed as 125 +/- 13 pmol of SP/min/10(6) cells. The N-terminal peptide SP (up to 3 x 10(-4) M), which was a major degrading product by NEP of the neutrophils, did not activate the neutrophils. We conclude that NEP modulates SP-induced activation of human neutrophils.

Acrolein increases airway sensitivity to substance P and decreases NEP activity in guinea pigs.

PubMed

Turner, C R; Stow, R B; Hubbs, S J; Gomes, B C; Williams, J C

1993-04-01

The effects of acrolein exposure on airway responses to intravenous substance P were determined in guinea pigs exposed to vehicle or 1.6 ppm acrolein for 7.5 h on 2 consecutive days and examined 1, 4, 8, 15, and 28 days after exposure by use of pulmonary mechanics and bronchoalveolar lavage (BAL). Lung, trachea, liver, and BAL fluid were also assayed for neutral endopeptidase (NEP) activity 1, 7, and 28 days after exposure. Pulmonary inflammation and epithelial damage were prominent 1 day after acrolein exposure. NEP activity was decreased in the lungs, trachea, and liver 1 and 7 days after acrolein. Twenty-eight days after exposure, NEP activity in the lungs and liver was not significantly different in vehicle- and acrolein-exposed guinea pigs but was still reduced in tracheal tissue. The BAL NEP activity in acrolein-exposed guinea pigs was approximately twice that of vehicle control guinea pigs at all three time points. Acrolein caused a prolonged increase in airway sensitivity to substance P. Experiments performed in the presence of thiorphan suggested that the acrolein-induced reduction in NEP may contribute to increased airway sensitivity to aerosolized substance P, but the increase in airway sensitivity to intravenous substance P may occur by additional mechanisms.

Altered Gene Expression in Three Plant Species in Response to Treatment with Nep1, a Fungal Protein That Causes Necrosis

PubMed Central

Keates, Sarah E.; Kostman, Todd A.; Anderson, James D.; Bailey, Bryan A.

2003-01-01

Nep1 is an extracellular fungal protein that causes necrosis when applied to many dicotyledonous plants, including invasive weed species. Using transmission electron microscopy, it was determined that application of Nep1 (1.0 μg mL–1, 0.1% [v/v] Silwet-L77) to Arabidopsis and two invasive weed species, spotted knapweed (Centaurea maculosa) and dandelion (Taraxacum officinale), caused a reduction in the thickness of the cuticle and a breakdown of chloroplasts 1 to 4 h after treatment. Membrane breakdown was most severe in cells closest to the surface of application. Differential display was used to isolate cDNA clones from the three species showing differential expression in response to Nep1 treatment. Differential gene expression was observed for a putative serpin (CmSER-1) and a calmodulin-like (CmCAL-1) protein from spotted knapweed, and a putative protein phosphatase 2C (ToPP2C-1) and cytochrome P-450 (ToCYP-1) protein from dandelion. In addition, differential expression was observed for genes coding for a putative protein kinase (AtPK-1), a homolog (AtWI-12) of wound-induced WI12, a homolog (AtLEA-1) of late embryogenesis abundant LEA-5, a WRKY-18 DNA-binding protein (AtWRKY-18), and a phospholipase D (AtPLD-1) from Arabidopsis. Genes showing elevated mRNA levels in Nep1-treated (5 μg mL–1, 0.1% [v/v] Silwet-L77) leaves 15 min after Nep1 treatment included CmSER-1 and CmCAL-1 for spotted knapweed, ToCYP-1 and CmCAL-1 for dandelion, and AtPK-1, AtWRKY-18, AtWI-12, and AtLEA-1 for Arabidopsis. Levels of mRNA for AtPLD-1 (Arabidopsis) and ToPP2C-1 (dandelion) decreased rapidly in Silwet-l77-treated plants between 15 min and 4 h of treatment, but were maintained or decreased more slowly over time in Nep1-treated (5 μg mL–1, 0.1% [v/v] Silwet-L77) leaves. In general, increases in mRNA band intensities were in the range of two to five times, with only ToCYP-1 in dandelion exceeding an increase of 10 times. The identified genes have been shown to be involved or are related to gene families that are involved in plant stress responses, including wounding, drought, senescence, and disease resistance. PMID:12857840

Administration of SIN-1 induces guinea pig airway hyperresponsiveness through inactivation of airway neutral endopeptidase.

PubMed

Kanazawa, H; Hirata, K; Yoshikawa, J

1999-12-01

Peroxynitrite plays an important role in the pathogenesis of airway inflammation. We have already found that peroxynitrite may contribute to decreased beta(2)-adrenoceptor responses in airway smooth muscle. However, it is not known whether peroxynitrite can alter neutral endopeptidase (EC 3.4.24.11; NEP) activity in the airways. This study was designed to determine whether peroxynitrite induces airway hyperresponsiveness to substance P (SP) and endothelin-1 (ET-1) through the inactivation of airway NEP. We examined whether the administration of S-morpholinosydnonimine (SIN-1), a compound that releases peroxynitrite, increased bronchoconstrictor responses to SP and ET-1 in anesthetized guinea pigs. In addition, we assayed NEP activity in the airways of SIN-1-exposed guinea pigs. Though SIN-1 (10(-7) M) alone had no effect on pulmonary resistance, pretreatment with SIN-1 significantly enhanced SP- and ET-1-induced bronchoconstriction. Pretreatment with phosphoramidon, an NEP inhibitor, also enhanced SP- and ET-1-induced bronchoconstriction. However, simultaneous administration of phosphoramidon and SIN-1 had no additive effect on SP- and ET-1-induced bronchoconstriction. Peroxynitrite formation by SIN-1 was completely inhibited by N-acetylcysteine (NAC) and glutathione (GSH) in vitro, and pretreatment with NAC and GSH significantly reversed the potentiation by SIN-1 of SP-induced bronchoconstriction. In addition, the NEP activity of the trachea after SIN-1 exposure was significantly reduced compared to the level in control guinea pigs (solvent for SIN-1: 30.0+/-4.2 fmol.min(-1).mg tissue(-1); 10(-7) M SIN-1; 15.5+/-4.5 fmol.min(-1).mg tissue(-1), p<0.05). These findings suggest that peroxynitrite induces airway hyperresponsiveness to SP and ET-1 through the inactivation of airway NEP, and that peroxynitrite is an important mediator of the alterations in airway functions.

Water and carbon dioxide fluxes over an alpine meadow in southwest China and the impact of a spring drought event.

PubMed

Wang, Lei; Liu, Huizhi; Sun, Jihua; Feng, Jianwu

2016-02-01

Based on the eddy covariance measurements from June 2011 to December 2013, the seasonal variations and the controls of water and CO2 fluxes were investigated over an alpine meadow in Lijiang, southwest China. The year 2012 had the largest total precipitation among years from 2011 to 2013 (1037.9, 1190.4, and 1066.1 mm, respectively). A spring drought event occurred from March to May 2012, and the peak normalized difference vegetation index (NDVI) in 2012 was the lowest. Throughout the whole year, net radiation (Rn), vapor pressure deficit, and air temperature (Ta) were the primary controls on evapotranspiration (ET), and R n is the most important factor. The influence of R n on ET was much more in the wet season (R(2) = 0.93) than in the dry season (R(2) = 0.28). In the wet season, the ratio of ET to equilibrium ET (ETeq) (0.92 ± 0.14; mean ± S.D.) did not show a clear seasonal pattern with NDVI when the soil water content (SWC) was usually more than 0.25 m(3) m(-3), indicating that ET could be predicted well by ETeq (or radiation and temperature). On half-hourly and daily scales, photosynthetic active radiation (PAR) and air temperature were the main meteorological factors in determining the net ecosystem production (NEP). The seasonal trends of NEP were closely related with the change of NDVI. The integrated NEP in the 2012 wet season (157.8 g C m(-2) year(-1)) was 19.5 and 23.8 % lower than in the 2011 and 2013 wet season (207.0 and 196.1 g C m(-2) year(-1)). The mean ET/ETeq for each of the wet seasons from 2011 to 2013 was 0.88. The 2012 spring drought and its reduction in NDVI decreased the total NEP significantly but had little effect on the total ET in the wet season. The different response of NEP and ET to the spring drought was attributed to the high SWC and small vapor pressure deficit during the wet season.

Applications of nuclear reactor power systems to electric propulsion missions.

NASA Technical Reports Server (NTRS)

Schaupp, R. W.; Sawyer, C. D.

1971-01-01

The performance of nuclear electric propulsion systems (NEP) has been evaluated for a wide variety of missions in an attempt to establish the commonality of NEP system requirements. Emphasis was given to those requirements and system characteristics that serve as guidelines for current technology development programs. Various interactions and tradeoffs between NEP system and mission parameters are described. The results show that the most significant factors in selecting NEP system size are launch mode (direct or spiral escape) and, to a weaker extent, launch vehicle capability. Other factors such as mission, payload, and thrust time constraints, have little influence, thus allowing one NEP system to be used for many missions. The results indicated that a 100 kWe NEP would be suitable for most direct escape missions and a 250 kWe NEP system would be suitable for more demanding missions that use the spiral escape mode.

Injured nerve-derived COX2/PGE2 contributes to the maintenance of neuropathic pain in aged rats.

PubMed

Ma, Weiya; Chabot, Jean-Guy; Vercauteren, Freya; Quirion, Remi

2010-07-01

Neuropathic pain (NeP) is a debilitating disease afflicting mostly the aged population. Inflammatory responses in injured nerves play a pivotal role in the pathogenesis of NeP. Injured nerve derived cyclooxygenase 2/prostaglandin E2 (COX2/PGE2) contributes to the genesis of NeP at the early stage in young rats. Here we show that COX2/PGE2 is involved in the maintenance of NeP at a chronic stage in aged rats. Eighteen months after partial sciatic nerve ligation (PSNL), NeP remained prominent in aged rats. COX2 expressing macrophages and PGE2 levels were increased in injured nerves. PGE2 receptors (EP1 and EP4) and pain-related ion channel transient receptor potential vanilloid-1 (TRPV1) were increased in the ipsilateral dorsal root ganglion (DRG) neurons of aged PSNL rats. Perineural injection of a selective COX2 inhibitor NS-398 relieved NeP, reversed PSNL increased expression of EP1, EP4 and TRPV1 and suppressed the levels of pain-related peptide substance P and calcitonin gene-related peptide in DRG neurons. These data suggest that injured nerve-derived PGE2 contributes to the maintenance of NeP at the chronic stage in aged rats. Chronically facilitating the synthesis of pain-related molecules in nociceptive DRG neurons is a novel mechanism underpinning the contribution of PGE2. Copyright 2008 Elsevier Inc. All rights reserved.

Role of substance P in cough.

PubMed

Sekizawa, K; Jia, Y X; Ebihara, T; Hirose, Y; Hirayama, Y; Sasaki, H

1996-01-01

The sensory neuropeptide, substance P (SP), is present in human airway nerves, beneath and within the epithelium where the condensed localization of neutral endopeptidase (NEP), the major enzyme degrading SP, is observed. To test the hypothesis whether SP stimulates the cough reflex and NEP modifies the cough reflex, we studied the cough response to various stimuli in awake guinea-pigs. Inhibition of NEP with phosphoramidon caused cough, which was inhibited by systemic capsaicin treatment and by aerosols of a specific NK1 receptor antagonist FK 888. Aerosols of FK 888 also inhibited cough induced by bronchoconstricting agents such as acetylcholine and histamine in non-sensitized animals and by ovalbumin antigen in animals sensitized to ovalbumin. The number of coughs induced by histamine aerosols was inhibited by systemic capsaicin treatment and enhanced by pretreatment with a NEP inhibitor phosphoramidon. Likewise, FK 888 inhibited the augmented cough response to aerosolized capsaicin in female guinea-pigs treated with a long-term medication of an angiotensin-converting enzyme inhibitor, cilazapril. In humans, aerosols of SP did not cause cough in normal subjects, whereas it did in patients with common colds. The SP fragment a major metabolite of SP produced by NEP, was less effective compared with SP in these patients, suggesting that damaged epithelium may facilitate the penetration of SP. These findings suggest that SP released from sensory nerves in response to stimuli may mediate cough and NEP may have a role in modulating SP-induced effects.

Negative feedback on the effects of stem cell factor on hematopoiesis is partly mediated through neutral endopeptidase activity on substance P: a combined functional and proteomic study.

PubMed

Joshi, D D; Dang, A; Yadav, P; Qian, J; Bandari, P S; Chen, K; Donnelly, R; Castro, T; Gascon, P; Haider, A; Rameshwar, P

2001-11-01

Hematopoietic regulation is a complex but dynamic process regulated by intercellular and intracellular interactions within the bone marrow (BM) microenvironment. Through neurokinin-1 (NK-1) and NK-2 receptors, peptides (eg, substance P [SP]) encoded by the preprotachykinin-I gene mediate distinct hematopoietic effects. Cytokines, associated with hematopoietic stimulation, and SP regulate the expression of each other in BM mesenchymal and immune cells. Neutral endopeptidase (NEP) uses SP as a substrate to produce SP(1-4), which inhibits the proliferation of matured myeloid progenitor. This study determines whether the degradation of SP to SP(1-4) by endogenous NEP in BM stroma could be a feedback on hematopoietic stimulation by stem cell factor (SCF). SP(1-4) induced the production of transforming growth factor (TGF)-beta and tumor necrosis factor-alpha in BM stroma. TGF-beta production accounted for part of the inhibitory effects by SP(1-4) on the proliferation of early (granulocyte-macrophage colony-forming units) and late (long-term culture-initiating cells) hematopoietic progenitors. Enzyme-linked immunosorbent assays and/or protein-chip arrays indicated a timeline change of SP to SP(1-4) in BM stroma stimulated with SCF, which correlated with increase in NEP messenger RNA. Since SP and its fragment, SP(1-4), interact with the same receptor to mediate opposing hematopoietic effects, 2 interactive studies were done to understand the dual responses of NK-1: (1) a 3-dimensional molecular model of NK-1 and SP and (2) screening of a random dodecapeptide library for SP(1-4) interacting sites. The effects of SP(1-4) on hematopoietic progenitors and the timeline change of SP to SP(1-4), together with the 3-dimensional model, provide a partial explanation for the feedback on the stimulatory effects of SCF and SP on hematopoiesis.

The Inhibitory Effects of Anti-Oxidants on Ultraviolet-Induced Up-Regulation of the Wrinkling-Inducing Enzyme Neutral Endopeptidase in Human Fibroblasts

PubMed Central

Nakajima, Hiroaki; Terazawa, Shuko; Niwano, Takao; Yamamoto, Yorihiro; Imokawa, Genji

2016-01-01

We recently reported that the over-expression of skin fibroblast-derived neutral endopeptidase (NEP) plays a pivotal role in impairing the three-dimensional architecture of dermal elastic fibers during the biological mechanism of ultraviolet (UV)-induced skin wrinkling. In that process, a UVB-associated epithelial-mesenchymal cytokine interaction as well as a direct UVA-induced cellular stimulation are associated with the up-regulation of NEP in human fibroblasts. In this study, we characterized the mode of action of ubiquinol10 which may abrogate the up-regulation of NEP by dermal fibroblasts, resulting in a reported in vivo anti-wrinkling action, and compared that with 3 other anti-oxidants, astaxanthin (AX), riboflavin (RF) and flavin mononucleotide (FMN). Post-irradiation treatment with all 4 of those anti-oxidants elicited an interrupting effect on the UVB-associated epithelial-mesenchymal cytokine interaction leading to the up-regulation of NEP in human fibroblasts but with different modes of action. While AX mainly served as an inhibitor of the secretion of wrinkle-inducing cytokines, such as interleukin-1α (IL-1α) and granulocyte macrophage colony stimulatory factor (GM-CSF) in UVB-exposed epidermal keratinocytes, ubiquinol10, RF and FMN predominantly interrupted the IL-1α and GM-CSF-stimulated expression of NEP in dermal fibroblasts. On the other hand, as for the UVA-associated mechanism, similar to the abrogating effects reported for AX and FMN, ubiquinol10 but not RF had the potential to abrogate the increased expression of NEP and matrix-metalloproteinase-1 in UVA-exposed human fibroblasts. Our findings strongly support the in vivo anti-wrinkling effects of ubiquinol10 and AX on human and animal skin and provide convincing proof of the UV-induced wrinkling mechanism that essentially focuses on the over-expression of NEP by dermal fibroblasts as an intrinsic causative factor. PMID:27648570

CD10/neutral endopeptidase 24.11 in developing human fetal lung. Patterns of expression and modulation of peptide-mediated proliferation.

PubMed

Sunday, M E; Hua, J; Torday, J S; Reyes, B; Shipp, M A

1992-12-01

The cell membrane-associated enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) functions in multiple organ systems to downregulate responses to peptide hormones. Recently, CD10/NEP was found to hydrolyze bombesin-like peptides (BLP), which are mitogens for normal bronchial epithelial cells and small cell lung carcinomas. Growth of BLP-responsive small cell lung carcinomas was potentiated by CD10/NEP inhibition, implicating CD10/NEP in regulation of BLP-mediated tumor growth. BLP are also likely to participate in normal lung development because high BLP levels are found in fetal lung, and bombesin induces proliferation and maturation of human fetal lung in organ cultures and murine fetal lung in utero. To explore potential roles for CD10/NEP in regulating peptide-mediated human fetal lung development, we have characterized temporal and cellular patterns of CD10/NEP expression and effects of CD10/NEP inhibition in organ cultures. Peak CD10/NEP transcript levels are identified at 11-13 wk gestation by Northern blots and localized to epithelial cells and mesenchyme of developing airways by in situ hybridization. CD10/NEP immunostaining is most intense in undifferentiated airway epithelium. In human fetal lung organ cultures, inhibition of CD10/NEP with either phosphoramidon or SCH32615 increases thymidine incorporation by 166-182% (P < 0.025). The specific BLP receptor antagonist, [Leu13-psi(CH2NH)Leu14]bombesin abolishes these effects on fetal lung growth, suggesting that CD10/NEP modulates BLP-mediated proliferation. CD10/NEP expression in the growing front of airway epithelium and the effects of CD10/NEP inhibitors in lung explants implicate the enzyme in the regulation of peptide-mediated fetal lung growth.

Influence of management and precipitation on carbon fluxes in greatplains grasslands

USGS Publications Warehouse

Rigge, Matthew B.; Wylie, Bruce K.; Zhang, Li; Boyte, Stephen P.

2013-01-01

Suitable management and sufficient precipitation on grasslands can provide carbon sinks. The net carbon accumulation of a site from the atmosphere, modeled as the Net Ecosystem Productivity (NEP), is a useful means to gauge carbon balance. Previous research has developed methods to integrate flux tower data with satellite biophysical datasets to estimate NEP across large regions. A related method uses the Ecosystem Performance Anomaly (EPA) as a satellite-derived indicator of disturbance intensity (e.g., livestock stocking rate, fire, and insect damage). To better understand the interactions among management, climate, and carbon dynamics, we evaluated the relationship between EPA and NEP data at the 250 m scale for grasslands in the Central Great Plains, USA (ranging from semi-arid to mesic). We also used weekly estimates of NEP to evaluate the phenology of carbon dynamics, classified by EPA (i.e., by level of disturbance impact). Results show that the cumulative carbon balance over these grasslands from 2000 to 2008 was a weak net sink of 13.7 g C m−2 yr−1. Overall, NEP increased with precipitation (R2 = 0.39, P < 0.05) from west to east. Disturbance influenced NEP phenology; however, climate and biophysical conditions were usually more important. The NEP response to disturbance varies by ecoregion, and more generally by grassland type, where the shortgrass prairie NEP is most sensitive to disturbance, the mixed-grass prairie displays a moderate response, and tallgrass prairie is the least impacted by disturbance (as measured by EPA). Sustainable management practices in the tallgrass and mixed-grass prairie may potentially induce a period of average net carbon sink until a new equilibrium soil organic carbon is achieved. In the shortgrass prairie, management should be considered sustainable if carbon stocks are simply maintained. The consideration of site carbon balance adds to the already difficult task of managing grasslands appropriately to site conditions. Results clarify the seasonal and interannual dynamics of NEP, specifically the influence of disturbance and moisture availability.

Neutral endopeptidase inhibition in diabetic wound repair.

PubMed

Spenny, Michelle L; Muangman, Pornprom; Sullivan, Stephen R; Bunnett, Nigel W; Ansel, John C; Olerud, John E; Gibran, Nicole S

2002-01-01

In response to cutaneous injury, sensory nerves release substance P, a proinflammatory neuropeptide. Substance P stimulates mitogenesis and migration of keratinocytes, fibroblasts, and endothelial cells. Neutral endopeptidase (NEP), a cell surface metallopeptidase, degrades substance P. Chronic nonhealing wounds and skin from patients with diabetes mellitus show increased NEP localization and activity. We hypothesized that increased NEP may retard wound healing and that NEP inhibition would improve closure kinetics in an excisional murine wound model. NEP enzyme activity was measured in skin samples from mutant diabetic mice (db/db) and nondiabetic (db/-) littermates by degradation of glutaryl-ala-ala-phe-4-methoxy-2-naphthylamine. Full-thickness 6-mm dorsal excisional wounds treated with normal saline or the NEP inhibitor thiorphan (10 microM or 25 microM) for 7 days were followed until closure. Histological examination and NEP activity were evaluated in a subset of wounds. NEP activity in unwounded db/db skin (20.6 pmol MNA/hr/ microg) significantly exceeded activity in db/-skin (7.9 pmol MNA/hr/ microg; p = 0.02). In db/db mice, 25 microM thiorphan shortened time to closure (18.0 days; p < 0.05) compared to normal saline (23.5 days). NEP inhibition did not alter closure kinetics in db/-mice. While the inflammatory response appeared enhanced in early wounds treated with thiorphan, blinded histological scoring of healed wounds using a semiquantitative scale showed no difference in inflammation. Unwounded skin from diabetic mice shows increased NEP activity and NEP inhibition improved wound closure kinetics without affecting contraction, suggesting that its principal effect was to augment epithelialization.

Impacts of droughts on carbon sequestration by China's terrestrial ecosystems from 2000 to 2011

NASA Astrophysics Data System (ADS)

Liu, Y.; Zhou, Y.; Ju, W.; Wang, S.; Wu, X.; He, M.; Zhu, G.

2014-05-01

In recent years, China's terrestrial ecosystems have experienced frequent droughts. How these droughts have affected carbon sequestration by the terrestrial ecosystems is still unclear. In this study, the process-based Boreal Ecosystem Productivity Simulator (BEPS) model, driven by remotely sensed vegetation parameters, was employed to assess the effects of droughts on net ecosystem productivity (NEP) of terrestrial ecosystems in China from 2000 to 2011. Droughts of differing severity, as indicated by a standard precipitation index (SPI), hit terrestrial ecosystems in China extensively in 2001, 2006, 2009, and 2011. The national total annual NEP exhibited the slight decline of -11.3 Tg C yr-2 during the aforementioned years of extensive droughts. The NEP reduction ranged from 61.1 Tg C yr-1 to 168.8 Tg C yr-1. National and regional total NEP anomalies were correlated with the annual mean SPI, especially in Northwest China, North China, Central China, and Southwest China. The reductions in annual NEP in 2001 and 2011 might have been caused by a larger decrease in annual gross primary productivity (GPP) than in annual ecosystem respiration (ER). The reductions experienced in 2009 might be due to a decrease in annual GPP and an increase in annual ER, while reductions in 2006 could stem from a larger increase in ER than in GPP. The effects of droughts on NEP lagged up to 3-6 months, due to different responses of GPP and ER. In eastern China, where is humid and warm, droughts have predominant and short-term lagged influences on NEP. In western regions, cold and arid, the drought effects on NEP were relatively weaker but prone to lasting longer.

Rapid changes in substance P signaling and neutral endopeptidase induced by skin-scratching stimulation in mice.

PubMed

Yamaoka, Junichi; Kawana, Seiji

2007-11-01

Skin-scratching is a commonly seen behavior in patients with pruritus which sometimes exacerbates original lesions. Substance P (SP) signaling may play a predominant role in the pathophysiology induced by skin-scratching, however, it has not been well-elucidated. To clarify changes in SP, its receptor NK-1R and a degradating enzyme neutral endopeptidase (NEP) induced by skin-scratching stimulation in mice. After skin-scratching stimulation was given to mice, changes in SP signaling were investigated as follows. Mast cell degranulation was examined with toluidine blue staining. SP-immunoreactive nerve fibers and the expressions of NK-1R and NEP were examined with immunofluorescence. Protein contents of SP and the enzymatic activity of NEP were examined with an ELISA and a colorimetric assay, respectively. After skin-scratching stimulation, mast cells significantly degranulated within several minutes. SP-immunoreactive nerve fibers disappeared immediately from sensory nerve fibers, indicating the quick secretion and the depletion of SP. Both protein contents of SP and NEP activity in skin decreased dramatically soon after skin-scratching stimulation and thereafter they returned to the basal level within a week. The expression of NK-1R was significantly upregulated in epidermal basal keratinocytes after several days, in which NEP and NK-1R were well-coexpressed. Blocking NK-1R by an NK-1R antagonist suppressed scratching-induced decreases in SP-immunoreactive nerve fibers and in NEP activity. The present study clarified changing patterns of factors involved in SP signaling and NEP induced by skin-scratching stimulation. These findings provide basic and useful information to understand the pathophysiology of scratching-associated pruritic skin diseases.

20-Hydroxyecdysone stimulates nuclear accumulation of BmNep1, a nuclear ribosome biogenesis-related protein in the silkworm, Bombyx mori.

PubMed

Ji, M-M; Liu, A-Q; Sima, Y-H; Xu, S-Q

2016-10-01

The pathway of communication between endocrine hormones and ribosome biogenesis critical for physiological adaptation is largely unknown. Nucleolar essential protein 1 (Nep1) is an essential gene for ribosome biogenesis and is functionally conserved in many in vertebrate and invertebrate species. In this study, we cloned Bombyx mori Nep1 (BmNep1) due to its high expression in silk glands of silkworms on day 3 of the fifth instar. We found that BmNep1 mRNA and protein levels were upregulated in silk glands during fourth-instar ecdysis and larval-pupal metamorphosis. By immunoprecipitation with the anti-BmNep1 antibody and liquid chromatography-tandem mass spectrometry analyses, it was shown that BmNep1 probably interacts with proteins related to ribosome structure formation. Immunohistochemistry, biochemical fractionation and immunocytochemistry revealed that BmNep1 is localized to the nuclei in Bombyx cells. Using BmN cells originally derived from ovaries, we demonstrated that 20-hydroxyecdysone (20E) induced BmNep1 expression and stimulated nuclear accumulation of BmNep1. Under physiological conditions, BmNep1 was also upregulated in ovaries during larval-pupal metamorphosis. Overall, our results indicate that the endocrine hormone 20E facilitates nuclear accumulation of BmNep1, which is involved in nuclear ribosome biogenesis in Bombyx. © 2016 The Royal Entomological Society.

The effect of acute angiotensin-converting enzyme and neutral endopeptidase 24.11 inhibition on plasma extravasation in the rat.

PubMed

Sulpizio, Anthony C; Pullen, Mark A; Edwards, Richard M; Brooks, David P

2004-06-01

The effect of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) inhibition on microvascular plasma leakage (extravasation) was evaluated in a rat model. Progressive inhibition of ACE using captopril caused increased extravasation when lung ACE was inhibited by >55%. In contrast, the selective inhibition of renal NEP by >90% using ecadotril did not increase extravasation. In NEP-inhibited rats, extravasation produced by the ACE inhibitors captopril and lisinopril was markedly enhanced. The dual ACE and NEP inhibitor omapatrilat, at oral doses of 0.03, 0.1, and 0.3 mg/kg, selectively inhibited lung ACE by 19, 61, and 76%, respectively, and did not cause significant extravasation. Doses of 1 and 10 mg/kg omapatrilat, which produced >90% inhibition of ACE and also inhibited renal NEP by 54 and 78%, respectively, significantly increased extravasation. In this model, bradykinin and substance P produced extravasation that could be abolished by the bradykinin 2 (B2) receptor antagonist Hoe 140 (icatibant) or the neurokinin1 (NK1) antagonist CP99994 [(+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine], respectively. Bradykinin induced extravasation was also partially ( approximately 40%) inhibited by CP99994, indicating that a portion of the response involves B2 receptor-mediated release of substance P. In conclusion, this study is the first to relate the degree of ACE and/or NEP inhibition to extravasation liability in the rat model. Our data clearly demonstrate that ACE inhibitor-induced plasma extravasation is enhanced by concomitant inhibition of NEP. In addition, this study provides further evidence for the role for B2 and NK1 receptors in mediating plasma extravasation in the rat.

[Effect of seasonal high temperature and drought on carbon flux of bamboo forest ecosystem in subtropical region].

PubMed

Chen, Xiao-feng; Jiang, Hong; Niu, Xiao-dong; Zhang, Jin-meng; Liu, Yu-li; Fang, Cheng-yuan

2016-02-01

The carbon flux of subtropical bamboo forest ecosystem was continuously measured using eddy covariance technique in Anji County of Zhejiang Province, China. The monthly net ecosystem productivity (NEP), ecosystem respiration (Re) and gross ecosystem productivity (GEP) data from 2011 to 2013 were selected to analyze the impacts of seasonal high temperature and drought on the carbon flux of bamboo forest ecosystem. The results showed that there were big differences among annual NEP of bamboo forest from 2011 to 2013. Because of the asynchronization of precipitation and heat, the seasonal high temperature and drought in July and August of 2013 caused significant decline in NEP by 59.9% and 80.0% when compared with the same months in 2011. Correlation analysis of the NEP, Re, GEP and environmental factors suggested that the atmosphere temperatures were significantly correlated with Re and GEP in 2011 and 2013 (P<0.05). However, to air and soil moisture, Re and GEP had different responses, that was, GEP was more vulnerable by the decrease of the soil moisture compared with Re. Besides, the raising of saturation vapour pressure promoted the Re modestly but inhibited the GEP, which was supposed to be the main reason for NEP decrease of bamboo forest ecosystem in Anji, from July to August in 2013.

Toluene diisocyanate increases airway responsiveness to substance P and decreases airway neutral endopeptidase.

PubMed

Sheppard, D; Thompson, J E; Scypinski, L; Dusser, D; Nadel, J A; Borson, D B

1988-04-01

Substance P and related tachykinins contribute to the airway hyperresponsiveness caused by toluene diisocyanate (TDI) in guinea pigs. Neutral endopeptidase (NEP) is an important modulator of substance P-induced responses. To test the hypothesis that exposure to TDI would increase responsiveness to substance P by inhibiting activity of this enzyme, we determined the dose of substance P required to increase pulmonary resistance by 200% above baseline (PD200) before and after administration of the pharmacologic inhibitor phosphoramidon in guinea pigs studied 1 h after a 1-h exposure to air or 3 ppm TDI. TDI exposure increased responsiveness to substance P significantly. However, phosphoramidon caused a significantly greater leftward shift of the substance P dose-response curve in air-exposed animals than it did in TDI-exposed animals, so that after phosphoramidon, mean values of PD200 in animals exposed to air or TDI did not differ. Tracheal NEP activity was significantly less after exposure to TDI than after exposure to air, whereas activity in the esophagus was the same in both groups. These results suggest that TDI exposure increases the bronchoconstrictor responsiveness of guinea pigs to substance P, in large part through inhibition of airway NEP.

Toluene diisocyanate increases airway responsiveness to substance P and decreases airway neutral endopeptidase.

PubMed Central

Sheppard, D; Thompson, J E; Scypinski, L; Dusser, D; Nadel, J A; Borson, D B

1988-01-01

Substance P and related tachykinins contribute to the airway hyperresponsiveness caused by toluene diisocyanate (TDI) in guinea pigs. Neutral endopeptidase (NEP) is an important modulator of substance P-induced responses. To test the hypothesis that exposure to TDI would increase responsiveness to substance P by inhibiting activity of this enzyme, we determined the dose of substance P required to increase pulmonary resistance by 200% above baseline (PD200) before and after administration of the pharmacologic inhibitor phosphoramidon in guinea pigs studied 1 h after a 1-h exposure to air or 3 ppm TDI. TDI exposure increased responsiveness to substance P significantly. However, phosphoramidon caused a significantly greater leftward shift of the substance P dose-response curve in air-exposed animals than it did in TDI-exposed animals, so that after phosphoramidon, mean values of PD200 in animals exposed to air or TDI did not differ. Tracheal NEP activity was significantly less after exposure to TDI than after exposure to air, whereas activity in the esophagus was the same in both groups. These results suggest that TDI exposure increases the bronchoconstrictor responsiveness of guinea pigs to substance P, in large part through inhibition of airway NEP. PMID:2450892

Upscaling carbon fluxes over the Great Plains grasslands: Sinks and sources

USGS Publications Warehouse

Zhang, Li; Wylie, Bruce K.; Ji, Lei; Gilmanov, Tagir G.; Tieszen, Larry L.; Howar, Daniel M.

2011-01-01

Previous studies suggested that the grasslands may be carbon sinks or near equilibrium, and they often shift between carbon sources in drought years and carbon sinks in other years. It is important to understand the responses of net ecosystem production (NEP) to various climatic conditions across the U.S. Great Plains grasslands. Based on 15 grassland flux towers, we developed a piecewise regression model and mapped the grassland NEP at 250 m spatial resolution over the Great Plains from 2000 to 2008. The results showed that the Great Plains was a net sink with an averaged annual NEP of 24 ± 14 g C m−2 yr−1, ranging from a low value of 0.3 g C m−2 yr−1 in 2002 to a high value of 47.7 g C m−2 yr−1 in 2005. The regional averaged NEP for the entire Great Plains grasslands was estimated to be 336 Tg C yr−1 from 2000 to 2008. In the 9 year period including 4 dry years, the annual NEP was very variable in both space and time. It appeared that the carbon gains for the Great Plains were more sensitive to droughts in the west than the east. The droughts in 2000, 2002, 2006, and 2008 resulted in increased carbon losses over drought-affected areas, and the Great Plains grasslands turned into a relatively low sink with NEP values of 15.8, 0.3, 20.1, and 10.2 g C m−2 yr−1 for the 4 years, respectively.

Neutral endopeptidase (EC 3.4.24.11) downregulates the onset of intestinal inflammation in the nematode infected mouse.

PubMed

Barbara, G; De Giorgio, R; Stanghellini, V; Corinaldesi, R; Cremon, C; Gerard, N; Gerard, C; Grady, E F; Bunnett, N W; Blennerhassett, P A; Collins, S M

2003-10-01

Substance P (SP) release from sensory nerves induces neurogenic inflammation. Neutral endopeptidase (NEP) degrades SP, thereby limiting its proinflammatory effects. Intestinal inflammation following Trichinella spiralis infection markedly downregulates NEP, resulting in diminished SP degradation, with unknown functional consequences. We hypothesised that diminished expression of NEP would exacerbate T spiralis induced enteritis. NEP knockout (NEP-/-) and wild-type (NEP+/+) mice were infected with T spiralis and studied at 6, 12, 24, and 48 hours post infection (PI). Tissue inflammation was quantified by computerised cell counting and myeloperoxidase activity (MPO). The leucocyte adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), and SP were assessed by immunohistochemistry. Before infection, the lack of NEP was not associated with changes in mucosal cellularity or MPO activity. Twelve hours PI, NEP-/- mice showed a 2.5-fold increase in MPO activity at a time when values in NEP+/+ mice were still within normal limits. MPO activity and cellularity peaked at 24 hours PI. This was accompanied by increased staining for both ICAM-1 and SP in NEP-/- mice. Infusion of rhNEP to NEP-/- mice significantly reduced MPO activity 24 hours PI. These findings demonstrate that NEP downregulates the early onset of nematode intestinal inflammation and that increased bioavailability of SP and overexpression of ICAM-1 in NEP-/- mice likely play a role in the earlier onset of intestinal inflammation.

Role of substance P in neutral endopeptidase modulation of hypoxic response of the carotid body.

PubMed

Kumar, G K; Yu, R K; Overholt, J L; Prabhakar, N R

2000-01-01

Carotid body expresses neutral endopeptidase (NEP)-like enzyme activity and phosphoramidon, an inhibitor of NEP augments sensory response of the carotid body to hypoxia (Kumar et al., 1990). NEP hydrolyzes substance P (SP) and methionine enkephalin (Met-ENK) in the nervous system. In the present study, we determined whether NEP hydrolyzes Met-ENK and SP in the carotid body and whether these peptides contribute to the phosphoramidon-induced potentiation of the sensory response to hypoxia. Experiments were performed on carotid bodies excised from anaesthetized adult cats. HPLC analysis showed that both SP and Met-ENK were hydrolyzed by the carotid body. Phosphoramidon (400 microM) markedly inhibited SP (approximately 90%) but had only marginal effect on Met-ENK hydrolysis (approximately 15%). Sensory responses of the carotid body in vitro to hypoxia (pO2, 68 +/- 6 mmHg) and SP (10 nmoles) were potentiated by phosphoramidon by approximately 80% and approximately 275% respectively (p < 0.01). SP-receptor antagonist abolished phosphoramidon-induced potentiation of the sensory response to hypoxia as well as to SP. These results demonstrate that SP is a preferred substrate for NEP in the carotid body and SP plays a major role in the potentiation of the hypoxic response of the carotid body by phosphoramidon.

Effects of neutral endopeptidase (neprilysin) inhibition on the response to other vasoactive peptides in small human resistance arteries: studies with thiorphan and omapatrilat.

PubMed

Dalzell, Jonathan R; Seed, Alison; Berry, Colin; Whelan, Carol J; Petrie, Mark C; Padmanabhan, Neal; Clarke, Amanda; Biggerstaff, Fiona; Hillier, Christopher; McMurray, John J V

2014-02-01

New compounds with neprilysin or neutral endopeptidase (NEP) inhibiting activity are under clinical investigation in heart failure and hypertension. We investigated the effect of NEP inhibition on the functional vasomotor responses to a range of vasoactive peptides in human blood vessels. Small human resistance arteries from patients with coronary artery disease and preserved left ventricular systolic function were studied. Thiorphan (a NEP inhibitor) was compared with captopril (an ACE inhibitor) and omapatrilat (a dual NEP-ACE inhibitor) with regard to their effects on the response of human arteries to key vasoactive peptides. As expected, both captopril and omapatrilat (but not thiorphan) inhibited the vasoconstrictor effect of angiotensin I (maximal response [SEM]: 27 ± 8% vehicle, 6 ± 2% captopril, 39 ± 10% thiorphan, 8 ± 7% omapatrilat, P < 0.05). Thiorphan, captopril, and omapatrilat all enhanced the vasodilator response to bradykinin (all P < 0.01). Omapatrilat markedly augmented the vasodilator action of adrenomedullin (P < 0.05), whilst thiorphan and captopril did not. None of the three inhibitors studied affected the vasodilator action of c-type natriuretic peptide, calcitonin gene-related peptide, vasoactive intestinal polypeptide or substance P. NEP inhibition with thiorphan modestly augmented the vasodilator action of bradykinin, but did not potentiate the response to adrenomedullin; dual ACE and NEP inhibition with omapatrilat, as expected, markedly augmented the response to bradykinin and also potentiated the effect of adrenomedullin. Thiorphan weakly enhanced the vasoconstrictor response to angiotensin I. Neither omapatrilat nor thiorphan had any effect on the action of a range of other vasoactive peptides including CNP. © 2013 John Wiley & Sons Ltd.

Characterization of available light for seagrass and patch reef productivity in Sugarloaf Key, Lower Florida Keys

USGS Publications Warehouse

Toro-Farmer, Gerardo; Muller-Karger, Frank E.; Vega-Rodriguez, Maria; Melo, Nelson; Yates, Kimberly K.; Johns, Elizabeth; Cerdeira-Estrada, Sergio; Herwitz, Stan R.

2016-01-01

Light availability is an important factor driving primary productivity in benthic ecosystems, but in situ and remote sensing measurements of light quality are limited for coral reefs and seagrass beds. We evaluated the productivity responses of a patch reef and a seagrass site in the Lower Florida Keys to ambient light availability and spectral quality. In situ optical properties were characterized utilizing moored and water column bio-optical and hydrographic measurements. Net ecosystem productivity (NEP) was also estimated for these study sites using benthic productivity chambers. Our results show higher spectral light attenuation and absorption, and lower irradiance during low tide in the patch reef, tracking the influx of materials from shallower coastal areas. In contrast, the intrusion of clearer surface Atlantic Ocean water caused lower values of spectral attenuation and absorption, and higher irradiance in the patch reef during high tide. Storms during the studied period, with winds >10 m·s−1, caused higher spectral attenuation values. A spatial gradient of NEP was observed, from high productivity in the shallow seagrass area, to lower productivity in deeper patch reefs. The highest daytime NEP was observed in the seagrass, with values of almost 0.4 g·O2·m−2·h−1. Productivity at the patch reef area was lower in May than during October 2012 (mean = 0.137 and 0.177 g·O2·m−2·h−1, respectively). Higher photosynthetic active radiation (PAR) levels measured above water and lower light attenuation in the red region of the visible spectrum (~666 to ~699 nm) had a positive correlation with NEP. Our results indicate that changes in light availability and quality by suspended or resuspended particles limit benthic productivity in the Florida Keys.

Cigarette smoke induces bronchoconstrictor hyperresponsiveness to substance P and inactivates airway neutral endopeptidase in the guinea pig. Possible role of free radicals.

PubMed

Dusser, D J; Djokic, T D; Borson, D B; Nadel, J A

1989-09-01

We examined the effects of acute exposure to cigarette smoke on the airway responses to substance P in anesthetized guinea pigs and on the activity of airway neutral endopeptidase (NEP). After exposure to air or to cigarette smoke we measured the change in total pulmonary resistance (RL) induced by increasing concentrations of aerosolized substance P in the absence or presence of the NEP inhibitor phosphoramidon. In the absence of phosphramidon the bronchoconstrictor responses to substance P were greater in cigarette smoke-exposed guinea pigs than in air-exposed animals. Phosphoramidon did not further potentiate the responses to substance P in smoke-exposed guinea pigs, whereas it did so in air-exposed animals. In the presence of phosphoramidon, bronchoconstrictor responses to substance P in animals exposed to air or to cigarette smoke were not different. Aerosols of SOD delivered before cigarette smoke exposures dramatically reduced smoke-induced hyperresponsiveness to substance P, whereas heat-inactivated SOD had no effect on smoke-induced hyper-responsiveness to substance P. Cigarette smoke solution inhibited NEP activity from tracheal homogenate in a concentration-dependent fashion, an inhibitory effect that was mostly due to the gas phase of the smoke, but not to nicotine. The mild chemical oxidant N-chlorosuccinimide mimicked the concentration-dependent inhibitory effect of smoke solution on airway NEP activity. We conclude that cigarette smoke causes enhanced airway responsiveness to substance P in vivo by inactivating airway NEP. We suggest that cigarette smoke-induced inhibition of airway NEP is due to effects of free radicals.

Cigarette smoke induces bronchoconstrictor hyperresponsiveness to substance P and inactivates airway neutral endopeptidase in the guinea pig. Possible role of free radicals.

PubMed Central

Dusser, D J; Djokic, T D; Borson, D B; Nadel, J A

1989-01-01

We examined the effects of acute exposure to cigarette smoke on the airway responses to substance P in anesthetized guinea pigs and on the activity of airway neutral endopeptidase (NEP). After exposure to air or to cigarette smoke we measured the change in total pulmonary resistance (RL) induced by increasing concentrations of aerosolized substance P in the absence or presence of the NEP inhibitor phosphoramidon. In the absence of phosphramidon the bronchoconstrictor responses to substance P were greater in cigarette smoke-exposed guinea pigs than in air-exposed animals. Phosphoramidon did not further potentiate the responses to substance P in smoke-exposed guinea pigs, whereas it did so in air-exposed animals. In the presence of phosphoramidon, bronchoconstrictor responses to substance P in animals exposed to air or to cigarette smoke were not different. Aerosols of SOD delivered before cigarette smoke exposures dramatically reduced smoke-induced hyperresponsiveness to substance P, whereas heat-inactivated SOD had no effect on smoke-induced hyper-responsiveness to substance P. Cigarette smoke solution inhibited NEP activity from tracheal homogenate in a concentration-dependent fashion, an inhibitory effect that was mostly due to the gas phase of the smoke, but not to nicotine. The mild chemical oxidant N-chlorosuccinimide mimicked the concentration-dependent inhibitory effect of smoke solution on airway NEP activity. We conclude that cigarette smoke causes enhanced airway responsiveness to substance P in vivo by inactivating airway NEP. We suggest that cigarette smoke-induced inhibition of airway NEP is due to effects of free radicals. PMID:2474576

CD10/NEP in non-small cell lung carcinomas. Relationship to cellular proliferation.

PubMed Central

Ganju, R K; Sunday, M; Tsarwhas, D G; Card, A; Shipp, M A

1994-01-01

The cell surface metalloproteinase CD10/neutral endopeptidase 24.11 (NEP) hydrolyzes a variety of peptide substrates and reduces cellular responses to specific peptide hormones. Because CD10/NEP modulates peptide-mediated proliferation of small cell carcinomas of the lung (SCLC) and normal fetal bronchial epithelium, we evaluated the enzyme's expression in non-small cell lung carcinomas (NSCLC). Bronchoalveolar and large cell carcinoma cell lines had low levels of CD10/NEP expression whereas squamous, adenosquamous, and adenocarcinoma cell lines had higher and more variable levels of the cell surface enzyme. Regional variations in CD10/NEP immunostaining in primary NSCLC specimens prompted us to correlate CD10/NEP expression with cell growth. In primary carcinomas of the lung, clonal NSCLC cell lines and SV40-transformed fetal airway epithelium, subsets of cells expressed primarily CD10/NEP or the proliferating cell nuclear antigen (PCNA). Cultured airway epithelial cells had the lowest levels of CD10/NEP expression when the highest percentage of cells were actively dividing; in addition, these cells grew more rapidly when cell surface CD10/NEP was inhibited. NSCLC cell lines had receptors for a variety of mitogenic peptides known to be CD10/NEP substrates, underscoring the functional significance of growth-related variability in CD10/NEP expression. Images PMID:7962523

Neprilysin participates in skeletal muscle regeneration and is accumulated in abnormal muscle fibres of inclusion body myositis.

PubMed

Broccolini, Aldobrando; Gidaro, Teresa; Morosetti, Roberta; Gliubizzi, Carla; Servidei, Tiziana; Pescatori, Mario; Tonali, Pietro A; Ricci, Enzo; Mirabella, Massimiliano

2006-02-01

Neprilysin (NEP, EP24.11), a metallopeptidase originally shown to modulate signalling events by degrading small regulatory peptides, is also an amyloid-beta- (Abeta) degrading enzyme. We investigated a possible role of NEP in inclusion body myositis (IBM) and other acquired and hereditary muscle disorders and found that in all myopathies NEP expression was directly associated with the degree of muscle fibre regeneration. In IBM muscle, NEP protein was also strongly accumulated in Abeta-bearing abnormal fibres. In vitro, during the experimental differentiation of myoblasts, NEP protein expression was regulated at the post-transcriptional level with a rapid increase in the early stage of myoblast differentiation followed by a gradual reduction thereafter, coincident with the progression of the myogenic programme. Treatment of differentiating muscle cells with the NEP inhibitor dl-3-mercapto-2-benzylpropanoylglycine resulted in impaired differentiation that was mainly associated with an abnormal regulation of Akt activation. Therefore, NEP may play an important role during muscle cell differentiation, possibly through the regulation, either directly or indirectly, of the insulin-like growth factor I-driven myogenic programme. In IBM muscle increased NEP may be instrumental in (i) reducing the Abeta accumulation in vulnerable fibres and (ii) promoting a repair/regenerative attempt of muscle fibres possibly through the modulation of insulin-like growth factor I-dependent pathways.

The Role of Neprilysin in Regulating the Hair Cycle

PubMed Central

Morisaki, Naoko; Ohuchi, Atsushi; Moriwaki, Shigeru

2013-01-01

In most mammals, each hair follicle undergoes a cyclic process of growing, regressing and resting phases (anagen, catagen, telogen, respectively) called the hair cycle. Various biological factors have been reported to regulate or to synchronize with the hair cycle. Some factors involved in the extracellular matrix, which is a major component of skin tissue, are also thought to regulate the hair cycle. We have focused on an enzyme that degrades elastin, which is associated with skin elasticity. Since our previous study identified skin fibroblast elastase as neprilysin (NEP), we examined the fluctuation of NEP enzyme activity and its expression during the synchronized hair cycle of rats. NEP activity in the skin was elevated at early anagen, and decreased during catagen to telogen. The expression of NEP mRNA and protein levels was modulated similarly. Immunostaining showed changes in NEP localization throughout the hair cycle, from the follicular epithelium during early anagen to the dermal papilla during catagen. To determine whether NEP plays an important role in regulating the hair cycle, we used a specific inhibitor of NEP (NPLT). NPLT was applied topically daily to the dorsal skin of C3H mice, which had been depilated in advance. Mice treated with NPLT had significantly suppressed hair growth. These data suggest that NEP plays an important role in regulating the hair cycle by its increased expression and activity in the follicular epithelium during early anagen. PMID:23418484

Suppression of atherosclerotic changes in cholesterol-fed rabbits treated with an oral inhibitor of neutral endopeptidase 24.11 (EC 3.4.24.11).

PubMed

Kugiyama, K; Sugiyama, S; Matsumura, T; Ohta, Y; Doi, H; Yasue, H

1996-08-01

Neutral endopeptidase 24.11 (NEP), widely distributed in the body, hydrolyzes and inactivates a number of endogenous vasoactive peptides, some of which could alter various functions of cells present in the arterial wall. Recently NEP has been found to exist in the vascular endothelium. The aim of this study was to assess the influence of chronic NEP inhibition by daily administration of UK79300 (candoxatril), an orally active NEP inhibitor (NEPI), on the development of atherosclerotic changes in high-cholesterol-fed rabbits. Male New Zealand White rabbits were fed for 8 weeks as follows: normal rabbit diet (Normal, n = 15), 1.5% cholesterol diet (Cholesterol, n = 15), or 1.5% cholesterol diet containing NEPI (20 mg.kg-1.d-1) (Cholesterol+NEPI, n = 15). At the end of the dietary period, NEPI treatment was found to suppress the surface area of the aorta covered by plaques (% surface area: Cholesterol, 59 +/- 6 versus Cholesterol+NEPI, 36 +/- 7, P < .01) and decreased contents of cholesterol and cholesterol esters in the aortas. NEPI also reduced plasma total cholesterol by 27% of Cholesterol rabbits (1781 +/- 130 mg/dL). The endothelial function, estimated by the endothelium-dependent relaxation of the isolated aortas in response to acetylcholine, was preserved in Cholesterol+NEPI rabbits compared with that in Cholesterol rabbits. NEP enzymatic activities in plasma and the particulate fraction of the homogenates from the aortas in Cholesterol rabbits were both increased, 3.1- and 3.9-fold, respectively, above those in Normal rabbits, but the activities in Cholesterol+NEPI rabbits were significantly lower than those in Cholesterol rabbits. UK73967, an active form of UK79300, or phosphoramidon partly reversed the atherosclerotic impairment of relaxation of the isolated thoracic aortic rings from Cholesterol rabbits in response to exogenous additions of C-type natriuretic peptide (CNP) and substance P, which are NEP substrates known to exist endogenously in the vascular endothelium. The results suggest that the increased NEP activity plays a significant role in atherogenesis, and NEPIs might be therapeutically useful in the prevention of atherosclerosis. Reduction of plasma cholesterol and suppression of degradations in the arteries of endogenously released CNP, substance P, or possibly other kinins known to have anti-atherosclerotic actions may at least partially contribute to the inhibitory effects of NEPIs on atherosclerotic changes.

Neutral endopeptidase inhibitors potentiate substance P-induced contraction in gut smooth muscle.

PubMed

Djokic, T D; Sekizawa, K; Borson, D B; Nadel, J A

1989-01-01

To determine the role of endogenous neutral endopeptidase (NEP), also called enkephalinase (EC 3.4.24.11), in regulating tachykinin-induced contraction of gut smooth muscle, we studied the effects of NEP inhibitors on the contractile responses to substance P (SP) in isolated longitudinal strips of ileum or duodenum in rats and ferrets. Leucine-thiorphan and phosphoramidon shifted the concentration-response curves of SP to lower concentrations in all tissues studied, but the sensitivity to SP was greater and the effect of leucine-thiorphan was less in the ferret, a finding that correlated with the observation that the ferret ileum contained substantially less NEP activity than rat ileum. Captopril, bestatin, MGTA, leupeptin, and physostigmine did not alter contractile responses to SP, suggesting that kininase II, aminopeptidases, carboxypeptidase N, serine proteinases, and acetylcholinesterase do not modulate the SP-induced effects. These studies suggest that, in the ileum and duodenum, NEP modulates the actions of SP and, furthermore, that the sensitivity of tissues may be determined, at least in part, by the amount of enzymatically active NEP present.

Lack of genetic association of neutral endopeptidase (NEP) with complex regional pain syndrome (CRPS).

PubMed

Huehne, Kathrin; Schaal, Ute; Leis, Stefan; Uebe, Steffen; Gosso, M Florencia; van den Maagdenberg, Arn M J M; Maihöfner, Christian; Birklein, Frank; Rautenstrauss, Bernd; Winterpacht, Andreas

2010-03-12

Complex regional pain syndrome (CRPS) is a condition that is characterized by severe pain and exaggerated neurogenic inflammation, which may develop after injury or surgery. Neurogenic inflammation is mediated by neuropeptides, such as calcitonin gene-related peptide (CGRP) and substance P (SP) that are released from nociceptors. Genetic factors may play a role in CRPS as was suggested by the occurrence of familial cases and several genetic association studies investigating mainly the human leukocyte antigen (HLA) system. Here we investigated the role of neutral endopeptidase (NEP), a key enzyme in neuropeptide catabolism. NEP dysfunction resulting in reduced inactivation of neuropeptides may be a possible pathomechanism in CRPS. To this end, we tested a GT-repeat polymorphism in the NEP promoter region as well as 18 tag-SNPs in six linkage disequilibrium (LD) blocks in the NEP gene region in 320 CRPS patients and 376 controls. No significant genetic association was observed. Thus, we conclude that the NEP gene does not seem to be a major risk factor for CRPS. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity

PubMed Central

Rougeot, Catherine; Messaoudi, Michaël; Hermitte, Véronique; Rigault, Anne Gaëlle; Blisnick, Thierry; Dugave, Christophe; Desor, Didier; Rougeon, François

2003-01-01

Sialorphin is an exocrine and endocrine signaling mediator, which has been identified by a genomic approach. It is synthesized predominantly in the submandibular gland and prostate of adult rats in response to androgen steroids and is released locally and systemically in response to stress. We now demonstrate that the cell surface molecule to which sialorphin binds in vivo in the rat kidney is the membrane-anchored neutral endopeptidase (neprilysin; NEP, EC 3.4.24.11). NEP plays an important role in nervous and peripheral tissues, as it turns off several peptide-signaling events at the cell surface. We show that sialorphin prevents spinal and renal NEP from breaking down its two physiologically relevant substrates, substance P and Met-enkephalin in vitro. Sialorphin inhibited the breakdown of substance P with an IC50 of 0.4–1 μM and behaved as a competitive inhibitor. In vivo, i.v. sialorphin elicited potent antinociceptive responses in two behavioral rat models of injury-induced acute and tonic pain, the pin-pain test and formalin test. The analgesia induced by 100–200 μg/kg doses of sialorphin required the activation of μ- and δ-opioid receptors, consistent with the involvement of endogenous opioid receptors in enkephalinergic transmission. We conclude that sialorphin protects endogenous enkephalins released after nociceptive stimuli by inhibiting NEP in vivo. Sialorphin is a natural systemically active regulator of NEP activity. Furthermore, our study provides evidence that it is a physiological modulator of pain perception after injury and might be the progenitor of a new class of therapeutic molecules. PMID:12835417

Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity.

PubMed

Rougeot, Catherine; Messaoudi, Michaël; Hermitte, Véronique; Rigault, Anne Gaëlle; Blisnick, Thierry; Dugave, Christophe; Desor, Didier; Rougeon, François

2003-07-08

Sialorphin is an exocrine and endocrine signaling mediator, which has been identified by a genomic approach. It is synthesized predominantly in the submandibular gland and prostate of adult rats in response to androgen steroids and is released locally and systemically in response to stress. We now demonstrate that the cell surface molecule to which sialorphin binds in vivo in the rat kidney is the membrane-anchored neutral endopeptidase (neprilysin; NEP, EC 3.4.24.11). NEP plays an important role in nervous and peripheral tissues, as it turns off several peptide-signaling events at the cell surface. We show that sialorphin prevents spinal and renal NEP from breaking down its two physiologically relevant substrates, substance P and Met-enkephalin in vitro. Sialorphin inhibited the breakdown of substance P with an IC50 of 0.4-1 microM and behaved as a competitive inhibitor. In vivo, i.v. sialorphin elicited potent antinociceptive responses in two behavioral rat models of injury-induced acute and tonic pain, the pin-pain test and formalin test. The analgesia induced by 100-200 mcicrog/kg doses of sialorphin required the activation of mu- and delta-opioid receptors, consistent with the involvement of endogenous opioid receptors in enkephalinergic transmission. We conclude that sialorphin protects endogenous enkephalins released after nociceptive stimuli by inhibiting NEP in vivo. Sialorphin is a natural systemically active regulator of NEP activity. Furthermore, our study provides evidence that it is a physiological modulator of pain perception after injury and might be the progenitor of a new class of therapeutic molecules.

Social and structural factors associated with HIV infection among female sex workers who inject drugs in the Mexico-US border region.

PubMed

Strathdee, Steffanie A; Lozada, Remedios; Martinez, Gustavo; Vera, Alicia; Rusch, Melanie; Nguyen, Lucie; Pollini, Robin A; Uribe-Salas, Felipe; Beletsky, Leo; Patterson, Thomas L

2011-04-25

FSWs who inject drugs (FSW-IDUs) can acquire HIV through high risk sexual and injection behaviors. We studied correlates of HIV infection among FSW-IDUs in northern Mexico, where sex work is quasi-legal and syringes can be legally obtained without a prescription. FSW-IDUs>18 years old who reported injecting drugs and recent unprotected sex with clients in Tijuana and Ciudad Juarez underwent surveys and HIV/STI testing. Logistic regression identified correlates of HIV infection. Of 620 FSW-IDUs, prevalence of HIV, gonorrhea, Chlamydia, trichomonas, syphilis titers ≥1:8, or any of these infections was 5.3%, 4%, 13%, 35%, 10% and 72%, respectively. Compared to other FSW-IDUs, HIV-positive women were more likely to: have syphilis titers ≥1:8 (36% vs. 9%, p<0.001), often/always inject drugs with clients (55% vs. 32%, p = 0.01), and experience confiscation of syringes by police (49% vs. 28%, p = 0.02). Factors independently associated with HIV infection were syphilis titers ≥1:8, often/always injecting with clients and police confiscation of syringes. Women who obtained syringes from NEPs (needle exchange programs) within the last month had lower odds of HIV infection associated with active syphilis, but among non-NEP attenders, the odds of HIV infection associated with active syphilis was significantly elevated. Factors operating in both the micro-social environment (i.e., injecting drugs with clients) and policy environment (i.e., having syringes confiscated by police, attending NEPs) predominated as factors associated with risk of HIV infection, rather than individual-level risk behaviors. Interventions should target unjustified policing practices, clients' risk behaviors and HIV/STI prevention through NEPs.

Social and Structural Factors Associated with HIV Infection among Female Sex Workers Who Inject Drugs in the Mexico-US Border Region

PubMed Central

Strathdee, Steffanie A.; Lozada, Remedios; Martinez, Gustavo; Vera, Alicia; Rusch, Melanie; Nguyen, Lucie; Pollini, Robin A.; Uribe-Salas, Felipe; Beletsky, Leo; Patterson, Thomas L.

2011-01-01

Background FSWs who inject drugs (FSW-IDUs) can acquire HIV through high risk sexual and injection behaviors. We studied correlates of HIV infection among FSW-IDUs in northern Mexico, where sex work is quasi-legal and syringes can be legally obtained without a prescription. Methods FSW-IDUs>18 years old who reported injecting drugs and recent unprotected sex with clients in Tijuana and Ciudad Juarez underwent surveys and HIV/STI testing. Logistic regression identified correlates of HIV infection. Results Of 620 FSW-IDUs, prevalence of HIV, gonorrhea, Chlamydia, trichomonas, syphilis titers ≥1∶8, or any of these infections was 5.3%, 4%, 13%, 35%, 10% and 72%, respectively. Compared to other FSW-IDUs, HIV-positive women were more likely to: have syphilis titers ≥1∶8 (36% vs. 9%, p<0.001), often/always inject drugs with clients (55% vs. 32%, p = 0.01), and experience confiscation of syringes by police (49% vs. 28%, p = 0.02). Factors independently associated with HIV infection were syphilis titers ≥1∶8, often/always injecting with clients and police confiscation of syringes. Women who obtained syringes from NEPs (needle exchange programs) within the last month had lower odds of HIV infection associated with active syphilis, but among non-NEP attenders, the odds of HIV infection associated with active syphilis was significantly elevated. Conclusions Factors operating in both the micro-social environment (i.e., injecting drugs with clients) and policy environment (i.e., having syringes confiscated by police, attending NEPs) predominated as factors associated with risk of HIV infection, rather than individual-level risk behaviors. Interventions should target unjustified policing practices, clients' risk behaviors and HIV/STI prevention through NEPs. PMID:21541349

High carbon dioxide uptake by subtropical forest ecosystems in the East Asian monsoon region

PubMed Central

Yu, Guirui; Chen, Zhi; Piao, Shilong; Peng, Changhui; Ciais, Philippe; Wang, Qiufeng; Li, Xuanran; Zhu, Xianjin

2014-01-01

Temperate- and high-latitude forests have been shown to contribute a carbon sink in the Northern Hemisphere, but fewer studies have addressed the carbon balance of the subtropical forests. In the present study, we integrated eddy covariance observations established in the 1990s and 2000s to show that East Asian monsoon subtropical forests between 20°N and 40°N represent an average net ecosystem productivity (NEP) of 362 ± 39 g C m−2 yr−1 (mean ± 1 SE). This average forest NEP value is higher than that of Asian tropical and temperate forests and is also higher than that of forests at the same latitudes in Europe–Africa and North America. East Asian monsoon subtropical forests have comparable NEP to that of subtropical forests of the southeastern United States and intensively managed Western European forests. The total NEP of East Asian monsoon subtropical forests was estimated to be 0.72 ± 0.08 Pg C yr−1, which accounts for 8% of the global forest NEP. This result indicates that the role of subtropical forests in the current global carbon cycle cannot be ignored and that the regional distributions of the Northern Hemisphere's terrestrial carbon sinks are needed to be reevaluated. The young stand ages and high nitrogen deposition, coupled with sufficient and synchronous water and heat availability, may be the primary reasons for the high NEP of this region, and further studies are needed to quantify the contribution of each underlying factor. PMID:24639529

Monitoring early tumor response to drug therapy with diffuse optical tomography

NASA Astrophysics Data System (ADS)

Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L.; Johung, Tessa B.; Gander, Jeffrey W.; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

2012-01-01

Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy--thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

Neutral endopeptidase promotes phorbol ester-induced apoptosis in prostate cancer cells by inhibiting neuropeptide-induced protein kinase C delta degradation.

PubMed

Sumitomo, M; Shen, R; Goldberg, J S; Dai, J; Navarro, D; Nanus, D M

2000-12-01

Phorbol esters induce apoptosis in androgen-sensitive LNCaP cells, which express neutral endopeptidase (NEP), but not in androgen-independent prostate cancer (PC) cells, which lack NEP expression. We investigated the role of NEP in PC cell susceptibility to 12-O-tetradecanoylphorbol-13-acetate (TPA). Western analysis showed that expression of NEP and protein kinase Cdelta (PKCdelta) correlated with PC cell sensitivity to TPA-induced growth arrest and apoptosis in LNCaP cells and in TSU-Prl cells expressing an inducible wild-type NEP protein. Inhibition of NEP enzyme activity using the specific NEP inhibitor CGS24592, or inhibition of PKCdelta using Rottlerin at concentrations that inhibit PKCdelta but not PKCalpha, significantly inhibited TPA-induced growth inhibition and cell death. Furthermore, pulse-chase experiments showed PKCdelta is stabilized in LNCaP cells and in TSU-Pr1 cells overexpressing wild-type NEP compared with PC cells lacking NEP expression. This results from NEP inactivation of its neuropeptide substrates (bombesin and endothelin-1), which in the absence of NEP stimulate cSrc kinase activity and induce rapid degradation of PKCdelta protein. These results indicate that expression of enzymatically active NEP by PC cells is necessary for TPA-induced apoptosis, and that NEP inhibits neuropeptide-induced, cSrc-mediated PKCdelta degradation.

NEP systems engineering efforts in FY-92: Plans and status

NASA Technical Reports Server (NTRS)

Doherty, Michael P.; Gilland, James H.

1992-01-01

A system engineering effort has been initiated by NASA in FY-92 to define, address, and resolve issues associated with the use of Nuclear Electric Propulsion (NEP) for megawatt (MW) space propulsion applications associated with the Space Exploration Initiative (SEI). It is intended that key technical issues will be addressed by activities conducted in the early years of a project in NEP, with the objective of resolving such issues. Also, in response to more recent programmatic direction, a concept definition activity for 100 kilowatt NEP is being initiated. This paper will present key issues associated with megawatt NEP, and the plans and status for their resolution, and present the scope and rationale for the 100 kilowatt concept definition activity.

CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung.

PubMed Central

Shipp, M A; Tarr, G E; Chen, C Y; Switzer, S N; Hersh, L B; Stein, H; Sunday, M E; Reinherz, E L

1991-01-01

Bombesin-like peptides are essential autocrine growth factors for many small cell carcinomas (SCCas) of the lung. Herein, we demonstrate that these malignant pulmonary neuroendocrine cells express low levels of the cell surface metalloendopeptidase CD10/neutral endopeptidase 24.11 (CD10/NEP, common acute lymphoblastic leukemia antigen) and that this enzyme hydrolyzes bombesin-like peptides. The growth of bombesin-like peptide-dependent SCC as is inhibited by CD10/NEP and potentiated by CD10/NEP inhibition. The results provide evidence that CD10/NEP is involved in the regulation of tumor cell proliferation. Since SCCa of the lung occurs almost exclusively in cigarette smokers and cigarette smoke inactivates CD10/NEP, decreased cell surface CD10/NEP enzymatic activity may be causally related to the development of SCCa of the lung. Images PMID:1660144

CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung.

PubMed

Shipp, M A; Tarr, G E; Chen, C Y; Switzer, S N; Hersh, L B; Stein, H; Sunday, M E; Reinherz, E L

1991-12-01

Bombesin-like peptides are essential autocrine growth factors for many small cell carcinomas (SCCas) of the lung. Herein, we demonstrate that these malignant pulmonary neuroendocrine cells express low levels of the cell surface metalloendopeptidase CD10/neutral endopeptidase 24.11 (CD10/NEP, common acute lymphoblastic leukemia antigen) and that this enzyme hydrolyzes bombesin-like peptides. The growth of bombesin-like peptide-dependent SCC as is inhibited by CD10/NEP and potentiated by CD10/NEP inhibition. The results provide evidence that CD10/NEP is involved in the regulation of tumor cell proliferation. Since SCCa of the lung occurs almost exclusively in cigarette smokers and cigarette smoke inactivates CD10/NEP, decreased cell surface CD10/NEP enzymatic activity may be causally related to the development of SCCa of the lung.

Inhibitors of neutral endopeptidase potentiate electrically and capsaicin-induced noncholinergic contraction in guinea pig bronchi.

PubMed

Djokic, T D; Nadel, J A; Dusser, D J; Sekizawa, K; Graf, P D; Borson, D B

1989-01-01

To evaluate the role of airway neutral endopeptidase (NEP) in the regulation of contraction of airway smooth muscle in response to endogenous tachykinins, we studied the effects of the NEP inhibitor phosphoramidon on contractions of guinea pig bronchial smooth muscle strips induced by either electrical field stimulation (EFS) or by capsaicin. In the presence of atropine (10(-6) M), propranolol (10(-6) M), phentolamine (10(-5) M), indomethacin (10(-6) M) and pyrilamine (5 x 10(-6) M) EFS (biphasic; pulse width, 1.0 msec; frequency 0.5-5 Hz for 30 sec; intensity, 20 V) produced noncholinergic, nonadrenergic muscle contraction in a frequency-dependent fashion (P less than .001). Phosphoramidon potentiated the contractile responses to EFS (P less than .01). Leucine-thiorphan (10(-5) M), another NEP inhibitor, potentiated EFS-induced contraction in a similar fashion as phosphoramidon (186 and 182% of control, respectively; each comparison, P less than .025). Captopril, bestatin, leupeptin and physostigmine (each drug, 10(-5) M) were without effect (P greater than .5, N = 5). Capsaicin (1.5 x 10(-8) M) produced long-lasting atropine-resistant smooth muscle contraction, an effect potentiated by phosphoramidon (10(-5) M (P less than .001). Removal of the epithelium slightly but significantly (P less than .05) increased the contractile responses to capsaicin and to EFS at impulse frequencies of 2 and 5 Hz, and phosphoramidon substantially increased contractions in tissues without epithelium. The trachea, bronchi and lungs each contained significant NEP activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of Ultra-Low-Noise TES Bolometer Arrays

NASA Astrophysics Data System (ADS)

Suzuki, T.; Khosropanah, P.; Ridder, M. L.; Hijmering, R. A.; Gao, J. R.; Akamatsu, H.; Gottardi, L.; van der Kuur, J.; Jackson, B. D.

2016-07-01

SRON is developing ultra-low-noise transition edge sensors (TESs) based on a superconducting Ti/Au bilayer on a suspended SiN island with SiN legs for SAFARI aboard SPICA. We have two major concerns about realizing TESs with an ultra-low NEP of 2× 10^{-19} hbox {W}/√{{ {Hz}}}: achieving lower thermal conductance and no excess noise with respect to the phonon noise. To realize TESs with phonon-noise-limited NEPs, we need to make thinner ({<}0.25 \\upmu hbox {m}) and narrower ({<}1 \\upmu hbox {m}) SiN legs. With deep reactive-ion etching, three types of TESs were fabricated in combination with different SiN island sizes and the presence or absence of an optical absorber. Those TESs have a thin (0.20 \\upmu hbox {m}), narrow (0.5-0.7 \\upmu hbox {m}), and long (340-460 \\upmu hbox {m}) SiN legs and show Tc of {˜ }93 hbox {mK} and Rn of {˜ }158 hbox {m}{Ω }. These TESs were characterized under AC bias using our frequency-division multiplexing readout (1-3 MHz) system. TESs without the absorber show NEPs as low as 1.1 × 10^{-19} hbox {W}/√{{ {Hz}}} with a reasonable response speed ({<}1 hbox {ms}), which achieved the phonon noise limit. For TESs with the absorber, we confirmed a higher hbox {NEP}_{el} ({˜ }5 × 10^{-19} hbox {W}/√{{ {Hz}}}) than that of TESs without the absorber likely due to stray light. The lowest NEP can make the new version of SAFARI with a grating spectrometer feasible.

Tachykinin receptor and neutral endopeptidase gene expression in the rat uterus: characterization and regulation in response to ovarian steroid treatment.

PubMed

Pinto, F M; Armesto, C P; Magraner, J; Trujillo, M; Martín, J D; Candenas, M L

1999-06-01

Tachykinin neuropeptides, such as substance P, are localized to a population of sensory fibers that innervate the mammalian female reproductive tract. In the present study, we have characterized tachykinin NK1 receptor (NK1R), NK2 receptor (NK2R), and NK3 receptor (NK3R) gene expression by semiquantitative RT-PCR in uteri from ovariectomized rats and studied their regulation in response to 17beta-estradiol (E2), progesterone (P4), or a combination of both. In addition, we analyzed the expression and regulation of the neutral endopeptidase 24.11 (NEP), the most important enzyme involved in tachykinin degradation in the rat uterus. In uteri from control (olive oil-treated) rats, RT-PCR assays revealed single bands corresponding to the expected product sizes encoding complementary DNA for NK1R (232 bp), NK2R (491 bp), NK3R (325 bp), and NEP (221 bp). The identity of the amplified fragments was confirmed by DNA sequence analysis. Compared with control rats, NK1R messenger RNA (mRNA) was increased by 2-fold in uteri from rats treated with E2, was decreased by 3.3-fold in rats treated with P4, and was decreased by 1.8-fold in rats treated with both E2 and P4. Uterine NK2R mRNA levels were not altered by any steroid treatment. E2 treatment decreased by 15-fold NK3R mRNA. P4 was without effect if administered alone and did not influence the E2-induced decrease in NK3R mRNA. NEP mRNA levels were about 4-fold lower in E2-treated than in P4-treated rats. Functional studies were carried out in uteri from E2- or P4-treated ovariectomized rats to characterize the contractile response evoked by the selective tachykinin receptor agonists [Sar9Met(O2)11]substance P (NK1R selective), [Nle10]NKA-(4-10) (NK2R selective), and [MePhe7]NKB (NK3R selective) in the presence of the NEP inhibitor phosphoramidon (1 microM). A marked correlation was observed between the magnitude of the contractile response to each agonist and the level of expression determined by RT-PCR for each tachykinin receptor. The present findings show that tachykinin NK1R, NK2R, NK3R, and NEP are expressed in the rat uterus and that ovarian steroids differentially regulate their expression.

Neutral endopeptidase inhibits prostate cancer cell migration by blocking focal adhesion kinase signaling.

PubMed

Sumitomo, M; Shen, R; Walburg, M; Dai, J; Geng, Y; Navarro, D; Boileau, G; Papandreou, C N; Giancotti, F G; Knudsen, B; Nanus, D M

2000-12-01

Neutral endopeptidase 24.11 (NEP, CD10) is a cell-surface enzyme expressed by prostatic epithelial cells that cleaves and inactivates neuropeptides implicated in the growth of androgen-independent prostate cancer (PC). NEP substrates such as bombesin and endothelin-1 induce cell migration. We investigated the mechanisms of NEP regulation of cell migration in PC cells, including regulation of phosphorylation on tyrosine of focal adhesion kinase (FAK). Western analyses and cell migration assays revealed an inverse correlation between NEP expression and the levels of FAK phosphorylation and cell migration in PC cell lines. Constitutively expressed NEP, recombinant NEP, and induced NEP expression using a tetracycline-repressive expression system inhibited bombesin- and endothelin-1-stimulated FAK phosphorylation and cell migration. This results from NEP-induced inhibition of neuropeptide-stimulated association of FAK with cSrc protein. Expression of a mutated catalytically inactive NEP protein also resulted in partial inhibition of FAK phosphorylation and cell migration. Coimmunoprecipitation experiments show that NEP associates with tyrosine-phosphorylated Lyn kinase, which then binds the p85 subunit of phosphatidylinositol 3-kinase (PI3-K) resulting in an NEP-Lyn-PI3-K protein complex. This complex competitively blocks FAK-PI3-K interaction, suggesting that NEP protein inhibits cell migration via a protein-protein interaction independent of its catalytic function. These experiments demonstrate that NEP can inhibit FAK phosphorylation on tyrosine and PC cell migration through multiple pathways and suggest that cell migration which contributes to invasion and metastases in PC cells can be regulated by NEP.

Neutral endopeptidase inhibits prostate cancer cell migration by blocking focal adhesion kinase signaling

PubMed Central

Sumitomo, Makoto; Shen, Ruoqian; Walburg, Marc; Dai, Jie; Geng, Yiping; Navarro, Daniel; Boileau, Guy; Papandreou, Christos N.; Giancotti, Filippo G.; Knudsen, Beatrice; Nanus, David M.

2000-01-01

Neutral endopeptidase 24.11 (NEP, CD10) is a cell-surface enzyme expressed by prostatic epithelial cells that cleaves and inactivates neuropeptides implicated in the growth of androgen-independent prostate cancer (PC). NEP substrates such as bombesin and endothelin-1 induce cell migration. We investigated the mechanisms of NEP regulation of cell migration in PC cells, including regulation of phosphorylation on tyrosine of focal adhesion kinase (FAK). Western analyses and cell migration assays revealed an inverse correlation between NEP expression and the levels of FAK phosphorylation and cell migration in PC cell lines. Constitutively expressed NEP, recombinant NEP, and induced NEP expression using a tetracycline-repressive expression system inhibited bombesin- and endothelin-1–stimulated FAK phosphorylation and cell migration. This results from NEP-induced inhibition of neuropeptide-stimulated association of FAK with cSrc protein. Expression of a mutated catalytically inactive NEP protein also resulted in partial inhibition of FAK phosphorylation and cell migration. Coimmunoprecipitation experiments show that NEP associates with tyrosine-phosphorylated Lyn kinase, which then binds the p85 subunit of phosphatidylinositol 3-kinase (PI3-K) resulting in an NEP-Lyn-PI3-K protein complex. This complex competitively blocks FAK-PI3-K interaction, suggesting that NEP protein inhibits cell migration via a protein-protein interaction independent of its catalytic function. These experiments demonstrate that NEP can inhibit FAK phosphorylation on tyrosine and PC cell migration through multiple pathways and suggest that cell migration which contributes to invasion and metastases in PC cells can be regulated by NEP. PMID:11104793

Aerosolized neutral endopeptidase reverses ozone-induced airway hyperreactivity to substance P.

PubMed

Murlas, C G; Lang, Z; Williams, G J; Chodimella, V

1992-03-01

We investigated the effects of ozone exposure (3.0 ppm, 2 h) on airway neutral endopeptidase (NEP) activity and bronchial reactivity to substance P in guinea pigs. Reactivity after ozone or air exposure was determined by measuring specific airway resistance in intact unanesthetized spontaneously breathing animals in response to increasing doses of intravenous substance P boluses. The effective dose of substance P (in micrograms) that produced a doubling of baseline specific airway resistance (ED200SP) was determined by interpolation of cumulative substance P dose-response curves. NEP activity was measured in tracheal homogenates made from each animal of other groups exposed to either ozone or room air. By reverse-phase high-pressure liquid chromatography, this activity was characterized by the phosphoramidon-inhibitable cleavage of alanine-p-nitroaniline from succinyl-(Ala)3-p-nitroaniline in the presence of 100 microM amastatin. Mean values of the changes in log ED200SP were 0.27 +/- 0.07 (SE) for the ozone-exposed group and 0.08 +/- 0.04 for the air-exposed group. We found that phosphoramidon significantly increased substance P reactivity in the air-exposed animals (P less than 0.01), but it had no effect in the ozone-exposed group. This finding was associated with a significant reduction in tracheal homogenate NEP activity of ozone-exposed animals compared with controls: mean values were 18.1 +/- 1.9 nmol.min-1.mg protein-1 for the ozone-exposed group and 25.1 +/- 2.4 nmol.min-1.mg protein-1 for air-exposed animals (P less than 0.05). Inhalation of an aerosolized NEP preparation, partially purified from guinea pig kidney, reversed the substance P hyperreactivity produced by ozone exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosolized neutral endopeptidase reverses ozone-induced airway hyperreactivity to substance P

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murlas, C.G.; Lang, Z.; Williams, G.J.

1992-03-01

The authors investigated the effects of ozone exposure (3.0 ppm, 2 h) on airway neutral endopeptidase (NEP) activity and bronchial reactivity to substance P in guinea pigs. Reactivity after ozone or air exposure was determined by measuring specific airway resistance in intact unanesthetized spontaneously breathing animals in response to increasing doses of intravenous substance P boluses. The effective dose of substance P (in micrograms) that produced a doubling of baseline specific airway resistance (ED200SP) was determined by interpolation of cumulative substance P dose-response curves. NEP activity was measured in tracheal homogenates made from each animal of other groups exposed tomore » either ozone or room air. By reverse-phase high-pressure liquid chromatography, this activity was characterized by the phosphoramidon-inhibitable cleavage of alanine-p-nitroaniline from succinyl-(Ala)3-p-nitroaniline in the presence of 100 microM amastatin. Mean values of the changes in log ED200SP were 0.27 +/- 0.07 (SE) for the ozone-exposed group and 0.08 +/- 0.04 for the air-exposed group. We found that phosphoramidon significantly increased substance P reactivity in the air-exposed animals (P less than 0.01), but it had no effect in the ozone-exposed group. This finding was associated with a significant reduction in tracheal homogenate NEP activity of ozone-exposed animals compared with controls: mean values were 18.1 +/- 1.9 nmol.min-1.mg protein-1 for the ozone-exposed group and 25.1 +/- 2.4 nmol.min-1.mg protein-1 for air-exposed animals (P less than 0.05). Inhalation of an aerosolized NEP preparation, partially purified from guinea pig kidney, reversed the substance P hyperreactivity produced by ozone exposure.(ABSTRACT TRUNCATED AT 250 WORDS)« less

Neutral endopeptidase determines the severity of pancreatitis-associated lung injury.

PubMed

Day, Amy Lightner; Wick, Elizabeth; Jordan, Thomas H; Jaffray, Colleen E; Bunnett, Nigel W; Grady, Eileen F; Kirkwood, Kimberly S

2005-09-01

Neutral endopeptidase (NEP) is a cell-surface metalloprotease that degrades proinflammatory peptides such as substance P, neurokinin A, and bradykinin. Inhibition of NEP exacerbates both experimental pancreatitis and the associated lung injury. It is unclear if worsened lung injury is the indirect result of more severe pancreatitis or if it is a direct effect of NEP inhibition in the lung. We used a model of pancreatitis-associated lung injury (PALI) to test the hypothesis that antagonism or genetic deletion of NEP augments PALI inflammation and pulmonary damage irregardless of the degree of pancreatitic inflammation. In NEP(+/+) mice, intraperitoneal injection of porcine pancreatic elastase (elastase, 0.085 U/g at t = 0 h and t = 1 h) caused a 7-fold increase in lung myeloperoxidase (MPO) activity and marked pulmonary edema, neutrophil infiltration, and hemorrhage at 4 h as compared to control animals. The pattern of lung injury induced by elastase mimicked that observed among a separate group of animals with PALI induced by cerulein but was not associated with pancreatitis. Both NEP(-/-) mice and NEP(+/+) mice pretreated with the NEP antagonist phosphoramidon (10 mg/kg s.c.) had significant elevations of lung MPO and worsened lung histology compared to NEP(+/+) mice given elastase alone. Antagonism of either the vanilloid receptor transient receptor vanilloid 1 or the substance P receptor NK1-R had no effect on elastase-mediated lung injury in NEP-deficient mice. NEP is an inhibitor of pancreatic elastase-induced lung injury, presumably via degradation of proinflammatory mediators.

Neutral endopeptidase: variable expression in human lung, inactivation in lung cancer, and modulation of peptide-induced calcium flux.

PubMed

Cohen, A J; Bunn, P A; Franklin, W; Magill-Solc, C; Hartmann, C; Helfrich, B; Gilman, L; Folkvord, J; Helm, K; Miller, Y E

1996-02-15

Neutral endopeptidase (NEP; CALLA, CD10, EC 3.4.24.11) is a cell surface endopeptidase that hydrolyses bioactive peptides, including the bombesin-like peptides, as well as other neuropeptides. Bombesin-like peptides and other neuropeptides are autocrine growth factors for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Low expression of NEP has been reported in SCLC and NSCLC cell lines. NEP inhibition has been shown to increase proliferation in one cell line. To date, NEP expression has not been quantitatively evaluated in normal adult lung, SCLC or NSCLC tumors, paired uninvolved lung from the same patient, or in other pulmonary neoplasms such as mesotheliomas and carcinoids. We examined the expression of NEP in these tissues and human cell lines using immunohistochemistry, flow cytometry, enzyme activity, ELISA, Western blot, and reverse transcription (RT)-PCR. Uninvolved lung tissue from different individuals displayed considerable variation in NEP activity and protein. By immunohistochemistry, NEP expression was detectable in alveolar and airway epithelium, fibroblasts of normal lung, and in mesotheliomas, whereas it was undetectable in most SCLC, adenocarcinoma, squamous cell carcinoma, and carcinoid tumors of the lung. NEP activity and protein levels were lower in all SCLC and adenocarcinoma tumors when compared to adjacent uninvolved lung, often at levels consistent with expression derived from contaminating stroma. NEP expression and activity were reduced or undetectable in most SCLC and lung adenocarcinoma cell lines. NEP mRNA by RT-PCR was not expressed or was in low abundance in the majority of lung cancer cell lines. The majority of lung tumors did not express NEP by RT-PCR as compared with normal adjacent lung. In addition, recombinant NEP abolished, whereas an NEP inhibitor potentiated, the calcium flux generated by neuropeptides in some lung cancer cell lines, demonstrating potential physiological significance for low NEP expression. NEP, therefore, is a signal transduction and possibly a growth modulator for both SCLC and NSCLC, emphasizing the role of neuropeptides in the pathogenesis of the major histological forms of lung cancer.

Impact of Insulin Degrading Enzyme and Neprilysin in Alzheimer's Disease Biology: Characterization of Putative Cognates for Therapeutic Applications.

PubMed

Jha, Niraj Kumar; Jha, Saurabh Kumar; Kumar, Dhiraj; Kejriwal, Noopur; Sharma, Renu; Ambasta, Rashmi K; Kumar, Pravir

2015-01-01

Alzheimer's disease (AD) is a neurodegenerative process primarily characterized by amyloid-β (Aβ) agglomeration, neuroinflammation, and cognitive dysfunction. The prominent cause for dementia is the deposition of Aβ plaques and tau-neurofibrillary tangles that hamper the neuronal organization and function. Aβ pathology further affects numerous signaling cascades that disturb the neuronal homeostasis. For instance, Aβ deposition is responsible for altered expression of insulin encoding genes that lead to insulin resistance, and thereby affecting insulin signaling pathway and glucose metabolism in the brain. As a result, the common pathology of insulin resistance between Type-2 diabetes mellitus and AD has led AD to be proposed as a form of diabetes and termed 'Type-3 diabetes'. Since accumulation of Aβ is the prominent cause of neuronal toxicity in AD, its clearance is the prime requisite for therapeutic prospects. This purpose is expertly fulfilled by the potential role of Aβ degrading enzymes such as insulin degrading enzyme (IDE) and Neprilysin (NEP). Therefore, their molecular study is important to uncover the proteolytic and regulatory mechanism of Aβ degradation. Herein, (i) In silico sequential and structural analysis of IDE and NEP has been performed to identify the molecular entities for proteolytic degradation of Aβ in the AD brain, (ii) to analyze their catalytic site to demonstrate the enzymatic action played by IDE and NEP, (iii) to identify their structural homologues that could behave as putative partners of IDE and NEP with similar catalytic action and (iv) to illustrate various IDE- and NEP-mediated therapeutic approaches and factors for clearing Aβ in AD.

Chronic intermittent hypoxia induces changes on the expression and activity of neprilysin (EC 3.4.24.11) in the brain of rats.

PubMed

de Oliveira, Renato W; Julian, Guilherme S; Perry, Juliana C; Tufik, Sergio; Chagas, Jair R

2018-06-21

Obstructive sleep apnea (OSA) is a frequent sleeping breathing disorder associated with cognitive impairments. Neprilysin (NEP) is responsible for degrading several substrates related to cognition; however, the effect of chronic intermittent hypoxia (CIH) on NEP is still unknown. This study aimed to evaluate the expression and activity of NEP in cognitive-related brain structures of rats submitted to CIH. Western blot, qRT-PCR and enzyme activity assay, demonstrated that a six-week intermittent hypoxia increased NEP expression and activity, selectively in temporal cortex, but not in the hippocampus and frontal cortex. The increase in NEP activity and expression was reverted followed by two weeks recovery in normoxia. These data show that CIH protocol increases the expression and activity of NEP selectively in the temporal cortex. Additional mechanisms must be investigated to elucidate the effects of CIH in cognition. Copyright © 2018 Elsevier B.V. All rights reserved.

Elucidating Pathogenic Mechanisms of Early-onset Alzheimer's Disease in Down Syndrome Patients.

PubMed

Asai, Masashi; Kawakubo, Takashi; Mori, Ryotaro; Iwata, Nobuhisa

2017-01-01

Down syndrome (DS) patients demonstrate the neuropathology of Alzheimer's disease (AD) characterized by the formation of senile plaques and neurofibrillary tangles by age 40-50 years. It has been considered for a number of years that 1.5-fold expression of the gene for the amyloid precursor protein (APP) located on chromosome 21 leading to overproduction of amyloid-β peptide (Aβ) results in the early onset of AD in adults with DS. However, the mean age of onset of familial AD with the Swedish mutation on APP which has high affinity for β-secretase associated with a dramatic increase in Aβ production is about 55 years. This paradox indicates that there is a poor correlation between average ages of AD onset and the theoretical amount of Aβ production and that there are factors exacerbating AD on chromosome 21. We therefore focused on dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), since overexpressing transgenic mice show AD-like brain pathology. The overexpression of DYRK1A caused suppression of the activity of neprilysin (NEP), which is a major Aβ-degrading enzyme in the brain, and phosphorylation at the NEP cytoplasmic domain. NEP activity was markedly reduced in fibroblasts derived from DS patients compared with that in fibroblasts derived from healthy controls. This impaired activity of NEP was rescued by DYRK1A inhibition. These results show that DYRK1A overexpression causes suppression of NEP activity through its phosphorylation in DS patients. Our results suggest that DYRK1A inhibitors could be effective against AD not only in adults with DS but also in sporadic AD patients.

Neprilysins: an evolutionarily conserved family of metalloproteases that play important roles in reproduction in Drosophila.

PubMed

Sitnik, Jessica L; Francis, Carmen; Hens, Korneel; Huybrechts, Roger; Wolfner, Mariana F; Callaerts, Patrick

2014-03-01

Members of the M13 class of metalloproteases have been implicated in diseases and in reproductive fitness. Nevertheless, their physiological role remains poorly understood. To obtain a tractable model with which to analyze this protein family's function, we characterized the gene family in Drosophila melanogaster and focused on reproductive phenotypes. The D. melanogaster genome contains 24 M13 class protease homologs, some of which are orthologs of human proteases, including neprilysin. Many are expressed in the reproductive tracts of either sex. Using RNAi we individually targeted the five Nep genes most closely related to vertebrate neprilysin, Nep1-5, to investigate their roles in reproduction. A reduction in Nep1, Nep2, or Nep4 expression in females reduced egg laying. Nep1 and Nep2 are required in the CNS and the spermathecae for wild-type fecundity. Females that are null for Nep2 also show defects as hosts of sperm competition as well as an increased rate of depletion for stored sperm. Furthermore, eggs laid by Nep2 mutant females are fertilized normally, but arrest early in embryonic development. In the male, only Nep1 was required to induce normal patterns of female egg laying. Reduction in the expression of Nep2-5 in the male did not cause any dramatic effects on reproductive fitness, which suggests that these genes are either nonessential for male fertility or perform redundant functions. Our results suggest that, consistent with the functions of neprilysins in mammals, these proteins are also required for reproduction in Drosophila, opening up this model system for further functional analysis of this protein class and their substrates.

