Adam Smith and the Moral Economy of the Classroom System.

ERIC Educational Resources Information Center

Hamilton, D.

1980-01-01

Traces the development of mass schooling to its origins in 19th-century Glasgow. Its importance as an intellectual and economic center enabled Glasgow to invent a solution to the problem of urban schooling, while the association of scholars like Adam Smith with Glasgow University made Scottish educational theories acceptable around the world. (DB)

Adam Bratis, Ph.D. | NREL

Science.gov Websites

Sciences & Technology Adam.Bratis@nrel.gov | 303-384-7852 Areas of Expertise Adam Bratis joined the managerial oversight in the areas of biochemical conversion, thermochemical conversion, algal biofuels with 11 years of experience with ExxonMobil in the areas of research and development, corporate

Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain

NASA Astrophysics Data System (ADS)

Miller, Miles A.; Moss, Marcia L.; Powell, Gary; Petrovich, Robert; Edwards, Lori; Meyer, Aaron S.; Griffith, Linda G.; Lauffenburger, Douglas A.

2015-10-01

Dysregulation of ErbB-family signaling underlies numerous pathologies and has been therapeutically targeted through inhibiting ErbB-receptors themselves or their cognate ligands. For the latter, “decoy” antibodies have been developed to sequester ligands including heparin-binding epidermal growth factor (HB-EGF); however, demonstrating sufficient efficacy has been difficult. Here, we hypothesized that this strategy depends on properties such as ligand-receptor binding affinity, which varies widely across the known ErbB-family ligands. Guided by computational modeling, we found that high-affinity ligands such as HB-EGF are more difficult to target with decoy antibodies compared to low-affinity ligands such as amphiregulin (AREG). To address this issue, we developed an alternative method for inhibiting HB-EGF activity by targeting its cleavage from the cell surface. In a model of the invasive disease endometriosis, we identified A Disintegrin and Metalloproteinase 12 (ADAM12) as a protease implicated in HB-EGF shedding. We designed a specific inhibitor of ADAM12 based on its recombinant prodomain (PA12), which selectively inhibits ADAM12 but not ADAM10 or ADAM17. In endometriotic cells, PA12 significantly reduced HB-EGF shedding and resultant cellular migration. Overall, specific inhibition of ligand shedding represents a possible alternative to decoy antibodies, especially for ligands such as HB-EGF that exhibit high binding affinity and localized signaling.

ADAM-17: The Enzyme That Does It All

PubMed Central

Gooz, Monika

2010-01-01

This review focuses on the role of ADAM-17 in disease. Since its debut as the tumor necrosis factor converting enzyme or TACE, ADAM-17 has been reported to be an indispensible regulator of almost every cellular event from proliferation to migration. The central role of ADAM-17 in cell regulation is rooted in its diverse array of substrates: cytokines, growth factors, and their receptors as well as adhesion molecules are activated or inactivated by their cleavage with ADAM-17. It is therefore not surprising that ADAM-17 is implicated in numerous human diseases including cancer, heart disease, diabetes, rheumatoid arthritis, kidney fibrosis, Alzheimer’s disease, and is a promising target for future treatments. The specific role of ADAM-17 in the pathophysiology of these diseases is very complex and depends on the cellular context. To exploit the therapeutic potential of ADAM-17, it is important to understand how its activity is regulated and how specific organs and cells can be targeted to inactivate or activate the enzyme. PMID:20184396

Structural Characterization of the Ectodomain of a Disintegrin and Metalloproteinase-22 (ADAM22), a Neural Adhesion Receptor Instead of Metalloproteinase INSIGHTS ON ADAM FUNCTION