Neprilysins: An Evolutionarily Conserved Family of Metalloproteases That Play Important Roles in Reproduction in Drosophila

PubMed Central

Sitnik, Jessica L.; Francis, Carmen; Hens, Korneel; Huybrechts, Roger; Wolfner, Mariana F.; Callaerts, Patrick

2014-01-01

Members of the M13 class of metalloproteases have been implicated in diseases and in reproductive fitness. Nevertheless, their physiological role remains poorly understood. To obtain a tractable model with which to analyze this protein family’s function, we characterized the gene family in Drosophila melanogaster and focused on reproductive phenotypes. The D. melanogaster genome contains 24 M13 class protease homologs, some of which are orthologs of human proteases, including neprilysin. Many are expressed in the reproductive tracts of either sex. Using RNAi we individually targeted the five Nep genes most closely related to vertebrate neprilysin, Nep1-5, to investigate their roles in reproduction. A reduction in Nep1, Nep2, or Nep4 expression in females reduced egg laying. Nep1 and Nep2 are required in the CNS and the spermathecae for wild-type fecundity. Females that are null for Nep2 also show defects as hosts of sperm competition as well as an increased rate of depletion for stored sperm. Furthermore, eggs laid by Nep2 mutant females are fertilized normally, but arrest early in embryonic development. In the male, only Nep1 was required to induce normal patterns of female egg laying. Reduction in the expression of Nep2-5 in the male did not cause any dramatic effects on reproductive fitness, which suggests that these genes are either nonessential for male fertility or perform redundant functions. Our results suggest that, consistent with the functions of neprilysins in mammals, these proteins are also required for reproduction in Drosophila, opening up this model system for further functional analysis of this protein class and their substrates. PMID:24395329

Development of Fast, Background-Limited Transition-Edge Sensors for the Background-Limited Infrared/Sub-mm Spectrograph (BLISS) for SPICA

NASA Technical Reports Server (NTRS)

Beyer, Andrew D.; Runyan, M. C.; Kenyon, M.; Echternach, P. M .; Chui, T.; Bumble, B.; Bradford, C. M.; Holmes, W. A.; Bock, J. J.

2012-01-01

We report experimental progress toward demonstrating background-limited arrays of membrane-isolated transition-edge sensors (TESs) for the Background Limited Infrared/Sub-mm Spectrograph (BLISS). BLISS is a space-borne instrument with grating spectrometers for wavelengths lambda=35-435 micron and with R=lambda/delta lambda approximately equals 500. The goals for BLISS TESs are: noise equivalent power (NEP) = 5x10 (sup -20) W/Hz(exp 1/2) and response time tau <30ms. We expect background-limited performance from bilayers TESs with T(sub c) = 65mK and G=15fW/K. However, such TESs cannot be operated at 50mK unless stray power on the devices, or dark power P(sub D), is less than 200aW. We describe criteria for measuring P(sub D) that requires accurate knowledge of TC. Ultimately, we fabricated superconducting thermistors from Ir (T(sub c) >= 135mK) and Mo/Cu proximitized bilayers, where T(sub c) is the thermistor transition temperature. We measured the Ir TES arrays in our 50mK adiabatic demagnetization refrigerator test system, which can measure up to eight 1x32 arrays simultaneously using a time-division multiplexer, as well as our single-pixel test system which can measure down to 15mK. In our previous Ir array measurements our best reported performance was NEP=2.5x10(exp -19) W/Hz(sub 1/2) and Tau approximately equals 5ms for straight-beam TESs. In fact, we expected NEP approximately equals 1.5x10(exp -19)?W/Hz(sup 1/2) for meander beam TESs, but did not achieve this previously due to 1/f noise. Here, we detail improvements toward measuring the expected NEP and demonstrate NEP=(1.3+0.2)x10 (sup -19)W/Hz(exp 1/2) in our single-pixel test system and NEP=(1.6+/-0.3)x10(sup -19)W/Hz(sup 1/2) in our array test system.

The impact of growing-season length variability on carbon assimilation and evapotranspiration over 88 years in the eastern US deciduous forest

PubMed

White; Running; Thornton

1999-02-01

Recent research suggests that increases in growing-season length (GSL) in mid-northern latitudes may be partially responsible for increased forest growth and carbon sequestration. We used the BIOME-BGC ecosystem model to investigate the impacts of including a dynamically regulated GSL on simulated carbon and water balance over a historical 88-year record (1900-1987) for 12 sites in the eastern USA deciduous broadleaf forest. For individual sites, the predicted GSL regularly varied by more than 15 days. When grouped into three climatic zones, GSL variability was still large and rapid. There is a recent trend in colder, northern sites toward a longer GSL, but not in moderate and warm climates. The results show that, for all sites, prediction of a long GSL versus using the mean GSL increased net ecosystem production (NEP), gross primary production (GPP), and evapotranspiration (ET); conversely a short GSL is predicted to decrease these parameters. On an absolute basis, differences in GPP between the dynamic and mean GSL simulations were larger than the differences in NEP. As a percentage difference, though, NEP was much more sensitive to changes in GSL than were either GPP or ET. On average, a 1-day change in GSL changed NEP by 1.6%, GPP by 0.5%, and ET by 0.2%. Predictions of NEP and GPP in cold climates were more sensitive to changes in GSL than were predictions in warm climates. ET was not similarly sensitive. First, our results strongly agree with field measurements showing a high correlation between NEP and dates of spring growth, and second they suggest that persistent increases in GSL may lead to long-term increases in carbon storage.

Glucocorticoids inhibit sulfur mustard-induced airway muscle hyperresponsiveness to substance P.

PubMed

Calvet, J H; D'Ortho, M P; Jarreau, P H; Levame, M; Harf, A; Macquin-Mavier, I

1994-11-01

To explore the mechanisms of airway hyperreactivity to aerosolized substance P observed in guinea pigs 14 days after intratracheal injection of sulfur mustard (SM), we studied the effects of epithelium removal and inhibition of neutral endopeptidase (NEP) activity on airway muscle responsiveness. Tracheal rings from SM-intoxicated guinea pigs expressed a greater contractile response to substance P than rings from nonintoxicated guinea pigs. After epithelium removal or incubation with the NEP inhibitor phosphoramidon, the contractile responses of tracheal rings to substance P did not differ in guinea pigs injected with SM or ethanol (SM solvent). Treatment of the guinea pigs with betamethasone for 7 days before measurement abolished the airway muscle hyperresponsiveness observed in untreated SM-intoxicated guinea pigs and partially restored tracheal epithelium NEP activity. In addition, the tracheal epithelium height and cell density of SM-intoxicated guinea pigs treated with betamethasone were significantly greater than in those without betamethasone. These results demonstrate that SM intoxication induces airway muscle hyperresponsiveness to substance P by reducing tracheal epithelial NEP activity and that glucocorticoids might inhibit this hyperresponsiveness by increasing this activity.

Involvement of substance P in neutral endopeptidase modulation of carotid body sensory responses to hypoxia.

PubMed

Kumar, G K; Kou, Y R; Overholt, J L; Prabhakar, N R

2000-01-01

Previously, we showed that carotid bodies express neutral endopeptidase (NEP)-like enzyme activity and that phosphoramidon, a potent inhibitor of NEP, potentiates the chemosensory response of the carotid body to hypoxia in vivo. NEP has been shown to hydrolyze methionine enkephalin (Met-Enk) and substance P (SP) in neuronal tissues. The purpose of the present study is to determine whether NEP hydrolyzes Met-Enk and SP in the carotid body and if so whether these peptides contribute to phosphoramidon-induced potentiation of the sensory response to hypoxia. Experiments were performed on carotid bodies excised from anesthetized adult cats (n = 72 carotid bodies). The hydrolysis of Met-Enk and SP was analyzed by HPLC. The results showed that both SP and Met-Enk were hydrolyzed by the carotid body, but the rate of Met-Enk hydrolysis was approximately fourfold higher than that of SP. Phosphoramidon (400 microM) markedly inhibited SP hydrolysis ( approximately 90%) but had only a marginal effect on Met-Enk hydrolysis ( approximately 15% inhibition). Hypoxia (PO(2), 68 +/- 6 Torr) as well as exogenous administration of SP (10 and 20 nmol) increased the sensory discharge of the carotid body in vitro. Sensory responses to hypoxia and SP (10 nmol) were potentiated by approximately 80 and approximately 275%, respectively (P < 0.01), in the presence of phosphoramidon. SP-receptor antagonists Spantide (peptidyl) and CP-96345 (nonpeptidyl) either abolished or markedly attenuated the phosphoramidon-induced potentiation of the sensory response of the carotid body to hypoxia as well as to SP. These results demonstrate that SP is a preferred substrate for NEP in the carotid body and that SP is involved in the potentiation of the hypoxic response of the carotid body by phosphoramidon.

Nuclear electric propulsion mission engineering study. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1973-01-01

Results of a mission engineering analysis of nuclear-thermionic electric propulsion spacecraft for unmanned interplanetary and geocentric missions are summarized. Critical technologies associated with the development of nuclear electric propulsion (NEP) are assessed. Outer planet and comet rendezvous mission analysis, NEP stage design for geocentric and interplanetary missions, NEP system development cost and unit costs, and technology requirements for NEP stage development are studied. The NEP stage design provides both inherent reliability and high payload mass capability. The NEP stage and payload integration was found to be compatible with the space shuttle.

Effects of the ECE/NEP inhibitor CGS 34225 on the big ET-1-induced pressor response and plasma atrial natriuretic peptide concentration in conscious rats.

PubMed

Trapani, Angelo J; Beil, Michael E; Bruseo, Charles W; Fink, Cynthia A; Hoyer, Denton; Savage, Paula; Jeng, Arco Y

2002-08-01

CGS 34226 is a thiol-containing, potent dual inhibitor of endothelin converting enzyme-1 (ECE-1) and neutral endopeptidase 24.11 (NEP) with IC(50) values of 11 and 5 nM respectively. The purpose of the present study was to characterize the inhibitory effects of CGS 34225, an orally active prodrug of CGS 34226, on ECE-1 and NEP in vivo. The effects on ECE-1 and NEP were assessed by determining the inhibition of big endothelin-1 (big ET-1)-induced increases in mean arterial pressure (MAP) and increases in plasma atrial natriuretic peptide (ANP) concentrations respectively, in conscious rats. Thirty and 120 min after the administration of vehicle, big ET-1 (0.3 nmol/kg, intravenously; i.v.) produced pressor responses of approximately 800 mmHg.min (area under the curve for change in MAPxtime). Treatment with CGS 34225 at 1 mgEq/kg, per os (p.o.), decreased the pressor effect of big ET-1 by 39 and 53% at 30 and 120 min respectively (P<0.05, both times). Increasing the dose of CGS 34255 to 30 mgEq/kg, p.o., resulted in greater inhibition, 84 and 92% (P<0.05) at 30 and 120 min respectively. Furthermore, at this higher dose, the inhibitory effect on ECE-1 was long-lasting, averaging 86, 75 and 30% (P<0.05, all times) at 4, 8 and 24 h respectively. In rats treated with vehicle, the infusion of ANP at 450 ng/kg per min i.v. resulted in plasma ANP concentrations of 3.9-4.8 ng/ml that remained relatively constant for 4 h. Treatment with CGS 34225 at 10 mgEq/kg, p.o., increased the ANP level to 7.7+/-1.0 and 10.6+/-1.8 ng/ml at 1 and 4 h after dosing (P<0.05, both times). These data demonstrate that CGS 34225 is a potent, orally active and long-acting inhibitor of ECE-1 and NEP in vivo. It is anticipated that compounds with this dual function may be useful in the treatment of cardiovascular diseases where the ET system plays a pathogenic role and the potentiation of ANP elicits therapeutic benefits.

Responses of the terrestrial carbon cycle to drought: modeling sensitivities of the interactive nitrogen and dynamic vegetation

NASA Astrophysics Data System (ADS)

Jia, B.; Wang, Y.; Xie, Z.

2016-12-01

Drought can trigger both immediate and time-lagged responses of terrestrial ecosystems and even cause sizeable positive feedbacks to climate warming. In this study, the influences of interactive nitrogen (N) and dynamic vegetation (DV) on the response of the carbon cycle in terrestrial ecosystems of China to drought were investigated using the Community Land Model version 4.5 (CLM4.5). Model simulations from three configurations of CLM4.5 (C, carbon cycle only; CN, dynamic carbon and nitrogen cycle; CNDV, dynamic carbon and nitrogen cycle as well as dynamic vegetation) between 1961 and 2010 showed that the incorporation of a prognostic N cycle and DV into CLM4.5 reduce the predicted annual means and inter-annual variability of predicted gross primary production (GPP) and net ecosystem production (NEP), except for a slight increase in NEP for CNDV compared to CN. These model improvements resulted in better agreement with observations (7.0 PgC yr-1) of annual GPP over the terrestrial ecosystems in China for CLM45-CN (7.5 PgC yr-1) and CLM45-CNDV (7.3 PgC yr-1) than for CLM45-C (10.9 PgC yr-1). Compared to the CLM45-C, the carbon-nitrogen coupling strengthened the predicted response of GPP to drought, resulting in a higher correlation with the standardized precipitation index (SPI; rC = 0.62, rCN = 0.67), but led to a weaker sensitivity of NEP to SPI (rC = 0.51, rCN = 0.45). The CLM45-CNDV had the longest lagged responses of GPP to drought among the three configurations. These results enhance our understanding of the response of the terrestrial carbon cycle to drought.

Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis.

PubMed

Sargın, Zeynep Gök; Erin, Nuray; Tazegul, Gokhan; Elpek, Gülsüm Özlem; Yıldırım, Bülent

2017-01-01

Neprilysin (NEP, CD10) acts to limit excessive inflammation partly by hydrolyzing neuropeptides. Although deletion of NEP exacerbates intestinal inflammation in animal models, its role in ulcerative colitis (UC) is not well explored. Herein, we aimed to demonstrate changes in NEP and associated neuropeptides at the same time in colonic tissue. 72 patients with UC and 27 control patients were included. Patients' demographic data and laboratory findings, five biopsy samples from active colitis sites and five samples from uninvolved mucosa were collected. Substance P (SP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) were extracted from freshly frozen tissues and measured using ELISA. Levels of NEP expression were determined using immunohistochemistry and immunoreactivity scores were calculated. GEBOES grading system was also used. We demonstrated a profound loss (69.4%) of NEP expression in UC, whereas all healthy controls had NEP expression. Patients with UC had lower neuronal SP; however non-neuronal SP remained similar. UC patients had also lower neuronal and non-neuronal VIP levels. CGRP were low in general and no significant changes were observed. Additionally, CRP positive patients with UC had higher rates of NEP loss (80% vs 51.9%) and lower SP levels when compared with CRP negative patients with UC. Concurrent decreases in SP and VIP with profound loss of NEP expression observed in UC is likely to be one of the factors in pathogenesis. Further studies are required to define the role of neuropeptides and NEP in UC.

Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis

PubMed Central

Sargın, Zeynep Gök; Tazegul, Gokhan; Elpek, Gülsüm Özlem; Yıldırım, Bülent

2017-01-01

Neprilysin (NEP, CD10) acts to limit excessive inflammation partly by hydrolyzing neuropeptides. Although deletion of NEP exacerbates intestinal inflammation in animal models, its role in ulcerative colitis (UC) is not well explored. Herein, we aimed to demonstrate changes in NEP and associated neuropeptides at the same time in colonic tissue. 72 patients with UC and 27 control patients were included. Patients’ demographic data and laboratory findings, five biopsy samples from active colitis sites and five samples from uninvolved mucosa were collected. Substance P (SP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) were extracted from freshly frozen tissues and measured using ELISA. Levels of NEP expression were determined using immunohistochemistry and immunoreactivity scores were calculated. GEBOES grading system was also used. We demonstrated a profound loss (69.4%) of NEP expression in UC, whereas all healthy controls had NEP expression. Patients with UC had lower neuronal SP; however non-neuronal SP remained similar. UC patients had also lower neuronal and non-neuronal VIP levels. CGRP were low in general and no significant changes were observed. Additionally, CRP positive patients with UC had higher rates of NEP loss (80% vs 51.9%) and lower SP levels when compared with CRP negative patients with UC. Concurrent decreases in SP and VIP with profound loss of NEP expression observed in UC is likely to be one of the factors in pathogenesis. Further studies are required to define the role of neuropeptides and NEP in UC. PMID:29232715

Neutral endopeptidase modulates substance P-induced vasodilation in vivo.

PubMed

Gao, X P; Rubinstein, I

1995-02-01

The purpose of this study was to investigate whether neutral endopeptidase (NEP; EC 3.4.24.11) modulates substance P-induced vasodilation in the oral mucosa in vivo. Using intravital microscopy, we measured the diameter of second-order arterioles (44-70 microns) in the hamster cheek pouch during suffusion of capsaicin and substance P. We found that capsaicin (0.1 and 10.0 nM) induced significant concentration-dependent vasodilations (13 +/- 4 and 39 +/- 7% increase from baseline, respectively; P < 0.05) that were significantly potentiated by phosphoramidon (10.0 nM), a selective NEP inhibitor (35 +/- 15 and 61 +/- 12% increase from baseline, respectively; P < 0.05). Substance P (0.1 and 10.0 nM) also induced significant concentration-dependent vasodilations (7 +/- 3 and 25 +/- 8% increase from baseline, respectively; P < 0.05) that were mediated by the COOH-terminal of the molecule. Substance P-induced responses were significantly potentiated by phosphoramidon (34 +/- 9 and 53 +/- 10% increase from baseline, respectively; P < 0.05) and thiorphan (10.0 microM), a selective NEP inhibitor (44 +/- 11 and 53 +/- 10% increase from baseline, respectively; P < 0.05). Substance P-(1-9) had no significant effects on arteriolar diameter. Suffusion of captopril, leupeptin, Bestatin, and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid together had no significant effects on substance P-induced vasodilation. Phosphoramidon did not potentiate nitroglycerin-induced vasodilation. These data indicate that NEP modulates substance P-induced vasodilation in the hamster cheek pouch in vivo. We suggest that any decrease in tissue NEP activity may amplify neurogenic vasodilation in the oral mucosa.

Neutral endopeptidase (EC 3.4.24.11) downregulates the onset of intestinal inflammation in the nematode infected mouse

PubMed Central

Barbara, G; De Giorgio, R; Stanghellini, V; Corinaldesi, R; Cremon, C; Gerard, N; Gerard, C; Grady, E F; Bunnett, N W; Blennerhassett, P A; Collins, S M

2003-01-01

Background and aims: Substance P (SP) release from sensory nerves induces neurogenic inflammation. Neutral endopeptidase (NEP) degrades SP, thereby limiting its proinflammatory effects. Intestinal inflammation following Trichinella spiralis infection markedly downregulates NEP, resulting in diminished SP degradation, with unknown functional consequences. We hypothesised that diminished expression of NEP would exacerbate T spiralis induced enteritis. Methods: NEP knockout (NEP−/−) and wild-type (NEP+/+) mice were infected with T spiralis and studied at 6, 12, 24, and 48 hours post infection (PI). Tissue inflammation was quantified by computerised cell counting and myeloperoxidase activity (MPO). The leucocyte adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), and SP were assessed by immunohistochemistry. Results: Before infection, the lack of NEP was not associated with changes in mucosal cellularity or MPO activity. Twelve hours PI, NEP−/− mice showed a 2.5-fold increase in MPO activity at a time when values in NEP+/+ mice were still within normal limits. MPO activity and cellularity peaked at 24 hours PI. This was accompanied by increased staining for both ICAM-1 and SP in NEP−/− mice. Infusion of rhNEP to NEP−/− mice significantly reduced MPO activity 24 hours PI. Conclusions: These findings demonstrate that NEP downregulates the early onset of nematode intestinal inflammation and that increased bioavailability of SP and overexpression of ICAM-1 in NEP−/− mice likely play a role in the earlier onset of intestinal inflammation. PMID:12970139

Neutral endopeptidase activity and airway hyperresponsiveness to neurokinin A in asthmatic subjects in vivo.

PubMed

Cheung, D; Timmers, M C; Zwinderman, A H; den Hartigh, J; Dijkman, J H; Sterk, P J

1993-12-01

In a previous study we have shown that inhibition of the endogenous neuropeptide-degrading enzyme, neutral endopeptidase (NEP), potentiates airway narrowing to neurokinin A (NKA) in normal humans in vivo. In the present study, we tested the hypothesis that hyperresponsiveness to NKA in asthma is caused by a reduction in endogenous NEP activity. To that end, we used the NEP inhibitor, thiorphan, or placebo as inhaled pretreatment to NKA challenge in eight atopic asthmatic men, who were controlled by on-demand usage of beta 2-agonists alone. The dose of thiorphan pretreatment was obtained from pilot experiments in which 0.5 ml of a 2.5-mg/ml concentration appeared to be the maximally effective nebulized dose. Dose-response curves to inhaled NKA (1 to 125 micrograms/ml, 0.5 ml/dose) were recorded on 2 randomized days 1 wk apart, in a cross-over study. To detect any effects of thiorphan on bronchoconstriction per se, we also investigated the effect of thiorphan or placebo on the dose-response curve to inhaled methacholine in a separate set of experiments. The response was measured by FEV1 and by partial expiratory flow-volume curves (V40p). The position of the dose-response curves was expressed as the concentration causing a 20% fall in FEV1 (PC20FEV1) or a 40% fall in V40p (PC40V40p). Baseline FEV1 and V40p were not affected by either pretreatment (p > 0.06). PC20FEV1 and PC40V40p to NKA were significantly lower after thiorphan pretreatment as compared with placebo (mean difference +/- SEM: 2.3 +/- 0.6 and 1.6 +/- 0.5 doubling dose, respectively; p < 0.015).(ABSTRACT TRUNCATED AT 250 WORDS)

Making sense of hypertrophic scar: a role for nerves.

PubMed

Scott, Jeffrey R; Muangman, Pornprom; Gibran, Nicole S

2007-01-01

Healed partial thickness wounds including burns and donor sites cause hypertrophic scar formation and patient discomfort. For many patients with hypertrophic scars, pruritus is the most distressing symptom, which leads to wound excoriation and chronic wound formation. In spite of the clinical significance of abnormal innervation in scars, the nervous system has been largely ignored in the pathophysiology of hypertrophic scars. Evidence that neuropeptides contribute to inflammatory responses to injury include inflammatory cell chemotaxis, cytokine and growth factor production. The neuropeptide substance P, which is released from nerve endings after injury, induces inflammation and mediates angiogenesis, keratinocyte proliferation, and fibrogenesis. Substance P activity is tightly regulated by neutral endopeptidase (NEP), a membrane bound metallopeptidase that degrades substance P at the cell membrane. Altered substance P levels may contribute to impaired cutaneous healing responses associated with diabetes mellitus or hypertrophic scar formation. Topical application of exogenous substance P or an NEP inhibitor enhances wound closure kinetics in diabetic murine wounds suggesting that diabetic wounds have insufficient substance P levels to promote a neuroinflammatory response necessary for normal wound repair. Conversely, increased nerve numbers and neuropeptide levels with reduced NEP levels in human and porcine hypertrophic scar samples suggest that excessive neuropeptide activity induces exuberant inflammation in hypertrophic scars. Given these observations about the role of neuropeptides in cutaneous repair, neuronal modulation of repair processes at two extremes of abnormal wound healing, chronic non-healing ulcers in type II diabetes mellitus and hypertrophic scars in deep partial thickness wounds, may provide therapeutic targets.

Superconducting Hot-Electron Submillimeter-Wave Detector

NASA Technical Reports Server (NTRS)

Karasik, Boris; McGrath, William; Leduc, Henry

2009-01-01

A superconducting hot-electron bolometer has been built and tested as a prototype of high-sensitivity, rapid-response detectors of submillimeter-wavelength radiation. There are diverse potential applications for such detectors, a few examples being submillimeter spectroscopy for scientific research; detection of leaking gases; detection of explosive, chemical, and biological weapons; and medical imaging. This detector is a superconducting-transition- edge device. Like other such devices, it includes a superconducting bridge that has a low heat capacity and is maintained at a critical temperature (T(sub c)) at the lower end of its superconducting-transition temperature range. Incident photons cause transient increases in electron temperature through the superconducting-transition range, thereby yielding measurable increases in electrical resistance. In this case, T(sub c) = 6 K, which is approximately the upper limit of the operating-temperature range of silicon-based bolometers heretofore used routinely in many laboratories. However, whereas the response speed of a typical silicon- based laboratory bolometer is characterized by a frequency of the order of a kilohertz, the response speed of the present device is much higher characterized by a frequency of the order of 100 MHz. For this or any bolometer, a useful figure of merit that one seeks to minimize is (NEP)(tau exp 1/2), where NEP denotes the noise-equivalent power (NEP) and the response time. This figure of merit depends primarily on the heat capacity and, for a given heat capacity, is approximately invariant. As a consequence of this approximate invariance, in designing a device having a given heat capacity to be more sensitive (to have lower NEP), one must accept longer response time (slower response) or, conversely, in designing it to respond faster, one must accept lower sensitivity. Hence, further, in order to increase both the speed of response and the sensitivity, one must make the device very small in order to make its heat capacity very small; this is the approach followed in developing the present device.

Effect of the NEP inhibitor SCH32615 on airway responses to intravenous substance P in guinea pigs.

PubMed

Shore, S A; Martins, M A; Drazen, J M

1992-11-01

We examined the effects of the selective neutral endopeptidase (NEP) inhibitor SCH32615 on airway responses to rapid intravenous infusions of substance P (SP) and neurokinin A (NKA) and on recovery of administered tachykinins from arterial blood in anesthetized mechanically ventilated guinea pigs. SCH32615, in doses that cause a marked increase in the magnitude of bronchoconstriction induced by infused NKA, had little effect on the changes in pulmonary conductance (GL) or dynamic compliance induced by SP. In animals in which SCH32615 (1 mg/kg) was administered in combination with the angiotensin-converting enzyme (ACE) inhibitor captopril (5.7 mg/kg), the dose of SP required to decrease GL by 50% was fourfold less than in animals that received captopril alone (P < 0.005). SP measured in arterial blood withdrawn within 45 s of intravenous administration of this tachykinin was not different in control and SCH32615-treated animals, whereas captopril caused an approximately threefold increase in SP concentrations (P < 0.005). When SCH32615 and captopril were administered together, significantly more SP was recovered than when captopril or SCH32615 was administered alone (P < 0.0005). Our results are consistent with the hypothesis that both NEP and ACE contribute to the degradation of intravenously infused SP. ACE degradation of SP is sufficient to limit SP-induced bronchoconstriction even in the presence of specific NEP inhibition.

Neutral endopeptidase inhibitor potentiates the tachykinin-induced increase in ciliary beat frequency in rabbit trachea.

PubMed

Kondo, M; Tamaoki, J; Takizawa, T

1990-08-01

We used cultured rabbit tracheal epithelium to determine the effect of mammalian-derived tachykinin on airway ciliary activity and its modulation by neutral endopeptidase EC 3.4.24.11 (NEP). Neurokinin A (NKA) caused dose-dependent increases in ciliary beat frequency (CBF), as measured by a photoelectric method, with the maximal increase from the baseline 15.7 +/- 1.7% (mean +/- SEM, p less than 0.01), whereas substance P (SP) had no effect. The NKA-induced increase in CBF was not inhibited by phentolamine, propranolol, or atropine, but it was abolished by the tachykinin antagonist [D-Pro2, D-Trp7,9]SP. Pretreatment of tissue with thiorphan (10(-5) M), a NEP inhibitor, had little effect on CBF responses to NKA; however, it significantly potentiated the responses to SP (14.9 +/- 3.0%, p less than 0.01). Other peptidase inhibitors, including captopril, bestatin, and leupeptin, did not alter the tachykinin-induced CBF response, suggesting that angiotensin converting enzyme, aminopeptidases, and serine proteinases do not modulate ciliary activity in response to tachykinins. These results suggest that NKA increases CBF by acting directly on tachykinin receptors and that NEP may play a role in modulating the tachykinin-induced stimulatory effects on CBF.

Continuous negative external pressure (cNEP) reduces respiratory impairment during screening colonoscopy: a pilot study.

PubMed

Kais, Susan S; Klein, Kenneth B; Rose, Richard M; Endemann, Sarah; Coyle, Walter J

2016-06-01

Drugs administered during gastrointestinal procedures cause increased collapsibility of the upper airway, which may lead to respiratory impairment. We evaluated the ability of continuous negative external pressure (cNEP) to lessen respiratory impairment during screening colonoscopy. The initial 24 patients served as controls, while the next 30 received cNEP. cNEP was delivered by a soft silicone collar placed over the anterior neck. The primary endpoint was the frequency of respiratory impairment, defined as either: (i) a decline from baseline of > 4 % in oxygen saturation, or (ii) apnea lasting ≥ 20 seconds. Mean respiratory impairment episodes were 3.50 in the no-cNEP group vs. 1.92 in the cNEP group, a reduction of 45 % (P = 0.022). Apneas ≥ 20 seconds occurred in 74 % of the no-cNEP group and 28 % of the cNEP group (P = 0.002). While 42 % of the no-cNEP group required increased supplemental oxygen, this was true for only 10 % of the cNEP group (P = 0.01). cNEP adverse events were minimal. During screening colonoscopy, sedation-related respiratory impairment is significantly reduced by cNEP.ClinicalTrials.gov NCT01895062. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of National Football League games on small animal emergency room caseload.

PubMed

Rozanski, Elizabeth A; Rondeau, Mark P; Shaw, Scott P; Rush, John E

2009-07-01

To evaluate whether games of popular professional football teams have an effect on small animal emergency room caseload and percentage of dogs and cats that subsequently are hospitalized, are euthanatized, or die following admission to veterinary emergency rooms located within a dedicated fan base. Prospective study. 818 dogs and cats admitted to the emergency room. During the 2007 New England Patriots (NEP) football season, small animal emergency room caseload was recorded for Sunday (4-hour blocks, 8:00 AM until 12:00 midnight) and Monday night (7:00 PM to 11:00 PM). Number of dogs and cats that subsequently were hospitalized, died, or were euthanatized was recorded. Mean game importance rating (GIR) was determined for NEP games (scale, 1 [mild] to 3 [great]). Percentage of dogs and cats admitted from 12:00 noon to 4:00 PM on Sundays during NEP games (mean GIR, 1.7) versus non-NEP games was not different. Mean +/- SD percentage of dogs and cats admitted from 4:00 PM to 8:00 PM on Sundays during NEP games (mean GIR, 2.4) versus non-NEP games was significantly different (18 +/- 5% and 25 +/- 7% of daily caseload, respectively). Percentage of dogs and cats admitted from 8:00 PM to 12:00 midnight on Sundays during NEP games (mean GIR, 2.1) versus non-NEP games was not different. Game type (NEP vs non-NEP) during emergency room admission did not influence whether dogs and cats subsequently were hospitalized, died, or were euthanatized. Professional sporting events may influence veterinary emergency room caseloads.

Increased pain and neurogenic inflammation in mice deficient of neutral endopeptidase.

PubMed

Krämer, Heidrun H; He, Lan; Lu, Bao; Birklein, Frank; Sommer, Claudia

2009-08-01

The complex regional pain syndrome (CRPS) is characterized by enhanced neurogenic inflammation, mediated by neuropeptides. Neutral endopeptidase (NEP) is a key enzyme in neuropeptide catabolism. We used NEP knock out (ko) mice to investigate whether NEP deficiency leads to increased pain behavior and signs of neurogenic inflammation after soft tissue trauma with and without nerve injury. After chronic constriction injury (CCI) of the right sciatic nerve, NEP ko mice were more sensitive to heat, to mechanical stimuli, and to cold than wild type mice. Tissue injury without nerve injury produced no differences between genotypes. After CCI, NEP ko mice showed increased hind paw edema but lower skin temperatures than wild type mice. Substance P (SP) and endothelin 1 (ET 1) determined by enzyme immuno assay (EIA) were increased in sciatic nerves from NEP ko mice after CCI. Tissue CGRP content did not differ between the genotypes. The results provide evidence that pain behavior and neurogenic inflammation are enhanced in NEP ko mice after nerve injury. These findings resemble human 'cold' CRPS and suggest that ET 1 plays an important role in the pathogenesis of CRPS with nerve injury.

Production of soluble Neprilysin by endothelial cells.

PubMed

Kuruppu, Sanjaya; Rajapakse, Niwanthi W; Minond, Dmitriy; Smith, A Ian

2014-04-04

A non-membrane bound form of Neprilysin (NEP) with catalytic activity has the potential to cleave substrates throughout the circulation, thus leading to systemic effects of NEP. We used the endothelial cell line Ea.hy926 to identify the possible role of exosomes and A Disintegrin and Metalloprotease 17 (ADAM-17) in the production of non-membrane bound NEP. Using a bradykinin based quenched fluorescent substrate (40 μM) assay, we determined the activity of recombinant human NEP (rhNEP; 12 ng), and NEP in the media of endothelial cells (10% v/v; after 24 h incubation with cells) to be 9.35±0.70 and 6.54±0.41 μmols of substrate cleaved over 3h, respectively. The presence of NEP in the media was also confirmed by Western blotting. At present there are no commercially available inhibitors specific for ADAM-17. We therefore synthesised two inhibitors TPI2155-14 and TPI2155-17, specific for ADAM-17 with IC50 values of 5.36 and 4.32 μM, respectively. Treatment of cells with TPI2155-14 (15 μM) and TPI2155-17 (4.3 μM) resulted in a significant decrease in NEP activity in media (62.37±1.43 and 38.30±4.70, respectively as a % of control; P<0.0001), implicating a possible role for ADAM-17 in NEP release. However, centrifuging media (100,000g for 1 h at 4 °C) removed all NEP activity from the supernatant indicating the likely role of exosomes in the release of NEP. Our data therefore indicated for the first time that NEP is released from endothelial cells via exosomes, and that this process is dependent on ADAM-17. Copyright © 2014 Elsevier Inc. All rights reserved.

Development of Fast, Background-Limited Transition-Edge Sensors for the Background-Limited Infrared/Sub-Millimetre Spectrograph (BLISS) for SPICA

NASA Technical Reports Server (NTRS)

Beyer, Andrew D.; Runyan, M. C.; Kenyon, M.; Echternach, P. M.; Chui, T.; Bumble, B.; Bradford, C. M.; Holmes, W. A.; Bock, J. J.

2012-01-01

We report experimental progress toward demonstrating background-limited arrays of membrane-isolated transition-edge sensors (TESs) for the Background Limited Infrared/Sub-mm Spectrograph (BLISS). BLISS is a space-borne instrument with grating spectrometers for wavelengths lambda = 35-435 microns and with R = lambda/(delta)lambda approx. 500. The goals for BLISS TESs are: noise equivalent power (NEP) = 5x10(exp -20) W/Hz(1/2) and response time t<30ms. We expect background-limited performance from bilayers TESs with T(sub c)=65mK and G=15fW/K. However, such TESs cannot be operated at 50mK unless stray power on the devices, or dark power PD, is less than 200aW. We describe criteria for measuring P? that requires accurate knowledge of TC. Ultimately, we fabricated superconducting thermistors from Ir (T(sub c) > or = 135mK) and Mo/Cu proximitized bilayers, where T(sub c) is the thermistor transition temperature. We measured the Ir TES arrays in our 50mK adiabatic demagnetization refrigerator test system, which can measure up to eight 1x32 arrays simultaneously using a time-division multiplexer, as well as our single-pixel test system which can measure down to 15mK. In our previous Ir array measurements our best reported performance was NEP=2.5x10(exp -19) W/Hz(1/2) and tapprox.5ms for straight-beam TESs. In fact, we expected NEPapprox.1.5x10(exp -19)W/Hz(1/2) for meander beam TESs, but did not achieve this previously due to 1/f noise. Here, we detail improvements toward measuring the expected NEP and demonstrate NEP=(1.3+0.2)x10(exp -19)W/Hz(1/2) in our single-pixel test system and NEP=(1.6+0.3)x10(exp -19)W/Hz(1/2) in our array test system.

Estimation of net ecosystem production in Asia using the diagnostic-type ecosystem model with a 10 km grid-scale resolution

NASA Astrophysics Data System (ADS)

Sasai, Takahiro; Obikawa, Hiroki; Murakami, Kazutaka; Kato, Soushi; Matsunaga, Tsuneo; Nemani, Ramakrishna R.

2016-06-01

The terrestrial carbon cycle in Asia is highly uncertain, and it affects our understanding of global warming. One of the important issues is the need for an enhancement of spatial resolution, since local regions in Asia are heterogeneous with regard to meteorology, land form, and land cover type, which greatly impacts the detailed spatial patterns in its ecosystem. Thus, an important goal of this study is to reasonably reproduce the heterogeneous biogeochemical patterns in Asia by enhancing the spatial resolution of the ecosystem model biosphere model integrating eco-physiological and mechanistic approaches using satellite data (BEAMS). We estimated net ecosystem production (NEP) over eastern Asia and examined the spatial differences in the factors controlling NEP by using a 10 km grid-scale approach over two different decades (2001-2010 and 2091-2100). The present and future meteorological inputs were derived from satellite observations and the downscaled Coupled Model Intercomparison Project Phase 5 (CMIP5) data set, respectively. The results showed that the present NEP in whole eastern Asia was carbon source (-214.9 TgC yr-1) and in future scenarios, the greatest positive (76.4 TgC yr-1) and least negative (-95.9 TgC yr-1) NEPs were estimated from the Representative Concentration Pathways (RCP) 6.0 and RCP8.5 scenarios, respectively. Calculated annual NEP in RCP8.5 was mostly positive in the southern part of East Asia and Southeast Asia and negative in northern and central parts of East Asia. Under the RCP scenario with higher greenhouse gases emission (RCP8.5), deciduous needleleaf and mixed forests distributed in the middle and high latitudes served as carbon source. In contrast, evergreen broadleaf forests distributed in low latitudes served as carbon sink. The sensitivity study demonstrated that the spatial tendency of NEP was largely influenced by atmospheric CO2 and temperature.

Advanced fiber information systems seed coat neps baseline response from diverse mediums

USDA-ARS?s Scientific Manuscript database

An extensive literature search has revealed that no papers have been published regarding selectivity calculation of the AFIS seed coat neps (SCN) determination over interfering material in cotton. A prerequisite to selectivity measurements is to identify suitable fiber medium(s) that give baseline ...

Two-color detector: Mercury-cadmium-telluride as a terahertz and infrared detector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sizov, F.; Zabudsky, V.; Petryakov, V.

2015-02-23

In this paper, issues associated with the development of infrared (IR) and terahertz (THz) radiation detectors based on HgCdTe are discussed. Two-color un-cooled and cooled to 78 K narrow-gap mercury-cadmium-telluride semiconductor thin layers with antennas were considered both as sub-THz (sub-THz) direct detection bolometers and 3–10 μm IR photoconductors. The noise equivalent power (NEP) for one of the detectors studied at ν ≈ 140 GHz reaches NEP{sub 300 K} ≈ 4.5 × 10{sup −10} W/Hz{sup 1/2} and NEP{sub 78 K} ≈ 5 × 10{sup −9} W/Hz{sup 1/2}. The same detector used as an IR photoconductor showed the responsivity at temperatures T = 78 K and 300 K with signal-to-noisemore » ratio S/N ≈ 750 and 50, respectively, under illumination by using IR monochromator and globar as a thermal source.« less

Interannual Variation in Carbon Sequestration Depends Mainly on the Carbon Uptake Period in Two Croplands on the North China Plain

PubMed Central

Bao, Xueyan; Wen, Xuefa; Sun, Xiaomin; Zhao, Fenghua; Wang, Yuying

2014-01-01

Interannual variation in plant phenology can lead to major modifications in the interannual variation of net ecosystem production (NEP) and net biome production (NBP) as a result of recent climate change in croplands. Continuous measurements of carbon flux using the eddy covariance technique were conducted in two winter wheat and summer maize double-cropped croplands during 2003–2012 in Yucheng and during 2007–2012 in Luancheng on the North China Plain. Our results showed that the difference between the NEP and the NBP, i.e., the crop economic yield, was conservative even though the NEP and the NBP for both sites exhibited marked fluctuations during the years of observation. A significant and positive relationship was found between the annual carbon uptake period (CUP) and the NEP as well as the NBP. The NEP and the NBP would increase by 14.8±5.2 and 14.7±6.6 g C m−2 yr−1, respectively, if one CUP-day was extended. A positive relationship also existed between the CUP and the NEP as well as the NBP for winter wheat and summer maize, respectively. The annual air temperature, through its negative effect on the start date of the CUP, determined the length of the CUP. The spring temperature was the main indirect factor controlling the annual carbon sequestration when a one-season crop (winter wheat) was considered. Thus, global warming can be expected to extend the length of the CUP and thus increase carbon sequestration in croplands. PMID:25313713

Tracheal smooth muscle responses to substance P and neurokinin A in the piglet.

PubMed

Haxhiu-Poskurica, B; Haxhiu, M A; Kumar, G K; Miller, M J; Martin, R J

1992-03-01

The tachykinins substance P (SP) and neurokinin A (NKA) have been shown to induce airway smooth muscle contraction in mature animals, and the enzyme neutral endopeptidase (NEP) modulates this effect. We evaluated maturation of SP- and NKA-induced tracheal smooth muscle contraction and modulation of their effects by NEP in anesthetized, paralyzed, and artificially ventilated piglets less than 4 days, 2-3 wk, and 10 wk of age. Tracheal smooth muscle tension was measured in vivo from an open tracheal segment by use of a force transducer. Intravenous SP caused a dose-dependent increase in tracheal tension in all three age groups; however, the response in less than 4-day-old piglets was significantly weaker than in 2- to 3- and 10-wk-old piglets. NKA caused a dose-dependent increase in tracheal tension only in 2- to 3- and 10-wk-old piglets. The response of tracheal tension to NKA was weaker than the response to SP in all age groups. Atropine (2 mg/kg) significantly diminished the responses of tracheal tension to SP and NKA, indicating a cholinergic contribution to these responses at all ages. Intravenous thiorphan, a known NEP inhibitor, potentiated the effects of SP only in 2- to 3- and 10-wk-old piglets and did not affect the response of tracheal tension to NKA at any age. Biochemical analyses demonstrated a significant increase in tracheal NEP activity in comparably aged piglets over the first 10 wk of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenomedullin (ADM) in the human forearm vascular bed: effect of neutral endopeptidase inhibition and comparison with proadrenomedullin NH2-terminal 20 peptide (PAMP)

PubMed Central

Wilkinson, Ian B; McEniery, Carmel M; Bongaerts, Katherine H; MacCallum, Helen; Webb, David J; Cockcroft, John R

2001-01-01

Aims To compare the haemodynamic responses of proadrenomedullin N-terminal 20 peptide (PAMP) and adrenomedullin (ADM) in the forearm vascular bed of healthy male volunteers, and to investigate the role of neutral endopeptidase (NEP) in the metabolism of ADM. Methods On two separate occasions, ADM (1–30 pmol min−1) and PAMP (100–3000 pmol min−1) were infused into the brachial artery of eight male subjects, and forearm blood flow (FBF) assessed using venous occlusion plethysmography. In a second study, eight male subjects received the same doses of ADM, co-infused with either the NEP inhibitor thiorphan (30 nmol min−1) or the control vasoconstrictor noradrenaline (120 pmol min−1), on separate occasions. Both studies were conducted in a double-blind, randomized manner. Results ADM and PAMP produced a dose-dependent increase in FBF (P ≤ 0.002). Based on the dose producing a 50% increase in FBF, ADM was ∼60 times more potent than PAMP. Thiorphan and noradrenaline produced similar reductions in FBF of 14 ± 4% (mean ± s.e. mean) and 22 ± 6%, respectively (P = 0.4). However, the area under the dose–response curve was significantly greater during co-infusion of ADM with thiorphan than with noradrenaline (P = 0.028), as was the maximum increase in FBF ratio (2.1 ± 1.0 vs 1.2 ± 0.2; P = 0.030). Conclusions ADM and PAMP both produce a local dose-related vasodilatation in the human forearm, but PAMP is ∼60 times less potent than ADM. In addition, NEP inhibition potentiates the haemodynamic effects of ADM. These findings suggest that PAMP may not play a role in the physiological regulation of blood flow. However, in pathophysiological conditions such as hypertension and heart failure, NEP inhibition may exert a beneficial effect by increasing the biological activity of ADM. PMID:11488772

NK-1 receptor desensitization and neutral endopeptidase terminate SP-induced pancreatic plasma extravasation.

PubMed

Maa, J; Grady, E F; Kim, E H; Yoshimi, S K; Hutter, M M; Bunnett, N W; Kirkwood, K S

2000-10-01

Substance P (SP) induces plasma extravasation and neutrophil infiltration by activating the neurokinin-1 receptor (NK1-R). We characterized the mechanisms regulating this response in the rat pancreas. Anesthetized rats were continuously infused with SP, and plasma extravasation was quantified using Evans blue (EB) dye. Continuous infusion of SP (8 nmol. kg(-1). h(-1)) resulted in a threshold increase in EB at 15 min, a peak effect at 30 min (150% increase), and a return to baseline by 60 min. The NK1-R antagonist CP-96,345 blocked SP-induced plasma extravasation. After 60 min, the NK1-R was desensitized to agonist challenge. Resensitization was first detected at 20 min and increased until full recovery was seen at 30 min. Inhibition of the cell-surface protease neutral endopeptidase (NEP) by phosphoramidon potentiated the effect of exogenous SP; therefore endogenous NEP attenuates SP-induced plasma extravasation. Thus the continuous infusion of SP stimulates plasma extravasation in the rat pancreas via activation of the NK1-R, and these effects are terminated by both desensitization of the NK1-R and the cell-surface protease NEP.

The control of microvascular permeability and blood pressure by neutral endopeptidase.

PubMed

Lu, B; Figini, M; Emanueli, C; Geppetti, P; Grady, E F; Gerard, N P; Ansell, J; Payan, D G; Gerard, C; Bunnett, N

1997-08-01

Plasma extravasation from postcapillary venules is one of the earliest steps of inflammation. Substance P (SP) and bradykinin (BK) mediate extravasation and cause hypotension. The cell-surface enzyme neutral endopeptidase (NEP) inactivates both peptides. Thus, absence of NEP may predispose development of inflammation and hypotension. We examined these possibilities in mice in which the NEP gene was deleted by homologous recombination. There was widespread basal plasma extravasation in postcapillary venular endothelia in NEP-/- mice, which was reversed by recombinant NEP and antagonists of SP (NK1) and BK (B2) receptors. Mean arterial blood pressure was 20% lower in NEP-/- animals, but this was unaffected by reintroduction of recombinant NEP and the kinin receptor antagonists. The hypotension was also independent of nitric oxide (NO), because NEP-/- mice treated with a NO synthase inhibitor remained hypotensive relative to the wild type. Thus, NEP has important roles in regulating basal microvascular permeability by degrading SP and BK, and may regulate blood pressure set point through a mechanism that is independent of SP, BK and NO. The use of NEP antagonists as candidate drugs in cardiovascular disease is suggested by the blood pressure data reported herein.

Zero-bias microwave detectors based on array of nanorectifiers coupled with a dipole antenna

NASA Astrophysics Data System (ADS)

Kasjoo, Shahrir R.; Singh, Arun K.; Mat Isa, Siti S.; Ramli, Muhammad M.; Mohamad Isa, Muammar; Ahmad, Norhawati; Mohd Nor, Nurul I.; Khalid, Nazuhusna; Song, Ai Min

2016-04-01

We report on zero-bias microwave detection using a large array of unipolar nanodevices, known as the self-switching diodes (SSDs). The large array was realized in a single lithography step without the need of interconnection layers, hence allowing for a simple and low-cost fabrication process. The SSD array was coupled with a narrowband dipole antenna with a resonant frequency of 890 MHz, to form a simple rectenna (rectifying antenna). The extrinsic voltage responsivity and noise-equivalent-power (NEP) of the rectenna were ∼70 V/W and ∼0.18 nW/Hz1/2, respectively, measured in the far-field region at unbiased condition. Nevertheless, the estimated intrinsic voltage responsivity can achieve up to ∼5 kV/W with NEP of ∼2.6 pW/Hz1/2.

Optimization of narrow width effect on titanium thermistor in uncooled antenna-coupled terahertz microbolometer

NASA Astrophysics Data System (ADS)

Banerjee, Amit; Satoh, Hiroaki; Elamaran, Durgadevi; Sharma, Yash; Hiromoto, Norihisa; Inokawa, Hiroshi

2018-04-01

Uncooled antenna-coupled terahertz microbolometer arrays are fabricated with a meander-type Ti thermistor, and design widths (DW) = 0.1 and 0.2 µm, considering the design requirement to miniaturize detectors. Each unit device with DW = 0.1 µm of the thermistor has about 4.7 time higher electrical responsivity (132 V/W) than that with DW = 0.2 µm (28.2 V/W) at 10 µA bias current. For DW = 0.2 µm, the calculated noise equivalent power (NEP) was 2.29 × 10‑9 W/\\sqrt{\\text{Hz}} , whereas the minimum NEP of 4.43 × 10‑10 W/\\sqrt{\\text{Hz}} was obtained for DW = 0.1 µm devices, both at 10 µA bias current. The bulk value of temperature coefficient of resistance (TCR) of the Ti thermistor is markedly compromised in low dimensional devices, still in terms of responsivity and NEP, unit devices with Ti thermistor with the lower DW shows better performance. This is because the narrow width effect is minimized owing to higher resistivity for DW = 0.1 than that for DW = 0.2 µm. In this current report, we highlights the optimization of the narrow width effect on TCR of metal interconnects in nanometer dimensions, which to the best of our knowledge is not available at present.

Energy utilisation of broiler chickens in response to guanidinoacetic acid supplementation in diets with various energy contents.

PubMed

Ale Saheb Fosoul, Sayed Sadra; Azarfar, Arash; Gheisari, Abbasali; Khosravinia, Heshmatollah

2018-07-01

This experiment was conducted to investigate the effects of guanidinoacetic acid (GAA) on productive performance, intestinal morphometric features, blood parameters and energy utilisation in broiler chickens. A total of 390 male broiler chicks (Ross 308) were assigned to six dietary treatments based on a factorial arrangement (2×3) across 1-15 and 15-35-d periods. Experimental treatments consisted of two basal diets with standard (STD; starter: 12·56 MJ/kg and grower: 12·97 MJ/kg) and reduction (LME; starter: 11·93 MJ/kg and grower: 12·33 MJ/kg) of apparent metabolisable energy (AME) requirement of broiler chickens each supplemented with 0, 0·6 and 1·2 g/kg GAA. Supplemental 1·2 g/kg GAA decreased the negative effects of feed energy reduction on weight gain across starter, growing and the entire production phases (P<0·05). Energy retention as fat and total energy retention were increased when birds received LME diets supplemented with 1·2 g/kg GAA (P<0·05). Net energy for production (NEp) and total heat production increased in birds fed LME diets containing 1·2 g/kg GAA (P<0·05). A significant correlation was observed between dietary NEp and weight gain of broilers (r 0·493; P=0·0055), whereas this relationship was not seen with AME. Jejunal villus height and crypt depth were lower in birds fed LME diets (P<0·05). Serum concentration of creatinine increased in broilers fed LME diets either supplemented with 1·2 g/kg GAA or without GAA supplementation (P<0·05). Supplemental GAA improved performance of chickens fed LME diet possibly through enhanced dietary NEp. The NEp could be preferred over the AME to assess response of broiler chickens to dietary GAA supplementation.

Methylprednisolone prevents nerve injury-induced hyperalgesia in neprilysin knockout mice.

PubMed

He, Lan; Uçeyler, Nurcan; Krämer, Heidrun H; Colaço, Maria Nandini; Lu, Bao; Birklein, Frank; Sommer, Claudia

2014-03-01

The pathophysiology of the complex regional pain syndrome involves enhanced neurogenic inflammation mediated by neuropeptides. Neutral endopeptidase (neprilysin, NEP) is a key enzyme in neuropeptide catabolism. Our previous work revealed that NEP knock out (ko) mice develop more severe hypersensitivity to thermal and mechanical stimuli after chronic constriction injury (CCI) of the sciatic nerve than wild-type (wt) mice. Because treatment with glucocorticoids is effective in early complex regional pain syndrome, we investigated whether methylprednisolone (MP) reduces pain and sciatic nerve neuropeptide content in NEP ko and wt mice with nerve injury. After CCI, NEP ko mice developed more severe thermal and mechanical hypersensitivity and hind paw edema than wt mice, confirming previous findings. Hypersensitivity was prevented by MP treatment in NEP ko but not in wt mice. MP treatment had no effect on protein levels of calcitonin-gene related peptide, substance P, and bradykinin in sciatic nerves of NEP ko mice. Endothelin-1 (ET-1) levels were higher in naïve and nerve-injured NEP ko than in wt mice, without an effect of MP treatment. Gene expression of the ET-1 receptors ETAR and ETBR was not different between genotypes and was not altered after CCI, but was increased after additional MP treatment. The ETBR agonist IRL-1620 was analgesic in NEP ko mice after CCI, and the ETBR antagonist BQ-788 showed a trend to reduce the analgesic effect of MP. The results provide evidence that MP reduces CCI-induced hyperalgesia in NEP ko mice, and that this may be related to ET-1 via analgesic actions of ETBR. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

A comparison of remote vs. local influence of El Niño on the coastal circulation of the northeast Pacific

NASA Astrophysics Data System (ADS)

Hermann, Albert J.; Curchitser, Enrique N.; Haidvogel, Dale B.; Dobbins, Elizabeth L.

2009-12-01

A set of spatially nested circulation models is used to explore interannual change in the northeast Pacific (NEP) during 1997-2002, and remote vs. local influence of the 1997-1998 El Niño on this region. Our nested set is based on the primitive equations of motion, and includes a basin-scale model of the north Pacific at ˜40-km resolution (NPac), and a regional model of the Northeast Pacific at ˜10-km resolution. The NEP model spans an area from Baja California through the Bering Sea, from the coast to ˜2000-km offshore. In this context, "remote influence" refers to effects driven by changes in ocean velocity and temperature outside of the NEP domain; "local influence" refers to direct forcing by winds and runoff within the NEP domain. A base run of this model using hindcast winds and runoff for 1996-2002 replicates the dominant spatial modes of sea-surface height anomalies from satellite data, and coastal sea level from tide gauges. We have performed a series of sensitivity runs with the NEP model for 1997-1998, which analyze the response of coastal sea level to: (1) hindcast winds and coastal runoff, as compared to their monthly climatologies and (2) hindcast boundary conditions (from the NPac model), as compared to their monthly climatologies. Results indicate penetration of sea-surface height (SSH) from the basin-scale model into the NEP domain (e.g., remote influence), with propagation as coastal trapped waves from Baja up through Alaska. Most of the coastal sea-level anomaly off Alaska in El Niño years appears due to direct forcing by local winds and runoff (local influence), and such anomalies are much stronger than those produced off California. We quantify these effects as a function of distance along the coastline, and consider how they might impact the coastal ecosystems of the NEP.

The Bartonella quintana Extracytoplasmic Function Sigma Factor RpoE Has a Role in Bacterial Adaptation to the Arthropod Vector Environment

PubMed Central

Abromaitis, Stephanie

2013-01-01

Bartonella quintana is a vector-borne bacterial pathogen that causes fatal disease in humans. During the infectious cycle, B. quintana transitions from the hemin-restricted human bloodstream to the hemin-rich body louse vector. Because extracytoplasmic function (ECF) sigma factors often regulate adaptation to environmental changes, we hypothesized that a previously unstudied B. quintana ECF sigma factor, RpoE, is involved in the transition from the human host to the body louse vector. The genomic context of B. quintana rpoE identified it as a member of the ECF15 family of sigma factors found only in alphaproteobacteria. ECF15 sigma factors are believed to be the master regulators of the general stress response in alphaproteobacteria. In this study, we examined the B. quintana RpoE response to two stressors that are encountered in the body louse vector environment, a decreased temperature and an increased hemin concentration. We determined that the expression of rpoE is significantly upregulated at the body louse (28°C) versus the human host (37°C) temperature. rpoE expression also was upregulated when B. quintana was exposed to high hemin concentrations. In vitro and in vivo analyses demonstrated that RpoE function is regulated by a mechanism involving the anti-sigma factor NepR and the response regulator PhyR. The ΔrpoE ΔnepR mutant strain of B. quintana established that RpoE-mediated transcription is important in mediating the tolerance of B. quintana to high hemin concentrations. We present the first analysis of an ECF15 sigma factor in a vector-borne human pathogen and conclude that RpoE has a role in the adaptation of B. quintana to the hemin-rich arthropod vector environment. PMID:23564167

End-boundary sheath potential, electron and ion energy distribution in the low-pressure non-ambipolar electron plasma

NASA Astrophysics Data System (ADS)

Chen, Lee; Chen, Zhiying; Funk, Merritt

2013-12-01

The end-boundary floating-surface sheath potential, electron and ion energy distribution functions (EEDf, IEDf) in the low-pressure non-ambipolar electron plasma (NEP) are investigated. The NEP is heated by an electron beam extracted from an inductively coupled electron-source plasma (ICP) through a dielectric injector by an accelerator located inside the NEP. This plasma's EEDf has a Maxwellian bulk followed by a broad energy continuum connecting to the most energetic group with energies around the beam energy. The NEP pressure is 1-3 mTorr of N2 and the ICP pressure is 5-15 mTorr of Ar. The accelerator is biased positively from 80 to 600 V and the ICP power range is 200-300 W. The NEP EEDf and IEDf are determined using a retarding field energy analyser. The EEDf and IEDf are measured at various NEP pressures, ICP pressures and powers as a function of accelerator voltage. The accelerator current and sheath potential are also measured. The IEDf reveals mono-energetic ions with adjustable energy and it is proportionally controlled by the sheath potential. The NEP end-boundary floating surface is bombarded by a mono-energetic, space-charge-neutral plasma beam. When the injected energetic electron beam is adequately damped by the NEP, the sheath potential is linearly controlled at almost a 1 : 1 ratio by the accelerator voltage. If the NEP parameters cannot damp the electron beam sufficiently, leaving an excess amount of electron-beam power deposited on the floating surface, the sheath potential will collapse and become unresponsive to the accelerator voltage.

The opposing effects of calmodulin, adenosine 5 prime -triphosphate, and pertussis toxin on phorbol ester induced inhibition of atrial natriuretic factor stimulated guanylate cyclase in SK-NEP-1 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sekiya, M.; Frohlich, E.D.; Cole, F.E.

1991-01-01

In the present study, we investigated the effects of calmodulin, adenosine 5{prime}-triphosphate (ATP) and pertussis toxin (PT) on phorbol ester (PMA) induced inhibition of ANF-stimulated cyclic GMP formation in cells from the human renal cell line, SK-NEP-1. PMA inhibited ANF-stimulated guanylate cyclase activity in particulate membranes by about 65%. Calmodulin reversed this inhibition in a dose dependent manner. ATP potentiated Mg++ but not Mn++ supported guanylate cyclase activity. In PMA treated membranes, ATP potentiating effects were abolished. PMA also inhibited ANF-stimulated cGMP accumulation, but pretreatment with PT prevented this PMA inhibition. PT did not affect basal or ANF-stimulated cGMP accumulation.more » In conclusion, these results demonstrated that PMA inhibited ANF stimulation of particulate guanylate cyclase in opposition to the activating effects of calmodulin or ATP in SK-NEP-1 cells. The protein kinase C inhibitory effects appeared to be mediated via a PT-sensitive G protein.« less

Neprilysin Inhibits Coagulation through Proteolytic Inactivation of Fibrinogen

PubMed Central

Burrell, Matthew; Henderson, Simon J.; Ravnefjord, Anna; Schweikart, Fritz; Fowler, Susan B.; Witt, Susanne; Hansson, Kenny M.; Webster, Carl I.

2016-01-01

Neprilysin (NEP) is an endogenous protease that degrades a wide range of peptides including amyloid beta (Aβ), the main pathological component of Alzheimer’s disease (AD). We have engineered NEP as a potential therapeutic for AD but found in pre-clinical safety testing that this variant increased prothrombin time (PT) and activated partial thromboplastin time (APTT). The objective of the current study was to investigate the effect of wild type NEP and the engineered variant on coagulation and define the mechanism by which this effect is mediated. PT and APTT were measured in cynomolgus monkeys and rats dosed with a human serum albumin fusion with an engineered variant of NEP (HSA-NEPv) as well as in control plasma spiked with wild type or variant enzyme. The coagulation factor targeted by NEP was determined using in vitro prothrombinase, calibrated automated thrombogram (CAT) and fibrin formation assays as well as N-terminal sequencing of fibrinogen treated with the enzyme. We demonstrate that HSA-NEP wild type and HSA-NEPv unexpectedly impaired coagulation, increasing PT and APTT in plasma samples and abolishing fibrin formation from fibrinogen. This effect was mediated through cleavage of the N-termini of the Aα- and Bβ-chains of fibrinogen thereby significantly impairing initiation of fibrin formation by thrombin. Fibrinogen has therefore been identified for the first time as a substrate for NEP wild type suggesting that the enzyme may have a role in regulating fibrin formation. Reductions in NEP levels observed in AD and cerebral amyloid angiopathy may contribute to neurovascular degeneration observed in these conditions. PMID:27437944

Absolute response and noise equivalent power of cyclotron resonance-assisted InSb detectors at submillimeter wavelengths

NASA Technical Reports Server (NTRS)

Brown, E. R.; Wengler, M. J.; Phillips, T. G.

1985-01-01

Spectra are presented of the responsivity and noise equivalent power (NEP) of liquid-helium-cooled InSb detectors as a function of magnetic field in the range 20-110 per cm. The measurements are all made using a Fourier transform spectrometer with thermal sources. The results show a discernable peak in the detector response at the conduction electron cyclotron resonance (CCR) frequency for magnetic fields as low as 3 kG. The magnitude of responsivity at the resonance peaks is roughly constant with magnetic field and is comparable to the low-frequency hot-electron bolometer response. The NEP at the peaks is found to be comparable to the best long wavelength results previously reported. For example, NEP = 4.5 x 10 to the 13th W/(square root of Hz) at 4.2 K, 6 kG, and 40 per cm was measured. The InSb CCR will provide a much improved detector for laboratory spectroscopy, as compared with hot electron bolometers, in the 20-100 per cm range.

Substance P and neutral endopeptidase in development of acute respiratory distress syndrome following fire smoke inhalation.

PubMed

Wong, Simon S; Sun, Nina N; Lantz, R Clark; Witten, Mark L

2004-10-01

To characterize the tachykininergic effects in fire smoke (FS)-induced acute respiratory distress syndrome (ARDS), we designed a series of studies in rats. Initially, 20 min of FS inhalation induced a significant increase of substance P (SP) in bronchoalveolar lavage fluid (BALF) at 1 h and persisted for 24 h after insult. Conversely, FS disrupted 51.4, 55.6, 46.3, and 43.0% enzymatic activity of neutral endopeptidase (NEP, a primary hydrolyzing enzyme for SP) 1, 6, 12, and 24 h after insult, respectively. Immunolabeling density of NEP in the airway epithelium largely disappeared 1 h after insult due to acute cell damage and shedding. These changes were also accompanied by extensive influx of albumin and granulocytes/lymphocytes in BALF. Furthermore, levels of BALF SP and tissue NEP activity dose dependently increased and decreased, respectively, following 0, low (10 min), and high (20 min) levels of FS inhalation. However, neither the time-course nor the dose-response study observed a significant change in the highest affinity neurokinin-1 receptor (NK-1R) for SP. Finally, treatment (10 mg/kg im) with SR-140333B, an NK-1R antagonist, significantly prevented 20-min FS-induced hypoxemia and pulmonary edema 24 h after insult. Further examination indicated that SR-140333B (1.0 or 10.0 mg/kg im) fully abolished early (1 h) plasma extravasation following FS. Collectively, these findings suggest that a combination of sustained SP and NEP inactivity induces an exaggerated neurogenic inflammation mediated by NK-1R, which may lead to an uncontrolled influx of protein-rich edema fluid and cells into the alveoli as a consequence of increased vascular permeability.

Comparison of the spatial distribution of endopeptidase-24.11 with substance P, substance P receptor (NK-1r) and gastric efferent neurons in the dorsal vagal complex of the rat.

PubMed

Ladic, L; Buchan, A

1997-01-24

The spatial location of neutral endopeptidase 24.11 (NEP) immunoreactivity was compared to that of substance P (SP), SP receptor (NK-1r) and identified gastric efferent neurons in the dorsal vagal complex in rat brainstem. The majority of NEP labeling was observed caudal to the obex. Neutral endopeptidase-immunoreactivity was associated with the central canal, ependyma and blood vessels, and surrounded the area postrema. A comparison of the results of immunocytochemical and retrograde tracing experiments demonstrated the absence of co-labeling of neurons or their process with NEP and either substance P or NK-1r. Furthermore, no NEP-immunoreactivity was observed in the vicinity of identified gastric efferents in the dorsal motor nucleus of the vagus. These results would suggest that NEP does not degrade SP in the vicinity of gastric efferent neurons.

Effects of aerosolised substance P on lung resistance in guinea-pigs: a comparison between inhibition of neutral endopeptidase and angiotensin-converting enzyme.

PubMed

Lötvall, J O; Skoogh, B E; Barnes, P J; Chung, K F

1990-05-01

1. We have examined in guinea-pigs, in vivo, the effects of inhibition of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) on the airway response to aerosolised substance P (SP). We aerosolised captopril (4.6 mM, 60 breaths; 210 nmol) to inhibit ACE and acetorphan (0.3, 1 and 3 mM, 60 breaths; 9 nmol, 33 nmol and 110 nmol respectively) to inhibit NEP. We also examined the effect of the highest dose of acetorphan (110 nmol) on the response to aerosolised acetylcholine (ACh). 2. Responsiveness to SP (or ACh) was measured as the change in lung resistance (RL) induced by nebulisation of increasing concentrations of SP (or ACh) before and after treatment with the inhibitor. PC200, defined as the provocative concentration inducing an increase in RL of 200% above baseline was calculated for each challenge. 3. Administration of acetorphan before the second SP-challenge induced a dose-dependent decrease in PC200 for SP amounting to 1.8 (+/- 0.3) log units after treatment with 11 nmol acetorphan. Treatment with vehicle before the second SP-challenge or with 3 mM acetorphan before the second ACh-challenge had no significant effect on PC200. 4. Treatment with captopril (21 nmol) induced only a small, nonsignificant leftward shift of PC200 to SP (0.3 +/- 0.2 log units). 5. We conclude that a NEP-like enzyme, but not ACE, regulates the response to aerosolised SP. We suggest that the same is true for SP released endogenously from sensory nerve endings in the airway epithelial layer.

Effects of aerosolised substance P on lung resistance in guinea-pigs: a comparison between inhibition of neutral endopeptidase and angiotensin-converting enzyme.

PubMed Central

Lötvall, J. O.; Skoogh, B. E.; Barnes, P. J.; Chung, K. F.

1990-01-01

1. We have examined in guinea-pigs, in vivo, the effects of inhibition of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) on the airway response to aerosolised substance P (SP). We aerosolised captopril (4.6 mM, 60 breaths; 210 nmol) to inhibit ACE and acetorphan (0.3, 1 and 3 mM, 60 breaths; 9 nmol, 33 nmol and 110 nmol respectively) to inhibit NEP. We also examined the effect of the highest dose of acetorphan (110 nmol) on the response to aerosolised acetylcholine (ACh). 2. Responsiveness to SP (or ACh) was measured as the change in lung resistance (RL) induced by nebulisation of increasing concentrations of SP (or ACh) before and after treatment with the inhibitor. PC200, defined as the provocative concentration inducing an increase in RL of 200% above baseline was calculated for each challenge. 3. Administration of acetorphan before the second SP-challenge induced a dose-dependent decrease in PC200 for SP amounting to 1.8 (+/- 0.3) log units after treatment with 11 nmol acetorphan. Treatment with vehicle before the second SP-challenge or with 3 mM acetorphan before the second ACh-challenge had no significant effect on PC200. 4. Treatment with captopril (21 nmol) induced only a small, nonsignificant leftward shift of PC200 to SP (0.3 +/- 0.2 log units). 5. We conclude that a NEP-like enzyme, but not ACE, regulates the response to aerosolised SP. We suggest that the same is true for SP released endogenously from sensory nerve endings in the airway epithelial layer. PMID:1695534

Climate controls over ecosystem metabolism: insights from a fifteen-year inductive artificial neural network synthesis for a subalpine forest.

PubMed

Albert, Loren P; Keenan, Trevor F; Burns, Sean P; Huxman, Travis E; Monson, Russell K

2017-05-01

Eddy covariance (EC) datasets have provided insight into climate determinants of net ecosystem productivity (NEP) and evapotranspiration (ET) in natural ecosystems for decades, but most EC studies were published in serial fashion such that one study's result became the following study's hypothesis. This approach reflects the hypothetico-deductive process by focusing on previously derived hypotheses. A synthesis of this type of sequential inference reiterates subjective biases and may amplify past assumptions about the role, and relative importance, of controls over ecosystem metabolism. Long-term EC datasets facilitate an alternative approach to synthesis: the use of inductive data-based analyses to re-examine past deductive studies of the same ecosystem. Here we examined the seasonal climate determinants of NEP and ET by analyzing a 15-year EC time-series from a subalpine forest using an ensemble of Artificial Neural Networks (ANNs) at the half-day (daytime/nighttime) time-step. We extracted relative rankings of climate drivers and driver-response relationships directly from the dataset with minimal a priori assumptions. The ANN analysis revealed temperature variables as primary climate drivers of NEP and daytime ET, when all seasons are considered, consistent with the assembly of past studies. New relations uncovered by the ANN approach include the role of soil moisture in driving daytime NEP during the snowmelt period, the nonlinear response of NEP to temperature across seasons, and the low relevance of summer rainfall for NEP or ET at the same daytime/nighttime time step. These new results offer a more complete perspective of climate-ecosystem interactions at this site than traditional deductive analyses alone.

Progress on Background-Limited Membrane-Isolated TES Bolometers for Far-IR/Submillimeter Spectroscopy

NASA Technical Reports Server (NTRS)

Kenyon, M.; Day, P. K.; Bradford, C. M.; Bock, J. J.; Leduc, H. G.

2006-01-01

To determine the lowest attainable phonon noise equivalent power (NEP) for membrane-isolation bolometers, we fabricated and measured the thermal conductance of suspended Si3N4 beams with different geometries via a noise thermometry technique. We measured beam cross-sectional areas ranging from 0.35 x 0.5 (micro)m(sup 2) to 135 x 1.0 (micro)m(sup 2) and beam lengths ranging from (micro)m to 8300 (micro)m. The measurements directly imply that membrane-isolation bolometers are capable of reaching a phonon noise equivalent power (NEP) of 4 x 10(sup -20)W/Hz(sup 1)/O . This NEP adequate for the Background-Limited Infrared-Submillimeter Spectrograph (BLISS) proposed for the Japanese SPICA observatory, and adequate for NASA's SAFIR observatory, a 10-meter, 4 K telescope to be deployed at L2. Further, we measured the heat capacity of a suspended Si3N4 membrane and show how this result implies that one can make membrane-isolation bolometers with a response time which is fast enough for BLISS.

Aβ-degrading enzymes: potential for treatment of Alzheimer disease.

PubMed

Miners, James Scott; Barua, Neil; Kehoe, Patrick Gavin; Gill, Steven; Love, Seth

2011-11-01

There is increasing evidence that deficient clearance of β-amyloid (Aβ) contributes to its accumulation in late-onset Alzheimer disease (AD). Several Aβ-degrading enzymes, including neprilysin (NEP), insulin-degrading enzyme, and endothelin-converting enzyme reduce Aβ levels and protect against cognitive impairment in mouse models of AD. The activity of several Aβ-degrading enzymes rises with age and increases still further in AD, perhaps as a physiological response to minimize the buildup of Aβ. The age- and disease-related changes in expression of more recently recognized Aβ-degrading enzymes (e.g. NEP-2 and cathepsin B) remain to be investigated, and there is strong evidence that reduced NEP activity contributes to the development of cerebral amyloid angiopathy. Regardless of the role of Aβ-degrading enzymes in the development of AD, experimental data indicate that increasing the activity of these enzymes (NEP in particular) has therapeutic potential in AD, although targeting their delivery to the brain remains a major challenge. The most promising current approaches include the peripheral administration of agents that enhance the activity of Aβ-degrading enzymes and the direct intracerebral delivery of NEP by convection-enhanced delivery. In the longer term, genetic approaches to increasing the intracerebral expression of NEP or other Aβ-degrading enzymes may offer advantages.

Climate variability and management impacts on carbon uptake in a temperate pine forest in Eastern Canada using flux data from 2003 to 2013

NASA Astrophysics Data System (ADS)

Arain, M. A.; Brodeur, J. J.; Thorne, R.; Peichl, M.; Huang, S.; Khomik, M.

2014-12-01

Temperate forests play an important role in global carbon cycle. In this study, we evaluate the impacts of climate variability and management regime on carbon uptake in a 75-year old temperate pine (Pinus strobus L.) forest, near Lake Erie in southern Ontario, Canada using eleven years (2003 to 2013) of eddy covariance flux data. These fluxes are compared with similar measurements made in an 80-year-old deciduous (Carolinian) forest, established in 2012. Both forests are managed stands and part of the Turkey Point Flux Station and global Fluxnet. Mean net ecosystem productivity, NEP, in the conifer stand is 145 (range 35 to 277) g C m2 y-1 over the 2003 to 2013 period, while mean NEP in the deciduous stand is 271 (226 and 317) g C m2 y-1 from 2012 to 2013. The study period experienced four distinct extreme weather patterns: warm and dry springs in 2005 and 2012, extremely wet and warm summer in 2006, a summer drought in 2007 and warm summers in 2010 and 2012. In February-March 2012, the conifer stand was selectively thinned and approximately 30% of trees were removed to improve light and water availability and stimulate growth of remaining trees. Thinning reduced NEP in the first post-thinning year, with mean annual NEP of 48 g C m2 y-1 in 2012. Increased supply of dead organic matter and warm temperatures in 2012 increased ecosystem respiration much more than photosynthesis, resulting in lower annual NEP. Heat stress and drought in spring of 2005 reduced NEP of the conifer stand to 35 g C m2 y-1. The impact of this extreme weather event on NEP was similar to that observed in 2012 when the stand experienced a drastic structural change, a dry spring and warm temperatures throughout the growing season. Observed fluxes from this forest and other Fluxnet sites were used to develop and validate a C and N coupled dynamic vegetation model, CLASS-CTEM-N that was applied to simulate terrestrial ecosystem's carbon, water and energy budgets at 0.5 x 0.5 degree spatial resolution across the globe from 1901 to 2010 as part of North American Carbon Program (NACP) site-level and model intercomparison initiatives. The inclusion of the N processes in CLASS-CTEM model has improved model response to changing climate and atmospheric CO2 concentration levels.

Substance P-induced bronchoconstriction in the guinea pig. Enhancement by inhibitors of neutral metalloendopeptidase and angiotensin-converting enzyme.

PubMed

Shore, S A; Stimler-Gerard, N P; Coats, S R; Drazen, J M

1988-02-01

We tested the effects of the neutral metalloendopeptidase (NEP) inhibitor, thiorphan (0.17, 0.5, and 1.7 mg i.v), and the angiotensin-converting enzyme (ACE) inhibitor, captopril (0.5, 1.7, and 5.0 mg i.v.), on the bronchoconstrictor response to rapid intravenous infusions of substance P (0.1 to 30 nmol/kg) in anesthetized, mechanically ventilated guinea pigs. The decreases in pulmonary conductance and dynamic compliance caused by substance P were greater in animals treated with either thiorphan or captopril than in control animals. Thiorphan (0.5 mg) had no effect on airway responsiveness to intravenously administered methacholine, whereas captopril (1.7 mg) caused a small increase in methacholine responsiveness. Both drugs significantly increased the recovery of immunoreactive substance P in arterial plasma after exogenous administration of the peptide. We conclude that degradation of substance P by both NEP and ACE is important for determining the magnitude of the bronchoconstriction caused by intravenous administration of this neuropeptide. These data suggest that conditions associated with diminished peptidase activity could result in enhanced responses to stimuli which cause the release of endogenous substance P.

Production of soluble Neprilysin by endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuruppu, Sanjaya, E-mail: Sanjaya.Kuruppu@monash.edu; Rajapakse, Niwanthi W.; Minond, Dmitriy

Highlights: • A soluble full-length form of Neprilysin exists in media of endothelial cells. • Exosomal release is the key mechanism for the production of soluble Neprilysin. • Inhibition of ADAM-17 by specific inhibitors reduce Neprilysin release. • Exosome mediated release of Neprilysin is dependent on ADAM-17 activity. - Abstract: A non-membrane bound form of Neprilysin (NEP) with catalytic activity has the potential to cleave substrates throughout the circulation, thus leading to systemic effects of NEP. We used the endothelial cell line Ea.hy926 to identify the possible role of exosomes and A Disintegrin and Metalloprotease 17 (ADAM-17) in the productionmore » of non-membrane bound NEP. Using a bradykinin based quenched fluorescent substrate (40 μM) assay, we determined the activity of recombinant human NEP (rhNEP; 12 ng), and NEP in the media of endothelial cells (10% v/v; after 24 h incubation with cells) to be 9.35 ± 0.70 and 6.54 ± 0.41 μmols of substrate cleaved over 3 h, respectively. The presence of NEP in the media was also confirmed by Western blotting. At present there are no commercially available inhibitors specific for ADAM-17. We therefore synthesised two inhibitors TPI2155-14 and TPI2155-17, specific for ADAM-17 with IC{sub 50} values of 5.36 and 4.32 μM, respectively. Treatment of cells with TPI2155-14 (15 μM) and TPI2155-17 (4.3 μM) resulted in a significant decrease in NEP activity in media (62.37 ± 1.43 and 38.30 ± 4.70, respectively as a % of control; P < 0.0001), implicating a possible role for ADAM-17 in NEP release. However, centrifuging media (100,000g for 1 h at 4 °C) removed all NEP activity from the supernatant indicating the likely role of exosomes in the release of NEP. Our data therefore indicated for the first time that NEP is released from endothelial cells via exosomes, and that this process is dependent on ADAM-17.« less

NEP technology: FY 1992 milestones (NASA LeRC)

NASA Technical Reports Server (NTRS)

Sovey, Jim

1993-01-01

A discussion of Nuclear Electric Propulsion (NEP) thrusters and facilities is presented in vugraph form. The NEP thrusters are discussed in the context of the following three items: (1) establishing a 100 H test capability for 100-kW magnetoplasmadynamic (MPD) thrusters; (2) demonstrating a lightweight 20-kW krypton ion thruster; and (3) the optimization of the design of low-mass power processor transformers. The primary accomplishment at NEP facilities was the completion of the Electric Propulsion Laboratory's (EPL's) tank 5 cryopump upgrade.

Historical and projected carbon balance of mature black spruce ecosystems across north america: The role of carbon-nitrogen interactions

USGS Publications Warehouse

Clein, Joy S.; McGuire, A.D.; Zhang, X.; Kicklighter, D.W.; Melillo, J.M.; Wofsy, S.C.; Jarvis, P.G.; Massheder, J.M.

2002-01-01

The role of carbon (C) and nitrogen (N) interactions on sequestration of atmospheric CO2 in black spruce ecosystems across North America was evaluated with the Terrestrial Ecosystem Model (TEM) by applying parameterizations of the model in which C-N dynamics were either coupled or uncoupled. First, the performance of the parameterizations, which were developed for the dynamics of black spruce ecosystems at the Bonanza Creek Long-Term Ecological Research site in Alaska, were evaluated by simulating C dynamics at eddy correlation tower sites in the Boreal Ecosystem Atmosphere Study (BOREAS) for black spruce ecosystems in the northern study area (northern site) and the southern study area (southern site) with local climate data. We compared simulated monthly growing season (May to September) estimates of gross primary production (GPP), total ecosystem respiration (RESP), and net ecosystem production (NEP) from 1994 to 1997 to available field-based estimates at both sites. At the northern site, monthly growing season estimates of GPP and RESP for the coupled and uncoupled simulations were highly correlated with the field-based estimates (coupled: R2= 0.77, 0.88 for GPP and RESP; uncoupled: R2 = 0.67, 0.92 for GPP and RESP). Although the simulated seasonal pattern of NEP generally matched the field-based data, the correlations between field-based and simulated monthly growing season NEP were lower (R2 = 0.40, 0.00 for coupled and uncoupled simulations, respectively) in comparison to the correlations between field-based and simulated GPP and RESP. The annual NEP simulated by the coupled parameterization fell within the uncertainty of field-based estimates in two of three years. On the other hand, annual NEP simulated by the uncoupled parameterization only fell within the field-based uncertainty in one of three years. At the southern site, simulated NEP generally matched field-based NEP estimates, and the correlation between monthly growing season field-based and simulated NEP (R2 = 0.36, 0.20 for coupled and uncoupled simulations, respectively) was similar to the correlations at the northern site. To evaluate the role of N dynamics in C balance of black spruce ecosystems across North America, we simulated historical and projected C dynamics from 1900 to 2100 with a global-based climatology at 0.5?? resolution (latitude ?? longitude) with both the coupled and uncoupled parameterizations of TEM. From analyses at the northern site, several consistent patterns emerge. There was greater inter-annual variability in net primary production (NPP) simulated by the uncoupled parameterization as compared to the coupled parameterization, which led to substantial differences in inter-annual variability in NEP between the parameterizations. The divergence between NPP and heterotrophic respiration was greater in the uncoupled simulation, resulting in more C sequestration during the projected period. These responses were the result of fundamentally different responses of the coupled and uncoupled parameterizations to changes in CO2 and climate. Across North American black spruce ecosystems, the range of simulated decadal changes in C storage was substantially greater for the uncoupled parameterization than for the coupled parameterization. Analysis of the spatial variability in decadal responses of C dynamics revealed that C fluxes simulated by the coupled and uncoupled parameterizations have different sensitivities to climate and that the climate sensitivities of the fluxes change over the temporal scope of the simulations. The results of this study suggest that uncertainties can be reduced through (1) factorial studies focused on elucidating the role of C and N interactions in the response of mature black spruce ecosystems to manipulations of atmospheric CO2 and climate, (2) establishment of a network of continuous, long-term measurements of C dynamics across the range of mature black spruce ecosystems in North America, and (3) ancillary measureme

Nogo-66 Receptor Antagonist Peptide (NEP1-40) Administration Promotes Functional Recovery and Axonal Growth After Lateral Funiculus Injury in the Adult Rat

PubMed Central

Cao, Y.; Shumsky, J. S.; Sabol, M. A.; Kushner, R. A.; Strittmatter, S.; Hamers, F. P. T.; Lee, D. H. S.; Rabacchi, S. A.; Murray, M.

2010-01-01

Objective The myelin protein Nogo inhibits axon regeneration by binding to its receptor (NgR) on axons. Intrathecal delivery of an NgR antagonist (NEP1-40) promotes growth of injured corticospinal axons and recovery of motor function following a dorsal hemisection. The authors used a similar design to examine recovery and repair after a lesion that interrupts the rubrospinal tract (RST). Methods Rats received a lateral funiculotomy at C4 and NEP1-40 or vehicle was delivered to the cervical spinal cord for 4 weeks. Outcome measures included motor and sensory tests and immunohistochemistry. Results Gait analysis showed recovery in the NEP1-40-treated group compared to operated controls, and a test of forelimb usage also showed a beneficial effect. The density of labeled RST axons increased ipsilaterally in the NEP1-40 group in the lateral funiculus rostral to the lesion and contralaterally in both gray and white matter. Thus, rubrospinal axons exhibited diminished dieback and/or growth up to the lesion site. This was accompanied by greater density of 5 HT and calcitonin gene-related peptide axons adjacent to and into the lesion/matrix site in the NEP1-40 group. Conclusions NgR blockade after RST injury is associated with axonal growth and/or diminished dieback of severed RST axons up to but not into or beyond the lesion/matrix site, and growth of serotonergic and dorsal root axons adjacent to and into the lesion/matrix site. NgR blockade also supported partial recovery of function. The authors’ results indicate that severed rubrospinal axons respond to NEP1-40 treatment but less robustly than corticospinal, raphe-spinal, or dorsal root axons. PMID:18056009

APP intracellular domain derived from amyloidogenic β- and γ-secretase cleavage regulates neprilysin expression

PubMed Central

Grimm, Marcus O. W.; Mett, Janine; Stahlmann, Christoph P.; Grösgen, Sven; Haupenthal, Viola J.; Blümel, Tamara; Hundsdörfer, Benjamin; Zimmer, Valerie C.; Mylonas, Nadine T.; Tanila, Heikki; Müller, Ulrike; Grimm, Heike S.; Hartmann, Tobias

2015-01-01

Alzheimer's disease (AD) is characterized by an accumulation of Amyloid-β (Aβ), released by sequential proteolytic processing of the amyloid precursor protein (APP) by β - and γ-secretase. Aβ peptides can aggregate, leading to toxic Aβ oligomers and amyloid plaque formation. Aβ accumulation is not only dependent on de novo synthesis but also on Aβ degradation. Neprilysin (NEP) is one of the major enzymes involved in Aβ degradation. Here we investigate the molecular mechanism of NEP regulation, which is up to now controversially discussed to be affected by APP processing itself. We found that NEP expression is highly dependent on the APP intracellular domain (AICD), released by APP processing. Mouse embryonic fibroblasts devoid of APP processing, either by the lack of the catalytically active subunit of the γ-secretase complex [presenilin (PS) 1/2] or by the lack of APP and the APP-like protein 2 (APLP2), showed a decreased NEP expression, activity and protein level. Similar results were obtained by utilizing cells lacking a functional AICD domain (APPΔCT15) or expressing mutations in the genes encoding for PS1. AICD supplementation or retransfection with an AICD encoding plasmid could rescue the down-regulation of NEP further strengthening the link between AICD and transcriptional NEP regulation, in which Fe65 acts as an important adaptor protein. Especially AICD generated by the amyloidogenic pathway seems to be more involved in the regulation of NEP expression. In line, analysis of NEP gene expression in vivo in six transgenic AD mouse models (APP and APLP2 single knock-outs, APP/APLP2 double knock-out, APP-swedish, APP-swedish/PS1Δexon9, and APPΔCT15) confirmed the results obtained in cell culture. In summary, in the present study we clearly demonstrate an AICD-dependent regulation of the Aβ-degrading enzyme NEP in vitro and in vivo and elucidate the underlying mechanisms that might be beneficial to develop new therapeutic strategies for the treatment of AD. PMID:26074811

The Legacy of Invasive Species on Ecosystem Carbon Dynamics in a Restored Tallgrass Prairie

NASA Astrophysics Data System (ADS)

Matamala, R.; Graham, S.; Cook, D.; Gonzalez-Meler, M.

2008-12-01

Restoration of degraded grassland and prairie ecosystems represents a target sink for offsetting rising atmospheric CO2 levels by increasing carbon sequestration in C-depleted soils, as two-thirds of the biomass is allocated belowground. When considering controls on ecosystem C cycling, biodiversity-led productivity has the potential to be a strong biotic influence. However, invasive species can disrupt ecosystem processes by exhibiting functional characteristics which are distinct from their native counterparts. Invasibility has been linked to disturbance history, which might lead to additional vulnerability of managed lands. The restoration of tallgrass prairie at Fermilab, Batavia, IL, is a known C sink, accruing soil organic matter at rates 43 g C m-2 y-1 during the past 20 years. This rate integrates environmental, climatic and vegetation variations that occurred over this period. Typically, the tallgrass prairie is dominated by warm season grasses and forbs with sporadic but recurrent years when invasive species increase productivity. We measured net ecosystem exchange, net ecosystem production (NEP) and soil C at a 19- year-old restored tallgrass prairie in a four year study where plant species dominance varied. In the first year, the prairie restoration was a strong C sink with a NEP 438 g C m-2 despite a pronounced spring drought. During the second year, dominance of the invasive biannual Melilotus alba L., led to a shorter growing season that resulted on a 47% reduction in NEP from the previous year. NEP did not recover in the third year, even when M. alba was present but not dominant and a number of prairie species re-emerged, showing the legacy of the previous year disturbance. At this time soil C for all years and a fourth NEP year is being analyzed. These data suggest that biotic factors can exert large memory effects on NEP and possibly influence the sink capacity of restored ecosystems. Management strategies should aim to control biotic limitations to NEP in order to maximize long term C sequestration of restorations.

Impacts of droughts on carbon sequestration by China's terrestrial ecosystems from 2000 to 2011

NASA Astrophysics Data System (ADS)

Liu, Y. B.; Zhou, Y. L.; Ju, W. M.; Wang, S. Q.; Wu, X. C.; He, M. Z.

2013-11-01

In recent years, droughts have frequently hit China's terrestrial ecosystems. How these droughts affected carbon sequestration by China's terrestrial ecosystems is still unclear. In this study, the process-based Boreal Ecosystem Productivity Simulator (BEPS) model, driven by remotely sensed vegetation parameters, was employed to assess the effects of droughts on net ecosystem productivity (NEP) of terrestrial ecosystems in China for the period from 2000 to 2011. Different categories of droughts, as indicated by a standard precipitation index (SPI), extensively hit terrestrial ecosystems in China, particularly in 2001, 2006, 2009 and 2011. The national total NEP exhibited a slight decline of -11.3 Tg C yr-2 during the study period, mainly due to large reductions of NEP in typical drought-hit years 2001, 2006, 2009 and 2011, ranging from 61.1 Tg C yr-1 to 168.8 Tg C yr-1. National and regional total NEP anomalies were correlated with corresponding annual mean SPI, especially in Northwest China, North China, Central China, and Southwest China. In drought years, the reductions of NEP might be caused by a larger decrease in gross primary productivity (GPP) than in respiration (RE) (2001 and 2011), a decrease in GPP and an increase in RE (2009), or a larger increase in RE than in GPP (2006). Droughts had lagged effects of up to 3-6 months on NEP due to different reactions of GPP and RE to droughts. In east humid and warm parts of China, droughts have predominant and short-term lagged influences on NEP. In western cold and arid regions, the effects of droughts on NEP were relatively weaker and might last for a longer period of time.

Neutral endopeptidase (EC 3.4.24.11) terminates colitis by degrading substance P.

PubMed

Sturiale, S; Barbara, G; Qiu, B; Figini, M; Geppetti, P; Gerard, N; Gerard, C; Grady, E F; Bunnett, N W; Collins, S M

1999-09-28

Neurogenic inflammation is regulated by sensory nerves and characterized by extravasation of plasma proteins and infiltration of neutrophils from post-capillary venules and arteriolar vasodilatation. Although it is well established that substance P (SP) interacts with the neurokinin 1 receptor (NK1R) to initiate neurogenic inflammation, the mechanisms that terminate inflammation are unknown. We examined whether neutral endopeptidase (NEP), a cell-surface enzyme that degrades SP in the extracellular fluid, terminates neurogenic inflammation in the colon. In NEP knockout mice, the SP concentration in the colon was approximately 2.5-fold higher than in wild-type mice, suggesting increased bioavailability of SP. The extravasation of Evans blue-labeled plasma proteins in the colon of knockout mice under basal conditions was approximately 4-fold higher than in wild-type mice. This elevated plasma leak was attenuated by recombinant NEP or the NK1R antagonist SR140333, and is thus caused by diminished degradation of SP. To determine whether deletion of NEP predisposes mice to uncontrolled inflammation, we compared dinitrobenzene sulfonic acid-induced colitis in wild-type and knockout mice. The severity of colitis, determined by macroscopic and histologic scoring and by myeloperoxidase activity, was markedly worse in knockout than wild-type mice after 3 and 7 days. The exacerbated inflammation in knockout mice was prevented by recombinant NEP and SR140333. Thus, NEP maintains low levels of SP in the extracellular fluid under basal conditions and terminates its proinflammatory effects. Because we have previously shown that intestinal inflammation results in down-regulation of NEP and diminished degradation of SP, our present results suggest that defects in NEP expression contribute to uncontrolled inflammation.

Neutral endopeptidase (EC 3.4.24.11) terminates colitis by degrading substance P

PubMed Central

Sturiale, S.; Barbara, G.; Qiu, B.; Figini, M.; Geppetti, P.; Gerard, N.; Gerard, C.; Grady, E. F.; Bunnett, N. W.; Collins, S. M.