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

Liu, Heli; Shim, Ann H.R.; He, Xiaolin

2009-12-01

ADAMs (adisintegrin and metalloproteinases) are a family of multidomain transmembrane glycoproteins with diverse roles in physiology and diseases, with several members being drug targets for cancer and inflammation therapies. The spatial organization of the ADAM extracellular segment and its influence on the function of ADAMs have been unclear. Although most members of the ADAM family are active zinc metalloproteinases, 8 of 21 ADAMs lack functional metalloproteinase domains and are implicated in protein-protein interactions instead of membrane protein ectodomain shedding. One of such non-proteinase ADAMs, ADAM22, acts as a receptor on the surface of the postsynaptic neuron to regulate synaptic signalmore » transmission. The crystal structure of the full ectodomain of mature human ADAM22 shows that it is a compact four-leaf clover with the metalloproteinase-like domain held in the concave face of a rigid module formed by the disintegrin, cysteine-rich, and epidermal growth factor-like domains. The loss of metalloproteinase activity is ensured by the absence of critical catalytic residues, the filling of the substrate groove, and the steric hindrance by the cysteine-rich domain. The structure, combined with calorimetric experiments, suggests distinct roles of three putative calcium ions bound to ADAM22, with one in the metalloproteinase-like domain being regulatory and two in the disintegrin domain being structural. The metalloproteinase-like domain contacts the rest of ADAM22 with discontinuous, hydrophilic, and poorly complemented interactions, suggesting the possibility of modular movement of ADAM22 and other ADAMs. The ADAM22 structure provides a framework for understanding how different ADAMs exert their adhesive function and shedding activities.« less

New Mathematical Dimensions: Adam's Story

ERIC Educational Resources Information Center

Manizade, Agida

2009-01-01

Adam, an 11th grader, was identified as gifted and accepted into a two week summer enrichment program. He signed up for "Geometry with Flash Programming." He had no prior programming experience but had a strong and healthy self-image as mathematics student. Although Adam had a positive attitude toward mathematics and saw himself as a successful…

ADAM9 is involved in pathological retinal neovascularization.

PubMed

Guaiquil, Victor; Swendeman, Steven; Yoshida, Tsunehiko; Chavala, Sai; Campochiaro, Peter A; Blobel, Carl P

2009-05-01

Pathological ocular neovascularization, caused by diabetic retinopathy, age-related macular degeneration, or retinopathy of prematurity, is a leading cause of blindness, yet much remains to be learned about its underlying causes. Here we used oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) to assess the contribution of the metalloprotease-disintegrin ADAM9 to ocular neovascularization in mice. Pathological neovascularization in both the OIR and CNV models was significantly reduced in Adam9(-/-) mice compared to wild-type controls. In addition, the level of ADAM9 expression was strongly increased in endothelial cells in pathological vascular tufts in the OIR model. Moreover, tumor growth from heterotopically injected B16F0 melanoma cells was reduced in Adam9(-/-) mice compared to controls. In cell-based assays, the overexpression of ADAM9 enhanced the ectodomain shedding of EphB4, Tie-2, Flk-1, CD40, VCAM, and VE-cadherin, so the enhanced expression of ADAM9 could potentially affect pathological neovascularization by increasing the shedding of these and other membrane proteins from endothelial cells. Finally, we provide the first evidence for the upregulation of ADAM9-dependent shedding by reactive oxygen species, which in turn are known to play a critical role in OIR. Collectively, these results suggest that ADAM9 could be an attractive target for the prevention of proliferative retinopathies, CNV, and cancer.

AMS -- The Unix ADAM Message System

NASA Astrophysics Data System (ADS)

Kelly, B. D.; Chipperfield, A. J.

The ADAM Message System (AMS) library, which implements the ADAM inter-task communications protocol under Unix, is described, along with its Fortran-callable interface (FAMS). The description of AMS is distinguished from the current implementation which uses the Message System Primitives (MSP).

ADAM9 Is Involved in Pathological Retinal Neovascularization▿

PubMed Central

Guaiquil, Victor; Swendeman, Steven; Yoshida, Tsunehiko; Chavala, Sai; Campochiaro, Peter A.; Blobel, Carl P.

2009-01-01

Pathological ocular neovascularization, caused by diabetic retinopathy, age-related macular degeneration, or retinopathy of prematurity, is a leading cause of blindness, yet much remains to be learned about its underlying causes. Here we used oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) to assess the contribution of the metalloprotease-disintegrin ADAM9 to ocular neovascularization in mice. Pathological neovascularization in both the OIR and CNV models was significantly reduced in Adam9−/− mice compared to wild-type controls. In addition, the level of ADAM9 expression was strongly increased in endothelial cells in pathological vascular tufts in the OIR model. Moreover, tumor growth from heterotopically injected B16F0 melanoma cells was reduced in Adam9−/− mice compared to controls. In cell-based assays, the overexpression of ADAM9 enhanced the ectodomain shedding of EphB4, Tie-2, Flk-1, CD40, VCAM, and VE-cadherin, so the enhanced expression of ADAM9 could potentially affect pathological neovascularization by increasing the shedding of these and other membrane proteins from endothelial cells. Finally, we provide the first evidence for the upregulation of ADAM9-dependent shedding by reactive oxygen species, which in turn are known to play a critical role in OIR. Collectively, these results suggest that ADAM9 could be an attractive target for the prevention of proliferative retinopathies, CNV, and cancer. PMID:19273593

Connective tissue growth factor is a substrate of ADAM28

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

Mochizuki, Satsuki; Tanaka, Rena; Shimoda, Masayuki

2010-11-26

Research highlights: {yields} The hyper-variable region in the cysteine-rich domain of ADAM28 binds to C-terminal domain of CTGF. {yields} ADAM28 cleaves CTGF alone and CTGF in the CTGF/VEGF{sub 165} complex. {yields} CTGF digestion by ADAM28 releases biologically active VEGF{sub 165} from the complex. {yields} ADAM28, CTGF and VEGF{sub 165} are commonly co-expressed by carcinoma cells in human breast carcinoma tissues. {yields} These suggest that ADAM28 promotes VEGF{sub 165}-induced angiogenesis in the breast carcinomas by selective CTGF digestion in the CTGF/VEGF{sub 165} complex. -- Abstract: ADAM28, a member of the ADAM (a disintegrin and metalloproteinase) gene family, is over-expressed by carcinomamore » cells and the expression correlates with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, information about substrates of ADAM28 is limited. We screened interacting molecules of ADAM28 in human lung cDNA library by yeast two-hybrid system and identified connective tissue growth factor (CTGF). Binding of CTGF to proADAM28 was demonstrated by yeast two-hybrid assay and protein binding assay. ADAM28 cleaved CTGF in dose- and time-dependent manners at the Ala{sup 181}-Tyr{sup 182} and Asp{sup 191}-Pro{sup 192} bonds in the hinge region of the molecule. ADAM28 selectively digested CTGF in the complex of CTGF and vascular endothelial growth factor{sub 165} (VEGF{sub 165}), releasing biologically active VEGF{sub 165} from the complex. RT-PCR and immunohistochemical analyses demonstrated that ADAM28, CTGF and VEGF are commonly co-expressed in the breast carcinoma tissues. These data provide the first evidence that CTGF is a novel substrate of ADAM28 and suggest that ADAM28 may promote VEGF{sub 165}-induced angiogenesis in the breast carcinomas by the CTGF digestion in the CTGF/VEGF{sub 165} complex.« less

How To Survive in Postindustrial Environments: Adam Smith's Advice for Today's Colleges and Universities.

ERIC Educational Resources Information Center

Ortmann, Andreas

1997-01-01

Adam Smith's discussion of the payment modes of teachers and resulting consequences for the quality of teaching and process of curricular innovation are reviewed through the conceptual lens of modern agency theory. Smith's analysis of higher education in his day (eighteenth century) sheds light on faculty incentive and assessment problems that…

The cysteine-rich domain regulates ADAM protease function in vivo.

PubMed

Smith, Katherine M; Gaultier, Alban; Cousin, Helene; Alfandari, Dominique; White, Judith M; DeSimone, Douglas W