1999-01-01

Neurogenic inflammation is regulated by sensory nerves and characterized by extravasation of plasma proteins and infiltration of neutrophils from post-capillary venules and arteriolar vasodilatation. Although it is well established that substance P (SP) interacts with the neurokinin 1 receptor (NK1R) to initiate neurogenic inflammation, the mechanisms that terminate inflammation are unknown. We examined whether neutral endopeptidase (NEP), a cell-surface enzyme that degrades SP in the extracellular fluid, terminates neurogenic inflammation in the colon. In NEP knockout mice, the SP concentration in the colon was ≈2.5-fold higher than in wild-type mice, suggesting increased bioavailability of SP. The extravasation of Evans blue-labeled plasma proteins in the colon of knockout mice under basal conditions was ≈4-fold higher than in wild-type mice. This elevated plasma leak was attenuated by recombinant NEP or the NK1R antagonist SR140333, and is thus caused by diminished degradation of SP. To determine whether deletion of NEP predisposes mice to uncontrolled inflammation, we compared dinitrobenzene sulfonic acid-induced colitis in wild-type and knockout mice. The severity of colitis, determined by macroscopic and histologic scoring and by myeloperoxidase activity, was markedly worse in knockout than wild-type mice after 3 and 7 days. The exacerbated inflammation in knockout mice was prevented by recombinant NEP and SR140333. Thus, NEP maintains low levels of SP in the extracellular fluid under basal conditions and terminates its proinflammatory effects. Because we have previously shown that intestinal inflammation results in down-regulation of NEP and diminished degradation of SP, our present results suggest that defects in NEP expression contribute to uncontrolled inflammation. PMID:10500232

What have we learned from global change manipulative experiments in China? A meta-analysis

PubMed Central

Fu, Zheng; Niu, Shuli; Dukes, Jeffrey S.

2015-01-01

Although China has the largest population in the world, a faster rate of warming than the global average, and an active global change research program, results from many of the global change experiments in Chinese terrestrial ecosystems have not been included in global syntheses. Here, we specifically analyze the observed responses of carbon (C) and nitrogen (N) cycling in global change manipulative experiments in China, and compare these responses to those from other regions of the world. Most global change factors, vegetation types, and treatment methods that have been studied or used elsewhere in the world have also been studied and applied in China. The responses of terrestrial ecosystem C and N cycles to N addition and climate warming in China are similar in both direction and intensity to those reported in global syntheses. In Chinese ecosystems as elsewhere, N addition significantly increased aboveground (AGB) and belowground biomass (BGB), litter mass, dissolved organic C, net ecosystem productivity (NEP), and gross ecosystem productivity (GEP). Warming stimulated AGB, BGB and the root-shoot ratio. Increasing precipitation accelerated GEP, NEP, microbial respiration, soil respiration, and ecosystem respiration. Our findings complement and support previous global syntheses and provide insight into regional responses to global change. PMID:26205333

Protection of ischemic preconditioning on renal neural function in rats with acute renal failure.

PubMed

Wu, Ming-Shiou; Chien, Chiang-Ting; Ma, Ming-Chieh; Chen, Chau-Fong

2009-11-30

We tested whether tolerance induced by ischemic preconditioning (IPC) in kidneys was related to renal nerves. Experimental acute renal failure (ARF) in a rat model was induced for 45 min of left renal arterial occlusion (RAO), followed by 6 or 24 h of reperfusion (ischemic reperfusion (I/R) group). The episode of IPC was four cycles of 4 min of RAO at 11 min intervals and then the I/R injury was treated as above (IPC-I/R group). After 6 h of reperfusion, polyuria was found in the I/R group associated with an enhancement of afferent renal nerve activity (ARNA) and a reflexive decrease in efferent renal nerve activity (ERNA). Changes in nerve responses were related with a reduction in neutral endopeptidase (NEP) activity and an increased release of substance P (SP). After 24 h of reperfusion, the I/R group showed oliguria which was associated with a lower ARNA, hyperactivity of ERNA and a nine-fold increase in SP release due to a further 52% loss in NEP activity. Prior IPC treatment did not affect the changed ischemia-induced excretory and nervous activity patterns during the first 6 h of reperfusion, but normalized both responses in the kidneys 24 h after ischemia. The IPC-mediated protection in oliguric ARF was related to the preservation of NEP activity to only 25% loss that caused an increase of SP amounts of only three-fold and a minor change in neurokinin 1 receptor (NK-1R) activities. Finally, both excretory and sensory responses in oliguric ARF after saline loading were significantly ameliorated by IPC. We conclude that IPC results in preservation of the renal sensory response in postischemic kidneys and has a beneficial effect on controlling efferent renal sympathetic nerve activity and excretion of solutes and water.

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP).

PubMed

Rowe, P S; Oudet, C L; Francis, F; Sinding, C; Pannetier, S; Econs, M J; Strom, T M; Meitinger, T; Garabedian, M; David, A; Macher, M A; Questiaux, E; Popowska, E; Pronicka, E; Read, A P; Mokrzycki, A; Glorieux, F H; Drezner, M K; Hanauer, A; Lehrach, H; Goulding, J N; O'Riordan, J L

1997-04-01

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.

Degradative enzymes modulate airway responses to intravenous neurokinins A and B.

PubMed

Shore, S A; Drazen, J M

1989-12-01

We studied the effects of the neutral endopeptidase (NEP) inhibitor thiorphan (1.7 mg/kg iv) and the angiotensin-converting enzyme (ACE) inhibitor captopril (5.7 mg/kg iv) on airway responses to rapid intravenous infusions of neurokinin A (NKA) and neurokinin B (NKB) in anesthetized, mechanically ventilated guinea pigs. The dose of NKA required to decrease pulmonary conductance to 50% of its base-line value (ED50GL) was fivefold less (P less than 0.0001) in animals treated with thiorphan compared with controls. NKA1-8, a product resulting from cleavage of NKA by NEP, had no bronchoconstrictor activity. Similar results were obtained by using NKB as the bronchoconstricting agent. Captopril had no significant effect on airway responses to NKA or NKB. In contrast, both thiorphan and captopril decrease the ED50GL for substance P (SP). We also compared the relative bronchoconstrictor potency of NKA, NKB, and SP. In control animals, the rank order of ED50GL values was NKA much less than NKB = SP. NKA also caused a more prolonged bronchoconstriction than SP or NKB. Thiorphan had no effect on the rank order of bronchoconstrictor potency, but in animals treated with captopril, the rank order of ED50GL values was altered to NKA less than SP less than NKB. These results suggest that degradation of NKA and NKB by NEP but not by ACE is an important determinant of the bronchoconstriction induced by these peptides. The degradation by ACE of SP but not NKA or NKB influences the observed relative potency of the three tachykinins as bronchoactive agents.

Omapatrilat, a dual angiotensin-converting enzyme and neutral endopeptidase inhibitor, prevents fatty streak deposit in apolipoprotein E-deficient mice.

PubMed

Arnal, J F; Castano, C; Maupas, E; Mugniot, A; Darblade, B; Gourdy, P; Michel, J B; Bayard, F

2001-04-01

Angiotensin-converting enzyme (ACE) is mainly responsible for converting angiotensin I (AI) to angiotensin II (AII), and ACE inhibitors prevent atherosclerosis in animal models. Neutral endopeptidase 24.11 (NEP) degrades substance P, kinins and atrial natriuretic peptide (ANP), and aortic wall NEP activity was found to be increased in atherosclerosis. In the present study, we have evaluated the effect of candoxatril, a NEP inhibitor, and of omapatrilat, a dual ACE and NEP inhibitor, on the development of fatty streak in apolipoprotein E (apoE)-deficient mice. Groups of ten male apoE-deficient mice were given either placebo, candoxatril 50 mg/kg per day, or omapatrilat 10, or 100 mg/kg per day for 4 months. None of the treatments influenced body weight, serum total or HDL-cholesterol. Compared with the placebo, candoxatril did not protect the mice from fatty streak deposit. In contrast, omapatrilat dose dependently inhibited the constitution of fatty streak in apoE-deficient mice. The precise advantages of the dual ACE and NEP inhibition versus the inhibition of only ACE should now be considered in the prevention of atherosclerosis as well as in the occurrence of its complications.

New aspects in acne inflammation.

PubMed

Toyoda, Masahiko; Morohashi, Masaaki

2003-01-01

There is ample clinical evidence suggesting that the nervous system such as emotional stress can influence the course of acne. We examined possible participation of cutaneous neurogenic factors including neuropeptides, neuropeptide-degrading enzymes and neurotrophic factors, in association with inflammation in the pathogenesis of acne. Immunohistochemical studies revealed that substance P (SP)-immunoreactive nerve fibers were in close apposition to the sebaceous glands, and that neutral endopeptidase (NEP) was expressed in the germinative cells of the sebaceous glands in the skin from acne patients. Nerve growth factor showed immunoreactivity only within the germinative cells. In addition, an increase in the number of mast cells and a strong expression of endothelial leukocyte adhesion molecule-1 on the postcapillary venules were observed in adjacent areas to the sebaceous glands. In vitro, the levels and the expression of stem cell factor by fibroblasts were upregulated by SP. When organ-cultured normal skin specimens were exposed to SP, we observed significant increases in the sizes of the sebaceous glands and in the number of sebum vacuoles in sebaceous cells. Furthermore, supplementation of SP to organ-cultured skin induced expression of NEP, and we demonstrated the subcellular localization of NEP in the endoplasmic reticulum and the Golgi apparatus within the sebaceous germinative cells using preembedding immunoelectron microscopy. These findings suggest that SP may stimulate lipogenesis of the sebaceous glands which may be followed by proliferation of Propionibacterium acnes, and may yield a potent influence on the sebaceous glands by provocation of inflammatory reactions via mast cells. Thus, cutaneous neurogenic factors should contribute to onset and/or exacerbation of acne inflammation. Copyright 2003 S. Karger AG, Basel

Impacts of Land Use Change on Net Ecosystem Production in China's Taihu Lake Basin in 1985-2010

NASA Astrophysics Data System (ADS)

Xu, X.; Yang, G.

2017-12-01

Land use change play a major role in determining sources and sinks of carbon at regional and global scales. This study employs a modified BIOME-BGC model to examine the changes in the spatio-temporal pattern of net ecosystem production (NEP) in China's Taihu Lake Basin in 1985-2010 and the extent to which land use change impacted NEP. The BIOME-BGC model was calibrated with observed NEP at three open-path eddy covariance flux sites for three dominant land-use types in the Basin including cropland, evergreen needleleaf forest, and mixed forest. Land use data were interpreted from Landsat TM images in 1985, 2000, 2005 and 2010 at the scale of 1:100,000 based on a decision tree method. Two simulations are conducted to distinguish the net effects of land use change and increasing atmospheric concentrations of CO2 and nitrogen deposition on NEP. S1 deals with the actual outcomes of NEP under the interactions between land use change and increasing atmospheric concentration of CO2 and N deposition. S2 assumes that atmospheric CO2 concentration and N deposition remain unchanged at their 1985 levels: 338.32 ppm and 0.0005 kg m-2, respectively. The study estimates that NEP in the Basin showed an overall downward trend, decreasing by 9.8% (1.57 TgC) and 3.21 TgC (or 20.9%) from 1985 to 2010 under situation S1 and S2, respectively. The NEP distribution exhibits an apparent spatial heterogeneity at the municipal level. Land use changesin 1985-2010 reduced the regional NEP (3.21 Tg C in year 2010) by 19.9% compared to its 1985 level, while the increasing atmospheric CO2 concentrations and nitrogen deposition compensated for a half of the total carbon loss. Critical measures for regulating rapid urban expansion and population growth and reinforcing environment protection programs are recommended to increase the regional carbon sink.

Substance P is a determinant of lethality in diet-induced hemorrhagic pancreatitis in mice.

PubMed

Maa, J; Grady, E F; Yoshimi, S K; Drasin, T E; Kim, E H; Hutter, M M; Bunnett, N W; Kirkwood, K S

2000-08-01

The neuropeptide substance P (SP) induces plasma extravasation and neutrophil infiltration by activating the neurokinin 1-receptor (NK1-R). SP-induced neurogenic inflammation is terminated by the cell surface enzyme neutral endopeptidase (NEP), which degrades SP. We determined whether genetic deletion of the NK1-R reduces mortality and, conversely, whether genetic deletion of NEP increases mortality in a lethal model of hemorrhagic pancreatitis. Necrotizing pancreatitis was induced by feeding mice a diet deficient in choline and supplemented with ethionine. We determined the length of survival, the severity of pancreatitis (by measuring the neutrophil enzyme myeloperoxidase [MPO] and by histologic evaluation), and the severity of pancreatitis-associated lung injury (lung MPO and histology) in NK1-R (+/+)/(-/-) and NEP (+/+)/(-/-) mice. Genetic deletion of the NK1-R significantly improved survival (100% vs 8% at 120 hours, P <.001) and reduced pancreatic MPO and acinar cell necrosis. Conversely, genetic deletion of NEP significantly worsened survival (0% vs 90% at 120 hours, P <.001) and exacerbated pancreatic MPO and pancreatitis-associated lung injury. Substance P is an important determinant of lethality in this model of necrotizing pancreatitis. Defects in NEP expression could lead to uncontrolled inflammation.

Sulfuric acid induces airway hyperresponsiveness to substance P in the guinea pig.

PubMed

Stengel, P W; Bendele, A M; Cockerham, S L; Silbaugh, S A

1993-01-01

We investigated whether sulfuric acid inhalation would cause hyperresponsiveness to substance P. Guinea pigs became dyspneic during a 1 h sulfuric acid exposure, but recovered by 24 h when they were challenged with substance P or histamine aerosols. Eight minutes after the start of challenge, animals were killed and excised lung gas volumes measured. Sulfuric acid slightly increased histamine responsiveness compared to controls. However, sulfuric acid caused a much more pronounced leftward shift in the dose response to substance P. Coadministration of the neutral endopeptidase (NEP) inhibitor, thiorphan, did not reduce sulfuric acid-related hyperresponsiveness to substance P. By 72 h, sensitization to substance P was absent. Histological evaluation of sulfuric acid-treated lungs revealed mild alveolitis at 24 h, but not at 72 h. We conclude that sulfuric acid produces a marked sensitization to substance P. Inactivation of NEP does not appear to account for this effect.

Peptidase modulation of the pulmonary effects of tachykinins.

PubMed

Martins, M A; Shore, S A; Drazen, J M

1991-01-01

The physiological effects of the tachykinin peptides substance P (SP) and neurokinin A (NKA) are limited by their microenvironmental degradation. We used the isolated tracheally superfused guinea pig lung to examine the importance of various degradative enzymes in limiting the physiological effects of exogenously administered and endogenously released tachykinins. When SP and NKA are administered via the airway epithelium, neutral endopeptidase (NEP; EC 3.4.24.11) is the major degradative enzyme as indicated by the effects of NEP inhibitors alone compared to the effects of a NEP inhibitor along with a cocktail of other peptidase inhibitors. The effects of enzyme inhibitors on physiological responses is mirrored in the amounts of peptide recovered from lung perfusates as determined using an enzyme-linked immunosorbent assay. We found similar effects when SP and NKA were released endogenously by the acute infusion of capsaicin. These data indicate that NEP is the predominant degradative enzyme modulating the effects of SP and NKA administered via the airways.

Pacific Northwest Regional and Ecozone-scale Carbon Cycle Responses to 25 Years of Variation in Climate and Disturbance

NASA Astrophysics Data System (ADS)

Turner, D. P.; Ritts, W. D.; Kennedy, R. E.; Gray, A. N.; Yang, Z.

2015-12-01

Spatial variation in climate, soils, disturbance regime, and forest management - as well as temporal variation in weather - all influence terrestrial carbon sources and sinks. Spatially-distributed, process-based, carbon cycle simulation models provide a means to integrate information from these various influences to estimate carbon pools and flux over large domains. Here we apply the Biome-BGC model over the 4 state (OR, WA, ID, Western MT) Northwest U.S. region for the interval from 1986-2010. Landsat data was used to characterize disturbances and revealed that the overall disturbance rate on forest land across the region was 0.8 % yr-1, with 49 % as harvests, 28 % as fire, and 23 % as pest/pathogen. A large proportion of the harvested area was on private forestland (62 %) and a large proportion of total burned area was on public forestland (89 %). Net ecosystem production (NEP) for the 2006-2010 interval on forestland was predominantly positive (a carbon sink) throughout the region, with maximum values in the Coast Range, intermediate values in the Cascade Mountains, and relatively low values in the Inland Rocky Mountain ecoregions. Croplands throughout the region had consistently high NEP. Localized negative NEPs were mostly associated with recent disturbances. There was large interannual variation in regional NEP, with notably low values across the region in 2003. In all ecoregions there was a downward trend in NEP over the 25 year study period. The net ecosystem carbon balance was positive in OR, near neutral in ID and WA, and negative (a carbon source) MT. The Northwest region as a whole was a carbon sink in the 2006-2010 period.

Coupling of remote sensing, field campaign, and mechanistic and empirical modeling to monitor spatiotemporal carbon dynamics of a Mediterranean watershed in a changing regional climate.

PubMed

Berberoglu, S; Donmez, C; Evrendilek, F

2015-04-01

The aim of this study was to simulate impacts of regional climate change in the 2070s on carbon (C) cycle of a Mediterranean watershed combining field measurements, Envisat MERIS and IKONOS data, and the Carnegie Ames Stanford Approach model. Simulation results indicated that the present total C sink status (1.36 Mt C year(-1)) of Mediterranean evergreen needleleaf forest, grassland and cropland ecosystems is expected to weaken by 7.6% in response to the climate change in the 2070s (Mt=10(12) g). This decreasing trend was mirrored in soil respiration (R H), aboveground and belowground net primary production (NPP), NEP, and net biome production (NBP). The decrease in NEP in the 2070s was the highest (21.9%) for mixed forest where the smallest present C sink of 0.03 Mt C year(-1) was estimated. The average present net ecosystem production (NEP) values were estimated at 110±15, 75±19, and 41±25 g C m(-2) years(-1) in forest, grassland, and cropland, respectively, with a watershed-scale mean of 95±30 g C m(-2) years(-1). The largest present C sink was in grassland, with a total C pool of 0.55 Mt C year(-1), through its greater spatial extent.

Application of the environmentally sensitive forest growth and mortality submodel, ESGM, for estimating the historic and future forest carbon budget for the Sooke Lake Watershed, British Columbia.

NASA Astrophysics Data System (ADS)

Trofymow, J. A.; Hember, R.; Smiley, B. P.; Morken, S.; Kurz, W. A.

2016-12-01

Forest resource managers require knowledge of how natural disturbances, harvest, land-use change, and climate change affect carbon (C) budgets of complex landscapes. In this study, a retrospective (1911-2012) forest C budget for the 8500 ha Sooke Lake watershed was developed based on forest inventories, disturbance, and stream monitoring data using the Canadian Forest Service's spatially-explicit Generic Carbon Budget Model (GCBM). This standard version of GCBM used species-specific volume-over-age curves and site indices to determine tree growth and thus does not explicitly account for environmental factors (climate, CO2, N deposition) that may affect trees and net ecosystem production (NEP). Therefore, a new submodel was developed for GCBM, ESGM, which uses empirical equations to account for influences of 8 environmental factors on tree growth and mortality, based on analysis of multi-decadal data from 19,777 field plots from western North America. Annual environmental variables were prepared (1910-2012) for input to GCBMesgm and temperature effects on decay rates were turned on in the GCBM soil submodel. In response to fires, harvesting, planting, and deforestation for drinking water reservoir expansions, the standard GCBM run showed over 100 years (1911, 1940, 1991, 2012) aboveground biomass C (262, 189, 148, 177 MgC/ha) and NEP (0.6, -1.3, 0.8, 2.3 Mg C/ha/yr) declined and then increased as harvest and deforestation ceased in 2002. From 1.5 -6.5% of terrestrial humified soil C losses (30,640 Mg C/100 yrs) were estimated to have been exported as dissolved organic carbon. Assuming no future disturbances, the standard GCBM run indicates NEP will peak at 2.64 MgC/ha/yr in 2024 and biomass C reach 1910 levels by 2075. Comparisons will be made between standard GCBM and GCBMesgmruns of the C budget for the historic period and for future climate scenarios (baseline, RCP4.5 and RCP8.5) from the CanESM2 GCM, to explore the potential implications of environmental change for future watershed management.

Interannual variability of terrestrial NEP and its attributions to carbon uptake amplitude and period

NASA Astrophysics Data System (ADS)

Niu, S.

2015-12-01

Earth system exhibits strong interannual variability (IAV) in the global carbon cycle as reflected in the year-to-year anomalies of the atmospheric CO2 concentration. Although various analyses suggested that land ecosystems contribute mostly to the IAV of atmospheric CO2 concentration, processes leading to the IAV in the terrestrial carbon (C) cycle are far from clear and hinder our effort in predicting the IAV of global C cycle. Previous studies on IAV of global C cycle have focused on the regulation of climatic variables in tropical or semiarid areas, but generated inconsistent conclusions. Using long-term eddy-flux measurements of net ecosystem production (NEP), atmospheric CO2 inversion NEP, and the MODIS-derived gross primary production (GPP), we demonstrate that seasonal carbon uptake amplitude (CUA) and period (CUP) are two key processes that control the IAV in the terrestrial C cycle. The two processes together explain 78% of the variations in the IAV in eddy covariance NEP, 70% in global atmospheric inversed NEP, and 53% in the IAV of GPP. Moreover, the three lines of evidence consistently show that variability in CUA is much more important than that of CUP in determining the variation of NEP at most eddy-flux sites, and most grids of global NEP and GPP. Our results suggest that the maximum carbon uptake potential in the peak-growing season is a determinant process of global C cycle internnual variability and carbon uptake period may play less important role than previous expectations. This study uncovers the most parsimonious, proximate processes underlying the IAV in global C cycle of the Earth system. Future research is needed to identify how climate factors affect the IAV in terrestrial C cycle through their influence on CUA and CUP.

Measurement theory in local quantum physics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okamura, Kazuya, E-mail: okamura@math.cm.is.nagoya-u.ac.jp; Ozawa, Masanao, E-mail: ozawa@is.nagoya-u.ac.jp

In this paper, we aim to establish foundations of measurement theory in local quantum physics. For this purpose, we discuss a representation theory of completely positive (CP) instruments on arbitrary von Neumann algebras. We introduce a condition called the normal extension property (NEP) and establish a one-to-one correspondence between CP instruments with the NEP and statistical equivalence classes of measuring processes. We show that every CP instrument on an atomic von Neumann algebra has the NEP, extending the well-known result for type I factors. Moreover, we show that every CP instrument on an injective von Neumann algebra is approximated bymore » CP instruments with the NEP. The concept of posterior states is also discussed to show that the NEP is equivalent to the existence of a strongly measurable family of posterior states for every normal state. Two examples of CP instruments without the NEP are obtained from this result. It is thus concluded that in local quantum physics not every CP instrument represents a measuring process, but in most of physically relevant cases every CP instrument can be realized by a measuring process within arbitrary error limits, as every approximately finite dimensional von Neumann algebra on a separable Hilbert space is injective. To conclude the paper, the concept of local measurement in algebraic quantum field theory is examined in our framework. In the setting of the Doplicher-Haag-Roberts and Doplicher-Roberts theory describing local excitations, we show that an instrument on a local algebra can be extended to a local instrument on the global algebra if and only if it is a CP instrument with the NEP, provided that the split property holds for the net of local algebras.« less

Inhibitors of endopeptidase and angiotensin-converting enzyme lead to an amplification of the morphological changes and an upregulation of the substance P system in a muscle overuse model.

PubMed

Song, Yafeng; Stål, Per S; Yu, Ji-Guo; Lorentzon, Ronny; Backman, Clas; Forsgren, Sture

2014-04-11

We have previously observed, in studies on an experimental overuse model, that the tachykinin system may be involved in the processes of muscle inflammation (myositis) and other muscle tissue alterations. To further evaluate the significance of tachykinins in these processes, we have used inhibitors of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), substances which are known to terminate the activity of various endogenously produced substances, including tachykinins. Injections of inhibitors of NEP and ACE, as well as the tachykinin substance P (SP), were given locally outside the tendon of the triceps surae muscle of rabbits subjected to marked overuse of this muscle. A control group was given NaCl injections. Evaluations were made at 1 week, a timepoint of overuse when only mild inflammation and limited changes in the muscle structure are noted in animals not treated with inhibitors. Both the soleus and gastrocnemius muscles were examined morphologically and with immunohistochemistry and enzyme immunoassay (EIA). A pronounced inflammation (myositis) and changes in the muscle fiber morphology, including muscle fiber necrosis, occurred in the overused muscles of animals given NEP and ACE inhibitors. The morphological changes were clearly more prominent than for animals subjected to overuse and NaCl injections (NaCl group). A marked SP-like expression, as well as a marked expression of the neurokinin-1 receptor (NK-1R) was found in the affected muscle tissue in response to injections of NEP and ACE inhibitors. The concentration of SP in the muscles was also higher than that for the NaCl group. The observations show that the local injections of NEP and ACE inhibitors led to marked SP-like and NK-1R immunoreactions, increased SP concentrations, and an amplification of the morphological changes in the tissue. The injections of the inhibitors thus led to a more marked myositis process and an upregulation of the SP system. Endogenously produced substances, out of which the tachykinins conform to one substance family, may play a role in mediating effects in the tissue in a muscle that is subjected to pronounced overuse.

Inhibition of metallopeptidases by flavonoids and related compounds.

PubMed

Bormann, H; Melzig, M F

2000-02-01

To elucidate possible mechanisms of activity in medicinal plants containing flavonoids, the inhibitory potency of twenty flavones, flavonols, flavanones, phenylacrylic acids and various hydroxylated phenylacetic acids on the activity of neutral endopeptidase (NEP; EC 3.4.24.11), angiotensin-converting enzyme (ACE; EC 3.4.15.1) and aminopeptidase N (APN; EC 3.4.11.2) was investigated in vitro. The screening generally resulted that inhibition of these enzymes requires free hydroxyl groups at the flavone molecule. Flavone and methoxylated compounds (sinensetin) were without effects. Flavonoids with free hydroxyl functions in position 3',4' and 5,7 inhibited the activity of NEP (quercetin, luteolin, fisetin), with myricetin (IC50 = 42 microM) as strongest inhibitor. Inhibition of ACE and APN did not depend on this class of compounds and substitution pattern. E.g. 3,4-dihydroxyphenylacetic acid and 4-methylcatechol (urinary metabolites of flavonoids) also inhibited both APN and ACE activity, but not NEP activity. The results demonstrate that some of the pharmacological activities of flavonoids might be related to the inhibition of metallopeptidases responsible for the splitting of regulatory neuropeptides.

Net ecosystem productivity of temperate grasslands in northern China: An upscaling study

USGS Publications Warehouse

Zhang, Li; Guo, Huadong; Jia, Gensuo; Wylie, Bruce; Gilmanov, Tagir; Howard, Daniel M.; Ji, Lei; Xiao, Jingfeng; Li, Jing; Yuan, Wenping; Zhao, Tianbao; Chen, Shiping; Zhou, Guangsheng; Kato, Tomomichi

2014-01-01

Grassland is one of the widespread biome types globally, and plays an important role in the terrestrial carbon cycle. We examined net ecosystem production (NEP) for the temperate grasslands in northern China from 2000 to 2010. We combined flux observations, satellite data, and climate data to develop a piecewise regression model for NEP, and then used the model to map NEP for grasslands in northern China. Over the growing season, the northern China's grassland had a net carbon uptake of 158 ± 25 g C m−2 during 2000–2010 with the mean regional NEP estimate of 126 Tg C. Our results showed generally higher grassland NEP at high latitudes (northeast) than at low latitudes (central and west) because of different grassland types and environmental conditions. In the northeast, which is dominated by meadow steppes, the growing season NEP generally reached 200–300 g C m−2. In the southwest corner of the region, which is partially occupied by alpine meadow systems, the growing season NEP also reached 200–300 g C m−2. In the central part, which is dominated by typical steppe systems, the growing season NEP generally varied in the range of 100–200 g C m−2. The NEP of the northern China's grasslands was highly variable through years, ranging from 129 (2001) to 217 g C m−2 growing season−1 (2010). The large interannual variations of NEP could be attributed to the sensitivity of temperate grasslands to climate changes and extreme climatic events. The droughts in 2000, 2001, and 2006 reduced the carbon uptake over the growing season by 11%, 29%, and 16% relative to the long-term (2000–2010) mean. Over the study period (2000–2010), precipitation was significantly correlated with NEP for the growing season (R2 = 0.35, p-value < 0.1), indicating that water availability is an important stressor for the productivity of the temperate grasslands in semi-arid and arid regions in northern China. We conclude that northern temperate grasslands have the potential to sequester carbon, but the capacity of carbon sequestration depends on grassland types and environmental conditions. Extreme climate events like drought can significantly reduce the net carbon uptake of grasslands.

HIgh-Q Optical Micro-cavity Resonators as High Sensitive Bio-chemical and Ultrasonic Sensors

NASA Astrophysics Data System (ADS)

Ling, Tao

Optical micro-cavity resonators have quickly emerged in the past few years as a new sensing platform in a wide range of applications, such as bio-chemical molecular detection, environmental monitoring, acoustic and electromagnetic waves detection. In this thesis, we will mainly focus on developing high sensitivity silica micro-tube resonator bio-chemical sensors and high sensitivity polymer micro-ring resonator acoustic sensors. In high sensitivity silica micro-tube resonator bio-chemical sensors part: We first demonstrated a prism coupled silica micro-tube bio-chemical sensing platform to overcome the reliability problem in a fiber coupled thin wall silica micro-tube sensing platform. In refractive index sensing experiment, a unique resonance mode with sensitivity around 600nm/refractive index unit (RIU) has been observed. Surface sensing experiments also have been performed in this platform to detect lipid monolayer, lipid bilayer, electrostatic self assemble layer-by-layer as well as the interaction between the lipid bilayer and proteins. Then a theoretical study on various sensing properties on the silica micro-tube based sensing platform has been realized. Furthermore, we have proposed a coupled cavity system to further enhance the device's sensitivity above 1000nm/RIU. In high sensitivity polymer micro-ring resonator acoustic sensors part: We first presented a simplified fabrication process and realized a polymer microring with a Q factor around 6000. The fabricated device has been used to detect acoustic wave with noise equivalent pressure (NEP) around 230Pa over 1-75MHz frequency rang, which is comparable to state-of-art piezoelectric transducer and the device's frequency response also have been characterized to be up to 90MHz. A new fabrication process combined with resist reflow and thermal oxidation process has been used to improve the Q factor up to 10 5 and the device's NEP has been tested to be around 88Pa over 1-75MHz range. Further improving the device's Q factor has been realized by shifting the device's working wavelength to near-visible wavelength and further reducing the device's sidewall roughness. A record new high Q-˜x105 has been measured and the device's NEP as low as 21Pa has been measured. Furthermore, a smaller size polymer microring device has been developed and fabricated to realize larger angle beam forming applications.

Controls on mangrove forest-atmosphere carbon dioxide exchanges in western Everglades National Park

USGS Publications Warehouse

Barr, Jordan G.; Engel, Vic; Fuentes, Jose D.; Zieman, Joseph C.; O'Halloran, Thomas L.; Smith, Thomas J.; Anderson, Gordon H.

2010-01-01

We report on net ecosystem production (NEP) and key environmental controls on net ecosystem exchange (NEE) of carbon dioxide (CO2) between a mangrove forest and the atmosphere in the coastal Florida Everglades. An eddy covariance system deployed above the canopy was used to determine NEE during January 2004 through August 2005. Maximum daytime NEE ranged from -20 to -25 μmol (CO2) m-2 s-1 between March and May. Respiration (Rd) was highly variable (2.81 ± 2.41 μmol (CO2) m-2 s-1), reaching peak values during the summer wet season. During the winter dry season, forest CO2 assimilation increased with the proportion of diffuse solar irradiance in response to greater radiative transfer in the forest canopy. Surface water salinity and tidal activity were also important controls on NEE. Daily light use efficiency was reduced at high (>34 parts per thousand (ppt)) compared to low (d by ~0.9 μmol (CO2) m-2 s-1 and nighttime Rd by ~0.5 μmol (CO2) m-2 s-1. The forest was a sink for atmospheric CO2, with an annual NEP of 1170 ± 127 g C m-2 during 2004. This unusually high NEP was attributed to year-round productivity and low ecosystem respiration which reached a maximum of only 3 g C m-2 d-1. Tidal export of dissolved inorganic carbon derived from belowground respiration likely lowered the estimates of mangrove forest respiration. These results suggest that carbon balance in mangrove coastal systems will change in response to variable salinity and inundation patterns, possibly resulting from secular sea level rise and climate change.

Circulating Neprilysin Clears Brain Amyloid

PubMed Central

Liu, Yinxing; Studzinski, Christa; Beckett, Tina; Murphy, M. Paul; Klein, Ronald L.; Hersh, Louis B.

2010-01-01

The use of the peptidase neprilysin (NEP) as a therapeutic for lowering brain amyloid burden is receiving increasing attention. We have previously demonstrated that peripheral expression of NEP on the surface of hindlimb muscle lowers brain amyloid burden in a transgenic mouse model of Alzheimer’s disease. In this study we now show that using adeno-associated virus expressing a soluble secreted form of NEP (secNEP-AAV8), NEP secreted into plasma is effective in clearing brain Aβ. Soluble NEP expression in plasma was sustained over the 3-month time period it was measured. Secreted NEP decreased plasma Aβ by 30%, soluble brain Aβ by ~28%, insoluble brain Aβ by ~55%, and Aβ oligomers by 12%. This secNEP did not change plasma levels of substance P or bradykinin, nor did it alter blood pressure. No NEP was detected in CSF, nor did the AAV virus produce brain expression of NEP. Thus the lowering of brain Aβ was due to plasma NEP which altered blood-brain Aβ transport dynamics. Expressing NEP in plasma provides a convenient way to monitor enzyme activity during the course of its therapeutic testing. PMID:20558294

Nogo-receptor 1 antagonization in combination with neurotrophin-4/5 is not superior to single factor treatment in promoting survival and morphological complexity of cultured dopaminergic neurons.

PubMed

Seiler, Stefanie; Di Santo, Stefano; Sahli, Sebastian; Andereggen, Lukas; Widmer, Hans Rudolf

2017-08-01

Cell transplantation using ventral mesencephalic tissue is an experimental approach to treat Parkinson's disease. This approach is limited by poor survival of the transplants and the high number of dopaminergic neurons needed for grafting. Increasing the yield of dopaminergic neurons in donor tissue is of great importance. We have previously shown that antagonization of the Nogo-receptor 1 by NEP1-40 promoted survival of cultured dopaminergic neurons and exposure to neurotrophin-4/5 increased dopaminergic cell densities in organotypic midbrain cultures. We investigated whether a combination of both treatments offers a novel tool to further improve dopaminergic neuron survival. Rat embryonic ventral mesencephalic neurons grown as organotypic free-floating roller tube or primary dissociated cultures were exposed to neurotrophin-4/5 and NEP1-40. The combined and single factor treatment resulted in significantly higher numbers of tyrosine hydroxylase positive neurons compared to controls. Significantly stronger tyrosine hydroxylase signal intensity was detected by Western blotting in the combination-treated cultures compared to controls but not compared to single factor treatments. Neurotrophin-4/5 and the combined treatment showed significantly higher signals for the neuronal marker microtubule-associated protein 2 in Western blots compared to control while no effects were observed for the astroglial marker glial fibrillary acidic protein between groups, suggesting that neurotrophin-4/5 targets mainly neuronal cells. Finally, NEP1-40 and the combined treatment significantly augmented tyrosine hydroxylase positive neurite length. Summarizing, our findings substantiate that antagonization of the Nogo-receptor 1 promotes dopaminergic neurons but does not further increase the yield of dopaminergic neurons and their morphological complexity when combined with neurotrophin-4/5 hinting to the idea that these treatments might exert their effects by activating common downstream pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

Protection against vascular leak in neprilysin transgenic mice with complex overexpression pattern.

PubMed

Wick, Marilee J; Loomis, Zoe L; Harral, Julie W; Le, Mysan; Wehling, Carol A; Miller, York E; Dempsey, Edward C

2016-12-01

Neprilysin (NEP) is a cell surface metallopeptidase found in many tissues. Based mostly on pharmacological manipulations, NEP has been thought to protect blood vessels from plasma extravasation. We have suggested that NEP may protect against pulmonary vascular injury. However, these prior studies did not utilize mice which overexpress NEP. The aims of the present investigation were to develop and characterize doubly transgenic (DT) mice that overexpress NEP universally and conditionally, and to investigate the protective effect that overexpressed NEP may have against plasma extravasation in the vasculature. The duodenum, which is often used to assess vascular permeability, and in which the NEP protein was overexpressed in our DT mice two-fold, was selected as our experimental preparation. We found that substance P-induced plasma extravasation was decreased substantially (3.5-fold) in the duodenums of our doxycycline-treated DT mice, giving independent evidence of NEP's protective effects against plasma extravasation. Transgenic lung NEP protein was not stably expressed in the DT mice, so we were not able to test the effect of NEP overexpression in the lung. Although initially overexpressed nearly nine-fold at that site, pulmonary NEP protein overexpression eventually dissipated. Surprisingly, at a time when there was no lung transgenic NEP protein overexpression, lung NEP mRNA expression was still increased 23-fold, indicating that the expression defect probably is not transcriptional. These studies help to characterize our complex transgenic model of NEP overexpression and further demonstrate NEP's protective effects against plasma extravasation.

Electrical NEP in hot-electron titanium superconducting bolometers

NASA Astrophysics Data System (ADS)

Karasik, Boris S.; Pereverzev, Sergey V.; Olaya, David; Wei, Jian; Gershenson, Michael E.; Sergeev, Andrei V.

2008-07-01

We are presenting the current progress on the titanium (Ti) hot-electron transition-edge devices. The ultimate goal of this work is to develop a submillimeter Hot-Electron Direct Detector (HEDD) with the noise equivalent power NEP = 10-18-10-20 W/Hz1/2 for the moderate resolution spectroscopy and Cosmic Microwave Background (CMB) studies on future space telescope (e.g., SPICA, SAFIR, SPECS, CMBPol) with cryogenically cooled (~ 4-5 K) mirrors. Recentlyi, we have achieved the extremely low thermal conductance (~ 20 fW/K at 300 mK and ~ 0.1 fW/K at 40 mK) due to the electron-phonon decoupling in Ti nanodevices with niobium (Nb) Andreev contacts. This thermal conductance translates into the "phonon-noise" NEP ~ 3×10-21 W/Hz1/2 at 40 mK and NEP ~ 3×10-19 W/Hz1/2 at 300 mK. These record data indicate the great potential of the hot-electron detector for meeting many application needs. Beside the extremely low phonon-noise NEP, the nanobolometers have a very low electron heat capacitance that makes them promising as detectors of single THz photonsii. As the next step towards the practical demonstration of the HEDD, we fabricated and tested somewhat larger than in Ref.1 devices (~ 6 μm × 0.35 μm × 40 nm) whose critical temperature is well reproduced in the range 300-350 mK. The output electrical noise measured in these devices with a low-noise dc SQUID is dominated by the thermal energy fluctuations (ETF) aka "phonon noise". This indicates the high electrothermal loop gain that effectively suppresses the contributions of the Johnson noise and the amplifier (SQUID) noise. The electrical NEP = 6.7×10-18 W/Hz1/2 derived from these measurements is in good agreement with the predictions based on the thermal conductance data. The very low NEP and the high speed (~ μs) are a unique combination not found in other detectors.

Distinct subcellular patterns of neprilysin protein and activity in the brains of Alzheimer’s disease patients, transgenic mice and cultured human neuronal cells

PubMed Central

Zhou, Li; Wei, Chunsheng; Huang, Wei; Bennett, David A; Dickson, Dennis W; Wang, Rui; Wang, Dengshun

2013-01-01

We investigated the subcellular distribution of NEP protein and activity in brains of human individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI) and AD dementia, as well as double transgenic mice and human neuronal cell line treated with Aβ and 4-hydroxy-2-nonenal (HNE). Total cortical neuronal-related NEP was significantly increased in MCI compared to NCI brains. NeuN was decreased in both MCI and AD, consistent with neuronal loss occurring in MCI and AD. Negative relationship between NEP protein and NeuN in MCI brains, and positive correlation between NEP and pan-cadherin in NCI and MCI brains, suggesting the increased NEP expression in NCI and MCI might be due to membrane associated NEP in non-neuronal cells. In subcellular extracts, NEP protein decreased in cytoplasmic fractions in MCI and AD, but increased in membrane fractions, with a significant increase in the membrane/cytoplasmic ratio of NEP protein in AD brains. By contrast, NEP activity was decreased in AD. Similar results were observed in AD-mimic transgenic mice. Studies of SH-SY5Y neuroblastoma showed an up-regulation of NEP protein in the cytoplasmic compartment induced by HNE and Aβ; however, NEP activity decreased in cytoplasmic fractions. Activity of NEP in membrane fractions increased at 48 hours and then significantly decreased after treatment with HNE and Aβ. The cytoplasmic/membrane ratio of NEP protein increased at 24 hours and then decreased in both HNE and Aβ treated cells. Both HNE and Aβ up-regulate NEP expression, but NEP enzyme activity did not show the same increase, possibly indicating immature cytoplasmic NEP is less active than membrane associated NEP. These observations indicate that modulation of NEP protein levels and its subcellular location influence the net proteolytic activity and this complex association might participate in deficiency of Aβ degradation that is associated with amyloid deposition in AD. PMID:24093058

Neutral Endopeptidase Inhibition Enhances Substance P Mediated Inflammation Due to Hypomagnesemia

PubMed Central

Weglicki, William B.; Chmielinska, Joanna J.; Tejero-Taldo, M. Isabel; Kramer, Jay H.; Spurney, Christopher; Viswalingham, Kandan; Lu, Bao; Mak, I. Tong

2013-01-01

During dietary deficiency of magnesium neurogenic inflammation is mediated, primarily, by elevated levels of substance P (SP). The enzyme most specific for degrading this neuropeptide is neutral endopeptidase (NEP). In recent studies we found that pharmacological inhibition of NEP by phosphoramidon resulted in elevated plasma levels of SP and greater oxidative stress. We also observed that hypomagnesemia reduced cardiac and intestinal expression of NEP. In these magnesium deficient rats increased intestinal permeability and impaired cardiac contractility occurred. In our colony of genetically-engineered NEP knockout mice that have reduced ability to degrade SP, we found increased oxidative stress that was prevented by SP (neurokinin-1) receptor blockade. Thus, we submit that inhibition of NEP by pharmacological, genetic and dietary approaches (magnesium restriction), causes greater neurogenic inflammation that may result in increased intestinal and cardiac dysfunction. PMID:19780404

Neutral endopeptidase inhibition enhances substance P mediated inflammation due to hypomagnesemia.

PubMed

Weglicki, William B; Chmielinska, Joanna J; Tejero-Taldo, Isabel; Kramer, Jay H; Spurney, Christopher F; Viswalingham, Kandan; Lu, Bao; Mak, I Tong

2009-09-01

During dietary deficiency of magnesium neurogenic inflammation is mediated, primarily, by elevated levels of substance P (SP). The enzyme most specific for degrading this neuropeptide is neutral endopeptidase (NEP). In recent studies we found that pharmacological inhibition of NEP by phosphoramidon resulted in elevated plasma levels of SP and greater oxidative stress. We also observed that hypomagnesemia reduced cardiac and intestinal expression of NEP. In these magnesium-deficient rats increased intestinal permeability and impaired cardiac contractility occurred. In our colony of genetically-engineered NEP knockout mice that have reduced ability to degrade SP, we found increased oxidative stress that was prevented by SP (neurokinin-1) receptor blockade. Thus, we submit that inhibition of NEP by pharmacological, genetic and dietary approaches (magnesium restriction), causes greater neurogenic inflammation that may result in increased intestinal and cardiac dysfunction.

A D-band Active Imager in a SiGe HBT Technology

NASA Astrophysics Data System (ADS)

Yoon, Daekeun; Song, Kiryong; Kim, Jungsoo; Kaynak, Mehmet; Tillack, Bernd; Rieh, Jae-Sung

2015-04-01

In this paper, an amplifier and a detector operating near 140 GHz have been developed and integrated together with an on-chip antenna for an integrated active imager based on a 0.13-μm SiGe HBT technology. The 5-stage differential common-emitter (CE) amplifier shows a peak gain of 14 dB and noise figure (NF) down to 10 dB around 140 GHz with a DC power dissipation of 18 mW. The common-base (CB) differential detector exhibits a peak responsivity of 52.5 kV/W and a noise equivalent power (NEP) of 3.3 pW/Hz1/2. For the integrated imager, a peak responsivity of 1,740 kV/W and a minimum NEP of 80 fW/Hz1/2 were achieved with a DC power dissipation of 18 mW. With the fabricated active imager with on-chip antenna, which occupies an area of 2,200 × 600 μm2 including the antenna and bonding pads, images of various objects were successfully acquired.

Responses of ecosystem water use efficiency to spring snow and summer water addition with or without nitrogen addition in a temperate steppe

PubMed Central

Zhai, Penghui; Huang, Jianhui; Zhao, Xiang; Dong, Kuanhu

2018-01-01

Water use efficiency (WUE) is an important indicator of ecosystem functioning but how ecosystem WUE responds to climate change including precipitation and nitrogen (N) deposition increases is still unknown. To investigate such responses, an experiment with a randomized block design with water (spring snowfall or summer water addition) and nitrogen addition was conducted in a temperate steppe of northern China. We investigated net ecosystem CO2 production (NEP), gross ecosystem production (GEP) and evapotranspiration (ET) to calculate ecosystem WUE (WUEnep = NEP/ET or WUEgep = GEP/ET) under spring snow and summer water addition with or without N addition from 2011 to 2013. The results showed that spring snow addition only had significant effect on ecosystem WUE in 2013 and summer water addition showed positive effect on ecosystem WUE in 2011 and 2013, as their effects on NEP and GEP is stronger than ET. N addition increased ecosystem WUE in 2012 and 2013 both in spring snow addition and summer water addition for its increasing effects on NEP and GEP but no effect on ET. Summer water addition had less but N addition had greater increasing effects on ecosystem WUE as natural precipitation increase indicating that natural precipitation regulates ecosystem WUE responses to water and N addition. Moreover, WUE was tightly related with atmospheric vapor-pressure deficit (VPD), photosynthetic active radiation (PAR), precipitation and soil moisture indicating the regulation of climate drivers on ecosystem WUE. In addition, it also was affected by aboveground net primary production (ANPP). The study suggests that ecosystem WUE responses to water and N addition is determined by the change in carbon process rather than that in water process, which are regulated by climate change in the temperate steppe of northern China. PMID:29529082

Responses of ecosystem water use efficiency to spring snow and summer water addition with or without nitrogen addition in a temperate steppe.

PubMed

Zhang, Xiaolin; Zhai, Penghui; Huang, Jianhui; Zhao, Xiang; Dong, Kuanhu

2018-01-01

Water use efficiency (WUE) is an important indicator of ecosystem functioning but how ecosystem WUE responds to climate change including precipitation and nitrogen (N) deposition increases is still unknown. To investigate such responses, an experiment with a randomized block design with water (spring snowfall or summer water addition) and nitrogen addition was conducted in a temperate steppe of northern China. We investigated net ecosystem CO2 production (NEP), gross ecosystem production (GEP) and evapotranspiration (ET) to calculate ecosystem WUE (WUEnep = NEP/ET or WUEgep = GEP/ET) under spring snow and summer water addition with or without N addition from 2011 to 2013. The results showed that spring snow addition only had significant effect on ecosystem WUE in 2013 and summer water addition showed positive effect on ecosystem WUE in 2011 and 2013, as their effects on NEP and GEP is stronger than ET. N addition increased ecosystem WUE in 2012 and 2013 both in spring snow addition and summer water addition for its increasing effects on NEP and GEP but no effect on ET. Summer water addition had less but N addition had greater increasing effects on ecosystem WUE as natural precipitation increase indicating that natural precipitation regulates ecosystem WUE responses to water and N addition. Moreover, WUE was tightly related with atmospheric vapor-pressure deficit (VPD), photosynthetic active radiation (PAR), precipitation and soil moisture indicating the regulation of climate drivers on ecosystem WUE. In addition, it also was affected by aboveground net primary production (ANPP). The study suggests that ecosystem WUE responses to water and N addition is determined by the change in carbon process rather than that in water process, which are regulated by climate change in the temperate steppe of northern China.

Angiotensin converting enzyme (ACE) and neprilysin hydrolyze neuropeptides: a brief history, the beginning and follow-ups to early studies.

PubMed

Skidgel, Randal A; Erdös, Ervin G

2004-03-01

Our investigations started when synthetic bradykinin became available and we could characterize two enzymes that cleaved it: kininase I or plasma carboxypeptidase N and kininase II, a peptidyl dipeptide hydrolase that we later found to be identical with the angiotensin I converting enzyme (ACE). When we noticed that ACE can cleave peptides without a free C-terminal carboxyl group (e.g., with a C-terminal nitrobenzylamine), we investigated inactivation of substance P, which has a C-terminal Met(11)-NH(2). The studies were extended to the hydrolysis of the neuropeptide, neurotensin and to compare hydrolysis of the same peptides by neprilysin (neutral endopeptidase 24.11, CD10, NEP). Our publication in 1984 dealt with ACE and NEP purified to homogeneity from human kidney. NEP cleaved substance P (SP) at Gln(6)-Phe(7), Phe(7)[see text]-Phe(8), and Gly(9)-Leu(10) and neurotensin (NT) at Pro(10)-Tyr(11) and Tyr(11)-Ile(12). Purified ACE also rapidly inactivated SP as measured in bioassay. HPLC analysis showed that ACE cleaved SP at Phe(8)-Gly(9) and Gly(9)-Leu(10) to release C-terminal tri- and dipeptide (ratio = 4:1). The hydrolysis was Cl(-) dependent and inhibited by captopril. ACE released only dipeptide from SP free acid. ACE hydrolyzed NT at Tyr(11)-Ile(12) to release Ile(12)-Leu(13). Then peptide substrates were used to inhibit ACE hydrolyzing Fa-Phe-Gly-Gly and NEP cleaving Leu(5)-enkephalin. The K(i) values in microM were as follows: for ACE, bradykinin = 0.4, angiotensin I = 4, SP = 25, SP free acid = 2, NT = 14, and Met(5)-enkephalin = 450, and for NEP, bradykinin = 162, angiotensin I = 36, SP = 190, NT = 39, Met(5)-enkephalin = 22. These studies showed that ACE and NEP, two enzymes widely distributed in the body, are involved in the metabolism of SP and NT. Below we briefly survey how NEP and ACE in two decades have gained the reputation as very important factors in health and disease. This is due to the discovery of more endogenous substrates of the enzymes and to the very broad and beneficial therapeutic applications of ACE inhibitors.

Community metabolism in shallow coral reef and seagrass ecosystems, lower Florida Keys

USGS Publications Warehouse

Turk, Daniela; Yates, Kimberly K.; Vega-Rodriguez, Maria; Toro-Farmer, Gerardo; L'Esperance, Chris; Melo, Nelson; Ramsewak, Deanesch; Estrada, S. Cerdeira; Muller-Karger, Frank E.; Herwitz, Stan R.; McGillis, Wade

2016-01-01

Diurnal variation of net community production (NEP) and net community calcification (NEC) were measured in coral reef and seagrass biomes during October 2012 in the lower Florida Keys using a mesocosm enclosure and the oxygen gradient flux technique. Seagrass and coral reef sites showed diurnal variations of NEP and NEC, with positive values at near-seafloor light levels >100–300 µEinstein m-2 s-1. During daylight hours, we detected an average NEP of 12.3 and 8.6 mmol O2 m-2 h-1 at the seagrass and coral reef site, respectively. At night, NEP at the seagrass site was relatively constant, while on the coral reef, net respiration was highest immediately after dusk and decreased during the rest of the night. At the seagrass site, NEC values ranged from 0.20 g CaCO3 m-2 h-1 during daylight to -0.15 g CaCO3 m-2 h-1 at night, and from 0.17 to -0.10 g CaCO3 m-2 h-1 at the coral reef site. There were no significant differences in pH and aragonite saturation states (Ωar) between the seagrass and coral reef sites. Decrease in light levels during thunderstorms significantly decreased NEP, transforming the system from net autotrophic to net heterotrophic.

Circulating neprilysin clears brain amyloid.

PubMed

Liu, Yinxing; Studzinski, Christa; Beckett, Tina; Murphy, M Paul; Klein, Ronald L; Hersh, Louis B

2010-10-01

The use of the peptidase neprilysin (NEP) as a therapeutic for lowering brain amyloid burden is receiving increasing attention. We have previously demonstrated that peripheral expression of NEP on the surface of hindlimb muscle lowers brain amyloid burden in a transgenic mouse model of Alzheimer's disease. In this study we now show that using adeno-associated virus expressing a soluble secreted form of NEP (secNEP-AAV8), NEP secreted into plasma is effective in clearing brain Abeta. Soluble NEP expression in plasma was sustained over the 3-month time period it was measured. Secreted NEP decreased plasma Abeta by 30%, soluble brain Abeta by approximately 28%, insoluble brain Abeta by approximately 55%, and Abeta oligomersby 12%. This secNEP did not change plasma levels of substance P or bradykinin, nor did it alter blood pressure. No NEP was detected in CSF, nor did the AAV virus produce brain expression of NEP. Thus the lowering of brain Abeta was due to plasma NEP which altered blood-brain Abeta transport dynamics. Expressing NEP in plasma provides a convenient way to monitor enzyme activity during the course of its therapeutic testing. Copyright 2010 Elsevier Inc. All rights reserved.

Inhibition of neutral endopeptidase potentiates bronchoconstriction induced by neurokinin A in asthmatic patients.

PubMed

Crimi, N; Palermo, F; Oliveri, R; Polosa, R; Magrì, S; Mistretta, A

1994-02-01

The endogenous tachykinins exhibit a range of properties which may be relevant in the pathophysiology of asthma. Their effects on the airways seem to be modulated by a variety of lung peptidases, including neutral endopeptidase (NEP). In order to evaluate the potential role of endogenous NEP activity in modulating tachykinins-induced bronchoconstriction in man in vivo, six atopic asthmatic patients, with a mean FEV1 value of 3.38 +/- 0.76 l, and a histamine PD20 mean value of 0.024 mg, were studied. The influence of inhaled phosphoramidon (a potent NEP inhibitor) was examined against the NKA-induced bronchospasm in a double-blind, placebo-controlled randomized study. Changes in airway calibre were followed as FEV1 and agonists responsiveness expressed as PD20 and PD15 for histamine and NKA respectively. Patients received nebulized phosphoramidon sodium salt (10(-5) M) or a control solution 10 min prior to the bronchoprovocation test with NKA. No significant difference was noticed between any of the study days and after inhaled phosphoramidon on baseline FEV1 values (3.29 +/- 0.90 l) in comparison with the control solution (3.31 +/- 0.79 l). Inhaled NKA produced a dose-dependent fall in FEV1 values in all the subjects studied with a mean PD15 value of 20.91 x 10(-9) mol. Phosphoramidon administered by inhalation elicited a significant (P < 0.01 vs baseline and control solution) potentiation in the airway responsiveness to inhaled NKA, the NKA PD15 value decreasing to 9.45 x 10(-9) mol. The present study confirms that inhaled NKA induces a dose-related bronchoconstriction in asthmatic patients and demonstrates that inhaled phosphoramidon potentiates NKA-induced bronchoconstriction.

Major amyloid-β-degrading enzymes, endothelin-converting enzyme-2 and neprilysin, are expressed by distinct populations of GABAergic interneurons in hippocampus and neocortex.

PubMed

Pacheco-Quinto, Javier; Eckman, Christopher B; Eckman, Elizabeth A

2016-12-01

Impaired clearance of amyloid-β peptide (Aβ) has been postulated to significantly contribute to the amyloid accumulation typical of Alzheimer's disease. Among the enzymes known to degrade Aβ in vivo are endothelin-converting enzyme (ECE)-1, ECE-2, and neprilysin (NEP), and evidence suggests that they regulate independent pools of Aβ that may be functionally significant. To better understand the differential regulation of Aβ concentration by its physiological degrading enzymes, we characterized the cell and region-specific expression pattern of ECE-1, ECE-2, and NEP by in situ hybridization and immunohistochemistry in brain areas relevant to Alzheimer's disease. In contrast to the broader distribution of ECE-1, ECE-2 and NEP were found enriched in GABAergic neurons. ECE-2 was majorly expressed by somatostatin-expressing interneurons and was active in isolated synaptosomes. NEP messenger RNA was found mainly in parvalbumin-expressing interneurons, with NEP protein localized to perisomatic parvalbuminergic synapses. The identification of somatostatinergic and parvalbuminergic synapses as hubs for Aβ degradation is consistent with the possibility that Aβ may have a physiological function related to the regulation of inhibitory signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

Multiple access to sterile syringes for injection drug users: vending machines, needle exchange programs and legal pharmacy sales in Marseille, France.

PubMed

Moatti, J P; Vlahov, D; Feroni, I; Perrin, V; Obadia, Y

2001-03-01

In Marseille, southeastern France, HIV prevention programs for injection drug users (IDUs) simultaneously include access to sterile syringes through needle exchange programs (NEPs), legal pharmacy sales and, since 1996, vending machines that mechanically exchange new syringes for used ones. The purpose of this study was to compare the characteristics of IDUs according to the site where they last obtained new syringes. During 3 days in September 1997, all IDUs who obtained syringes from 32 pharmacies, four NEPs and three vending machines were offered the opportunity to complete a self-administered questionnaire on demographics, drug use characteristics and program utilization. Of 485 individuals approached, the number who completed the questionnaire was 141 in pharmacies, 114 in NEPs and 88 at vending machines (response rate = 70.7%). Compared to NEP users, vending machine users were younger and less likely to be enrolled in a methadone program or to report being HIV infected, but more likely to misuse buprenorphine. They also had lower financial resources and were less likely to be heroin injectors than both pharmacy and NEP users. Our results suggest that vending machines attract a very different group of IDUs than NEPs, and that both programs are useful adjuncts to legal pharmacy sales for covering the needs of IDUs for sterile syringes in a single city. Assessment of the effectiveness and cost-effectiveness of combining such programs for the prevention of HIV and other infectious diseases among IDUs requires further comparative research. Copyright 2001 S. Karger AG, Basel

Moniliophthora perniciosa necrosis- and ethylene-inducing protein 2 (MpNep2) as a metastable dimer in solution: structural and functional implications.

PubMed

de Oliveira, Guilherme A P; Pereira, Elen G; Dias, Cristiano V; Souza, Theo L F; Ferretti, Giulia D S; Cordeiro, Yraima; Camillo, Luciana R; Cascardo, Júlio; Almeida, Fabio C; Valente, Ana Paula; Silva, Jerson L

2012-01-01

Understanding how Nep-like proteins (NLPs) behave during the cell cycle and disease progression of plant pathogenic oomycetes, fungi and bacteria is crucial in light of compelling evidence that these proteins play a role in Witches` Broom Disease (WBD) of Theobroma cacao, one of the most important phytopathological problems to afflict the Southern Hemisphere. The crystal structure of MpNep2, a member of the NLP family and the causal agent of WBD, revealed the key elements for its activity. This protein has the ability to refold after heating and was believed to act as a monomer in solution, in contrast to the related homologs MpNep1 and NPP from the oomyceteous fungus Phytophthora parasitica. Here, we identify and characterize a metastable MpNep2 dimer upon over-expression in Escherichia coli using different biochemical and structural approaches. We found using ultra-fast liquid chromatography that the MpNep2 dimer can be dissociated by heating but not by dilution, oxidation or high ionic strength. Small-angle X-ray scattering revealed a possible tail-to-tail interaction between monomers, and nuclear magnetic resonance measurements identified perturbed residues involved in the putative interface of interaction. We also explored the ability of the MpNep2 monomer to refold after heating or chemical denaturation. We observed that MpNep2 has a low stability and cooperative fold that could be an explanation for its structure and activity recovery after stress. These results can provide new insights into the mechanism for MpNep2's action in dicot plants during the progression of WBD and may open new avenues for the involvement of NLP- oligomeric species in phytopathological disorders.

Moniliophthora perniciosa Necrosis- and Ethylene-Inducing Protein 2 (MpNep2) as a Metastable Dimer in Solution: Structural and Functional Implications

PubMed Central

de Oliveira, Guilherme A. P.; Pereira, Elen G.; Dias, Cristiano V.; Souza, Theo L. F.; Ferretti, Giulia D. S.; Cordeiro, Yraima; Camillo, Luciana R.; Almeida, Fabio C.; Valente, Ana Paula; Silva, Jerson L.

2012-01-01

Understanding how Nep-like proteins (NLPs) behave during the cell cycle and disease progression of plant pathogenic oomycetes, fungi and bacteria is crucial in light of compelling evidence that these proteins play a role in Witches` Broom Disease (WBD) of Theobroma cacao, one of the most important phytopathological problems to afflict the Southern Hemisphere. The crystal structure of MpNep2, a member of the NLP family and the causal agent of WBD, revealed the key elements for its activity. This protein has the ability to refold after heating and was believed to act as a monomer in solution, in contrast to the related homologs MpNep1 and NPP from the oomyceteous fungus Phytophthora parasitica. Here, we identify and characterize a metastable MpNep2 dimer upon over-expression in Escherichia coli using different biochemical and structural approaches. We found using ultra-fast liquid chromatography that the MpNep2 dimer can be dissociated by heating but not by dilution, oxidation or high ionic strength. Small-angle X-ray scattering revealed a possible tail-to-tail interaction between monomers, and nuclear magnetic resonance measurements identified perturbed residues involved in the putative interface of interaction. We also explored the ability of the MpNep2 monomer to refold after heating or chemical denaturation. We observed that MpNep2 has a low stability and cooperative fold that could be an explanation for its structure and activity recovery after stress. These results can provide new insights into the mechanism for MpNep2′s action in dicot plants during the progression of WBD and may open new avenues for the involvement of NLP- oligomeric species in phytopathological disorders. PMID:23029140

Quantifying Fast and Slow Responses of Terrestrial Carbon Exchange across a Water Availability Gradient in North American Flux Sites

NASA Astrophysics Data System (ADS)

Biederman, J. A.; Scott, R. L.; Goulden, M.

2014-12-01

Climate change is predicted to increase the frequency and severity of water limitation, altering terrestrial ecosystems and their carbon exchange with the atmosphere. Here we compare site-level temporal sensitivity of annual carbon fluxes to interannual variations in water availability against cross-site spatial patterns over a network of 19 eddy covariance flux sites. This network represents one order of magnitude in mean annual productivity and includes western North American desert shrublands and grasslands, savannahs, woodlands, and forests with continuous records of 4 to 12 years. Our analysis reveals site-specific patterns not identifiable in prior syntheses that pooled sites. We interpret temporal variability as an indicator of ecosystem response to annual water availability due to fast-changing factors such as leaf stomatal response and microbial activity, while cross-site spatial patterns are used to infer ecosystem adjustment to climatic water availability through slow-changing factors such as plant community and organic carbon pools. Using variance decomposition, we directly quantify how terrestrial carbon balance depends on slow- and fast-changing components of gross ecosystem production (GEP) and total ecosystem respiration (TER). Slow factors explain the majority of variance in annual net ecosystem production (NEP) across the dataset, and their relative importance is greater at wetter, forest sites than desert ecosystems. Site-specific offsets from spatial patterns of GEP and TER explain one third of NEP variance, likely due to slow-changing factors not directly linked to water, such as disturbance. TER and GEP are correlated across sites as previously shown, but our site-level analysis reveals surprisingly consistent linear relationships between these fluxes in deserts and savannahs, indicating fast coupling of TER and GEP in more arid ecosystems. Based on the uncertainty associated with slow and fast factors, we suggest a framework for improved prediction of terrestrial carbon balance. We will also present results of ongoing work to quantify fast and slow contributions to the relationship between evapotranspiration and precipitation across a precipitation gradient.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ura, N.; Carretero, O.A.; Erdoes, E.G.

Studies were done in 2 phases in rats. (1) Bradykinin was added catheter-collected urine, and its hydrolysis was determined by RIA. Three different kiniases were found by application of specific inhibitors. Kininase I-type carboxypeptidase was inhibited by 2-mercaptomethyl-3-guanidinoethyl-thiopropanoic acid, kiniase II by captopril and NEP by phosphoramidon (PA). Surprisingly, NEP was responsible for 68% of total kininase, while kininase I and II contributed only 9 and 23%. (2) To study the effects of inhibition of NEP on renal function, rats were infused with PA (330 ..mu..g/hr/kg, n=6). Urinary kinin level, kininase, GFR, RBF, U/sub Na/V, U/sub K/V and UV weremore » measured. PA decreased total urinary kininase activity from 284 to 58 ng/min/kg (77%, p < 0.01) and increased urinary kinin excretion from 74 to 128 pg/min/kg (73%, p < 0.02), UV from 72 to 82 ..mu..l/min/kg (15%, p < 0.01) and U/sub Na/V from 12 to 17 ..mu.. Eq/min/kg (37%, p < 0.02). PA did not change BP, RBF, GFR or U/sub K/V. /sup 125/I-Tyr-bradykinin infused into the aorta did not appear in urine intact during PA administration. In conclusion, this is the first demonstration of NEP catabolizing kinins in vivo; its inhibition increased the excretion of intrarenally generated kinins. Changes in water and electrolyte excretion may be caused by kinins generated in the distal nephron.« less

Inhibition of neutral endopeptidase increases airway responsiveness to ACh in nonsensitized normal rats.

PubMed

Chiba, Y; Misawa, M

1995-02-01

The effects of sensory neuropeptides on the airway responsiveness to acetylcholine (ACh) were investigated in normal nonsensitized rats. The airway responsiveness to inhaled ACh was significantly increased after treatment with neurokinin A (NKA; 0.001%) or substance P (SP; 0.01%) aerosol in the presence of the neutral endopeptidase (NEP) inhibitor. NKA had a more potent effect than SP. Interestingly, the intravenous treatment with NEP inhibitor alone also induced airway hyperresponsiveness (AHR) to inhaled ACh. This AHR was significantly attenuated by pretreatment with a nonselective NK-receptor antagonist, [D-Pro2,D-Trp7,9]SP, systemic capsaicin, or bilateral cervical vagotomy, indicating that decreased NEP activity results in accumulation of endogenous sensory neuropeptide(s) and enhancement of vagal reflex to cause AHR. The airway responsiveness to ACh of isolated left main bronchus was also increased after treatment with 10(-6) M NKA, but not SP, together with 10(-6) M phosphoramidon. This in vitro AHR to ACh induced by phosphoramidon plus NKA was significantly attenuated by pretreatment with 10(-6) M tetrodotoxin. These findings suggest that overaccumulated sensory neuropeptides, especially NKA, may enhance the probability of transmitter release, probably via NK2 receptors, and that the enhanced transmitter release might be involved in AHR in rats.

Changes in net ecosystem productivity of boreal black spruce stands in response to changes in temperature at diurnal and seasonal time scales.

PubMed

Grant, R F; Margolis, H A; Barr, A G; Black, T A; Dunn, A L; Bernier, P Y; Bergeron, O

2009-01-01

Net ecosystem productivity (NEP) of boreal coniferous forests is believed to rise with climate warming, thereby offsetting some of the rise in atmospheric CO(2) concentration (C(a)) by which warming is caused. However, the response of conifer NEP to warming may vary seasonally, with rises in spring and declines in summer. To gain more insight into this response, we compared changes in CO(2) exchange measured by eddy covariance and simulated by the ecosystem process model ecosys under rising mean annual air temperatures (T(a)) during 2004-2006 at black spruce stands in Saskatchewan, Manitoba and Quebec. Hourly net CO(2) uptake was found to rise with warming at T(a) < 15 degrees C and to decline with warming at T(a) > 20 degrees C. As mean annual T(a) rose from 2004 to 2006, increases in net CO(2) uptake with warming at lower T(a) were greater than declines with warming at higher T(a) so that annual gross primary productivity and hence NEP increased. Increases in net CO(2) uptake measured at lower T(a) were explained in the model by earlier recovery of photosynthetic capacity in spring, and by increases in carboxylation activity, using parameters for the Arrhenius temperature functions of key carboxylation processes derived from independent experiments. Declines in net CO(2) uptake measured at higher T(a) were explained in the model by sharp declines in mid-afternoon canopy stomatal conductance (g(c)) under higher vapor pressure deficits (D). These declines were modeled from a hydraulic constraint to water uptake imposed by low axial conductivity of conifer roots and boles that forced declines in canopy water potential (psi(c)), and hence in g(c) under higher D when equilibrating water uptake with transpiration. In a model sensitivity study, the contrasting responses of net CO(2) uptake to specified rises in T(a) caused annual NEP of black spruce in the model to rise with increases in T(a) of up to 6 degrees C, but to decline with further increases at mid-continental sites with lower precipitation. However, these contrasting responses to warming also indicate that rises in NEP with climate warming would depend on the seasonality (spring versus summer) as well as the magnitude of rises in T(a).

Substance P induced preprotachykinin-a mRNA, neutral endopeptidase mRNA and substance P in cultured normal fibroblasts.

PubMed

Bae, Sang-Jae; Matsunaga, Yoshitaka; Takenaka, Motoi; Tanaka, Yoichi; Hamazaki, Yoichiro; Shimizu, Kazuhiro; Katayama, Ichiro

2002-04-01

In certain skin diseases, stress can modulate the induction and/or progression of cutaneous manifestations. However, little is known about the circuit in neuroendocrine and in the immune systems of the skin. To address this question, we have analyzed the regulatory mechanisms of autocrine induction of substance P (SP) by cultured normal human fibroblasts that compose the major population of the skin and might augment stress-induced skin inflammatory responses. In nonstimulated conditions, normal fibroblasts express a moderate amount of preprotachykinin-A (PPT-A), a precursor of SP mRNA, and exogenous SP significantly upregulated PPT-A mRNA expression. Maximum response of SP peptide and SP mRNA in fibroblasts was observed 1-3 h after stimulation with SP. In contrast, the expression of neutral endopeptidase (NEP), a cell surface peptide with hydrolyzing activity of SP, was increased in fibroblasts stimulated with SP after 24 h. The administration of NEP inhibitor (phosphoramidon) to the fibroblasts induced higher SP production. In addition, the neurokinin (NK) receptor antagonists (spantide, FK224 and FK888) and protein synthesis inhibitor (cycloheximide) inhibited SP production by 30-40% of control response. In immunostaining study, specific cytoplasmic staining of SP was observed in fibroblasts stimulated with SP. Finally, we confirmed that the nucleotide sequence of the PPT-A expressed in fibroblasts perfectly corresponded to the gene bank human PPT-A cDNA. This is the first report that SP mRNA, NEP mRNA and SP peptide can be induced by normal human skin fibroblasts in response to exogenous SP, and that fibroblast-derived SP might play an important role in the induction and acceleration of certain cutaneous diseases. Copyright 2002 S. Karger AG, Basel

Nitrogen Fertilization Effects on Net Ecosystem and Net Primary Productivities as Determined from Flux Tower, Biometric, and Model Estimates for a Coastal Douglas-fir Forest in British Columbia

NASA Astrophysics Data System (ADS)

Trofymow, J. A.; Metsaranta, J. M.; Black, T. A.; Jassal, R. S.; Filipescu, C.

2013-12-01

In coastal BC, 6,000-10,000 ha of public and significant areas of private forest land are annually fertilized with nitrogen, with or without thinning, to increase merchantable wood and reduce rotation age. Fertilization has also been viewed as a way to increase carbon (C) sequestration in forests and obtain C offsets. Such offset projects must demonstrate additionality with reference to a baseline and include monitoring to verify net C gains over the project period. Models in combination with field-plot measurements are currently the accepted methods for most C offset protocols. On eastern Vancouver Island, measurements of net ecosystem production (NEP), ecosystem respiration (Re) and gross primary productivity (GPP) using the eddy-covariance (EC) technique as well as component C fluxes and stocks have been made since 1998 in an intermediate-aged Douglas-fir dominated forest planted in 1949. In January 2007 an area around the EC flux tower was aerially fertilized with 200 kg urea-N ha-1. Ground plots in the fertilized area and an adjacent unfertilized control area were also monitored for soil (Rs) and heterotrophic (Rh) respiration, litterfall, and tree growth. To determine fertilization effects on whole tree growth, sample trees were felled in both areas for the 4-year (2003-06) pre- and the 4-year (2007-10) post-fertilization periods and were compared with EC NEP estimates and tree-ring based NEP estimates from Carbon Budget Model - Canadian Forest Sector (CBM-CFS3) for the same periods. Empirical equations using climate and C fluxes from 1998-2006 were derived to estimate what the EC fluxes would have been in 2007-10 for the fertilized area had it been unfertilized. Mean EC NEP for 2007-10 was 561 g C m2 y-1 , a 64% increase above pre-fertilization NEP (341 g C m2 y-1) or 28% increase above estimated unfertilized NEP (438 g C m2 y-1). Most of the increase was attributed to increased tree C uptake (i.e., GPP), with little change in Re. In 2007 fertilization caused a small increase in Rs and litter decay, and a small decrease in Rh. Litterfall rates averaged 100 g C m2 y-1 and did not differ between fertilized and control plots. Stem wood increments for 2007-10 indicated aboveground growth in fertilized trees was 35% greater than in control trees. However this was due to fertilized tree growth being 30% greater and control trees 5% less when compared to growth in the pre-fertilization period. Preliminary examination of root wood increments indicated that the post-fertilization growth was less than pre-fertilization growth, suggesting that the post-fertilization NPP was lower than if just estimated from stem wood. Mean CBM-CFS3 NEP for seven groundplots around the tower were 465 g C m2 y-1 for 2007-10, a 34% increase above pre-fertilization model NEP (347 g C m2 y-1). Using post- and pre-fertilization values, fertilization effects on EC NEP (64%) were nearly twice that of CBM-CFS3 model NEP (34%) or biometric tree growth (30%). However, if fertilized and unfertilized control values for 2007-10 were used; fertilization effects on EC NEP (28%) were comparable to those from biometric tree growth (35%). Results suggest choice of an appropriate baseline will be important in determining the C gains of forest C offset projects.

Electrical NEP in Hot-Electron Titanium Superconducting Bolometers

NASA Technical Reports Server (NTRS)

Karasik, Boris S.; Pereverzev, Sergey V.; Olaya, David; Wei, Jian; Gershenson, Michael E.; Sergeev, Andrei V.

2008-01-01

We are presenting the current progress on the titanium (Ti) hot-electron transition-edge devices. The ultimate goal of this work is to develop a submillimeter Hot-Electron Direct Detector (HEDD) with the noise equivalent power NEP = 10(sup -1) - 10(sup -20) W/Hz(sup 1/2) for the moderate resolution spectroscopy and Cosmic Microwave Background (CMB) studies on future space telescope (e.g., SPICA, SAFIR, SPECS, CMBPol) with cryogenically cooled (approximately 4-5 K) mirrors. Recently, we have achieved the extremely low thermal conductance (approximately 20 fW/K at 300 mK and approximately 0.1 fW/K at 40 mK) due to the electron-phonon decoupling in Ti nanodevices with niobium (Nb) Andreev contacts. This thermal conductance translates into the "phonon-noise" NEP approximately equal to 3 x 10(sup -21) W/Hz(sup 1/2) at 40 mK and NEP approximately equal to 3 x 10(sup -19) W/Hz(sup 1/2) at 300 mK. These record data indicate the great potential of the hot-electron detector for meeting many application needs. Beside the extremely low phonon-noise NEP, the nanobolometers have a very low electron heat capacitance that makes them promising as detectors of single THz photons. As the next step towards the practical demonstration of the HEDD, we fabricated and tested somewhat larger than in Ref.1 devices (approximately 6 micrometers x 0.35 micrometers x 40 nm) whose critical temperature is well reproduced in the range 300-350 mK. The output electrical noise measured in these devices with a low-noise dc SQUID is dominated by the thermal energy fluctuations (ETF) aka "phonon noise". This indicates the high electrothermal loop gain that effectively suppresses the contributions of the Johnson noise and the amplifier (SQUID) noise. The electrical NEP = 6.7 x 10(sup -18) W/Hz(sup 1/2) derived from these measurements is in good agreement with the predictions based on the thermal conductance data. The very low NEP and the high speed (approximately microns) are a unique combination not found in other detectors.

HOCl causes airway substance P hyperresponsiveness and neutral endopeptidase hypoactivity.

PubMed

Murlas, C G; Murphy, T P; Lang, Z

1990-06-01

We investigated whether exposure of guinea pig tracheal tissue to hypochlorous acid (HOCl) or hydrogen peroxide (H2O2) by perfusion through the airway lumen affected the responsiveness of airway muscle to ACh, KCl, or substance P in the presence or absence of 1 microM phosphoramidon, an inhibitor of neutral endopeptidase (NEP). Pairs of tracheal segments were immersed in a Krebs solution (pH 7.40 at 37 degrees C) and connected to perfusion circuits so that the lumen of one segment of each pair could be perfused with Krebs solution while the other was perfused for the same time (10 min) with either 0.1 microM HOCl or 10 mM H2O2. Segments after perfusion were cut into rings of similar size and placed in muscle chambers so that airway muscle force generation in vitro could be measured on stimulation by cumulative agonist doses. In addition, cell homogenates were made from other, similarly perfused tracheal segments to assess NEP activity using reverse-phase, high-pressure liquid chromatography (HPLC). We found that smooth muscle of mucosa-intact guinea pig airways perfused with HOCl, but not H2O2, was hyperresponsive to substance P but not to ACh or KCl. HOCl-perfused rings were not different from Krebs solution-exposed rings pretreated with phosphoramidon. There was no increase in substance P responsiveness of HOCl-exposed airways in which the mucosa had been removed before testing in vitro. The substance P hyperresponsiveness of HOCl-exposed, mucosa-intact airways was associated with decreased NEP activity.(ABSTRACT TRUNCATED AT 250 WORDS)

When vegetation change alters ecosystem water availability.

PubMed

Scott, Russell L; Huxman, Travis E; Barron-Gafford, Greg A; Darrel Jenerette, G; Young, Jessica M; Hamerlynck, Erik P

2014-07-01

The combined effects of vegetation and climate change on biosphere-atmosphere water vapor (H2 O) and carbon dioxide (CO2 ) exchanges are expected to vary depending, in part, on how biotic activity is controlled by and alters water availability. This is particularly important when a change in ecosystem composition alters the fractional covers of bare soil, grass, and woody plants so as to influence the accessibility of shallower vs. deeper soil water pools. To study this, we compared 5 years of eddy covariance measurements of H2 O and CO2 fluxes over a riparian grassland, shrubland, and woodland. In comparison with the surrounding upland region, groundwater access at the riparian sites increased net carbon uptake (NEP) and evapotranspiration (ET), which were sustained over more of the year. Among the sites, the grassland used less of the stable groundwater resource, and increasing woody plant density decoupled NEP and ET from incident precipitation (P), resulting in greater exchange rates that were less variable year to year. Despite similar gross patterns, how groundwater accessibility affected NEP was more complex than ET. The grassland had higher respiration (Reco ) costs. Thus, while it had similar ET and gross carbon uptake (GEP) to the shrubland, grassland NEP was substantially less. Also, grassland carbon fluxes were more variable due to occasional flooding at the site, which both stimulated and inhibited NEP depending upon phenology. Woodland NEP was large, but surprisingly similar to the less mature, sparse shrubland, even while having much greater GEP. Woodland Reco was greater than the shrubland and responded strongly and positively to P, which resulted in a surprising negative NEP response to P. This is likely due to the large accumulation of carbon aboveground and in the surface soil. These long-term observations support the strong role that water accessibility can play when determining the consequences of ecosystem vegetation change. © 2013 John Wiley & Sons Ltd.

Differential effects of phosphoramidon on neurokinin A- and substance P-induced airflow obstruction and airway microvascular leakage in guinea-pig.

PubMed Central

Lötvall, J. O.; Elwood, W.; Tokuyama, K.; Barnes, P. J.; Chung, K. F.

1991-01-01

1. The effects of the inhaled neuropeptides, neurokinin A (NKA) and substance P (SP) on lung resistance (RL) and airway microvascular permeability were studied in anaesthetized guinea-pigs. 2. Single doses of inhaled NKA (3 x 10(-5), 1 x 10(-4), 3 x 10(-4) M; 45 breaths) and SP (1 x 10(-4), 3 x 10(-4), 1 x 10(-3); 45 breaths) caused a dose-dependent increase in both RL and airway microvascular leakage, assessed as extravasation of the albumin marker, Evans blue dye. 3. NKA at 1 x 10(-4) and 3 x 10(-4) M resulted in a significantly higher increase in RL than SP at the same doses. 4. Inhaled SP (3 x 10(-4) M; 45 breaths) caused significantly higher Evans blue dye extravasation in main bronchi and proximal intrapulmonary airways compared to the same dose of NKA. 5. Pretreatment with the specific inhibitor of neural endopeptidase (NEP24.11), phosphoramidon, caused an approximately 100 fold leftward shift of the RL responses to inhaled NKA and SP. 6. Phosphoramidon significantly potentiated both NKA- and SP-induced airway microvascular leakage at proximal intrapulmonary airways, but not at any other airway level. 7. Inhibition of NEP24.11 potentiate both the SP- or NKA-induced airflow obstruction to a larger extent than the induced airway microvascular leakage, suggesting that NEP24.11 is more important in the modulation of the airflow obstruction observed after these mediators. PMID:1725766

Differential effects of phosphoramidon on neurokinin A- and substance P-induced airflow obstruction and airway microvascular leakage in guinea-pig.

PubMed

Lötvall, J O; Elwood, W; Tokuyama, K; Barnes, P J; Chung, K F

1991-12-01

1. The effects of the inhaled neuropeptides, neurokinin A (NKA) and substance P (SP) on lung resistance (RL) and airway microvascular permeability were studied in anaesthetized guinea-pigs. 2. Single doses of inhaled NKA (3 x 10(-5), 1 x 10(-4), 3 x 10(-4) M; 45 breaths) and SP (1 x 10(-4), 3 x 10(-4), 1 x 10(-3); 45 breaths) caused a dose-dependent increase in both RL and airway microvascular leakage, assessed as extravasation of the albumin marker, Evans blue dye. 3. NKA at 1 x 10(-4) and 3 x 10(-4) M resulted in a significantly higher increase in RL than SP at the same doses. 4. Inhaled SP (3 x 10(-4) M; 45 breaths) caused significantly higher Evans blue dye extravasation in main bronchi and proximal intrapulmonary airways compared to the same dose of NKA. 5. Pretreatment with the specific inhibitor of neural endopeptidase (NEP24.11), phosphoramidon, caused an approximately 100 fold leftward shift of the RL responses to inhaled NKA and SP. 6. Phosphoramidon significantly potentiated both NKA- and SP-induced airway microvascular leakage at proximal intrapulmonary airways, but not at any other airway level. 7. Inhibition of NEP24.11 potentiate both the SP- or NKA-induced airflow obstruction to a larger extent than the induced airway microvascular leakage, suggesting that NEP24.11 is more important in the modulation of the airflow obstruction observed after these mediators.

Impacts of land use changes on net ecosystem production in the Taihu Lake Basin of China from 1985 to 2010

NASA Astrophysics Data System (ADS)

Xu, Xibao; Yang, Guishan; Tan, Yan; Tang, Xuguang; Jiang, Hong; Sun, Xiaoxiang; Zhuang, Qianlai; Li, Hengpeng

2017-03-01

Land use changes play a major role in determining sources and sinks of carbon at regional and global scales. This study employs a modified Global biome model-biogeochemical cycle model to examine the changes in the spatiotemporal pattern of net ecosystem production (NEP) in the Taihu Lake Basin of China during 1985-2010 and the extent to which land use change impacted NEP. The model is calibrated with observed NEP at three flux sites for three dominant land use types in the basin including cropland, evergreen needleleaf forest, and mixed forest. Two simulations are conducted to distinguish the net effects of land use change and increasing atmospheric concentrations of CO2 and nitrogen deposition on NEP. The study estimates that NEP in the basin decreased by 9.8% (1.57 Tg C) from 1985 to 2010, showing an overall downward trend. The NEP distribution exhibits an apparent spatial heterogeneity at the municipal level. Land use changes during 1985-2010 reduced the regional NEP (3.21 Tg C in year 2010) by 19.9% compared to its 1985 level, while the increasing atmospheric CO2 concentrations and nitrogen deposition compensated for a half of the total carbon loss. Critical measures for regulating rapid urban expansion and population growth and reinforcing environment protection programs are recommended to increase the regional carbon sink.

Rational redesign of neutral endopeptidase binding to merlin and moesin proteins

PubMed Central

Niv, Masha Y; Iida, Katsuyuki; Zheng, Rong; Horiguchi, Akio; Shen, Ruoqian; Nanus, David M

2009-01-01

Neutral endopeptidase (NEP) is a 90- to 110-kDa cell-surface peptidase that is normally expressed by numerous tissues but whose expression is lost or reduced in a variety of malignancies. The anti-tumorigenic function of NEP is mediated not only by its catalytic activity but also through direct protein–protein interactions of its cytosolic region with several binding partners, including Lyn kinase, PTEN, and ezrin/radixin/moesin (ERM) proteins. We have previously shown that mutation of the K19K20K21 basic cluster in NEPs' cytosolic region to residues QNI disrupts binding to the ERM proteins. Here we show that the ERM-related protein merlin (NF2) does not bind NEP or its cytosolic region. Using experimental data, threading, and sequence analysis, we predicted the involvement of moesin residues E159Q160 in binding to the NEP cytosolic domain. Mutation of these residues to NL (to mimic the corresponding N159L160 residues in the nonbinder merlin) disrupted moesin binding to NEP. Mutation of residues N159L160Y161K162M163 in merlin to the corresponding moesin residues resulted in NEP binding to merlin. This engineered NEP peptide–merlin interaction was diminished by the QNI mutation in NEP, supporting the role of the NEP basic cluster in binding. We thus identified the region of interaction between NEP and moesin, and engineered merlin into a NEP-binding protein. These data form the basis for further exploration of the details of NEP-ERM binding and function. PMID:19388049

Differential cerebral deposition of IDE and NEP in sporadic and familial Alzheimer's disease.

PubMed

Dorfman, Verónica Berta; Pasquini, Laura; Riudavets, Miguel; López-Costa, Juan José; Villegas, Andrés; Troncoso, Juan Carlos; Lopera, Francisco; Castaño, Eduardo Miguel; Morelli, Laura

2010-10-01

Alzheimer's disease (AD) is characterized by amyloid beta (A beta) accumulation in the brain and is classified as familial early-onset (FAD) or sporadic late-onset (SAD). Evidences suggest that deficits in the brain expression of insulin degrading enzyme (IDE) and neprilysin (NEP), both proteases involved in amyloid degradation, may promote A beta deposition in SAD. We studied by immunohistochemistry IDE and NEP cortical expression in SAD and FAD samples carrying the E280A presenilin-1 missense mutation. We showed that IDE, a soluble peptidase, is linked with aggregated A beta 40 isoform while NEP, a membrane-bound protease, negatively correlates with amyloid angiopathy and its expression in the senile plaques is independent of aggregated amyloid and restricted to SAD cases. NEP, but not IDE, is over-expressed in dystrophic neurites, both proteases are immunoreactive in activated astrocytes but not in microglia and IDE was the only one detected in astrocytes of white matter from FAD cases. Collectively, our results support the notion that gross conformational changes involved in the modification from "natively folded-active" to "aggregated-inactive" IDE and NEP may be a relevant pathogenic mechanism in SAD. (c) 2008 Elsevier Inc. All rights reserved.

Police Encounters Among Needle Exchange Clients in Baltimore: Drug Law Enforcement as a Structural Determinant of Health.

PubMed

Beletsky, Leo; Cochrane, Jess; Sawyer, Anne L; Serio-Chapman, Chris; Smelyanskaya, Marina; Han, Jennifer; Robinowitz, Natanya; Sherman, Susan G

2015-09-01

We piloted a monitoring mechanism to document police encounters around programs targeting people who inject drugs (PWID), and assessed their demographic predictors at 2 Baltimore, Maryland, needle exchange program (NEP) sites. In a brief survey, 308 clients quantified, characterized, and sited recent police encounters. Multivariate linear regression determined encounter predictors, and we used geocoordinate maps to illustrate clusters. Within the past 6 months, clients reported a median of 3 stops near NEP sites (interquartile range [IQR] = 0-7.5) and a median of 1 arrest in any location (IQR = 0-2). Three respondents reported police referral to the NEP. Being younger (P = .009), being male (P = .033), and making frequent NEP visits (P = .02) were associated with reported police stops. Among clients reporting arrest or citation for syringe possession, Whites were significantly less likely than non-Whites to report being en route to or from an NEP (P < .001). Reported encounters were clustered around NEPs. Systematic surveillance of structural determinants of health for PWID proved feasible when integrated into service activities. Improved monitoring is critical to informing interventions to align policing with public health, especially among groups subject to disproportionate levels of drug law enforcement.

Inhibitors of endopeptidase and angiotensin-converting enzyme lead to an amplification of the morphological changes and an upregulation of the substance P system in a muscle overuse model

PubMed Central

2014-01-01

Background We have previously observed, in studies on an experimental overuse model, that the tachykinin system may be involved in the processes of muscle inflammation (myositis) and other muscle tissue alterations. To further evaluate the significance of tachykinins in these processes, we have used inhibitors of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), substances which are known to terminate the activity of various endogenously produced substances, including tachykinins. Methods Injections of inhibitors of NEP and ACE, as well as the tachykinin substance P (SP), were given locally outside the tendon of the triceps surae muscle of rabbits subjected to marked overuse of this muscle. A control group was given NaCl injections. Evaluations were made at 1 week, a timepoint of overuse when only mild inflammation and limited changes in the muscle structure are noted in animals not treated with inhibitors. Both the soleus and gastrocnemius muscles were examined morphologically and with immunohistochemistry and enzyme immunoassay (EIA). Results A pronounced inflammation (myositis) and changes in the muscle fiber morphology, including muscle fiber necrosis, occurred in the overused muscles of animals given NEP and ACE inhibitors. The morphological changes were clearly more prominent than for animals subjected to overuse and NaCl injections (NaCl group). A marked SP-like expression, as well as a marked expression of the neurokinin-1 receptor (NK-1R) was found in the affected muscle tissue in response to injections of NEP and ACE inhibitors. The concentration of SP in the muscles was also higher than that for the NaCl group. Conclusions The observations show that the local injections of NEP and ACE inhibitors led to marked SP-like and NK-1R immunoreactions, increased SP concentrations, and an amplification of the morphological changes in the tissue. The injections of the inhibitors thus led to a more marked myositis process and an upregulation of the SP system. Endogenously produced substances, out of which the tachykinins conform to one substance family, may play a role in mediating effects in the tissue in a muscle that is subjected to pronounced overuse. PMID:24725470

Nuclear Electric Propulsion Technology Panel findings and recommendations

NASA Technical Reports Server (NTRS)

Doherty, Michael P.

1992-01-01

Summarized are the findings and recommendations of a triagency (NASA/DOE/DOD) panel on Nuclear Electric Propulsion (NEP) Technology. NEP has been identified as a candidate nuclear propulsion technology for exploration of the Moon and Mars as part of the Space Exploration Initiative (SEI). The findings are stated in areas of system and subsystem considerations, technology readiness, and ground test facilities. Recommendations made by the panel are summarized concerning: (1) existing space nuclear power and propulsion programs, and (2) the proposed multiagency NEP technology development program.

Role of endothelin-converting enzyme, chymase and neutral endopeptidase in the processing of big ET-1, ET-1(1-21) and ET-1(1-31) in the trachea of allergic mice.