2002-12-09

ADAMs are membrane-anchored proteases that regulate cell behavior by proteolytically modifying the cell surface and ECM. Like other membrane-anchored proteases, ADAMs contain candidate "adhesive" domains downstream of their metalloprotease domains. The mechanism by which membrane-anchored cell surface proteases utilize these putative adhesive domains to regulate protease function in vivo is not well understood. We address this important question by analyzing the relative contributions of downstream extracellular domains (disintegrin, cysteine rich, and EGF-like repeat) of the ADAM13 metalloprotease during Xenopus laevis development. When expressed in embryos, ADAM13 induces hyperplasia of the cement gland, whereas ADAM10 does not. Using chimeric constructs, we find that the metalloprotease domain of ADAM10 can substitute for that of ADAM13, but that specificity for cement gland expansion requires a downstream extracellular domain of ADAM13. Analysis of finer resolution chimeras indicates an essential role for the cysteine-rich domain and a supporting role for the disintegrin domain. These and other results reveal that the cysteine-rich domain of ADAM13 cooperates intramolecularly with the ADAM13 metalloprotease domain to regulate its function in vivo. Our findings thus provide the first evidence that a downstream extracellular adhesive domain plays an active role in regulating ADAM protease function in vivo. These findings are likely relevant to other membrane-anchored cell surface proteases.

Potential Role for ADAM15 in Pathological Neovascularization in Mice

PubMed Central

Horiuchi, Keisuke; Weskamp, Gisela; Lum, Lawrence; Hammes, Hans-Peter; Cai, Hui; Brodie, Thomas A.; Ludwig, Thomas; Chiusaroli, Riccardo; Baron, Roland; Preissner, Klaus T.; Manova, Katia; Blobel, Carl P.

2003-01-01

ADAM15 (named for a disintegrin and metalloprotease 15, metargidin) is a membrane-anchored glycoprotein that has been implicated in cell-cell or cell-matrix interactions and in the proteolysis of molecules on the cell surface or extracellular matrix. To characterize the potential roles of ADAM15 during development and in adult mice, we analyzed its expression pattern by mRNA in situ hybridization and generated mice carrying a targeted deletion of ADAM15 (adam15−/− mice). A high level of expression of ADAM15 was found in vascular cells, the endocardium, hypertrophic cells in developing bone, and specific areas of the hippocampus and cerebellum. However, despite the pronounced expression of ADAM15 in these tissues, no major developmental defects or pathological phenotypes were evident in adam15−/− mice. The elevated levels of ADAM15 in endothelial cells prompted an evaluation of its role in neovascularization. In a mouse model for retinopathy of prematurity, adam15−/− mice had a major reduction in neovascularization compared to wild-type controls. Furthermore, the size of tumors resulting from implanted B16F0 mouse melanoma cells was significantly smaller in adam15−/− mice than in wild-type controls. Since ADAM15 does not appear to be required for developmental angiogenesis or for adult homeostasis, it may represent a novel target for the design of inhibitors of pathological neovascularization. PMID:12897135

The plasma membrane: Penultimate regulator of ADAM sheddase function.

PubMed

Reiss, Karina; Bhakdi, Sucharit

2017-11-01

ADAM10 and ADAM17 are the best characterized members of the ADAM (A Disintegrin and Metalloproteinase) - family of transmembrane proteases. Both are involved diverse physiological and pathophysiological processes. ADAMs are known to be regulated by posttranslational mechanisms. However, emerging evidence indicates that the plasma membrane with its unique dynamic properties may additionally play an important role in controlling sheddase function. Membrane events that could contribute to regulation of ADAM-function are summarized. Surface expression of peptidolytic activity should be differentiated from ADAM-sheddase function since the latter additionally requires that the protease finds its substrate in the lipid bilayer. We propose that this is achieved through horizontal and vertical reorganization of membrane nanoarchitecture coordinately occurring at the sites of sheddase activation. Reshuffling of nanodomains thereby guides traffic of enzyme and substrate to each other. For ADAM17 phosphatidylserine exposure is required to then induce its shedding function. The novel concept that physicochemical properties of the lipid bilayer govern the action of ADAM-proteases may be extendable to other functional proteins that act at the cell surface. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John. Copyright © 2017. Published by Elsevier B.V.

Effects of ADAM10 and ADAM17 Inhibitors on Natural Killer Cell Expansion and Antibody-dependent Cellular Cytotoxicity Against Breast Cancer Cells In Vitro.

PubMed

Pham, Dang-Huan; Kim, Ju-Sun; Kim, Sang-Ki; Shin, Dong-Jun; Uong, Nguyen-Thanh-Tung; Hyun, Hoon; Yoon, Mee Sun; Kang, Sin Jae; Ryu, Young Jae; Cho, Jin Seong; Yoon, Jung Han; Lee, Ji Shin; Cho, Duck; Lee, Soo-Hyeon; Park, Min Ho

2017-10-01

The inhibition of a disintegrin and metalloproteinase (ADAM) has the potential to become a novel approach for natural killer (NK) cell-based cancer immunotherapy. Thus, the aim of this study was to investigate the influence of ADAM10 and ADAM17 inhibitors on expanded NK cell to enhance antibody-dependent cellular cytotoxicity (ADCC) in breast cancer cell lines. NK cells were expanded in medium supplemented with an ADAM10 or ADAM17 inhibitor to prevent the shedding of soluble CD16/FcγRIII. The expression level of CD16 and production of interferon-gamma (IFN-γ) was detected by flow cytometry using specific antibodies. ADCC activity of expanded NK cells was estimated in trastuzumab treated breast cancer cell lines such as MCF-7, MDA-MB-231, SKBR3, and BT-474 cells. The ADAM17 inhibitor increased the purity of expanded NK cells to 90% after 14 days at 5 and 10 μM in vitro (p=0.043). However, the expansion rate of NK cells was decreased at 10 μM of the ADAM 17 inhibitor (p=0.043). Inhibition of ADAM10 suppressed the expansion of NK cells, although the NK purity was increased at 1 μM of the inhibitor. The expression of CD16 was significantly increased at 1 and 5 μM of the ADAM17 inhibitor (p=0.046, 0.028, respectively) during the culturing period. Inhibition of ADAM10 reduced the expression of CD16 on NK cells. The cytotoxic activity of the ADAM17 inhibitor treated NK cells against MCF-7 (p=0.039) and BT-474 (p=0.027) cells was significantly elevated. The ADCC activity of NK cells treated with 5 μM of ADAM17 inhibitor was significantly increased against SKBR-3 and BT-474 (p=0.027). Inhibition of ADAM17 increased the production of IFN-γ in expanded NK cells. The inhibition of ADAM17 enhanced the purity of expanded NK cells and the ADCC activity of these cells against trastuzumab treated breast cancer cell lines. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

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

Ungerer, Christopher; Doberstein, Kai; Buerger, Claudia

2010-10-22

Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far.more » In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.« less

Adam8 Limits the Development of Allergic Airway Inflammation in Mice

PubMed Central

Knolle, Martin D.; Nakajima, Takahiro; Hergrueter, Anja; Gupta, Kushagra; Polverino, Francesca; Craig, Vanessa J.; Fyfe, Susanne E.; Zahid, Muhammad; Permaul, Perdita; Cernadas, Manuela; Montano, Gilbert; Tesfaigzi, Yohannes; Sholl, Lynette; Kobzik, Lester; Israel, Elliot; Owen, Caroline A.

2013-01-01

To determine whether a disintegrin and a metalloproteinase-8 (Adam8) regulates allergic airway inflammation (AAI) and airway hyper-responsiveness (AHR), we compared AAI and AHR in wild type (WT) versus Adam8−/− mice in different genetic backgrounds sensitized and challenged with ovalbumin (OVA) or house dust mite protein extract (HDM). OVA- and HDM-treated Adam8−/− mice had higher lung leukocyte counts, more airway mucus metaplasia, greater lung levels of some TH2 cytokines, and higher methacholine-induced increases in central airway resistance than allergen-treated WT mice. Studies of OVA-treated Adam8 bone marrow chimeric mice confirmed that leukocyte-derived Adam8 predominantly mediated Adam8’s anti-inflammatory activities in murine airways. Airway eosinophils and macrophages both expressed Adam8 in WT mice with AAI. Adam8 limited AAI and AHR in mice by reducing leukocyte survival because: 1) Adam8−/− mice with AAI had fewer apoptotic eosinophils and macrophages in their airways than WT mice with AAI; and 2) Adam8−/− macrophages and eosinophils had reduced rates of apoptosis compared with WT leukocytes when the intrinsic (but not the extrinsic) apoptosis pathway was triggered in the cells in vitro. ADAM8 was robustly expressed by airway granulocytes in lung sections from human asthma patients but, surprisingly, airway macrophages had less ADAM8 staining than airway eosinophils. Thus, ADAM8 has anti-inflammatory activities during AAI in mice by activating the intrinsic apoptosis pathway in myeloid leukocytes. Strategies that increase ADAM8 levels in myeloid leukocytes may have therapeutic efficacy in asthma. PMID:23670189

Automation of TL brick dating by ADAM-1

NASA Astrophysics Data System (ADS)

Čechák, T.; Gerndt, J.; Hiršl, P.; Jiroušek, P.; Kanaval, J.; Kubelík, M.; Musílek, L.