PubMed

De Campo, Benjamin A; Goldie, Roy G; Jeng, Arco Y; Henry, Peter J

2002-08-01

The present study examined the roles of endothelin-converting enzyme (ECE), neutral endopeptidase (NEP) and mast cell chymase as processors of the endothelin (ET) analogues ET-1(1-21), ET-1(1-31) and big ET-1 in the trachea of allergic mice. Male CBA/CaH mice were sensitized with ovalbumin (10 microg) delivered intraperitoneal on days 1 and 14, and exposed to aerosolized ovalbumin on days 14, 25, 26 and 27 (OVA mice). Mice were killed and the trachea excised for histological analysis and contraction studies on day 28. Tracheae from OVA mice had 40% more mast cells than vehicle-sensitized mice (sham mice). Ovalbumin (10 microg/ml) induced transient contractions (15+/-3% of the C(max)) in tracheae from OVA mice. The ECE inhibitor CGS35066 (10 microM) inhibited contractions induced by big ET-1 (4.8-fold rightward shift of dose-response curve; P<0.05), but not those induced by either ET-1(1-21) or ET-1(1-31). The chymase inhibitors chymostatin (10 microM) and Bowman-Birk inhibitor (10 microM) had no effect on contractions induced by any of the ET analogues used. The NEP inhibitor CGS24592 (10 microM) inhibited contractions induced by ET-1(1-31) (6.2-fold rightward shift; P<0.05) but not ET-1(1-21) or big ET-1. These data suggest that big ET-1 is processed predominantly by a CGS35066-sensitive ECE within allergic airways rather than by mast cell-derived proteases such as chymase. If endogenous ET-1(1-31) is formed within allergic airways, it is likely to undergo further conversion by NEP to more active products.

Substance P and neprilysin in chronic pancreatitis.

PubMed

Mascetta, G; di Mola, F F; Tavano, F; Selvaggi, F; Giese, N; Bassi, C; Büchler, M W; Friess, H; di Sebastiano, P

2012-01-01

We aimed to analyze substance P (SP) and neprilysin (NEP), the membrane metallopeptidase that degrades SP, in chronic pancreatitis (CP). SP and NEP mRNA levels were analyzed by qRT-PCR in tissue samples from 30 patients with CP and 8 organ donors. In addition, SP serum levels were determined before and after surgery in the same patients, by means of a competitive ELISA assay. Genetic and epigenetic analyses of the NEP gene were also performed. SP mRNA expression levels were higher in CP tissues compared to controls (p = 0.0152), while NEP mRNA showed no significant differences between CP and healthy subjects (p = 0.2102). In CP patients, SP serum levels correlated with those in tissue, and after surgical resection SP serum levels were reduced compared to the preoperative values. Failure of NEP to overexpress in CP tissues was associated with significant miR-128a overexpression (p = 0.02), rather than with mutations in the NEP coding region or the presence of hypermethylation sites in the NEP promoter region. Tissue and serum levels of SP were increased in CP, while NEP levels remained unaltered. In an SP/NEP-mediated pathway, it would appear that NEP fails to provide adequate surveillance of SP levels. Failure of NEP to overexpress could be associated with miRNA regulation. Copyright © 2012 S. Karger AG, Basel.

Impact of the Mountain Pine Beetle on the Forest Carbon Cycle in British Columbia from 1999 TO 2008 (Invited)

NASA Astrophysics Data System (ADS)

Chen, J. M.; Czurylowicz, P.; Mo, G.; Black, T. A.

2013-12-01

The unprecedented mountain pine beetle (Dendroctonus ponderosae) (MPB) outbreak in British Columbia starting in 1998 affected about 50% of the lodgepole pine (Pinus contorta var. latifolia) forests occupying about 50% of the land area of the province. The impact of this outbreak on the C cycle is assessed in this study. Annual leaf area index (LAI) maps of the affected area from 1999 to 2008 were produced using SPOT VEGETATION data, and net ecosystem production (NEP) was modeled using inputs of LAI, land cover, soil texture and daily meteorological data with the Boreal Ecosystem Productivity Simulator (BEPS). Both LAI and NEP were validated using field measurements. LAI was found to decrease on average by 20% compared to pre-outbreak conditions, while NEP decreased on average by 90%. Annual NEP values ranged from 2.4 to -8.0 Tg C between 1999 and 2008, with the ecosystem changing from a carbon sink to a carbon source in 2000. The annual average NEP was -2.9 Tg C over the 10 years, resulting in a total loss of carbon of 29 Tg C to the atmosphere. The inter-annual variability of both LAI and NEP was characterized by substantial initial decreases followed by steady increases from 2006 to 2008 with NEP returning to near carbon neutrality in 2008 (-1.8 Pg C/y). The impact of this MPB outbreak appears to be less dramatic than previously anticipated. The apparent fast recovery of LAI and NEP after MPB attacks is examined under the framework of ecosystem resilience which was manifested in the form of secondary overstory and understory growth and increased production of non-attacked host trees.

A Highly Sensitive Multi-Element HgCdTe E-APD Detector for IPDA Lidar Applications

NASA Technical Reports Server (NTRS)

Beck, Jeff; Welch, Terry; Mitra, Pradip; Reiff, Kirk; Sun, Xiaoli; Abshire, James

2014-01-01

An HgCdTe electron avalanche photodiode (e-APD) detector has been developed for lidar receivers, one application of which is integrated path differential absorption lidar measurements of such atmospheric trace gases as CO2 and CH4. The HgCdTe APD has a wide, visible to mid-wave-infrared, spectral response, high dynamic range, substantially improved sensitivity, and an expected improvement in operational lifetime. A demonstration sensor-chip assembly consisting of a 4.3 lm cutoff HgCdTe 4 9 4 APD detector array with 80 micrometer pitch pixels and a custom complementary metal-oxide-semiconductor readout integrated circuit was developed. For one typical array the APD gain was 654 at 12 V with corresponding gain normalized dark currents ranging from 1.2 fA to 3.2 fA. The 4 9 4 detector system was characterized at 77 K with a 1.55 micrometer wavelength, 1 microsecond wide, laser pulse. The measured unit gain detector photon conversion efficiency was 91.1%. At 11 V bias the mean measured APD gain at 77 K was 307.8 with sigma/mean uniformity of 1.23%. The average, noise-bandwidth normalized, system noise-equivalent power (NEP) was 1.04 fW/Hz(exp 1/2) with a sigma/mean of 3.8%. The measured, electronics-limited, bandwidth of 6.8 MHz was more than adequate for 1 microsecond pulse detection. The system had an NEP (3 MHz) of 0.4 fW/Hz(exp 1/2) at 12 V APD bias and a linear dynamic range close to 1000. A gain-independent quantum-limited SNR of 80% of full theoretical was indicative of a gain-independent excess noise factor very close to 1.0 and the expected APD mode quantum efficiency.

Neuropeptide-stimulated cell migration in prostate cancer cells is mediated by RhoA kinase signaling and inhibited by neutral endopeptidase.

PubMed

Zheng, R; Iwase, A; Shen, R; Goodman, O B; Sugimoto, N; Takuwa, Y; Lerner, D J; Nanus, D M

2006-09-28

The neuropeptides bombesin and endothelin-1 stimulate prostate cancer (PC) cell migration and invasion (J Clin Invest, 2000; 106: 1399-1407). The intracellular signaling pathways that direct this cell movement are not well delineated. The monomeric GTPase RhoA is required for migration in several cell types including neutrophils, monocytes and fibroblasts. We demonstrate that bombesin-stimulated PC cell migration occurs via the heterotrimeric G-protein-coupled receptors (G-protein) G alpha 13 subunit leading to activation of RhoA, and Rho-associated coiled-coil forming protein kinase (ROCK). Using siRNA to suppress expression of the three known G-protein alpha-subunit-associated RhoA guanine nucleotide exchange factors (GEFs), we also show that two of these RhoA GEFs, PDZ-RhoGEF and leukemia-associated RhoGEF (LARG), link bombesin receptors to RhoA in a non-redundant manner in PC cells. We next show that focal adhesion kinase, which activates PDZ-RhoGEF and LARG, is required for bombesin-stimulated RhoA activation. Neutral endopeptidase (NEP) is expressed on normal prostate epithelium whereas loss of NEP expression contributes to PC progression. We also demonstrate that NEP inhibits neuropeptide activation of RhoA. Together, these results establish a contiguous signaling pathway from the bombesin receptor to ROCK in PC cells, and they implicate NEP as a major regulator of neuropeptide-stimulated RhoA in these cells. This work also identifies members of this signaling pathway as potential targets for rational pharmacologic manipulation of neuropeptide-stimulated migration of PC cells.

Effect of neutral endopeptidase inhibition on substance-P-induced increase in short-circuit current of canine cultured tracheal epithelium.

PubMed

Tamaoki, J; Sakai, N; Isono, K; Kanemura, T; Chiyotani, A; Yamauchi, F; Takizawa, T; Konno, K

1991-01-01

We studied the effect of substance P (SP) on the electric properties of cultured canine tracheal epithelium and its possible modulation by neutral endopeptidase (NEP) by Ussing's short-circuited technique in vitro. Addition of SP (5 x 10(-6) M) to the mucosal side increased short-circuit current (SCC) from 5.1 +/- 0.9 to 10.3 +/- 2.2 microA/cm2 (mean +/- SE; p less than 0.01), which was accompanied by increases in transepithelial potential difference and conductance. The effect of the mucosal SP on SCC was dose-dependent, with the maximal increase from the baseline value being 5.8 +/- 1.0 microA/cm2 observed at 5 x 10(-5) M. The NEP inhibitor phosphoramidon (10(-5) M) did not affect these responses. On the other hand, SCC was not altered by the addition of SP to the submucosal side. However, it was increased dose-dependently in the presence of phosphoramidon (10(-5) M) but not in the presence of captopril, bestatin or leupeptin. This stimulatory effect of submucosal SP was abolished by furosemide, diphenylamine-2-carboxylate and Cl-free medium, but not by amiloride. These results suggest that SP may selectively stimulate Cl secretion across the airway epithelium and that this effect may be modulated by submucosal NEP.

Neutral endopeptidase knockout induces hyperalgesia in a model of visceral pain, an effect related to bradykinin and nitric oxide.

PubMed

Fischer, Hanspeter S; Zernig, Gerald; Hauser, Kurt F; Gerard, Craig; Hersh, Louis B; Saria, Alois

2002-01-01

Neutral endopeptidase (EC3.4.24.11, NEP, enkephalinase) is a zinc-metalloendopeptidase, cleaving a variety of substrates like enkephalins, substance P, and bradykinin. In the brain, NEP is a key enzyme in the degradation of enkephalins. Pharmacological inhibition of NEP-activity causes analgesia resulting from enhanced extracellular enkephalin concentrations. Recently, transgenic mice lacking the enzyme NEP have been developed (Lu, 1995). The present study was designed to investigate the nociceptive behavior of these NEP-knockout mice. Interestingly, NEP-deficient mice did not respond with decreased pain perception, but exhibited hyperalgesia in the hot-plate jump, warm-water tail-withdrawal, and mostnotablyin theacetic-acid writhing test. Inhibition of aminopeptidase N by bestatin reduced writhing in both strains, whereas NEP-inhibition by thiorphan reduced writhing selectively in wild-type mice. Naloxone increased writhing in wild-type but not in knockouts, whereas the bradykinin B2-receptor antagonist HOE140 reduced writhing selectively in NEP-knockouts. Similarly, the nitric oxide synthase inhibitor L-NAME reduced writhing in NEP-knockouts. These results indicate that genetic elimination of NEP, in contrast to pharmacological inhibition, leads to bradykinin-induced hyperalgesia instead of enkephalin-mediated analgesia. Nitric oxide (NO) is suggested to be involved in this process.

Police Encounters Among Needle Exchange Clients in Baltimore: Drug Law Enforcement as a Structural Determinant of Health

PubMed Central

Cochrane, Jess; Sawyer, Anne L.; Serio-Chapman, Chris; Smelyanskaya, Marina; Han, Jennifer; Robinowitz, Natanya; Sherman, Susan G.

2015-01-01

Objectives. We piloted a monitoring mechanism to document police encounters around programs targeting people who inject drugs (PWID), and assessed their demographic predictors at 2 Baltimore, Maryland, needle exchange program (NEP) sites. Methods. In a brief survey, 308 clients quantified, characterized, and sited recent police encounters. Multivariate linear regression determined encounter predictors, and we used geocoordinate maps to illustrate clusters. Results. Within the past 6 months, clients reported a median of 3 stops near NEP sites (interquartile range [IQR] = 0–7.5) and a median of 1 arrest in any location (IQR = 0–2). Three respondents reported police referral to the NEP. Being younger (P = .009), being male (P = .033), and making frequent NEP visits (P = .02) were associated with reported police stops. Among clients reporting arrest or citation for syringe possession, Whites were significantly less likely than non-Whites to report being en route to or from an NEP (P < .001). Reported encounters were clustered around NEPs. Conclusions. Systematic surveillance of structural determinants of health for PWID proved feasible when integrated into service activities. Improved monitoring is critical to informing interventions to align policing with public health, especially among groups subject to disproportionate levels of drug law enforcement. PMID:26180948

Neutral endopeptidase and kininase II mediate glucocorticoid inhibition of neurogenic inflammation in the rat trachea.

PubMed Central

Piedimonte, G; McDonald, D M; Nadel, J A

1991-01-01

Glucocorticoids inhibit plasma extravasation induced in the rat tracheal mucosa by substance P and other tachykinins released from sensory nerves. This study was performed to determine whether this antiinflammatory effect of glucocorticoids is mediated by the tachykinin-degrading enzymes neutral endopeptidase (NEP) and kininase II (angiotensin converting enzyme, ACE). In addition, we studied the effect of dexamethasone on a nonpeptide inflammatory mediator, platelet-activating factor (PAF), which is not degraded by NEP or ACE. Adult male pathogen-free F344 rats were treated for 2 d with dexamethasone (0.5 mg/kg per d i.p.), or with the vehicle used to dissolve the steroid. The magnitude of plasma extravasation produced by an intravenous injection of substance P (5 micrograms/kg) or PAF (10 micrograms/kg) was then assessed by using Monastral blue pigment as an intravascular tracer. The role of NEP and ACE activities in the changes produced by dexamethasone was investigated by examining the effect of the selective inhibitors of these enzymes, phosphoramidon and captopril. Dexamethasone reduced the substance P-induced extravasation by 57% but did not affect the PAF-induced extravasation. The suppressive effect of dexamethasone on substance P-induced extravasation was completely reversed by simultaneously inhibiting NEP and ACE activities, but the inhibition of these enzymes had no effect on PAF-induced extravasation, regardless of whether the rats were pretreated with dexamethasone or not. These results suggest that NEP and ACE mediate a selective inhibitory effect of glucocorticoids on neurogenic plasma extravasation. PMID:1711545

Combustible dust tests

USDA-ARS?s Scientific Manuscript database

The sugar dust explosion in Georgia on February 7, 2008 killed 14 workers and injured many others (OSHA, 2009). As a consequence of this explosion, OSHA revised its Combustible Dust National Emphasis (NEP) program. The NEP targets 64 industries with more than 1,000 inspections and has found more tha...

The effect of an inhaled neutral endopeptidase inhibitor, thiorphan, on airway responses to neurokinin A in normal humans in vivo.

PubMed

Cheung, D; Bel, E H; Den Hartigh, J; Dijkman, J H; Sterk, P J

1992-06-01

Neuropeptides such as neurokinin A (NKA) have been proposed as important mediators of bronchoconstriction and airway hyperresponsiveness in asthma. Inhaled NKA causes bronchoconstriction in patients with asthma, but not in normal subjects. This is possibly due to the activity of an endogenous neuropeptide-degrading enzyme: neutral endopeptidase (NEP). We investigated whether a NEP-inhibitor, thiorphan, reveals bronchoconstriction to NKA or NKA-induced changes in airway responsiveness to methacholine in normal humans in vivo. Eight normal male subjects participated in a double-blind crossover study, using thiorphan as pretreatment to NKA challenge. Dose-response curves to inhaled NKA (8 to 1,000 micrograms/ml, 0.5 ml/dose) were recorded on 2 randomized days 1 wk apart, and methacholine tests were performed 48 h before and 24 h after the NKA challenge. Ten minutes prior to NKA challenge the subjects inhaled either thiorphan (2.5 mg/ml, 0.5 ml) or placebo. To detect a possible nonspecific effect of thiorphan, we investigated the effect of the same pretreatment with thiorphan or placebo on the dose-response curve to methacholine in a separate set of experiments. The response was measured by the flow from standardized partial expiratory flow-volume curves (V40p), expressed in percent fall from baseline. NKA log dose-response curves were analyzed using the area under the curve (AUC) and the response to the highest dose of 1,000 micrograms/ml (V40p,1000). The methacholine dose-response curves were characterized by their position (PC40V40p) and the maximal-response plateau (MV40p). Baseline V40p was not affected by either pretreatment (p greater than 0.15).(ABSTRACT TRUNCATED AT 250 WORDS)

Patterns of NPP, GPP, respiration, and NEP during boreal forest succession

USGS Publications Warehouse

Goulden, M.L.; Mcmillan, A.M.S.; Winston, G.C.; Rocha, A.V.; Manies, K.L.; Harden, J.W.; Bond-Lamberty, B. P.

2011-01-01

We combined year-round eddy covariance with biometry and biomass harvests along a chronosequence of boreal forest stands that were 1, 6, 15, 23, 40, 74, and 154 years old to understand how ecosystem production and carbon stocks change during recovery from stand-replacing crown fire. Live biomass (Clive) was low in the 1 and 6 year old stands, and increased following a logistic pattern to high levels in the 74 and 154year old stands. Carbon stocks in the forest floor (Cforest floor) and coarse woody debris (CCWD) were comparatively high in the 1year old stand, reduced in the 6 through 40year old stands, and highest in the 74 and 154year old stands. Total net primary production (TNPP) was reduced in the 1 and 6year old stands, highest in the 23 through 74year old stands and somewhat reduced in the 154year old stand. The NPP decline at the 154year old stand was related to increased autotrophic respiration rather than decreased gross primary production (GPP). Net ecosystem production (NEP), calculated by integrated eddy covariance, indicated the 1 and 6 year old stands were losing carbon, the 15year old stand was gaining a small amount of carbon, the 23 and 74year old stands were gaining considerable carbon, and the 40 and 154year old stands were gaining modest amounts of carbon. The recovery from fire was rapid; a linear fit through the NEP observations at the 6 and 15year old stands indicated the transition from carbon source to sink occurred within 11-12 years. The NEP decline at the 154year old stand appears related to increased losses from Clive by tree mortality and possibly from Cforest floor by decomposition. Our findings support the idea that NPP, carbon production efficiency (NPP/GPP), NEP, and carbon storage efficiency (NEP/TNPP) all decrease in old boreal stands. ?? 2010 Blackwell Publishing Ltd.

Successional changes in live and dead wood carbon stores: implications for net ecosystem productivity.

PubMed

Janisch, J E; Harmon, M E

2002-02-01

If forests are to be used in CO2 mitigation projects, it is essential to understand and quantify the impacts of disturbance on net ecosystem productivity (NEP; i.e., the change in ecosystem carbon (C) storage with time). We examined the influence of live tree and coarse woody debris (CWD) on NEP during secondary succession based on data collected along a 500-year chronosequence on the Wind River Ranger District, Washington. We developed a simple statistical model of live and dead wood accumulation and decomposition to predict changes in the woody component of NEP, which we call NEP(w). The transition from negative to positive NEP(w), for a series of scenarios in which none to all wood was left after disturbance, occurred between 0 and 57 years after disturbance. The timing of this transition decreased as live-tree growth rates increased, and increased as CWD left after disturbance increased. Maximum and minimum NEP(w) for all scenarios were 3.9 and -14.1 Mg C ha-1 year-1, respectively. Maximum live and total wood C stores of 319 and 393 Mg C ha(-1), respectively, were reached approximately 200 years after disturbance. Decomposition rates (k) of CWD ranged between 0.013 and 0.043 year-1 for individual stands. Regenerating stands took 41 years to attain a mean live wood mass equivalent to the mean mass of CWD left behind after logging, 40 years to equal the mean CWD mass in 500-year-old forest, and more than 150 years to equal the mean total live and dead wood in an old-growth stand. At a rotation age of 80 years, regenerating stands stored approximately half the wood C of the remaining nearby old-growth forests (predominant age 500 years), indicating that conversion of old-growth forests to younger managed forests results in a significant net release of C to the atmosphere.

Net carbon exchange across the Arctic tundra-boreal forest transition in Alaska 1981-2000

USGS Publications Warehouse

Thompson, Catharine Copass; McGuire, A.D.; Clein, Joy S.; Chapin, F. S.; Beringer, J.

2006-01-01

Shifts in the carbon balance of high-latitude ecosystems could result from differential responses of vegetation and soil processes to changing moisture and temperature regimes and to a lengthening of the growing season. Although shrub expansion and northward movement of treeline should increase carbon inputs, the effects of these vegetation changes on net carbon exchange have not been evaluated. We selected low shrub, tall shrub, and forest tundra sites near treeline in northwestern Alaska, representing the major structural transitions expected in response to warming. In these sites, we measured aboveground net primary production (ANPP) and vegetation and soil carbon and nitrogen pools, and used these data to parameterize the Terrestrial Ecosystem Model. We simulated the response of carbon balance components to air temperature and precipitation trends during 1981-2000. In areas experiencing warmer and dryer conditions, Net Primary Production (NPP) decreased and heterotrophic respiration (R H ) increased, leading to a decrease in Net Ecosystem Production (NEP). In warmer and wetter conditions NPP increased, but the response was exceeded by an increase in R H ; therefore, NEP also decreased. Lastly, in colder and wetter regions, the increase in NPP exceeded a small decline in R H , leading to an increase in NEP. The net effect for the region was a slight gain in ecosystem carbon storage over the 20 year period. This research highlights the potential importance of spatial variability in ecosystem responses to climate change in assessing the response of carbon storage in northern Alaska over the last two decades. ?? Springer 2005.

Hydrological and Climate Controls on Hyporheic Contributions to River Net Ecosystem Productivity

NASA Astrophysics Data System (ADS)

Newcomer, M. E.; Hubbard, S. S.; Fleckenstein, J. H.; Maier, U.; Schmidt, C.; Laube, G.; Chen, N.; Ulrich, C.; Dwivedi, D.; Steefel, C. I.; Rubin, Y.

2016-12-01

Hyporheic zone contributions to river net ecosystem productivity (NEP) can represent a substantial source or sink for organic and inorganic carbon (C). Hyporheic zone processes are estimated to vary with network location as a function of river-aquifer interactions as well as with climatic factors supporting riverbed gross primary productivity (GPP) and ecosystem respiration. Even though hyporheic zone NEP is hypothesized to be a significant budgetary component to river-aquifer biogeochemical cycling, models of river NEP often parameterize hyporheic zone contributions as a space-time constant input of CO2 to rivers, leading to overestimation of hyporheic zone NEP and underestimation of C storage. This assumption is problematic during the summer growing season, when GPP is largest and C is stored in surface and subsurface biomass. We investigated the dynamic role of hyporheic zone NEP using the MIN3P flow and reactive transport model with surface water GPP and ecosystem respiration simulated as a function of light, depth, temperature, pH, and atmospheric CO2. We simulated hyporheic zone NEP for low-order and high-order streams, which collectively represent a range of characteristic flow paths and subsurface residence times. Downscaled climate predictions of temperature and atmospheric CO2 representing carbon emission futures were used to force the models and to compare future and current hyporheic zone NEP. Our results show that river-aquifer flow conditions determine the relative role of the river as either a store or sink of C through direct contributions of O2 and dissolved organic content from river GPP. Modeled results show that high discharge, high order rivers are net stores of CO2 from the atmosphere; however this is dependent on perturbation events that allow stored C from summer GPP to be released (i.e. rising water tables during winter storms). Lacking a perturbation event, C remains in pore-water storage as dissolved CO2 and biomass. Conversely, low-discharge mountainous streams with continuous hyporheic zone flow represent a net source of CO2, with future temperature rises stimulating additional heterotrophic activity. Our work contributes to a better understanding of how river and hyporheic zone processes significantly influence biogeochemical cycling under changing climate conditions.

Enhanced Monitoring of Nanosecond Electric Pulse-Evoked Membrane Conductance Changes in Whole-Cell Patch Clamp Experiments.

PubMed

Yoon, Jihwan; Leblanc, Normand; Zaklit, Josette; Vernier, P Thomas; Chatterjee, Indira; Craviso, Gale L

2016-10-01

Patch clamp electrophysiology serves as a powerful method for studying changes in plasma membrane ion conductance induced by externally applied high-intensity nanosecond electric pulses (NEPs). This paper describes an enhanced monitoring technique that minimizes the length of time between pulse exposure and data recording in a patch-clamped excitable cell. Whole-cell membrane currents were continuously recorded up to 11 ms before and resumed 8 ms after delivery of a 5-ns, 6 MV/m pulse by a pair of tungsten rod electrodes to a patched adrenal chromaffin cell maintained at a holding potential of -70 mV. This timing was achieved by two sets of relay switches. One set was used to disconnect the patch pipette electrode from the pre-amplifier and connect it to a battery to maintain membrane potential at -70 mV, and also to disconnect the reference electrode from the amplifier. The other set was used to disconnect the electrodes from the pulse generator until the time of NEP/sham exposure. The sequence and timing of both sets of relays were computer-controlled. Using this procedure, we observed that a 5-ns pulse induced an instantaneous inward current that decayed exponentially over the course of several minutes, that a second pulse induced a similar response, and that the current was carried, at least in part, by Na + . This approach for characterizing ion conductance changes in an excitable cell in response to NEPs will yield information essential for assessing the potential use of NEP stimulation for therapeutic applications.

Developmental toxic effects of N-ethyl-2-pyrrolidone administered orally to rats.

PubMed

Saillenfait, A M; Gallissot, F; Sabaté, J P

2007-01-01

The developmental toxicity of N-ethyl-2-pyrrolidone (NEP) was studied in Sprague-Dawley rats after oral administration. Pregnant rats were given NEP at doses of 0 (distilled water), 50, 250, 500 and 750 mg kg(-1) day(-1), by gavage (5 ml kg(-1)), on gestational days (GD) 6-20. Maternal toxicity, as evidenced by reduction in body weight gain and food consumption, was observed in all NEP groups at the beginning of treatment (GD 6-9). The incidence of resorptions was significantly increased at 500 mg kg(-1) day(-1), and reached 83% at 750 mg kg(-1) day(-1). There was a dose-related decrease in fetal weight, which was significantly lower than control at 250 mg kg(-1) day(-1) and higher doses. The incidence of malformed fetuses per litter and the number of litters with malformed fetuses were significantly increased at 500 and 750 mg kg(-1) day(-1). Malformations mainly consisted of edema, anal atresia with absent tail, cardiovascular defects and fused cervical arches. Ossification of skull bones and sternebrae was significantly reduced at 500 and 750 mg kg(-1) day(-1). The incidence of supernumerary ribs was significantly elevated at 250 mg kg(-1) day(-1) and higher doses. In conclusion, NEP administered by gavage is embryotoxic and teratogenic at maternal toxic doses. (c) 2007 John Wiley & Sons, Ltd.

Heterologous Expression and Isolation of Influenza A Virus Nuclear Export Protein NEP.

PubMed

Golovko, A O; Koroleva, O N; Drutsa, V L

2017-12-01

Influenza A virus nuclear export protein NEP (NS2, 14.4 kDa) plays a key role in various steps of the virus life cycle. Highly purified protein preparations are required for structural and functional studies. In this study, we designed a series of Escherichia coli plasmid constructs for highly efficient expression of the NEP gene under control of the constitutive trp promoter. An efficient method for extraction of NEP from inclusion bodies based on dodecyl sulfate treatment was developed. Preparations of purified NEP with either N- or C-terminal (His) 6 -tag were obtained using Ni-NTA agarose affinity chromatography with yield of more than 20 mg per liter of culture. According to CD data, the secondary structure of the proteins matched that of natural NEP. A high propensity of NEP to aggregate over a wide range of conditions was observed.

n-Ethyl Pentylone-Related Deaths in Alabama.

PubMed

Atherton, Daniel; Dye, Daniel; Robinson, C Andrew; Beck, Rachel

2018-05-16

n-Ethyl pentylone (NEP) is a chemical substance derived from cathinone. Synthetic cathinones are an evolving group of drugs with stimulating, mind-altering effects sometimes referred to as novel or new psychoactive substances (NPS). There is scarce information in the medical literature regarding forensic cases in which NEP is detected in toxicological testing. We present four fatalities involving NEP from Alabama in 2017. Deaths were attributed to NEP toxicity in two cases (peripheral blood concentrations of 0.121 and 0.953 mg/L) and injuries caused by gunshot wounds in two cases (peripheral blood concentrations of 0.045 and 0.031 mg/L). One case involving NEP described an individual who exhibited classic CNS-stimulant induced erratic behavior before being found dead. These cases enhance the forensic literature regarding specific NPS like NEP and provide contextual reference for professionals considering the significance of NEP in toxicological interpretation. © 2018 American Academy of Forensic Sciences.

3D Nanochannel Array Platform for High-throughput Cell Manipulation and Nano-electroporation

NASA Astrophysics Data System (ADS)

Chang, Lingqian

Electroporation is one of the most common non-viral methods for gene delivery. Recent progress in gene therapy has offered special opportunities to electroporation for in vitro and in vivo applications. However, conventional bulk electroporation (BEP) inevitably causes serious cell damage and stochastic transfection between cells. Microfluidic electroporation (MEP) has been claimed to provide benign single cell transfection for the last decade. Nevertheless, the intracellular transport in both MEP and BEP systems is highly diffusion-dominant, which prevents precise dose control and high uniformity. In this Ph.D. research, we developed a 3D nanochannel-electroporation (3D NEP) platform for mass cell transfection. A silicon-based nanochannel array (3D NEP) chip was designed and fabricated for cell manipulation and electroporation. The chip, designed as Z-directional microchannel - nanochannel array, was fabricated by clean room techniques including projection photolithography and deep reactive-ion etching (DRIE). The fabricated 3D NEP chip is capable of handling 40,000 cells per 1 cm2, up to 1 million per wafer (100 mm diameter). High-throughput cell manipulation technologies were investigated for precise alignment of individual cells to the nanochannel array, a key step for NEP to achieve dose control. We developed three techniques for cell trapping in this work. (1) Magnetic tweezers (MTs) were integrated on the chip to remotely control cells under a programmed magnetic field. (2) A positive dielectrophoresis (pDEP) power system was built as an alternative to trap cells onto the nanochannel array using DEP force. (3) A novel yet simple 'dipping-trap' method was used to rapidly trap cells onto a nanochannel array, aligned by a micro-cap array pattern on the 3D NEP chip, which eventually offered 70 - 90 % trapping efficiency and 90 % specificity. 3D NEP platforms were assembled for cell transfection based on the Si-based nanochannel array chip and cell manipulation techniques. Cells were patterned on the nanochannel array and collectively were electroporated in parallel, injected with cargo in Z-direction. Controlling the dose was demonstrated with the external pulse durations at high-throughput. The 'electrophoretic'- expedited delivery of large molecular weight plasmids were demonstrated with large numbers of primary cells simultaneously, which cannot be achieved in BEP and MEP. Two clinically valuable case studies were performed with our 3D NEP for living cell sensing / interrogation. (1) In the case of in vitro transfection of primary cardiomyocytes, we studied the dose-effects of miR-29 on mitochondrial changes and the suppression of the Mcl-1 gene in adult mouse cardiomyocytes by precisely controlling the miR-29 dose injected. (2) Glioma stem cells (GSCs), a type of cell hypothesized to be highly aggressive and to lead to the relapses of gliobastoma in human brain, was studied at single cell resolution on 3D NEP platform. The developed 3D NEP system moves towards clinically oriented and user-friendly tools for life science applications. The batch-treated cells with controlled dosage delivery provide a useful tool for single cell analysis. The pioneering experiments in this work have demonstrated the 3D NEP for the applications of cell reprogramming, adoptive immunotherapy, in vitro cardiomyocytes transfection and glioma stem cells study.

Structure-based design of NS2 mutants for attenuated influenza A virus vaccines.

PubMed

Akarsu, Hatice; Iwatsuki-Horimoto, Kiyoko; Noda, Takeshi; Kawakami, Eiryo; Katsura, Hiroaki; Baudin, Florence; Horimoto, Taisuke; Kawaoka, Yoshihiro

2011-01-01

We previously characterised the matrix 1 (M1)-binding domain of the influenza A virus NS2/nuclear export protein (NEP), reporting a critical role for the tryptophan (W78) residue that is surrounded by a cluster of glutamate residues in the C-terminal region that interacts with the M1 protein (Akarsu et al., 2003). To gain further insight into the functional role of this interaction, here we used reverse genetics to generate a series of A/WSN/33 (H1N1)-based NS2/NEP mutants for W78 or the C-terminal glutamate residues and assessed their effect on virus growth. We found that simultaneous mutations at three positions (E67S/E74S/E75S) of NS2/NEP were important for inhibition of influenza viral polymerase activity, although the W78S mutant and other glutamate mutants with single substitutions were not. In addition, double and triple substitutions in the NS2/NEP glutamine residues, which resulted in the addition of seven amino acids to the C-terminus of NS1 due to gene overlapping, resulted in virus attenuation in mice. Animal studies with this mutant suggest a potential benefit to incorporating these NS mutations into live vaccines. Copyright © 2010 Elsevier B.V. All rights reserved.

Neprilysin and Aβ Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer’s Disease

PubMed Central

Grimm, Marcus O. W.; Mett, Janine; Stahlmann, Christoph P.; Haupenthal, Viola J.; Zimmer, Valerie C.; Hartmann, Tobias

2013-01-01

One of the characteristic hallmarks of Alzheimer’s disease (AD) is an accumulation of amyloid β (Aβ) leading to plaque formation and toxic oligomeric Aβ complexes. Besides the de novo synthesis of Aβ caused by amyloidogenic processing of the amyloid precursor protein (APP), Aβ levels are also highly dependent on Aβ degradation. Several enzymes are described to cleave Aβ. In this review we focus on one of the most prominent Aβ degrading enzymes, the zinc-metalloprotease Neprilysin (NEP). In the first part of the review we discuss beside the general role of NEP in Aβ degradation the alterations of the enzyme observed during normal aging and the progression of AD. In vivo and cell culture experiments reveal that a decreased NEP level results in an increased Aβ level and vice versa. In a pathological situation like AD, it has been reported that NEP levels and activity are decreased and it has been suggested that certain polymorphisms in the NEP gene result in an increased risk for AD. Conversely, increasing NEP activity in AD mouse models revealed an improvement in some behavioral tests. Therefore it has been suggested that increasing NEP might be an interesting potential target to treat or to be protective for AD making it indispensable to understand the regulation of NEP. Interestingly, it is discussed that the APP intracellular domain (AICD), one of the cleavage products of APP processing, which has high similarities to Notch receptor processing, might be involved in the transcriptional regulation of NEP. However, the mechanisms of NEP regulation by AICD, which might be helpful to develop new therapeutic strategies, are up to now controversially discussed and summarized in the second part of this review. In addition, we review the impact of AICD not only in the transcriptional regulation of NEP but also of further genes. PMID:24391587

Risk Informed Design and Analysis Criteria for Nuclear Structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salmon, Michael W.

2015-06-17

Target performance can be achieved by defining design basis ground motion from results of a probabilistic seismic hazards assessment, and introducing known levels of conservatism in the design above the DBE. ASCE 4, 43, DOE-STD-1020 defined the DBE at 4x10-4 and introduce only slight levels of conservatism in response. ASCE 4, 43, DOE-STD-1020 assume code capacities shoot for about 98% NEP. There is a need to have a uniform target (98% NEP) for code developers (ACI, AISC, etc.) to aim for. In considering strengthening options, one must also consider cost/risk reduction achieved.

Workplace nutrition knowledge questionnaire: psychometric validation and application.

PubMed

Guadagnin, Simone C; Nakano, Eduardo Y; Dutra, Eliane S; de Carvalho, Kênia M B; Ito, Marina K

2016-11-01

Workplace dietary intervention studies in low- and middle-income countries using psychometrically sound measures are scarce. This study aimed to validate a nutrition knowledge questionnaire (NQ) and its utility in evaluating the changes in knowledge among participants of a Nutrition Education Program (NEP) conducted at the workplace. A NQ was tested for construct validity, internal consistency and discriminant validity. It was applied in a NEP conducted at six workplaces, in order to evaluate the effect of an interactive or a lecture-based education programme on nutrition knowledge. Four knowledge domains comprising twenty-three items were extracted in the final version of the NQ. Internal consistency of each domain was significant, with Kuder-Richardson formula values>0·60. These four domains presented a good fit in the confirmatory factor analysis. In the discriminant validity test, both the Expert and Lay groups scored>0·52, but the Expert group scores were significantly higher than those of the Lay group in all domains. When the NQ was applied in the NEP, the overall questionnaire scores increased significantly because of the NEP intervention, in both groups (P<0·001). However, the increase in NQ scores was significantly higher in the interactive group than in the lecture group, in the overall score (P=0·008) and in the healthy eating domain (P=0·009). The validated NQ is a short and useful tool to assess gain in nutrition knowledge among participants of NEP at the workplace. According to the NQ, an interactive nutrition education had a higher impact on nutrition knowledge than a lecture programme.

An Empirical Test of Anchoring the NEP Scale in Environmental Ethics

ERIC Educational Resources Information Center

Noblet, Caroline L.; Anderson, Mark; Teisl, Mario F.

2013-01-01

Some argue that the new ecological paradigm (NEP) scale is incomplete and does not adequately reflect contemporary debates in environmental ethics. We focus on one specific shortcoming of the NEP, its lack of an item to reflect an ecocentric viewpoint. To test this concern, we administered the NEP to three different audiences and included one…

Summary and recommendations on nuclear electric propulsion technology for the space exploration initiative

NASA Technical Reports Server (NTRS)

Doherty, Michael P.; Holcomb, Robert S.

1993-01-01

A project in Nuclear Electric Propulsion (NEP) technology is being established to develop the NEP technologies needed for advanced propulsion systems. A paced approach has been suggested which calls for progressive development of NEP component and subsystem level technologies. This approach will lead to major facility testing to achieve TRL-5 for megawatt NEP for SEI mission applications. This approach is designed to validate NEP power and propulsion technologies from kilowatt class to megawatt class ratings. Such a paced approach would have the benefit of achieving the development, testing, and flight of NEP systems in an evolutionary manner. This approach may also have the additional benefit of synergistic application with SEI extraterrestrial surface nuclear power applications.

Injecting Drug Users Retention in Needle-Exchange Program and its Determinants in Iran Prisons

PubMed Central

Shahbazi, Mohammad; Farnia, Marzieh; Moradi, Ghobad; Karamati, Mohammadreza; Paknazar, Fatemeh; Mirmohammad Khani, Majid

2015-01-01

Background: Participation and to stay in a health program depends on many factors. One of these programs is Needle Exchange Program (NEP) in prisons. Objectives: The current study aimed to evaluate the retention of injecting drug prisoners and find the related factors in Iran. Patients and Methods: This cohort study analyzed data about injecting drug male prisoners who were participated in NEP in three Iranian prisons. Data was collected from October 2009 to June 2010. A proper approach of survival analyses including Kaplan-Meier method, Log-Rank test, and Cox Proportional Hazard Model were used to evaluate Injecting Drug Users (IDUs) retention in NEP and its determinants. Results: Out of 320 prisoners, 167 were from Isfahan Central Prison, 82 from Tehran-Ghezel-Hesar Prison, and 71 from Hamadan Central Prison. Two-hundred and fifty prisoners (78.4%) had history of drug injection; and drug injection was the most common choice for 115 persons (35.9%). Participants were followed up for 29 weeks, the mean (SD) time of retention in the program was 24.1 (0.6) weeks. There was a significant relationship between age, number of used needles per week, duration of addiction, age of addiction onset, as well as imprisonment age, main method of drug use, type of main using drug, Hepatitis B Virus (HBV) infection, job status, reason of arrestment, history of involvement in harm reduction programs, and the length of retention (P < 0.05). There was also significant relationship between the history of using harm reduction services (P = 0.007), tattooing (P = 0.01), longer durations of addiction (P = 0.048), and retention. Conclusions: Tattooing and longer duration of addiction were two important factors that significantly increased retention in the program. In contrast, history of using harm reduction services was the factor that decreased persistence. The risk of quitting the program may decrease about 68% in those who did not involve in harm reduction programs. PMID:26405681

Effect of Land Use Legacy on Forest Carbon Dynamics in the NE U.S.

NASA Astrophysics Data System (ADS)

Felzer, B. S.

2016-12-01

Forest stand age is a prime determinant of the strength of the carbon sink, as younger, growing forests tend to be stronger sinks than more mature forests. The substantial carbon sink in the NE U.S. is due to forests regrowing from previous disturbance. The particular type of disturbance, whether agricultural abandonment, timber harvest, or fire, can have an impact on the Net Ecosystem Productivity (NEP) observed today, especially for more recently disturbed forests. Nutrient levels, particularly nitrogen, are the most important factor determining the rate of regrowth following disturbance. Agriculture results in depletion of nutrients from the soil, so often results in slower regrowth than timber harvest, for example. If fire is also used during harvesting, nutrient depletion may be even more severe. This study will use the 1 km USDA forest stand age data for the NE U.S. for a series of model sensitivity experiments with the TEM-Hydro model. Three simulations will apply a single disturbance to result in the correct stand age, with agricultural abandonment, timber harvest, and fire applied at the year of disturbance, respectively. A 1/8o run will explore how aggregated stand age affects NEP relative to higher resolution stand age. Preliminary results for a single grid in PA show timber harvest has faster regrowth than regrowth from agricultural abandonment, though fertilization quickens regrowth rates. The effect of crops on NEP is a larger sink than timber harvest in the 5 years following disturbance, but a smaller sink in the decades following, with equivalent NEP values after about 50 years. A simple stand age mixture experiment shows that heterogeneous stand age matters most in the first 20 years following disturbance. These methods will be applied to realistic stand ages for the entire NE U.S. to determine the importance of disturbance type on forest regrowth.

Vasopeptidase inhibition with omapatrilat increases fluid and protein microvascular permeability in cat skeletal muscle.

PubMed

Persson, Johan; Morsing, Peter; Grände, Per-Olof

2004-03-01

Vasopeptidase inhibition is a new antihypertensive approach combining inhibition of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), but severe oedema, mainly angio-oedema, has been reported. As ACE and NEP catalyse degradation of the permeability-increasing peptide bradykinin, and NEP also catalyses degradation of permeability-increasing peptides such as atrial natriuretic peptide, substance P, endothelin-1 and angiotensin II, vasopeptidase inhibition may increase microvascular permeability. To analyse the effects of vasopeptidase inhibition on permeability. The study was performed on the autoperfused cat calf skeletal muscle, evaluating the effects on fluid and protein permeability of a clinically relevant dose of the vasopeptidase inhibitor, omapatrilat. The effects were compared with those of the vehicle, of selective ACE and NEP inhibition, and of omapatrilat during bradykinin receptor blockade. Effects on fluid permeability were determined with a capillary filtration coefficient (CFC) technique, and effects on protein permeability were assessed from changes in the osmotic reflection coefficient for albumin. After 1.5 h of intravenous infusion of omapatrilat (0.35 mg/kg per hour), mean arterial pressure was reduced from 114 mmHg to 86 mmHg (P < 0.01) and skeletal muscle vascular resistance was reduced from 14.5 peripheral resistance units (PRU) to 11.5 PRU (P < 0.05). CFC was increased by 22% (P < 0.01) and the reflection coefficient was decreased by 17% (P < 0.01). Infusion of vehicle had no effects. Inhibition of NEP increased permeability without affecting blood pressure, whereas ACE inhibition decreased blood pressure without affecting permeability. The increase in permeability associated with omapatrilat was reduced by bradykinin blockade. A clinically relevant antihypertensive dose of omapatrilat reduces vascular resistance and increases fluid and protein permeability, the permeability effect more by inhibition of NEP than by inhibition of ACE, by a mechanism involving bradykinin.

A Polyphenol-Rich Fraction Obtained from Table Grapes Decreases Adiposity, Insulin Resistance, and Markers of Inflammation and Impacts Gut Microbiota in High-Fat Fed Mice

PubMed Central

Collins, Brian; Hoffman, Jessie; Martinez, Kristina; Grace, Mary; Lila, Mary Ann; Cockrell, Chase; Nadimpalli, Anuradha; Chang, Eugene; Chuang, Chia-Chi; Zhong, Wei; Mackert, Jessica; Shen, Wan; Cooney, Paula; Hopkins, Robin; McIntosh, Michael

2016-01-01

The objective of this study was to determine if consuming an extractable or non-extractable fraction of table grapes reduced the metabolic consequences of consuming a high-fat, American-type diet. Male C57BL/6J mice were fed a low fat (LF) diet, a high fat (HF) diet, or a HF diet containing whole table grape powder (5% w/w), an extractable, polyphenol-rich (HF-EP) fraction, a non-extractable, polyphenol-poor (HF-NEP) fraction, or equal combinations of both fractions (HF-EP+NEP) from grape powder for 16 weeks. Mice fed the HF-EP and HF-EP+NEP diets had lower percentages of body fat and amounts of white adipose tissue (WAT) and improved glucose tolerance compared to the HF-fed controls. Mice fed the HF-EP+NEP diet had lower liver weights and triglyceride (TG) levels compared to the HF-fed controls. Mice fed the HF-EP+NEP diets had higher hepatic mRNA levels of hormone sensitive lipase and adipose TG lipase, and decreased expression of c-reactive protein compared to the HF-fed controls. In epididymal (visceral) WAT, the expression levels of several inflammatory genes were lower in mice fed the HF-EP and HF-EP+NEP diets compared to the HF-fed controls. Mice fed the HF diets had increased myeloperoxidase activity and impaired localization of the tight junction protein zonula occludens-1 in ileal mucosa compared to the HF-EP and HF-NEP diets. Several of these treatment effects were associated with alterations in gut bacterial community structure. Collectively, these data demonstrate that the polyphenol-rich, EP fraction from table grapes attenuated many of the adverse health consequences associated with consuming a HF diet. PMID:27133434

Meta-analysis of expression and function of neprilysin in Alzheimer's disease.

PubMed

Zhang, Huifeng; Liu, Dan; Wang, Yixing; Huang, Huanhuan; Zhao, Yujia; Zhou, Hui

2017-09-14

Neprilysin (NEP) is one of the most important Aβ-degrading enzymes, and its expression and activity in Alzheimer's brain have been widely reported, but the results remain debatable. Thus, the meta-analysis was performed to elucidate the role of NEP in Alzheimer's disease (AD). The relevant case-control or cohort studies were retrieved according to our inclusion/exclusion criteria. Six studies with 123 controls and 141 AD cases, seven studies with 102 controls and 90 AD cases, and four studies with 93 controls and 132 AD cases were included in meta-analysis of NEP's protein, mRNA, and enzyme activity respectively. We conducted Meta regression to detect the sources of heterogeneity and further performed cumulative meta-analysis or subgroup analysis. Our meta-analysis revealed a significantly lower level of NEP mRNA (SMD=-0.44, 95%CI: -0.87, -0.00, p=0.049) in AD cases than in non-AD cases, and such pattern was not altered over time in the cumulative meta-analysis. However, the decrease of NEP protein (SMD=-0.18, 95%CI: -0.62, 0.25) and enzyme activity (SMD=-0.35, 95%CI: -1.03, 0.32) in AD cases did not pass the significance check, while the cumulative meta-analysis by average age showed the pooled effect became insignificant as adding the studies with younger subjects, which indicates that the protein expression and enzyme activity of NEP in the cortex are affected by age. Therefore, the present meta-analysis suggests the need of further investigation of roles of NEP in AD pathogenesis and treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Diagnostic Accuracy of the Slump Test for Identifying Neuropathic Pain in the Lower Limb.

PubMed

Urban, Lawrence M; MacNeil, Brian J

2015-08-01

Diagnostic accuracy study with nonconsecutive enrollment. To assess the diagnostic accuracy of the slump test for neuropathic pain (NeP) in those with low to moderate levels of chronic low back pain (LBP), and to determine whether accuracy of the slump test improves by adding anatomical or qualitative pain descriptors. Neuropathic pain has been linked with poor outcomes, likely due to inadequate diagnosis, which precludes treatment specific for NeP. Current diagnostic approaches are time consuming or lack accuracy. A convenience sample of 21 individuals with LBP, with or without radiating leg pain, was recruited. A standardized neurosensory examination was used to determine the reference diagnosis for NeP. Afterward, the slump test was administered to all participants. Reports of pain location and quality produced during the slump test were recorded. The neurosensory examination designated 11 of the 21 participants with LBP/sciatica as having NeP. The slump test displayed high sensitivity (0.91), moderate specificity (0.70), a positive likelihood ratio of 3.03, and a negative likelihood ratio of 0.13. Adding the criterion of pain below the knee significantly increased specificity to 1.00 (positive likelihood ratio = 11.9). Pain-quality descriptors did not improve diagnostic accuracy. The slump test was highly sensitive in identifying NeP within the study sample. Adding a pain-location criterion improved specificity. Combining the diagnostic outcomes was very effective in identifying all those without NeP and half of those with NeP. Limitations arising from the small and narrow spectrum of participants with LBP/sciatica sampled within the study prevent application of the findings to a wider population. Diagnosis, level 4-.

Acute effect of the dual angiotensin-converting enzyme and neutral endopeptidase 24-11 inhibitor mixanpril on insulin sensitivity in obese Zucker rat

PubMed Central

Arbin, V; Claperon, N; Fournié-Zaluski, M -C; Roques, B P; Peyroux, J

2001-01-01

The aim of this study was to determine whether acute dual angiotensin-converting enzyme (ACE)/neutral endopeptidase 24-11 (NEP) inhibition could improve whole body insulin-mediated glucose disposal (IMGD) more than ACE inhibition alone and whether this effect was mediated by the kinin-nitric oxide (NO) pathway activation.We therefore compared in anaesthetized obese (fa/fa) Zucker rats (ZOs) the effects of captopril (2 mg kg−1, i.v.+2 mg kg−1 h−1), retrothiorphan (25 mg kg−1, i.v. +25 mg  kg−1 h−1), a selective NEP inhibitor, and mixanpril (25 mg kg−1, i.v.+25 mg kg−1 h−1), a dual ACE/NEP inhibitor, on IMGD using hyperinsulinaemic euglycaemic clamp technique. The role of the kinin-NO pathway in the effects of mixanpril was tested using a bradykinin B2 receptor antagonist (Hoe-140, 300 μg kg−1) and a NO-synthase inhibitor (Nω-nitro-L-arginine methyl ester, L-NAME, 10 mg kg−1 i.v. +10 mg kg−1 h−1) as pretreatments.Insulin sensitivity index (ISI) was lower in ZO controls than in lean littermates. Increases in ISI were observed in captopril- and retrothiorphan-treated ZOs. In mixanpril-treated ZOs, ISI was further increased, compared to captopril- and retrothiorphan-treated ZOs.In ZOs, Hoe-140 and L-NAME alone did not significantly alter and slightly reduced the ISI respectively. Hoe-140 and L-NAME markedly inhibited the ISI improvement induced by mixanpril.These results show that in obese insulin-resistant Zucker rats, under acute conditions, NEP or ACE inhibition can improve IMGD and that dual ACE/NEP inhibition improves IMGD more effectively than does either single inhibition. This effect is linked to an increased activation of the kinin-NO pathway. PMID:11399666

New Function for an Old Enzyme: NEP Deficient Mice Develop Late-Onset Obesity

PubMed Central

Becker, Matthias; Siems, Wolf-Eberhard; Kluge, Reinhart; Gembardt, Florian; Schultheiss, Heinz-Peter; Schirner, Michael; Walther, Thomas

2010-01-01

Background According to the World Health Organization (WHO) there is a pandemic of obesity with approximately 300 million people being obese. Typically, human obesity has a polygenetic causation. Neutral endopeptidase (NEP), also known as neprilysin, is considered to be one of the key enzymes in the metabolism of many active peptide hormones. Methodology/Principal Findings An incidental observation in NEP-deficient mice was a late-onset excessive gain in body weight exclusively from a ubiquitous accumulation of fat tissue. In accord with polygenetic human obesity, mice were characterized by deregulation of lipid metabolism, higher blood glucose levels, with impaired glucose tolerance. The key role of NEP in determining body mass was confirmed by the use of the NEP inhibitor candoxatril in wild-type mice that increased body weight due to increased food intake. This is a peripheral and not a central NEP action on the switch for appetite control, since candoxatril cannot cross the blood-brain barrier. Furthermore, we demonstrated that inhibition of NEP in mice with cachexia delayed rapid body weight loss. Thus, lack in NEP activity, genetically or pharmacologically, leads to a gain in body fat. Conclusions/Significance In the present study, we have identified NEP to be a crucial player in the development of obesity. NEP-deficient mice start to become obese under a normocaloric diet in an age of 6–7 months and thus are an ideal model for the typical human late-onset obesity. Therefore, the described obesity model is an ideal tool for research on development, molecular mechanisms, diagnosis, and therapy of the pandemic obesity. PMID:20862277

New function for an old enzyme: NEP deficient mice develop late-onset obesity.

PubMed

Becker, Matthias; Siems, Wolf-Eberhard; Kluge, Reinhart; Gembardt, Florian; Schultheiss, Heinz-Peter; Schirner, Michael; Walther, Thomas

2010-09-16

According to the World Health Organization (WHO) there is a pandemic of obesity with approximately 300 million people being obese. Typically, human obesity has a polygenetic causation. Neutral endopeptidase (NEP), also known as neprilysin, is considered to be one of the key enzymes in the metabolism of many active peptide hormones. An incidental observation in NEP-deficient mice was a late-onset excessive gain in body weight exclusively from a ubiquitous accumulation of fat tissue. In accord with polygenetic human obesity, mice were characterized by deregulation of lipid metabolism, higher blood glucose levels, with impaired glucose tolerance. The key role of NEP in determining body mass was confirmed by the use of the NEP inhibitor candoxatril in wild-type mice that increased body weight due to increased food intake. This is a peripheral and not a central NEP action on the switch for appetite control, since candoxatril cannot cross the blood-brain barrier. Furthermore, we demonstrated that inhibition of NEP in mice with cachexia delayed rapid body weight loss. Thus, lack in NEP activity, genetically or pharmacologically, leads to a gain in body fat. In the present study, we have identified NEP to be a crucial player in the development of obesity. NEP-deficient mice start to become obese under a normocaloric diet in an age of 6-7 months and thus are an ideal model for the typical human late-onset obesity. Therefore, the described obesity model is an ideal tool for research on development, molecular mechanisms, diagnosis, and therapy of the pandemic obesity.

Peptidases of the peripheral chemoreceptors: biochemical, immunological, in vitro hydrolytic studies and electron microscopic analysis of neutral endopeptidase-like activity of the carotid body.

PubMed

Kumar, G K

1997-02-14

The purposes of the present study are to identify and characterize the major peptidase(s) that may be involved in the inactivation of neuropeptides in the mammalian carotid body. Measurements of a number of peptidase activities in the cell-free extract of the cat carotid body using specific substrates and inhibitors indicated that the previously identified neutral endopeptidase (NEP)-like activity [Kumar et al., Brain Res., 517 (1990) 341-343] is the major peptidase in the chemoreceptor tissue. The NEP-like activity of the carotid body was further characterized using a monoclonal antibody to human neutral endopeptidase, EC 3.4.24.11. Immune blot analysis indicated strong immunoreactivity toward the cat and calf carotid bodies but a weak cross-reactivity with the rabbit carotid body. Furthermore, western blot analysis of the cat carotid body extract revealed the presence of a major 97-kDa protein and a minor 200-kDa protein. The 97-kDa NEP form of the carotid body was comparable to EC 3.4.24.11 and was consistent with its reported molecular weight suggesting NEP-like activity of the carotid body is structurally similar to the neutral endopeptidase, EC 3.4.24.11. In order to assess whether NEP is the primary peptide degrading activity in the cat carotid body in vitro hydrolysis studies using substance P (SP) as a model peptide were performed. HPLC analysis showed that SP is hydrolyzed maximally at pH 7.0 by carotid body peptidases with the formation of SP(1-7) and SP(1-8) as stable intermediates. Inhibitors specific to NEP also inhibited the SP-hydrolyzing activity of the carotid body. Analyses of the cell-free extracts showed the occurrence of both NEP and SP-hydrolyzing activities in the rabbit and rat carotid bodies although at 2- and 4-fold lower levels respectively than that observed in the cat carotid body. Immunoelectron microscopy showed that NEP-specific immunoreactivity is associated with the intercellular region between the type I cells and cell clusters of the carotid body. Taken together, the results from this investigation demonstrate that neutral endopeptidase (EC 3.4.24.11) is one of the major endopeptidases which mediates the degradation and inactivation of neuropeptides in the carotid body.

Stressed and unstressed Ge:Ga detector arrays for airborne astronomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stacey, G.J.; Beeman, J.W.; Haller, E.E.

1992-11-01

We have constructed and used two dimensional arrays of both unstressed and stressed Ge:GA photoconductive detectors for far-infrared astronomy from the Kuiper Airborne Observatory (KAO). The 25 element (5 x 5) arrays are designed for a new cryogenically cooled spectrometer, the MPE/UCB Far-Infrared Imaging Fabry-Perot Interferometer (FIFI). All of the pixels for the stressed array performed well on the first flights with FIFI; 25% of the detectors in the array are more sensitive than our best single element detector, with background limited noise equivalent powers (NEPs) [approx lt] 3.0 [times] 10[sup [minus]15] W Hz[sup [minus]1/2] at 158 [mu]m and 40more » km s[sup [minus]1] spectral resolution. The average array element performs within [plus minus] 15% of this value. With a bias field of 0.1 V/cm, the average detector response is 20 [plus minus] 6 Amp/Watt at 158 [mu]m. The cutoff wavelength and response also compare well with our single element detectors. The unstressed array delivers significantly better performance than our single element detector due to the lower thermal background in the new spectrometer. The average background limited NEP at 88 [mu]m and 35 km s[sup [minus]1] spectral resolution is approx. 7 [times] 10[sup [minus]15] W Hz[sup [minus]1/2]. 18 refs., 10 figs., 2 tabs.« less

Quantitative Biology of Exercise-Induced Signal Transduction Pathways.

PubMed

Liu, Timon Cheng-Yi; Liu, Gang; Hu, Shao-Juan; Zhu, Ling; Yang, Xiang-Bo; Zhang, Quan-Guang

2017-01-01

Exercise is essential in regulating energy metabolism. Exercise activates cellular, molecular, and biochemical pathways with regulatory roles in training response adaptation. Among them, endurance/strength training of an individual has been shown to activate its respective signal transduction pathways in skeletal muscle. This was further studied from the viewpoint of quantitative difference (QD). For the mean values, [Formula: see text], of two sets of data, their QD is defined as [Formula: see text] ([Formula: see text]). The function-specific homeostasis (FSH) of a function of a biosystem is a negative-feedback response of the biosystem to maintain the function-specific conditions inside the biosystem so that the function is perfectly performed. A function in/far from its FSH is called a normal/dysfunctional function. A cellular normal function can resist the activation of other signal transduction pathways so that there are normal function-specific signal transduction pathways which full activation maintains the normal function. An acute endurance/strength training may be dysfunctional, but its regular training may be normal. The normal endurance/strength training of an individual may resist the activation of other signal transduction pathways in skeletal muscle so that there may be normal endurance/strength training-specific signal transduction pathways (NEPs/NSPs) in skeletal muscle. The endurance/strength training may activate NSPs/NEPs, but the QD from the control is smaller than 0.80. The simultaneous activation of both NSPs and NEPs may enhance their respective activation, and the QD from the control is larger than 0.80. The low level laser irradiation pretreatment of rats may promote the activation of NSPs in endurance training skeletal muscle. There may be NEPs/NSPs in skeletal muscle trained by normal endurance/strength training.

The effect of peptidase inhibitors on bradykinin-induced bronchoconstriction in guinea-pigs in vivo.

PubMed Central

Ichinose, M.; Barnes, P. J.

1990-01-01

1. Bradykinin (BK) instilled directly into the airway lumen caused bronchoconstriction in anaesthetized, mechanically ventilated guinea-pigs in the presence of propranolol (1 mg kg-1 i.v.). The geometric mean dose of BK required to produce 100% increase in airway opening pressure (PD100) was 22.9 nmol (95% c.i. 11.7-44.6 nmol). 2. The dose-response curve for the effect of instilled BK was significantly shifted to the left by the angiotensin converting enzyme (ACE) inhibitor, captopril (5 and 50 nmol instillation, PD100 = 3.0, 95% c.i. 0.98-8.9, and 2.0 nmol, 95% c.i. 0.65-6.2 nmol, respectively). 3. The neutral endopeptidase (NEP) inhibitor, phosphoramidon (5 and 50 nmol instillation) also shifted the dose-response curve for the effect of instilled BK; the PD100 values = 2.2 (95% c.i. 0.40-11.7) and 1.8 nmol (95% c.i. 0.87-3.5 nmol), respectively. 4. After pretreatment with captopril (50 nmol) and phosphoramidon (50 nmol) in combination, the dose-response curve for the effect of instilled BK (PD100 = 1.1 nmol, 95% c.i. 0.37-3.2 nmol) was similar to that obtained in the presence of each inhibitor used alone. 5. The kinase I inhibitor, DL-2-mercaptomethyl-3-guanidinoethylthiopropionic acid (50 nmol instillation) failed to alter the dose-response curve to instilled BK (PD100 = 14.6 nmol, 95% c.i. 6.7-32.0 nmol). 6. These data suggest that both ACE and NEP degrade BK in the airway lumen, but that kininase I is not involved. PMID:2282470

Neurokinin-2 receptor levels correlate with intensity, frequency, and duration of pain in chronic pancreatitis.

PubMed

Michalski, Christoph W; Shi, Xin; Reiser, Carolin; Fachinger, Patrick; Zimmermann, Arthur; Büchler, Markus W; Di Sebastiano, Pierluigi; Friess, Helmut

2007-11-01

Generation and maintenance of pain in chronic pancreatitis (CP) have been shown to be partially attributable to neuroimmune interactions, which involve neuropeptides such as substance P (SP). So far, expression of SP receptors NK-2R, NK-3R, the SP-encoding gene preprotachykinin A (PPT-A), and the SP degradation enzyme neutral endopeptidase (NEP) and their relation to pain in CP have not been determined. Tissue samples from patients with CP (n = 25) and from healthy donors (n = 20) were analyzed for PPT-A, NK-2R, NK-3R, and NEP expression using quantitative RT-PCR. NEP protein levels were examined by immunoblot analysis and its localization was determined using immunohistochemistry. A scoring system was used to grade the extent of fibrosis on hematoxylin and eosin- and Masson-Trichrome-stained sections. Messenger RNA levels and the extent of pain were analyzed for correlations. In CP tissues, NK-2R and PPT-A expression was increased, whereas NK-3R and NEP mRNA levels were comparable with normal pancreas. Overexpression of NK-2R was related to the intensity, frequency, and duration of pain in CP patients. NK-1R and NEP expression was significantly related to the extent of fibrosis. Expression of NK-2R and PPT-A is increased in CP and is associated with pain. Failure to up-regulate NEP may contribute to the disruption of the neuropeptides loop balance in CP and thus may exacerbate the severe pain syndrome.

Thiorphan-induced survival and proliferation of rat thymocytes by activation of Akt/survivin pathway and inhibition of caspase-3 activity.

PubMed

Amantini, Consuelo; Mosca, Michela; Lucciarini, Roberta; Perfumi, Marina Cecilia; Santoni, Giorgio

2008-10-01

The activity of substance P (SP) in the rat thymus seems to be tightly controlled by its bioavailability. In this study, we provide evidence for the expression of the SP-degrading enzyme, neutral endopeptidase (NEP)/CD10, by rat thymocyte subsets, and we illustrate its involvement in the in vivo SP/neurokinin-1 receptor (NK(1)R)-mediated regulation of thymocyte survival and proliferation. NEP/CD10 was expressed at both mRNA and protein levels on a substantial portion (45.5%) of CD5(+) thymocytes, namely on the CD4(+)CD8(+) (double positive; DP) and CD4(+) subsets. Continuous administration of thiorphan, a specific NEP/CD10 inhibitor, by means of miniosmotic pumps, enhanced rat thymocyte preprotachykinin-A (PPT-A) and NK(1)R mRNA expression as well as SP and NK(1)R protein levels in an NK(1)R-dependent manner. Thiorphan increased CD10(+)CD4(+) and CD10(+)DP thymocyte numbers, and an NK(1)R antagonist, (S)1-{2-[3(3-4-dichlorophenyl)-1-(3-iso-propoxyphenylacetyl)-piperidine-3-yl]ethyl}-4-pheny-1-azoniabicyclo[2.2.2]octane, chloride (SR140333), abrogated these stimulatory effects. In addition, the NEP/CD10 inhibitor stimulated interleukin (IL)-2 production, IL-2 receptor alpha chain expression, and concanavalin A-induced proliferation of CD5(+) thymocytes, and it inhibited spontaneous and NK(1)R-dependent thymocyte apoptosis. The thiorphan-protective antiapoptotic and proliferative effects involved the activation of Akt serine-threonine kinase, subsequent up-regulation of survivin mRNA, down-regulation of procaspase-3 mRNA levels, and suppression of caspase-3 activity, which were inhibited by SR140333 and mimicked by exogenous SP administration. Overall, our findings suggest that by controlling SP availability, NEP/CD10 negatively regulates thymocyte homeostasis and development.

Effect of neutral endopeptidase inhibitor on bradykinin-induced bronchoconstriction.

PubMed

Kamijo, Y; Hayashi, I; Soma, K; Ohwada, T; Majima, M

2001-11-21

To evaluate whether neutral endopeptidase (NEP) inhibitors have adverse respiratory effects, the influence of a NEP inhibitor on bradykinin (BK)-induced bronchoconstriction was investigated. In anesthetized and artificially ventilated guinea pigs, changes in airway opening pressure (Pao) were measured as an index of bronchoconstriction. An infusion of phosphoramidon (3 mg kg(-1) h(-1)), a NEP inhibitor, significantly enhanced the bronchoconstriction induced by high-dose BK (30 nmol kg(-1), i.v.). Capsaicin (0.1 mg kg(-1), i.v.) and SR48968 (0.3 mg kg(-1), i.v.), an NK2 receptor antagonist, significantly inhibited the phosphoramidon-induced enhancement of BK-induced bronchoconstriction, although FK888 (3 mg kg(-1), i.v.), an NK1 receptor antagonist, did not. Both neurokinin A (NKA) (0.1-3 nmol kg(-1), i.v.) and substance P (SP) (0.1-3 nmol kg(-1), i.v.) induced dose-dependent bronchoconstriction which was enhanced by phosphoramidon infusion, although these enhancements were more prominent in the NKA series. Phosphoramidon partially inhibited BK degradation in lung homogenate, and both NKA and SP degradation in the lung homogenate were significantly suppressed by phosphoramidon. In bronchoalveolar lavage fluid (BALF), levels of NKA and SP were significantly elevated after a bolus of BK with a phosphoramidon infusion. These results suggest that NEP inhibitors may have adverse respiratory effects resulting from inhibition of the degradation of neurokinins, but mainly of NKA, when a large amount of BK is generated.

Development of HgCdTe single-element APDs based detectors for low flux short wave infrared applications

NASA Astrophysics Data System (ADS)

Foubert, K.; Lasfargues, G.; Mathieu, L.; Benahmed, S.; Vojetta, G.; Rothman, J.; Benoît à la Guillaume, Q.; Calvo, Vincent; Picot-Clemente, Jérémy; Le Mounier, Florent; Gibert, Fabien

2013-03-01

The remarkable properties (internal gain larger than 100 and close to unity excess noise factor) of Short Wave Infrared (SWIR) HgCdTe electron-initiated Avalanche Photodiodes (e-APDs) are put to good use to demanding applications, i.e. spectroscopy and LIDAR. Knowing the requirements of both situations, we have designed specific models based on highly sensitive single elements APDs and adapted proximity electronics. On one hand, we use the e-APDs low noise equivalent power (NEP) at 180K (few fW/Hz1/2). We simultaneously designed a specific Transimpedance Amplifier (TIA) which allows us to take advantage of the low APD NEP. The combination of both elements along with a dedicated cryostat enables direct LIDAR detection at moderate bandwidth (BW = 20 MHz) without the need for long time averaging, which is crucial in far field (>= 5 km) analysis. One the other hand, we have optimized a low-noise and low-frequency LN2 cooled prototype operating with an external commercial amplifier. It allows us to observe the photoluminescence of Ge nanostructures in the range 1.5-2.5 μm with a significantly increased SNR along with a reduce pump laser power. The possibility to use these detectors in the photon counting limit will be discussed in light of our recent results. In parallel, we present preliminary time response measurements performed on SWIR APD suggesting that a higher GHz BW could be reached with this type of detector. This is however subjected to optical optimization at the moment.

Carbon balance of a partially-harvested mixed conifer forest following mountain pine beetle attack and its comparison to a clearcut

NASA Astrophysics Data System (ADS)

Mathys, A.; Black, T. A.; Nesic, Z.; Nishio, G.; Brown, M.; Spittlehouse, D. L.; Fredeen, A. L.; Bowler, R.; Jassal, R. S.; Grant, N. J.; Burton, P. J.; Trofymow, J. A.

2013-03-01

The recent mountain pine beetle (MPB) outbreak has had an impact on the carbon (C) cycling of lodgepole pine forests in British Columbia. This study examines how partial harvesting as a forest management response to MPB infestation affects the net ecosystem production (NEP) of a mixed conifer forest (MPB-09) in Interior BC. MPB-09 is a 70-yr old stand that was partially harvested in 2009 after it had been attacked by MPB. Using the eddy-covariance technique, the C dynamics of the stand were studied over two years and compared to an adjacent clearcut (MPB-09C) over the growing season. The annual NEP at MPB-09 increased from -108 g C m-2 in 2010 to -57 g C m-2 in 2011. The increase of NEP was due to the associated increase in annual gross ecosystem photosynthesis (GEP) from 812 g C m-2 in 2010 to 954 g C m-2 in 2011 exceeding the increase in annual respiration (Re) from 920 g C m-2 to 1011 g C m-2 during the two years. During the growing season of 2010, NEP at MPB-09C was -132 g C m-2 indicating high C losses in the clearcut. MPB-09 was a C sink during the growing season of both years, increasing from 9 g C m-2 in 2010 to 47 g C m-2 in 2011. The increase of NEP in the partially-harvested stand amounted to a recovery corresponding to a 25% increase in the maximum assimilation rate in the second year. This study shows that retaining the healthy residual forest can result in higher C sequestration of MPB-attacked stands compared to clearcut harvesting.

Impacts of droughts and extreme-temperature events on gross primary production and ecosystem respiration: a systematic assessment across ecosystems and climate zones

NASA Astrophysics Data System (ADS)

von Buttlar, Jannis; Zscheischler, Jakob; Rammig, Anja; Sippel, Sebastian; Reichstein, Markus; Knohl, Alexander; Jung, Martin; Menzer, Olaf; Altaf Arain, M.; Buchmann, Nina; Cescatti, Alessandro; Gianelle, Damiano; Kiely, Gerard; Law, Beverly E.; Magliulo, Vincenzo; Margolis, Hank; McCaughey, Harry; Merbold, Lutz; Migliavacca, Mirco; Montagnani, Leonardo; Oechel, Walter; Pavelka, Marian; Peichl, Matthias; Rambal, Serge; Raschi, Antonio; Scott, Russell L.; Vaccari, Francesco P.; van Gorsel, Eva; Varlagin, Andrej; Wohlfahrt, Georg; Mahecha, Miguel D.

2018-03-01

Extreme climatic events, such as droughts and heat stress, induce anomalies in ecosystem-atmosphere CO2 fluxes, such as gross primary production (GPP) and ecosystem respiration (Reco), and, hence, can change the net ecosystem carbon balance. However, despite our increasing understanding of the underlying mechanisms, the magnitudes of the impacts of different types of extremes on GPP and Reco within and between ecosystems remain poorly predicted. Here we aim to identify the major factors controlling the amplitude of extreme-event impacts on GPP, Reco, and the resulting net ecosystem production (NEP). We focus on the impacts of heat and drought and their combination. We identified hydrometeorological extreme events in consistently downscaled water availability and temperature measurements over a 30-year time period. We then used FLUXNET eddy covariance flux measurements to estimate the CO2 flux anomalies during these extreme events across dominant vegetation types and climate zones. Overall, our results indicate that short-term heat extremes increased respiration more strongly than they downregulated GPP, resulting in a moderate reduction in the ecosystem's carbon sink potential. In the absence of heat stress, droughts tended to have smaller and similarly dampening effects on both GPP and Reco and, hence, often resulted in neutral NEP responses. The combination of drought and heat typically led to a strong decrease in GPP, whereas heat and drought impacts on respiration partially offset each other. Taken together, compound heat and drought events led to the strongest C sink reduction compared to any single-factor extreme. A key insight of this paper, however, is that duration matters most: for heat stress during droughts, the magnitude of impacts systematically increased with duration, whereas under heat stress without drought, the response of Reco over time turned from an initial increase to a downregulation after about 2 weeks. This confirms earlier theories that not only the magnitude but also the duration of an extreme event determines its impact. Our study corroborates the results of several local site-level case studies but as a novelty generalizes these findings on the global scale. Specifically, we find that the different response functions of the two antipodal land-atmosphere fluxes GPP and Reco can also result in increasing NEP during certain extreme conditions. Apparently counterintuitive findings of this kind bear great potential for scrutinizing the mechanisms implemented in state-of-the-art terrestrial biosphere models and provide a benchmark for future model development and testing.

High expression of neutral endopeptidase in idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells.

PubMed

Cohen, A J; King, T E; Gilman, L B; Magill-Solc, C; Miller, Y E

1998-11-01

Idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells (IDHPNC) is a clinicopathological entity characterized by a diffuse hyperplasia of neuroendocrine cells involving distal bronchi and bronchioles. The pathogenesis of this syndrome remains unknown. The hyperplastic neuroendocrine (NE) cells contain multiple neuropeptides, including the bombesinlike peptides (BLP), which are likely important in the pathogenesis of the disorder by stimulating proliferation of fibroblasts in a paracrine fashion and the NE cells themselves in an autocrine manner. Neutral endopeptidase (NEP) is a cell-surface enzyme that hydrolyzes BLP and other bioactive peptides. Low or undetectable NEP is present in many primary lung cancers and cell lines. Low NEP expression could increase neuropeptide-induced autocrine effects by increasing local levels of neuropeptides. We hypothesized that IDHPNC was associated with low or absent NEP expression. NEP expression was assayed in patients with IDHPNC (n = 3) and was compared with expression in patients with idiopathic pulmonary fibrosis (n = 5), hypersensitivity pneumonitis (n = 5), and normal lung (n = 4) using immunohistochemistry, ELISA, activity assay, and Western blot analysis. By these assays, NEP expression was highest in lungs affected by IDHPNC. NEP mRNA, as assessed in IDHPNC lung tissue by RT-PCR, was the expected size and free of mutation between bp 238-2437. Therefore, IDHPNC is unlikely to be the result of a defect in NEP expression. The apparent increase in NEP expression in lung tissue from patients with IDHPNC may reflect a compensatory increase that partly counteracts abundant neuropeptides, including BLP, present in this disorder.

Phylogeography of Littorina sitkana in the northwestern Pacific Ocean: evidence of eastward trans-Pacific colonization after the Last Glacial Maximum.

PubMed

Azuma, Noriko; Zaslavskaya, Nadezhda I; Yamazaki, Tomoyasu; Nobetsu, Takahiro; Chiba, Susumu

2017-04-01

We investigated genetic diversity and population structure of the Sitka periwinkle Littorina sitkana along the coastlines of the northwestern Pacific (NWP) to evaluate the possibility of trans-Pacific colonization of this species from the NWP to the northeastern Pacific (NEP) after the Last Glacial Maximum. We sampled L. sitkana from 32 populations in the NWP, and sequenced a region of the mitochondrial cytochrome b oxidase gene for population genetic analyses. The results were compared with those of previous reports from the NEP. The genetic diversity of L. sitkana was much higher in the NWP than in the NEP. Genetic connectivity between the NWP and NEP populations was indicated by an extremely abundant haplotype in the NEP that was also present in eastern Hokkaido and the Kuril Islands. To confirm these results, we compared sequences of the longest intron of the aminopeptidase N gene (APN54) in the nuclear genome in four populations of L. sitkana in the NWP with previous results from the NEP. Again, much higher genetic diversity was found in the NWP than in the NEP and genetic connectivity was supported between the Kuril Islands and the NEP. These results imply postglacial colonization of this species from the NWP to the NEP, probably along the Kuril and Aleutian Island chains. This study is the first report of possible trans-Pacific postglacial colonization of a direct-developing gastropod, inferred from genetic data.

Community production modulates coral reef pH and the sensitivity of ecosystem calcification to ocean acidification

NASA Astrophysics Data System (ADS)

DeCarlo, Thomas M.; Cohen, Anne L.; Wong, George T. F.; Shiah, Fuh-Kwo; Lentz, Steven J.; Davis, Kristen A.; Shamberger, Kathryn E. F.; Lohmann, Pat

2017-01-01

Coral reefs are built of calcium carbonate (CaCO3) produced biogenically by a diversity of calcifying plants, animals, and microbes. As the ocean warms and acidifies, there is mounting concern that declining calcification rates could shift coral reef CaCO3 budgets from net accretion to net dissolution. We quantified net ecosystem calcification (NEC) and production (NEP) on Dongsha Atoll, northern South China Sea, over a 2 week period that included a transient bleaching event. Peak daytime pH on the wide, shallow reef flat during the nonbleaching period was ˜8.5, significantly elevated above that of the surrounding open ocean (˜8.0-8.1) as a consequence of daytime NEP (up to 112 mmol C m-2 h-1). Diurnal-averaged NEC was 390 ± 90 mmol CaCO3 m-2 d-1, higher than any other coral reef studied to date despite comparable calcifier cover (25%) and relatively high fleshy algal cover (19%). Coral bleaching linked to elevated temperatures significantly reduced daytime NEP by 29 mmol C m-2 h-1. pH on the reef flat declined by 0.2 units, causing a 40% reduction in NEC in the absence of pH changes in the surrounding open ocean. Our findings highlight the interactive relationship between carbonate chemistry of coral reef ecosystems and ecosystem production and calcification rates, which are in turn impacted by ocean warming. As open-ocean waters bathing coral reefs warm and acidify over the 21st century, the health and composition of reef benthic communities will play a major role in determining on-reef conditions that will in turn dictate the ecosystem response to climate change.

Comparing soil carbon loss through respiration and leaching under extreme precipitation events in arid and semiarid grasslands

NASA Astrophysics Data System (ADS)

Liu, Ting; Wang, Liang; Feng, Xiaojuan; Zhang, Jinbo; Ma, Tian; Wang, Xin; Liu, Zongguang

2018-03-01

Respiration and leaching are two main processes responsible for soil carbon loss. While the former has received considerable research attention, studies examining leaching processes are limited, especially in semiarid grasslands due to low precipitation. Climate change may increase the extreme precipitation event (EPE) frequency in arid and semiarid regions, potentially enhancing soil carbon loss through leaching and respiration. Here we incubated soil columns of three typical grassland soils from Inner Mongolia and the Qinghai-Tibetan Plateau and examined the effect of simulated EPEs on soil carbon loss through respiration and leaching. EPEs induced a transient increase in CO2 release through soil respiration, equivalent to 32 and 72 % of the net ecosystem productivity (NEP) in the temperate grasslands (Xilinhot and Keqi) and 7 % of NEP in the alpine grasslands (Gangcha). By comparison, leaching loss of soil carbon accounted for 290, 120, and 15 % of NEP at the corresponding sites, respectively, with dissolved inorganic carbon (DIC, biogenic DIC + lithogenic DIC) as the main form of carbon loss in the alkaline soils. Moreover, DIC loss increased with recurring EPEs in the soil with the highest pH due to an elevated contribution of dissolved CO2 from organic carbon degradation (indicated by DIC-δ13C). These results highlight the fact that leaching loss of soil carbon (particularly in the form of DIC) is important in the regional carbon budget of arid and semiarid grasslands and also imply that SOC mineralization in alkaline soils might be underestimated if only measured as CO2 emission from soils into the atmosphere. With a projected increase in EPEs under climate change, soil carbon leaching processes and the influencing factors warrant a better understanding and should be incorporated into soil carbon models when estimating carbon balance in grassland ecosystems.

Benefits of Nuclear Electric Propulsion for Outer Planet Exploration

NASA Technical Reports Server (NTRS)

Kos, Larry; Johnson, Les; Jones, Jonathan; Trausch, Ann; Eberle, Bill; Woodcock, Gordon; Brady, Hugh J. (Technical Monitor)

2002-01-01

Nuclear electric propulsion (NEP) offers significant benefits to missions for outer planet exploration. Reaching outer planet destinations, especially beyond Jupiter, is a struggle against time and distance. For relatively near missions, such as a Europa lander, conventional chemical propulsion and NEP offer similar performance and capabilities. For challenging missions such as a Pluto orbiter, neither chemical nor solar electric propulsion are capable while NEP offers acceptable performance. Three missions are compared in this paper: Europa lander, Pluto orbiter, and Titan sample return, illustrating how performance of conventional and advanced propulsion systems vary with increasing difficulty. The paper presents parametric trajectory performance data for NEP. Preliminary mass/performance estimates are provided for a Europa lander and a Titan sample return system, to derive net payloads for NEP. The NEP system delivers payloads and ascent/descent spacecraft to orbit around the target body, and for sample return, delivers the sample carrier system from Titan orbit to an Earth transfer trajectory. A representative scientific payload 500 kg was assumed, typical for a robotic mission. The resulting NEP systems are 100-kWe class, with specific impulse from 6000 to 9000 seconds.

Neuropeptide Levels as well as Neprilysin Activity Decrease in Renal Cell Carcinoma.

PubMed

Erin, Nuray; İpekçi, Tümay; Akkaya, Bahar; Özbudak, İrem Hicran; Baykara, Mehmet

2016-12-01

Calcitonin Gene-related Peptide (CGRP), Vasoactive Intestinal Peptide (VIP) and Substance P (SP) are sensory neuropeptides which may alter cancer growth through modulation of chronic inflammation. We recently reported that SP suppresses breast cancer growth and metastasis through neuroimmune modulation. These neuropeptides are hydrolyzed by Neprilysin (NEP) to bioactive fragments. Decreased activity of NEP was reported in clear cell and chromophobe type renal cell carcinoma (RCC). It is however not known how the levels of neuropeptides hydrolyzed with NEP changes in RCC. Decrease activity of SP and CGRP containing sensory nerve endings was previously reported to increase cancer metastasis in animal models. It is however not known how peptidergic nerve endings are altered in RCC. Hence we here evaluated the levels of neuronal and non-neuronal neuropeptides and NEP activity in RCC including papillary type as well as neighboring uninvolved kidney. A cross-sectional study was conducted in 57 patients undergoing radical nephrectomy and diagnosed with RCC. NEP activity, levels and expression were determined using flourogenic substrate, western blot and qPCR respectively in freshly-frozen tissues. Immunohistochemical analyses were also performed. Neuronal and non-neuronal levels of CGRP, SP and VIP levels were determined using two-step acetic acid extraction. Levels and activity of NEP were markedly decreased in RCC regardless of subtype. Similar levels of VIP were detected in first and second extractions. VIP levels were higher in clear cell and papillary RCC compared to nearby kidney tissue. VIP levels of neighboring kidney tissue of papillary type RCC was significantly lower compared to kidney samples from clear cell RCC. CGRP levels were higher in second extraction. Similar to VIP levels, CGRP levels of neighboring kidney tissue from clear cell and chromophobe type RCC was significantly lower compared to corresponding tumor samples, an effect observed in the second extraction. VIP and CGRP levels of nearby kidney tissue varied subtype dependently demonstrating that different subtypes of RCC alter their local environment differently. Furthermore NEP-induce hydrolysis of VIP creates selective VPAC-1 receptor agonist which has anti-proliferative and anti-inflammatory effects. Hence loss of NEP activity may prevent anti-tumoral effects of VIP on RCC.

Strong Links Between Teleconnections and Ecosystem Exchange Found at a Pacific Northwest Old-Growth Forest from Flux Tower and MODIS EVI Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wharton, S; Chasmer, L; Falk, M

2009-03-12

Variability in three Pacific teleconnection patterns are examined to see if net carbon exchange at a low-elevation, old-growth forest is affected by climatic changes associated with these periodicities. Examined are the Pacific Decadal Oscillation (PDO), Pacific/North American Oscillation (PNA) and El Nino-Southern Oscillation (ENSO). We use nine years of eddy covariance CO{sub 2}, H{sub 2}O and energy fluxes measured at the Wind River AmeriFlux site, Washington, USA and eight years of tower-pixel remote sensing data from the Moderate Resolution Imaging Spectroradiometer (MODIS) to address this question. We compute a new Composite Climate Index (CCI) based on the three Pacific Oscillationsmore » to divide the measurement period into positive- (2003 and 2005), negative- (1999 and 2000) and neutral-phase climate years (2001, 2002, 2004, 2006 and 2007). The forest transitioned from an annual net carbon sink (NEP = + 217 g C m{sup -2} year{sup -1}, 1999) to a source (NEP = - 100 g C m{sup -2} year{sup -1}, 2003) during two dominant teleconnection patterns. Net ecosystem productivity (NEP), water use efficiency (WUE) and light use efficiency (LUE) were significantly different (P < 0.01) during positive (NEP = -0.27 g C m{sup -2} day{sup -1}, WUE = 4.1 mg C/g H{sub 2}O, LUE = 0.94 g C MJ{sup -1}) and negative (NEP = +0.37 g C m{sup -2} day{sup -1}, WUE = 3.4 mg C/g H{sub 2}O, LUE = 0.83 g C MJ{sup -1}) climate phases. The CCI was linked to variability in the MODIS Enhanced Vegetation Index (EVI) but not to MODIS Fraction of absorbed Photosynthetically Active Radiation (FPAR). EVI was highest during negative climate phases (1999 and 2000) and was positively correlated with NEP and showed potential for using MODIS to estimate teleconnection-driven anomalies in ecosystem CO{sub 2} exchange in old-growth forests. This work suggests that any increase in the strength or frequency of ENSO coinciding with in-phase, low frequency Pacific oscillations (PDO and PNA) will likely increase CO{sub 2} uptake variability in Pacific Northwest conifer forests.« less

Autocrine regulation of human sperm motility by tachykinins

PubMed Central

2010-01-01

Background We examined the presence and function of tachykinins and the tachykinin-degrading enzymes neprilysin (NEP) and neprilysin-2 (NEP2) in human spermatozoa. Methods Freshly ejaculated semen was collected from forty-eight normozoospermic human donors. We analyzed the expression of substance P, neurokinin A, neurokinin B, hemokinin-1, NEP and NEP2 in sperm cells by reverse-transcriptase polymerase chain reaction (RT-PCR), western blot and immunocytochemistry assays and evaluated the effects of the neprilysin and neprilysin-2 inhibitor phosphoramidon on sperm motility in the absence and presence of tachykinin receptor-selective antagonists. Sperm motility was measured using WHO procedures or computer-assisted sperm analysis (CASA). Results The mRNAs of the genes that encode substance P/neurokinin A (TAC1), neurokinin B (TAC3), hemokinin-1 (TAC4), neprilysin (MME) and neprilysin-2 (MMEL1) were expressed in human sperm. Immunocytochemistry studies revealed that tachykinin and neprilysin proteins were present in spermatozoa and show specific and differential distributions. Phosphoramidon increased sperm progressive motility and its effects were reduced in the presence of the tachykinin receptor antagonists SR140333 (NK1 receptor-selective) and SR48968 (NK2 receptor-selective) but unmodified in the presence of SR142801 (NK3 receptor-selective). Conclusion These data show that tachykinins are present in human spermatozoa and participate in the regulation of sperm motility. Tachykinin activity is regulated, at least in part, by neprilysins. PMID:20796280

Autocrine regulation of human sperm motility by tachykinins.

PubMed

Pinto, Francisco M; Ravina, Cristina G; Subiran, Nerea; Cejudo-Román, Antonio; Fernández-Sánchez, Manuel; Irazusta, Jon; Garrido, Nicolas; Candenas, Luz

2010-08-26

We examined the presence and function of tachykinins and the tachykinin-degrading enzymes neprilysin (NEP) and neprilysin-2 (NEP2) in human spermatozoa. Freshly ejaculated semen was collected from forty-eight normozoospermic human donors. We analyzed the expression of substance P, neurokinin A, neurokinin B, hemokinin-1, NEP and NEP2 in sperm cells by reverse-transcriptase polymerase chain reaction (RT-PCR), western blot and immunocytochemistry assays and evaluated the effects of the neprilysin and neprilysin-2 inhibitor phosphoramidon on sperm motility in the absence and presence of tachykinin receptor-selective antagonists. Sperm motility was measured using WHO procedures or computer-assisted sperm analysis (CASA). The mRNAs of the genes that encode substance P/neurokinin A (TAC1), neurokinin B (TAC3), hemokinin-1 (TAC4), neprilysin (MME) and neprilysin-2 (MMEL1) were expressed in human sperm. Immunocytochemistry studies revealed that tachykinin and neprilysin proteins were present in spermatozoa and show specific and differential distributions. Phosphoramidon increased sperm progressive motility and its effects were reduced in the presence of the tachykinin receptor antagonists SR140333 (NK1 receptor-selective) and SR48968 (NK2 receptor-selective) but unmodified in the presence of SR142801 (NK3 receptor-selective). These data show that tachykinins are present in human spermatozoa and participate in the regulation of sperm motility. Tachykinin activity is regulated, at least in part, by neprilysins.

Peptidase modulation of the pulmonary effects of tachykinins in tracheal superfused guinea pig lungs.

PubMed Central

Martins, M A; Shore, S A; Gerard, N P; Gerard, C; Drazen, J M

1990-01-01

The effects of the angiotensin converting enzyme (ACE) inhibitor captopril and the neutral endopeptidase (NEP) inhibitors thiorphan and SCH 32615 on the changes in airway opening pressure (PaO) and the recovery of offered peptide were studied after intratracheal administration of substance P (SP) and neurokinin A (NKA) in isolated guinea pig lungs superfused through the trachea. Pao changes and the recovery of offered peptide were significantly greater in NEP inhibitor-treated lungs than in control lungs. Captopril did not cause a significant change in the physiological effects or the recovery of SP and NKA. HPLC analysis of [3H]Pro2,4-SP and 125I-Histidyl1-NKA perfused through the airways showed major cleavage products consistent with NEP action. We conclude that there is significant degradation of both SP and NKA after tracheal infusion of peptides by NEP-like but not by ACE activity; this effect significantly influences the physiological effects of these peptides. Images PMID:1688568

Peptidase modulation of the pulmonary effects of tachykinins in tracheal superfused guinea pig lungs.

PubMed

Martins, M A; Shore, S A; Gerard, N P; Gerard, C; Drazen, J M

1990-01-01

The effects of the angiotensin converting enzyme (ACE) inhibitor captopril and the neutral endopeptidase (NEP) inhibitors thiorphan and SCH 32615 on the changes in airway opening pressure (PaO) and the recovery of offered peptide were studied after intratracheal administration of substance P (SP) and neurokinin A (NKA) in isolated guinea pig lungs superfused through the trachea. Pao changes and the recovery of offered peptide were significantly greater in NEP inhibitor-treated lungs than in control lungs. Captopril did not cause a significant change in the physiological effects or the recovery of SP and NKA. HPLC analysis of [3H]Pro2,4-SP and 125I-Histidyl1-NKA perfused through the airways showed major cleavage products consistent with NEP action. We conclude that there is significant degradation of both SP and NKA after tracheal infusion of peptides by NEP-like but not by ACE activity; this effect significantly influences the physiological effects of these peptides.

The impacts of disturbance on the spatial and temporal variations of carbon balance in forest ecosystems on Hokkaido, Japan

NASA Astrophysics Data System (ADS)

Hirata, R.; Ito, A.; Saigusa, N.

2013-12-01

Carbon balance in a forest ecosystem can be quite variable if the forest ecosystem structure and function change abruptly as a result of disturbance and subsequent recovery processes. A map of forest age is useful for upscaling carbon balance from the site level to a regional scale because it provides information about when disturbance occurred and how it spread over a wide area. In this study, we used maps of forest age to help evaluate spatial and temporal variations in the carbon balance of forest ecosystems with a process-based ecosystem model. Forests less than 60 years old account for more than 70% of Japanese forests because forest stands have been quickly replaced after disturbance caused by thinning, harvesting, plantations, fires, typhoons, and insect damage. However, few studies have attempted to quantify how much disturbance affects the spatial and temporal variations of carbon balance. In this study, we focused on how disturbance and subsequent re-growth affected the spatial and temporal variations of the carbon balance of forests. We adapted the Vegetation Integrative SImulator for Trace Gases (VISIT) model in order to simulate carbon balance on Hokkaido, which is the northernmost island of Japan. The model was validated with tower flux data obtained from forests with ages between 0 and 43 years. Simulations of the carbon balance were conducted for the period 1948-2010 after a 1000-year spin-up at a spatial resolution of 1 km × 1 km. We investigated two case studies of simulated carbon balance: one that took into account the spatial distribution of forest ages derived from forest inventory data, and another that ignored the impact of disturbance (i.e., no disturbance and a homogeneous distribution of ages). We first focused on the difference from 2000-2010 in the spatial distribution of net ecosystem production (NEP) between the disturbance and non-disturbance cases. In the non-disturbance case, the temporal and spatial changes in NEP were gradual and ranged from 0 to 1 t C ha-1 y-1, depending on meteorological conditions such as temperature or solar radiation. In the disturbance case, however, large NEP changes ranging from 3 to 5 t C ha-1 y-1 were distributed in patches like hotspots, because the forests in those spots ranged in age from 20 to 100 years and were younger than the forests in the non-disturbance case. In the 1970s, wood harvesting and tree planting were conducted intensively on Hokkaido. In the disturbance case during this period, there were many hotspots where NEP was negative. We next focused on the difference between the disturbance and non-disturbance cases of temporal variations of spatially averaged NEP on Hokkaido. Until 1970, the difference between the two cases of average NEP was less than 0.01 t C ha-1 y-1. After 1970, the difference became large and reached about 0.5 t C ha-1 y-1, the implication being that the regional NEP in the disturbance case increased to as much as 2-5 times the regional NEP of the non-disturbance case. Our results show the importance of considering forest age when simulating the carbon balance of forests. Carbon balance maps that take forest age into account are useful for carbon management and prediction of ecosystem feedbacks on climate change.

NEP: web server for epitope prediction based on antibody neutralization of viral strains with diverse sequences

PubMed Central

Chuang, Gwo-Yu; Liou, David; Kwong, Peter D.; Georgiev, Ivelin S.

2014-01-01

Delineation of the antigenic site, or epitope, recognized by an antibody can provide clues about functional vulnerabilities and resistance mechanisms, and can therefore guide antibody optimization and epitope-based vaccine design. Previously, we developed an algorithm for antibody-epitope prediction based on antibody neutralization of viral strains with diverse sequences and validated the algorithm on a set of broadly neutralizing HIV-1 antibodies. Here we describe the implementation of this algorithm, NEP (Neutralization-based Epitope Prediction), as a web-based server. The users must supply as input: (i) an alignment of antigen sequences of diverse viral strains; (ii) neutralization data for the antibody of interest against the same set of antigen sequences; and (iii) (optional) a structure of the unbound antigen, for enhanced prediction accuracy. The prediction results can be downloaded or viewed interactively on the antigen structure (if supplied) from the web browser using a JSmol applet. Since neutralization experiments are typically performed as one of the first steps in the characterization of an antibody to determine its breadth and potency, the NEP server can be used to predict antibody-epitope information at no additional experimental costs. NEP can be accessed on the internet at http://exon.niaid.nih.gov/nep. PMID:24782517

Amyloid-clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer’s disease

PubMed Central

Nalivaeva, Natalia N.; Belyaev, Nikolai D.; Kerridge, Caroline; Turner, Anthony J.

2014-01-01

Abnormal elevation of amyloid β-peptide (Aβ) levels in the brain is the primary trigger for neuronal cell death specific to Alzheimer’s disease (AD). It is now evident that Aβ levels in the brain are manipulable due to a dynamic equilibrium between its production from the amyloid precursor protein (APP) and removal by amyloid clearance proteins. Clearance can be either enzymic or non-enzymic (binding/transport proteins). Intriguingly several of the main amyloid-degrading enzymes (ADEs) are members of the M13 peptidase family (neprilysin (NEP), NEP2 and the endothelin converting enzymes (ECE-1 and -2)). A distinct metallopeptidase, insulin-degrading enzyme (IDE), also contributes to Aβ degradation in the brain. The ADE family currently embraces more than 20 members, both membrane-bound and soluble, and of differing cellular locations. NEP plays an important role in brain function terminating neuropeptide signals. Its decrease in specific brain areas with age or after hypoxia, ischaemia or stroke contribute significantly to the development of AD pathology. The recently discovered mechanism of epigenetic regulation of NEP (and other genes) by the APP intracellular domain (AICD) and its dependence on the cell type and APP isoform expression suggest possibilities for selective manipulation of NEP gene expression in neuronal cells. We have also observed that another amyloid-clearing protein, namely transthyretin (TTR), is also regulated in the neuronal cell by a mechanism similar to NEP. Dependence of amyloid clearance proteins on histone deacetylases and the ability of HDAC inhibitors to up-regulate their expression in the brain opens new avenues for developing preventive strategies in AD. PMID:25278875

Post-junctional facilitation of substance P signaling in a tibia fracture rat model of complex regional pain syndrome type I

PubMed Central

Wei, Tzuping; Li, Wen-wu; Guo, Tian-Zhi; Zhao, Rong; Wang, Liping; Clark, David J; Oaklander, Ann Louise; Schmelz, Martin; Kingery, Wade S.

2009-01-01

Tibia fracture in rats evokes nociceptive, vascular, and bone changes resembling complex regional pain syndrome (CRPS). Substance P (SP) signaling contributes to the hindpaw warmth, increased vascular permeability, and edema observed in this model, suggesting that neurogenic inflammatory responses could be enhanced after fracture. Four weeks after tibia fracture we measured SP and calcitonin gene-related peptide (CGRP) protein levels in the sciatic nerve and serum. Hindpaw skin extravasation responses and SP receptor (NK1), CGRP receptor (calcitonin receptor-like receptor, CRLR) and neutral endopeptidase (NEP) protein levels were also determined. Gene expression levels of these peptides, receptors, and peptidase were examined in the DRG and skin. Spontaneous and intravenous SP-evoked extravasation responses were increased ipsilateral, but not contralateral to the fracture. Fracture increased SP and CGRP gene expression in the ipsilateral L4,L5 DRG and neuropeptide protein levels in the sciatic nerve and in serum, but had no effect on electrically-evoked SP and CGRP release. NK1 receptor expression was increased in the ipsilateral hindpaw skin keratinocytes and endothelial cells after injury, but CRLR and NEP expression were unchanged. Fracture also increased epidermal thickness, but had no effect on epidermal skin neurite counts. These results demonstrate that spontaneous and intravenous SP-evoked extravasation responses are enhanced in the ipsilateral hindlimb after fracture and that fracture chronically increases the expression of endothelial and keratinocyte NK1 receptors in the injured limb. We postulate that SP activation of these up-regulated NK1 receptors results in skin warmth, protein leakage, edema, and keratinocyte proliferation in the injured limb. PMID:19464118

Post-junctional facilitation of Substance P signaling in a tibia fracture rat model of complex regional pain syndrome type I.

PubMed

Wei, Tzuping; Li, Wen-Wu; Guo, Tian-Zhi; Zhao, Rong; Wang, Liping; Clark, David J; Oaklander, Anne Louise; Schmelz, Martin; Kingery, Wade S

2009-08-01

Tibia fracture in rats evokes nociceptive, vascular, and bone changes resembling complex regional pain syndrome (CRPS). Substance P (SP) signaling contributes to the hindpaw warmth, increased vascular permeability, and edema observed in this model, suggesting that neurogenic inflammatory responses could be enhanced after fracture. Four weeks after tibia fracture we measured SP and calcitonin gene-related peptide (CGRP) protein levels in the sciatic nerve and serum. Hindpaw skin extravasation responses and SP receptor (NK1), CGRP receptor (calcitonin receptor-like receptor, CRLR) and neutral endopeptidase (NEP) protein levels were also determined. Gene expression levels of these peptides, receptors, and peptidase were examined in the DRG and skin. Spontaneous and intravenous SP-evoked extravasation responses were increased ipsilateral, but not contralateral to the fracture. Fracture increased SP and CGRP gene expression in the ipsilateral L4,L5 DRG and neuropeptide protein levels in the sciatic nerve and in serum, but had no effect on electrically evoked SP and CGRP release. NK1 receptor expression was increased in the ipsilateral hindpaw skin keratinocytes and endothelial cells after injury, but CRLR and NEP expression were unchanged. Fracture also increased epidermal thickness, but had no effect on epidermal skin neurite counts. These results demonstrate that spontaneous and intravenous SP-evoked extravasation responses are enhanced in the ipsilateral hindlimb after fracture and that fracture chronically increases the expression of endothelial and keratinocyte NK1 receptors in the injured limb. We postulate that SP activation of these up-regulated NK1 receptors results in skin warmth, protein leakage, edema, and keratinocyte proliferation in the injured limb.

Nuclear electric propulsion mission engineering study. Volume 2: Final report

NASA Technical Reports Server (NTRS)

1973-01-01

Results of a mission engineering analysis of nuclear-thermionic electric propulsion spacecraft for unmanned interplanetary and geocentric missions are summarized. Critical technologies associated with the development of nuclear electric propulsion (NEP) are assessed, along with the impact of its availability on future space programs. Outer planet and comet rendezvous mission analysis, NEP stage design for geocentric and interplanetary missions, NEP system development cost and unit costs, and technology requirements for NEP stage development are studied.

How Human and Natural Disturbance Affects the U.S. Carbon Sink

NASA Astrophysics Data System (ADS)

Felzer, B. S.

2015-12-01

Gridded datasets of Net Ecosystem Exchange derived from eddy covariance and remote sensing measurements (EC-MOD and FLUXNET-MTE) provide a means of validating Net Ecosystem Productivity (NEP, opposite of NEE) from terrestrial ecosystem models. While most forested regions in the U.S. are observed to be moderate to strong carbon sinks, models not including human or natural disturbances will tend to be more carbon neutral, which is expected of mature ecosystems. I have developed the Terrestrial Ecosystems Model Hydro version (TEM-Hydro) to include both human and natural disturbances to compare against gridded NEP datasets. Human disturbances are based on the Hurtt et al. land use transition dataset and include transient agricultural (crops and pasture) conversion and abandonment and timber harvest. Natural disturbances include tropical storms and hurricane and fires based on stochastic return intervals. Model results indicate that forests are the largest carbon sink, seconded by croplands and pastures, if not accounting for decomposition of agricultural products and animal respiration. Grasslands and shrublands are both small sinks or carbon neutral. The NEP of forests in EC-MOD from 2001-2006 is 240 gCm2yr-1 and for FLUXNET-MTE from 1982-2007 is 375 gCm-2yr-1. With potential vegetation, the respective forest sinks for those two time periods are 54 and 62 gCm-2yr-1, respectively. Including the effects of human disturbance increases the sinks to 154 and 147 gCm-2yr-1. The effect of stochastic fire and storms is to reduce the NEP to 114 and 108 gCm-2yr-1. While the positive carbon sink today is the result of past land use disturbance, net carbon sequestration, including product decomposition, conversion fluxes, and animal respiration, has not yet returned to predisturbance levels as seen in the potential vegetation. Differences in response to disturbance have to do with the type, frequency, and intensity of disturbance. Fire, in particular, is seen to have a net negative effect on carbon storage in forests due to decomposition of coarse woody debris and the fact that some nitrogen is lost during volatilization. Croplands become a carbon source if assuming product decomposition occurs where the crops are grown, and pasturelands become carbon neutral if accounting for animal respiration.

Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers.

PubMed

Grouzmann, Eric; Bigliardi, Paul; Appenzeller, Monique; Pannatier, André; Buclin, Thierry

2011-03-01

Substance P (SP), an undecapeptide belonging to the tachykinin family, is released during the activation of sensory nerves, and causes vasodilation, edema and pain through activation of tissular Neurokinin 1 receptors. SP proinflammatory effects are terminated by angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), while the aminopeptidase dipeptidylpeptidase IV (DPPIV) can also play a role. The aim of this randomized, crossover, double-blind study was to assess the cutaneous vasoreactivity (flare and wheal reaction, burning pain sensation) to intradermal injection of ascending doses of SP in six volunteers receiving a single therapeutic dose of the DPPIV inhibitor sitagliptin or a matching placebo. Cutaneous SP challenges produced the expected, dose-dependent flare and wheal response, while eliciting mild to moderate local pain sensation with little dose dependency. However, no differences were shown in the responses observed under sitagliptin compared with placebo, while the study would have been sufficiently powered to detect a clinically relevant increase in sensitivity to SP. The results of this pilot study are in line with proteolytic cleavage of SP by ACE and NEP compensating the blockade of DPPIV to prevent an augmentation of its proinflammatory action.

Landslides, floods and sinkholes in a karst environment: the 1-6 September 2014 Gargano event, southern Italy

NASA Astrophysics Data System (ADS)

Martinotti, Maria Elena; Pisano, Luca; Marchesini, Ivan; Rossi, Mauro; Peruccacci, Silvia; Brunetti, Maria Teresa; Melillo, Massimo; Amoruso, Giuseppe; Loiacono, Pierluigi; Vennari, Carmela; Vessia, Giovanna; Trabace, Maria; Parise, Mario; Guzzetti, Fausto

2017-03-01

In karst environments, heavy rainfall is known to cause multiple geohydrological hazards, including inundations, flash floods, landslides and sinkholes. We studied a period of intense rainfall from 1 to 6 September 2014 in the Gargano Promontory, a karst area in Puglia, southern Italy. In the period, a sequence of torrential rainfall events caused severe damage and claimed two fatalities. The amount and accuracy of the geographical and temporal information varied for the different hazards. The temporal information was most accurate for the inundation caused by a major river, less accurate for flash floods caused by minor torrents and even less accurate for landslides. For sinkholes, only generic information on the period of occurrence of the failures was available. Our analysis revealed that in the promontory, rainfall-driven hazards occurred in response to extreme meteorological conditions and that the karst landscape responded to the torrential rainfall with a threshold behaviour. We exploited the rainfall and the landslide information to design the new ensemble-non-exceedance probability (E-NEP) algorithm for the quantitative evaluation of the possible occurrence of rainfall-induced landslides and of related geohydrological hazards. The ensemble of the metrics produced by the E-NEP algorithm provided better diagnostics than the single metrics often used for landslide forecasting, including rainfall duration, cumulated rainfall and rainfall intensity. We expect that the E-NEP algorithm will be useful for landslide early warning in karst areas and in other similar environments. We acknowledge that further tests are needed to evaluate the algorithm in different meteorological, geological and physiographical settings.

Carbon Fluxes at the AmazonFACE Research Site

NASA Astrophysics Data System (ADS)

Norby, R.; De Araujo, A. C.; Cordeiro, A. L.; Fleischer, K.; Fuchslueger, L.; Garcia, S.; Hofhansl, F.; Garcia, M. N.; Grandis, A.; Oblitas, E.; Pereira, I.; Pieres, N. M.; Schaap, K.; Valverde-Barrantes, O.

2017-12-01

The free-air CO2 enrichment (FACE) experiment to be implemented in the Amazon rain forest requires strong pretreatment characterization so that eventual responses to elevated CO2 can be detected against a background of substantial species diversity and spatial heterogeneity. Two 30-m diameter plots have been laid out for initial characterization in a 30-m tall, old-growth, terra firme forest. Intensive measurements have been made of aboveground tree growth, leaf area, litter production, and fine-root production; these data sets together support initial estimates of plot-scale net primary productivity (NPP). Leaf-level measurements of photosynthesis throughout the canopy and over a daily time course in both the wet and dry season, coupled with meterological monitoring, support an initial estimate of gross primary productivity (GPP) and carbon-use efficiency (CUE = NPP/GPP). Monthly monitoring of CO2 efflux from the soil, partitioned into autotrophic and heterotrophic components, supports an estimate of net ecosystem production (NEP). Our estimate of NPP in the two plots (1.2 and 1.4 kg C m-2 yr-1) is 16-38% greater than previously reported for the site, primarily due to our more complete documentation of fine-root production, including root production deeper than 30 cm. The estimate of CUE of the ecosystem (0.52) is greater than most others in Amazonia; this discrepancy reflects large uncertainty in GPP, which derived from just two days of measurement, or to underestimates of the fine-root component of NPP in previous studies. Estimates of NEP (0 and 0.14 kg C m-2 yr-1) are generally consistent with a landscape-level estimate from flux tower data. Our C flux estimates, albeit very preliminary, provide initial benchmarks for a 12-model a priori evaluation of this forest. The model means of GPP, NPP, and NEP are mostly consistent with our field measurements. Predictions of C flux responses to elevated CO2 from the models become hypotheses to be tested in the FACE experiment. Although carbon fluxes on small plots cannot be expected to represent the fluxes across the wider and more diverse region, our integrated measurements, coupled with a model framework, provide a strong foundation for understanding the mechanistic basis of responses and for extending results of experimental CO2 fertilization to the wider region.

Impact of clinically tested NEP/ACE inhibitors on tumor uptake of [(111)In-DOTA]MG11-first estimates for clinical translation.

PubMed

Kaloudi, Aikaterini; Nock, Berthold A; Lymperis, Emmanouil; Valkema, Roelf; Krenning, Eric P; de Jong, Marion; Maina, Theodosia

2016-12-01

We have recently shown that treatment of mice with the neutral endopeptidase (NEP) inhibitor phosphoramidon (PA) improves the bioavailability and tumor uptake of biodegradable radiopeptides. For the truncated gastrin radiotracer [(111)In-DOTA]MG11 ([(DOTA)DGlu(10)]gastrin(10-17)), this method led to impressively high tumor-to-kidney ratios. Translation of this concept in the clinic requires the use of certified NEP inhibitors, such as thiorphan (TO) and its orally administered prodrug racecadotril (Race). Besides NEP, angiotensin-converting enzyme (ACE) has also been implicated in the catabolism of gastrin analogs. In the present study, we first compared the effects induced by NEP inhibition (using PA, TO, or Race) and/or by ACE inhibition (using lisinopril, Lis) on the biodistribution profile of [(111)In-DOTA]MG11 in mice. In addition, we compared the efficacy of PA and TO at different administered doses to enhance tumor uptake. [(111)In-DOTA]MG11 was coinjected with (a) vehicle, (b) PA (300 μg), (c) TO (150 μg), (d) Lis (100 μg), (e) PA (300 μg) plus Lis (100 μg), or (f) 30-40 min after intraperitoneal (ip) injection of Race (3 mg) in SCID mice bearing AR42J xenografts. In addition, [(111)In-DOTA]MG11 was coinjected with vehicle, or with progressively increasing amounts of PA (3, 30, or 300 μg) or TO (1.5, 15, and 150 μg) in SCID mice bearing twin A431-CCK2R(+/-) tumors. In all above cases, biodistribution was conducted at 4 h postinjection (pi). During NEP inhibition, the uptake of [(111)In-DOTA]MG11 in the AR42J tumors impressively increased from 1.8 ± 1.0 % ID/g (controls) to 15.3 ± 4.7 % ID/g (PA) and 12.3 ± 3.6 % ID/g (TO), while with Race tumor values reached 6.8 ± 2.8 % ID/g. Conversely, Lis had no effect on tumor uptake and no additive effect when coinjected with PA. During the dose dependence study in mice, PA turned out to be more efficacious in enhancing tumor uptake of [(111)In-DOTA]MG11 in the CCK2R-positive tumors compared to equimolar amounts of TO. In all cases, renal accumulation remained low, resulting in notable increases of tumor-to-kidney ratios. This study has confirmed NEP as the predominant degrading enzyme of [(111)In-DOTA]MG11 and ruled out the involvement of ACE in the in vivo catabolism of the radiotracer. NEP inhibition with the clinically tested NEP inhibitors TO and Race resulted in significant enhancement of tumor-to-kidney ratios vs. However, compared with PA, TO and its prodrug Race induced less potent increases of tumor uptake, highlighting the significance of inhibitor type, administration route, and dose for implementing a first proof-of-principle study in human.

Development of the Nano-HEB Array for Low-Background Far-IR Applications

NASA Technical Reports Server (NTRS)

Karasik, Boris S.; Pereverzev, Sergey V.; Olaya, David; Gershenson, Michael E.; Cantor, Robin; Kawamura, Jonathan H.; Day, Peter K.; Bumble, Bruce; LeDuc, Henry G.; Monacos, Steve P.;

Identification of neuropathic pain in patients with neck/upper limb pain: application of a grading system and screening tools.

PubMed

Tampin, Brigitte; Briffa, Noelle Kathryn; Goucke, Roger; Slater, Helen

2013-12-01

The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain has proposed a grading system for the presence of neuropathic pain (NeP) using the following categories: no NeP, possible, probable, or definite NeP. To further evaluate this system, we investigated patients with neck/upper limb pain with a suspected nerve lesion, to explore: (i) the clinical application of this grading system; (ii) the suitability of 2 NeP questionnaires (Leeds Assessment of Neuropathic Symptoms and Signs pain scale [LANSS] and the painDETECT questionnaire [PD-Q]) in identifying NeP in this patient cohort; and (iii) the level of agreement in identifying NeP between the NeuPSIG classification system and 2 NeP questionnaires. Patients (n = 152; age 52 ± 12 years; 53% male) completed the PD-Q and LANSS questionnaire and underwent a comprehensive clinical examination. The NeuPSIG grading system proved feasible for application in this patient cohort, although it required considerable time and expertise. Both questionnaires failed to identify a large number of patients with clinically classified definite NeP (LANSS sensitivity 22%, specificity 88%; PD-Q sensitivity 64%, specificity 62%). These lowered sensitivity scores contrast with those from the original PD-Q and LANSS validation studies and may reflect differences in the clinical characteristics of the study populations. The diagnostic accuracy of LANSS and PD-Q for the identification of NeP in patients with neck/upper limb pain appears limited. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Expression of neuropeptides and their degrading enzymes in ACD.

PubMed

Bak, H; Lee, W J; Lee, Y W; Chang, S-E; Choi, J-H; Kim, M N; Kim, B J; Choi, Y S; Suh, H S

2010-04-01

Sensory neuropeptides such as neurokinin A or substance P modulate skin and immune cells the functions of neurokinin receptor activation during neurogenic inflammation. Zinc metalloproteases, such as neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), effectively control the bioavailability of these neuropeptide mediators, which are released from sensory nerves, immune and skin cells during cutaneous responses to endogenous or exogenous noxious stimuli. Recently, studies have suggested that neuropeptides are one of the major pathogenetic fact in many dermatoses, such as allergic contact dermatitis (ACD), atopic dermatitis and psoriasis. To investigate the expression of major neuropeptides, SP and its degrading enzymes such as NEP and ACE, in the lesions of ACD. A skin biopsy was obtained from 10 patients with ACD. We analysed the expression of these molecules by immunohistochemical staining, confocal laser scanning microscopy, western blotting and reverse transcription PCR. There was a significant increase in expression of SP in keratinocytes from ACD lesions compared with those in control skin. There was also increased expression of ACE but not NEP in ACD. Neuropeptides and their degrading enzymes, particularly SP and ACE, have a significant role in the pathogenesis of ACD.

(99m)Tc-labeled gastrins of varying peptide chain length: Distinct impact of NEP/ACE-inhibition on stability and tumor uptake in mice.

PubMed

Kaloudi, Aikaterini; Nock, Berthold A; Lymperis, Emmanouil; Krenning, Eric P; de Jong, Marion; Maina, Theodosia

2016-06-01

In situ inhibition of neutral endopeptidase (NEP) has been recently shown to impressively increase the bioavailability and tumor uptake of biodegradable gastrin radioligands. Furthermore, angiotensin converting enzyme (ACE) has been previously shown to cleave gastrin analogs in vitro. In the present study, we have assessed the effects induced by single or dual NEP/ACE-inhibition on the pharmacokinetic profile of three (99m)Tc-labeled gastrins of varying peptide chain length: [(99m)Tc]SG6 ([(99m)Tc-N4-Gln(1)]gastrin(1-17)), [(99m)Tc]DG2 ([(99m)Tc-N4-Gly(4),DGlu(5)]gastrin(4-17)) and [(99m)Tc]DG4 ([(99m)Tc-N4-DGlu(10)]gastrin(10-17)). Mouse blood samples were collected 5min after injection of each of [(99m)Tc]SG6/DG2/DG4 together with: a) vehicle, b) the NEP-inhibitor phosphoramidon (PA), c) the ACE-inhibitor lisinopril (Lis), or d) PA plus Lis and were analyzed by RP-HPLC for radiometabolite detection. Biodistribution was studied in SCID mice bearing A431-CCK2R(+/-) xenografts at 4h postinjection (pi). [(99m)Tc]SG6 or [(99m)Tc]DG4 was coinjected with either vehicle or the above described NEP/ACE-inhibitor regimens; for [(99m)Tc]DG2 control and PA animal groups were only included. Treatment of mice with PA induced significant stabilization of (99m)Tc-radiotracers in peripheral blood, while treatment with Lis or Lis+PA affected the stability of des(Glu)5 [(99m)Tc]DG4 only. In line with these findings, PA coinjection led to notable amplification of tumor uptake of radiopeptides compared to controls (P<0.01). Only [(99m)Tc]DG4 profited by single Lis (2.06±0.39%ID/g vs 0.99±0.13%ID/g in controls) or combined Lis+PA coinjection (8.91±1.61%ID/g vs 4.89±1.33%ID/g in PA-group). Furthermore, kidney uptake remained favourably low and unaffected by PA and/or Lis coinjection only in the case of [(99m)Tc]DG4 (<1.9%ID/g) resulting in the most optimal tumor-to-kidney ratios. In situ NEP/ACE-inhibition diversely affected the in vivo profile of (99m)Tc-radioligands based on different-length gastrins. Truncated [(99m)Tc]DG4 exhibited overall the most attractive profile during combined NEP/ACE-inhibition in mouse models, providing new opportunities for CCK2R-expressing tumor imaging in man with SPECT. Copyright © 2016 Elsevier Inc. All rights reserved.

Throughfall reduction and nutrient availability effects on carbon balance in loblolly pine plantations in the southeastern United States

NASA Astrophysics Data System (ADS)

Bracho, R. G.; Vogel, J.; Jokela, E. J.; Cucinella, J.; Noormets, A.; Laviner, M. A.; Gonzalez-Benecke, C. A.; Samuelson, L. J.; Markewitz, D.; Will, R.; Meek, C.; Seiler, J.; Strahm, B. D.; McElligott, K.; Martin, T.

2016-12-01

Planted loblolly pine covers over 11 million hectares in the southeastern United States. Occurring across a range of climatic conditions, these pine plantations are critical for the regional economy and offset a significant fraction of anthropogenic CO2 emissions. Loblolly pine productivity has been enhanced through genetic improvement and intensive silviculture. However, climate projections forecast higher air temperature and more variable precipitation patterns for the region. A critical question is how silvicultural practices will interact with projected climate change to affect loblolly pine carbon balance. A fertilization by throughfall reduction experiment was established in the spring of 2012 at four loblolly pine plantations at the margins of the natural range of the specie (Florida FL, Georgia GA, Oklahoma OK and Virginia VA). Net primary productivity (NPP) was estimated from repeated tree inventories and net ecosystem productivity (NEP) as the difference between NPP and heterotrophic respiration (RH). Soil respiration (RS) and RH were measured simultaneously several times during the experiment. Throughfall reduction significantly decreased surface soil water content at all sites. After four years of treatment, fertilization increased NPP at all sites and throughfall reduction had a negative effect on NPP at the GA and OK sites. The combination fertilization x throughfall reduction did not have a significant effect on NPP. RS and RH were, in general negatively affected by fertilization and throughfall reduction with differential responses between sites, leading to significant NEP increases under fertilization, while throughfall reduction increased NEP at FL and VA due to no effect on NPP and negative effect on RS. Fertilization offset the negative effect of throughfall reduction on NEP in the fertilization x throughfall reduction treatment. All sites were significant carbon sinks, accumulating from 3.5 to 24 Mg C ha-1 in a 3 year period under a range of climatic conditions, age and treatments.

Neutral Endopeptidase Inhibits Neuropeptide Mediated Growth of Androgen-Independent Prostate Cancer

DTIC Science & Technology

2000-09-01

The objective of this project is to elucidate the involvement of neutral endopeptidase (NEP), a cell-surface peptidase which inactivates active...pathways. Recombinant NEP and induced NEP can inhibit the bombesin and endothelin-l stimulated FAK phosphorylation and cell migration. These studies will

Overview of North Ecliptic Pole Deep Multi-Wavelength Survey Nep-Deep

NASA Astrophysics Data System (ADS)

Matsuhara, H.; Wada, T.; Oi, N.; Takagi, T.; Nakagawa, T.; Murata, K.; Goto, T.; Oyabu, S.; Takeuchi, T. T.; Malek, K.; Solarz, A.; Ohyama, Y.; Miyaji, T.; Krumpe, M.; Lee, H. M.; Im, M.; Serjeant, S.; Pearson, C. P.; White, G. J.; Malkan, M. A.; Hanami, H.; Ishigaki, T.; Burgarella, D.; Buat, V.; Pollo, A.

2017-03-01

The recent updates of the North Ecliptic Pole deep (0.5~deg$^2$, NEP-Deep) multi-wavelength survey covering from X-ray to radio-wave is presented. The NEP-Deep provides us with several thousands of 15~$\\mu$m or 18~$\\mu$m selected sample of galaxies, which is the largest sample ever made at this wavelengths. A continuous filter coverage in the mid-infrared wavelength (7, 9, 11, 15, 18, and 24~$\\mu$m) is unique and vital to diagnose the contributions from starbursts and AGNs in the galaxies out to $z$=2.The new goal of the project is to resolve the nature of the cosmic star formation history at the violent epoch (e.g. $z$=1--2), and to find a clue to understand its decline from $z$=1 to present universe by utilizing the unique power of the multi-wavelength survey. The progress in this context is briefly mentioned.

Analysis of Grassland Ecosystem Physiology at Multiple Scales Using Eddy Covariance, Stable Isotope and Remote Sensing Techniques

NASA Astrophysics Data System (ADS)

Flanagan, L. B.; Geske, N.; Emrick, C.; Johnson, B. G.

2006-12-01

Grassland ecosystems typically exhibit very large annual fluctuations in above-ground biomass production and net ecosystem productivity (NEP). Eddy covariance flux measurements, plant stable isotope analyses, and canopy spectral reflectance techniques have been applied to study environmental constraints on grassland ecosystem productivity and the acclimation responses of the ecosystem at a site near Lethbridge, Alberta, Canada. We have observed substantial interannual variation in grassland productivity during 1999-2005. In addition, there was a strong correlation between peak above-ground biomass production and NEP calculated from eddy covariance measurements. Interannual variation in NEP was strongly controlled by the total amount of precipitation received during the growing season (April-August). We also observed significant positive correlations between a multivariate ENSO index and total growing season precipitation, and between the ENSO index and annual NEP values. This suggested that a significant fraction of the annual variability in grassland productivity was associated with ENSO during 1999-2005. Grassland productivity varies asymmetrically in response to changes in precipitation with increases in productivity during wet years being much more pronounced than reductions during dry years. Strong increases in plant water-use efficiency, based on carbon and oxygen stable isotope analyses, contribute to the resilience of productivity during times of drought. Within a growing season increased stomatal limitation of photosynthesis, associated with improved water-use efficiency, resulted in apparent shifts in leaf xanthophyll cycle pigments and changes to the Photochemical Reflectance Index (PRI) calculated from hyper-spectral reflectance measurements conducted at the canopy-scale. These shifts in PRI were apparent before seasonal drought caused significant reductions in leaf area index (LAI) and changes to canopy-scale "greenness" based on NDVI values. With further progression of the seasonal drought, LAI and canopy-scale NDVI also declined in strong correlation. In addition, we have observed strong correlation between NDVI calculated from canopy-scale reflectance measurements and NDVI determined by MODIS. Continued reflectance measurements will help to understand and document the response of the grassland to seasonal and annual environmental change.

TcCYS4, a cystatin from cocoa, reduces necrosis triggered by MpNEP2 in tobacco plants.

PubMed

Santana, L S; Costa, M G C; Pirovani, N M; Almeida, A F; Alvim, F C; Pirovani, C P

2014-09-26

In Brazil, most cocoa bean production occurs in Southern Bahia. Witches' broom disease arrived in this area in 1989 and has since caused heavy losses in production. The disease is caused by the basidiomycete fungus Moniliophthora perniciosa, a hemibiotrophic fungus that produces the necrosis and ethylene-inducting protein (MpNEP2) during infection; this protein can activate cysteine proteases and induce programmed cell death. Cysteine proteases can be modulated by cystatin. In this study, we overexpressed TcCYS4, a cocoa cystatin, in tobacco plants and evaluated the effect on MpNEP2 in model plants. Tccys4 cDNA was cloned into the pCAMBIA 1390 vector and inserted into the tobacco plants via Agrobacterium tumefaciens. Transgene expression was analyzed by reverse transcription-quantitative PCR and Western blot analysis. Transcript and protein levels in Tcccys4:tobacco lines were 8.9- and 1.5-fold higher than in wild-type plants (wt). Tcccys4:tobacco lines showed no change in growth compared to wt plants. CO2 net assimilation (A) increased in Tcccys4:tobacco lines compared to wt plants. Only one line showed statistically significant stomatal conductance (gs) and transpiration rate (E) changes. MpNEP2 was infiltered into the foliar mesophyll of Tcccys4:tobacco lines and wt plants, and necrotic lesions were attenuated in lines highly expressing Tccys4. Our results suggest that cocoa cystatin TcCYS4 affects MpNEP2 activity related to the progression of programmed cell death in tobacco plants. This may occur through the action of cystatin to inhibit cysteine proteases activated by MpNEP2 in plant tissues. Further studies are necessary to examine cystatin in the Theobroma cacao-M. perniciosa pathosystem.

Fracture network evaluation program (FraNEP): A software for analyzing 2D fracture trace-line maps

NASA Astrophysics Data System (ADS)

Zeeb, Conny; Gomez-Rivas, Enrique; Bons, Paul D.; Virgo, Simon; Blum, Philipp

2013-10-01

Fractures, such as joints, faults and veins, strongly influence the transport of fluids through rocks by either enhancing or inhibiting flow. Techniques used for the automatic detection of lineaments from satellite images and aerial photographs, LIDAR technologies and borehole televiewers significantly enhanced data acquisition. The analysis of such data is often performed manually or with different analysis software. Here we present a novel program for the analysis of 2D fracture networks called FraNEP (Fracture Network Evaluation Program). The program was developed using Visual Basic for Applications in Microsoft Excel™ and combines features from different existing software and characterization techniques. The main novelty of FraNEP is the possibility to analyse trace-line maps of fracture networks applying the (1) scanline sampling, (2) window sampling or (3) circular scanline and window method, without the need of switching programs. Additionally, binning problems are avoided by using cumulative distributions, rather than probability density functions. FraNEP is a time-efficient tool for the characterisation of fracture network parameters, such as density, intensity and mean length. Furthermore, fracture strikes can be visualized using rose diagrams and a fitting routine evaluates the distribution of fracture lengths. As an example of its application, we use FraNEP to analyse a case study of lineament data from a satellite image of the Oman Mountains.

Forecasting carbon budget under climate change and CO2 fertilization for subtropical region in China using integrated biosphere simulator (IBIS) model

USGS Publications Warehouse

Zhu, Q.; Jiang, H.; Liu, J.; Peng, C.; Fang, X.; Yu, S.; Zhou, G.; Wei, X.; Ju, W.

2011-01-01

The regional carbon budget of the climatic transition zone may be very sensitive to climate change and increasing atmospheric CO2 concentrations. This study simulated the carbon cycles under these changes using process-based ecosystem models. The Integrated Biosphere Simulator (IBIS), a Dynamic Global Vegetation Model (DGVM), was used to evaluate the impacts of climate change and CO2 fertilization on net primary production (NPP), net ecosystem production (NEP), and the vegetation structure of terrestrial ecosystems in Zhejiang province (area 101,800 km2, mainly covered by subtropical evergreen forest and warm-temperate evergreen broadleaf forest) which is located in the subtropical climate area of China. Two general circulation models (HADCM3 and CGCM3) representing four IPCC climate change scenarios (HC3AA, HC3GG, CGCM-sresa2, and CGCM-sresb1) were used as climate inputs for IBIS. Results show that simulated historical biomass and NPP are consistent with field and other modelled data, which makes the analysis of future carbon budget reliable. The results indicate that NPP over the entire Zhejiang province was about 55 Mt C yr-1 during the last half of the 21st century. An NPP increase of about 24 Mt C by the end of the 21st century was estimated with the combined effects of increasing CO2 and climate change. A slight NPP increase of about 5 Mt C was estimated under the climate change alone scenario. Forests in Zhejiang are currently acting as a carbon sink with an average NEP of about 2.5 Mt C yr-1. NEP will increase to about 5 Mt C yr-1 by the end of the 21st century with the increasing atmospheric CO2 concentration and climate change. However, climate change alone will reduce the forest carbon sequestration of Zhejiang's forests. Future climate warming will substantially change the vegetation cover types; warm-temperate evergreen broadleaf forest will be gradually substituted by subtropical evergreen forest. An increasing CO2 concentration will have little contribution to vegetation changes. Simulated NPP shows geographic patterns consistent with temperature to a certain extent, and precipitation is not the limiting factor for forest NPP in the subtropical climate conditions. There is no close relationship between the spatial pattern of NEP and climate condition.

Forecasting carbon budget under climate change and CO 2 fertilization for subtropical region in China using integrated biosphere simulator (IBIS) model

USGS Publications Warehouse

Zhu, Q.; Jiang, H.; Liu, J.; Peng, C.; Fang, X.; Yu, S.; Zhou, G.; Wei, X.; Ju, W.

2011-01-01

The regional carbon budget of the climatic transition zone may be very sensitive to climate change and increasing atmospheric CO 2 concentrations. This study simulated the carbon cycles under these changes using process-based ecosystem models. The Integrated Biosphere Simulator (IBIS), a Dynamic Global Vegetation Model (DGVM), was used to evaluate the impacts of climate change and CO 2 fertilization on net primary production (NPP), net ecosystem production (NEP), and the vegetation structure of terrestrial ecosystems in Zhejiang province (area 101,800 km 2, mainly covered by subtropical evergreen forest and warm-temperate evergreen broadleaf forest) which is located in the subtropical climate area of China. Two general circulation models (HADCM3 and CGCM3) representing four IPCC climate change scenarios (HC3AA, HC3GG, CGCM-sresa2, and CGCM-sresb1) were used as climate inputs for IBIS. Results show that simulated historical biomass and NPP are consistent with field and other modelled data, which makes the analysis of future carbon budget reliable. The results indicate that NPP over the entire Zhejiang province was about 55 Mt C yr -1 during the last half of the 21 st century. An NPP increase of about 24 Mt C by the end of the 21 st century was estimated with the combined effects of increasing CO 2 and climate change. A slight NPP increase of about 5 Mt C was estimated under the climate change alone scenario. Forests in Zhejiang are currently acting as a carbon sink with an average NEP of about 2.5 Mt C yr -1. NEP will increase to about 5 Mt C yr -1 by the end of the 21 st century with the increasing atmospheric CO 2 concentration and climate change. However, climate change alone will reduce the forest carbon sequestration of Zhejiang's forests. Future climate warming will substantially change the vegetation cover types; warm-temperate evergreen broadleaf forest will be gradually substituted by subtropical evergreen forest. An increasing CO 2 concentration will have little contribution to vegetation changes. Simulated NPP shows geographic patterns consistent with temperature to a certain extent, and precipitation is not the limiting factor for forest NPP in the subtropical climate conditions. There is no close relationship between the spatial pattern of NEP and climate condition.

Grassland and cropland net ecosystem production of the U.S. Great Plains: Regression tree model development and comparative analysis

USGS Publications Warehouse

Wylie, Bruce K.; Howard, Daniel; Dahal, Devendra; Gilmanov, Tagir; Ji, Lei; Zhang, Li; Smith, Kelcy

2016-01-01

This paper presents the methodology and results of two ecological-based net ecosystem production (NEP) regression tree models capable of up scaling measurements made at various flux tower sites throughout the U.S. Great Plains. Separate grassland and cropland NEP regression tree models were trained using various remote sensing data and other biogeophysical data, along with 15 flux towers contributing to the grassland model and 15 flux towers for the cropland model. The models yielded weekly mean daily grassland and cropland NEP maps of the U.S. Great Plains at 250 m resolution for 2000–2008. The grassland and cropland NEP maps were spatially summarized and statistically compared. The results of this study indicate that grassland and cropland ecosystems generally performed as weak net carbon (C) sinks, absorbing more C from the atmosphere than they released from 2000 to 2008. Grasslands demonstrated higher carbon sink potential (139 g C·m−2·year−1) than non-irrigated croplands. A closer look into the weekly time series reveals the C fluctuation through time and space for each land cover type.

Effect of quercetin on plasma extravasation in rat CNS and dura mater by ACE and NEP inhibition.

PubMed

Cyrino, Luiz A R; Cardoso, Ronie C F; Hackl, Luciane P N; Nicolau, Mauro

2002-09-01

The effects of quercetin on substance P-induced plasma protein extravasation (PE) in the rat dura mater, cerebellum, olfactory bulb and cortex and also its modulation by endopeptidases, angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) were studied. PE was assessed by photometric measurement of extravasated Evans blue. Substance P (SP) and NEP or ACE inhibitors increased the PE in dura mater. Pretreatment with captopril or phosphoramidon potentiated PE induced by SP in the dura mater and cerebellum, respectively. Quercetin increased the PE in the dura mater, cerebellum and cortex. Further results suggested that the PE induced by SP in the dura mater was enhanced by pretreatment with quercetin, similar to that observed with selective peptidase inhibitors. Quercetin-stimulated extravasation in all tissues was abolished by NK-1 receptor blockade. These results suggest that quercetin increases PE in the dura mater and CNS tissues by inhibiting NEP and/or ACE, showing that the effect induced in the dura mater, cerebellum and cortex occurs through endogenous SP accumulation. Copyright 2002 John Wiley & Sons, Ltd.

The peptidase inhibitor CGS-26303 increases endothelin converting enzyme-1 expression in endothelial cells through accumulation of big endothelin-1

PubMed Central

Raoch, V; Martinez-Miguel, P; Arribas-Gomez, I; Rodriguez-Puyol, M; Rodriguez-Puyol, D; Lopez-Ongil, S

2007-01-01

Background and purpose: CGS-26303 inhibits endothelin converting enzyme (ECE)-1 more specifically than phosphoramidon. We have studied the effect of CGS-26303 on ECE-1 expression in bovine aortic endothelial cells. Methods: ECE-1 activity and big endothelin (ET)-1 levels were measured by ELISA, ECE-1 expression using western and northern blot and promoter activity using transfection assays. Key results: ECE-1 activity was completely inhibited by CGS-26303 25 μ M and phosphoramidon 100 μ M. CGS-26303 and phosphoramidon, though not thiorphan, a neutral endopeptidase (NEP) inhibitor, stimulated ECE-1 expression in cells (maximal effect at 16 h, 25 μ M). Cycloheximide abolished that effect. CGS-26303 induced ECE-1 mRNA expression and ECE-1 promoter activity. CGS-35066, a selective ECE-1 inhibitor, mimicked the effects of CGS-26303, suggesting that the effect was specific to ECE-1 inhibition. Big ET-1 accumulated in the cells and in the supernatants after CGS-26303 treatment. Neither exogenously added ET-1 nor the blockade of their receptors with bosentan modified ECE-1 protein. When big ET-1 was added to cells, significant increases in ECE-1 protein content and ECE-1 promoter activity were found. Bosentan did not block those effects. CGS-26303 did not modify prepro-ET-1 expression. CGS-26303 and big ET-1 induced the same effects in human endothelial cells, at lower doses. Conclusions: These results suggest that the accumulation of big ET-1 is responsible for the effects of CGS-26303 on ECE-1 and they did not depend on NEP blockade. Changes in ECE-1 protein after the administration of CGS-26303 could lead to a decreased response in long-term treatments. PMID:17643133

High sensitivity operation of discrete solid state detectors at 4 K

NASA Technical Reports Server (NTRS)

Rieke, G. H.; Montgomery, E. F.; Lebofsky, M. J.; Eisenhardt, P. R.

1981-01-01

Techniques are described to allow operation of discrete, solid state detectors at 4 K with optimized JFET amplifiers. Three detector types cover the 0.6 to 4 mm spectral range with NEP approximately equal to 10 to the 16th power Hz (-1/2) for two of the types and potential improvement to this performance for the third. Lower NEP's are anticipated at longer infrared wavelengths.

Record Low NEP in the Hot-Electron Titanium Nanobolometers

NASA Technical Reports Server (NTRS)

Karasik, Boris S.; Olaya, David; Wei, Jian; Pereverzev, Sergey; Gershenson, Michael E.; Kawamura, Jonathan H.; McGrath, William R.; Sergeev, Andrei V.

2006-01-01

We are developing hot-electron superconducting transition-edge sensors (TES) capable of counting THz photons and operating at T = 0.3K. We fabricated superconducting Ti nanosensors with Nb contacts with a volume of approx. 3x10(exp -3) cu microns on planar Si substrate and have measured the thermal conductance due to the weak electron-phonon coupling in the material G = 4x10(exp -14) W/K at 0.3 K. The corresponding phonon-noise NEP = 3x10(exp -19) W/Hz(sup 1/2). Detection of single optical photons (1550nm and 670nm wavelength) has been demonstrated for larger devices and yielded the thermal time constants of 30 microsec at 145 mK and of 25 microsec at 190 mK. This Hot-Electron Direct Detector (HEDD) is expected to have a sufficient energy resolution for detecting individual photons with (nu) > 1 THz where NEP approx. 3x10(exp -20) W/Hz(sup 1/2) is needed for spectroscopy in space.

Cognitive impairment in patients with fibromyalgia syndrome as assessed by the mini-mental state examination.

PubMed

Rodríguez-Andreu, Jose; Ibáñez-Bosch, Rosario; Portero-Vázquez, Amparo; Masramon, Xavier; Rejas, Javier; Gálvez, Rafael

2009-12-21

This study evaluated the frequency of cognitive impairment in patients with Fibromyalgia syndrome (FMS) using the Mini Mental State Examination (MMSE). We analyzed baseline data from all 46 patients with FMS and 92 age- and sex-matched controls per diagnosis of neuropathic (NeP) or mixed pain (MP) selected from a larger prospective study. FMS had a slight but statistically significant lower score in the adjusted MMSE score (26.9; 95% CI 26.7-27.1) than either NeP (27.3; 95% CI 27.2-27.4) or MP (27.3; 27.2-27.5). The percentage of patients with congnitive impairment (adjusted MMSE

Net Ecosystem Production and Actionable Negative Emissions Strategies

NASA Astrophysics Data System (ADS)

DeCicco, J. M.; Heo, J.

2016-12-01

Negative emissions strategies, designed to increase the rate at which carbon dioxide (CO2) and other greenhouse gases are removed from the atmosphere, are an important aspect of broader strategies for mitigating climate change. Not only is CO2 the dominant greenhouse gas and the one most intimately tied to existing commercial energy use, but it is also part of the global carbon cycle. On the order of 200 PgC•yr-1 circulates between the atmosphere and the major carbon stocks of the terrestrial biosphere, oceans and geosphere. Anthropogenic flows of roughly 10 PgC•yr-1 from fossil fuel use and 1 PgC•yr-1 from land-use change significantly exceed the Earth's natural carbon sink, and this imbalance causes the buildup of carbon in the atmosphere. In addition to strategies for reducing CO2 emissions, increasing negative emissions through carbon dioxide removal (CDR) is crucial for reducing carbon cycle imbalance in the near term as well as meeting long-term goals such as a 2°C limit. Terrestrial carbon management is important for both reducing emissions and enhancing sinks. Photosynthesis in terrestrial ecosystems is the form of CDR that is now most actionable, referring to mechanisms that can be economically implemented at meaningful scales without technology breakthroughs. Net ecosystem production (NEP) is a crucial metric for guiding CDR involving the terrestrial biosphere, including options such as bioenergy with carbon capture and storage (BECCS) and other forms of bio-based mitigation. We derive the necessary conditions for effective implementation of this category of negative emissions measures, emphasizing the importance of NEP measurement, baselines and appropriate methods of carbon accounting. We present a method for quantitative spatio-temporal analysis of land-use and land-cover changes for estimating landscape-scale NEP; provide a preliminary baseline NEP estimate for the continental United States; apply the method to reveal a cautionary tale regarding NEP and biofuel production; and discuss the implications for negative emissions research and public policy going forward.

Importance of Past Human and Natural Disturbance in Present-Day Net Ecosystem Productivity

NASA Astrophysics Data System (ADS)

Felzer, B. S.; Phelps, P.

2014-12-01

Gridded datasets of Net Ecosystem Exchange derived from eddy covariance and remote sensing measurements provide a means of validating Net Ecosystem Productivity (NEP, opposite of NEE) from terrestrial ecosystem models. While most forested regions in the U.S. are observed to be moderate to strong carbon sinks, models not including human or natural disturbances will tend to be more carbon neutral, which is expected of mature ecosystems. We have developed the Terrestrial Ecosystems Model Hydro version (TEM-Hydro) to include both human and natural disturbances to compare against gridded NEP datasets. Human disturbances are based on the Hurtt et al. (2006) land use transition dataset and include transient agricultural (crops and pasture) conversion and abandonment and timber harvest. We include natural disturbances of storms and fires based on stochastic return intervals. Tropical storms and hurricane return intervals are based on Zheng et al. (2009) and occur only along the U.S. Atlantic and Gulf coasts. Fire return intervals are based on LANDFIRE Rapid Assessment Vegetation Models and vegetation types from the Hurtt dataset. We are running three experiments with TEM-Hydro from 1700-2011 for the conterminous U.S.: potential vegetation (POT), human disturbance only (agriculture and timber harvest, LULC), and human plus natural disturbance (agriculture, timber harvest, storms, and fire, DISTURB). The goal is to compare our NEP values to those obtained by FLUXNET-MTE (Jung et al. 2009) from 1982-2008 and ECMOD (Xiao et al., 2008) from 2000-2006 for different plant functional types (PFTs) within the conterminous U.S. Preliminary results show that, for the entire U.S., potential vegetation yields an NEP of 10.8 gCm-2yr-1 vs 128.1 gCm-2yr-1 for LULC and 89.8 gCm-2yr-1 for DISTURB from 1982-2008. The effect of regrowth following agricultural and timber harvest disturbance therefore contributes substantially to the present-day carbon sink, while stochastic storms and fires have a negative effect on NEP. Even though the current NEP reflects the carbon uptake from regrowth, a full carbon accounting would also include the carbon released to the atmosphere during disturbance or carbon lost to decomposition of agricultural or timber products

Evidence for metalloprotease involvement in the in vivo effects of big endothelin 1.

PubMed

Pollock, D M; Opgenorth, T J

1991-07-01

The potent vasoconstrictor endothelin 1 (ET-1) is thought to arise from the proteolytic processing of big endothelin 1 (Big ET) by a unique endothelin-converting enzyme, possibly a metalloprotease. Experiments were conducted to determine the effects of Big ET on cardiovascular and renal functions during inhibition of metalloprotease activity in vivo. Intravenous infusion of Big ET (0.1 nmol.kg-1.min-1) in anesthetized euvolemic rats produced a significant increase in mean arterial pressure (MAP; 39 +/- 8%) and a decrease in effective renal plasma flow (ERPF; -39 +/- 2%), whereas glomerular filtration rate (GFR) remained unchanged (-8 +/- 8%). Simultaneous intravenous infusion of phosphoramidon (0.25 mg.kg-1.min-1), an inhibitor of metalloprotease activity including neutral endopeptidase EC 3.4.24.11 (NEP), completely prevented these effects of Big ET. Thiorphan (0.1 mg.kg-1.min-1), also an inhibitor of NEP, had absolutely no effect on either the renal or cardiovascular response to Big ET. Similarly, the response to Big ET was unaffected by infusion of enalaprilat (0.1 mg.kg-1.min-1), an inhibitor of the angiotensin-converting enzyme, which is also a metalloprotease. To determine whether the effect of phosphoramidon was due to antagonism of ET-1, an identical series of experiments was performed using ET-1 infusion (0.02 nmol.kg-1.min-1). Although the increase in MAP (24 +/- 5%) produced by ET-1 was less than that observed for the given dose of Big ET, the renal vasoconstriction was much more severe; the smaller peptide changed ERPF and GFR by -66 +/- 7 and -54 +/- 9%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacologic Comparison of Clinical Neutral Endopeptidase Inhibitors in a Rat Model of Acute Secretory Diarrhea

PubMed Central

Prinsen, Michael J.; Oliva, Jonathan; Campbell, Mary A.; Arnett, Stacy D.; Tajfirouz, Deena; Ruminski, Peter G.; Yu, Ying; Bond, Brian R.; Ji, Yuhua; Neckermann, Georg; Choy, Robert K. M.; de Hostos, Eugenio; Meyers, Marvin J.

2016-01-01

Racecadotril (acetorphan) is a neutral endopeptidase (NEP) inhibitor with known antidiarrheal activity in animals and humans; however, in humans, it suffers from shortcomings that might be improved with newer drugs in this class that have progressed to the clinic for nonenteric disease indications. To identify potentially superior NEP inhibitors with immediate clinical utility for diarrhea treatment, we compared their efficacy and pharmacologic properties in a rat intestinal hypersecretion model. Racecadotril and seven other clinical-stage inhibitors of NEP were obtained or synthesized. Enzyme potency and specificity were compared using purified peptidases. Compounds were orally administered to rats before administration of castor oil to induce diarrhea. Stool weight was recorded over 4 hours. To assess other pharmacologic properties, select compounds were orally administered to normal or castor oil–treated rats, blood and tissue samples collected at multiple time points, and active compound concentrations determined by mass spectroscopy. NEP enzyme activity was measured in tissue homogenates. Three previously untested clinical NEP inhibitors delayed diarrhea onset and reduced total stool output, with little or no effect on intestinal motility assessed by the charcoal meal test. Each was shown to be a potent, highly specific inhibitor of NEP. Each exhibited greater suppression of NEP activity in intestinal and nonintestinal tissues than did racecadotril and sustained this inhibition longer. These results suggest that newer clinical-stage NEP inhibitors originally developed for other indications may be directly repositioned for treatment of acute secretory diarrhea and offer advantages over racecadotril, such as less frequent dosing and potentially improved efficacy. PMID:26907621

Carbon balance of a partially harvested mixed conifer forest following mountain pine beetle attack and its comparison to a clear-cut

NASA Astrophysics Data System (ADS)

Mathys, A.; Black, T. A.; Nesic, Z.; Nishio, G.; Brown, M.; Spittlehouse, D. L.; Fredeen, A. L.; Bowler, R.; Jassal, R. S.; Grant, N. J.; Burton, P. J.; Trofymow, J. A.; Meyer, G.

2013-08-01

The recent mountain pine beetle (MPB) outbreak has had an impact on the carbon (C) cycling of lodgepole pine forests in British Columbia. This study examines how partial harvesting as a forest management response to MPB infestation affects the net ecosystem production (NEP) of a mixed conifer forest (MPB-09) in Interior BC. MPB-09 is a 70-year-old stand that was partially harvested in 2009 after it had been attacked by MPB. Using the eddy-covariance technique, the C dynamics of the stand were studied over two years and compared to an adjacent clear-cut (MPB-09C) over the summertime. The annual NEP at MPB-09 increased from -108 g C m-2 in 2010 to -57 g C m-2 in 2011. The increase of NEP was due to the associated increase in annual gross ecosystem photosynthesis (GEP) from 812 g C m-2 in 2010 to 954 g C m-2 in 2011, exceeding the increase in annual respiration (Re) from 920 g C m-2 to 1011 g C m-2 during the two years. During the four month period between June and September 2010, NEP at MPB-09C was -103 g C m-2, indicating high C losses in the clear-cut. MPB-09 was a C sink during the growing season of both years, increasing from 9 g C m-2 in 2010 to 47 g C m-2 in 2011. The increase of NEP in the partially harvested stand amounted to a recovery corresponding to a 26% increase in the maximum assimilation rate in the second year. This study shows that retaining the healthy residual forest can result in higher C sequestration of MPB-attacked stands compared to clear-cut harvesting.

Effects of four antitussives on airway neurogenic inflammation in a guinea pig model of chronic cough induced by cigarette smoke exposure.

PubMed

Luo, Yu-long; Li, Pei-bo; Zhang, Chen-chen; Zheng, Yan-fang; Wang, Sheng; Nie, Yi-chu; Zhang, Ke-jian; Su, Wei-wei

2013-12-01

The effects of four antitussives, including codeine phosphate (CP), moguisteine, levodropropizine (LVDP) and naringin, on airway neurogenic inflammation and enhanced cough were investigated in guinea pig model of chronic cough. Guinea pigs were exposed to CS for 8 weeks. At the 7th and 8th week, the animals were treated with vehicle, CP (4.8 mg/kg), moguisteine (24 mg/kg), LVDP (14 mg/kg) and naringin (18.4 mg/kg) respectively. Then the cough and the time-enhanced pause area under the curve (Penh-AUC) during capsaicin challenge were recorded. The substance P (SP) content, NK-1 receptor expression and neutral endopeptidase (NEP) activity in lung were determined. Chronic CS exposure induced a bi-phase time course of cough responsiveness to capsaicin. Eight weeks of CS exposure significantly enhanced the airway neurogenic inflammation and cough response in guinea pigs. Two weeks of treatment with CP, moguisteine, LVDP or naringin effectively attenuated the chronic CS-exposure enhanced cough. Only naringin exerted significant effect on inhibiting Penh-AUC, SP content and NK-1 receptor expression, as well as preventing the declining of NEP activity in lung. Chronic CS-exposed guinea pig is suitable for studying chronic pathological cough, in which naringin is effective on inhibiting both airway neurogenic inflammation and enhanced cough.

Transcription of G-protein coupled receptors in corporal smooth muscle is regulated by sialorphin (an endogenous neutral endopeptidase inhibitor)

PubMed Central

Tong, Yuehong; Tiplitsky, Scott I.; Tar, Moses; Melman, Arnold; Davies, Kelvin P.

2009-01-01

Purpose Several reports have suggested the rat Vcsa1 gene is down-regulated in models of erectile dysfunction (ED). Vcsa’s protein product, sialorphin, is an endogenous neutral endopeptidase (NEP), and its down-regulation could result in prolonged activation of G-protein activated signaling pathways by their peptide agonists. We investigated if down- regulation of Vcsa1 could result in adaptive change in the expression of G-protein coupled receptors (GPCR). Materials and Methods Gene expression in cultured rat corporal smooth muscle cells (CSM) following treatment with siRNA directed against Vcsa1 or the NEP gene was analyzed using microarray and quantitative RT-PCR. In rats Vcsa1 is one of the most down-regulated genes following bilateral transection of the cavernosal nerves. Using that animal model, we also investigated whether the down-regulation of Vcsa1 is accompanied by similar changes in gene expression observed in the CSM cells where Vcsa1 was knocked-down in vitro. Results Microarray analysis and quantitative RT-PCR demonstrated that CSM cells treated in vitro with siRNA against Vcsa1 resulted in up-regulation of GPCR as a functional group. In contrast, treatment of CSM cells that lowered NEP activity resulted in decreases in GPCR expression. These results suggest that the peptide product of Vcsa1, sialorphin, can effect GPCR expression by acting on NEP. In animals with bilaterally transected cavernous nerves the reduced expression of Vcsa1 is accompanied by increased GPCR expression in cavernosal tissue. Conclusions These experiments suggest that the mechanism by which Vcsa1 modulates erectile function is partly mediated through changes in GPCR expression. PMID:18554633

Nuclear electric propulsion

NASA Technical Reports Server (NTRS)

Keaton, Paul W.; Tubb, David J.

1986-01-01

The feasibility is investigated of using nuclear electric propulsion (NEP) for slow freighter ships traveling from a 500 km low Earth orbit (LEO) to the Moon's orbit about the Earth, and on to Mars. NEP is also shown to be feasible for transporting people to Mars on long conjunction-class missions lasting about nine months one way, and on short sprint missions lasting four months one way. Generally, it was not attempted to optimize ion exhaust velocities, but rather suitable parameters to demonstrate NEP feasibility were chosen. Various combinations of missions are compared with chemical and nuclear thermal propulsion (NTR) systems. Typically, NEP and NTR can accomplish the same lifting task with similar mass in LEO. When compared to chemical propulsion, NEP was found to accomplish the same missions with 40% less mass in LEO. These findings are sufficiently encouraging as to merit further studies with optimum systems.

Multi-aged Forest: an Optimal Management Strategy for Carbon Sequestration

NASA Astrophysics Data System (ADS)

Yao, L.; Tang, X.; Ma, M.

2017-12-01

Disturbances and climatic changes significantly affect forest ecosystem productivity, water use efficiency (WUE) and carbon (C) flux dynamics. A deep understanding of terrestrial feedbacks to such effects and recovery mechanisms in forests across contrasting climatic regimes is essential to predict future regional/global C and water budgets, which are also closely related to the potential forest management decisions. However, the resilience of multi-aged and even-aged forests to disturbances has been debated for more than 60 years because of technical measurement constraints. Here we evaluated 62 site-years of eddy covariance measurements of net ecosystem production (NEP), evapotranspiration (ET), the estimates of gross primary productivity (GPP), ecosystem respiration (Re) and ecosystem-level WUE, as well as the relationships with environmental controls in three chronosequences of multi- and even-aged coniferous forests covering the Mediterranean, temperate and boreal regions. Age-specific dynamics in multi-year mean annual NEP and WUE revealed that forest age is a key variable that determines the sign and magnitude of recovering forest C source-sink strength from disturbances. However, the trends of annual NEP and WUE across succession stages between two stand structures differed substantially. The successional patterns of NEP exhibited an inverted-U trend with age at the two even-aged chronosequences, whereas NEP of the multi-aged chronosequence increased steadily through time. Meanwhile, site-level WUE of even-aged forests decreased gradually from young to mature, whereas an apparent increase occurred for the same forest age in multi-aged stands. Compared with even-aged forests, multi-aged forests sequestered more CO2 with forest age and maintained a relatively higher WUE in the later succession periods. With regard to the available flux measurements in this study, these behaviors are independent of tree species, stand ages and climate conditions . We also found that distinctly different environmental factors controlled forest C and water fluxes under three climatic regimes.These findings will provide important implications for forest management strategies to mitigate global climate change.

Remote SST Forcing and Local Land-Atmosphere Moisture Coupling as Drivers of Amazon Temperature and Carbon Cycle Variability

NASA Astrophysics Data System (ADS)

Levine, P. A.; Xu, M.; Chen, Y.; Randerson, J. T.; Hoffman, F. M.

2017-12-01

Interannual variability of climatic conditions in the Amazon rainforest is associated with El Niño-Southern Oscillation (ENSO) and ocean-atmosphere interactions in the North Atlantic. Sea surface temperature (SST) anomalies in these remote ocean regions drive teleconnections with Amazonian surface air temperature (T), precipitation (P), and net ecosystem production (NEP). While SST-driven NEP anomalies have been primarily linked to T anomalies, it is unclear how much the T anomalies result directly from SST forcing of atmospheric circulation, and how much result indirectly from decreases in precipitation that, in turn, influence surface energy fluxes. Interannual variability of P associated with SST anomalies lead to variability in soil moisture (SM), which would indirectly affect T via partitioning of turbulent heat fluxes between the land surface and the atmosphere. To separate the direct and indirect influence of the SST signal on T and NEP, we performed a mechanism-denial experiment to decouple SST and SM anomalies. We used the Accelerated Climate Modeling for Energy (ACMEv0.3), with version 5 of the Community Atmosphere Model and version 4.5 of the Community Land Model. We forced the model with observed SSTs from 1982-2016. We found that SST and SM variability both contribute to T and NEP anomalies in the Amazon, with relative contributions depending on lag time and location within the Amazon basin. SST anomalies associated with ENSO drive most of the T variability at shorter lag times, while the ENSO-driven SM anomalies contribute more to T variability at longer lag times. SM variability and the resulting influence on T anomalies are much stronger in the eastern Amazon than in the west. Comparing modeled T with observations demonstrate that SST alone is sufficient for simulating the correct timing of T variability, but SM anomalies are necessary for simulating the correct magnitude of the T variability. Modeled NEP indicated that variability in carbon fluxes results from both SST and SM anomalies. As with T, SM anomalies affect NEP at a much longer lag time than SST anomalies. These results highlight the role of land-atmosphere coupling in driving climate variability within the Amazon, and suggest that land atmospheric coupling may amplify and delay carbon cycle responses to ocean-atmosphere teleconnections.

Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka

An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 bindsmore » at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. - Highlights: •DP2392-E10 inhibits replication of a broad range of influenza A subtypes. •DP2392-E10 inhibits nuclear exports of NP and NEP via their NP-NES3 and NEP-NES2 domains, respectively. •DP2392-E10 is predicted to directly bind CRM1 in the region near the HEAT9 and HEAT10 repeats.« less

NEP: web server for epitope prediction based on antibody neutralization of viral strains with diverse sequences.

PubMed

Chuang, Gwo-Yu; Liou, David; Kwong, Peter D; Georgiev, Ivelin S

2014-07-01

Delineation of the antigenic site, or epitope, recognized by an antibody can provide clues about functional vulnerabilities and resistance mechanisms, and can therefore guide antibody optimization and epitope-based vaccine design. Previously, we developed an algorithm for antibody-epitope prediction based on antibody neutralization of viral strains with diverse sequences and validated the algorithm on a set of broadly neutralizing HIV-1 antibodies. Here we describe the implementation of this algorithm, NEP (Neutralization-based Epitope Prediction), as a web-based server. The users must supply as input: (i) an alignment of antigen sequences of diverse viral strains; (ii) neutralization data for the antibody of interest against the same set of antigen sequences; and (iii) (optional) a structure of the unbound antigen, for enhanced prediction accuracy. The prediction results can be downloaded or viewed interactively on the antigen structure (if supplied) from the web browser using a JSmol applet. Since neutralization experiments are typically performed as one of the first steps in the characterization of an antibody to determine its breadth and potency, the NEP server can be used to predict antibody-epitope information at no additional experimental costs. NEP can be accessed on the internet at http://exon.niaid.nih.gov/nep. Published by Oxford University Press on behalf of Nucleic Acids Research 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Loss of neutral endopeptidase activity contributes to neutrophil activation and cardiac dysfunction during chronic hypomagnesemia: Protection by substance P receptor blockade.

PubMed

Mak, I Tong; Chmielinska, Joanna J; Kramer, Jay H; Spurney, Christopher F; Weglicki, William B

2011-01-01

Hypomagnesemia (Hypo-Mg) in rodents leads to neurogenic inflammation associated with substance P (SP) elevations; neutral endopeptidase (NEP) is a principle cell surface proteolytic enzyme, which degrades SP. The effects of chronic Hypo-Mg on neutrophil NEP activity, cell activation and the associated cardiac dysfunction were examined. Male Sprague-Dawley rats (180 g) were fed Mg-sufficient or Mg-deficient (Hypo-Mg) diets for five weeks. Enriched blood neutrophils were isolated at the end of one, three and five weeks by step gradient centrifugation. NEP enzymatic activity decreased by 20% (P value was nonsignificant), 50% (P<0.025) and 57% (P<0.01), respectively, for week 1, 3 and 5 Hypo-Mg rats. In association, neutrophil basal superoxide (•O(2) (-))-generating activities were elevated: 30% at week 1 (P value was nonsignificant), and fourfold to sevenfold for weeks 3 to 5 (P<0.01). Maximal phorbol myristate acetate-stimulated •O(2) (-) production by Hypo-Mg neutrophils increased twofold at week 5. Also, plasma 8-isoprostane levels were elevated twofold to threefold, and red blood cell glutathione decreased by 50% (P<0.01) after three to five weeks of chronic Hypo-Mg. When Hypo-Mg rats were treated with the SP receptor blocker (L-703,606), neutrophil NEP activities were retained at 75% (week 3) and 77% (week 5) (P<0.05); activation of neutrophil •O(2) (-) and other oxidative indexes were also significantly (P<0.05) attenuated. After five weeks, histochemical (hematoxylin and eosin) staining of Hypo-Mg-treated rat ventricles revealed significant white blood cell infiltration, which was substantially reduced by L-703,606. Echocardiography after three weeks of Hypo-Mg only showed modest diastolic impairment, but five weeks resulted in significant (P<0.05) depression in both left ventricular systolic and diastolic functions; changes in these functional parameters were attenuated by L-703,606. NEP activity regulates neutrophil •O(2) (-) formation by controlling SP bioavailability. When oxidative inactivation of NEP is prevented by SP receptor blockade, partial protection is afforded against cardiac contractile dysfunction.

Loss of neutral endopeptidase activity contributes to neutrophil activation and cardiac dysfunction during chronic hypomagnesemia: Protection by substance P receptor blockade

PubMed Central

Mak, I Tong; Chmielinska, Joanna J; Kramer, Jay H; Spurney, Christopher F; Weglicki, William B

2011-01-01

BACKGROUND/OBJECTIVE: Hypomagnesemia (Hypo-Mg) in rodents leads to neurogenic inflammation associated with substance P (SP) elevations; neutral endopeptidase (NEP) is a principle cell surface proteolytic enzyme, which degrades SP. The effects of chronic Hypo-Mg on neutrophil NEP activity, cell activation and the associated cardiac dysfunction were examined. METHODS/RESULTS: Male Sprague-Dawley rats (180 g) were fed Mg-sufficient or Mg-deficient (Hypo-Mg) diets for five weeks. Enriched blood neutrophils were isolated at the end of one, three and five weeks by step gradient centrifugation. NEP enzymatic activity decreased by 20% (P value was nonsignificant), 50% (P<0.025) and 57% (P<0.01), respectively, for week 1, 3 and 5 Hypo-Mg rats. In association, neutrophil basal superoxide (•O2−)-generating activities were elevated: 30% at week 1 (P value was nonsignificant), and fourfold to sevenfold for weeks 3 to 5 (P<0.01). Maximal phorbol myristate acetate-stimulated •O2− production by Hypo-Mg neutrophils increased twofold at week 5. Also, plasma 8-isoprostane levels were elevated twofold to threefold, and red blood cell glutathione decreased by 50% (P<0.01) after three to five weeks of chronic Hypo-Mg. When Hypo-Mg rats were treated with the SP receptor blocker (L-703,606), neutrophil NEP activities were retained at 75% (week 3) and 77% (week 5) (P<0.05); activation of neutrophil •O2− and other oxidative indexes were also significantly (P<0.05) attenuated. After five weeks, histochemical (hematoxylin and eosin) staining of Hypo-Mg-treated rat ventricles revealed significant white blood cell infiltration, which was substantially reduced by L-703,606. Echocardiography after three weeks of Hypo-Mg only showed modest diastolic impairment, but five weeks resulted in significant (P<0.05) depression in both left ventricular systolic and diastolic functions; changes in these functional parameters were attenuated by L-703,606. CONCLUSION: NEP activity regulates neutrophil •O2− formation by controlling SP bioavailability. When oxidative inactivation of NEP is prevented by SP receptor blockade, partial protection is afforded against cardiac contractile dysfunction. PMID:22131854

Spatial patterns and climate drivers of carbon fluxes in terrestrial ecosystems of China.

PubMed

Yu, Gui-Rui; Zhu, Xian-Jin; Fu, Yu-Ling; He, Hong-Lin; Wang, Qiu-Feng; Wen, Xue-Fa; Li, Xuan-Ran; Zhang, Lei-Ming; Zhang, Li; Su, Wen; Li, Sheng-Gong; Sun, Xiao-Min; Zhang, Yi-Ping; Zhang, Jun-Hui; Yan, Jun-Hua; Wang, Hui-Min; Zhou, Guang-Sheng; Jia, Bing-Rui; Xiang, Wen-Hua; Li, Ying-Nian; Zhao, Liang; Wang, Yan-Fen; Shi, Pei-Li; Chen, Shi-Ping; Xin, Xiao-Ping; Zhao, Feng-Hua; Wang, Yu-Ying; Tong, Cheng-Li

2013-03-01

Understanding the dynamics and underlying mechanism of carbon exchange between terrestrial ecosystems and the atmosphere is one of the key issues in global change research. In this study, we quantified the carbon fluxes in different terrestrial ecosystems in China, and analyzed their spatial variation and environmental drivers based on the long-term observation data of ChinaFLUX sites and the published data from other flux sites in China. The results indicate that gross ecosystem productivity (GEP), ecosystem respiration (ER), and net ecosystem productivity (NEP) of terrestrial ecosystems in China showed a significantly latitudinal pattern, declining linearly with the increase of latitude. However, GEP, ER, and NEP did not present a clear longitudinal pattern. The carbon sink functional areas of terrestrial ecosystems in China were mainly located in the subtropical and temperate forests, coastal wetlands in eastern China, the temperate meadow steppe in the northeast China, and the alpine meadow in eastern edge of Qinghai-Tibetan Plateau. The forest ecosystems had stronger carbon sink than grassland ecosystems. The spatial patterns of GEP and ER in China were mainly determined by mean annual precipitation (MAP) and mean annual temperature (MAT), whereas the spatial variation in NEP was largely explained by MAT. The combined effects of MAT and MAP explained 79%, 62%, and 66% of the spatial variations in GEP, ER, and NEP, respectively. The GEP, ER, and NEP in different ecosystems in China exhibited 'positive coupling correlation' in their spatial patterns. Both ER and NEP were significantly correlated with GEP, with 68% of the per-unit GEP contributed to ER and 29% to NEP. MAT and MAP affected the spatial patterns of ER and NEP mainly by their direct effects on the spatial pattern of GEP. © 2012 Blackwell Publishing Ltd.

How do disturbances and climate effects on carbon and water fluxes differ between multi-aged and even-aged coniferous forests?

PubMed

Tang, Xuguang; Li, Hengpeng; Ma, Mingguo; Yao, Li; Peichl, Matthias; Arain, Altaf; Xu, Xibao; Goulden, Michael

2017-12-01

Disturbances and climatic changes significantly affect forest ecosystem productivity, water use efficiency (WUE) and carbon (C) flux dynamics. A deep understanding of terrestrial feedbacks to such effects and recovery mechanisms in forests across contrasting climatic regimes is essential to predict future regional/global C and water budgets, which are also closely related to the potential forest management decisions. However, the resilience of multi-aged and even-aged forests to disturbances has been debated for >60years because of technical measurement constraints. Here we evaluated 62site-years of eddy covariance measurements of net ecosystem production (NEP), evapotranspiration (ET), the estimates of gross primary productivity (GPP), ecosystem respiration (R e ) and ecosystem-level WUE, as well as the relationships with environmental controls in three chronosequences of multi- and even-aged coniferous forests covering the Mediterranean, temperate and boreal regions. Age-specific dynamics in multi-year mean annual NEP and WUE revealed that forest age is a key variable that determines the sign and magnitude of recovering forest C source-sink strength from disturbances. However, the trends of annual NEP and WUE across succession stages between two stand structures differed substantially. The successional patterns of NEP exhibited an inverted-U trend with age at the two even-aged chronosequences, whereas NEP of the multi-aged chronosequence increased steadily through time. Meanwhile, site-level WUE of even-aged forests decreased gradually from young to mature, whereas an apparent increase occurred for the same forest age in multi-aged stands. Compared with even-aged forests, multi-aged forests sequestered more CO 2 with forest age and maintained a relatively higher WUE in the later succession periods. With regard to the available flux measurements in this study, these behaviors are independent of tree species, stand ages and climate conditions. We also found that distinctly different environmental factors controlled forest C and water fluxes under three climatic regimes. Typical weather events such as temperature anomalies or drying-wetting cycles severely affected forest functions. Particularly, a summer drought in the boreal forest resulted in an increased NEP owing to a considerable decrease in R e , but at the cost of greater water loss from deeper groundwater resources. These findings will provide important implications for forest management strategies to mitigate global climate change. Copyright © 2017 Elsevier B.V. All rights reserved.

Small-angle X-Ray analysis of macromolecular structure: the structure of protein NS2 (NEP) in solution

NASA Astrophysics Data System (ADS)

Shtykova, E. V.; Bogacheva, E. N.; Dadinova, L. A.; Jeffries, C. M.; Fedorova, N. V.; Golovko, A. O.; Baratova, L. A.; Batishchev, O. V.

2017-11-01

A complex structural analysis of nuclear export protein NS2 (NEP) of influenza virus A has been performed using bioinformatics predictive methods and small-angle X-ray scattering data. The behavior of NEP molecules in a solution (their aggregation, oligomerization, and dissociation, depending on the buffer composition) has been investigated. It was shown that stable associates are formed even in a conventional aqueous salt solution at physiological pH value. For the first time we have managed to get NEP dimers in solution, to analyze their structure, and to compare the models obtained using the method of the molecular tectonics with the spatial protein structure predicted by us using the bioinformatics methods. The results of the study provide a new insight into the structural features of nuclear export protein NS2 (NEP) of the influenza virus A, which is very important for viral infection development.

Quantifying and reducing the differences in forest CO 2-fluxes estimated by eddy covariance, biometric and chamber methods: A global synthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xingchang; Wang, Chuankuan; Bond-Lamberty, Benjamin

Carbon dioxide (CO 2) fluxes between terrestrial ecosystems and the atmosphere are primarily measured with eddy covariance (EC), biometric, and chamber methods. However, it is unclear why the estimates of CO 2-fluxes, when measured using these different methods, converge at some sites but diverge at others. We synthesized a novel global dataset of forest CO 2-fluxes to evaluate the consistency between EC and biometric or chamber methods for quantifying CO 2 budget in forests. The EC approach, comparing with the other two methods, tended to produce 25% higher estimate of net ecosystem production (NEP, 0.52Mg C ha-1 yr-1), mainly resultingmore » from lower EC-estimated Re; 10% lower ecosystem respiration (Re, 1.39Mg C ha-1 yr-1); and 3% lower gross primary production (0.48 Mg C ha-1 yr-1) The discrepancies between EC and the other methods were higher at sites with complex topography and dense canopies versus those with flat topography and open canopies. Forest age also influenced the discrepancy through the change of leaf area index. The open-path EC system induced >50% of the discrepancy in NEP, presumably due to its surface heating effect. These results provided strong evidence that EC produces biased estimates of NEP and Re in forest ecosystems. A global extrapolation suggested that the discrepancies in CO 2 fluxes between methods were consistent with a global underestimation of Re, and overestimation of NEP, by the EC method. Accounting for these discrepancies would substantially improve the our estimates of the terrestrial carbon budget .« less

A Data Acquisition System Using Single-Chip Microcomputer

NASA Astrophysics Data System (ADS)

Yonyjiang, Dai; Jingkuan, Gao; Lin, Wan; Mingjia, Pi; Jingda, Nan

1989-12-01

A data acquisition system by single-chip microcomputer was designed. It is suitable to the future devlopment of the miniature tidar signal processing epuipment . The characteristics of frequecy response, SNR, D* and NEP of FM-CW CO2 coherent tidar were discussed.

Viral infection potentiates the increase in airway blood flow produced by substance P.

PubMed

Yamawaki, I; Geppetti, P; Bertrand, C; Chan, B; Massion, P; Piedimonte, G; Nadel, J A

1995-08-01

We examined the effect of respiratory tract infection with Sendai virus on the responsiveness of airway blood flow to substance P (SP) in rats. Pathogen-free rats were inoculated with either Sendai virus suspension or sterile viral growth medium into each nostril. Five days later, we measured airway and esophageal blood flows before and immediately after injection of SP or histamine into the left ventricle of rats in both groups using a modification of the reference-sample microsphere technique. Viral infection potentiated the increase in airway blood flow evoked by SP but not by histamine. We also examined the effect of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) on the SP-induced increase in airway blood flow. Both phosphoramidon (NEP inhibitor) and captopril (ACE inhibitor) potentiated the increase in airway blood flow produced by SP in pathogen-free rats. In the presence of both peptidase inhibitors, a submaximal dose of SP increased blood flow to a similar level in infected and pathogen-free rats. Thus decreased activity of both ACE and NEP may be involved in the exaggerated increase in airway blood flow evoked by SP in virus-infected rats.

Nuclear Electric Propulsion for Deep Space Exploration

NASA Astrophysics Data System (ADS)

Schmidt, G.

Nuclear electric propulsion (NEP) holds considerable promise for deep space exploration in the future. Research and development of this technology is a key element of NASA's Nuclear Systems Initiative (NSI), which is a top priority in the President's FY03 NASA budget. The goal is to develop the subsystem technologies that will enable application of NEP for missions to the outer planets and beyond by the beginning of next decade. The high-performance offered by nuclear-powered electric thrusters will benefit future missions by (1) reducing or eliminating the launch window constraints associated with complex planetary swingbys, (2) providing the capability to perform large spacecraft velocity changes in deep space, (3) increasing the fraction of vehicle mass allocated to payload and other spacecraft systems, and, (3) in some cases, reducing trip times over other propulsion alternatives. Furthermore, the nuclear energy source will provide a power-rich environment that can support more sophisticated science experiments and higher- speed broadband data transmission than current deep space missions. This paper addresses NASA's plans for NEP, and discusses the subsystem technologies (i.e., nuclear reactors, power conversion and electric thrusters) and system concepts being considered for the first generation of NEP vehicles.

Phenological and physiological mechanisms underlying interannual variability of terrestrial net ecosystem production

NASA Astrophysics Data System (ADS)

Niu, S.; Luo, Y.; Hui, D.; Chen, J.

2013-12-01

The interannual variability (IAV) of atmospheric CO2 concentration varies substantial and is largely ascribed to IAV of terrestrial ecosystem carbon fluxes. However, we have limited understanding on the mechanisms that control the IAV on the carbon flux of terrestrial ecosystems. Here, we hypothesized that physiological and phonological processes regulate IAV significantly in terrestrial carbon uptake (i.e., net ecosystem production, NEP). To test this hypothesis, we analyzed eddy-covariance data from 24 sites with more than 8 years data in deciduous broadleaf forests (DBF), evergreen forests (EF), and grasslands (GRA) in the northern hemisphere. Ecosystem physiology is represented by the maximum carbon uptake capacity (NEPmax) in one year whereas phonology is represented by carbon uptake period (CUP). We found that yearly anomalies of CUP and NEPmax accounted for 40% and 60% separately, and 73% in combination, of the anomalies in annual NEP across all the 253 site-years, with their relative contributions varying among the sites. The IAV of CUP was determined by the anomalies of spring and autumn carbon uptake phenology, both of which were sensitive to climate changes but controlled by different environmental factors in different biomes. IAV of NEPmax was determined by summer precipitation anomalies in DBF and GRA. The results suggest that IAV of NEP is consistently co-determined by CUP and NEPmax anomalies among sites in the northern hemisphere. Overall, the mechanisms revealed by our study on NEP anomalies through changing in phenology and physiology contribute to predictive understanding of temporal dynamics of terrestrial carbon uptake.

Expression of an oxalate decarboxylase impairs the necrotic effect induced by Nep1-like protein (NLP) of Moniliophthora perniciosa in transgenic tobacco.

PubMed

da Silva, Leonardo F; Dias, Cristiano V; Cidade, Luciana C; Mendes, Juliano S; Pirovani, Carlos P; Alvim, Fátima C; Pereira, Gonçalo A G; Aragão, Francisco J L; Cascardo, Júlio C M; Costa, Marcio G C

2011-07-01

Oxalic acid (OA) and Nep1-like proteins (NLP) are recognized as elicitors of programmed cell death (PCD) in plants, which is crucial for the pathogenic success of necrotrophic plant pathogens and involves reactive oxygen species (ROS). To determine the importance of oxalate as a source of ROS for OA- and NLP-induced cell death, a full-length cDNA coding for an oxalate decarboxylase (FvOXDC) from the basidiomycete Flammulina velutipes, which converts OA into CO(2) and formate, was overexpressed in tobacco plants. The transgenic plants contained less OA and more formic acid compared with the control plants and showed enhanced resistance to cell death induced by exogenous OA and MpNEP2, an NLP of the hemibiotrophic fungus Moniliophthora perniciosa. This resistance was correlated with the inhibition of ROS formation in the transgenic plants inoculated with OA, MpNEP2, or a combination of both PCD elicitors. Taken together, these results have established a pivotal function for oxalate as a source of ROS required for the PCD-inducing activity of OA and NLP. The results also indicate that FvOXDC represents a potentially novel source of resistance against OA- and NLP-producing pathogens such as M. perniciosa, the causal agent of witches' broom disease of cacao (Theobroma cacao L.).

Active Site Mutations Change the Cleavage Specificity of Neprilysin

PubMed Central

Sexton, Travis; Hitchcook, Lisa J.; Rodgers, David W.; Bradley, Luke H.; Hersh, Louis B.

2012-01-01

Neprilysin (NEP), a member of the M13 subgroup of the zinc-dependent endopeptidase family is a membrane bound peptidase capable of cleaving a variety of physiological peptides. We have generated a series of neprilysin variants containing mutations at either one of two active site residues, Phe563 and Ser546. Among the mutants studied in detail we observed changes in their activity towards leucine5-enkephalin, insulin B chain, and amyloid β1–40. For example, NEPF563I displayed an increase in preference towards cleaving leucine5-enkephalin relative to insulin B chain, while mutant NEPS546E was less discriminating than neprilysin. Mutants NEPF563L and NEPS546E exhibit different cleavage site preferences than neprilysin with insulin B chain and amyloid ß1–40 as substrates. These data indicate that it is possible to alter the cleavage site specificity of neprilysin opening the way for the development of substrate specific or substrate exclusive forms of the enzyme with enhanced therapeutic potential. PMID:22384224

Cognitive impairment in patients with Fibromyalgia syndrome as assessed by the Mini-Mental State Examination

PubMed Central

2009-01-01

Background This study evaluated the frequency of cognitive impairment in patients with Fibromyalgia syndrome (FMS) using the Mini Mental State Examination (MMSE). Methods We analyzed baseline data from all 46 patients with FMS and 92 age- and sex-matched controls per diagnosis of neuropathic (NeP) or mixed pain (MP) selected from a larger prospective study. Results FMS had a slight but statistically significant lower score in the adjusted MMSE score (26.9; 95% CI 26.7-27.1) than either NeP (27.3; 95% CI 27.2-27.4) or MP (27.3; 27.2-27.5). The percentage of patients with congnitive impairment (adjusted MMSE ≤ 26) was numerically higher in FMS (15%; 95% CI 6.3-29) compared with NeP (5%; 95% CI 1.8-12.2) or MP (5%; 95% CI 1.8-12.2) and higher than in the same age stratum of the general population (0.05%). Conclusions Compared with the population reference value, patients with FMS showed high frequency of cognitive impairment. PMID:20025750

A Novel CMOS Multi-band THz Detector with Embedded Ring Antenna

NASA Astrophysics Data System (ADS)

Xu, Lei-jun; Guan, Jia-ning; Bai, Xue; Li, Qin; Mao, Han-ping

2017-10-01

To overcome the large chip area occupation for the traditional terahertz multi-frequency detector by using the antenna elements in a different frequency, a novel structure for a multi-frequency detector is proposed and studied. Based on the ring antenna detector, an embedded multi-ring antenna with multi-port is proposed for the multi-frequency detector. A single-ring and dual-ring detectors are analyzed and designed in 0.18 μ m CMOS. For the single-ring detector, the best responsivity and NEP is 701 V/W and 261 pW/Hz0.5 at the frequency of 290 GHz. For the dual-ring detector, the best responsivity is 367 V/W and 297 V/W, NEP is 578 pW/Hz0.5 and 713pW/Hz0.5, at the frequency of 600 GHz and 806 GHz, respectively. This embedded multi-ring detector has a simple structure which can be expanded easily in a compact size.

A potassium Rankine multimegawatt nuclear electric propulsion concept

NASA Technical Reports Server (NTRS)

Baumeister, E.; Rovang, R.; Mills, J.; Sercel, J.; Frisbee, R.

1990-01-01

Multimegawatt nuclear electric propulsion (NEP) has been identified as a potentially attractive option for future space exploratory missions. A liquid-metal-cooled reactor, potassium Rankine power system that is being developed is suited to fulfill this application. The key features of the nuclear power system are described, and system characteristics are provided for various potential NEP power ranges and operational lifetimes. The results of recent mission studies are presented to illustrate some of the potential benefits to future space exploration to be gained from high-power NEP. Specifically, mission analyses have been performed to assess the mass and trip time performance of advanced NEP for both cargo and piloted missions to Mars.

Twin-Slot Antenna-Coupled Superconducting Ti Transition-Edge Sensor at 350 GHz

NASA Astrophysics Data System (ADS)

Zhang, W.; Miao, W.; Wang, Z.; Guo, X. H.; Liu, D.; Zhong, J. Q.; Yao, Q. J.; Shi, S. C.

2018-05-01

We have developed four-leg-supported superconducting Ti transition-edge sensors (TES) formed by KOH wet etching. Energy relaxation mechanism is changed from electron-phonon coupling to diffusive phonon after wet etching. The current-voltage curves of the same TES device were measured before and after wet etching. After wet etching, its thermal conductance (G) is reduced to 500 pW/K from 8950 pW/K. The measured effective response time (τ eff) is 143 μs, about 30 times larger. In addition, we have studied the optical noise equivalent power (NEP) with a cryogenic blackbody in combination with metal-mesh filters to define the radiation bandwidth. The obtained optical NEP is 5 × 10-16 W/√Hz, which is suitable for ground-based astronomical applications.

Dynamic Computer Model of a Stirling Space Nuclear Power System

DTIC Science & Technology

2006-05-04

diagram of electric propulsion…………………………………. 17 Figure 2-1. General NEP structure……………………………………………………….20 Figure 2-2. Fission of uranium -235...Figure 2-1. General NEP structure. [20] 21 Figure 2-2. Fission of uranium -235. In a fast reactor, the average number of neutrons...that is modeled for this project is a 600 kW(t) fast fission reactor consisting of uranium nitride fuel and sodium potassium coolant. Its dynamic

Blazing the trailway: Nuclear electric propulsion and its technology program plans

NASA Technical Reports Server (NTRS)

Doherty, Michael P.

1992-01-01

An overview is given of the plans for a program in nuclear electric propulsion (NEP) technology for space applications being considered by NASA, DOE, and DOD. Possible missions using NEP are examined, and NEP technology plans are addressed regarding concept development, systems engineering, nuclear fuels, power conversion, thermal management, power management and distribution, electric thrusters, facilities, and issues related to safety and environment. The programmatic characteristics are considered.

Hydrologic support of carbon dioxide flux revealed by whole-lake carbon budgets

USGS Publications Warehouse

Stets, E.G.; Striegl, Robert G.; Aiken, G.R.; Rosenberry, D.O.; Winter, T.C.

2009-01-01

Freshwater lakes are an important component of the global carbon cycle through both organic carbon (OC) sequestration and carbon dioxide (CO 2) emission. Most lakes have a net annual loss of CO2 to the atmosphere and substantial current evidence suggests that biologic mineralization of allochthonous OC maintains this flux. Because net CO 2 flux to the atmosphere implies net mineralization of OC within the lake ecosystem, it is also commonly assumed that net annual CO2 emission indicates negative net ecosystem production (NEP). We explored the relationship between atmospheric CO2 emission and NEP in two lakes known to have contrasting hydrologie characteristics and net CO2 emission. We calculated NEP for calendar year 2004 using whole-lake OC and inorganic carbon (IC) budgets, NEPoc and NEPIC, respectively, and compared the resulting values to measured annual CO 2 flux from the lakes. In both lakes, NEPIc and NEP Ic were positive, indicating net autotrophy. Therefore CO2 emission from these lakes was apparently not supported by mineralization of allochthonous organic material. In both lakes, hydrologie CO2 inputs, as well as CO2 evolved from netcalcite precipitation, could account for the net CO2 emission. NEP calculated from diel CO2 measurements was also affected by hydrologie inputs of CO2. These results indicate that CO2 emission and positive NEP may coincide in lakes, especially in carbonate terrain, and that all potential geologic, biogeochemical, and hydrologie sources of CO2 need to be accounted for when using CO2 concentrations to infer lake NEP. Copyright 2009 by the American Geophysical Union.

Nuclear electric propulsion: A better, safer, cheaper transportation system for human exploration of Mars

NASA Technical Reports Server (NTRS)

Clark, John S.; George, Jeffrey A.; Gefert, Leon P.; Doherty, Michael P.; Sefcik, Robert J.

1994-01-01

NASA has completed a preliminary mission and systems study of nuclear electric propulsion (NEP) systems for 'split-sprint' human exploration and related robotic cargo missions to Mars. This paper describes the study, the mission architecture selected, the NEP system and technology development needs, proposed development schedules, and estimated development costs. Since current administration policy makers have delayed funding for key technology development activities that could make Mars exploration missions a reality in the near future, NASA will have time to evaluate various alternate mission options, and it appears prudent to ensure that Mars mission plans focus on astronaut and mission safety, while reducing costs to acceptable levels. The split-sprint nuclear electric propulsion system offers trip times comparable to nuclear thermal propulsion (NTP) systems, while providing mission abort opportunities that are not possible with 'reference' mission architectures. Thus, NEP systems offer short transit times for the astronauts, reducing the exposure of the crew to intergalactic cosmic radiation. The high specific impulse of the NEP system, which leads to very low propellant requirements, results in significantly lower 'initial mass in low earth orbit' (IMLEO). Launch vehicle packaging studies show that the NEP system can be launched, assembled, and deployed, with about one less 240-metric-ton heavy lift launch vehicle (HLLV) per mission opportunity - a very Technology development cost of the nuclear reactor for an NEP system would be shared with the proposed nuclear surface power systems, since nuclear systems will be required to provide substantial electrical power on the surface of Mars. The NEP development project plan proposed includes evolutionary technology development for nuclear electric propulsion systems that expands upon SP-100 (Space Power - 100 kw(e)) technology that has been developed for lunar and Mars surface nuclear power, and small NEP systems for interplanetary probes. System upgrades are expected to evolve that will result in even shorter trip times, improved payload capabilities, and enhanced safety and reliability.

Lightweight Damage Tolerant, High-Temperature Radiators for Nuclear Power and Propulsion

NASA Technical Reports Server (NTRS)

Craven, Paul D.; SanSoucie, Michael P.

2015-01-01

NASA is increasingly emphasizing exploration to bodies beyond near-Earth orbit. New propulsion systems and new spacecraft are being built for these missions. As the target bodies get further out from Earth, high energy density systems, e.g., nuclear fusion, for propulsion and power will be advantageous. The mass and size of these systems, including supporting systems such as the heat exchange system, including thermal radiators, will need to be as small as possible. Conventional heat exchange systems are a significant portion of the total thermal management mass and size. Nuclear electric propulsion (NEP) is a promising option for high-speed, in-space travel due to the high energy density of nuclear fission power sources and efficient electric thrusters. Heat from the reactor is converted to power for use in propulsion or for system power. The heat not used in the power conversion is then radiated to space as shown in figure 1. Advanced power conversion technologies will require high operating temperatures and would benefit from lightweight radiator materials. Radiator performance dictates power output for nuclear electric propulsion systems. Pitch-based carbon fiber materials have the potential to offer significant improvements in operating temperature, thermal conductivity, and mass. These properties combine to allow significant decreases in the total mass of the radiators and significant increases in the operating temperature of the fins. A Center-funded project at NASA Marshall Space Flight Center has shown that high thermal conductivity, woven carbon fiber fins with no matrix material, can be used to dissipate waste heat from NEP systems and because of high specific power (kW/kg), will require less mass and possibly less total area than standard metal and composite radiator fins for radiating the same amount of heat. This project uses an innovative approach to reduce the mass and size required for the thermal radiators to the point that in-space NEP and power is enabled. High thermal conductivity carbon fibers are lightweight, damage tolerant, and can be heated to high temperature. Areal densities in the NASA set target range of 2 to 4 kg/m2 (for enabling NEP) are achieved and with specific powers (kW/kg) a factor of about 7 greater than conventional metal fins and about 1.5 greater than carbon composite fins. Figure 2 shows one fin under test. All tests were done under vacuum conditions.

Hydrolysis of substance p and neurotensin by converting enzyme and neutral endopeptidase.

PubMed

Skidgel, R A; Engelbrecht, S; Johnson, A R; Erdös, E G

1984-01-01

Angiotensin I converting enzyme (ACE) and neutral endopeptidase ("enkephalinase"; NEP), were purified to homogeneity from human kidney. NEP cleaved substance P (SP) at Gln6-Phe7,-Phe8, and Gly9-Leu10 and neurotensin (NT) at Pro10-Tyr11 and Tyr11-Ile12. NEP hydrolyzed 0.1 mM SP, NT and their C-terminal fragments at the following rates (mumol/min/mg): SP1-11 = 7.8, SP4-11 = 11.7, SP5-11 = 15.4, SP6-11 = 15.6, SP8-11 = 6.7, NT1-13 = 2.9, and NT8-13 = 4.0. Purified ACE rapidly inactivated SP as measured in bioassay. HPLC analysis showed that ACE cleaved SP at Phe8-Gly9 and Gly9-Leu10 to release C-terminal tri- and dipeptide (ratio = 4:1). The hydrolysis was Cl- dependent and inhibited by captopril. ACE released mainly C-terminal tripeptide from SP methyl ester, but only dipeptide from SP free acid. Modification of arginine residues in ACE with cyclohexanedione or butanedione similarly inhibited hydrolysis of SP, bradykinin and Bz-Gly-Phe-Arg (80-93%) indicating an active site arginine is required for hydrolysis of SP. ACE hydrolyzed NT at Tyr11-Ile12 to release Ile12-Leu13. SP, NT and their derivatives (0.1 mM) were cleaved by ACE at the following rates (mumol/min/mg): SP1-11 = 1.2, SP methyl ester = 0.7, SP free acid = 8.5, SP4-11 = 2.4, SP5-11 = 0.9, SP6-11 = 1.4, SP8-11 = 0, NT1-13 = 0.2, and NT8-13 = 1.3. Peptide substrates were used as inhibitors of ACE (substrate = FA-Phe-Gly-Gly) and NEP (substrate = Leu5-enkephalin).(ABSTRACT TRUNCATED AT 250 WORDS)

A role for tachykinins in female mouse and rat reproductive function.

PubMed

Pintado, C Oscar; Pinto, Francisco M; Pennefather, Jocelyn N; Hidalgo, Agustin; Baamonde, Ana; Sanchez, Teresa; Candenas, M Luz

2003-09-01

Tachykinins may be involved in reproduction. A reverse transcription-polymerase chain reaction assay was used to analyze the expression of tachykinins and tachykinin receptors in different types of reproductive cells from mice. The preprotachykinin (PPT) genes, PPT-A, PPT-B and PPT-C, that encode substance P/neurokinin A, neurokinin B, and hemokinin-1, respectively, and the genes that encode the tachykinin NK1, NK2, and NK3 receptors were all expressed, at different levels, in the uterus of superovulated, unfertilized mice. The mRNA of neprilysin (NEP), the main enzyme involved in tachykinin metabolism, was also expressed in the uterus. Isolated cumulus granulosa cells expressed PPT-A, PPT-B, PPT-C, and NEP and low levels of the tachykinin NK1 and NK2 receptors. Mouse oocytes expressed PPT-A and -B mRNA transcripts. A low expression of the three tachykinin receptors was observed but PPT-C and NEP were undetectable. Two- and 8- to 16-cell mouse embryos expressed only a low-abundance transcript corresponding to the NK1 receptor. However, the mRNAs of PPT-B, PPT-C and NEP appeared in blastocyst-stage embryos. A low-abundance transcript corresponding to the NK2 receptor was the only target gene detected in mice sperm. Female mice or rats treated neonatally with capsaicin showed a reduced fertility. A reduction in litter size was observed in female rats treated in vivo with the tachykinin NK3 receptor antagonist SR 142801. These data show that tachykinins of both neuronal and nonneuronal origin are differentially expressed in various types of reproductive cells and may play a role in female reproductive function.

Nedocromil sodium reduces cigarette smoke-induced bronchoconstrictor hyperresponsiveness to substance P in the guinea-pig.

PubMed

Dusser, D J; Lacroix, H; Desmazes-Dufeu, N; Mordelet-Dambrine, M; Roisman, G L

1995-01-01

Acute exposure to cigarette smoke provokes airway hyperresponsiveness to substance P and inactivates neutral endopeptidase (NEP). To determine whether nedocromil sodium can prevent cigarette smoke-induced hyperresponsiveness to substance P, we studied two groups of anaesthetized guinea-pigs. One group of guinea-pigs was pretreated with aerosolized 0.9% NaCl solution (90 breaths), the other group was pretreated with aerosolized nedocromil sodium (10(-4) M, 90 breaths). In each animal, pretreatment was followed by either exposure to the smoke of one cigarette or exposure to air. After acute exposure to cigarette smoke or to air, we measured the change in total pulmonary resistance (RL) induced by increasing concentrations of aerosolized substance P. In the absence of nedocromil sodium, the bronchoconstrictor responses to substance P were greater in cigarette smoke-exposed guinea-pigs than in air-exposed animals. Aerosolized nedocromil sodium had no effect on the response to substance P in air-exposed animals, but it reduced cigarette smoke-induced hyperresponsiveness to substance P. The preventive effect on cigarette smoke-induced hyperresponsiveness to substance P was observed at concentrations of aerosolized nedocromil sodium of 3 x 10(-5), 10(-4), and 3 x 10(-4) M. In vitro, cigarette smoke solution inhibited NEP activity from lung membrane preparations, but this inhibitory effect was not modified by nedocromil sodium (10(-4) M). We conclude that aerosolized nedocromil sodium reduces cigarette smoke-induced airway hyperresponsiveness to substance P in vivo. This action of nedocromil sodium is not due to a protective effect on cigarette smoke-induced inactivation of NEP in vitro.

Observational study on efficacy of negative expiratory pressure test proposed as screening for obstructive sleep apnea syndrome among commercial interstate bus drivers - protocol study

PubMed Central

2011-01-01

Abstract Background Obstructive sleep apnea (OSA) is a respiratory disease characterized by the collapse of the extrathoracic airway and has important social implications related to accidents and cardiovascular risk. The main objective of the present study was to investigate whether the drop in expiratory flow and the volume expired in 0.2 s during the application of negative expiratory pressure (NEP) are associated with the presence and severity of OSA in a population of professional interstate bus drivers who travel medium and long distances. Methods/Design An observational, analytic study will be carried out involving adult male subjects of an interstate bus company. Those who agree to participate will undergo a detailed patient history, physical examination involving determination of blood pressure, anthropometric data, circumference measurements (hips, waist and neck), tonsils and Mallampati index. Moreover, specific questionnaires addressing sleep apnea and excessive daytime sleepiness will be administered. Data acquisition will be completely anonymous. Following the medical examination, the participants will perform a spirometry, NEP test and standard overnight polysomnography. The NEP test is performed through the administration of negative pressure at the mouth during expiration. This is a practical test performed while awake and requires little cooperation from the subject. In the absence of expiratory flow limitation, the increase in the pressure gradient between the alveoli and open upper airway caused by NEP results in an increase in expiratory flow. Discussion Despite the abundance of scientific evidence, OSA is still underdiagnosed in the general population. In addition, diagnostic procedures are expensive, and predictive criteria are still unsatisfactory. Because increased upper airway collapsibility is one of the main determinants of OSA, the response to the application of NEP could be a predictor of this disorder. With the enrollment of this study protocol, the expectation is to encounter predictive NEP values for different degrees of OSA in order to contribute toward an early diagnosis of this condition and reduce its impact and complications among commercial interstate bus drivers. Trial registration Registro Brasileiro de Ensaios Clinicos (local acronym RBEC) [Internet]: Rio de Janeiro (RJ): Instituto de Informaçao Cientifica e Tecnologica em Saude (Brazil); 2010 - Identifier RBR-7dq5xx. Cross-sectional study on efficacy of negative expiratory pressure test proposed as screening for obstructive sleep apnea syndrome among commercial interstate bus drivers; 2011 May 31 [7 pages]. Available from http://www.ensaiosclinicos.gov.br/rg/RBR-7dq5xx/. PMID:22151802

Inhibition of neutral endopeptidase potentiates neutrophil activation during Mg-deficiency in the rat

PubMed Central

Mak, I. T.; Kramer, J. H.; Chmielinska, J. J.; Khalid, M. H.; Landgraf, K. M.; Weglicki, W. B.

2013-01-01

Neutral endopeptidase (NEP), which degrades substance P (SP), may regulate neutrophil activation during Mg-deficiency (MgD). Male Sprague-Dawley rats (180g) were fed MgD (~50 mg Mg/kg) or Mg-sufficient (MgS, 608 mg Mg/kg) diets for 7 days ± NEP inhibitor phosphoramidon (PR, 5 mg/kg/day, s. c.). MgD alone induced a 9-fold (vs. MgS, p <0.01) elevation in plasma SP; MgD+PR enhanced it further to 18-fold (p <0.001). Neutrophils from MgD+PR rats displayed a 3.9-fold higher (p <0.01) basal ·O2- generation, but those from MgD or PR alone were not activated. Plasma PGE2-metabolite levels rose 2.67- (p <0.01) and 1.56- (p <0.05) fold, respectively, in MgD+PR and MgD groups; the corresponding red blood cell glutathione levels were decreased 21 % (p <0.025) and 7 % (NS). MgD+PR significantly reduced neutrophil NEP activity by 48 % (p <0.02); PR or MgD alone only reduced this activity 26 % and 15 %, respectively. We conclude that NEP inhibition potentiates SP-mediated neutrophil ·O2- production and may promote other inflammatory activities during MgD. PMID:18607539

Inhibition of neutral endopeptidase potentiates neutrophil activation during Mg-deficiency in the rat.

PubMed

Mak, I T; Kramer, J H; Chmielinska, J J; Khalid, M H; Landgraf, K M; Weglicki, W B

2008-07-01

Neutral endopeptidase (NEP), which degrades substance P (SP), may regulate neutrophil activation during Mg-deficiency (MgD). Male Sprague-Dawley rats (180g) were fed MgD (approximately 50 mg Mg/kg) or Mg-sufficient (MgS, 608 mg Mg/kg) diets for 7 days +/- NEP inhibitor phosphoramidon (PR, 5 mg/kg/day, s.c.). MgD alone induced a 9-fold (vs. MgS, p <0.01) elevation in plasma SP; MgD+PR enhanced it further to 18-fold (p <0.001). Neutrophils from MgD+PR rats displayed a 3.9-fold higher (p <0.01) basal .O(2-) generation, but those from MgD or PR alone were not activated. Plasma PGE2-metabolite levels rose 2.67- (p <0.01) and 1.56- (p <0.05) fold, respectively, in MgD+PR and MgD groups; the corresponding red blood cell glutathione levels were decreased 21% (p <0.025) and 7% (NS). MgD+PR significantly reduced neutrophil NEP activity by 48% (p <0.02); PR or MgD alone only reduced this activity 26% and 15%, respectively. We conclude that NEP inhibition potentiates SP-mediated neutrophil .O(2-) production and may promote other inflammatory activities during MgD.

Net ecosystem productivity of temperate and boreal forests after clearcutting - a Fluxnet-Canada measurement and modelling synthesis

NASA Astrophysics Data System (ADS)

Grant, R. F.; Barr, A.; Black, T. A.; Margolis, H. A.; McCaughey, J. H.; Trofymow, J. A.

2010-05-01

Clearcutting strongly affects subsequent forest net ecosystem productivity (NEP). Hypotheses for ecological controls on NEP in the ecosystem model ecosys were tested with CO2 fluxes measured by eddy covariance (EC) in three post-clearcut conifer chronosequences. An algorithm for microbial colonization of fine and woody debris allowed the model to reproduce sigmoidal declines in debris observed after clearcutting. In the model, Rh drove debris decomposition that drove microbial growth, N mineralization and asymbiotic N2 fixation. These processes controlled root N uptake, and thereby CO2 fixation in regrowing vegetation. Interactions among soil and plant processes allowed the model to simulate hourly CO2 fluxes and annual NEP within the uncertainty of EC measurements from 2003 through 2007 over forest stands from 1 to 80 years of age in all three chronosequences without site- or species-specific parameterization. The model was then used to study the impacts of increasing harvest removals on subsequent C stocks at one of the chronosequence sites. Model results indicated that increasing harvest removals would hasten recovery of NEP during the first 30 years after clearcutting, but would reduce ecosystem C stocks by about 15% of the increased removals at the end of an 80 year harvest cycle.

Effect of passive sensitization on the mechanical activity of human isolated bronchial smooth muscle induced by substance P, neurokinin A and VIP.

PubMed

Ben-Jebria, A; Marthan, R; Rossetti, M; Savineau, J P

1993-05-01

1. The effect of passive sensitization on the mechanical activity of human isolated bronchial smooth muscle induced by the following neuropeptides substance P (SP), neurokinin A (NKA) and vasoactive intestinal peptide (VIP) was studied both in the absence and in the presence of the neutral endopeptidase (NEP) inhibitor, phosphoramidon. 2. Cumulative concentration-response curves (CCRC) to these neuropeptides were constructed in human passively sensitized isolated bronchial rings and compared to those in paired controls. Passively sensitized human isolated bronchial rings were tissues incubated overnight in serum from asthmatic patients atopic to Dermatophagoides pteronyssinus and paired controls were tissues originating from the same lung specimens but incubated overnight in serum from healthy donors. 3. In the absence of phosphoramidon, passive sensitization significantly increased the amplitude of the contractile responses to SP and NKA including that to the maximal concentration given from 50 +/- 5% to 76 +/- 6% (n = 5, P < 0.05) and from 70 +/- 7% to 101 +/- 6% (n = 5, P < 0.05) of the maximal response to acetylcholine, respectively. Passive sensitization significantly shifted to the left the CCRC for both tachykinins as measured by the geometric means dose-ratios which were 8.5 (95% confidence limits (CL): 3.1-13.9) and 7.3 (95% CL: 4.2-10.3) for SP and NKA, respectively. 4. In the presence of phosphoramidon (10 microM), passive sensitization still increased significantly the amplitude of the contractile responses to SP and NKA including that to the maximal concentration given from 74 +/- 4% to 115 +/- 7% (n = 5, P<0.05) and from 104 +/- 9% to 146 +/- 16% (n = 5, P<0.05)of the maximal response to acetylcholine, respectively. Passive sensitization still significantly shifted to the left the CCRC for both tachykinins as measured by the dose-ratios which were 9.0 (95% CL:4.3-13.6) and 5.4 (95% CL: 2.9-7.9) for SP and NKA, respectively.5. The relaxant response to the maximal concentration of VIP given in tissues precontracted with histamine (0.5 mM) was significantly reduced by passive sensitization from 41 +/- 4% to 25 +/- 3% (n = 5,P <0.05) of the amplitude of the precontraction in the absence of phosphoramidon and from 72 +/- 1%to 49 +/- 4% (n = 5, P<0.05) in the presence of phosphoramidon (10 microM). Passive sensitization significantly shifted to the right the CCRC for VIP as measured by the dose-ratios which were 10.4(95% CL: 6.6-14.1) and 6.4 (95% CL: 3.0-9.8) in the absence and in the presence of phosphoramidon,respectively.6. We conclude that passive sensitization enhances the mechanical response to neuropeptides which contract human isolated bronchial smooth muscle and reduces that to a neuropeptide which relaxes it.The mechanism of passive sensitization-induced changes in the mechanical activity appears to be independent of a decrease in NEP activity since these changes persist in the presence of the NEP inhibitor, phosphoramidon.

Input-decomposition balance of heterotrophic processes in a warm-temperate mixed forest in Japan

NASA Astrophysics Data System (ADS)

Jomura, M.; Kominami, Y.; Ataka, M.; Makita, N.; Dannoura, M.; Miyama, T.; Tamai, K.; Goto, Y.; Sakurai, S.

2010-12-01

Carbon accumulation in forest ecosystem has been evaluated using three approaches. One is net ecosystem exchange (NEE) estimated by tower flux measurement. The second is net ecosystem production (NEP) estimated by biometric measurements. NEP can be expressed as the difference between net primary production and heterotrophic respiration. NEP can also be expressed as the annual increment in the plant biomass (ΔW) plus soil (ΔS) carbon pools defined as follows; NEP = ΔW+ΔS The third approach needs to evaluate annual carbon increment in soil compartment. Soil carbon accumulation rate could not be measured directly in a short term because of the small amount of annual accumulation. Soil carbon accumulation rate can be estimated by a model calculation. Rothamsted carbon model is a soil organic carbon turnover model and a useful tool to estimate the rate of soil carbon accumulation. However, the model has not sufficiently included variations in decomposition processes of organic matters in forest ecosystems. Organic matter in forest ecosystems have a different turnover rate that creates temporal variations in input-decomposition balance and also have a large variation in spatial distribution. Thus, in order to estimate the rate of soil carbon accumulation, temporal and spatial variation in input-decomposition balance of heterotrophic processes should be incorporated in the model. In this study, we estimated input-decomposition balance and the rate of soil carbon accumulation using the modified Roth-C model. We measured respiration rate of many types of organic matters, such as leaf litter, fine root litter, twigs and coarse woody debris using a chamber method. We can illustrate the relation of respiration rate to diameter of organic matters. Leaf and fine root litters have no diameter, so assumed to be zero in diameter. Organic matters in small size, such as leaf and fine root litter, have high decomposition respiration. It could be caused by the difference in structure of organic matter. Because coarse woody debris has shape of cylinder, microbes decompose from the surface of it. Thus, respiration rate of coarse woody debris is lower than that of leaf and fine root litter. Based on this result, we modified Roth-C model and estimate soil carbon accumulation rate in recent years. Based on the results from a soil survey, the forest soil stored 30tC ha-1 in O and A horizon. We can evaluate the modified model using this result. NEP can be expressed as the annual increment in the plant biomass plus soil carbon pools. So if we can estimate NEP using this approach, then we can evaluate NEP estimated by micrometeorological and ecological approaches and reduce uncertainty of NEP estimation.

Substance P as an immunomodulatory neuropeptide in a mouse model for autoimmune hair loss (alopecia areata).

PubMed

Siebenhaar, Frank; Sharov, Andrey A; Peters, Eva M J; Sharova, Tatyana Y; Syska, Wolfgang; Mardaryev, Andrei N; Freyschmidt-Paul, Pia; Sundberg, John P; Maurer, Marcus; Botchkarev, Vladimir A

2007-06-01

Alopecia areata (AA) is an autoimmune disorder of the hair follicle characterized by inflammatory cell infiltrates around actively growing (anagen) hair follicles. Substance P (SP) plays a critical role in the cutaneous neuroimmune network and influences immune cell functions through the neurokinin-1 receptor (NK-1R). To better understand the role of SP as an immunomodulatory neuropeptide in AA, we studied its expression and effects on immune cells in a C3H/HeJ mouse model for AA. During early stages of AA development, the number of SP-immunoreactive nerve fibers in skin is increased, compared to non-affected mice. However, during advanced stages of AA, the number of SP-immunoreactive nerves and SP protein levels in skin are decreased, whereas the expression of the SP-degrading enzyme neutral endopeptidase (NEP) is increased, compared to control skin. In AA, NK-1R is expressed on CD8+ lymphocytes and macrophages accumulating around affected hair follicles. Additional SP supply to the skin of AA-affected mice leads to a significant increase of mast cell degranulation and to accelerated hair follicle regression (catagen), accompanied by an increase of CD8+ cells-expressing granzyme B. These data suggest that SP, NEP, and NK-1R serve as important regulators in the molecular signaling network modulating inflammatory response in autoimmune hair loss.

Depression of belowground respiration is more pronounced than enhancement of photosynthesis during the first year after nitrogen fertilization of a mature Pacific Northwest Douglas-fir forest

NASA Astrophysics Data System (ADS)

Chen, B.; Black, T. A.; Jassal, R.; Nesic, Z.; Bruemmer, C.

2008-05-01

Nitrogen (N) additions to forest have shown variable effects on both respiration and photosynthesis. With increasing rates of anthropogenic N deposition, there is a strong need to understand the ecosystem response to N inputs. We investigated how N fertilization affects the ecosystem carbon (C) balance of a 57-year-old coast Douglas-fir stand in British Columbia, Canada, based on eddy-covariance (EC) and soil-chamber (fertilized and control plots) measurements and process-based modeling. The stand was fertilized by helicopter with urea at 200 kg N ha-1 in January 2007. A land surface model (Ecosystem Atmosphere Simulation Scheme, EASS) was combined with an ecosystem model (Boreal Ecosystem Productivity Simulator, BEPS) and a coupled C and N subroutine was incorporated into the integrated EASS-BEPS model in this study. This half-hourly time step model was run continuously for the period from 2001 to 2007 in two scenarios: with and without fertilization. Modeled C fluxes without fertilization [net ecosystem productivity (NEP), gross primary productivity (GPP), ecosystem respiration (Re) and belowground respiration (Rs)] agreed well with EC and soil chamber measurements over diurnal, seasonal and annual time scales for 2001 to 2006; while simulated NEP, GPP, Re and Rs with fertilization reasonably followed EC and chamber measurements in 2007 (545 vs. 520, 2163 vs. 2155, 1618 vs. 1635, and 920 vs. 906 g C m-2 yr-1, respectively). Comparison of EC-determined C fluxes in 2007 with model simulations without fertilization suggests that annual Re decreased by 6.7% (1635 vs. 1752 g C m-2), gross primary productivity (GPP) increased by 6.8% (2155 vs. 2017 g C m-2), and annual NEP increased by 96.2% (520 vs. 265 g C m-2) due to fertilization. The modeled reduction in Rs (9.6%, comparing modeled values without and with fertilization: 1008 vs. 920 g C m-2 yr-1) is consistent with that measured using the soil chambers (~11.5%, comparing CO2 effluxes from control and fertilized plots measured from late summer to fall). The model also indicated that the effect of fertilization on aboveground (leaf and stem) respiration was very small. These experimental and modeling results suggest N fertilization significantly increased NEP mainly as a result of strongly reduced Rs (~10-12%) and moderately enhanced GPP (~6.8%) in the first year after fertilization.

Study of a heat rejection system for the Nuclear Electric Propulsion (NEP) spacecraft

NASA Technical Reports Server (NTRS)

Ernest, D. M.

1982-01-01

Two different heat pipe radiator elements, one intended for use with the power conversion subsystem of the NASA funded nuclear electric propulsion (NEP) spacecraft, and one intended for use with the DOE funded space power advanced reactor (SPAR) system were tested and evaluated. The NEP stainless steel/sodium heat pipe was 4.42 meters long and had a 1 cm diameter. Thermal performance testing at 920 K showed a non-limited power level of 3560 watts, well in excess of the design power of 2600 watts. This test verified the applicability of screen arteries for use in long radiator heat pipes. The SPAR titanium/potassium heat pipe was 5.5 meters long and had a semicircular crossection with a 4 cm diameter. Thermal performance testing at 775 K showed a maximum power level of 1.86 kW, somewhat short of the desired 2.6 kW beginning of life design requirement. The reduced performance was shown to be the result of the inability of the evaporator wall wick (shot blasted evaporator wall) to handle the required liquid flow.

Structures and Evolutions of Explosive Cyclones over the Northwestern and Northeastern Pacific

NASA Astrophysics Data System (ADS)

Zhang, Shuqin; Fu, Gang

2018-06-01

In this study, the structures and evolutions of moderate (MO) explosive cyclones (ECs) over the Northwestern Pacific (NWP) and Northeastern Pacific (NEP) are investigated and compared using composite analysis with cyclone-relative coordinates. Final Operational Global Analysis data gathered during the cold seasons (October-April) of the 15 years from 2000 to 2015 are used. The results indicate that MO NWP ECs have strong baroclinicity and abundant latent heat release at low levels and strong upper-level forcing, which favors explosive cyclogenesis. The rapid development of MO NEP ECs results from their interaction with a northern cyclone and a large middle-level advection of cyclonic vorticity. The structural differences between MO NWP ECs and MO NEP ECs are significant. This results from their specific large-scale atmospheric and oceanic environments. MO NWP ECs usually develop rapidly in the east and southeast of the Japan Islands; the intrusion of cold dry air from the East Asian continent leads to strong baroclinicity, and the Kuroshio/Kuroshio Extension provides abundant latent heat release at low levels. The East Asian subtropical westerly jet stream supplies strong upper-level forcing. While MO NEP ECs mainly occur over the NEP, the low-level baroclinicity, upper-level jet stream, and warm ocean currents are relatively weaker. The merged cyclone associated with a strong middle-level trough transports large cyclonic vorticity to MO NEP ECs, which favors their rapid development.

Strategies for the extraction and analysis of non-extractable polyphenols from plants.

PubMed

Domínguez-Rodríguez, Gloria; Marina, María Luisa; Plaza, Merichel

2017-09-08

The majority of studies based on phenolic compounds from plants are focused on the extractable fraction derived from an aqueous or aqueous-organic extraction. However, an important fraction of polyphenols is ignored due to the fact that they remain retained in the residue of extraction. They are the so-called non-extractable polyphenols (NEPs) which are high molecular weight polymeric polyphenols or individual low molecular weight phenolics associated to macromolecules. The scarce information available about NEPs shows that these compounds possess interesting biological activities. That is why the interest about the study of these compounds has been increasing in the last years. Furthermore, the extraction and characterization of NEPs are considered a challenge because the developed analytical methodologies present some limitations. Thus, the present literature review summarizes current knowledge of NEPs and the different methodologies for the extraction of these compounds, with a particular focus on hydrolysis treatments. Besides, this review provides information on the most recent developments in the purification, separation, identification and quantification of NEPs from plants. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a P-I-N HgCdTe photomixer for laser heterodyne spectrometry

NASA Technical Reports Server (NTRS)

Bratt, Peter R.

1987-01-01

An improved HgCdTe photomixer technology was demonstrated employing a p-i-n photodiode structure. The i-region was near intrinsic n-type HgCdTe; the n-region was formed by B+ ion implantation; and the p-region was formed either by a shallow Au diffusion or by a Pt Schottky barrier. Experimental devices in a back-side illuminated mesa diode configuration were fabricated, tested, and delivered. The best photomixer was packaged in a 24-hour LN2 dewar along with a cooled GaAs FET preamplifier. Testing was performed by mixing black-body radiation with a CO2 laser beam and measuring the IF signal, noise, and signal-to-noise ratio in the GHz frequency range. Signal bandwidth for this photomixer was 1.3 GHz. The heterodyne NEP was 4.4 x 10 to the -20 W/Hz out to 1 GHz increasing to 8.6 x 10 to the -10 W/Hz at 2 GHz. Other photomixers delivered on this program had heterodyne NEPs at 1 GHz ranging from 8 x 10 to the -20 to 4.4 x 10 to the -19 W/Hz and NEP bandwidths from 2 to 4 GHz.

Nuclear electric propulsion stage requirements and description

NASA Technical Reports Server (NTRS)

Mondt, J. F.; Peelgren, M. L.; Nakashima, A. M.; Nsieh, T. M.; Phillips, W. M.; Kikin, G. M.

1974-01-01

The application of a nuclear electric propulsion (NEP) stage in the exploration of near-earth, cometary, and planetary space was discussed. The NEP stage is powered by a liquid-metal-cooled, fast spectrum thermionic reactor capable of providing 120 kWe for 20,000 hours. This power is used to drive a number of mercury ion bombardment thrusters with specific impulse in the range of 4000-5000 seconds. The NEP description, characteristics, and functional requirements are discussed. These requirements are based on a set of five coordinate missions, which are described in detail. These five missions are a representative part of a larger set of missions used as a basic for an advanced propulsion comparison study. Additionally, the NEP stage development plan and test program is outlined and a schedule presented.

Optimize out-of-core thermionic energy conversion for nuclear electric propulsion

NASA Technical Reports Server (NTRS)

Morris, J. F.

1978-01-01

Thermionic energy conversion (TEC) potentialities for nuclear electric propulsion (NEP) are examined. Considering current designs, their limitations, and risks raises critical questions about the use of TEC for NEP. Apparently a reactor cooled by hotter-than-1675 K heat pipes has good potentialities. TEC with higher temperatures and greater power densities than the currently proposed 1650 K, 5-to-6 W/sq cm version offers substantial gains. Other approaches to high-temperature electric isolation appear also promising. A high-power-density, high-temperature TEC for NEP appears, therefore, attainable. It is recommended to optimize out-of-core thermionic energy conversion for nuclear electric propulsion. Although current TEC designs for NEP seem unnecessary compared with Brayton versions, large gains are apparently possible with increased temperatures and greater power densities.

Evaluation of the Therapeutic Potential of a CNP Analog in a Fgfr3 Mouse Model Recapitulating Achondroplasia

PubMed Central

Lorget, Florence; Kaci, Nabil; Peng, Jeff; Benoist-Lasselin, Catherine; Mugniery, Emilie; Oppeneer, Todd; Wendt, Dan J.; Bell, Sean M.; Bullens, Sherry; Bunting, Stuart; Tsuruda, Laurie S.; O'Neill, Charles A.; Di Rocco, Federico; Munnich, Arnold; Legeai-Mallet, Laurence

2012-01-01

Achondroplasia (ACH), the most common form of dwarfism, is an inherited autosomal-dominant chondrodysplasia caused by a gain-of-function mutation in fibroblast-growth-factor-receptor 3 (FGFR3). C-type natriuretic peptide (CNP) antagonizes FGFR3 downstream signaling by inhibiting the pathway of mitogen-activated protein kinase (MAPK). Here, we report the pharmacological activity of a 39 amino acid CNP analog (BMN 111) with an extended plasma half-life due to its resistance to neutral-endopeptidase (NEP) digestion. In ACH human growth-plate chondrocytes, we demonstrated a decrease in the phosphorylation of extracellular-signal-regulated kinases 1 and 2, confirming that this CNP analog inhibits fibroblast-growth-factor-mediated MAPK activation. Concomitantly, we analyzed the phenotype of Fgfr3Y367C/+ mice and showed the presence of ACH-related clinical features in this mouse model. We found that in Fgfr3Y367C/+ mice, treatment with this CNP analog led to a significant recovery of bone growth. We observed an increase in the axial and appendicular skeleton lengths, and improvements in dwarfism-related clinical features included flattening of the skull, reduced crossbite, straightening of the tibias and femurs, and correction of the growth-plate defect. Thus, our results provide the proof of concept that BMN 111, a NEP-resistant CNP analog, might benefit individuals with ACH and hypochondroplasia. PMID:23200862

Stimulation of Mojave Desert net ecosystem CO2 uptake after winter precipitation with the opposite effect after summer rains based on 7 years of flux data

NASA Astrophysics Data System (ADS)

Jasoni, Richard; Arnone, John; Fenstermaker, Lynn; Wohlfahrt, Georg

2014-05-01

Eddy covariance measurements of net ecosystem CO2 exchange (NEE) in the Mojave Desert (Jasoni et al. 2005-Global Change Biology 11:749-756; Wohlfahrt et al. 2008-Global Change Biology 14:1475-1487), and in other deserts of the world (e.g., Hastings et al. 2005- Global Change Biology 14:927-939, indicate greater rates of net CO2 uptake (more negative NEE values) and net ecosystem productivity (NEP) than would have been expected for deserts (as high as -120 g C m-2 year-1). We continue to observe high rates of NEE and NEP and seek explanations for these findings at interannual, seasonal, and sub-seasonal time scales. Because moisture availability most strongly constrains biological activity in deserts, responses to rains probably play a significant role in defining components of NEE-namely net primary productivity (NPP, or roughly net photosynthesis by vascular and non-vascular plants) and heterotrophic respiration (Rh, mainly by soil microorganisms). Most precipitation in the Mojave Desert falls from October through April and periodically in the summer as convective storms. The main objective of this study was to quantify the extent to which NEE and the net flux of CO2 from/to biological soil crust (BSC) covered soil surfaces respond to rain pulses occurring during cool/cold and warm/hot times of the year. Flux data from 7 years (2005-2011) of measurements at our shub land desert site (average 150 mm rain per year) located 120 km northwest of Las Vegas showed a range in NEP from -111±34 to -47±28 g C m-2 year-1. Cool season rains usually stimulated NEE (more negative NEE values or net CO2 uptake) while warm season rains reversed this effect and led to positive NEE values (net ecosystem CO2 efflux. Cool season stimulation of NEE often occurred in the absence of green leaves on vascular plants, suggesting that photosynthesis of BSCs (up to 70% of soil surface covered by cyanobacteria, mosses, and lichens) were responsible for this net uptake. At other times during the cool season, herbaceous vascular plants also contributed to increases in NEE. Parallel experiments in which we simulated rain pulses (10 mm) in the cool (February) and warm (May) seasons and measured net CO2 fluxes from BSC covered soil surfaces showed responses similar to those observed at the level of the ecosystem. Earlier continuous measurements of soil air relative humidity (RH; 2001-2006) showed that soil moisture increases occurring after rains in the cool season persist up to 3 weeks after events (a total of 48-108 day equivalent per year at >98% RH) indicating conditions favorable for photosynthetic activity. Thus, net CO2 uptake by BSCs during cool months may largely determine large NEEs measured under moist conditions during this time of year and, together with NPP of herbaceous vascular plants, help explain overall consistently high annual NEP in these ecosystems.

Specific memory B cell response and participation of CD4+ central and effector memory T cells in mice immunized with liposome encapsulated recombinant NE protein based Hepatitis E vaccine candidate.

PubMed

Kulkarni, Shruti P; Thanapati, Subrat; Arankalle, Vidya A; Tripathy, Anuradha S

2016-11-21

Liposome encapsulated neutralizing epitope protein of Hepatitis E virus (HEV), rNEp, our Hepatitis E vaccine candidate, was shown to be immunogenic and safe in pregnant and non-pregnant mice and yielded sterilizing immunity in rhesus monkeys. The current study in Balb/c mice assessed the levels and persistence of anti-HEV IgG antibodies by ELISA, frequencies of B, memory B, T and memory T cells by flow cytometry and HEV-specific IgG secreting memory B cells by ELISPOT till 420days post immunization (PI) with 5?g rNEp encapsulated in liposome based adjuvant (2 doses, 4weeks apart). Mice immunized with a lower dose (1?g) were assessed only for anamnestic response post booster dose. Vaccine candidate immunized mice (5?g dose) elicited strong anti-HEV IgG response that was estimated to persist for lifetime. At day 120 PI, frequency of memory B cells was higher in immunized mice than those receiving adjuvant alone. Anti-HEV IgG titers were lower in mice immunized with 1?g dose. A booster dose yielded a heightened antibody response in mice with both high (>800GMT, 5?g) and low (?100GMT, 1?g) anti-HEV IgG titers. At day 6th post booster dose, HEV-specific antibody secreting plasma cells (ASCs) were detected in 100% and 50% of mice with high and low anti-HEV IgG titers, respectively, whereas the frequencies of CD4 + central and effector memory T cells were high in mice with high anti-HEV IgG titers only. Taken together, the vaccine candidate effectively generates persistent and anamnestic antibody response, elicits participation of CD4 + memory T cells and triggers memory B cells to differentiate into ASCs upon boosting. This approach of assessing the immunogenicity of vaccine candidate could be useful to explore the longevity of HEV-specific memory response in future HEV vaccine trials in human. Copyright © 2016. Published by Elsevier Ltd.

Gender, race, and electrophysiologic characteristics of the branched recurrent laryngeal nerve.

PubMed

Fontenot, Tatyana E; Randolph, Gregory W; Friedlander, Paul L; Masoodi, Hammad; Yola, Ibrahim M; Kandil, Emad

2014-10-01

The extralaryngeal branching of recurrent laryngeal nerves (RLN) conveys an increased risk of nerve injury during thyroid surgery. We hypothesized that racial and gender variations in prevalence of branched RLN exist. A retrospective review of all patients who underwent thyroid surgery in a 4-year period in a single surgeon practice. The RLN was routinely identified during thyroid surgery. Presence of RLN branching, its distance from the laryngeal nerve entry point (NEP), and functionality of the branches were ascertained. Patient demographics, rates of neural branching, and distance of bifurcation from the NEP were evaluated using statistical analysis. We identified 719 RLNs at risk in 491 patients who underwent central neck surgery. Four hundred and five (82.5%) patients were female and 86 (17.5%) patients were male. There were 218 (44.4%) African American patients and 251 (51.1 %) Caucasian patients. In African American patients, 42.1% RLNs bifurcated compared to 33.2% RLNs in Caucasian (P = 0.017) patients. The RLNs of African American and Caucasian patients bifurcated at comparable distances (P = 0.30). In male patients, 39.1% RLNs bifurcated; whereas in female patients 36.2% RLNs bifurcated (P = 0.53). On average, RLN bifurcation in female patients was at a longer distance from NEP compared to that of male patients (P = 0.012). Electrophysiologic testing found motor fibers in all anterior branches and three posterior extralaryngeal RLN branches. African American patients have a higher rate of RLN bifurcation compared to Caucasian patients but no statistically significant difference in distance from NEP. Female patients tend to have longer branching variants of bifid RLNs. RLN motor fibers reside primarily in the anterior branch but may occur in the posterior branch. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Proliferation of prostate cancer cells and activity of neutral endopeptidase is regulated by bombesin and IL-1beta with IL-1beta acting as a modulator of cellular differentiation.

PubMed

Albrecht, Martin; Doroszewicz, Jolanta; Gillen, Sonja; Gomes, Iara; Wilhelm, Beate; Stief, Thomas; Aumüller, Gerhard

2004-01-01

Neutral endopeptidase (NEP) is a cell-surface bound enzyme that cleaves and inactivates neuropeptides such as bombesin and substance P and is involved in the transition from hormonally regulated androgen-dependent prostate cancer (PC) to androgen-independent PC. Neuropeptides are implicated in growth regulation of different cell types and function as transmitters between the neuroendocrine and the immune system. NEP-expression, enzymatic activity of the membrane bound protein, cell proliferation, procalcitonin (PCT) production, and secretion as well as changes in cell morphology of prostatic cells were evaluated after treatment with the immunomodulatory cytokine interleukin-1beta (IL-1beta), neuropeptides (bombesin, substance P), and neuropeptide-conditioned media derived from a human neuroendocrine cell line. Incubation of LNCaP tumor cells with IL-1beta resulted in a diminished proliferative activity, induction of neurite-like outgrowth which was accompanied by the formation of tubular-type mitochondria typical for neuronal/neuroendocrine cells, and an increased production and secretion of PCT. Conversely, proliferation of prostatic stromal cells was enhanced by the cytokine coming along with an increased number of Golgi-apparatuses and ER-cisternae. Bombesin had an antimitotic effect on LNCaP, but not on stromal cells. Substance P did not influence the growth of any of the cell types investigated, whereas neuropeptide-conditioned media exerted a slightly mitogenic effect on both cell types. The activity of LNCaP cell-surface bound NEP was enhanced by bombesin, but was diminished by substance P and neuropeptide-conditioned media. Proliferation and activity of neuropeptide degrading NEP is regulated differently by immunomodulatory substances in PC cells and cells derived from the prostatic stroma with IL-1beta being a potent modulator of cellular differentiation and a potential target for anticancer drug design in PC cells. Copyright 2003 Wiley-Liss, Inc.

Atrial natriuretic peptide degradation by CPA47 cells: evidence for a divalent cation-independent cell-surface proteolytic activity.

PubMed

Frost, S J; Chen, Y M; Whitson, P A

1992-11-23

Atrial natriuretic peptide (ANP) is rapidly cleared and degraded in vivo. Nonguanylate-cyclase receptors (C-ANPR) and a metalloproteinase, neutral endopeptidase (EC 3.4.24.11) (NEP 24.11), are thought to be responsible for its metabolism. We investigated the mechanisms of ANP degradation by an endothelial-derived cell line, CPA47. CPA47 cells degraded 88% of 125I-ANP after 1 h at 37 degrees C as determined by HPLC. Medium preconditioned by these cells degraded 41% of the 125I-ANP, and this activity was inhibited by a divalent cation chelator, EDTA. Furthermore, a cell-surface proteolytic activity degraded 125I-ANP in the presence of EDTA when receptor-mediated endocytosis was inhibited either by low temperature (4 degrees C) or by hyperosmolarity at 37 degrees C. The metalloproteinase, NEP 24.11, is unlikely to be the cell-surface peptidase because 125I-ANP is degraded by CPA47 cells at 4 degrees C in the presence of 5 mM EDTA. These data indicate that CPA47 cells can degrade ANP by a novel divalent cation-independent cell-surface proteolytic activity.

Effects of neuropeptides on human lung fibroblast proliferation and chemotaxis.

PubMed

Harrison, N K; Dawes, K E; Kwon, O J; Barnes, P J; Laurent, G J; Chung, K F

1995-02-01

An increase in subepithelial mesenchymal cells and associated connective tissue is a feature of bronchial asthma. We determined whether neuropeptides could modulate fibroblast activity, particularly with respect to proliferation and chemotaxis. Human lung fibroblasts were cultured with neurokinin A (NKA), substance P (SP), vasoactive intestinal peptide (VIP), and calcitonin-gene-related peptide (CGRP). After 48 h, fibroblast proliferation was measured by a colorimetric assay based on the uptake and subsequent release of methylene blue. The chemotactic response to neuropeptides was determined with the use of a modified Boyden chamber. Both NKA and SP (10(-7)-10(-4) M) stimulated human lung fibroblast proliferation in HFL1 and IMR-90 fibroblasts. VIP and CGRP had no effect on fibroblast proliferation. NKA alone stimulated fibroblast chemotaxis maximally at 10(-10) M. Neutral endopeptidase (NEP) activity of 0.52 and 5.2 pmol/10(6) cells was assayed in IMR-90 and Hs68 fibroblasts, respectively. Phosphoramidon (5 x 10(-6)-10(-5) M), an NEP inhibitor, enhanced fibroblast proliferation in a dose-dependent manner. Thus neuropeptides have the potential to cause activation of mesenchymal cells, and neuropeptide release may contribute to the structural abnormalities observed in asthmatic airways.

Atrial natriuretic peptide degradation by CPA47 cells - Evidence for a divalent cation-independent cell-surface proteolytic activity

NASA Technical Reports Server (NTRS)

Frost, S. J.; Chen, Y. M.; Whitson, P. A.

1992-01-01

Atrial natriuretic peptide (ANP) is rapidly cleared and degraded in vivo. Nonguanylate-cyclase receptors (C-ANPR) and a metalloproteinase, neutral endopeptidase (EC 3.4.24.11) (NEP 24.11), are thought to be responsible for its metabolism. We investigated the mechanisms of ANP degradation by an endothelial-derived cell line, CPA47. CPA47 cells degraded 88 percent of 125I-ANP after 1 h at 37 degrees C as determined by HPLC. Medium preconditioned by these cells degraded 41 percent of the 125I-ANP, and this activity was inhibited by a divalent cation chelator, EDTA. Furthermore, a cell-surface proteolytic activity degraded 125I-ANP in the presence of EDTA when receptor-mediated endocytosis was inhibited either by low temperature (4 degrees C) or by hyperosmolarity at 37 degrees C. The metalloproteinase, NEP 24.11, is unlikely to be the cell-surface peptidase because 125I-ANP is degraded by CPA47 cells at 4 degrees C in the presence of 5 mM EDTA. These data indicate that CPA47 cells can degrade ANP by a novel divalent cation-independent cell-surface proteolytic activity.

Thiorphan, a neutral endopeptidase inhibitor used for diarrhoea, is neuroprotective in newborn mice.

PubMed

Medja, Fadia; Lelièvre, Vincent; Fontaine, Romain H; Lebas, Fanny; Leroux, Philippe; Ouimet, Tanja; Saria, Alois; Rougeot, Catherine; Dournaud, Pascal; Gressens, Pierre

2006-12-01

Excitotoxic damage appears to be a critical factor in the formation of perinatal brain lesions associated with cerebral palsy (CP). When injected into newborn mice, the glutamatergic analogue, ibotenate, produces cortical lesions and white matter cysts that mimic human perinatal brain lesions. Neuropeptides are neuronal activity modulators and could therefore modulate glutamate-induced lesions. However, neuropeptides are rapidly degraded by peptidases. Racecadotril, which is rapidly metabolized to its active metabolite thiorphan, is a neutral endopeptidase (NEP) inhibitor used in clinical practice for diarrhoea with a remarkable safety profile. This study aimed to test the original hypothesis that thiorphan could be neuroprotective against ibotenate-induced lesions in newborn mice. Intraperitoneal administration of thiorphan reduced ibotenate-induced cortical lesions by up to 57% and cortical caspase-3 cleavage by up to 59%. This neuroprotective effect was long-lasting and was still observed when thiorphan was administered 12 h after the insult, showing a remarkable window for therapeutic intervention. Further supporting the neuroprotective effect of pharmacological blockade of NEP, mouse pups with a genetic deletion of NEP displayed a significantly reduced size of the ibotenate-induced cortical grey matter lesion when compared with wild-type animals. Thiorphan effects were mimicked by substance P (SP) and, in a less potent manner, by neurokinin A. Thiorphan effects were inhibited by blockers of NK1 and NK2 receptors. Real-time reverse transcription-polymerase chain reaction, autoradiography and immunohistochemistry confirmed the expression of NK1 and NK2 receptors in the neonatal murine neocortex. These data demonstrate that thiorphan prevents neonatal excitotoxic cortical damage, an effect largely mediated by SP. Thiorphan could represent a promising drug for the prevention of CP, which remains a challenging disease. In a broader context, these results also raise potential implications for the prevention of neurodegenerative diseases involving glutamate-mediated excitotoxic neuronal death.

Net ecosystem production and organic carbon balance of U.S. East Coast estuaries: A synthesis approach

USGS Publications Warehouse

Herrmann, Maria; Najjar, Raymond G.; Kemp, W. Michael; Alexander, Richard B.; Boyer, Elizabeth W.; Cai, Wei-Jun; Griffith, Peter C.; Kroeger, Kevin D.; McCallister, S. Leigh; Smith, Richard A.

2015-01-01

Net ecosystem production (NEP) and the overall organic carbon budget for the estuaries along the East Coast of the United States are estimated. We focus on the open estuarine waters, excluding the fringing wetlands. We developed empirical models relating NEP to loading ratios of dissolved inorganic nitrogen to total organic carbon, and carbon burial in the sediment to estuarine water residence time and total nitrogen input across the landward boundary. Output from a data-constrained water quality model was used to estimate inputs of total nitrogen and organic carbon to the estuaries across the landward boundary, including fluvial and tidal-wetland sources. Organic carbon export from the estuaries to the continental shelf was computed by difference, assuming steady state. Uncertainties in the budget were estimated by allowing uncertainties in the supporting model relations. Collectively, U.S. East Coast estuaries are net heterotrophic, with the area-integrated NEP of −1.5 (−2.8, −1.0) Tg C yr−1 (best estimate and 95% confidence interval) and area-normalized NEP of −3.2 (−6.1, −2.3) mol C m−2 yr−1. East Coast estuaries serve as a source of organic carbon to the shelf, exporting 3.4 (2.0, 4.3) Tg C yr−1 or 7.6 (4.4, 9.5) mol C m−2 yr−1. Organic carbon inputs from fluvial and tidal-wetland sources for the region are estimated at 5.4 (4.6, 6.5) Tg C yr−1 or 12 (10, 14) mol C m−2 yr−1 and carbon burial in the open estuarine waters at 0.50 (0.33, 0.78) Tg C yr−1 or 1.1 (0.73, 1.7) mol C m−2 yr−1. Our results highlight the importance of estuarine systems in the overall coastal budget of organic carbon, suggesting that in the aggregate, U.S. East Coast estuaries assimilate (via respiration and burial) ~40% of organic carbon inputs from fluvial and tidal-wetland sources and allow ~60% to be exported to the shelf.

NEP processing, operations, and disposal

NASA Technical Reports Server (NTRS)

Stancati, Mike

1993-01-01

Several recent studies by ASAO/NPO staff members at LeRC and by other organizations have highlighted the potential benefits of using Nuclear Electric Propulsion (NEP) as the primary transportation means for some of the proposed missions of the Space Exploration Initiative. These include the potential to reduce initial mass in orbit and Mars transit time. Modular NEP configurations also introduce fully redundant main propulsion to Mars flight systems adding several abort or fall back options not otherwise available. Recent studies have also identified mission operations, such as on orbital assembly, refurbishment, and reactor disposal, as important discriminators for propulsion system evaluation. This study is intended to identify and assess 'end-to-end' operational issues associated with using NEP for transporting crews and cargo between Earth and Mars. We also include some consideration of lunar cargo transfer as well.

Environmental Impacts by Fragments Released from Nanoenabled Products: A Multiassay, Multimaterial Exploration by the SUN Approach.

PubMed

Amorim, Mónica J B; Lin, Sijie; Schlich, Karsten; Navas, José M; Brunelli, Andrea; Neubauer, Nicole; Vilsmeier, Klaus; Costa, Anna L; Gondikas, Andreas; Xia, Tian; Galbis, Liliana; Badetti, Elena; Marcomini, Antonio; Hristozov, Danail; Kammer, Frank von der; Hund-Rinke, Kerstin; Scott-Fordsmand, Janeck J; Nel, André; Wohlleben, Wendel

2018-02-06

Nanoenabled products (NEPs) have numerous outdoor uses in construction, transportation or consumer scenarios, and there is evidence that their fragments are released in the environment at low rates. We hypothesized that the lower surface availability of NEPs fragment reduced their environmental effects with respect to pristine nanomaterials. This hypothesis was explored by testing fragments generated by intentional micronisation ("the SUN approach"; Nowack et al. Meeting the Needs for Released Nanomaterials Required for Further Testing: The SUN Approach. Environmental Science & Technology, 2016 (50), 2747). The NEPs were composed of four matrices (epoxy, polyolefin, polyoxymethylene, and cement) with up to 5% content of three nanomaterials (carbon nanotubes, iron oxide, and organic pigment). Regardless of the type of nanomaterial or matrix used, it was observed that nanomaterials were only partially exposed at the NEP fragment surface, indicating that mostly the intrinsic and extrinsic properties of the matrix drove the NEP fragment toxicity. Ecotoxicity in multiple assays was done covering relevant media from terrestrial to aquatic, including sewage treatment plant (biological activity), soil worms (Enchytraeus crypticus), and fish (zebrafish embryo and larvae and trout cell lines). We designed the studies to explore the possible modulation of ecotoxicity by nanomaterial additives in plastics/polymer/cement, finding none. The results support NEPs grouping by the matrix material regarding ecotoxicological effect during the use phase. Furthermore, control results on nanomaterial-free polymer fragments representing microplastic had no significant adverse effects up to the highest concentration tested.

CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides.

PubMed

King, K A; Hua, J; Torday, J S; Drazen, J M; Graham, S A; Shipp, M A; Sunday, M E

1993-05-01

Bombesin-like peptides (BLPs) are mitogens for bronchial epithelial cells and small cell lung carcinomas, and increase fetal lung growth and maturation in utero and in organ cultures. BLPs are hydrolyzed by the enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) which is expressed in bronchial epithelium and functions to inhibit BLP-mediated growth of small cell lung carcinomas. To determine whether CD10/NEP regulates peptide-mediated lung development, we administered a specific CD10/NEP inhibitor, SCH32615, to fetal mice in utero from gestational days e15-17. Fetal lung tissues were evaluated on e18 for: (a) growth using [3H]thymidine incorporation into nuclear DNA; and (b) maturation using: [3H]-choline incorporation into surfactant phospholipids, electron microscopy for type II pneumocytes, and Northern blot analyses for surfactant apoproteins A, B, and C. Inhibition of CD10/NEP stimulated [3H]thymidine incorporation into DNA (70% above baseline, P < 0.005), [3H]choline incorporation into surfactant phospholipids (38% above baseline, P < 0.005), increased numbers of type II pneumocytes (36% above baseline, P = 0.07), and fivefold higher surfactant protein A transcripts (P < 0.05). CD10/NEP-mediated effects were completely blocked by the specific bombesin receptor antagonist, [D-Phe12, Leu14]bombesin. These observations suggest that CD10/NEP regulates fetal lung growth and maturation mediated by endogenous BLPs.

CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides.

PubMed Central

King, K A; Hua, J; Torday, J S; Drazen, J M; Graham, S A; Shipp, M A; Sunday, M E

1993-01-01

Bombesin-like peptides (BLPs) are mitogens for bronchial epithelial cells and small cell lung carcinomas, and increase fetal lung growth and maturation in utero and in organ cultures. BLPs are hydrolyzed by the enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) which is expressed in bronchial epithelium and functions to inhibit BLP-mediated growth of small cell lung carcinomas. To determine whether CD10/NEP regulates peptide-mediated lung development, we administered a specific CD10/NEP inhibitor, SCH32615, to fetal mice in utero from gestational days e15-17. Fetal lung tissues were evaluated on e18 for: (a) growth using [3H]thymidine incorporation into nuclear DNA; and (b) maturation using: [3H]-choline incorporation into surfactant phospholipids, electron microscopy for type II pneumocytes, and Northern blot analyses for surfactant apoproteins A, B, and C. Inhibition of CD10/NEP stimulated [3H]thymidine incorporation into DNA (70% above baseline, P < 0.005), [3H]choline incorporation into surfactant phospholipids (38% above baseline, P < 0.005), increased numbers of type II pneumocytes (36% above baseline, P = 0.07), and fivefold higher surfactant protein A transcripts (P < 0.05). CD10/NEP-mediated effects were completely blocked by the specific bombesin receptor antagonist, [D-Phe12, Leu14]bombesin. These observations suggest that CD10/NEP regulates fetal lung growth and maturation mediated by endogenous BLPs. Images PMID:8486767

Investigation of ac-magnetic field stimulated nanoelectroporation of magneto-electric nano-drug-carrier inside CNS cells.

PubMed

Kaushik, Ajeet; Nikkhah-Moshaie, Roozbeh; Sinha, Raju; Bhardwaj, Vinay; Atluri, Venkata; Jayant, Rahul Dev; Yndart, Adriana; Kateb, Babak; Pala, Nezih; Nair, Madhavan

2017-04-04

In this research, we demonstrate cell uptake of magneto-electric nanoparticles (MENPs) through nanoelectroporation (NEP) using alternating current (ac)-magnetic field stimulation. Uptake of MENPs was confirmed using focused-ion-beam assisted transmission electron microscopy (FIB-TEM) and validated by a numerical simulation model. The NEP was performed in microglial (MG) brain cells, which are highly sensitive for neuro-viral infection and were selected as target for nano-neuro-therapeutics. When the ac-magnetic field optimized (60 Oe at 1 kHz), MENPs were taken up by MG cells without affecting cell health (viability > 92%). FIB-TEM analysis of porated MG cells confirmed the non-agglomerated distribution of MENPs inside the cell and no loss of their elemental and crystalline characteristics. The presented NEP method can be adopted as a part of future nanotherapeutics and nanoneurosurgery strategies where a high uptake of a nanomedicine is required for effective and timely treatment of brain diseases.

A three-dimensional construction of the active site (region 507-749) of human neutral endopeptidase (EC.3.4.24.11).

PubMed

Tiraboschi, G; Jullian, N; Thery, V; Antonczak, S; Fournie-Zaluski, M C; Roques, B P

1999-02-01

A three-dimensional model of the 507-749 region of neutral endopeptidase-24.11 (NEP; E.C.3.4.24.11) was constructed integrating the results of secondary structure predictions and sequence homologies with the bacterial endopeptidase thermolysin. Additional data were extracted from the structure of two other metalloproteases, astacin and stromelysin. The resulting model accounts for the main biological properties of NEP and has been used to describe the environment close to the zinc atom defining the catalytic site. The analysis of several thiol inhibitors, complexed in the model active site, revealed the presence of a large hydrophobic pocket at the S1' subsite level. This is supported by the nature of the constitutive amino acids. The computed energies of bound inhibitors correspond with the relative affinities of the stereoisomers of benzofused macrocycle derivatives of thiorphan. The model could be used to facilitate the design of new NEP inhibitors, as illustrated in the paper.

Investigation of ac-magnetic field stimulated nanoelectroporation of magneto-electric nano-drug-carrier inside CNS cells

PubMed Central

Kaushik, Ajeet; Nikkhah-Moshaie, Roozbeh; Sinha, Raju; Bhardwaj, Vinay; Atluri, Venkata; Jayant, Rahul Dev; Yndart, Adriana; Kateb, Babak; Pala, Nezih; Nair, Madhavan

2017-01-01

In this research, we demonstrate cell uptake of magneto-electric nanoparticles (MENPs) through nanoelectroporation (NEP) using alternating current (ac)-magnetic field stimulation. Uptake of MENPs was confirmed using focused-ion-beam assisted transmission electron microscopy (FIB-TEM) and validated by a numerical simulation model. The NEP was performed in microglial (MG) brain cells, which are highly sensitive for neuro-viral infection and were selected as target for nano-neuro-therapeutics. When the ac-magnetic field optimized (60 Oe at 1 kHz), MENPs were taken up by MG cells without affecting cell health (viability > 92%). FIB-TEM analysis of porated MG cells confirmed the non-agglomerated distribution of MENPs inside the cell and no loss of their elemental and crystalline characteristics. The presented NEP method can be adopted as a part of future nanotherapeutics and nanoneurosurgery strategies where a high uptake of a nanomedicine is required for effective and timely treatment of brain diseases. PMID:28374799

Nuclear electric propulsion development and qualification facilities

NASA Technical Reports Server (NTRS)

Dutt, D. S.; Thomassen, K.; Sovey, J.; Fontana, Mario

1991-01-01

This paper summarizes the findings of a Tri-Agency panel consisting of members from the National Aeronautics and Space Administration (NASA), U.S. Department of Energy (DOE), and U.S. Department of Defense (DOD) that were charged with reviewing the status and availability of facilities to test components and subsystems for megawatt-class nuclear electric propulsion (NEP) systems. The facilities required to support development of NEP are available in NASA centers, DOE laboratories, and industry. However, several key facilities require significant and near-term modification in order to perform the testing required to meet a 2014 launch date. For the higher powered Mars cargo and piloted missions, the priority established for facility preparation is: (1) a thruster developmental testing facility, (2) a thruster lifetime testing facility, (3) a dynamic energy conversion development and demonstration facility, and (4) an advanced reactor testing facility (if required to demonstrate an advanced multiwatt power system). Facilities to support development of the power conditioning and heat rejection subsystems are available in industry, federal laboratories, and universities. In addition to the development facilities, a new preflight qualifications and acceptance testing facility will be required to support the deployment of NEP systems for precursor, cargo, or piloted Mars missions. Because the deployment strategy for NEP involves early demonstration missions, the demonstration of the SP-100 power system is needed by the early 2000's.

Bioinformatic analysis of the neprilysin (M13) family of peptidases reveals complex evolutionary and functional relationships.

PubMed

Bland, Nicholas D; Pinney, John W; Thomas, Josie E; Turner, Anthony J; Isaac, R Elwyn

2008-01-23

The neprilysin (M13) family of endopeptidases are zinc-metalloenzymes, the majority of which are type II integral membrane proteins. The best characterised of this family is neprilysin, which has important roles in inactivating signalling peptides involved in modulating neuronal activity, blood pressure and the immune system. Other family members include the endothelin converting enzymes (ECE-1 and ECE-2), which are responsible for the final step in the synthesis of potent vasoconstrictor endothelins. The ECEs, as well as neprilysin, are considered valuable therapeutic targets for treating cardiovascular disease. Other members of the M13 family have not been functionally characterised, but are also likely to have biological roles regulating peptide signalling. The recent sequencing of animal genomes has greatly increased the number of M13 family members in protein databases, information which can be used to reveal evolutionary relationships and to gain insight into conserved biological roles. The phylogenetic analysis successfully resolved vertebrate M13 peptidases into seven classes, one of which appears to be specific to mammals, and insect genes into five functional classes and a series of expansions, which may include inactive peptidases. Nematode genes primarily resolved into groups containing no other taxa, bar the two nematode genes associated with Drosophila DmeNEP1 and DmeNEP4. This analysis reconstructed only one relationship between chordate and invertebrate clusters, that of the ECE sub-group and the DmeNEP3 related genes. Analysis of amino acid utilisation in the active site of M13 peptidases reveals a basis for their biochemical properties. A relatively invariant S1' subsite gives the majority of M13 peptidases their strong preference for hydrophobic residues in P1' position. The greater variation in the S2' subsite may be instrumental in determining the specificity of M13 peptidases for their substrates and thus allows M13 peptidases to fulfil a broad range of physiological roles. The M13 family of peptidases have diversified extensively in all species examined, indicating wide ranging roles in numerous physiological processes. It is predicted that differences in the S2' subsite are fundamental to determining the substrate specificities that facilitate this functional diversity.

Thermal Properties of Whispering Gallery Mode Resonators

DTIC Science & Technology

2014-12-22

in a vacuum chamber, to lower the noise floor and increase the SNR. To study the frequency response of the IR detector , we varied the modulation...performance at a fixed IR modulation (chopping) frequency. Finally, we estimated the noise equivalent power (NEP) of our IR detector . Note that the...the thennal relaxation time of the resonator to estimate the response time of the resonator based infrared (IR) detector . We found that, depending on

Long term carbon fluxes in south eastern U.S. pine ecosystems.

NASA Astrophysics Data System (ADS)

Bracho, R. G.; Martin, T.; Gonzalez-Benecke, C. A.; Sharp, J.

2015-12-01

Forests in the southeastern U.S. are a critical component of the national carbon balance storing a third of the total forest carbon (C) in conterminous USA. South eastern forests occupy 60% of the land area, with a large fraction dominated by the genus Pinus distributed in almost equal proportions of naturally-regenerated and planted stands. These stands often differ in structure (e.g., stem density, leaf area index (LAI)) and in the intensity with which they are managed (e.g. naturally-regenerated, older pine stands are often managed less intensively, with prescribed fire). We measured C fluxes using the eddy covariance approach (net ecosystem production, -NEP) in planted (Pinus elliottii var. elliottii) and naturally-regenerated mixed stand of long leaf (Pinus palustris Mill) and slash pine (Pinus elliottii var. elliottii) accompanied by biometric estimations of C balance. Measurements spanned more than a decade and included interannual climatic variability ranging from severe droughts (e.g. Palmer Drought severity index (PDSI) averaged -2.7 from January 2000 to May 2002, and -3.3 from June 2006 to April 2008), to years with tropical storms. Annual NEP for the older, naturally-regenerated stand fluctuated from -1.60 to -5.38 Mg C ha-1 yr-1 with an average of -2.73 ± 1.17 Mg C ha-1 yr-1 while in plantations after canopy closure NEP fluctuated from -4.0 to -8.2 Mg C ha-1 yr-1 with an average of -6.17 ± 1.34 Mg C ha-1 yr-1. Annual NEP in naturally-regenerated pine was mainly driven by a combination of water availability and understory burning while in plantations it was driven by water availability after canopy closure. Woody and above ground net primary productivity (NPP) followed gross ecosystem carbon exchange (GEE) in both ecosystems. Naturally-regenerated and planted pine are a strong carbon sink under the current management and environmental fluctuations accumulating 28 and 130 Mg C ha-1 in a decade, respectively, and are among the most productive forests in the world.

ACUTE CHANGES IN SPUTUM COLLECTED FROM EXPOSED HUMAN SUBJECTS IN MINING CONDITIONS

PubMed Central

Wong, Simon S.; Sun, Nina N.; Miller, Hugh B.; Witten, Mark L.; Burgess, Jefferey L.

2015-01-01

Neprilysin (NEP) is a key cell surface peptidase in the maintenance of airway homeostasis and the development of pulmonary disorders. However, little information is available about the effect of particulate matter (PM) on airway NEP. In this controlled human exposure study, changes in induced sputum were measured in eleven subjects at baseline, overshot (OS) mucking, and diesel exhaust (DE) exposure days. Neither OS condition nor DE exposure was found to induce significant changes in total protein, but DE induced significant increases in cell numbers of macrophages and epithelium. Moreover, significant increases in soluble NEP were observed following OS mining dust particulates (0.43 ± 0.06, p = 0.023) and DE exposure (0.30 ± 0.04, p = 0.035) when compared with the baseline control (0.40 ± 0.03), with 42% and 31% average net increase, respectively. Pearson’s correlation analyses indicated that sputum NEP activity were significantly associated with personal exposure product [Elemental carbon concentration, mg/m3 X time, min. (C X T)]. Data suggest that the changes in NEP activity may be an early, accurate endpoint for airway epithelial injury and provided a new insight into the mechanism of the airway effects in these exposure conditions. PMID:20384431

The Alzheimer's Amyloid-Degrading Peptidase, Neprilysin: Can We Control It?

PubMed Central

Nalivaeva, N. N.; Belyaev, N. D.; Zhuravin, I. A.; Turner, A. J.

2012-01-01

The amyloid cascade hypothesis of Alzheimer's disease (AD) postulates that accumulation in the brain of amyloid β-peptide (Aβ) is the primary trigger for neuronal loss specific to this pathology. In healthy brain, Aβ levels are regulated by a dynamic equilibrium between Aβ release from the amyloid precursor protein (APP) and its removal by perivascular drainage or by amyloid-degrading enzymes (ADEs). During the last decade, the ADE family was fast growing, and currently it embraces more than 20 members. There are solid data supporting involvement of each of them in Aβ clearance but a zinc metallopeptidase neprilysin (NEP) is considered as a major ADE. NEP plays an important role in brain function due to its role in terminating neuropeptide signalling and its decrease during ageing or after such pathologies as hypoxia or ischemia contribute significantly to the development of AD pathology. The recently discovered mechanism of epigenetic regulation of NEP by the APP intracellular domain (AICD) opens new avenues for its therapeutic manipulation and raises hope for developing preventive strategies in AD. However, consideration needs to be given to the diverse physiological roles of NEP. This paper critically evaluates general biochemical and physiological functions of NEP and their therapeutic relevance. PMID:22900228

Forest Carbon Storage in the Northern Midwest, USA: A Bottom-Up Scaling Approach Combining Local Meteorological and Biometric Data With Regional Forest Inventories

NASA Astrophysics Data System (ADS)

Curtis, P. S.; Gough, C. M.; Vogel, C. S.

2005-12-01

Carbon (C) storage increasingly is considered an important part of the economic return of forestlands, making easily parameterized models for assessing current and future C storage important for both ecosystem and money managers. For the deciduous forests of the northern midwest, USA, detailed information relating annual C storage to local site characteristics can be combined with spatially extensive forest inventories to produce simple, robust models of C storage useful at a variety of scales. At the University of Michigan Biological Station (45o35`' N, 84o42`' W) we measured C storage, or net ecosystem production (NEP), in 65 forest stands varying in age, disturbance history, and productivity (site index) using biometric methods, and independently measured net C exchange at the landscape level using meteorological methods. Our biometric and meteorological estimates of NEP converged to within 1% of each other over five years, providing important confirmation of the robustness of these two approaches applied within northern deciduous forests (Gough et al. 2005). We found a significant relationship between NEP, stand age ( A, yrs), and site index ( Is, m), where NEP = 0.134 + 0.022 * (LN[ A* Is]) (r2 = 0.50, P < 0.02). Site index is an integrated measure of site quality, expressed as 50 yr canopy height. We then used stand age and site index data from forests of similar species composition reported in the USDA Forest Inventory and Analysis database (ncrs2.fs.fed.us/4801/fiadb/) to estimate forest C storage at different scales across the upper midwest, Great Lakes region. Model estimates were validated against independent estimates of C storage for other forests in the region. At the local ecosystem-level (~1 km2) C storage averaged 1.52 Mg ha-1 yr-1. Scaling to the two-county area surrounding our meteorological and biometric study sites, average stand age decreased and site index increased, resulting in estimated storage of 1.62 Mg C ha-1 yr-1, or 0.22 Tg C yr-1 in the 1350 km2 of deciduous forest in this area. For the state of Michigan (31,537 km2 of deciduous forest), average uptake was estimated at 1.55 Mg C ha-1 yr-1, or 4.9 Tg C yr-1 total storage. For the three state region encompassing Minnesota, Michigan, and Wisconsin (97,769 km2 of deciduous forest), we estimated average storage in these forests of 1.51 Mg C ha-1 yr-1, or 14.1 Tg C yr-1 total storage. This storage represents ~ 13 % of regional anthropogenic C emissions (US Department of Energy, 2003). This modest rate of C storage by forests in the region may decrease due to changes in forest succession and land-use, and also in response to climate-driven shifts in the balance between photosynthesis and respiration. Gough C.M., Vogel C.S., Schmid H.P., Su H.-B., and Curtis P.S. 2005. Multi-year convergence of biometric and meteorological estimates of forest carbon storage. Agricultural and Forest Meteorology, In Press.

Tests of the Rockwell Si:As Back-Illuminated Blocked-Impurity Band (BIBIB) detectors

NASA Technical Reports Server (NTRS)

Wolf, J.; Groezinger, U.; Burgdorf, M.; Salama, A.

1989-01-01

Two arrays of Rockwell's Si:As back-illuminated blocked-impurity-band detectors were tested at the Max-Planck-Institute for Astronomy (MPIA) at low background and low temperature for possible use in the astronomical space experiment ISOPHOT. For these measurements special test equipment was put together. A cryostat was mechanically modified to accommodate the arrays and special peripheral electronics was added to a microprocessor system to drive the cold multiplexer and to acquire the output data. The first device, a 16x50 element array on a fan-out board was used to test individual pixels with a trans-impedance-amplifier at a photon background of 10(exp 8) Ph s(-1)cm(-2) and at temperatures of 2.7 to 4.4 K. The noise-equivalent-power NEP is in the range 5 - 7 x 10(exp -18) WHz(exp -1/2), the responsivity is less than or equal to 100 AW(exp -1)(f = 10 Hz). The second device was a 10x50 array including a cold readout electronics of switched FETs (SWIFET). Measurements of this array were done in a background range of 5 x 10(exp 5) to 5 x 10(exp 11) Ph s(exp-1)cm(exp-2) and at operating temperatures between 3.0 and 4.8 K. The NEP ranges from less than 10(exp -18) at the lowest background to 2 x 10(exp -16) WHz(exp -1/2) at the highest flux.

Inter-annual variation of carbon uptake by a plantation oak woodland in south-eastern England

NASA Astrophysics Data System (ADS)

Wilkinson, M.; Eaton, E. L.; Broadmeadow, M. S. J.; Morison, J. I. L.

2012-07-01

The carbon balance of an 80 yr old deciduous oak plantation in the temperate oceanic climate of the south-east of Britain was measured by eddy covariance over 12 yr (1999-2010). The mean annual net ecosystem productivity (NEP) was 486 g C m-2 y-1 (95% CI of ±73 g C m-2 y-1), and this was partitioned into a Gross Primary Productivity (GPP) of 2034 ± 145 g C m-2 y-1, over a 165 (±6) day growing season, and an annual loss of carbon through respiration and decomposition (ecosystem respiration, Reco) of 1548 ± 122 g C m-2 y-1. The interannual variation of NEP was large (coefficient of variation (CV) 23%), although the variation for GPP and Reco was smaller (12%) and the ratio of Reco/GPP was relatively constant (0.76 ± 0.02 CI). Some anomalies in the annual patterns of the carbon balance could be linked to particular combinations of anomalous weather events, such as high summer air temperature and low soil moisture content. The Europe-wide heat-wave and drought of 2003 had little effect on the C balance of this woodland on a surface water gley soil. Annual variation in precipitation (CV 18%) was not a main factor in the variation in NEP. The inter-annual variation in estimated intercepted radiation only accounted for ~ 47% of the variation in GPP, although a significant relationship (p<0.001) was found between peak leaf area index and annual GPP which in turn played an important role in modifying the efficiency with which incident radiation was used in net CO2 uptake. Whilst the spring start and late autumn end of the net CO2 uptake period varied substantially (range of 24 and 27 days, respectively), annual GPP was not related to growing season length. Severe outbreaks of defoliating moth caterpillars, mostly Tortrix viridana L. and Operophtera brumata L., caused considerable damage to the forest canopy in 2009 and 2010, resulting in reduced GPP in these years.

Conceptual definition of a 50-100 kWe NEP system for planetary science missions

NASA Technical Reports Server (NTRS)

Friedlander, Alan

1993-01-01

The Phase 1 objective of this project is to assess the applicability of a common Nuclear Electric Propulsion (NEP) flight system of the 50-100 kWe power class to meet the advanced transportation requirements of a suite of planetary science (robotic) missions, accounting for differences in mission-specific payloads and delivery requirements. The candidate missions are as follows: (1) Comet Nucleus Sample Return; (2) Multiple Mainbelt Asteroid Rendezvous; (3) Jupiter Grand Tour (Galilean satellites and magnetosphere); (4) Uranus Orbiter/Probe (atmospheric entry and landers); (5) Neptune Orbiter/Probe (atmospheric entry and landers); and (6) Pluto-Charon Orbiter/Lander. The discussion is presented in vugraph form.

Atlas of nonindigenous marine and estuarine species in the North Pacific

USGS Publications Warehouse

Lee,; Reusser, Deborah A.

2012-01-01

In terms of how the NIS were transported, hull fouling was potentially the most important vector in the NEP, NWP, and Hawaii, with ballast water discharges the second most important in all three regions. Intentional stocking and aquaculture escapees were relatively more important in the NWP than the NEP or Hawaii, reflecting the extensive aquaculture in Asia. Aquaculture associated species (i.e., aquaculture hitchhikers) was relatively important in the NEP, reflecting the historical influx of invaders with the importation of Atlantic and Pacific oysters. 

Messenger RNA-based therapeutics for brain diseases: An animal study for augmenting clearance of beta-amyloid by intracerebral administration of neprilysin mRNA loaded in polyplex nanomicelles.

PubMed

Lin, Chin-Yu; Perche, Federico; Ikegami, Masaru; Uchida, Satoshi; Kataoka, Kazunori; Itaka, Keiji

2016-08-10

Alzheimer's disease (AD) pathogenesis is considered to be the metabolic imbalance between anabolism and clearance of amyloid-beta (Aβ), and the strategy of breaking the equilibrium between soluble and insoluble forms of Aβ is likely to help prevent the progression of AD. Neprilysin (NEP) plays a major role in the clearance of Aβ in the brain, and its supplementation using viral vectors has shown to decrease Aβ deposition and prevent pathogenic changes in the brain. In this study, we developed a new therapeutic strategy by mRNA-based gene introduction. mRNA has the advantages of negligible risk of random integration into genome and not needing to be transcribed precludes the need for nuclear entry. This allows efficient protein expression in slowly-dividing or non-dividing cells, such as neural cells. We constructed mRNA encoding the mouse NEP protein and evaluated its ability degrade Aβ. In vitro transfection of NEP mRNA to primary neurons exhibited Amyloid Precursor Protein (APP) degradation activity superior to that of NEP encoding plasmid DNA. We then evaluated the in vivo activity of NEP mRNA by intracerebroventricular (i.c.v.) infusion using a cationic polymer-based PEGylated nanocarrier to form polyplex nanomicelles, which have been shown to have a high potential to deliver mRNA to various target tissues and organs. Nanomicelles carrying a GFP-NEP fusion mRNA produced efficient protein expression in a diffuse manner surrounding the ventricular space. An ELISA evaluation revealed that the mRNA infusion significantly augmented NEP level and effectively reduced the concentration of Aβ that had been supplemented in the mouse brain. To the best of our knowledge, this is the first study to demonstrate the therapeutic potential of introducing exogenous mRNA for the treatment of brain diseases, opening the new era of mRNA-based therapeutics. Copyright © 2016 Elsevier B.V. All rights reserved.

In Situ Boundary Layer Coral Metabolism in the Atlantic Ocean Acidification Test Bed

NASA Astrophysics Data System (ADS)

McGillis, Wade

2013-04-01

and Chris Langdon, Brice Loose, Dwight Gledhill, Diana Hsueh, Derek Manzello, Ian Enochs, Ryan Moyer We present net ecosystem productivity (nep) and net ecosystem calcification (nec) in coral and seagrass ecosystems using the boundary layer gradient flux technique (CROSS). Coastal anthropogenic inputs and changes in global ocean chemistry in response to rising levels of atmospheric carbon dioxide has emerged in recent years as a topic of considerable concern. Coral reefs are particularly vulnerable from eroded environmental conditions including ocean acidification and water pollution. The Atlantic Ocean Acidification Testbed (AOAT) project monitors metabolism to ascertain the continuing health of coral reef ecosystems. The CROSS boundary layer nep/nec approach is one component of this diagnostic program. Certification of CROSS as an operational monitoring tool is underway in the AOAT. CROSS inspects a benthic community and measures productivity/respiration and calcification/dissolution over an area of 10 square meters. Being a boundary layer tool, advection and complex mesoscale flows are not a factor or concern and CROSS is autonomous and can be used at deep benthic sites. The interrogation area is not enclosed therefore exposed to ambient light, flow, and nutrient levels. CROSS is easy to deploy, unambiguous, and affordable. Repeated measurements have been made from 2011-2012 in reefal systems in La Parguera Puerto Rico and the Florida Keys, USA. Diurnal, seasonal and regional metabolism will be compared and discussed. The ability to accurately probe benthic ecosystems provides a powerful management and research tool to policy makers and researchers.

Attenuation of tachykinin-induced airflow obstruction and microvascular leakage in immature airways.

PubMed Central

Tokuyama, K.; Yokoyama, T.; Morikawa, A.; Mochizuki, H.; Kuroume, T.; Barnes, P. J.

1993-01-01

1. To study the effect of maturation on substance P (SP)- and neurokinin A (NKA)-induced airflow obstruction and airway microvascular leakage (MVL), we have measured changes in both lung resistance (RL) and extravasation of Evans blue dye in anaesthetized immature (aged 14 +/- 1 days) and adult guinea-pigs (aged 80 +/- 3 days). 2. RL and its recovery after hyperinflation at 5 min were measured for 6 min after i.v. SP (0.2, 1 and 30 nmol kg-1), NKA (1 and 10 nmol kg-1) or vehicle (0.9% NaCl). After measurement of RL, MVL in trachea, main bronchi and intrapulmonary airways was also examined. 3. The order of potency in inducing airflow obstruction did not change with age (NKA > SP) but immature animals required a larger dose of SP or NKA than adults to cause a significant increase in RL. 4. The order of potency in inducing airway microvascular leakage was SP > NKA in both immature and adult animals. The amount of extravasated dye after SP was significantly less in immature airways, especially in central airways. 5. Phosphoramidon (2.5 mg kg-1), a neutral endopeptidase (NEP) inhibitor, significantly increased RL after 0.2 nmol kg-1 SP only in adult airways. Phosphoramidon enhanced the dye extravasation after 0.2 nmol kg-1 SP in both immature and adult airways with a significantly greater amount of dye in adult animals, suggesting that mechanisms other than changes in NEP activity may be responsible for this age-related difference.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7679033

A Network Enabled Platform for Canadian Space Science Data

NASA Astrophysics Data System (ADS)

Rankin, R.; Boteler, D. R.; Jayachandran, T. P.; Mann, I. R.; Sofko, G.; Yau, A. W.

2008-12-01

The internet is an example of a pervasive disruptive technology that has transformed society on a global scale. The term "cyberinfrastructure" refers to technology underpinning the collaborative aspect of large science projects and is synonymous with terms such as e-Science, intelligent infrastructure, and/or e- infrastructure. In the context of space science, a significant challenge is to exploit the internet and cyberinfrastructure to form effective virtual organizations (VOs) of scientists that have common or agreed- upon objectives. A typical VO is likely to include universities and government agencies specializing in types of instrumentation (ground and/or space based), which in deployment produce large quantities of space data. Such data is most effectively described by metadata, which if defined in a standard way, facilitates discovery and retrieval of data over the internet by intelligent interfaces and cyberinfrastructure. One recent and significant approach is SPASE, which is being developed by NASA as a data-standard for its Virtual Observatories (VxOs) programs. The space science community in Canada has recently formed a VO designed to complement the e-POP microsatellite mission, and new ground-based observatories (GBOs) that collect data over a large fraction of the Canadian land-mass. The VO includes members of the CGSM community (www.cgsm.ca), which is funded operationally by the Canadian Space Agency. It also includes the UCLA VMO team, and scientists in the NASA THEMIS mission. CANARIE (www.canarie.ca), the federal agency responsible for management, design and operation of Canada's research internet, has recently recognized the value of cyberinfrastucture through the creation of a Network-Enabled-Platforms (NEPs) program. An NEP for space science was funded by CANARIE in its first competition. When fully implemented, the Space Science NEP will consist of a front-end portal providing access to CGSM data. It will utilize an adaptation of the SPASE-based registry developed by Ray Walker et. al at UCLA, along with a common set of services and federation of CGSM data. An important aspect of the space science NEP is the development of scientific workflows that allow users to more easily develop data analysis tools that can be stored on their desktop for re-use. The presentation will include a high-level view of the methodology and software architecture to be implemented through the development of the CANARIE NEP for space science.

Endorsement of the New Ecological Paradigm in Systematic and E-Mail Samples of College Students

ERIC Educational Resources Information Center

Rideout, Bruce E.; Hushen, Katherine; McGinty, Dawn; Perkins, Stephanie; Tate, Jennifer

2005-01-01

As the initial phase of a longitudinal study of environmental perspective in college students, resident student opinion was sampled using the New Ecological Paradigm (NEP) scale administered through systematic alphabetical sampling. Sampling was also carried out by a blanket e-mail distribution of surveys for voluntary response. Results showed…

Determination of 20Ne(p ,γ )21Na cross sections from Ep=500 -2000 keV

NASA Astrophysics Data System (ADS)

Lyons, S.; Görres, J.; deBoer, R. J.; Stech, E.; Chen, Y.; Gilardy, G.; Liu, Q.; Long, A. M.; Moran, M.; Robertson, D.; Seymour, C.; Vande Kolk, B.; Wiescher, M.; Best, A.

2018-06-01

Background: The reaction 20Ne(p ,γ )21Na influences the nucleosynthesis of Ne, Na, and Mg isotopes while contributing to hydrogen burning in several stellar sites, such as red giants, asymptotic giant branch (AGB) stars, massive stars, and oxygen-neon (ONe) novae. In the relevant temperature range for these environments (T = 0.05-0.5 GK), the main contributions to this reaction rate are from the direct capture process as well as the high-energy tail of a subthreshold resonance in the ground-state transition at Ex = 2425 keV in the 21Na compound nucleus. Purpose: The previous measurement of this reaction reports cross sections with large uncertainties for the ground-state transition. At higher energies, where the subthreshold resonance makes a smaller contribution to the total cross section, only upper limits are provided. This work aims to reduce the uncertainty in the cross section where direct capture dominates, as well as provide cross-section data in previously unmeasured regions. Method: The 20Ne(p ,γ )21Na reaction was measured over a wide proton energy range (Ep = 0.5-2.0 MeV) at θlab = 90∘. Transitions to the ground state and to the 332 and 2425 keV excited states were observed. The primary transitions to these three bound states were utilized in an R -matrix analysis to determine the contributions of the direct capture and the subthreshold resonance to the total cross section. Results: The cross sections of the present measurements have been found to be in good agreement with the previous data at low energy. Significantly improved cross-section measurements have been obtained over the Ep = 1300-1900 keV region. The narrow resonance at Ec.m. = 1113 keV (Ex = 3544.3 keV) has also been remeasured and its strength has been found to be in good agreement with previous measurements. Conclusions: An extrapolation of the S factor of 20Ne(p ,γ )21Na has been made to low energies using the R -matrix fit. The reaction rate from the subthreshold resonance was found to be the main contributor to the reaction rate at temperatures below about 0.1 GK. The present rate is lower in the temperature range of interest than those presented in current reaction rate libraries by up to 20%.

Opiorphin causes a panicolytic-like effect in rat panic models mediated by μ-opioid receptors in the dorsal periaqueductal gray.

PubMed

Maraschin, Jhonatan Christian; Rangel, Marcel Pereira; Bonfim, Antonio Joaquim; Kitayama, Mariana; Graeff, Frederico Guilherme; Zangrossi, Hélio; Audi, Elisabeth Aparecida

2016-02-01

Reported evidence indicates that endogenous opioid peptides regulate the expression of escape behavior in rats, a panic-related defensive response, through μ-opioid receptors (MORs) in the dorsal periaqueductal gray (dPAG). These peptides are rapidly catabolized by degrading enzymes, including neutral endopeptidase (NEP) and aminopeptidase N (APN). Opiorphin is a peptide inhibitor of both NEP and APN and potentiates the action of endogenous enkephalins. This study evaluated the effects of intravenous and intra-dPAG administration of opiorphin on escape responses in the elevated T-maze and in a dPAG electrical stimulation test in rats. We also evaluated the involvement of MORs in the effects of opiorphin using the selective MOR antagonist CTOP. A dose of 2.0 mg/kg, i.v., of opiorphin impaired escape performance in both tests. Similar effects were observed with intra-dPAG administration of 5.0 nmol of opiorphin. Local pretreatment with 1.0 nmol CTOP antagonized the anti-escape effects of intra-dPAG opiorphin in both tests, as well as the effect of systemically administered opiorphin (2.0 mg/kg, i.v.) in the electrical stimulation test. These results indicate that opiorphin has an antipanic-like effect that is mediated by MORs in the dPAG. They may open new perspectives for the development of opiorphin analogues with greater bioavailability and physicochemical characteristics in the pursuit of new medications for the treatment of panic disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phonon Recycling for Ultrasensitive Kinetic Inductance Detectors

NASA Astrophysics Data System (ADS)

Zmuidzinas, Jonas

Initially proposed (Day et al. 2003; Zmuidzinas 2012) in 1999 by our Caltech/JPL group, and thanks to strong support from NASA, the superconducting (microwave) kinetic inductance detector (MKID or KID) technology continues to develop rapidly as it transitions into applications. The development effort worldwide is intensifying and NASA's continued support of KID development is essential in order to keep pace. Here we propose to investigate and demonstrate a new, low-TRL concept, which we call phonon recycling, that promises to open broad new avenues in KID design and performance. Briefly, phonon recycling allows the detector designer to tailor the responsivity and sensitivity of a KID to match the needs of the application by using geometry to restrict the rate at which recombination phonons are allowed to escape from the detector. In particular, phonon recycling should allow very low noise-equivalent power (NEP) to be achieved without requiring very low operating tem- peratures. Phonon recycling is analogous to the use of micromachined suspension legs to control the flow of heat in a bolometer, as measured by the thermal conductivity G. However, phonon recycling exploits the non-thermal distribution of recombination phonons as well as their very slow decay in crystals at low temperatures. These properties translate to geometrical and mechanical requirements for a phonon-recycled KID that are considerably more relaxed than for a bolometer operating at the same temperature and NEP. Our ultimate goal is to develop detector arrays suitable for a far-infrared (FIR) space mission, which will impose strict requirements on the array sensitivity, yield, uniformity, multiplexing density, etc. Through previous NASA support under the Strategic Astrophysics Technology (SAT) program, we have successfully demonstrated the MAKO submillimeter camera at the Caltech Submillimeter Observatory and have become familiar with these practical issues. If our demonstration of phonon recycling is successful, we will have a path for continuously adapting the high-background, high-NEP detectors we have demonstrated on the ground to the ultralow-NEP detectors needed for space.

Patterns of NPP, GPP, Respiration and NEP During Boreal Forest Succession

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goulden, Michael L.; McMillan, Andrew; Winston, Greg

2010-12-15

We deployed a mesonet of year-round eddy covariance towers in boreal forest stands that last burned in ~1850, ~1930, 1964, 1981, 1989, 1998, and 2003 to understand how CO2 exchange changes during secondary succession.The strategy of using multiple methods, including biometry and micrometeorology, worked well. In particular, the three independent measures of NEP during succession gave similar results. A stratified and tiered approach to deploying eddy covariance systems that combines many lightweight and portable towers with a few permanent ones is likely to maximize the science return for a fixed investment. The existing conceptual models did a good job ofmore » capturing the dominant patterns of NPP, GPP, Respiration and NEP during succession. The initial loss of carbon following disturbance was neither as protracted nor large as predicted. This muted response reflects both the rapid regrowth of vegetation following fire and the prevalence of standing coarse woody debris following the fire, which is thought to decay slowly. In general, the patterns of forest recovery from disturbance should be expected to vary as a function of climate, ecosystem type and disturbance type. The NPP decline at the older stands appears related to increased Rauto rather than decreased GPP. The increase in Rauto in the older stands does not appear to be caused by accelerated maintenance respiration with increased biomass, and more likely involves increased allocation to fine root turnover, root metabolism, alternative forms of respiration, mycorrhizal relationships, or root exudates, possibly associated with progressive nutrient limitation. Several studies have now described a similar pattern of NEP following boreal fire, with 10-to-15 years of modest carbon loss followed by 50-to-100 years of modest carbon gain. This trend has been sufficiently replicated and evaluated using independent techniques that it can be used to quantify the likely effects of changes in boreal fire frequency and stand age structure on regional carbon balance.« less

Peptidase modulation of vasoactive intestinal peptide pulmonary relaxation in tracheal superfused guinea pig lungs.

PubMed Central

Lilly, C M; Martins, M A; Drazen, J M

1993-01-01

The effects of enzyme inhibitors on vasoactive intestinal peptide (VIP)-induced decreases in airway opening pressure (PaO) and VIP-like immunoreactivity (VIP-LI) recovery were studied in isolated tracheal superfused guinea pig lungs. In the absence of inhibitors, VIP 0.38 (95% CI 0.33-0.54) nmol/kg animal, resulted in a 50% decrease in PaO and 33% of a 1 nmol/kg VIP dose was recovered as intact VIP. In the presence of two combinations of enzyme inhibitors, SCH 32615 (S, 10 microM) and aprotinin (A, 500 tyrpsin inhibitor units [TIU]/kg) or S and soybean trypsin inhibitor (T, 500 TIU/kg), VIP caused a significantly greater decrease in PaO and greater quantities of VIP were recovered from lung effluent (both P < 0.001). The addition of captopril, (3 microM), leupeptin (4 microM), or bestatin (1 microM) failed to further increase pulmonary relaxation or recovery of VIP-LI. When given singly, A, T, and S did not augment the effects or recovery of VIP. The efficacy of S (a specific inhibitor of neutral endopeptidase [NEP]) and A and T (serine protease inhibitors) thus implicated NEP and at least one serine protease as primary modulators of VIP activity in the guinea pig lung. We sought to corroborate this finding by characterizing the predominant amino acid sites at which VIP is hydrolized in the lung. When [mono(125I)iodo-Tyr10]VIP was offered to the lung, in the presence and absence of the active inhibitors, cleavage products consistent with activity by NEP and a tryptic enzyme were recovered. These data demonstrate that NEP and a peptidase with an inhibitor profile and cleavage pattern compatible with a tryptic enzyme inactivate VIP in a physiologically competitive manner. PMID:7678603

Development costs for a nuclear electric propulsion stage.

NASA Technical Reports Server (NTRS)

Mondt, J. F.; Prickett, W. Z.

1973-01-01

Development costs are presented for an unmanned nuclear electric propulsion (NEP) stage based upon a liquid metal cooled, in-core thermionic reactor. A total of 120 kWe are delivered to the thrust subsystem which employs mercury ion engines for electric propulsion. This study represents the most recent cost evaluation of the development of a reactor power system for a wide range of nuclear space power applications. These include geocentric, and outer planet and other deep space missions. The development program is described for the total NEP stage, based upon specific development programs for key NEP stage components and subsystems.

Substance P and neurokinin A metabolism by cultured human skeletal muscle myocytes and fibroblasts.

PubMed

Russell, J S; Chi, H; Lantry, L E; Stephens, R E; Ward, P E

1996-01-01

A recent study determined that cultured human skeletal muscle adult myoblasts, myotubes, and fibroblasts degraded angiotensins and kinins via neutral endopeptidase-24.11 (NEP-24.11: EC 3.4.24.11) and aminopeptidase N (APN: EC 3.4.11.2). Due to the possible importance of other peptides to skeletal muscle blood flow and function, the present study looked specifically at the metabolism of the neurokinins substance P (SP) and neurokinin A (NKA) by skeletal muscle peptidases. The results show that SP is degraded not only by NEP-24.11, but also sequentially by dipeptidyl(amino)peptidase IV (DAP IV: EC 3.4.14.5)/APN. NKA is unaffected by DAP IV but is metabolized by NEP-24.11 and APN. NEP-24.11 was inhibited by phosphoramidon (IC50 = 80 nM), thiorphan and ZINCOV, DAP IV by diprotin A (IC50 = 8 microM), and APN by amastatin (IC50 = 50 nM) and bestatin (IC50 = 100 microM). Skeletal muscle myocyte and fibroblast metabolism of SP and NKA may regulate local skeletal muscle vascular and extravascular functions including SP- and NKA-mediated nerve-induced vasodilation. Inhibition of both NEP-24.11 and DAP IV/APN may increase skeletal muscle blood flow and decrease peripheral vascular resistance via potentiation of local neurokinin levels.

Collaborative Potential between National Estuary Programs ...

EPA Pesticide Factsheets

Estuaries are among the most productive ecosystems in the world, providing unique habitat for freshwater and marine species as well as valuable social and economic benefits. The wealth of ecosystem goods and services from estuaries has led to growth and development of human communities in adjacent areas and an increase in human activities that can adversely affect water quality and critical habitat. Managing for sustainable estuaries requires a balance of environmental concerns with community social and economic values. This has created an opportunity to leverage Environmental Protection Agency (EPA) scientific knowledge and tools with National Estuary Program (NEP) planning and management expertise to address environmental challenges in important estuarine ecosystems. The non-regulatory National Estuary Program (NEP) was outlined in the Clean Water Act to provide stakeholders an opportunity to monitor and manage ‘nationally significant’ estuaries. Currently there are 28 estuaries in the NEP, broadly distributed across the Atlantic, Pacific and Gulf Coasts, and in Puerto Rico. The local NEP management conferences must address a variety of environmental issues, from water quality and natural resources to coastal and watershed development. While the underlying objectives of each NEP are quite similar, each has unique landscapes, land uses, waterbodies, habitats, biological resources, economies and social culture. Consequently, the effects and severity of anthr

Introduction to Northeast Pacific Shark Biology, Research, and Conservation, Part B.

PubMed

Larson, Shawn E; Lowry, Dayv

Sharks are iconic, sometimes apex, predators found in every ocean. Because of their ecological role as predators and concern over the stability of their populations, there has been an increasing amount of work focused on shark conservation around the world in recent decades. The populations of sharks that reside in the Northeast Pacific (NEP) Ocean bordering the west coast of the United States reside in one of the most economically and ecologically important oceanic regions in the world. Volume 78 of Advances in Marine Biology (AMB) is a companion to Volume 77, which focused primarily on NEP shark biodiversity, organismal biology, and ecology. Volume 78 highlights fisheries and the conservation implications of fisheries management; shark population modelling and the conservation impacts of these models given that many life history metrics of NEP sharks necessary to accurately run these models are still unknown; the value of captive sharks to the biology, outreach, and conservation of NEP sharks; and the conservation value of citizen science and shark ecotourism. Together these volumes encapsulate the current state of the knowledge for sharks in the NEP and lay the foundation for protecting, managing, and learning from these species in the face evolving natural conditions and societal opinions. © 2017 Elsevier Ltd All rights reserved.

Pharmacokinetics of erythropoietin in intact and anephric dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, J.S.; Lertora, J.J.; Brookins, J.

1988-06-01

The present studies were performed to determine the pharmacokinetic parameters of erythropoietin in intact and anephric dogs by use of unlabeled crude native erythropoietin (nEp) and iodine 125-labeled purified recombinant erythropoietin (rEp) given by intravenous infusion for 15 minutes. Sephadex G-75 gel filtration was used to confirm that the 125I-rEp molecule remained iodinated in dog plasma during the 24-hour period of these studies. The plasma disappearance of erythropoietin conformed to a biexponential equation for both nEp and 125I-rEp, with the central compartment being larger than the peripheral compartment. The mean distribution half-life of 75.3 +/- 21.2 minutes for nEp wasmore » significantly (p less than 0.05) longer than that of 125I-rEp (23.7 +/- 5.0 minutes) in intact dogs. The intercompartmental clearance (CIic) for nEp (0.018 +/- 0.006 L/kg/hr) was significantly smaller than that of 125I-rEp (0.068 +/- 0.018 L/kg/hr) in intact dogs (p less than 0.05). There were no significant differences in apparent volume of distribution, elimination half-life, and elimination clearance (CIe) for nEp and rEp in intact dogs. The mean elimination half-life for 125I-rEp in intact dogs (9.0 +/- 0.6 hours) and anephric dogs (13.8 +/- 1.4 hours) was significantly different (p less than 0.05). The CIe for 125I-rEp in anephric dogs (0.008 +/- 0.001 L/kg/hr) was significantly (p less than 0.05) smaller than that of 125I-rEp in intact dogs (0.011 +/- 0.001 L/kg/hr). There were no significant differences in apparent volume of distribution, distribution half-life, and CIic for 125I-rEp in intact and anephric dogs.« less

New Anti-Nephrin Antibody Mediated Podocyte Injury Model Using a C57BL/6 Mouse Strain.

PubMed

Takeuchi, Kazuhiro; Naito, Shokichi; Kawashima, Nagako; Ishigaki, Naoko; Sano, Takashi; Kamata, Kouju; Takeuchi, Yasuo

2018-01-01

Focal segmental glomerulosclerosis (FSGS) is considered a subset of the podocytopathies. The molecular pathogenesis of podocytopathy is still unknown. There has not been an experimental animal model of isolated podocytopathy induced by antibody in C57BL/6 strain, which is widely used as the genetic background. Nephrin is closely associated with the slit diaphragm of the glomerular podocyte, and has recently received attention as a potential therapeutic target. The function of nephrin, especially its role in FSGS development via podocytopathy, is being elucidated. We report our experience with a C57BL/6 FSGS model induced by polyclonal rabbit anti-mouse nephrin antibody (α-mNep Ab). α-mNep Ab, which was generated by genetic immunization, was administered into C57BL/6 mice at once, intravenously. Urinary protein excretion, the development of glomerulosclerosis and the number of podocyte in mouse kidney were evaluated. The α-mNep Ab-induced FSGS was associated with massive proteinuria and nephrotic syndrome. In periodic acid-Schiff staining, FSGS was observed from day 7 after antibody injection. Podocyte numbers and podocyte marker (anti-Wilms tumor 1 and anti-synaptopodin)-positive areas were clearly decreased. These results suggest that this FSGS mouse model reliably reproduces the human nephrotic syndrome and FSGS. We succeeded in making the nephrotic syndrome model mice induced by α-mNep Ab using C57BL/6. This model may be useful for studying the mechanisms of podocytopathy. © 2017 S. Karger AG, Basel.

The 2-24 μm source counts from the AKARI North Ecliptic Pole survey

NASA Astrophysics Data System (ADS)

Murata, K.; Pearson, C. P.; Goto, T.; Kim, S. J.; Matsuhara, H.; Wada, T.

2014-11-01

We present herein galaxy number counts of the nine bands in the 2-24 μm range on the basis of the AKARI North Ecliptic Pole (NEP) surveys. The number counts are derived from NEP-deep and NEP-wide surveys, which cover areas of 0.5 and 5.8 deg2, respectively. To produce reliable number counts, the sources were extracted from recently updated images. Completeness and difference between observed and intrinsic magnitudes were corrected by Monte Carlo simulation. Stellar counts were subtracted by using the stellar fraction estimated from optical data. The resultant source counts are given down to the 80 per cent completeness limit; 0.18, 0.16, 0.10, 0.05, 0.06, 0.10, 0.15, 0.16 and 0.44 mJy in the 2.4, 3.2, 4.1, 7, 9, 11, 15, 18 and 24 μm bands, respectively. On the bright side of all bands, the count distribution is flat, consistent with the Euclidean universe, while on the faint side, the counts deviate, suggesting that the galaxy population of the distant universe is evolving. These results are generally consistent with previous galaxy counts in similar wavebands. We also compare our counts with evolutionary models and find them in good agreement. By integrating the models down to the 80 per cent completeness limits, we calculate that the AKARI NEP survey revolves 20-50 per cent of the cosmic infrared background, depending on the wavebands.

Co-culture of oligodendrocytes and neurons can be used to assess drugs for axon regeneration in the central nervous system

PubMed Central

Gang, Lin; Yao, Yu-chen; Liu, Ying-fu; Li, Yi-peng; Yang, Kai; Lu, Lei; Cheng, Yuan-chi; Chen, Xu-yi; Tu, Yue

2015-01-01

We present a novel in vitro model in which to investigate the efficacy of experimental drugs for the promotion of axon regeneration in the central nervous system. We co-cultured rat hippocampal neurons and cerebral cortical oligodendrocytes, and tested the co-culture system using a Nogo-66 receptor antagonist peptide (NEP1–40), which promotes axonal growth. Primary cultured oligodendrocytes suppressed axonal growth in the rat hippocampus, but NEP1–40 stimulated axonal growth in the co-culture system. Our results confirm the validity of the neuron-oligodendrocyte co-culture system as an assay for the evaluation of drugs for axon regeneration in the central nervous system. PMID:26692858

Spatially explicit simulation of hydrologically controlled carbon and nitrogen cycles and associated feedback mechanisms in a boreal ecosystem

NASA Astrophysics Data System (ADS)

Govind, Ajit; Chen, Jing Ming; Ju, Weimin

2009-06-01

Ecosystem models that simulate biogeochemical processes usually ignore hydrological controls that govern them. It is quite possible that topographically driven water fluxes significantly influence the spatial distribution of C sources and sinks because of their large contribution to the local water balance. To investigate this, we simulated biogeochemical processes along with the associated feedback mechanisms in a boreal ecosystem using a spatially explicit hydroecological model, boreal ecosystem productivity simulator (BEPS)-TerrainLab V2.0, that has a tight coupling of ecophysiological, hydrological, and biogeochemical processes. First, the simulated dynamics of snowpack, soil temperature, net ecosystem productivity (NEP), and total ecosystem respiration (TER) were validated with high-frequency measurements for 2 years. The model was able to explain 80% of the variability in NEP and 84% of the variability in TER. Further, we investigated the influence of topographically driven subsurface base flow on soil C and N cycling and on the spatiotemporal patterns of C sources and sinks using three hydrological modeling scenarios that differed in hydrological conceptualizations. In general, the scenarios that had nonexplicit hydrological representation overestimated NEP, as opposed to the scenario that had an explicit (realistic) representation. The key processes controlling the NEP differences were attributed to the combined effects of variations in photosynthesis (due to changes in stomatal conductance and nitrogen (N) availability), heterotrophic respiration, and autotrophic respiration, all of which occur simultaneously affecting NEP. Feedback relationships were also found to exacerbate the differences. We identified six types of NEP differences (biases), of which the most commonly found was due to an underestimation of the existing C sources, highlighting the vulnerability of regional-scale ecosystem models that ignore hydrological processes.

Whole-system carbon balance for a regional temperate forest in Northern Wisconsin, USA

NASA Astrophysics Data System (ADS)

Peckham, S. D.; Gower, S. T.

2010-12-01

The whole-system (biological + industrial) carbon (C) balance was estimated for the Chequamegon-Nicolet National Forest (CNNF), a temperate forest covering 600,000 ha in Northern Wisconsin, USA. The biological system was modeled using a spatially-explicit version of the ecosystem process model Biome-BGC. The industrial system was modeled using life cycle inventory (LCI) models for wood and paper products. Biome-BGC was used to estimate net primary production, net ecosystem production (NEP), and timber harvest (H) over the entire CNNF. The industrial carbon budget (Ci) was estimated by applying LCI models of CO2 emissions resulting from timber harvest and production of specific wood and paper products in the CNNF region. In 2009, simulated NEP of the CNNF averaged 3.0 tC/ha and H averaged 0.1 tC/ha. Despite model uncertainty, the CNNF region is likely a carbon sink (NEP - Ci > 0), even when CO2 emissions from timber harvest and production of wood and paper products are included in the calculation of the entire forest system C budget.

New Ecological Paradigm and Sustainability Attitudes with Respect to a Multi-Cultural Educational Milieu in China

ERIC Educational Resources Information Center

Wells, Mona; Petherick, Lynda

2016-01-01

Institutions of higher education are increasingly interested in how the student experience may or may not influence world views and particularly with respect to sustainability. Here we report preliminary results from a New Ecological Paradigm (NEP) study in China to benchmark student responses, and we relate these results to findings from other…

Aβ degradation or cerebral perfusion? Divergent effects of multifunctional enzymes.

PubMed

Miners, J Scott; Palmer, Jennifer C; Tayler, Hannah; Palmer, Laura E; Ashby, Emma; Kehoe, Patrick G; Love, Seth

2014-01-01

There is increasing evidence that deficient clearance of β-amyloid (Aβ) contributes to its accumulation in late-onset Alzheimer disease (AD). Several Aβ-degrading enzymes, including neprilysin (NEP), endothelin-converting enzyme (ECE), and angiotensin-converting enzyme (ACE) reduce Aβ levels and protect against cognitive impairment in mouse models of AD. In post-mortem human brain tissue we have found that the activity of these Aβ-degrading enzymes rise with age and increases still further in AD, perhaps as a physiological response that helps to minimize the build-up of Aβ. ECE-1/-2 and ACE are also rate-limiting enzymes in the production of endothelin-1 (ET-1) and angiotensin II (Ang II), two potent vasoconstrictors, increases in the levels of which are likely to contribute to reduced blood flow in AD. This review considers the possible interdependence between Aβ-degrading enzymes, ischemia and Aβ in AD: ischemia has been shown to increase Aβ production both in vitro and in vivo, whereas increased Aβ probably enhances ischemia by vasoconstriction, mediated at least in part by increased ECE and ACE activity. In contrast, NEP activity may help to maintain cerebral perfusion, by reducing the accumulation of Aβ in cerebral blood vessels and lessening its toxicity to vascular smooth muscle cells. In assessing the role of Aβ-degrading proteases in the pathogenesis of AD and, particularly, their potential as therapeutic agents, it is important to bear in mind the multifunctional nature of these enzymes and to consider their effects on other substrates and pathways.

`Human nature': Chemical engineering students' ideas about human relationships with the natural world

NASA Astrophysics Data System (ADS)

Goldman, Daphne; Ben-Zvi Assaraf, Orit; Shemesh, Julia

2014-05-01

While importance of environmental ethics, as a component of sustainable development, in preparing engineers is widely acknowledged, little research has addressed chemical engineers' environmental concerns. This study aimed to address this void by exploring chemical engineering students' values regarding human-nature relationships. The study was conducted with 247 3rd-4th year chemical engineering students in Israeli Universities. It employed the New Ecological Paradigm (NEP)-questionnaire to which students added written explanations. Quantitative analysis of NEP-scale results shows that the students demonstrated moderately ecocentric orientation. Explanations to the NEP-items reveal diverse, ambivalent ideas regarding the notions embodied in the NEP, strong scientific orientation and reliance on technology for addressing environmental challenges. Endorsing sustainability implies that today's engineers be equipped with an ecological perspective. The capacity of Higher Education to enable engineers to develop dispositions about human-nature interrelationships requires adaptation of curricula towards multidisciplinary, integrative learning addressing social-political-economic-ethical perspectives, and implementing critical-thinking within the socio-scientific issues pedagogical approach.

Effects of the calcium ionophore A23187 on airway responsiveness to histamine and substance P in guinea pigs.

PubMed

Uno, D; Tsukagoshi, H; Hisada, T; Iwamae, S; Mori, M

1997-03-01

We evaluated the mechanism of the airway hyperresponsiveness (AHR) induced by a calcium ionophore in guinea pigs. Airway responsiveness to intravenous histamine (HS) and substance P (SP) was measured 24 h after a 1-h exposure to aerosolized A23187 (0.03 or 0.1 mg/ml) or its vehicle (10% DMSO). Changes were assessed by calculating -logPC350HS and logPC350SP. Neutral endopeptidase (NEP) activity in the airway tissues, as well as the nitrite (NO2) levels and the cell population in bronchoalveolar lavage fluid (BALF) was determined after measurement of pulmonary function. Changes in SP-induced vascular permeability 24 h after exposure to A23187 were measured by the Evans Blue dye extravasation technique. Exposure to A23187 caused a significant AHR to SP, along with a significant increase in the number of neutrophils and epithelial cells in the BALF. While there was no significant change in NEP activity in the airway tissues, the levels of nitrite in the BALF were significantly decreased in A23187-exposed animals. Significant correlations were found between the number of epithelial cells in the BALF and logPC350SP (r = 0.477, p < 0.05) and between nitrite levels in the BALF and -logPC350SP (r = 0.491, p < 0.05) A23187 exposure did not significantly change the SP-induced airway microvascular leakage. These data suggest that A23187 exposure induced AHR to SP possibly by reducing NO levels in the airway tissues. This may be due to damaged airway epithelium and/or NO breakdown by activated inflammatory cells in the airways of these guinea pigs.

Thermionic reactor ion propulsion system /TRIPS/ - Its multi-mission capability.

NASA Technical Reports Server (NTRS)

Peelgren, M. L.

1972-01-01

The unmanned planetary exploration to be conducted in the last two decades of this century includes many higher energy missions which tax all presently available propulsion systems beyond their limit. One candidate with the versatility and performance to meet these mission objectives is nuclear electric propulsion (NEP). Additionally, the NEP System is feasible in orbit raising operations with the Shuttle or Shuttle/Tug combination. A representative planetary mission is described (Uranus-Neptune flyby with probe), and geocentric performance and tradeoffs are discussed. The NEP System is described in more detail with particular emphasis on the power subsystem consisting of the thermionic reactor, heat rejection subsystem, and neutron shield.

Carbon cycle dynamics within Oregon’s urban-suburban-forested-agricultural landscapes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Law, Beverly E.; Still, Christopher Jason; Schmidt, Andres

Our overarching goal was to develop and utilize an observation-based analysis framework to assess interactions between climate and mosaics of land use, land cover and urbanization on regional carbon, water, and energy dynamics, and potential changes associated with land management and climate. Carbon, water and energy cycling was quantified for the range of current and potential land uses under present and future climates. The study region of Oregon has a strong climatic gradient from the coastal mesic forests (2500mm ppt) to the Willamette Valley, Cascade Mountains, and the Northern Great Basin semi-arid “cold desert” to the east (300 mm). Themore » study was focused on the effects of (1) conversion of semi-arid sagebrush and Willamette Valley agricultural crops to bioenergy production; (2) afforestation of idle land and rangelands deemed suitable for forests or poplar crops under future climate conditions. We found that net ecosystem production (NEP), the net of ecosystem photosynthesis and respiration, was 10 times higher in the high biomass forests of the Coast Range compared with drier regions like sagebrush in the Northern Great Basin, which was nearly zero (Schmidt et al. 2016). The state total NEP averaged about 30 teragrams carbon (Tg C) per year for the years 2012 to 2014 using our model framework that we developed for predictions of current and future NEP, and compared well with our detailed inventory estimates (28 Tg C annual average for 2011-2015 for forests only; Law et al. 2017). Running our model framework until the year 2050, we found that climate alone only increased NEP by less than 1 Tg C per decade (~3%) using the current trajectory of carbon dioxide emissions, however, changes are expected to be more rapid in subsequent years. We evaluated the possibility of land use change from grass seed crops to poplar for bioenergy, which slightly increased NEP by 2050. The most important variable for carbon sequestration estimates (net carbon sources and sinks) is net ecosystem carbon balance (NECB), which accounts for NEP and losses associated with harvest removals and wildfire emissions. Here, we focus on forests because they have the largest effect on carbon sequestration. We found that NECB in Oregon averaged 18.8 Tg C per year in 2011-2015, offsetting fossil fuel emissions (16 Tg C per year). Annual fire emissions reducing NECB by about 5% (0.97 Tg C per year) in the state. The mesic Coast Range and West Cascades ecoregions that make up the western third of Oregon account for 60% of the forest NECB. This analysis illustrates that annual emissions from forests disturbances are low relative to annual fossil fuel emissions for the same area (Law et al. 2017, Hudiburg et al. in review).« less

Comparing the impact of the 2003 and 2010 heatwaves on Net Ecosystem Production in Europe

NASA Astrophysics Data System (ADS)

Bastos, A. F.; Gouveia, C. M.; Trigo, R. M.

2012-12-01

Climate variability is known to influence primary productivity on land ecosystems (Nemani et al., 2003). In particular, extreme climatic events such as major droughts and heatwaves are known to have severe impact on primary productivity and, therefore, to affect significantly the carbon dioxide uptake by land ecosystems at regional (Ciais et al., 2005) or even global scale (Zhao and Running, 2010). In the last decade, Europe was struck by two outstanding heatwaves, the 2003 event in Western Europe and the recent 2010 episode over Eastern Europe. Both were characterised by record breaking temperatures at the daily, weekly, monthly and seasonal scales, although the amplitude and spatial extent of the 2010 mega-heatwave surpassed the 2003 event (Barriopedro et al., 2011). This work aims to assess the influence of both mega-heatwaves on seasonal and yearly Net Ecosystem Production (NEP). The work relies on monthly NEP data derived from satellite imagery obtained from MODIS (Moderate Resolution Imaging Spectroradiometer) sensor at 1km spatial resolution. Data were selected for the period between 2000 and 2011 over a region extending from 34.6 oN to 73.5 oN and 12.1 oW to 46.8 oE, covering Eurasia. In 2010 very low NEP anomalies are observed over a very large area in Eastern Europe, at the monthly, seasonal and yearly scale. In western Russia, yearly NEP anomalies fall below 50% of average cumulative NEP. These widespread negative anomalous values of NEP fields over the western Russia region match the patterns of very high temperature values combined with below-average precipitation, at the seasonal (summer) scale. Moreover, the impact of the heatwave is not only evident at the regional level but also at the wider continental (European) scale and is significantly more extensive and intense than the corresponding heatwave of 2003 in Western Europe (Ciais et al., 2005). References: Barriopedro, D., E. M. Fischer, J. Luterbacher, R. M. Trigo, and R. Garcia-Herrera (2011), The hot summer of 2010: Redrawing the temperature record map of Europe, Science, 332 (6026), 220 224, doi:10.1126/science.1201224. Ciais, P., et al. (2005), Europe-wide reduction in primary productivity caused by the heat and drought in 2003, Nature, 437 (7058), 529-533. Nemani, R. R., C. D. Keeling, H. Hashimoto, W. M. Jolly, S. C. Piper, C. J. Tucker, R. B. Myneni, and S. W. Running (2003), Climate-driven increases in global terrestrial net primary production from 1982 to 1999, Science, 300 (5625), 156-1563, doi:10.1126/science.1082750. Zhao, M., and S. W. Running (2010), Drought-induced reduction in global terrestrial net primary production from 2000 through 2009, Science, 329 (5994), 940-943, doi:10.1126/science.1192666.

Reconciling carbon-cycle concepts, terminology, and methodology

Treesearch

F.S. III Chapin; G.M Woodwell; J.T. Randerson; G.M. Lovett; E.B. Rastetter; D.D. Baldocchi; D.A. Clark; M.E. Harmon; D.S. Schimel; Valentini R.; Wirth C.; Aber J.D.; Cole J.J.; Goulden M.L.; Harden J.W.; Heimann M.; Howarth R.W.; Matson P.A.; McGuire A.D.; Melillo J.M.; H.A. Mooney; J.C. Neff; R.A. Houghton; M.L. Pace; M.G. Ryan; S.W. Running; O.E. Sala; W.H. Schlesinger; E. D. Schulze

2005-01-01

Recent projections of climatic change have focused a great deal of scientific and public attention on patterns of carbon (C) cycling as well as its controls, particularly the factors that determine whether an ecosystem is a net source or sink of atmospheric carbon dioxide (CO2). Net ecosystem production (NEP), a central concept in C-cycling research, has been used by...

A Climate Ready Estuaries Vulnerability Assessment

EPA Science Inventory

The purpose of the the Climate Ready Estuaries program is to build capacity in the National Estuary Programs (NEPs) for local leadership and expertise to adapt to the effects of climate change through a joint effort with the NEPs and EPA.

Background

Identifying and organizing objectives across the 28 National Estuary Programs

EPA Science Inventory

The National Estuary Program (NEP), established in 1987 by amendments to the Clean Water Act, is intended to support local communities to restore, protect and manage estuaries of national significance. Currently there a 28 NEPs spread widely across the U.S. and its territories. E...

Role of the neutral endopeptidase 24.11 in the conversion of big endothelins in guinea-pig lung parenchyma.

PubMed Central

Lebel, N.; D'Orléans-Juste, P.; Fournier, A.; Sirois, P.

1996-01-01

1. We have studied the conversion of big endothelin-1 (big ET-1), big endothelin-2 (big ET-2) and big endothelin-3 (big ET-3) and characterized the enzyme involved in the conversion of the three peptides in guinea-pig lung parenchyma (GPLP). 2. Endothelin-1 (ET-1), endothelin-2 (ET-2) and endothelin-3 (ET-3) (10 nM to 100 nM) caused similar concentration-dependent contractions of strips of GPLP. 3. Big ET-1 and big ET-2 also elicited concentration-dependent contractions of GPLP strips. In contrast, big ET-3, up to a concentration of 100 nM, failed to induce a contraction of the GPLP. 4. Incubation of strips of GPLP with the dual endothelin converting enzyme (ECE) and neutral endopeptidase (NEP) inhibitor, phosphoramidon (10 microM), as well as two other NEP inhibitors thiorphan (10 microM) or SQ 28,603 (10 microM) decreased by 43% (P < 0.05), 42% (P < 0.05) and 40% (P < 0.05) the contractions induced by 30 nM of big ET-1 respectively. Captopril (10 microM), an angiotensin-converting enzyme inhibitor, had no effect on the contractions induced by big ET-1. 5. The incubation of strips of GPLP with phosphoramidon (10 microM), thiorphan (10 microM) or SQ 28,603 (10 microM) also decreased by 74% (P < 0.05), 34% and 50% (P < 0.05) the contractions induced by 30 nM big ET-2 respectively. As for the contractions induced by big ET-1, captopril (10 microM) had no effect on the concentration-dependent contractions induced by big ET-2. 6. Phosphoramidon (10 microM), thiorphan (10 microM) and SQ 28,603 (10 microM) significantly potentiated the contractions of strips of GPLP induced by both ET-1 (30 nM) and ET-3 (30 nM). However, the enzymatic inhibitors did not significantly affect the contractions induced by ET-2 (30 nM) in this tissue. 7. These results suggest that the effects of big ET-1 and big ET-2 result from the conversion to ET-1 and ET-2 by at least one enzyme sensitive to phosphoramidon, thiorphan and SQ 28,603. This enzyme corresponds possibly to EC 3.4.24.11 (NEP 24.11) and could also be responsible for the degradation of ETs in the GPLP. Images Figure 4 PMID:8825361

Preliminary scientific rationale for a voyage to a thousand astronomical units

NASA Technical Reports Server (NTRS)

Etchegaray, M. I. (Compiler)

1987-01-01

A proposed mission to 1000 astronomical units (TAU) is under study by the Jet Propulsion Laboratory. Launch date for a TAU mission is likely to be well into the first decade of the 21st century. Study of TAU has focused on the technologies required to carry out this ambitious mission and the identification of preliminary scientific rationale for such a deep space flight. A 1-MW nuclear-powered electric propulsion (NEP) system forms the baseline method for achieving the high velocities required. A solar system escape velocity of 106 km/s is needed to propel the TAU vehicle to 1000 AU in 50 years. The NEP system must accelerate the vehicle for about ten years before this velocity is attained because of the extremely low thrust nature of the xenon-fueled ion engines. At the end of the thrusting phase the NEP system is jettisoned to allow the TAU spacecraft and science experiments to coast out to 1000 AU. Another important technology for TAU is advanced optical communication systems, which are envisioned for transmitting science data to Earth. A 1-m optical telescope combined with a 10-W laser transponder can transmit 20 kbps to a 10-m Earth-orbit-based telescope from 1000 AU.

Acute Pain Perception During Different Sampling Methods for Respiratory Culture in Cystic Fibrosis Patients.

PubMed

Eyns, Hanneke; De Wachter, Elke; Malfroot, Anne; Vaes, Peter

2018-03-01

Reliable identification of lower respiratory tract pathogens is crucial in the management of cystic fibrosis (CF). The multitude of treatments and clinical procedures are a considerable burden and are potentially provoking pain. As part of another study (NCT02363764), investigating the bacterial yield of three sampling methods, nasal swabs (NSs), cough swabs (CSs), and (induced) sputum samples ([I]SSs), in both expectorating patients (EPs) and non-expectorating patients (NEPs) with CF, the present study aimed to explore the prevalence of respiratory culture sampling-related pain as assessed by self-report within a cohort of children and adults. Literate patients with CF (aged six years or older) completed a questionnaire on pain perception related to the three aforementioned sampling methods (No/Yes; visual analogue scale for pain [VAS-Pain] [0-10 cm]). In addition, patients were asked to rank these methods by their own preference without taking into account the presumed bacterial yield. In total, 119 questionnaires were returned. In the EPs-group, CS was most frequently (n%; mean VAS-Pain if pain [range]) reported as painful method: overall (n = 101; 12.9%; 1.8 [0.2-4.8]), children (n = 41; 22.0%; 1.4 [0.2-2.7]), and adults (n = 60; 6.7%; 2.5 [0.5-4.8]). Highest pain intensity scores were observed with NS overall (3.0%; 2.4 [0.3-6.2]) and in children (4.9%; 3.3 [0.3-6.2]), but not in adults (1.7%; 0.6 [-]).NEPs-children (n = 17) reported ISS most frequently and as most painful sampling method (17.6%; 2.0 [1.0-4.0]). The only NEP-adult did not perceive pain. NEPs preferred NS > CS > ISS (61.1%, 33.3%, 5.6%, respectively [P = 0.001]) as primary sampling method, whereas EPs preferred SS > NS > CS (65.7%, 26.3%, 8.1%, respectively [P < 0.0001]). Patients' preference for a specific method inversely correlated to pain perception and intensity in EPs (φ = -0.155 [P = 0.007] and ρ = -0.926 [P = 0.008], respectively), but not in NEPs (φ = -0.226 [P = 0.097] and ρ = -0.135 [P = 0.798], respectively). A relatively large range of pain experiences was observed in patients with CF during respiratory culture sampling, which underlines the importance of individual pain assessment. Nevertheless, clinicians can confidently choose the sampling method based on validity over patients' preference. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

A Decrease in Glomerular Endothelial Cells and Endothelial-mesenchymal Transition during Glomerulosclerosis in the Tensin2-deficient Mice (ICGN strain).

PubMed

Kato, Takashi; Mizuno, Shinya; Ito, Akihiko

2014-01-01

The ICR-derived glomerulonephritis (ICGN) mouse is a unique model of nephrotic syndrome, and albuminuria becomes evident in a neonatal stage, due to a genetic mutation of tensin2. We previously provided evidence that an apparent decrease in nephrin, caused by tensin2-deficiencient states, leads to podocytopathy, albuminuria and eventually, chronic renal failure. In general, glomerular endothelial cells (ECs) function as a barrier through tight attachment of glomerular basement membrane to podocytes, while decreased ECs can worsen renal failure. Nevertheless, it is still unknown whether glomerular ECs are altered under the tensin-2-deficient states during the manifestation of chronic renal failure. Herein, we examined the changes of glomerular ECs, with focus on the expression of PECAM-1 and VE-cadherin (EC-specific markers), or of α-SMA (myofibroblast marker) in this mouse model by histological methods. Compared with the non-nephrotic (+/nep) mice, the nephrotic (nep/nep) mice exhibited the reduced expression of PECAM-1, or of VE-cadherin, in glomerular area. Notably, some glomerular ECs showed the positive stainings for both PECAM-1 and α-SMA, suggesting endothelial-to-mesenchymal transition (EndoMT) during progression of glomerular sclerosis. This is the first report showing that a decrease in glomerular ECs, at least in part, via EndoMT is involved in tensin2-deficient pathological conditions.

Hyper Suprime-Camera Survey of the Akari NEP Wide Field

NASA Astrophysics Data System (ADS)

Goto, Tomotsugu; Toba, Yoshiki; Utsumi, Yousuke; Oi, Nagisa; Takagi, Toshinobu; Malkan, Matt; Ohayma, Youichi; Murata, Kazumi; Price, Paul; Karouzos, Marios; Matsuhara, Hideo; Nakagawa, Takao; Wada, Takehiko; Serjeant, Steve; Burgarella, Denis; Buat, Veronique; Takada, Masahiro; Miyazaki, Satoshi; Oguri, Masamune; Miyaji, Takamitsu; Oyabu, Shinki; White, Glenn; Takeuchi, Tsutomu; Inami, Hanae; Perason, Chris; Malek, Katarzyna; Marchetti, Lucia; Lee, Hyung Mok; Im, Myung; Kim, Seong Jin; Koptelova, Ekaterina; Chao, Dani; Wu, Yi-Han; AKARI NEP Survey Team; AKARI All Sky Survey Team

2017-03-01

The extragalactic background suggests half the energy generated by stars was reprocessed into the infrared (IR) by dust. At z ∼1.3, 90% of star formation is obscured by dust. To fully understand the cosmic star formation history, it is critical to investigate infrared emission. AKARI has made deep mid-IR observation using its continuous 9-band filters in the NEP field (5.4 deg^2), using ∼10% of the entire pointed observations available throughout its lifetime. However, there remain 11,000 AKARI infrared sources undetected with the previous CFHT/Megacam imaging (r ∼25.9ABmag). Redshift and IR luminosity of these sources are unknown. These sources may contribute significantly to the cosmic star-formation rate density (CSFRD). For example, if they all lie at 1 < z < 2, the CSFRD will be twice as high at the epoch. We are carrying out deep imaging of the NEP field in 5 broad bands (g,r,i,z, and y) using Hyper Suprime-Camera (HSC), which has 1.5 deg field of view in diameter on Subaru 8m telescope. This will provide photometric redshift information, and thereby IR luminosity for the previously-undetected 11,000 faint AKARI IR sources. Combined with AKARI's mid-IR AGN/SF diagnosis, and accurate mid-IR luminosity measurement, this will allow a complete census of cosmic star-formation/AGN accretion history obscured by dust.

Toxicological Implications of Released Particulate Matter during Thermal Decomposition of Nano-Enabled Thermoplastics

PubMed Central

Watson-Wright, Christa; Singh, Dilpreet; Demokritou, Philip

2017-01-01

Nano-enabled thermoplastics are part of the growing market of nano-enabled products (NEPs) that have vast utility in several industries and consumer goods. The use and disposal of NEPs at their end of life has raised concerns about the potential release of constituent engineered nanomaterials (ENMs) during thermal decomposition and their impact on environmental health and safety. To investigate this issue, industrially relevant nano-enabled thermoplastics including polyurethane, polycarbonate, and polypropylene containing carbon nanotubes (0.1 and 3% w/v, respectively), polyethylene containing nanoscale iron oxide (5% w/v), and ethylene vinyl acetate containing nanoscale titania (2 and 5% w/v) along with their pure thermoplastic matrices were thermally decomposed using the recently developed lab based Integrated Exposure Generation System (INEXS). The life cycle released particulate matter (called LCPM) was monitored using real time instrumentation, size fractionated, sampled, extracted and prepared for toxicological analysis using primary small airway epithelial cells to assess potential toxicological effects. Various cellular assays were used to assess reactive oxygen species and total glutathione as measurements of oxidative stress along with mitochondrial function, cellular viability, and DNA damage. By comparing toxicological profiles of LCPM released from polymer only (control) with nano-enabled LCPM, potential nanofiller effects due to the use of ENMs were determined. We observed associations between NEP properties such as the percent nanofiller loading, host matrix, and nanofiller chemical composition and the physico-chemical properties of released LCPM, which were linked to biological outcomes. More specifically, an increase in percent nanofiller loading promoted a toxicological response independent of increasing LCPM dose. Importantly, differences in host matrix and nanofiller composition were shown to enhance biological activity and toxicity of LCPM. This work highlights the importance of assessing the toxicological properties of LCPM and raises environmental health and safety concerns of nano-enabled products at their end of life during thermal decomposition/incineration. PMID:29333505

Toxicological Implications of Released Particulate Matter during Thermal Decomposition of Nano-Enabled Thermoplastics.

PubMed

Watson-Wright, Christa; Singh, Dilpreet; Demokritou, Philip

2017-01-01

Nano-enabled thermoplastics are part of the growing market of nano-enabled products (NEPs) that have vast utility in several industries and consumer goods. The use and disposal of NEPs at their end of life has raised concerns about the potential release of constituent engineered nanomaterials (ENMs) during thermal decomposition and their impact on environmental health and safety. To investigate this issue, industrially relevant nano-enabled thermoplastics including polyurethane, polycarbonate, and polypropylene containing carbon nanotubes (0.1 and 3% w/v, respectively), polyethylene containing nanoscale iron oxide (5% w/v), and ethylene vinyl acetate containing nanoscale titania (2 and 5% w/v) along with their pure thermoplastic matrices were thermally decomposed using the recently developed lab based Integrated Exposure Generation System (INEXS). The life cycle released particulate matter (called LCPM) was monitored using real time instrumentation, size fractionated, sampled, extracted and prepared for toxicological analysis using primary small airway epithelial cells to assess potential toxicological effects. Various cellular assays were used to assess reactive oxygen species and total glutathione as measurements of oxidative stress along with mitochondrial function, cellular viability, and DNA damage. By comparing toxicological profiles of LCPM released from polymer only (control) with nano-enabled LCPM, potential nanofiller effects due to the use of ENMs were determined. We observed associations between NEP properties such as the percent nanofiller loading, host matrix, and nanofiller chemical composition and the physico-chemical properties of released LCPM, which were linked to biological outcomes. More specifically, an increase in percent nanofiller loading promoted a toxicological response independent of increasing LCPM dose. Importantly, differences in host matrix and nanofiller composition were shown to enhance biological activity and toxicity of LCPM. This work highlights the importance of assessing the toxicological properties of LCPM and raises environmental health and safety concerns of nano-enabled products at their end of life during thermal decomposition/incineration.

Nep-Akari Evolution with Redshift of Dust Attenuation in 8 ㎛ Selected Galaxies

NASA Astrophysics Data System (ADS)

Buat, V.; Oi, N.; Burgarella, D.; Malek, K.; Matsuhara, H.; Murata, K.; Serjeant, S.; Takeuchi, T. T.; Malkan, M.; Pearson, C.; Wada, T.

2017-03-01

We built a 8um selected sample of galaxies in the NEP-AKARI field by defining 4 redshift bins with the four AKARI bands at 11, 15, 18 and 24 microns (0.15

Identification of a second family of genes in Moniliophthora perniciosa, the causal agent of witches' broom disease in cacao, encoding necrosis-inducing proteins similar to cerato-platanins.

PubMed

Zaparoli, Gustavo; Cabrera, Odalys García; Medrano, Francisco Javier; Tiburcio, Ricardo; Lacerda, Gustavo; Pereira, Gonçalo Guimarães

2009-01-01

The hemibiotrophic basidiomycete Moniliophthora perniciosa is the causal agent of witches' broom disease in cacao. This is a dimorphic species, with monokaryotic hyphae during the biotrophic phase, which is converted to dikaryotic mycelia during the saprophytic phase. The infection in pod is characterized by the formation of hypertrophic and hyperplasic tissues in the biotrophic phase, which is followed by necrosis and complete degradation of the organ. We found at least five sequences in the fungal genome encoding putative proteins similar to cerato-platanin (CP)-like proteins, a novel class of proteins initially found in the phytopathogen Ceratocystis fimbriata. One M. perniciosa CP gene (MpCP1) was expressed in vitro and proved to have necrosis-inducing ability in tobacco and cacao leaves. The protein is present in solution as dimers and is able to recover necrosis activity after heat treatment. Transcription analysis ex planta showed that MpCP1 is more expressed in biotrophic-like mycelia than saprotrophic mycelia. The necrosis profile presented is different from that caused by M. perniciosa necrosis and ethylene-inducing proteins (MpNEPs), another family of elicitors expressed by M. perniciosa. Remarkably, a mixture of MpCP1 with MpNEP2 led to a synergistic necrosis effect very similar to that found in naturally infected plants. This is the first report of a basidiomycete presenting both NEP1-like proteins (NLPs) and CPs in its genome.

Responsivity boosting in FIR TiN LEKIDs using phonon recycling: simulations and array design

NASA Astrophysics Data System (ADS)

Fyhrie, Adalyn; McKenney, Christopher; Glenn, Jason; LeDuc, Henry G.; Gao, Jiansong; Day, Peter; Zmuidzinas, Jonas

2016-07-01

To characterize further the cosmic star formation history at high redshifts, a large-area survey by a cryogenic 4-6 meter class telescope with a focal plane populated by tens of thousands of far-infrared (FIR, 30-300 μm) detectors with broadband detector noise equivalent powers (NEPs) on the order of 3×10-9 W/√ Hz is needed. Ideal detectors for such a surveyor do not yet exist. As a demonstration of one technique for approaching the ultra-low NEPs required by this surveyor, we present the design of an array of 96 350 µm KIDs that utilize phonon recycling to boost responsivity. Our KID array is fabricated with TiN deposited on a silicon-on-insulator (SOI) wafer, which is a 2 μm thick layer of silicon bonded to a thicker slab of silicon by a thin oxide layer. The backside thick slab is etched away underneath the absorbers so that the inductors are suspended on just the 2 μm membrane. The intent is that quasiparticle recombination phonons are trapped in the thin membrane, thereby increasing their likelihood of being re-absorbed by the KID to break additional Cooper pairs and boost responsivity. We also present a Monte-Carlo simulation that predicts the amount of signal boost expected from phonon recycling given different detector geometries and illumination strategies. For our current array geometry, the simulation predicts a measurable 50% boost in responsivity.

Bioinformatic analysis of the neprilysin (M13) family of peptidases reveals complex evolutionary and functional relationships

PubMed Central

2008-01-01

Background The neprilysin (M13) family of endopeptidases are zinc-metalloenzymes, the majority of which are type II integral membrane proteins. The best characterised of this family is neprilysin, which has important roles in inactivating signalling peptides involved in modulating neuronal activity, blood pressure and the immune system. Other family members include the endothelin converting enzymes (ECE-1 and ECE-2), which are responsible for the final step in the synthesis of potent vasoconstrictor endothelins. The ECEs, as well as neprilysin, are considered valuable therapeutic targets for treating cardiovascular disease. Other members of the M13 family have not been functionally characterised, but are also likely to have biological roles regulating peptide signalling. The recent sequencing of animal genomes has greatly increased the number of M13 family members in protein databases, information which can be used to reveal evolutionary relationships and to gain insight into conserved biological roles. Results The phylogenetic analysis successfully resolved vertebrate M13 peptidases into seven classes, one of which appears to be specific to mammals, and insect genes into five functional classes and a series of expansions, which may include inactive peptidases. Nematode genes primarily resolved into groups containing no other taxa, bar the two nematode genes associated with Drosophila DmeNEP1 and DmeNEP4. This analysis reconstructed only one relationship between chordate and invertebrate clusters, that of the ECE sub-group and the DmeNEP3 related genes. Analysis of amino acid utilisation in the active site of M13 peptidases reveals a basis for their biochemical properties. A relatively invariant S1' subsite gives the majority of M13 peptidases their strong preference for hydrophobic residues in P1' position. The greater variation in the S2' subsite may be instrumental in determining the specificity of M13 peptidases for their substrates and thus allows M13 peptidases to fulfil a broad range of physiological roles. Conclusion The M13 family of peptidases have diversified extensively in all species examined, indicating wide ranging roles in numerous physiological processes. It is predicted that differences in the S2' subsite are fundamental to determining the substrate specificities that facilitate this functional diversity. PMID:18215274

Electrothermal feedback in kinetic inductance detectors

NASA Astrophysics Data System (ADS)

Guruswamy, T.; Thomas, C. N.; Withington, S.; Goldie, D. J.

2017-06-01

In kinetic inductance detectors (KIDs) and other similar applications of superconducting microresonators, both the large and small-signal behaviour of the device may be affected by electrothermal feedback. Microwave power applied to read out the device is absorbed by and heats the superconductor quasiparticles, changing the superconductor conductivity and hence the readout power absorbed in a positive or negative feedback loop. In this work, we explore numerically the implications of an extensible theoretical model of a generic superconducting microresonator device for a typical KID, incorporating recent work on the power flow between superconductor quasiparticles and phonons. This model calculates the large-signal (changes in operating point) and small-signal behaviour of a device, allowing us to determine the effect of electrothermal feedback on device responsivity and noise characteristics under various operating conditions. We also investigate how thermally isolating the device from the bath, for example by designing the device on a membrane only connected to the bulk substrate by thin legs, affects device performance. We find that at a typical device operating point, positive electrothermal feedback reduces the effective thermal conductance from the superconductor quasiparticles to the bath, and so increases responsivity to signal (pair-breaking) power, increases noise from temperature fluctuations, and decreases the noise equivalent power (NEP). Similarly, increasing the thermal isolation of the device while keeping the quasiparticle temperature constant decreases the NEP, but also decreases the device response bandwidth.

Nuclear Electric Propulsion Application: RASC Mission Robotic Exploration of Venus

NASA Technical Reports Server (NTRS)

McGuire, Melissa L.; Borowski, Stanley K.; Packard, Thomas W.

2004-01-01

The following paper documents the mission and systems analysis portion of a study in which Nuclear Electric Propulsion (NEP) is used as the in-space transportation system to send a series of robotic rovers and atmospheric science airplanes to Venus in the 2020 to 2030 timeframe. As part of the NASA RASC (Revolutionary Aerospace Systems Concepts) program, this mission analysis is meant to identify future technologies and their application to far reaching NASA missions. The NEP systems and mission analysis is based largely on current technology state of the art assumptions. This study looks specifically at the performance of the NEP transfer stage when sending a series of different payload package point design options to Venus orbit.

The New Ecological Paradigm Revisited: Anchoring the NEP Scale in Environmental Ethics

ERIC Educational Resources Information Center

Lundmark, Carina

2007-01-01

The New Environmental or Ecological Paradigm (NEP) is widely acknowledged as a reliable multiple-item scale to capture environmental attitudes or beliefs. It has been used in statistical analyses for almost 30 years, primarily by psychologists, but also by political scientists, sociologists and geographers. The scale's theoretical foundation is,…

National Policy on Education and Higher Education

ERIC Educational Resources Information Center

Varughese, Rajan

2017-01-01

The Ministry of Human Resource Development (MHRD) has come out with the draft of 'National Education Policy (NEP) 2016' in April 2016. The new NEP 2016 seeks to create conditions to improve the quality of teaching, learning and assessment, and promote transparency in the management of education in the country. The policy prescriptions enunciated…

NEP (Children@School): An Instrument for Measuring Environmental Attitudes in Middle Childhood

ERIC Educational Resources Information Center

Izadpanahi, Parisa; Tucker, Richard

2018-01-01

While there are many environmental education programs for children, few studies have used an appropriately developed scale for evaluating how such education might have on impact on children's environmental orientations. The research presented in this article adapted the NEP (New Ecological Paradigm) for Children scale to develop a new instrument…

Combined alkaline hydrolysis and ultrasound-assisted extraction for the release of nonextractable phenolics from cauliflower (Brassica oleracea var. botrytis) waste.

PubMed

Gonzales, Gerard Bryan; Smagghe, Guy; Raes, Katleen; Van Camp, John

2014-04-16

Cauliflower waste contains high amounts phenolic compounds, but conventional solvent extraction misses high amounts of nonextractable phenolics (NEP), which may contribute more to the valorization of these waste streams. In this study, the NEP content and composition of cauliflower waste were investigated. The ability of alkaline hydrolysis, sonication, and their combination to release NEP was assessed. Alkaline hydrolysis with sonication was found to extract the highest NEP content (7.3 ± 0.17 mg gallic acid equivalents (GAE)/g dry waste), which was higher than the extractable fraction. The highest yield was obtained after treatment of 2 M NaOH at 60 °C for 30 min of sonication. Quantification and identification were done using U(H)PLC-DAD and U(H)PLC-ESI-MS(E). Kaempferol and quercetin glucosides along with several phenolic acids were found. The results of the study show that there are higher amounts of valuable health-promoting compounds from cauliflower waste than what is currently described in the literature.

Tropopause Pressure May Explain California Droughts and Wet Period

NASA Astrophysics Data System (ADS)

Mazdiyasni, O.; AghaKouchak, A.

2017-12-01

Sea surface temperatures and teleconnection patterns such as El Nino/La Nina are considered the main culprits behind major California droughts. However, the underlying relationship between sea surface temperatures (SSTs) and precipitation anomalies is relatively weak. In 2015-2016 the most extreme El Nino did not lead to a wet season as expected, which triggered a series of studies on this topic. Here we show that tropopause level pressure in a region in the northeastern Pacific Ocean (dubbed the PARS-NEP region) plays a major role in whether California will experience a wet or dry year and often dominates the role of SST-based teleconnections. Our results indicate that pressure in the PARS-NEP region Granger-Causes precipitation in California during the wet season. We show that when pressure in the PARS-NEP region is in the lower (upper) tertile, 85% of wet seasons across California have a positive (negative) precipitation anomaly. The observed relationship between PARS-NEP and California precipitation is stronger than all the commonly used SST-based climatic indictors frequently used for understanding causes of droughts.

VizieR Online Data Catalog: AKARI NEP Survey sources at 18um (Pearson+, 2014)

NASA Astrophysics Data System (ADS)

Pearson, C. P.; Serjeant, S.; Oyabu, S.; Matsuhara, H.; Wada, T.; Goto, T.; Takagi, T.; Lee, H. M.; Im, M.; Ohyama, Y.; Kim, S. J.; Murata, K.

2015-04-01

The NEP-Deep survey at 18u in the IRC-L18W band is constructed from a total of 87 individual pointed observations taken between May 2006 to August 2007, using the IRC Astronomical Observing Template (AOT) designed for deep observations (IRC05), with approximately 2500 second exposures per IRC filter in all mid-infrared bands. The deep imaging IRC05 AOT has no explicit dithering built into the AOT operation, therefore dithering is achieved by layering separate pointed observations on at least three positions on a given piece of sky. The NEP-Wide survey consists of 446 pointed observations with .300 second exposures for each filter. The NEP-Wide survey uses the shallower IRC03 AOT optimized for large area multi-band mapping with the dithering included within the AOT. Note that for both surveys, although images are taken simultaneously in all three IRC channels, the target area of sky in the MIR-L channel is offset from the corresponding area of sky in the NIR/MIR-S channel by ~20arcmin. (2 data files).

Selective neurotensin-derived internally quenched fluorogenic substrates for neurolysin (EC 3.4.24.16): comparison with thimet oligopeptidase (EC 3.4.24.15) and neprilysin (EC 3.4.24.11).

PubMed

Oliveira, V; Campos, M; Hemerly, J P; Ferro, E S; Camargo, A C; Juliano, M A; Juliano, L

2001-05-15

Internally quenched fluorescent peptides derived from neurotensin (pELYENKPRRPYIL) sequence were synthesized and assayed as substrates for neurolysin (EC 3.4.24.16), thimet oligopeptidase (EC 3.4.24.15 or TOP), and neprilysin (EC 3.4.24.11 or NEP). Abz-LYENKPRRPYILQ-EDDnp (where EDDnp is N-(2,4-dinitrophenyl)ethylenediamine and Abz is ortho-aminobenzoic acid) was derived from neurotensin by the introduction of Q-EDDnp at the C-terminal end of peptide and by the substitution of the pyroglutamic (pE) residue at N-terminus for Abz and a series of shorter peptides was obtained by deletion of amino acids residues from C-terminal, N-terminal, or both sides. Neurolysin and TOP hydrolyzed the substrates at P--Y or Y--I or R--R bonds depending on the sequence and size of the peptides, while NEP cleaved P-Y or Y-I bonds according to its S'(1) specificity. One of these substrates, Abz-NKPRRPQ-EDDnp was a specific and sensitive substrate for neurolysin (k(cat) = 7.0 s(-1), K(m) = 1.19 microM and k(cat)/K(m) = 5882 mM(-1). s(-1)), while it was completely resistant to NEP and poorly hydrolyzed by TOP and also by prolyl oligopeptidase (EC 3.4.21.26). Neurolysin concentrations as low as 1 pM were detected using this substrate under our conditions and its analogue Abz-NKPRAPQ-EDDnp was hydrolyzed by neurolysin with k(cat) = 14.03 s(-1), K(m) = 0.82 microM, and k(cat)/K(m) = 17,110 mM(-1). s(-1), being the best substrate so far described for this peptidase. Copyright 2001 Academic Press.

No-Enclave Percolation Corresponds to Holes in the Cluster Backbone.

PubMed

Hu, Hao; Ziff, Robert M; Deng, Youjin

2016-10-28

The no-enclave percolation (NEP) model introduced recently by Sheinman et al. can be mapped to a problem of holes within a standard percolation backbone, and numerical measurements of such holes give the same size-distribution exponent τ=1.82(1) as found for the NEP model. An argument is given that τ=1+d_{B}/2≈1.822 for backbone holes, where d_{B} is the backbone dimension. On the other hand, a model of simple holes within a percolation cluster yields τ=1+d_{f}/2=187/96≈1.948, where d_{f} is the fractal dimension of the cluster, and this value is consistent with the experimental results of gel collapse of Sheinman et al., which give τ=1.91(6). This suggests that the gel clusters are of the universality class of percolation cluster holes. Both models give a discontinuous maximum hole size at p_{c}, signifying explosive percolation behavior.

A structural model of anti-anti-[sigma] inhibition by a two-component receiver domain: the PhyR stress response regulator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrou, Julien; Foreman, Robert; Fiebig, Aretha

2012-05-09

PhyR is a hybrid stress regulator conserved in {alpha}-proteobacteria that contains an N-terminal {sigma}-like (SL) domain and a C-terminal receiver domain. Phosphorylation of the receiver domain is known to promote binding of the SL domain to an anti-{sigma} factor. PhyR thus functions as an anti-anti-{sigma} factor in its phosphorylated state. We present genetic evidence that Caulobacter crescentus PhyR is a phosphorylation-dependent stress regulator that functions in the same pathway as {sigma}{sup T} and its anti-{sigma} factor, NepR. Additionally, we report the X-ray crystal structure of PhyR at 1.25 {angstrom} resolution, which provides insight into the mechanism of anti-anti-{sigma} regulation. Directmore » intramolecular contact between the PhyR receiver and SL domains spans regions {sigma}{sub 2} and {sigma}{sub 4}, likely serving to stabilize the SL domain in a closed conformation. The molecular surface of the receiver domain contacting the SL domain is the structural equivalent of {alpha}4-{beta}5-{alpha}5, which is known to undergo dynamic conformational change upon phosphorylation in a diverse range of receiver proteins. We propose a structural model of PhyR regulation in which receiver phosphorylation destabilizes the intramolecular interaction between SL and receiver domains, thereby permitting regions {sigma}{sub 2} and {sigma}{sub 4} in the SL domain to open about a flexible connector loop and bind anti-{sigma} factor.« less

A structural model of anti-anti-[sigma];#963; inhibition by a two-component receiver domain: the PhyR stress response regulator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrou, Julien; Foreman, Robert; Fiebig, Aretha

2012-03-30

PhyR is a hybrid stress regulator conserved in {alpha}-proteobacteria that contains an N-terminal {sigma}-like (SL) domain and a C-terminal receiver domain. Phosphorylation of the receiver domain is known to promote binding of the SL domain to an anti-{sigma} factor. PhyR thus functions as an anti-anti-{sigma} factor in its phosphorylated state. We present genetic evidence that Caulobacter crescentus PhyR is a phosphorylation-dependent stress regulator that functions in the same pathway as {sigma}{sup T} and its anti-{sigma} factor, NepR. Additionally, we report the X-ray crystal structure of PhyR at 1.25 {angstrom} resolution, which provides insight into the mechanism of anti-anti-{sigma} regulation. Directmore » intramolecular contact between the PhyR receiver and SL domains spans regions {sigma}{sub 2} and {sigma}{sub 4}, likely serving to stabilize the SL domain in a closed conformation. The molecular surface of the receiver domain contacting the SL domain is the structural equivalent of {alpha}4-{beta}5-{alpha}5, which is known to undergo dynamic conformational change upon phosphorylation in a diverse range of receiver proteins. We propose a structural model of PhyR regulation in which receiver phosphorylation destabilizes the intramolecular interaction between SL and receiver domains, thereby permitting regions {sigma}{sub 2} and {sigma}{sub 4} in the SL domain to open about a flexible connector loop and bind anti-{sigma} factor.« less

An analysis of the decadal variability of Carbon fluxes in three evergreen European forests through modelling

NASA Astrophysics Data System (ADS)

Delpierre, N.; Dufrêne, E.

2009-04-01

With several sites measuring mass and energy turbulent fluxes for more than ten years, the CarboEurope database appears as a valuable resource for addressing the question of the determinism of the interannual variability of carbon (C) and water balances in forests ecosystems. Apart from major climate-driven anomalies during the anomalous 2003 summer and 2007 spring, little is known about the factors driving interannual variability (IAV) of the C balance in forest ecosystems. We used the CASTANEA process-based model to simulate the C and W fluxes and balances of three European evergreen forests for the 2000-2007 period (FRPue Quercus ilex, 44°N; DETha Picea abies, 51°N; FIHyy Pinus sylvestris, 62°N). The model fairly reproduced the day-to-day variability of measured fluxes, accounting for 70-81%, 77-91% and 59-90% of the daily variance of measured NEP, GPP and TER, respectively. However, the model was challenged in representing the IAV of fluxes integrated on an annual time scale. It reproduced ca. 80% of the interannual variance of measured GPP, but no significant relationship could be established between annual measured and modelled NEP or TER. Accordingly, CASTANEA appeared as a suitable tool for disentangling the influence of climate and biological processes on GPP at mutiple time scales. We show that climate and biological processes relative influences on the modelled GPP vary from year to year in European evergreen forests. Water-stress related and phenological processes (i.e. release of the winter thermal constraint on photosynthesis in evergreens) appear as primary drivers for the particular 2003 and 2007 years, respectively, but the relative influence of other climatic factors widely varies for less remarkable years at all sites. We discuss shortcomings of the method, as related to the influence of compensating errors in the simulated fluxes, and assess the causes of the model poor ability to represent the IAV of the annual sums of NEP and TER.

Fabrication of Ultrasensitive TES Bolometric Detectors for HIRMES

NASA Astrophysics Data System (ADS)

Brown, Ari-David; Brekosky, Regis; Franz, David; Hsieh, Wen-Ting; Kutyrev, Alexander; Mikula, Vilem; Miller, Timothy; Moseley, S. Harvey; Oxborrow, Joseph; Rostem, Karwan; Wollack, Edward

2018-04-01

The high-resolution mid-infrared spectrometer (HIRMES) is a high resolving power (R 100,000) instrument operating in the 25-122 μm spectral range and will fly on board the Stratospheric Observatory for Far-Infrared Astronomy in 2019. Central to HIRMES are its two transition edge sensor (TES) bolometric cameras, an 8 × 16 detector high-resolution array and a 64 × 16 detector low-resolution array. Both types of detectors consist of Mo/Au TES fabricated on leg-isolated Si membranes. Whereas the high-resolution detectors, with a noise equivalent power (NEP) 1.5 × 10-18 W/rt (Hz), are fabricated on 0.45 μm Si substrates, the low-resolution detectors, with NEP 1.0 × 10-17 W/rt (Hz), are fabricated on 1.40 μm Si. Here, we discuss the similarities and differences in the fabrication methodologies used to realize the two types of detectors.

Evaluating climate variability and management impacts on carbon dynamics of a temperate forest using a variety of techniques

NASA Astrophysics Data System (ADS)

Arain, M. A.

2015-12-01

Climate variability, extreme weather events, forest age and management history impacts carbon sequestration in forest ecosystems. A variety of measurement techniques such as eddy covariance, dendrochronology, automatic soil CO2 chambers and remote sensing are employed fully understand forest carbon dynamics. Here, we present carbon flux measurements from 2003-2014 in a 76-year old managed temperate pine ((-Pinus strobus L.) forest, near Lake Erie in southern Ontario, Canada. Forest was partially thinned (30% tree harvested) in 1983 and 2012. The thinning in 2012 did not significantly impact carbon fluxes as post-thinning fluxes were within the range of inter-annual variability. Mean annual post-thinning (2012-2104) gross ecosystem productivity (GEP) measure by the eddy covariance technique was 1518 ± 78 g C m-2 year-1 as compared to pre-thinning (2003-2011) GEP of 1384 ± 121 g C m-2·year-1. Over the same period, mean post-thinning net ecosystem productivity (NEP) was 185 ± 75 g C m-2 year-1 as compared to post-thinning NEP of 180 ± 70 g C m-2 year-1, indicating that pre-thinning NEP was not significantly different than post-thinning NEP. Only post-thinning mean annual ecosystem respiration (Re; 1322 ± 54 g C m-2 year-1) was higher than pre-thinning Re (1195 ± 101 g C m-2 year-1). Soil CO2 efflux measurements showed similar trends. We also evaluated the impacts of climate variability and management regime on the full life cycle of the forest using annual radial tree-ring growths from 15 trees and compared them with historical climate (temperature and precipitation) data. While the annual growth rates displayed weak correlation with long-term climatic records, the growth was generally reduced during years with extreme drought (-36% of mean annual precipitation) and extreme temperature variability (±0.6 - 1.0°C). Overall, forest was more sensitive to management regime than climate variability. It showed higher growth stress during low light condition after crown closure. When partial thinning was introduced in 1983, it responded slowly and took about 5 to 7 years to show measureable increase in its growth, despite favorable climatic conditions. This study will help to advance our understanding of carbon dynamic of forest ecosystems.

Using the Lives Saved Tool to aid country planning in meeting mortality targets: a case study from Mali.

PubMed

Keita, Youssouf; Sangho, Hamadoun; Roberton, Timothy; Vignola, Emilia; Traoré, Mariam; Munos, Melinda

2017-11-07

Mali is one of four countries implementing a National Evaluation Platform (NEP) to build local capacity to answer evaluation questions for maternal, newborn, child health and nutrition (MNCH&N). In 2014-15, NEP-Mali addressed questions about the potential impact of Mali's MNCH&N plans and strategies, and identified priority interventions to achieve targeted mortality reductions. The NEP-Mali team modeled the potential impact of three intervention packages in the Lives Saved Tool (LiST) from 2014 to 2023. One projection included the interventions and targets from Mali's ten-year health strategy (PDDSS) for 2014-2023, and two others modeled intervention packages that included scale up of antenatal, intrapartum, and curative interventions, as well as reductions in stunting and wasting. We modeled the change in maternal, newborn and under-five mortality rates under these three projections, as well as the number of lives saved, overall and by intervention. If Mali were to achieve the MNCH&N coverage targets from its health strategy, under-5 mortality would be reduced from 121 per 1000 live births to 93 per 1000, far from the target of 69 deaths per 1000. Projections 1 and 2 produced estimated mortality reductions from 121 deaths per 1000 to 70 and 68 deaths per 1000, respectively. With respect to neonatal mortality, the mortality rate would be reduced from 39 to 32 deaths per 1000 live births under the current health strategy, and to 25 per 1000 under projections 1 and 2. This study revealed that achieving the coverage targets for the MNCH&N interventions in the 2014-23 PDDSS would likely not allow Mali to achieve its mortality targets. The NEP-Mali team was able to identify two packages of MNCH&N interventions (and targets) that achieved under-5 and neonatal mortality rates at, or very near, the PDDSS targets. The Malian Ministry of Health and Public Hygiene is using these results to revise its plans and strategies.

Characterization of PgPepO, a bacterial homologue of endothelin-converting enzyme-1.

PubMed

Carson, Julie A; Ansai, Toshihiro; Awano, Shuji; Yu, Weixian; Takehara, Tadamichi; Turner, Anthony J

2002-08-01

PgPepO is a homologue of endothelin-converting enzyme-1 (ECE-1), with which it shares 31% identity. PgPepO was isolated from the periodontal pathogen Porphyromonas gingivalis. Recent studies have suggested a link between periodontal and cardiovascular disease, and several groups have suggested that bacterial and viral infections may contribute to the latter. P. gingivalis possesses the ability to invade, and multiply within, aortic endothelial cells and has been localized to atherosclerotic plaques. PgPepO was expressed and purified to homogeneity and we have begun detailed functional analysis, in terms of substrate preference and inhibitor specificity, in order to provide active-site comparisons with other members of the neprilysin (NEP)/ECE family. PgPepO possesses similar substrate specificity to ECE-1 and has been shown to cleave big endothelin-1 (big ET-1), big ET-2 and big ET-3, converting the substrates into their respective mature endothelin peptides. Substance P, angiotensin I, angiotensin II and neurotensin are all cleaved at multiple sites by PgPepO and the kinetics of these reactions have been compared. The potent vasoconstrictor urotensin II is not hydrolysed by PgPepO. Cleavage of bradykinin by PgPepO occurs at the Pro(7)-Phe(8) bond and is inhibited by the NEP and ECE-1 inhibitor phosphoramidon in a pH-dependent fashion (IC(50) =10 microM at pH 7.0) but not by thiorphan, an NEP-specific inhibitor. PgPepO activity is completely inhibited by EDTA. Characterization of this enzyme is important in elucidating possible links between periodontal pathogens and cardiovascular disorders such as atherosclerosis, and provides an opportunity to gain structural information on a bacterial protein with striking similarity to human ECE-1.

Needle Exchange Programs and Drug Injection Behavior

ERIC Educational Resources Information Center

DeSimone, Jeff

2005-01-01

This study examines how drug injection and needle sharing propensities respond when a needle exchange program (NEP) is introduced into a city. I analyze 1989-1995 Drug Use Forecasting data on adult male arrestees from 24 large U.S. cities, in nine of which NEPs opened during the sample period. After controlling for cocaine and heroin prices, AIDS…

Disturbance and net ecosystem production across three climatically distinct forest landscapes

Treesearch

John L. Campbell; O.J. Sun; B.E. Law

2004-01-01

Biometric techniques were used to measure net ecosystem production (NEP) across three climatically distinct forest chronosequences in Oregon. NEP was highly negative immediately following stand-replacing disturbance in all forests and recovered to positive values by 10, 20, and 30 years of age for the mild mesic Coast Range, mesic West Cascades, and semi-arid East...

The New Environmental Paradigm Scale: From Marginality to Worldwide Use

ERIC Educational Resources Information Center

Dunlap, Riley E.

2008-01-01

The New Environmental Paradigm (NEP) Scale, published in "The Journal of Environmental Education" by R. E. Dunlap and K. D. Van Liere (1978), has become the most widely used measure of environmental concern in the world and been employed in hundreds of studies in dozens of nations. This article tells the story of the NEP Scale, beginning…

Fundamental research on spiking, recovery and understanding seed coat nep counts in AFIS analysis of pre-opened cotton

USDA-ARS?s Scientific Manuscript database

Understanding seed coat fragment (SCF) spiking results in Advanced Fiber Information Systems (AFIS) analysis of seed coat neps (SCN) in ginned cottons was confounded by side processes in the system such as particle crushing that results in inflated recoveries. A high degree of machine (AFIS)-fiber ...

Drivers of temporal beta diversity of a benthic community in a seasonally hypoxic fjord

PubMed Central

Curkan, Curtis; Tunnicliffe, Verena

2018-01-01

Global expansion of oxygen-deficient (hypoxic) waters will have detrimental effects on marine life in the Northeast Pacific Ocean (NEP) where some of the largest proportional losses in aerobic habitat are predicted to occur. However, few in situ studies have accounted for the high environmental variability in this region while including natural community-assembly dynamics. Here, we present results from a 14-month deployment of a benthic camera platform tethered to the VENUS cabled observatory in the seasonally hypoxic Saanich Inlet. Our time series continuously recorded natural cycles of deoxygenation and reoxygenation that allowed us to test whether a community from the NEP showed hysteresis in its recovery compared to hypoxia-induced decline, and to address the processes driving temporal beta diversity under variable states of hypoxia. Using high-frequency ecological time series, we reveal (i) differences in the response and recovery of the epibenthic community are rate-limited by recovery of the sessile species assemblage; (ii) both environmental and biological processes influence community assembly patterns at multiple timescales; and (iii) interspecific processes can drive temporal beta diversity in seasonal hypoxia. Ultimately, our results illustrate how different timescale-dependent drivers can influence the response and recovery of a marine habitat under increasing stress from environmental change. PMID:29765677

Drivers of temporal beta diversity of a benthic community in a seasonally hypoxic fjord

NASA Astrophysics Data System (ADS)

Chu, Jackson W. F.; Curkan, Curtis; Tunnicliffe, Verena

2018-04-01

Global expansion of oxygen-deficient (hypoxic) waters will have detrimental effects on marine life in the Northeast Pacific Ocean (NEP) where some of the largest proportional losses in aerobic habitat are predicted to occur. However, few in situ studies have accounted for the high environmental variability in this region while including natural community-assembly dynamics. Here, we present results from a 14-month deployment of a benthic camera platform tethered to the VENUS cabled observatory in the seasonally hypoxic Saanich Inlet. Our time series continuously recorded natural cycles of deoxygenation and reoxygenation that allowed us to test whether a community from the NEP showed hysteresis in its recovery compared to hypoxia-induced decline, and to address the processes driving temporal beta diversity under variable states of hypoxia. Using high-frequency ecological time series, we reveal (i) differences in the response and recovery of the epibenthic community are rate-limited by recovery of the sessile species assemblage; (ii) both environmental and biological processes influence community assembly patterns at multiple timescales; and (iii) interspecific processes can drive temporal beta diversity in seasonal hypoxia. Ultimately, our results illustrate how different timescale-dependent drivers can influence the response and recovery of a marine habitat under increasing stress from environmental change.

Net ecosystem production, calcification and CO2 fluxes on a reef flat in Northeastern Brazil

NASA Astrophysics Data System (ADS)

Longhini, Cybelle M.; Souza, Marcelo F. L.; Silva, Ananda M.

2015-12-01

The carbon cycle in coral reefs is usually dominated by the organic carbon metabolism and precipitation-dissolution of CaCO3, processes that control the CO2 partial pressure (pCO2) in seawater and the CO2 fluxes through the air-sea interface. In order to characterize these processes and the carbonate system, four sampling surveys were conducted at the reef flat of Coroa Vermelha during low tide (exposed flat). Net ecosystem production (NEP), net precipitation-dissolution of CaCO3 (G) and CO2 fluxes across the air-water interface were calculated. The reef presented net autotrophy and calcification at daytime low tide. The NEP ranged from -8.7 to 31.6 mmol C m-2 h-1 and calcification from -13.1 to 26.0 mmol C m-2 h-1. The highest calcification rates occurred in August 2007, coinciding with the greater NEP rates. The daytime CO2 fluxes varied from -9.7 to 22.6 μmol CO2 m-2 h-1, but reached up to 13,900 μmol CO2 m-2 h-1 during nighttime. Carbon dioxide influx to seawater was predominant in the reef flat during low tide. The regions adjacent to the reef showed a supersaturation of CO2, acting as a source of CO2 to the atmosphere (from -22.8 to -2.6 mol CO2 m-2 h-1) in the reef flat during ebbing tide. Nighttime gas release to the atmosphere indicates a net CO2 release from the Coroa Vermelha reef flat within 24 h, and that these fluxes can be important to carbon budget in coral reefs.

The impact of poverty on fertility in Peninsular Malaysia: a cohort analysis.

PubMed

Teo, P

1991-02-01

Data from the 1980 census of Malaysia are used to analyze the impact of the New Economic Policy (NEP), formulated in 1970, on reducing ethnic fertility differentials and inequalities in wealth. The relationship between fertility and income differentials is explored. The author concludes that the NEP has had relatively little impact on either reducing fertility or achieving income equity.

Application of Molten Salt Reactor Technology to MMW In-Space NEP and Surface Power Missions

NASA Technical Reports Server (NTRS)

Patton, Bruce; Sorensen, Kirk; Rodgers, Stephen (Technical Monitor)

2002-01-01

Anticipated manned nuclear electric propulsion (NEP) and planetary surface power missions will require multimegawatt nuclear reactors that are lightweight, operationally robust, and scalable in power for widely varying scientific mission objectives. Molten salt reactor technology meets all of these requirements and offers an interesting alternative to traditional multimegawatt gas-cooled and liquid metal concepts.

Exploring the Use of the Revised New Ecological Paradigm Scale (NEP) to Monitor the Development of Students' Ecological Worldviews

ERIC Educational Resources Information Center

Harraway, John; Broughton-Ansin, Freya; Deaker, Lynley; Jowett, Tim; Shephard, Kerry

2012-01-01

Higher education institutions are interested in the impact that they and concurrent life experiences may have on students' sustainability attitudes, but they lack formal processes to monitor changes. We used the NEP to monitor changes in students' ecological-worldviews. We were interested in what variation there would be in a multidisciplinary…

Progress report on understanding AFIS seed coat nep levels in pre-opened slivers on the Advanced Fiber Information System (AFIS)

USDA-ARS?s Scientific Manuscript database

The Advanced Fiber Information System (AFIS) is utilized in this segment of the research project to study how seed coat neps are measured. A patent search was conducted, and studied to assist with the understanding of the AFIS measurement of this impurity in raw cotton. The older AFIS 2 is primari...

The Actualization of the Malaysian National Education Philosophy in Secondary Schools: Student and Teacher Perspectives

ERIC Educational Resources Information Center

Al-Hudawi, Shafeeq Hussain Vazhathodi; Fong, Rosy Lai Su; Musah, Mohammed Borhandden; Tahir, Lokman Mohd

2014-01-01

In the Malaysian context, all educational processes at the national level are envisioned by the National Education Philosophy (NEP). The NEP was formed in 1988 in line with the National Principles (Rukun Negara) with the ultimate aims of building a united and progressive society (Ministry of Education, 2001). However, there is uncertainty whether…

Anti-Angiogenic Action of Neutral Endopeptidase

DTIC Science & Technology

2007-11-01

message levels of NEP in hypoxia treated PC cells. Messenger RNA levels of NEP decreased between 50-75% relative to normoxic controls with high...GAGCATC-3 (sense) and 5-ATATGAATTCTCAGCTCT- TAGCAGACATGGAAGAAAG-3 ( antisense ) for glutathione S-transferase (GST) fusion proteins and 5-ATGGCAGCCGG...GAGCATC-3 (sense) and 5-CCCCAAGCTTTTAGCTCT- TAGCAGACAT-3 ( antisense ) for maltose-binding protein fusion proteins, as previously described (13

Design considerations for a Space Station radiation shield for protection from both man-made and natural sources

NASA Technical Reports Server (NTRS)

Bolch, Wesley E.; Peddicord, K. Lee; Felsher, Harry; Smith, Simon

1994-01-01

This study was conducted to analyze scenarios involving the use of nuclear-power vehicles in the vicinity of a manned Space Station (SS) in low-earth-orbit (LEO) to quantify their radiological impact to the station crew. In limiting the radiant dose to crew members, mission planners may (1) shut the reactor down prior to reentry, (2) position the vehicle at a prescribed parking distance, and (3) deploy radiation shield about the shutdown reactor. The current report focuses on the third option in which point-kernel gamma-ray shielding calculations were performed for a variety of shield configurations for both nuclear electric propulsion (NEP) and nuclear thermal rocket (NTR) vehicles. For a returning NTR vehicle, calculations indicate that a 14.9 MT shield would be needed to limit the integrated crew exposure to no more than 0.05 Sv over a period of six months (25 percent of the allowable exposure to man-made radiation sources). During periods of low vehicular activity in LEO, the shield may be redeployed about the SS habitation module in order to decrease crew exposures to trapped proton radiations by approximately a factor of 10. The corresponding shield mass required for deployment at a returning NEP vehicle is 2.21 MT. Additional scenarios examined include the radioactivation of various metals as might be found in tools used in EVA activities.

New targets for neuropathic pain therapeutics.

PubMed

Kinloch, Ross A; Cox, Peter J

2005-08-01

Neuropathic pain (NeP) is initiated by a lesion or dysfunction in the nervous system. Unlike physiological pain it serves no useful purpose and is usually sustained and chronic. NeP encompasses a wide range of pain syndromes of diverse aetiologies which together account for > 12 million sufferers in the US. Currently, there are a number of therapies available for NeP, including gabapentin, pregabalin, anticonvulsants (tiagabine HCl), tricyclic antidepressants (amitriptyline, nortriptyline) and acetaminophen/opioid combination products (Vicodin, Tylenol #3). However, these products do not provide sufficient pain relief and a significant proportion of sufferers are refractory (60%). Therefore, there is a need for new therapies that provide more predictable efficacy in all patients with improved tolerability. Over the last decade, understanding of the basic mechanisms contributing to the generation of NeP in preclinical animal models has greatly improved. Together with the completion of the various genome sequencing projects and significant advances in microarray and target validation strategies, new therapeutic approaches are being rigourously pursued. This article reviews the rationale behind a number of these mechanism-based approaches, briefly discusses specific challenges that they face, and finally, speculates on the potential of emerging technologies as alternative therapeutic strategies to the traditional 'small-molecule' approach.

Leptin inhibits amyloid β-protein degradation through decrease of neprilysin expression in primary cultured astrocytes.

PubMed

Yamamoto, Naoki; Tanida, Mamoru; Ono, Yoko; Kasahara, Rika; Fujii, Yuko; Ohora, Kentaro; Suzuki, Kenji; Sobue, Kazuya

2014-02-28

Pathogenesis of Alzheimer's disease (AD) is characterized by accumulation of extracellular deposits of amyloid β-protein (Aβ) in the brain. The steady state level of Aβ in the brain is determined by the balance between its production and removal; the latter occurring through egress across blood and CSF barriers as well as Aβ degradation. The major Aβ-degrading enzymes in the brain are neprilysin (NEP) and insulin-degrading enzyme (IDE), which may promote Aβ deposition in patients with sporadic late-onset AD. Epidemiological studies have suggested an inverse relationship between the adipocytokine leptin levels and the onset of AD. However, the mechanisms underlying the relationship remain uncertain. We investigated whether leptin is associated with Aβ degradation by inducing NEP and IDE expression within primary cultured astrocytes. Leptin significantly decreased the expression of NEP but not IDE in a concentration- and time-dependent manner through the activation of extracellular signal-regulated kinase (ERK) in cultured rat astrocytes. Furthermore, leptin inhibited the degradation of exogenous Aβ in primary cultured astrocytes. These results suggest that leptin suppresses Aβ degradation by NEP through activation of ERK. Copyright © 2014 Elsevier Inc. All rights reserved.

Prevalence of tidal expiratory flow limitation in preschool children with and without respiratory symptoms: application of the negative expiratory pressure (NEP) method.

PubMed

JIRICKOVA, A; SULC, J; POHUNEK, P; KITTNAR, O; DOHNALOVA, A; KOFRANEK, J

2009-01-01

Negative expiratory pressure (NEP) applied at the mouth during tidal expiration provides a non-invasive method for detecting expiratory flow limitation. Forty-two children were studied, i.e. 25 children with different respiratory symptoms (R) and 17 without any respiratory symptoms (NR). Children were examined without any sedation. A preset NEP of -5 cm H(2)O was applied; its duration did not exceed duration of tidal expiration. A significance of FL was judged by determining of a flow-limited range (in % of tidal volume). FL was found in 48 % children of R group. No patient of the NR group elicited FL (P<0.001 R vs. NR). The frequency of upper airway collapses was higher in R group (12 children) than in NR group (5 children). In conclusion, a high frequency of tidal FL in the R group was found, while it was not present in NR group. A relatively high frequency of expiratory upper airway collapses was found in both groups, but it did not differ significantly. NEP method represents a reasonable approach for tidal flow limitation testing in non-sedated preschool children.

Identification of combinatorial host-specific signatures with a potential to affect host adaptation in influenza A H1N1 and H3N2 subtypes.

PubMed

Khaliq, Zeeshan; Leijon, Mikael; Belák, Sándor; Komorowski, Jan

2016-07-29

The underlying strategies used by influenza A viruses (IAVs) to adapt to new hosts while crossing the species barrier are complex and yet to be understood completely. Several studies have been published identifying singular genomic signatures that indicate such a host switch. The complexity of the problem suggested that in addition to the singular signatures, there might be a combinatorial use of such genomic features, in nature, defining adaptation to hosts. We used computational rule-based modeling to identify combinatorial sets of interacting amino acid (aa) residues in 12 proteins of IAVs of H1N1 and H3N2 subtypes. We built highly accurate rule-based models for each protein that could differentiate between viral aa sequences coming from avian and human hosts. We found 68 host-specific combinations of aa residues, potentially associated to host adaptation on HA, M1, M2, NP, NS1, NEP, PA, PA-X, PB1 and PB2 proteins of the H1N1 subtype and 24 on M1, M2, NEP, PB1 and PB2 proteins of the H3N2 subtypes. In addition to these combinations, we found 132 novel singular aa signatures distributed among all proteins, including the newly discovered PA-X protein, of both subtypes. We showed that HA, NA, NP, NS1, NEP, PA-X and PA proteins of the H1N1 subtype carry H1N1-specific and HA, NA, PA-X, PA, PB1-F2 and PB1 of the H3N2 subtype carry H3N2-specific signatures. M1, M2, PB1-F2, PB1 and PB2 of H1N1 subtype, in addition to H1N1 signatures, also carry H3N2 signatures. Similarly M1, M2, NP, NS1, NEP and PB2 of H3N2 subtype were shown to carry both H3N2 and H1N1 host-specific signatures (HSSs). To sum it up, we computationally constructed simple IF-THEN rule-based models that could distinguish between aa sequences of avian and human IAVs. From the rules we identified HSSs having a potential to affect the adaptation to specific hosts. The identification of combinatorial HSSs suggests that the process of adaptation of IAVs to a new host is more complex than previously suggested. The present study provides a basis for further detailed studies with the aim to elucidate the molecular mechanisms providing the foundation for the adaptation process.

Inter-annual variation of carbon uptake by a plantation oak woodland in south-eastern England

NASA Astrophysics Data System (ADS)

Wilkinson, M.; Eaton, E. L.; Broadmeadow, M. S. J.; Morison, J. I. L.

2012-12-01

The carbon balance of an 80-yr-old deciduous oak plantation in the temperate oceanic climate of the south-east of Great Britain was measured by eddy covariance over 12 yr (1999-2010). The mean annual net ecosystem productivity (NEP) was 486 g C m-2 yr-1 (95% CI of ±73 g C m-2 yr-1), and this was partitioned into a gross primary productivity (GPP) of 2034 ± 145 g C m-2 yr-1, over a 165 (±6) day growing season, and an annual loss of carbon through respiration and decomposition (ecosystem respiration, Reco) of 1548 ± 122 g C m-2 yr-1. Although the maximum variation of NEP between years was large (333 g C m-2 yr-1), the ratio of Reco/GPP remained relatively constant (0.76 ± 0.02 CI). Some anomalies in the annual patterns of the carbon balance could be linked to particular weather events, such as low summer solar radiation and low soil moisture content (values below 30% by volume). The European-wide heat wave and drought of 2003 did not reduce the NEP of this woodland because of good water supply from the surface-water gley soil. The inter-annual variation in estimated intercepted radiation only accounted for ~ 47% of the variation in GPP, although a significant relationship (p < 0.001) was found between peak leaf area index and annual GPP, which modified the efficiency with which incident radiation was used in net CO2 uptake. Whilst the spring start and late autumn end of the net CO2 uptake period varied substantially (range of 24 and 27 days respectively), annual GPP was not related to growing season length. Severe outbreaks of defoliating moth caterpillars, mostly Tortrix viridana L. and Operophtera brumata L., caused considerable damage to the forest canopy in 2009 and 2010, resulting in reduced GPP in these two years. Inter-annual variation in the sensitivity of Reco to temperature was found to be strongly related to summer soil moisture content. The eddy covariance estimates of NEP closely matched mensuration-based estimates, demonstrating that this forest was a substantial sink of carbon over the 12-yr measurement period.

Low Noise Titanium Nitride KIDs for SuperSpec: A Millimeter-Wave On-Chip Spectrometer

NASA Astrophysics Data System (ADS)

Hailey-Dunsheath, S.; Shirokoff, E.; Barry, P. S.; Bradford, C. M.; Chapman, S.; Che, G.; Glenn, J.; Hollister, M.; Kovács, A.; LeDuc, H. G.; Mauskopf, P.; McKenney, C.; O'Brient, R.; Padin, S.; Reck, T.; Shiu, C.; Tucker, C. E.; Wheeler, J.; Williamson, R.; Zmuidzinas, J.

2016-07-01

SuperSpec is a novel on-chip spectrometer we are developing for multi-object, moderate resolution (R = 100-500), large bandwidth ({˜ }1.65:1), submillimeter and millimeter survey spectroscopy of high-redshift galaxies. The spectrometer employs a filter bank architecture, and consists of a series of half-wave resonators formed by lithographically-patterned superconducting transmission lines. The signal power admitted by each resonator is detected by a lumped element titanium nitride (TiN) kinetic inductance detector operating at 100-200 MHz. We have tested a new prototype device that achieves the targeted R=100 resolving power, and has better detector sensitivity and optical efficiency than previous devices. We employ a new method for measuring photon noise using both coherent and thermal sources of radiation to cleanly separate the contributions of shot and wave noise. We report an upper limit to the detector NEP of 1.4× 10^{-17} W Hz^{-1/2}, within 10 % of the photon noise-limited NEP for a ground-based R=100 spectrometer.

Trade Studies for a Manned High-Power Nuclear Electric Propulsion Vehicle

NASA Technical Reports Server (NTRS)

SanSoucie, Michael; Hull, Patrick V.; Irwin, Ryan W.; TInker, Michael L.; Patton, Bruce W.

2005-01-01

Nuclear electric propulsion (NEP) vehicles will be needed for future manned missions to Mars and beyond. Candidate vehicles must be identified through trade studies for further detailed design from a large array of possibilities. Genetic algorithms have proven their utility in conceptual design studies by effectively searching a large design space to pinpoint unique optimal designs. This research combines analysis codes for NEP subsystems with genetic algorithm-based optimization. Trade studies for a NEP reference mission to the asteroids were conducted to identify important trends, and to determine the effects of various technologies and subsystems on vehicle performance. It was found that the electric thruster type and thruster performance have a major impact on the achievable system performance, and that significant effort in thruster research and development is merited.

Time series of the northeast Pacific

NASA Astrophysics Data System (ADS)

Peña, M. Angelica; Bograd, Steven J.

2007-10-01

In July 2006, the North Pacific Marine Science Organization (PICES) and Fisheries & Oceans Canada sponsored the symposium “Time Series of the Northeast Pacific: A symposium to mark the 50th anniversary of Line P”. The symposium, which celebrated 50 years of oceanography along Line P and at Ocean Station Papa (OSP), explored the scientific value of the Line P and other long oceanographic time series of the northeast Pacific (NEP). Overviews of the principal NEP time-series were presented, which facilitated regional comparisons and promoted interaction and exchange of information among investigators working in the NEP. More than 80 scientists from 8 countries attended the symposium. This introductory essay is a brief overview of the symposium and the 10 papers that were selected for this special issue of Progress in Oceanography.

Spitzer Observations of the North Ecliptic Pole

NASA Astrophysics Data System (ADS)

Nayyeri, H.; Ghotbi, N.; Cooray, A.; Bock, J.; Clements, D. L.; Im, M.; Kim, M. G.; Korngut, P.; Lanz, A.; Lee, H. M.; Lee, D. H.; Malkan, M.; Matsuhara, H.; Matsumoto, T.; Matsuura, S.; Nam, U. W.; Pearson, C.; Serjeant, S.; Smidt, J.; Tsumura, K.; Wada, T.; Zemcov, M.

2018-02-01

We present a photometric catalog for Spitzer Space Telescope warm mission observations of the North Ecliptic Pole (NEP; centered at R.A. = 18h00m00s, decl. = 66d33m38.ˢ552). The observations are conducted with IRAC in the 3.6 and 4.5 μm bands over an area of 7.04 deg2, reaching 1σ depths of 1.29 μJy and 0.79 μJy in the 3.6 μm and 4.5 μm bands, respectively. The photometric catalog contains 380,858 sources with 3.6 and 4.5 μm band photometry over the full-depth NEP mosaic. Point-source completeness simulations show that the catalog is 80% complete down to 19.7 AB. The accompanying catalog can be used for constraining the physical properties of extragalactic objects, studying the AGN population, measuring the infrared colors of stellar objects, and studying the extragalactic infrared background light.

Purification and characterization of substance P endopeptidase activities in the rat spinal cord.

PubMed

Karlsson, K; Eriksson, U; Andrén, P; Nyberg, F

1997-02-01

Two enzymes with substance P degrading activity were purified from the membrane bound fraction of the rat spinal cord. The purified enzymes were characterized with regard to biochemical and kinetic properties. One of the enzymes exhibited close similarity to neutral endopeptidase 24.11 (NEP, EC 3.4.24.11), while the other resembled a substance P converting endopeptidase (SPE), which has previously been identified and purified from human cerebrospinal fluid (CSF). Detergent treated spinal cord homogenates from male Sprague Dawley rats were purified by anion-exchange chromatography (DEAE-sepharose CL-6B), hydrophobic-interaction chromatography (phenyl-sepharose CL-4B) and molecular sieving (Sephadex G-50). Two fractions with enzymes differing in size were recovered and allowed for further purification to apparent homogeneity by ion-exchange chromatography and molecular sieving on a micro-purification system (SMART). The enzyme activities were monitored by following the conversion of synthetic substance P using a radioimmunoassay specific for the heptapeptide product, substance P (1-7). By SDS-polyacrylamide gel electrophoresis of the purified enzymes molecular weights of 43 and 70 kDa were estimated for the SPE-like and NEP-like activity, respectively. A K(m) of 5 microM was determined for the conversion of substance P to its (1-7) fragment by the SPE-like activity. Reversed-phase HPLC together with mass spectrometry permitted identification of all fragments released from substance P by the peptidases. The released fragments were for both enzymes identified as substance P (1-7), substance P (8-11), substance P (1-8), substance P (9-11). The NEP-like enzyme preparation also gave substance P (1-6) as a major product.

Occupational and Educational Biographies of Older Workers and Their Participation in Further Education in Germany

ERIC Educational Resources Information Center

Schmidt-Hertha, Bernhard; Müller, Margaretha

2017-01-01

The adult cohort of the German National Educational Panel Study (NEPS) provides data from six sets of longitudinal data derived from 11,932 German adults. We used the NEPS data to look at the effects of formal education in adulthood and occupational changes on participation in further vocational education and training in order to gain a better…

The National Educational Panel Study (NEPS) in Germany: An Overview of Design, Research Options and Access, with a Focus on Lower-Secondary School

ERIC Educational Resources Information Center

Strietholt, Rolf; Naujokat, Kerstin; Mai, Tobias; Kretschmer, Sara; Jarsinski, Stephan; Goy, Martin; Frahm, Sarah; Kanders, Michael; Bos, Wilfried; Blatt, Inge

2013-01-01

This article introduces the National Educational Panel Study (NEPS). This German longitudinal study produces a vast amount of data for the scientific community, and researchers all around Europe are invited to use the data to address various research questions empirically. Therefore, the authors provide information about the purpose as well as the…

A diagnostic carbon flux model to monitor the effects of disturbance and interannual variation in climate on regional NEP.

Treesearch

D.P. Turner; W.D. Ritts; J.M. Styles; Z. Yang; W.B. Cohen; B.E. Law; P.E. Thornton

2006-01-01

Net ecosystem production (NEP) was estimated over a 10.9 x 104 km2 forested region in western Oregon USA for 2 yr (2002-2003) using a combination of remote sensing, distributed meteorological data, and a carbon cycle model (CFLUX). High spatial resolution satellite data (Landsat, 30 m) provided information on land cover and...

Environmental and biogeochemical changes following a decade's reclamation in the Dapeng (Tapong) Bay, southwestern Taiwan

NASA Astrophysics Data System (ADS)

Hung, J.-J.; Huang, W.-C.; Yu, C.-S.

2013-09-01

This study examines the environmental and biogeochemical changes in Dapeng (formerly spelled Tapong) Bay, a semi-enclosed coastal lagoon in southwestern Taiwan, after two major reclamation works performed between 1999 and 2010. The lagoon was largely occupied by oyster culture racks and fish farming cages before December, 2002. Substantial external inputs of nutrients and organic carbon and the fairly long water exchange time (τ) (10 ± 2 days) caused the lagoon to enter a eutrophic state, particularly at the inner lagoon, which directly received nutrient inputs. However, the entire lagoon showed autotrophic, and the estimated net ecosystem production (NEP) during the first stage was 5.8 mol C m-2 yr-1. After January, 2003, the aquaculture structures were completely removed, and the τ decreased to 6 ± 2 days. The annual mean concentrations of dissolved oxygen increased, and nutrients decreased substantially, likely due to improved water exchange, absence of feeding and increased biological utilization. The NEP increased 37% to 7.7 mol C m-2 yr-1 after structure removal. The second reclamation work beginning from July, 2006, focused on establishing artificial wetlands for wastewater treatment and on dredging bottom sediment. Although the τ did not change significantly (8 ± 3 days), substantial decreases in nutrient concentrations and dissolved organic matter continued. The NEP (14.3 mol C m-2 yr-1) increased 85% compared to that in the second stage. The data suggest that the reclamations substantially improved water quality, carbon and nutrient biogeochemical processes and budgets in this semi-enclosed ecosystem.

Increase in substance P precursor mRNA in noninflamed small-bowel sections in patients with Crohn's disease.

PubMed

Michalski, Christoph W; Autschbach, Frank; Selvaggi, Federico; Shi, Xin; Di Mola, Fabio Francesco; Roggo, Antoine; Müller, Michael W; Di Sebastiano, Pierluigi; Büchler, Markus W; Giese, Thomas; Friess, Helmut

2007-04-01

Neuropeptides, such as substance P (SP), are mediators of neurogenic inflammation and play an important role in inflammatory disorders. To further investigate the role of the SP pathway in inflammatory bowel disease (IBD), we analyzed the following in normal intestinal tissue specimens and in tissue specimens from patients with Crohn's disease (CD) and ulcerative colitis (UC): neurokinin receptor-1 (NK-1R); its isoforms (NK-1R-L and NK-1R-S); its ligand SP, encoded by preprotachykinin-A (PPT-A); and the SP-degradation enzyme, neutral endopeptidase (NEP). Real-time quantitative reverse transcription-polymerase chain reaction was used to simultaneously determine the expression of NK-1R-L, NK-1R-S, and PPT-A. Protein levels of NK-1R and NEP were determined by immunoblot analysis. In noninflamed small-bowel tissue samples of CD patients, PPT-A mRNA expression was significantly increased, whereas there was no difference between inflamed or noninflamed UC and normal intestinal tissue samples. Examining subgroups of diverse intestinal segments from CD and UC samples with various levels of inflammation revealed no differences in NK-1R-L and NK-1R-S mRNA expression, whereas there was a tendency toward overall lower NK-1R-S mRNA copy numbers. Immunoblot analysis showed upregulation of NK-1R protein levels in cases of IBD, with more pronounced enhancement in cases of CD than in UC. For NEP, there were no differences in protein levels in normal, CD, and UC intestinal tissues. These observations suggest a contribution of SP and its receptor, NK-1R, in the local inflammatory reaction in IBD and particularly in ileal CD. Moreover, significant upregulation of PPT-A mRNA in the noninflamed ileum of these patients suggests an influence of inflamed intestines on their healthy counterparts.

Importance of Absent Neoplastic Epithelium in Patients Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

PubMed

Enblad, Malin; Birgisson, Helgi; Wanders, Alkwin; Sköldberg, Filip; Ghanipour, Lana; Graf, Wilhelm

2016-04-01

The importance of absent neoplastic epithelium in specimens from cytoreductive surgery (CRS) is unknown. This study aimed to investigate the prevalence and prognostic value of histopathology without neoplastic epithelium in patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Data were extracted from medical records and histopathology reports for patients treated with initial CRS and HIPEC at Uppsala University Hospital, Sweden, between 2004 and 2012. Patients with inoperable disease and patients undergoing palliative non-CRS surgery were excluded from the study. Patients lacking neoplastic epithelium in surgical specimens from CRS, with or without mucin, were classified as "neoplastic epithelium absent" (NEA), and patients with neoplastic epithelium were classified as "neoplastic epithelium present" (NEP). The study observed NEA in 78 of 353 patients (22 %). Mucin was found in 28 of the patients with NEA. For low-grade appendiceal mucinous neoplasms and adenomas, the 5-year overall survival rate was 100 % for NEA and 84 % for NEP, and the 5-year recurrence-free survival rate was 100 % for NEA and 59 % for NEP. For appendiceal/colorectal adenocarcinomas (including tumors of the small intestine), the 5-year overall survival rate was 61 % for NEA and 38 % for NEP, and the 5-year recurrence-free survival rate was 60 % for NEA and 14 % for NEP. Carcinoembryonic antigen level, peritoneal cancer index, and completeness of the cytoreduction score were lower in patients with NEA. A substantial proportion of patients undergoing CRS and HIPEC have NEA. These patients have a favorable prognosis and a decreased risk of recurrence. Differences in patient selection can affect the proportion of NEA and hence explain differences in survival rates between reported series.

Combined Inhibition of the Renin-Angiotensin System and Neprilysin Positively Influences Complex Mitochondrial Adaptations in Progressive Experimental Heart Failure

PubMed Central

Reinders, Jörg; Schröder, Josef; Dietl, Alexander; Schmid, Peter M.; Jungbauer, Carsten; Resch, Markus; Maier, Lars S.; Luchner, Andreas; Birner, Christoph

2017-01-01

Background Inhibitors of the renin angiotensin system and neprilysin (RAS-/NEP-inhibitors) proved to be extraordinarily beneficial in systolic heart failure. Furthermore, compelling evidence exists that impaired mitochondrial pathways are causatively involved in progressive left ventricular (LV) dysfunction. Consequently, we aimed to assess whether RAS-/NEP-inhibition can attenuate mitochondrial adaptations in experimental heart failure (HF). Methods and Results By progressive right ventricular pacing, distinct HF stages were induced in 15 rabbits, and 6 animals served as controls (CTRL). Six animals with manifest HF (CHF) were treated with the RAS-/NEP-inhibitor omapatrilat. Echocardiographic studies and invasive blood pressure measurements were undertaken during HF progression. Mitochondria were isolated from LV tissue, respectively, and further worked up for proteomic analysis using the SWATH technique. Enzymatic activities of citrate synthase and the electron transfer chain (ETC) complexes I, II, and IV were assessed. Ultrastructural analyses were performed by transmission electron microscopy. During progression to overt HF, intricate expression changes were mainly detected for proteins belonging to the tricarboxylic acid cycle, glucose and fat metabolism, and the ETC complexes, even though ETC complex I, II, or IV enzymatic activities were not significantly influenced. Treatment with a RAS-/NEP-inhibitor then reversed some maladaptive metabolic adaptations, positively influenced the decline of citrate synthase activity, and altered the composition of each respiratory chain complex, even though this was again not accompanied by altered ETC complex enzymatic activities. Finally, ultrastructural evidence pointed to a reduction of autophagolytic and degenerative processes with omapatrilat-treatment. Conclusions This study describes complex adaptations of the mitochondrial proteome in experimental tachycardia-induced heart failure and shows that a combined RAS-/NEP-inhibition can beneficially influence mitochondrial key pathways. PMID:28076404

Spatially explicit simulation of hydrologically controlled carbon and nitrogen cycles and associated feedback mechanisms in a boreal ecosystem in Eastern Canada.

NASA Astrophysics Data System (ADS)

Govind, A.; Chen, J. M.; Margolis, H.

2007-12-01

Current estimates of terrestrial carbon overlook the effects of topographically-driven lateral flow of soil water. We hypothesize that this component, which occur at a landscape or watershed scale have significant influences on the spatial distribution of carbon, due to its large contribution to the local water balance. To this end, we further developed a spatially explicit ecohydrological model, BEPS-TerrainLab V2.0. We simulated the coupled hydrological and carbon cycle processes in a black spruce-moss ecosystem in central Quebec, Canada. The carbon stocks were initialized using a long term carbon cycling model, InTEC, under a climate change and disturbance scenario, the accuracy of which was determined with inventory plot measurements. Further, we simulated and validated several ecosystem indicators such as ET, GPP, NEP, water table, snow depth and soil temperature, using the measurements for two years, 2004 and 2005. After gaining confidence in the model's ability to simulate ecohydrological processes, we tested the influence of lateral water flow on the carbon cycle. We made three hydrological modeling scenarios 1) Explicit, were realistic lateral water routing was considered 2) Implicit where calculations were based on a bucket modeling approach 3) NoFlow, where the lateral water flow was turned off in the model. The results showed that pronounced anomalies exist among the scenarios for the simulated GPP, ET and NEP. In general, Implicit calculation overestimated GPP and underestimated NEP, as opposed to Explicit simulation. NoFlow underestimated GPP and overestimated NEP. The key processes controlling GPP were manifested through stomatal conductance which reduces under conditions of rapid soil saturation ( NoFlow ) or increases in the Implicit case, and, nitrogen availability which affects Vcmax, the maximum carboxylation rate. However, for NEP, the anomalies were attributed to differences in soil carbon pool decomposition, which determine the heterotrophic respiration and the resultant nitrogen mineralization which affects GPP and several other feedback mechanisms. These results suggest that lateral water flow does play a significant role in the terrestrial carbon distribution. Therefore, regional or global scale terrestrial carbon estimates could have significant errors if proper hydrological constrains are not considered for modeling ecological processes due to large topographic variations on the Earth's surface. For more info please visit: http://ajit.govind.googlepages.com/agu2007

Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure.

PubMed

Fu, Shihui; Ping, Ping; Wang, Fengqi; Luo, Leiming

2018-01-01

As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on chromosome 2. NPs are synthesized and secreted through certain mechanisms by cardiomyocytes, fibroblasts, endotheliocytes, immune cells (neutrophils, T-cells and macrophages) and immature cells (embryonic stem cells, muscle satellite cells and cardiac precursor cells). They are mainly produced by cardiovascular, brain and renal tissues in response to wall stretch and other causes. NPs provide natriuresis, diuresis, vasodilation, antiproliferation, antihypertrophy, antifibrosis and other cardiometabolic protection. NPs represent body's own antihypertensive system, and provide compensatory protection to counterbalance vasoconstrictor-mitogenic-sodium retaining hormones, released by renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS). NPs play central roles in regulation of heart failure (HF), and are inactivated through not only NP receptor-C, but also neutral endopeptidase (NEP), dipeptidyl peptidase-4 and insulin degrading enzyme. Both BNP and N-terminal proBNP are useful biomarkers to not only make the diagnosis and assess the severity of HF, but also guide the therapy and predict the prognosis in patients with HF. Current NP-augmenting strategies include the synthesis of NPs or agonists to increase NP bioactivity and inhibition of NEP to reduce NP breakdown. Nesiritide has been established as an available therapy, and angiotensin receptor blocker NEP inhibitor (ARNI, LCZ696) has obtained extremely encouraging results with decreased morbidity and mortality. Novel pharmacological approaches based on NPs may promote a therapeutic shift from suppressing the RAAS and SNS to re-balancing neuroendocrine dysregulation in patients with HF. The current review discussed the synthesis, secretion, function and metabolism of NPs, and their diagnostic, therapeutic and prognostic values in HF.

Upregulated expression of Nogo-A and NgR in an experimental model of focal microgyria regulates the migration, proliferation and self-renewal of subventricular zone neural progenitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Sixun; Shu, Haifeng; Yang, Tao

Nogo-A and its receptor (NgR) were first described as myelin-associated inhibitors of neuronal regeneration in response to injury. In recent years, knowledge about the important role of the Nogo-A protein in several neuronal pathologies has grown considerably. Here, we employed a neonatal cortex freeze-lesion (NFL) model in neonatal rats and measured the expression of Nogo-A and NgR in the resulting cerebrocortical microdysgenesis 5–75 days after freezing injury. We observed marked upregulation of Nogo-A and NgR in protein levels. Furthermore, the migration of neural precursor cells (NPCs) derived from the subventricular zone (SVZ) toward the sits of injury was perturbed bymore » treatment of NgR antagonist peptide NEP1-40. In vitro analysis showed that the knockdown of NgR by lentivirus-delivered siRNA promoted in axonal regeneration and SVZ-derived neural stem cell/progenitor cell (SVZ-NPCs) adhesion and migration, findings which were similar to the effects of NEP1-40. Taken together, our results indicate an important role for NgR in regulating the physiological processes of SVZ-NPCs. The observation of upregulated Nogo-A/NgR in lesion sites in the NFL model suggest that the effects of the perturbed Nogo-A are a key feature during the development and/or the progression of cortical malformation. - Highlights: • NFL model is an accurate experimental reproduction of focal microgyria of FCD. • The increase of the Nogo-A Levels occurs in response to freeze-induced focal lesioning. • Nogo-A/NgR may play a critical role for in the pathologic progression of FCD. • Nogo-A is associated with the migration, proliferation and self-renewal of SVZ-NPCs.« less

Ultra-Sensitive Transition-Edge Sensors (TESs) for Far-IR/Submm Space-Borne Spectroscopy

NASA Technical Reports Server (NTRS)

Kenyon, M.; Day, P. K.; Bradford, C. M.; Bock, J .J.; Leduc, H. G.

2011-01-01

We have built surface micromachined thin-film metallized Si(x)N(y) optical absorbers for transition-edge sensors (TESs) suitable for the Background - Limited far-IR/Submm Spectrograph (BLISS). BLISS is a broadband (38 micrometers - 433 micrometers), grating spectrometer consisting of five wavebands each with a modest resolution of R (is) approx. 1000. Because BLISS requires the effective noise equivalent power (NEP) of the TES to be below 10 (exp 19) W/Hz(exp 1/2), our TESs consist of four long (1000 micrometers), narrow (0.4 micrometers ), and thin (0.25 micrometers ) Si(x) N(y) support beams that reduce the thermal conductance G between the substrate and the optical absorber. To reduce the heat capacity of the absorber and make the response time tau fast enough for BLISS, our absorbers are patterned into a mesh geometry with a fill factor of less than 10%. We use a bilayer of Ti/Au to make the effective impedance of the absorber match the impedance of the incoming radiation for each band. Measurements of the response time of the metallized absorbers to heat pulses show that their heat capacity exceeds the predictions of the Debye model. Our results are suggestive that the surface of the low pressure chemical vapor deposition (LPCVD) Si(x)N(y) used in the absorbers' construction is the source of microstates that dominate the heat capacity.

How Seasonal Drought Affect Carbon and Water Fluxes of Alternative Energy Crops in the US?

NASA Astrophysics Data System (ADS)

Joo, E.; Hussain, M. Z.; Zeri, M.; Masters, M.; Gomez-Casanovas, N.; DeLucia, E. H.; Bernacchi, C.

2014-12-01

The cellulosic biomass of Switchgrass (Panicum virgatum L.), Miscanthus (Miscanthus giganteus) and native prairie are considered candidate second-generation biofuels, potentially resulting in partial replacement annual row crops within the Midwestern US. There is an increasing focus to study the environmental impact of agricultural crops, however not much is known on the influence on the energy, carbon and water cycles of energy crops, especially under drought conditions. This study compares the impact of drought episodes (in 2011 and 2012) on evapotranspiration (ET), net ecosystem productivity (NEP) and water use efficiency (WUE; equals to NEP/ET) for Switchgrass (SW), Miscanthus (MXG), Maize (MZ) and native prairie (NP) grown in Central Illinois using the eddy covariance technique. Due to the prolonged drought and the rapid growth development with increasing ET of MXG in 2012, large water deficit (precipitation-ET) was observed for each species up to the highest deficit of -360 mm for this species. The gross primary production (GPP) of MZ was radically decreased by the drought in 2011 and 2012, while SW and NP were not influenced. MXG increased NEP throughout the typically wet and drought years, mainly due to the decrease in respiration and by the largest GPP upon the drought in 2012. Despite having the largest water deficit, MXG showed an enhanced WUE of 12.8 and 11.4 Kg C ha-1mm-1 in 2011 and 2012, respectively, in comparison to years typical to the region with WUE of 3.7-7.3 Kg C ha-1mm-1. Other species did not show a significant enhancement of WUE. Therefore we conclude that out of the studied species, MXG has more access to water, and uses this water the most efficiently to store carbon, under drought conditions.

Accounting for Forest Harvest and Wildfire in a Spatially-distributed Carbon Cycle Process Model

NASA Astrophysics Data System (ADS)

Turner, D. P.; Ritts, W.; Kennedy, R. E.; Yang, Z.; Law, B. E.

2009-12-01

Forests are subject to natural disturbances in the form of wildfire, as well as management-related disturbances in the form of timber harvest. These disturbance events have strong impacts on local and regional carbon budgets, but quantifying the associated carbon fluxes remains challenging. The ORCA Project aims to quantify regional net ecosystem production (NEP) and net biome production (NBP) in Oregon, California, and Washington, and we have adopted an integrated approach based on Landsat imagery and ecosystem modeling. To account for stand-level carbon fluxes, the Biome-BGC model has been adapted to simulate multiple severities of fire and harvest. New variables include snags, direct fire emissions, and harvest removals. New parameters include fire-intensity-specific combustion factors for each carbon pool (based on field measurements) and proportional removal rates for harvest events. To quantify regional fluxes, the model is applied in a spatially-distributed mode over the domain of interest, with disturbance history derived from a time series of Landsat images. In stand-level simulations, the post disturbance transition from negative (source) to positive (sink) NEP is delayed approximately a decade in the case of high severity fire compared to harvest. Simulated direct pyrogenic emissions range from 11 to 25 % of total non-soil ecosystem carbon. In spatial mode application over Oregon and California, the sum of annual pyrogenic emissions and harvest removals was generally less that half of total NEP, resulting in significant carbon sequestration on the land base. Spatially and temporally explicit simulation of disturbance-related carbon fluxes will contribute to our ability to evaluate effects of management on regional carbon flux, and in our ability to assess potential biospheric feedbacks to climate change mediated by changing disturbance regimes.

Extreme late-summer drought causes neutral annual carbon balance in southwestern ponderosa pine forests and grasslands

NASA Astrophysics Data System (ADS)

Kolb, Thomas; Dore, Sabina; Montes-Helu, Mario

2013-03-01

We assessed the impacts of extreme late-summer drought on carbon balance in a semi-arid forest region in Arizona. To understand drought impacts over extremes of forest cover, we measured net ecosystem production (NEP), gross primary production (GPP), and total ecosystem respiration (TER) with eddy covariance over five years (2006-10) at an undisturbed ponderosa pine (Pinus ponderosa) forest and at a former forest converted to grassland by intense burning. Drought shifted annual NEP from a weak source of carbon to the atmosphere to a neutral carbon balance at the burned site and from a carbon sink to neutral at the undisturbed site. Carbon fluxes were particularly sensitive to drought in August. Drought shifted August NEP at the undisturbed site from sink to source because the reduction of GPP (70%) exceeded the reduction of TER (35%). At the burned site drought shifted August NEP from weak source to neutral because the reduction of TER (40%) exceeded the reduction of GPP (20%). These results show that the lack of forest recovery after burning and the exposure of undisturbed forests to late-summer drought reduce carbon sink strength and illustrate the high vulnerability of forest carbon sink strength in the southwest US to predicted increases in intense burning and precipitation variability.

76 FR 25593 - Endangered and Threatened Wildlife and Plants; Establishment of a Nonessential Experimental...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-05

...We, the U.S. Fish and Wildlife Service (Service), are reestablishing the Sonoran pronghorn, a federally listed endangered mammal, in its historical habitat in King Valley, Kofa National Wildlife Refuge, in Yuma County, and the Barry M. Goldwater Range-- East, Maricopa County, in southwestern Arizona. We are reestablishing the Sonoran pronghorn under section 10(j) of the Endangered Species Act of 1973, as amended, and classify that reestablished population as a nonessential experimental population (NEP). The NEP is located in southwestern Arizona in an area north of Interstate 8 and south of Interstate 10, bounded by the Colorado River on the west and Interstate 10 on the east; and an area south of Interstate 8, bounded by Highway 85 on the west, Interstates 10 and 19 on the east, and the United States-Mexico border on the south. This action is one of the recovery actions that the Service, Federal and State agencies, and other partners are conducting throughout the historical range of the species. This final rule establishes the NEP and provides for limited allowable legal taking of Sonoran pronghorn within the defined NEP area. An Environmental Assessment and Finding of No Significant Impact have been prepared for this action (see ADDRESSES section below).

Quantification of four major metabolites of embryotoxic N-methyl- and N-ethyl-2-pyrrolidone in human urine by cooled-injection gas chromatography and isotope dilution mass spectrometry.

PubMed

Schindler, Birgit K; Koslitz, Stephan; Meier, Swetlana; Belov, Vladimir N; Koch, Holger M; Weiss, Tobias; Brüning, Thomas; Käfferlein, Heiko U

2012-04-17

N-Methyl- and N-ethyl-2-pyrollidone (NMP and NEP) are frequently used industrial solvents and were shown to be embryotoxic in animal experiments. We developed a sensitive, specific, and robust analytical method based on cooled-injection (CIS) gas chromatography and isotope dilution mass spectrometry to analyze 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI), two newly identified presumed metabolites of NEP, and their corresponding methyl counterparts (5-HNMP, 2-HMSI) in human urine. The urine was spiked with deuterium-labeled analogues of these metabolites. The analytes were separated from urinary matrix by solid-phase extraction and silylated prior to quantification. Validation of this method was carried out by using both, spiked pooled urine samples and urine samples from 56 individuals of the general population with no known occupational exposure to NMP and NEP. Interday and intraday imprecision was better than 8% for all metabolites, while the limits of detection were between 5 and 20 μg/L depending on the analyte. The high sensitivity of the method enables us to quantify NMP and NEP metabolites at current environmental exposures by human biomonitoring.

Hyposialylation of neprilysin possibly affects its expression and enzymatic activity in hereditary inclusion-body myopathy muscle.

PubMed

Broccolini, Aldobrando; Gidaro, Teresa; De Cristofaro, Raimondo; Morosetti, Roberta; Gliubizzi, Carla; Ricci, Enzo; Tonali, Pietro A; Mirabella, Massimiliano

2008-05-01

Autosomal recessive hereditary inclusion-body myopathy (h-IBM) is caused by mutations of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene, a rate-limiting enzyme in the sialic acid metabolic pathway. Previous studies have demonstrated an abnormal sialylation of glycoproteins in h-IBM. h-IBM muscle shows the abnormal accumulation of proteins including amyloid-beta (Abeta). Neprilysin (NEP), a metallopeptidase that cleaves Abeta, is characterized by the presence of several N-glycosylation sites, and changes in these sugar moieties affect its stability and enzymatic activity. In the present study, we found that NEP is hyposialylated and its expression and enzymatic activity reduced in all h-IBM muscles analyzed. In vitro, the experimental removal of sialic acid by Vibrio Cholerae neuraminidase in cultured myotubes resulted in reduced expression of NEP. This was most likely because of a post-translational modification consisting in an abnormal sialylation of the protein that leads to its reduced stability. Moreover, treatment with Vibrio Cholerae neuraminidase was associated with an increased immunoreactivity for Abeta mainly in the form of distinct cytoplasmic foci within myotubes. We hypothesize that, in h-IBM muscle, hyposialylated NEP has a role in hampering the cellular Abeta clearing system, thus contributing to its abnormal accumulation within vulnerable fibers and possibly promoting muscle degeneration.

The Coupling of Ecosystem Productivity and Water Availability in Dryland Regions

NASA Astrophysics Data System (ADS)

Scott, R. L.; Biederman, J. A.; Barron-Gafford, G.

2014-12-01

Land cover and climatic change will alter biosphere-atmosphere exchanges of water vapor and carbon dioxide depending, in part, on feedbacks between biotic activity and water availability. Eddy covariance observations allow us to estimate ecosystem-scale productivity and respiration, and these datasets are now becoming sufficiently mature to advance understanding of these ecohydrological interactions. Here we use a network of sites in semiarid western North America representing gradients of water availability and functional plant type. We examine how precipitation (P) controls evapotranspiration (ET), net ecosystem production (NEP), and its component fluxes of ecosystem respiration (Reco) and gross ecosystem production (GEP). Despite the high variability in seasonal and annual precipitation timing and amounts that we expect to influence ecosystem function, we find persistent overall relationships between P or ET and the fluxes of NEP, Reco and GEP across the network, indicating a commonality and resilience in ecosystem soil and plant response to water availability. But we also observe several important site differences such as prior seasonal legacy effects on subsequent fluxes which vary depending on dominant plant functional type. For example, multiyear droughts, episodic cool-season droughts, and hard winter freezes seem to affect the herbaceous species differently than the woody ones. Nevertheless, the overall, strong coupling between hydrologic and ecologic processes at these sites bolsters our ability to predict the response of dryland ecosystems to future precipitation change.

Pulmonary actions of the neurokinin1-specific agonist [Sar9,Met(O2)11]-substance P.

PubMed

Yiamouyiannis, C A; Stengel, P W; Cockerham, S L; Silbaugh, S A

1995-01-01

We examined the relationship between airway obstruction and plasma extravasation produced by the intravenous administration of the selective NK1 receptor agonist [Sar9, Met(O2)11]-substance P(SP). Conscious guinea-pigs were injected with Evans' blue dye followed by intravenous [Sar9,Met(O2)11]-SP. Animals were killed 3 min later and airway obstruction, determined via excised lung gas volumes, and plasma extravasation in the trachea, mainstem bronchi and intrapulmonary airways quantitated. Maximal plasma protein extravasation occurred at a dose about 30 times less than that required to elicit airway obstruction. Neither the neutral endopeptidase (NEP) inhibitor, thiorphan, or the angiotensin-converting enzyme (ACE) inhibitor, captopril, altered the extravasation response to [Sar9,Met(O2)11]-SP. However, thiorphan alone or combined with captopril produced a small but significant potentiation of the airway obstructive response. The marked difference between pulmonary gas trapping and Evans' blue extravasation responses suggest that [Sar9,Met(O2)11]-SP-induced airway obstruction is not secondary to increased pulmonary edema.

Stand age and climate drive forest carbon balance recovery

NASA Astrophysics Data System (ADS)

Besnard, Simon; Carvalhais, Nuno; Clevers, Jan; Herold, Martin; Jung, Martin; Reichstein, Markus

2016-04-01

Forests play an essential role in the terrestrial carbon (C) cycle, especially in the C exchanges between the terrestrial biosphere and the atmosphere. Ecological disturbances and forest management are drivers of forest dynamics and strongly impact the forest C budget. However, there is a lack of knowledge on the exogenous and endogenous factors driving forest C recovery. Our analysis includes 68 forest sites in different climate zones to determine the relative influence of stand age and climate conditions on the forest carbon balance recovery. In this study, we only included forest regrowth after clear-cut stand replacement (e.g. harvest, fire), and afforestation/reforestation processes. We synthesized net ecosystem production (NEP), gross primary production (GPP), ecosystem respiration (Re), the photosynthetic respiratory ratio (GPP to Re ratio), the ecosystem carbon use efficiency (CUE), that is NEP to GPP ratio, and CUEclimax, where GPP is derived from the climate conditions. We implemented a non-linear regression analysis in order to identify the best model representing the C flux patterns with stand age. Furthermore, we showed that each C flux have a non-linear relationship with stand age, annual precipitation (P) and mean annual temperature (MAT), therefore, we proposed to use non-linear transformations of the covariates for C fluxes'estimates. Non-linear stand age and climate models were, therefore, used to establish multiple linear regressions for C flux predictions and for determining the contribution of stand age and climate in forest carbon recovery. Our findings depicted that a coupled stand age-climate model explained 33% (44%, average site), 62% (76%, average site), 56% (71%, average site), 41% (59%, average site), 50% (65%, average site) and 36% (50%, average site) of the variance of annual NEP, GPP, Re, photosynthetic respiratory ratio, CUE and CUEclimax across sites, respectively. In addition, we showed that gross fluxes (e.g. GPP and Re) are mainly climatically driven with 54.2% (68.4%, average site) and 54.1% (71.0%, average site) of GPP and Re variability, respectively, explained by the sum of MAT and P. However, annual NEP, GPP to Re ratio and CUEclimax are affected by both forest stand age and climate conditions, in particular MAT. The key result is that forest stand age plays a crucial role in determining CUE (36.4% and 48.2% for all years per site and average site, respectively), while climate conditions have less effect on CUE (13.6% and 15.4% for all years per site and average site, respectively). These findings are relevant for the implementation of Earth system models and imply that information both on forest stand age and climate conditions are critical to improve the accuracy of global terrestrial C models's estimates.

Development of the GaAs-based THz Photoconductor and Balloon-borne Experiment Module TG-ZERO

NASA Astrophysics Data System (ADS)

Watanabe, Kentaroh; Kataza, Hirokazu; Wada, Takehiko; Murakami, Hiroshi; Kamizuka, Takafumi; Makitsubo, Hironobu; Yamashita, Kyohei; Wakaki, Moriaki; Abe, Osamu

2009-08-01

The far-infrared (around 1 terahertz (THz)) extrinsic photoconductor is fabricated by a LPE-grown GaAs semiconductor. This GaAs detector can detect longer wavelength photons than the stressed Ge:Ga conventionally used for astronomical infrared observation. We applied the liquid phase epitaxy to obtain a suitable purity of GaAs crystals, and the test N-GaAs photoconductor device shows spectroscopic response over a wide wavelength range of 150-300 micron. The best sample shows 30 A/W of responsivity and 10-16 W/Hz0.5 of NEP is expected at 295 micron of wavelength and T = 1.6 K. In addition, we constructed the terahertz photometer module (TG-ZERO) using our N-GaAs photoconductors. TG-ZERO has four channel bands with N-GaAs and Ge:Ga photoconductors. The development process, the result of experiments, and the basic specifications of TG-ZERO are all reported in this paper.

Generation of a variety of stable Influenza A reporter viruses by genetic engineering of the NS gene segment

PubMed Central

Reuther, Peter; Göpfert, Kristina; Dudek, Alexandra H.; Heiner, Monika; Herold, Susanne; Schwemmle, Martin

2015-01-01

Influenza A viruses (IAV) pose a constant threat to the human population and therefore a better understanding of their fundamental biology and identification of novel therapeutics is of upmost importance. Various reporter-encoding IAV were generated to achieve these goals, however, one recurring difficulty was the genetic instability especially of larger reporter genes. We employed the viral NS segment coding for the non-structural protein 1 (NS1) and nuclear export protein (NEP) for stable expression of diverse reporter proteins. This was achieved by converting the NS segment into a single open reading frame (ORF) coding for NS1, the respective reporter and NEP. To allow expression of individual proteins, the reporter genes were flanked by two porcine Teschovirus-1 2A peptide (PTV-1 2A)-coding sequences. The resulting viruses encoding luciferases, fluorescent proteins or a Cre recombinase are characterized by a high genetic stability in vitro and in mice and can be readily employed for antiviral compound screenings, visualization of infected cells or cells that survived acute infection. PMID:26068081

Renewing the New Environmental Paradigm Scale: The Underlying Diversity of Contemporary Environmental Worldviews

NASA Astrophysics Data System (ADS)

Bernstein, Jennifer M.

This dissertation explored the attitudes, values, and beliefs underlying the contemporary environmental movement. At present, the most widely used means of measuring environmental attitudes is the New Environmental Paradigm (NEP) Scale. This dissertation chronicles the development and establishment of the NEP and the important role it has played in social science research. It also reviews key empirical and theoretical critiques of the scale, arguing that the worldview embodied by the NEP is representative of a narrow understanding of pro-environmental thought and that there remains the need for a new scale built using the core dimensions underlying contemporary environmentalism's diversity. Based on an assessment of contemporary environmental discourse, it was theorized that the key areas in which environmentalists diverge are with respect to nature, technology, and scale of societal response. To test this assertion, this project deeply explored a small sample of carefully selected participants with strong environmental identities and diverse attitudes and values. Quantitative and qualitative data was collected using survey question items and in-depth Repertory Grid interviews. Foremost, analysis showed that the sample of environmentalists studied were far from ideologically homogenous. While they agreed with respect to certain issues, such as the seriousness of environmental problems and the inability of the earth to accommodate unlimited resource demands, they also disagreed in key areas, such as the ability of technology to solve environmental problems and the scale at which effective change occurs. With respect to effective environmental problem solving, respondents mentioned green technologies, reducing resource consumption, and policy changes, and they differentiated between these solutions based on cost, the type of social change needed to bring these solutions to fruition, and how difficult they would be to enact. Demographic differences were also assessed: younger respondents were more likely to mention green technology and alternative transportation while older respondents discussed individual political engagement and education and awareness. Respondents were also clustered on the basis of their shared worldviews, which suggested that participants formed four key ideologically coherent groups. Analysis of the attitudes, values, and worldviews of each group and its members showed both internal cohesiveness as well as heterogeneity. The conclusion suggests the components of the NEP that should be retained, points to topical and theoretical additions, and establishes a framework for future research at the population level.

SuperSpec, The On-Chip Spectrometer: Improved NEP and Antenna Performance

NASA Astrophysics Data System (ADS)

Wheeler, Jordan; Hailey-Dunsheath, S.; Shirokoff, E.; Barry, P. S.; Bradford, C. M.; Chapman, S.; Che, G.; Doyle, S.; Glenn, J.; Gordon, S.; Hollister, M.; Kovács, A.; LeDuc, H. G.; Mauskopf, P.; McGeehan, R.; McKenney, C.; Reck, T.; Redford, J.; Ross, C.; Shiu, C.; Tucker, C.; Turner, J.; Walker, S.; Zmuidzinas, J.

2018-05-01

SuperSpec is a new technology for mm and sub-mm spectroscopy. It is an on-chip spectrometer being developed for multi-object, moderate-resolution (R˜ 300 ), large bandwidth survey spectroscopy of high-redshift galaxies for the 1 mm atmospheric window. This band accesses the CO ladder in the redshift range of z = 0-4 and the [CII] 158 μm line from redshift z = 5-9. SuperSpec employs a novel architecture in which detectors are coupled to a series of resonant filters along a single microwave feedline instead of using dispersive optics. This construction allows for the creation of a full spectrometer occupying only ˜ 10 cm^2 of silicon, a reduction in size of several orders of magnitude when compared to standard grating spectrometers. This small profile enables the production of future multi-beam spectroscopic instruments envisioned for the millimeter band to measure the redshifts of dusty galaxies efficiently. The SuperSpec collaboration is currently pushing toward the deployment of a SuperSpec demonstration instrument in fall of 2018. The progress with the latest SuperSpec prototype devices is presented; reporting increased responsivity via a reduced inductor volume (2.6 μm^3 ) and the incorporation of a new broadband antenna. A detector NEP of 3-4 × 10^{-18} W/Hz^{0.5} is obtained, sufficient for background-limited observation on mountaintop sites. In addition, beam maps and efficiency measurements of a new wide-band dual bow-tie slot antenna are shown.

Quality assurance and reliability sub-committee W88-0/Mk5 weapon assessment NSA lab test results (u)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whitney, Earl M

2010-11-29

The purpose of this report is to gather appropriate level of relevant stockpile surveillance data to assess trends in the NEP quality, reliability, performance, and safety over the life of the system. The objectives are to gather relevant stockpile data to assess NEP quality and trends and to develop metrics to assess the suitability of the surveillance sampling regime to meet assessment process requirements.

Towards an optimal adaptation of exposure to NOAA assessment methodology in Multi-Source Industrial Scenarios (MSIS): the challenges and the decision-making process

NASA Astrophysics Data System (ADS)

López de Ipiña, JM; Vaquero, C.; Gutierrez-Cañas, C.

2017-06-01

It is expected a progressive increase of the industrial processes that manufacture of intermediate (iNEPs) and end products incorporating ENMs (eNEPs) to bring about improved properties. Therefore, the assessment of occupational exposure to airborne NOAA will migrate, from the simple and well-controlled exposure scenarios in research laboratories and ENMs production plants using innovative production technologies, to much more complex exposure scenarios located around processes of manufacture of eNEPs that, in many cases, will be modified conventional production processes. Here will be discussed some of the typical challenging situations in the process of risk assessment of inhalation exposure to NOAA in Multi-Source Industrial Scenarios (MSIS), from the basis of the lessons learned when confronted to those scenarios in the frame of some European and Spanish research projects.

Mission operations for unmanned nuclear electric propulsion outer planet exploration with a thermionic reactor spacecraft.

NASA Technical Reports Server (NTRS)

Spera, R. J.; Prickett, W. Z.; Garate, J. A.; Firth, W. L.

1971-01-01

Mission operations are presented for comet rendezvous and outer planet exploration NEP spacecraft employing in-core thermionic reactors for electric power generation. The selected reference missions are the Comet Halley rendezvous and a Jupiter orbiter at 5.9 planet radii, the orbit of the moon Io. The characteristics of the baseline multi-mission NEP spacecraft are presented and its performance in other outer planet missions, such as Saturn and Uranus orbiters and a Neptune flyby, are discussed. Candidate mission operations are defined from spacecraft assembly to mission completion. Pre-launch operations are identified. Shuttle launch and subsequent injection to earth escape by the Centaur D-1T are discussed, as well as power plant startup and the heliocentric mission phases. The sequence and type of operations are basically identical for all missions investigated.

Taxation of oil and gas revenues: Canada

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helliwell, J.F.

1982-04-01

The policy of Canadianization must be included in any analysis of energy taxation in Canada, where energy resources are unevenly divided among the provinces. The provinces own most natural resources, but the oil and gas industry is dominated by foreign ownership and control. The Federal National Energy Program (NEP) of 1980 target of 50% Canadian ownership by 1990 conflicts with provincial practices by shifting incentives from depletion allowance to ownership grants for buy backs. The NEP compares unfavorably with US taxation, and that, combined with US deregulation, has shifted drilling activity to the US. The controversial tax elements do comparemore » with those of the United Kingdom and other North Sea producers. Although recent controversy has caused investors to defer projects, Canadian investment is competitive with most countries. 5 references, 1 table. (DCK)« less

Relational values resonate broadly and differently than intrinsic or instrumental values, or the New Ecological Paradigm.

PubMed

Klain, Sarah C; Olmsted, Paige; Chan, Kai M A; Satterfield, Terre

2017-01-01

Value orientations used to explain or justify conservation have been rooted in arguments about how much and in what context to emphasize the intrinsic versus instrumental value of nature. Equally prominent are characterizations of beliefs known as the New Ecological Paradigm (NEP), often used to help explain pro-environmental behaviour. A recent alternative to these positions has been identified as 'relational value'-broadly, values linking people and ecosystems via tangible and intangible relationships to nature as well as the principles, virtues and notions of a good life that may accompany these. This paper examines whether relational values are distinct from other value orientation and have potential to alleviate the intrinsic-instrumental debate. To test this possibility, we sought to operationalize the construct-relational values-by developing six relational statements. We ask: 1) Do the individual statements used to characterize relational values demonstrate internal coherence as either a single or multi-dimensional construct? 2) Do relational value statements (including those strongly stated) resonate with diverse populations? 3) Do people respond to relational value statements in a consistently different way than NEP scale statements? Data for this work is drawn from an online panel of residents of northeastern US (n = 400), as well as a sample of Costa Rican farmers (n = 253) and tourists in Costa Rica (n = 260). Results indicate relational values are distinct as a construct when compared to the NEP.

Seroepidemiological study of Toxoplasma gondii infection in a population of Iranian epileptic patients.

PubMed

Babaie, Jalal; Sayyah, Mohammad; Gharagozli, Kourosh; Mostafavi, Ehsan; Golkar, Majid

2017-01-01

Epilepsy is one of the most common neurologic disorders. Underlying cause of epilepsy is unknown in 60 % of the patients. Toxoplasma gondii is an intracellular parasite which is capable of forming tissue cysts in brain of chronically infected hosts including humans. Some epidemiological studies suggested an association between toxoplasmosis and acquisition of epilepsy. In this study we determined seroprevalence of latent Toxoplasma infection in a population of Iranian epileptic patients. Participants were classified in three groups as Iranian epileptic patients (IEP, n = 414), non-epileptic patients who had other neurologic disorders (NEP, n = 150), and healthy people without any neurologic disorders (HP, n = 63). The presence of anti- Toxoplasma IgG antibodies and IgG titer in the sera were determined by ELISA method. Anti- T. gondii IgG seroprevalence obtained 35.3 %, 34.7 % and 38.1 % in IEP, NEP and HP, respectively. The seroprevalence rate was not significantly different among the three groups (P = 0.88). Anti- T. gondii IgG titer was 55.7 ± 78, 52.4 ± 74 and 69.7 ± 92 IU/ml in IEP, NEP and HP, respectively. There was not any statistically significant difference in the antibody titer between the study groups (P = 0.32). The rate of T. gondii infection in epileptic patients was not higher than non-epileptic patients and healthy people in the Iranian population.

Sound Radiation from a Supersonic Jet Passing Through a Partially Open Exhaust Duct

NASA Technical Reports Server (NTRS)

Kandula, Max

2011-01-01

The radiation of sound from a perfectly expanded Mach 2.5 cold supersonic jet of 25.4 mm exit diameter flowing through a partially open rigid-walled duct with an upstream i-deflector has been studied experimentally. In the experiments, the nozzle is mounted vertically, with the nozzle exit plane at a height of 73 jet diameters above ground level. Relative to the nozzle exit plane (NEP), the location of the duct inlet is varied at 10, 5, and -1 jet diameters. Far-field sound pressure levels were obtained at 54 jet diameters above ground with the aid of acoustic sensors equally spaced around a circular arc of radius equal to 80 jet diameters from the jet axis. Data on the jet acoustic field for the partially open duct were obtained and compared with those with a free jet and with a closed duct. The results suggest that for the partially open duct the overall sound pressure level (OASPL) decreases as the distance between the NEP and the duct inlet plane decreases, while the opposite trend is observed for the closed duct. It is also concluded that the observed peak frequency in the partially open duct increases above the free jet value as the angle from the duct axis is increased, and as the duct inlet plane becomes closer to the NEP.

The drought response of Theobroma cacao (cacao) and the regulation of genes involved in polyamine biosynthesis by drought and other stresses.

PubMed

Bae, Hanhong; Kim, Soo-Hyung; Kim, Moon S; Sicher, Richard C; Lary, David; Strem, Mary D; Natarajan, Savithiry; Bailey, Bryan A

2008-02-01

Drought can negatively impact pod production despite the fact that cacao production usually occurs in tropical areas having high rainfall. Polyamines (PAs) have been associated with the response of plants to drought in addition to their roles in responses to many other stresses. The constitutive and drought inducible expression patterns of genes encoding enzymes involved in PA biosynthesis were determined: an ornithine decarboxylase (TcODC), an arginine decarboxylase (TcADC), an S-adenosylmethionine decarboxylase (TcSAMDC), a spermidine synthase (TcSPDS), and a spermine synthase (TcSPMS). Expression analysis using quantitative real-time reverse transcription-PCR (QPCR) results showed that the PA biosynthesis genes were expressed in all plant tissues examined. Constitutive expression of PA biosynthesis genes was generally highest in mature leaves and open flowers. Expression of TcODC, TcADC, and TcSAMDC was induced with the onset of drought and correlated with changes in stomatal conductance, photosynthesis, photosystem II efficiency, leaf water potential and altered emission of blue-green fluorescence from cacao leaves. Induction of TcSAMDC in leaves was most closely correlated with changes in water potential. The earliest measured responses to drought were enhanced expression of TcADC and TcSAMDC in roots along with decreases in stomatal conductance, photosynthesis, and photosystem II efficiency. Elevated levels of putrescine, spermidine, and spermine were detected in cacao leaves 13days after the onset of drought. Expression of all five PA associated transcripts was enhanced (1.5-3-fold) in response to treatment with abscisic acid. TcODC and TcADC, were also responsive to mechanical wounding, infection by Phytophthora megakarya (a causal agent of black pod disease in cacao), the necrosis- and ethylene-inducing protein (Nep1) of Fusarium oxysporum, and flower abscission. TcSAMDC expression was responsive to all stresses except flower abscission. TcODC, although constitutively expressed at much lower levels than TcADC, TcSAMDC, TcSPDS, and TcSPMS, was highly inducible by the fungal protein Nep1 (135-fold) and the cacao pathogen Phytophthora megakarya (671-fold). The full length cDNA for ODC was cloned and characterized. Among the genes studied, TcODC, TcADC, and TcSAMDC were most sensitive to induction by drought in addition to other abiotic and biotic stresses. TcODC, TcADC, and TcSAMDC may share signal transduction pathways and/or the stress induced signal induction pathways may converge at these three genes leading to similar although not identical patterns of expression. It is possible altering PA levels in cacao will result in enhanced tolerance to multiple stresses including drought and disease as has been demonstrated in other crops.

Wideband infrared heterodyne receiver front-end. [for use in CO2 laser communications

NASA Technical Reports Server (NTRS)

Peyton, B. J.; Wolczok, J.

1974-01-01

A 10.6 micron infrared heterodyne receiver front end was developed for use in a wideband CO2 laser communications link. The infrared receiver employs an 850 MHz response PV HgCdTe photomixer which is mounted in a space quality housing, a low-noise 5 to 1500 MHz IF preamplifier, and a remote control panel. The receiver was designed to handle + or - 750 MHz of Doppler shift while providing an instantaneous information bandwidth of 400 MHz. The measured receiver sensitivity NEP was 1.0 x 10 to the 19th power W/Hz for a photomixer temperature of T sub m = 77 K and an IF beat frequency of 20 MHz and degraded to 1.75 x 10 to the 19th power W/Hz for T sub m = 130 K.

Southeast Asia Report

DTIC Science & Technology

1985-08-28

5 Jul 85) 77 DAP To Launch Campaign Against Injustice of NEP (KIN KWOK DAILY NEWS, 7 Jun 85) 79 Gerakan on Possible Withdrawal of Michael Chen...also elected on the occasion were K. H. Tarmudji, H. M. Soedjono, Prof. K. H. Ibrahim Hosen, K. H. Abdul Rachman Wachid, H. Abdul Qadir Basalamah, Dr...JPRS-SEA-85-131 28 August 1985 MALAYSIA DAP TO LAUNCH CAMPAIGN AGAINST INJUSTICE OF NEP Selangor KIN KWOK DAILY NEWS in Chinese 7 Jun 85 p 3 [Text

Power-Conversion Concept Designed for the Jupiter Icy Moons Orbiter

NASA Technical Reports Server (NTRS)

Mason, Lee S.

2004-01-01

The Jupiter Icy Moons Orbiter (JIMO) is a bold new mission being developed by NASA's Office of Space Science under Project Prometheus. JIMO is examining the potential of nuclear electric propulsion (NEP) technology to efficiently deliver scientific payloads to three of Jupiter's moons: Callisto, Ganymede, and Europa. A critical element of the NEP spacecraft is the space reactor power system (SRPS), consisting of the nuclear reactor, power conversion, heat rejection, and power management and distribution (PMAD).

Ex vivo effects of an Oenothera paradoxa extract on the reactive oxygen species generation and neutral endopeptidase activity in neutrophils from patients after acute myocardial infarction.

PubMed

Kiss, Anna K; Kapłon-Cieślicka, Agnieszka; Filipiak, Krzysztof J; Opolski, Grzegorz; Naruszewicz, Marek

2012-04-01

Oxidative stress induced by reactive oxygen species (ROS) is considered to play an important part in the aetiology of coronary heart disease. Apart from ROS, neutrophils are a source of neutral endopeptidase (NEP) that inactivates protective natriuretic peptides. The aim of the present study was to evaluate the in vitro ROS generation and inhibition of NEP activity in neutrophils obtained from healthy volunteers and from patients after acute myocardial infarction (AMI) by an aqueous extract of Oenothera paradoxa. Neutrophils isolated from AMI patients showed two-fold higher ROS generation compared with cells from healthy donors, especially in the lucigenin-enhanced luminescence model, which suggests intensive O₂⁻ generation. The addition of O. paradoxa extract at concentrations of 0.2, 2 and 20 µg/mL resulted in a significant reduction in ROS generation. The extracellular NEP activity was higher in patients after AMI compared with healthy individuals (15.0 ± 0.9 versus 10.3 ± 0.5 nmol AMC/10(6) cells/60 min; p = 0.001). The addition of O. paradoxa extract at concentrations of 20, 50 and 100 µg/mL resulted in a significant reduction in NEP activity in both groups. O. paradoxa extract appears to be an interesting candidate for supplementation in the prevention of cardiovascular diseases. Copyright © 2011 John Wiley & Sons, Ltd.

CARBON BALANCE OF FOREST BIOMES IN THE FORMER USSR

EPA Science Inventory

Sources and sinks of carbon and the sequestration potential of forest biomes in the former Soviet Union (FSU) were assessed under non-equilibrium conditions by considering, 1) net ecosystem productivity (NEP) of different age forest stands and actual forest coverage, 2) carbon fl...

Amide-to-triazole switch vs. in vivo NEP-inhibition approaches to promote radiopeptide targeting of GRPR-positive tumors.

PubMed

Maina, Theodosia; Kaloudi, Aikaterini; Valverde, Ibai E; Mindt, Thomas L; Nock, Berthold A

2017-09-01

Radiolabeled bombesin (BBN)-analogs have been proposed for diagnosis and therapy of gastrin-releasing peptide receptor (GRPR)-expressing tumors, such as prostate, breast and lung cancer. Metabolic stability represents a crucial factor for the success of this approach by ensuring sufficient delivery of circulating radioligand to tumor sites. The amide-to-triazole switch on the backbone of DOTA-PEG 4 -[Nle 14 ]BBN(7-14) (1) was reported to improve the in vitro stability of resulting 177 Lu-radioligands. On the other hand, in-situ inhibition of neutral endopeptidase (NEP) by coinjection of phosphoramidon (PA) was shown to significantly improve the in vivo stability and tumor uptake of biodegradable radiopeptides. We herein compare the impact of the two methods on the bioavailability and localization of 177 Lu-DOTA-PEG 4 -[Nle 14 ]BBN(7-14) analogs in GRPR-positive tumors in mice. The 1,4-disubstituted [1-3]-triazole was used to replace one (2: Gly 11 -His 12 ; 3: Ala 9 -Val 10 ) or two (4: Ala 9 -Val 10 and Gly 11 -His 12 ) peptide bonds in 1 (reference) and all compounds were labeled with 177 Lu. Each of [ 177 Lu]1-[ 177 Lu]4 was injected without (control) or with PA in healthy mice. Blood samples collected 5min post-injection (pi) were analyzed by HPLC. Biodistribution of [ 177 Lu]1-[ 177 Lu]4 was conducted in SCID mice bearing human prostate adenocarcinoma PC-3 xenografts at 4h pi. Groups of 4 animals were injected with radioligand, alone (controls), or with coinjection of PA, or of a mixture of PA and excess and [Tyr 4 ]BBN to determine GRPR-specificity of uptake (Block). The in vivo stability of the radioligands was: [ 177 Lu]1 (25% intact), [ 177 Lu]2 (45% intact), [ 177 Lu]3 (30% intact) and [ 177 Lu]4 (40% intact). By PA-coinjection these values notably increased to 90%-93%. Moreover, treatment with PA induced an impressive and GRPR-specific uptake of all radioligands in the PC-3 xenografts at 4h pi: [ 177 Lu]1: 4.7±0.4 to 24.8±4.9%ID/g; [ 177 Lu]2: 8.3±1.2 to 26.0±1.1%ID/g; [ 177 Lu]3: 6.6±0.4 to 21.3±4.4%ID/g; and [ 177 Lu]4: 4.8±1.6 to 13.7±3.8%ID/g. This study has shown that amide-to-triazole substitutions in 177 Lu-DOTA-PEG 4 -[Nle 14 ]BBN(7-14) induced minor effects on bioavailability and tumor uptake in mice models, whereas in-situ NEP-inhibition(s) by PA impressively improved in vivo profiles. Copyright © 2017 Elsevier Inc. All rights reserved.

Status report on nuclear electric propulsion systems

NASA Technical Reports Server (NTRS)

Stearns, J. W.

1975-01-01

Progress in nuclear electric propulsion (NEP) systems for a multipayload multimission vehicle needed in both deep-space missions and a variety of geocentric missions is reviewed. The space system power level is a function of the initial launch vehicle mass, but developments in out-of-core nuclear thermionic direct conversion have broadened design options. Cost, design, and performance parameters are compared for reusable chemical space tugs and NEP reusable space tugs. Improvements in heat pipes, ion engines, and magnetoplasmadynamic arc jet thrust subsystems are discussed.

Nuclear propulsion technology development - A joint NASA/Department of Energy project

NASA Technical Reports Server (NTRS)

Clark, John S.

1992-01-01

NASA-Lewis has undertaken the conceptual development of spacecraft nuclear propulsion systems with DOE support, in order to establish the bases for Space Exploration Initiative lunar and Mars missions. This conceptual evolution project encompasses nuclear thermal propulsion (NTP) and nuclear electric propulsion (NEP) systems. A technology base exists for NTP in the NERVA program files; more fundamental development efforts are entailed in the case of NEP, but this option is noted to offer greater advantages in the long term.

Fabrication of Ultrasensitive Transition Edge Sensor Bolometric Detectors for HIRMES

NASA Technical Reports Server (NTRS)

Brown, Ari-David; Brekosky, Regis; Franz, David; Hsieh, Wen-Ting; Kutyrev, Alexander; Mikula, Vilem; Miller, Timothy; Moseley, S. Harvey; Oxborrow, Joseph; Rostem, Karwan;

A superconducting bolometer camera for APEX

NASA Astrophysics Data System (ADS)

Jethava, N.; Kreysa, E.; Siringo, G.; Esch, W.; Gemünd, H.-P.; May, T.; Anders, S.; Fritzsch, L.; Boucher, R.; Zakosarenko, V.; Meyer, H.-G.

2006-06-01

We present the experimental results of voltage-biased superconducting bolometers (VSB) on silicon nitride (Si 3N 4) membranes with niobium wiring developed in collaboration between the Institut fur Physikalische Hochtechnologie (IPHT), Jena, Germany and the Max-Planck-Institut fur Radioastronomie (MPIfR), Bonn, Germany. The bolometer current is measured with the superconducting quantum interference device (SQUID), and as expected, the current responsivity is proportional to the inverse of the bias voltage. The experiments were performed with bilayer gold-palladium molybdenum thermistor at 300 mK 3He cooled cryostat and the desired transition temperature of T c = 450 mK is achieved. The strong negative electro-thermal feedback of the VSB maintains the constant bolometer temperature and reduces the response time from 4 ms to 100 μs. We have tested thermistors of various size and shape on a continuous membrane and achieved a noise equivalent power (NEP) of 3.5 × 10 -16 W/√Hz. The measured NEP is relatively high due to the comparatively high background and high thermal conductance of the unstructured silicon nitride (Si 3N 4) membrane. We have fabricated 8-leg spider structured membranes in three different geometries and the relation between the geometry and the thermal conductance (G) is studied. Using the COSMOS finite element analysis tool, we have modeled the TES bolometers to determine the thermal conductance for different geometries and calculated the various parameters. Due to the demands of large number pixel bolometer camera we plan to implement multiplex readout with integrated SQUIDs in our design.

Enhancement in the upper tropospheric humidity associated with aerosol loading over tropical Pacific

NASA Astrophysics Data System (ADS)

Kottayil, Ajil; Satheesan, K.

2015-12-01

Many modeling studies have indicated that aerosol interactions with clouds increase the upper tropospheric humidity (UTH), but observational evidences are sparse. Using satellite datasets of upper tropospheric humidity and aerosols, this study shows that aerosols increase the upper tropospheric humidity over the tropical North West Pacific (NWP) and North East Pacific (NEP). The observations show an increase in the UTH by 2.8%RH over NEP for an increment of 0.12 in aerosol optical depth (AOD) and 2%RH increase in UTH over NWP for an increment of 0.19 in AOD. The study also quantifies the change in longwave cloud radiative forcing (LWCRF) as a consequence of the increase in UTH due to aerosols. The LWCRF increases by 3.38 W m-2 over NEP and by 4.46 W m-2 over NWP. The result that aerosols increase the upper tropospheric humidity is significant since the latter plays a crucial role in regulating the Earth's radiation budget and water vapor feedback.

Ectopic expression of LEAFY COTYLEDON1-LIKE gene and localized auxin accumulation mark embryogenic competence in epiphyllous plants of Helianthus annuus × H. tuberosus

PubMed Central

Chiappetta, A.; Fambrini, M.; Petrarulo, M.; Rapparini, F.; Michelotti, V.; Bruno, L.; Greco, M.; Baraldi, R.; Salvini, M.; Pugliesi, C.; Bitonti, M. B.

2009-01-01

Background and Aims The clone EMB-2 of the interspecific hybrid Helianthus annuus × H. tuberosus provides an interesting system to study molecular and physiological aspects of somatic embryogenesis. Namely, in addition to non-epiphyllous (NEP) leaves that expand normally, EMB-2 produces epiphyllous (EP) leaves bearing embryos on the adaxial surface. This clone was used to investigate if the ectopic expression of H. annuus LEAFY COTYLEDON1-LIKE (Ha-L1L) gene and auxin activity are correlated with the establishment of embryogenic competence. Methods Ha-L1L expression was evaluated by semi-quantitative RT-PCR and in situ hybridization. The endogenous level and spatial distribution of free indole-3-acetic acid (IAA) were estimated by a capillary gas chromatography–mass spectrometry–selected ion monitoring method and an immuno-cytochemical approach. Key Results Ectopic expression of Ha-L1L was detected in specific cell domains of the adaxial epidermis of EP leaves prior to the development of ectopic embryos. Ha-L1L was expressed rapidly when NEP leaves were induced to regenerate somatic embryos by in vitro culture. Differences in auxin distribution pattern rather than in absolute level were observed between EP and A-2 leaves. More precisely, a strong IAA immuno-signal was detected in single cells or in small groups of cells along the epidermis of EP leaves and accompanied the early stages of embryo development. Changes in auxin level and distribution were observed in NEP leaves induced to regenerate by in vitro culture. Exogenous auxin treatments lightly influenced Ha-L1L transcript levels in spite of an enhancement of the regeneration frequency. Conclusions In EP leaves, Ha-L1L activity marks the putative founder cells of ectopic embryos. Although the ectopic expression of Ha-L1L seems to be not directly mediated by auxin levels per se, it was demonstrated that localized Ha-L1L expression and IAA accumulation in leaf epidermis domains represent early events of somatic embryogenesis displayed by the epiphyllous EMB-2 clone. PMID:19151043

Net ecosystem production: A comprehensive measure of net carbon accumulation by ecosystems

USGS Publications Warehouse

Randerson, J.T.; Chapin, F. S.; Harden, J.W.; Neff, J.C.; Harmon, M.E.

2002-01-01

The conceptual framework used by ecologists and biogeochemists must allow for accurate and clearly defined comparisons of carbon fluxes made with disparate techniques across a spectrum of temporal and spatial scales. Consistent with usage over the past four decades, we define "net ecosystem production" (NEP) as the net carbon accumulation by ecosystems. Past use of this term has been ambiguous, because it has been used conceptually as a measure of carbon accumulation by ecosystems, but it has often been calculated considering only the balance between gross primary production (GPP) and ecosystem respiration. This calculation ignores other carbon fluxes from ecosystems (e.g., leaching of dissolved carbon and losses associated with disturbance). To avoid conceptual ambiguities, we argue that NEP be defined, as in the past, as the net carbon accumulation by ecosystems and that it explicitly incorporate all the carbon fluxes from an ecosystem, including autotrophic respiration, heterotrophic respiration, losses associated with disturbance, dissolved and particulate carbon losses, volatile organic compound emissions, and lateral transfers among ecosystems. Net biome productivity (NBP), which has been proposed to account for carbon loss during episodic disturbance, is equivalent to NEP at regional or global scales. The multi-scale conceptual framework we describe provides continuity between flux measurements made at the scale of soil profiles and chambers, forest inventories, eddy covariance towers, aircraft, and inversions of remote atmospheric flask samples, allowing a direct comparison of NEP estimates made at all temporal and spatial scales.

Nuclear traffic of influenza virus proteins and ribonucleoprotein complexes.

PubMed

Boulo, Sébastien; Akarsu, Hatice; Ruigrok, Rob W H; Baudin, Florence

2007-03-01

Influenza virus is a negative strand RNA virus and is one of the rare RNA viruses to replicate in the nucleus. The viral RNA is associated with 4 viral proteins to form ribonucleoprotein particles (RNPs). After cell entry the RNPs are dissociated from the viral matrix protein in the low pH of the endosome and are actively imported into the cell nucleus. After translation of viral mRNAs, the proteins necessary for the assembly of new RNPs (the nucleoprotein and the three subunits of the polymerase complex) are also imported into the nucleus. Apart from these four proteins, part of the newly made matrix protein is also imported and the nuclear export protein (NEP) enters the nucleus probably through diffusion. Finally, NS1 also enters the nucleus in order to regulate a number of nuclear processes. The nuclear localization signals on all these viral proteins and their interaction with the cellular transport system are discussed. In the nucleus, the matrix protein binds to the newly assembled RNPs and NEP then binds to the matrix protein. NEP contains the nuclear export signal necessary for transport of the RNPs to the cytoplasm, necessary for the budding of new virus particles. There appears to be a intricate ballet in exposing and hiding nuclear transport signals which leads to a unidirectional transport of the RNPs to the nucleus at the start of the infection process and an opposite unidirectional export of RNPs at the end of the infection.

Relational values resonate broadly and differently than intrinsic or instrumental values, or the New Ecological Paradigm

PubMed Central

Chan, Kai M. A.; Satterfield, Terre

2017-01-01

Value orientations used to explain or justify conservation have been rooted in arguments about how much and in what context to emphasize the intrinsic versus instrumental value of nature. Equally prominent are characterizations of beliefs known as the New Ecological Paradigm (NEP), often used to help explain pro-environmental behaviour. A recent alternative to these positions has been identified as ‘relational value’—broadly, values linking people and ecosystems via tangible and intangible relationships to nature as well as the principles, virtues and notions of a good life that may accompany these. This paper examines whether relational values are distinct from other value orientation and have potential to alleviate the intrinsic-instrumental debate. To test this possibility, we sought to operationalize the construct—relational values—by developing six relational statements. We ask: 1) Do the individual statements used to characterize relational values demonstrate internal coherence as either a single or multi-dimensional construct? 2) Do relational value statements (including those strongly stated) resonate with diverse populations? 3) Do people respond to relational value statements in a consistently different way than NEP scale statements? Data for this work is drawn from an online panel of residents of northeastern US (n = 400), as well as a sample of Costa Rican farmers (n = 253) and tourists in Costa Rica (n = 260). Results indicate relational values are distinct as a construct when compared to the NEP. PMID:28854227

Evaluating carbon fluxes of global forest ecosystems by using an individual tree-based model FORCCHN.

PubMed

Ma, Jianyong; Shugart, Herman H; Yan, Xiaodong; Cao, Cougui; Wu, Shuang; Fang, Jing

2017-05-15

The carbon budget of forest ecosystems, an important component of the terrestrial carbon cycle, needs to be accurately quantified and predicted by ecological models. As a preamble to apply the model to estimate global carbon uptake by forest ecosystems, we used the CO 2 flux measurements from 37 forest eddy-covariance sites to examine the individual tree-based FORCCHN model's performance globally. In these initial tests, the FORCCHN model simulated gross primary production (GPP), ecosystem respiration (ER) and net ecosystem production (NEP) with correlations of 0.72, 0.70 and 0.53, respectively, across all forest biomes. The model underestimated GPP and slightly overestimated ER across most of the eddy-covariance sites. An underestimation of NEP arose primarily from the lower GPP estimates. Model performance was better in capturing both the temporal changes and magnitude of carbon fluxes in deciduous broadleaf forest than in evergreen broadleaf forest, and it performed less well for sites in Mediterranean climate. We then applied the model to estimate the carbon fluxes of forest ecosystems on global scale over 1982-2011. This application of FORCCHN gave a total GPP of 59.41±5.67 and an ER of 57.21±5.32PgCyr -1 for global forest ecosystems during 1982-2011. The forest ecosystems over this same period contributed a large carbon storage, with total NEP being 2.20±0.64PgCyr -1 . These values are comparable to and reinforce estimates reported in other studies. This analysis highlights individual tree-based model FORCCHN could be used to evaluate carbon fluxes of forest ecosystems on global scale. Copyright © 2017 Elsevier B.V. All rights reserved.

Decreases in net primary production and net ecosystem production along a repeated-fires induced forest/grassland gradient

NASA Astrophysics Data System (ADS)

Cheng, C. H.; Huang, Y. H.; Chung-Yu, L.; Menyailo, O.

2016-12-01

Fire is one of the most important disturbances in ecosystems. Fire rapidly releases stored carbon into atmosphere and also plays critical roles on soil properties, light and moisture regimes, and plant structures and communities. With the interventions of climate change and human activities, fire regimes become more severe and frequent. In many parts of world, forest fire regimes can be further altered by grass invasion because the invasive grasses create a positive feedback cycle through their rapid recovery after fires and their high flammability during dry periods and allow forests to be burned repeatedly in a relatively short time. For such invasive grass-fire cycle, a great change of native vegetation community can occur. In this study, we examined a C4 invasive grass () fire-induced forest/grassland gradient to quantify the changes of net primary production (NPP) and net ecosystem production (NEP) from an unburned forest to repeated fire grassland. Our results demonstrated negative effects of repeated fires on NPP and NEP. Within 4 years of the onset of repeated fires on the unburned forest, NPP declined by 14%, mainly due to the reduction in aboveground NPP but offset by increase of belowground NPP. Subsequent fires cumulatively caused reductions in both aboveground and belowground NPP. A total of 40% reduction in the long-term repeated fire induced grassland was found. Soil respiration rate were not significantly different along the forest/grassland gradient. Thus, a great reduction in NEP were shown in grassland, which shifted from 4.6 Mg C ha-1 yr-1 in unburnt forest to -2.6 Mg C ha-1 yr-1. Such great losses are critical within the context of forest carbon cycling and long-term sustainability. Forest management practices that can effectively reduce the likelihood of repeated fires and consequent likelihood of establishment of the grass fire cycle are essential for protecting the forest.

Energy Value of Cassava Products in Broiler Chicken Diets with or without Enzyme Supplementation

PubMed Central

Bhuiyan, M. M.; Iji, P. A.

2015-01-01

This study investigated the metabolizable energy (ME) intake, net energy of production (NEp), heat production (HP), efficiencies of ME use for energy, lipid and protein retention as well as the performance of broiler chickens fed diets based on cassava chips or pellets with or without supplementation with an enzyme product containing xylanase, amylase, protease and phytase. The two products, cassava chips and pellets, were analysed for nutrient composition prior to feed formulation. The cassava chips and pellets contained 2.2% and 2.1% crude protein; 1.2% and 1.5% crude fat; and 75.1% and 67.8% starch, respectively. Lysine and methionine were 0.077%, 0.075%, and 0.017%, 0.020% protein material, respectively, while calculated ME was 12.6 and 11.7 MJ/kg, respectively. Feed intake to day 21 was lower (p<0.01) on the diet containing cassava chips compared to diets with cassava pellets. Enzyme supplementation increased (p<0.01) feed intake on all diets. Live weight at day 21 was significantly (p<0.01) reduced on the diet based on cassava chips compared to pellets, but an improvement (p<0.01) was noticed with the enzyme supplementation. Metabolizable energy intake was reduced (p<0.01) by both cassava chips and pellets, but was increased (p<0.01) on all diets by enzyme supplementation. The NEp was higher (p<0.01) in the maize-based diets than the diets containing cassava. Enzyme supplementation improved (p<0.01) NEp in all the diets. Heat production was highest (p<0.01) on diets containing cassava pellets than on cassava chips. It is possible to use cassava pellets in diets for broiler chickens at a level close to 50% of the diet to reduce cost of production, and the nutritive value of such diets can be improved through supplementation of enzyme products containing carbohydrases, protease, and phytase. PMID:26194227

TES arrays for the short wavelength band of the SAFARI instrument on SPICA

NASA Astrophysics Data System (ADS)

Khosropanah, P.; Hijmering, R.; Ridder, M.; Gao, J. R.; Morozov, D.; Mauskopf, P. D.; Trappe, N.; O'Sullivan, C.; Murphy, A.; Griffin, D.; Goldie, D.; Glowacka, D.; Withington, S.; Jackson, B. D.; Audley, M. D.; de Lange, G.

2012-09-01

SPICA is an infra-red (IR) telescope with a cryogenically cooled mirror (~5K) with three instruments on board, one of which is SAFARI that is an imaging Fourier Transform Spectrometer (FTS) with three bands covering the wavelength of 34-210 μm. We develop transition edge sensors (TES) array for short wavelength band (34-60 μm) of SAFARI. These are based on superconducting Ti/Au bilayer as TES bolometers with a Tc of about 105 mK and thin Ta film as IR absorbers on suspended silicon nitride (SiN) membranes. These membranes are supported by long and narrow SiN legs that act as weak thermal links between the TES and the bath. Previously an electrical noise equivalent power (NEP) of 4×10-19 W/√Hz was achieved for a single pixel of such detectors. As an intermediate step toward a full-size SAFARI array (43×43), we fabricated several 8×9 detector arrays. Here we describe the design and the outcome of the dark and optical tests of several of these devices. We achieved high yield (<93%) and high uniformity in terms of critical temperature (<5%) and normal resistance (7%) across the arrays. The measured dark NEPs are as low as 5×10-19 W/√Hz with a response time of about 1.4 ms at preferred operating bias point. The optical coupling is implemented using pyramidal horns array on the top and hemispherical cavity behind the chip that gives a measured total optical coupling efficiency of 30±7%.

Terrestrial carbon balance in a drier world: the effects of water availability in southwestern North America.

PubMed

Biederman, Joel A; Scott, Russell L; Goulden, Michael L; Vargas, Rodrigo; Litvak, Marcy E; Kolb, Thomas E; Yepez, Enrico A; Oechel, Walter C; Blanken, Peter D; Bell, Tom W; Garatuza-Payan, Jaime; Maurer, Gregory E; Dore, Sabina; Burns, Sean P

2016-05-01

Global modeling efforts indicate semiarid regions dominate the increasing trend and interannual variation of net CO2 exchange with the atmosphere, mainly driven by water availability. Many semiarid regions are expected to undergo climatic drying, but the impacts on net CO2 exchange are poorly understood due to limited semiarid flux observations. Here we evaluated 121 site-years of annual eddy covariance measurements of net and gross CO2 exchange (photosynthesis and respiration), precipitation, and evapotranspiration (ET) in 21 semiarid North American ecosystems with an observed range of 100 - 1000 mm in annual precipitation and records of 4-9 years each. In addition to evaluating spatial relationships among CO2 and water fluxes across sites, we separately quantified site-level temporal relationships, representing sensitivity to interannual variation. Across the climatic and ecological gradient, photosynthesis showed a saturating spatial relationship to precipitation, whereas the photosynthesis-ET relationship was linear, suggesting ET was a better proxy for water available to drive CO2 exchanges after hydrologic losses. Both photosynthesis and respiration showed similar site-level sensitivity to interannual changes in ET among the 21 ecosystems. Furthermore, these temporal relationships were not different from the spatial relationships of long-term mean CO2 exchanges with climatic ET. Consequently, a hypothetical 100-mm change in ET, whether short term or long term, was predicted to alter net ecosystem production (NEP) by 64 gCm(-2) yr(-1). Most of the unexplained NEP variability was related to persistent, site-specific function, suggesting prioritization of research on slow-changing controls. Common temporal and spatial sensitivity to water availability increases our confidence that site-level responses to interannual weather can be extrapolated for prediction of CO2 exchanges over decadal and longer timescales relevant to societal response to climate change. © 2016 John Wiley & Sons Ltd.

Detecting a Terrestrial Biosphere Sink for Carbon Dioxide: Interannual Ecosystem Modeling for the Mid-1980s

NASA Technical Reports Server (NTRS)

Potter, Christopher S.; Klooster, Steven A.; Brooks, Vanessa; Gore, Warren J. (Technical Monitor)

1998-01-01

There is considerable uncertainty as to whether interannual variability in climate and terrestrial ecosystem production is sufficient to explain observed variation in atmospheric carbon content over the past 20-30 years. In this paper, we investigated the response of net CO2 exchange in terrestrial ecosystems to interannual climate variability (1983 to 1988) using global satellite observations as drivers for the NASA-CASA (Carnegie-Ames-Stanford Approach) simulation model. This computer model of net ecosystem production (NEP) is calibrated for interannual simulations driven by monthly satellite vegetation index data (NDVI) from the NOAA Advanced Very High Resolution Radiometer (AVHRR) at 1 degree spatial resolution. Major results from NASA-CASA simulations suggest that from 1985 to 1988, the northern middle-latitude zone (between 30 and 60 degrees N) was the principal region driving progressive annual increases in global net primary production (NPP; i.e., the terrestrial biosphere sink for carbon). The average annual increase in NPP over this predominantly northern forest zone was on the order of +0.4 Pg (10 (exp 15) g) C per year. This increase resulted mainly from notable expansion of the growing season for plant carbon fixation toward the zonal latitude extremes, a pattern uniquely demonstrated in our regional visualization results. A net biosphere source flux of CO2 in 1983-1984, coinciding with an El Nino event, was followed by a major recovery of global NEP in 1985 which lasted through 1987 as a net carbon sink of between 0.4 and 2.6 Avg C per year. Analysis of model controls on NPP and soil heterotrophic CO2 fluxes (Rh) suggests that regional warming in northern forests can enhance ecosystem production significantly. In seasonally dry tropical zones, periodic drought and temperature drying effects may carry over with at least a two-year lag time to adversely impact ecosystem production. These yearly patterns in our model-predicted NEP are consistent in magnitude with the estimated exchange of CO2 by the terrestrial biosphere with the atmosphere, as determined by previous isotopic (delta (sup 13 C) convolution analysis. Ecosystem simulation results can help further target locations where net carbon sink fluxes have occurred in the past or may be verified in subsequent field studies.

Development of Aluminum LEKIDs for Balloon-Borne Far-IR Spectroscopy

NASA Astrophysics Data System (ADS)

Hailey-Dunsheath, S.; Barlis, A. C. M.; Aguirre, J. E.; Bradford, C. M.; Redford, J. G.; Billings, T. S.; LeDuc, H. G.; McKenney, C. M.; Hollister, M. I.

2018-04-01

We are developing lumped-element kinetic inductance detectors (LEKIDs) designed to achieve background-limited sensitivity for far-infrared (FIR) spectroscopy on a stratospheric balloon. The spectroscopic terahertz airborne receiver for far-infrared exploration will study the evolution of dusty galaxies with observations of the [CII] 158 μm and other atomic fine-structure transitions at z=0.5 -1.5, both through direct observations of individual luminous infrared galaxies, and in blind surveys using the technique of line intensity mapping. The spectrometer will require large format (˜ 1800 detectors) arrays of dual-polarization sensitive detectors with NEPs of 1 × 10^{-17} W Hz^{-1/2} . The low-volume LEKIDs are fabricated with a single layer of aluminum (20-nm-thick) deposited on a crystalline silicon wafer, with resonance frequencies of 100-250 MHz. The inductor is a single meander with a linewidth of 0.4 μm , patterned in a grid to absorb optical power in both polarizations. The meander is coupled to a circular waveguide, fed by a conical feedhorn. Initial testing of a small array prototype has demonstrated good yield and a median NEP of 4 × 10^{-18} W Hz^{-1/2}.

Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development.

PubMed

Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka, Michinori; Sato, Hirotaka; Kondoh, Yasumitsu; Osada, Hiroyuki; Kotani, Osamu; Yokoyama, Masaru; Sato, Hironori; Aida, Yoko

2017-07-01

An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. Copyright © 2017 Elsevier Inc. All rights reserved.

Low Thermal Conductance Transition Edge Sensor (TES) for SPICA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khosropanah, P.; Dirks, B.; Kuur, J. van der

2009-12-16

We fabricated and characterized low thermal conductance transition edge sensors (TES) for SAFARI instrument on SPICA. The device is based on a superconducting Ti/Au bilayer deposited on suspended SiN membrane. The critical temperature of the device is 113 mK. The low thermal conductance is realized by using long and narrow SiN supporting legs. All measurements were performed having the device in a light-tight box, which to a great extent eliminates the loading of the background radiation. We measured the current-voltage (IV) characteristics of the device in different bath temperatures and determine the thermal conductance (G) to be equal to 320more » fW/K. This value corresponds to a noise equivalent power (NEP) of 3x10{sup -19} W/{radical}(Hz). The current noise and complex impedance is also measured at different bias points at 55 mK bath temperature. The measured electrical (dark) NEP is 1x10{sup -18} W/{radical}(Hz), which is about a factor of 3 higher than what we expect from the thermal conductance that comes out of the IV curves. Despite using a light-tight box, the photon noise might still be the source of this excess noise. We also measured the complex impedance of the same device at several bias points. Fitting a simple first order thermal-electrical model to the measured data, we find an effective time constant of about 2.7 ms and a thermal capacity of 13 fJ/K in the middle of the transition.« less

Cardiovascular and intestinal responses to oxidative and nitrosative stress during prolonged magnesium deficiency.

PubMed

Weglicki, William B; Chmielinska, Joanna J; Kramer, Jay H; Mak, I Tong

2011-08-01

In rodents with dietary magnesium deficiency (Mg deficiency), hypomagnesemia, occurs leading to a rise in circulating substance P from neuronal tissues to trigger systemic inflammatory stress in cardiac and intestinal tissues. Sustained elevations of substance P may result from impaired neutral endopeptidase (NEP) activity due to reactive oxygen and reactive nitrogen species. Associated increase in intestinal permeability includes infiltration of WBC and endotoxemia, which can further amplify the systemic inflammatory response that leads to impaired contractile function associated with up-regulation of the cardiac CD14 endotoxin receptor. The neurogenic signal transduction pathways that we have identified in the pro-oxidant/pro-inflammatory processes found with prolonged hypomagnesemia are described in this report.

Sensitivity of regional forest carbon budgets to continuous and stochastic climate change pressures

NASA Astrophysics Data System (ADS)

Sulman, B. N.; Desai, A. R.; Scheller, R. M.

2010-12-01

Climate change is expected to impact forest-atmosphere carbon budgets through three processes: 1. Increased disturbance rates, including fires, mortality due to pest outbreaks, and severe storms 2. Changes in patterns of inter-annual variability, related to increased incidence of severe droughts and defoliating insect outbreaks 3. Continuous changes in forest productivity and respiration, related to increases in mean temperature, growing season length, and CO2 fertilization While the importance of these climate change effects in future regional carbon budgets has been established, quantitative characterization of the relative sensitivity of forested landscapes to these different types of pressures is needed. We present a model- and- data-based approach to understanding the sensitivity of forested landscapes to climate change pressures. Eddy-covariance and biometric measurements from forests in the northern United States were used to constrain two forest landscape models. The first, LandNEP, uses a prescribed functional form for the evolution of net ecosystem productivity (NEP) over the age of a forested grid cell, which is reset following a disturbance event. This model was used for investigating the basic statistical properties of a simple landscape’s responses to climate change pressures. The second model, LANDIS-II, includes different tree species and models forest biomass accumulation and succession, allowing us to investigate the effects of more complex forest processes such as species change and carbon pool accumulation on landscape responses to climate change effects. We tested the sensitivity of forested landscapes to these three types of climate change pressures by applying ensemble perturbations of random disturbance rates, distribution functions of inter-annual variability, and maximum potential carbon uptake rates, in the two models. We find that landscape-scale net carbon exchange responds linearly to continuous changes in potential carbon uptake and inter-annual variability, while responses to stochastic changes are non-linear and become more important at shorter mean disturbance intervals. These results provide insight on how to better parameterize coupled carbon-climate models to more realistically simulate feedbacks between forests and the atmosphere.

A Power Conversion Concept for the Jupiter Icy Moons Orbiter

NASA Technical Reports Server (NTRS)

Mason, Lee S.

2003-01-01

The Jupiter Icy Moons Orbiter (JIMO) is a bold new mission under development by the Office of Space Science at NASA Headquarters. ITMO is examining the potential of Nuclear Electric Propulsion (NEP) technology to efficiently deliver scientific payloads to three Jovian moons: Callisto, Ganymede, and Europa. A critical element of the NEP vehicle is the reactor power system, consisting of the nuclear reactor, power conversion, heat rejection, and power management and distribution (PMAD). The emphasis of this paper is on the non-nuclear elements of the reactor power system.

A filterless, visible-blind, narrow-band, and near-infrared photodetector with a gain

NASA Astrophysics Data System (ADS)

Shen, Liang; Zhang, Yang; Bai, Yang; Zheng, Xiaopeng; Wang, Qi; Huang, Jinsong

2016-06-01

In many applications of near-infrared (NIR) light detection, a band-pass filter is needed to exclude the noise caused by visible light. Here, we demonstrate a filterless, visible-blind, narrow-band NIR photodetector with a full-width at half-maximum of <50 nm for the response spectrum. These devices have a thick (>4 μm) nanocomposite absorbing layers made of polymer-fullerene:lead sulfide (PbS) quantum dots (QDs). The PbS QDs yield a photoconductive gain due to their hole-trapping effect, which effectively enhances both the responsivity and the visible rejection ratio of the external quantum efficiency by >10 fold compared to those without PbS QDs. Encouragingly, the inclusion of the PbS QDs does not increase the device noise. We directly measured a noise equivalent power (NEP) of 6.1 pW cm-2 at 890 nm, and a large linear dynamic range (LDR) over 11 orders of magnitude. The highly sensitive visible-blind NIR narrow-band photodetectors may find applications in biomedical engineering.

Development of a Bolometer Detector System for the NIST High Accuracy Infrared Spectrophotometer

PubMed Central

Zong, Y.; Datla, R. U.

1998-01-01

A bolometer detector system was developed for the high accuracy infrared spectrophotometer at the National Institute of Standards and Technology to provide maximum sensitivity, spatial uniformity, and linearity of response covering the entire infrared spectral range. The spatial response variation was measured to be within 0.1 %. The linearity of the detector output was measured over three decades of input power. After applying a simple correction procedure, the detector output was found to deviate less than 0.2 % from linear behavior over this range. The noise equivalent power (NEP) of the bolometer system was 6 × 10−12 W/Hz at the frequency of 80 Hz. The detector output 3 dB roll-off frequency was 200 Hz. The detector output was stable to within ± 0.05 % over a 15 min period. These results demonstrate that the bolometer detector system will serve as an excellent detector for the high accuracy infrared spectrophotometer. PMID:28009364

The effect of angiotensin receptor neprilysin inhibitor, sacubitril/valsartan, on central nervous system amyloid-β concentrations and clearance in the cynomolgus monkey.

PubMed

Schoenfeld, Heidi A; West, Tim; Verghese, Philip B; Holubasch, Mary; Shenoy, Neeta; Kagan, David; Buono, Chiara; Zhou, Wei; DeCristofaro, Marc; Douville, Julie; Goodrich, Geoffrey G; Mansfield, Keith; Saravanan, Chandra; Cumin, Frederic; Webb, Randy L; Bateman, Randall J

2017-05-15

Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system clearance of Aβ isoforms in cynomolgus monkeys using the sensitive Stable Isotope Labeling Kinetics (SILK™)-Aβ methodology. The in vitro selectivity of valsartan, sacubitril, and its active metabolite sacubitrilat was established; sacubitrilat did not inhibit other human Aβ-degrading metalloproteases. In a 2-week study, sacubitril/valsartan (50mg/kg/day) or vehicle was orally administered to female cynomolgus monkeys in conjunction with SILK™-Aβ. Despite low cerebrospinal fluid (CSF) and brain penetration, CSF exposure to sacubitril was sufficient to inhibit NEP and resulted in an increase in the elimination half-life of Aβ1-42 (65.3%; p=0.026), Aβ1-40 (35.2%; p=0.04) and Aβtotal (29.8%; p=0.04) acutely; this returned to normal as expected with repeated dosing for 15days. CSF concentrations of newly generated Aβ (AUC (0-24h) ) indicated elevations in the more aggregable form Aβ1-42 on day 1 (20.4%; p=0.039) and day 15 (34.7%; p=0.0003) and in shorter forms Aβ1-40 (23.4%; p=0.009), Aβ1-38 (64.1%; p=0.0001) and Aβtotal (50.45%; p=0.00002) on day 15. However, there were no elevations in any Aβ isoforms in the brains of these monkeys on day 16. In a second study cynomolgus monkeys were administered sacubitril/valsartan (300mg/kg) or vehicle control for 39weeks; no microscopic brain changes or Aβ deposition, as assessed by immunohistochemical staining, were present. Further clinical studies are planned to address the relevance of these findings. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Characterization of Low Noise TES Detectors Fabricated by D-RIE Process for SAFARI Short-Wavelength Band

NASA Astrophysics Data System (ADS)

Khosropanah, P.; Suzuki, T.; Hijmering, R. A.; Ridder, M. L.; Lindeman, M. A.; Gao, J.-R.; Hoevers, H.

2014-08-01

SRON is developing TES detectors based on a superconducting Ti/Au bilayer on a suspended SiN membrane for the short-wavelength band of the SAFARI instrument on SPICA mission. We have recently replaced the wet KOH etching of the Si substrate by deep reactive ion etching. The new process enables us to fabricate the detectors on the substrate and release the membrane at the very last step. Therefore the production of SAFARI large arrays (4343) on thin SiN membrane (250 nm) is feasible. It also makes it possible to realize narrow supporting SiN legs of 1 m, which are needed to meet SAFARI NEP requirements. Here we report the current-voltage characteristics, noise performance and impedance measurement of these devices. The measured results are then compared with the distributed leg model that takes into account the thermal fluctuation noise due to the SiN legs. We measured a dark NEP of 0.7 aW/, which is 1.6 times higher than the theoretically expected phonon noise.