2001-06-01

A specially adapted machine ADAM-1 for the thermoluminescence fine grain dating of bricks was constructed in an interdisciplinary research project, undertaken by a team recruited from three faculties of the Czech Technical University in Prague. This TL-reader is able to measure and evaluate automatically numerous samples. The sample holder has 60 sample positions, which allow the irradiation and evaluation of samples taken from two locations. All procedures of alpha and beta irradiation by varying doses and the TL-signal measurement as also the age evaluation and error assessment are programmable and fully automated.

The ADAM workshops and meeting summary

NASA Astrophysics Data System (ADS)

Chipperfield, Alan J.

1990-01-01

ADAM is now a major software project; it provides a fully integrated environment for both data reduction and data acquisition. It is being used in Hawaii, Australia and the Canary Islands, as well as the UK, and has been adopted by Starlink as the environment in which Starlink data reduction software should run. One of the most remarkable things about ADAM is that it has been developed as a co-operative effort between groups that are spread across the world. Although the initial system came out of RGO, and ROE provided by far the major effort in designing and implementing the VAX version, various parts of what is now regarded as 'ADAM' have also come from other establishments. Co-ordinating a project being developed in this way is not an easy job, but the somewhat varied parentage of ADAM - although sometimes an administrative nightmare - is also one of its strengths; it is not a system developed in one place to serve the specific needs of that one place. One way in which this development is co-ordinated is by a series of workshops. These have taken place at about 18 month intervals since the first one in late 1985. The workshops are attended by people actively developing and/or making extensive use of ADAM, and provide a forum for detailed discussion of the problems in the current system and plans for its extension. The 1989 ADAM Workshop was held at Cosener's House, Abingdon from 3rd to 7th July 1989. An 'Open Meeting' was held on Friday 30th June at RAL to enable members of the Starlink community to provide input to the Workshop discussions. Before the previous workshop, in Hawaii, a trend had started to emerge for different establishments to plug the gaps in ADAM (which at the time was missing a number of important facilities) with local solutions. The Hawaii Workshop consolidated these local extensions, adopting some and rejecting others. As a result, ADAM, as reviewed by this third workshop, was a much more complete and uniform system, and it was possible to

Proceedings of the 1989 ADAM Workshop

NASA Astrophysics Data System (ADS)

Chipperfield, Alan

ADAM is now a major software project; it provides a fully integrated environment for both data reduction and data acquisition. It is being used in Hawaii, Australia and the Canary Islands, as well as the UK, and has been adopted by Starlink as the environment in which Starlink data reduction software should run. One of the most remarkable things about ADAM is that it has been developed as a co-operative effort between groups that are spread across the world. Although the initial system came out of RGO, and ROE provided by far the major effort in designing and implementing the VAX version, various parts of what is now regarded as 'ADAM' have also come from other establishments. Co-ordinating a project being developed in this way is not an easy job, but the somewhat varied parentage of ADAM - although sometimes an administrative nightmare - is also one of its strengths; it is not a system developed in one place to serve the specific needs of that one place. One way in which this development is co-ordinated is by a series of workshops. These have taken place at about 18 month intervals since the first one in late 1985. The workshops are attended by people actively developing and/or making extensive use of ADAM, and provide a forum for detailed discussion of the problems in the current system and plans for its extension. The 1989 ADAM Workshop was held at Cosener's House, Abingdon from 3rd to 7th July 1989. An 'Open Meeting' was held on Friday 30th June at RAL to enable members of the Starlink community to provide input to the Workshop discussions. Before the previous workshop, in Hawaii, a trend had started to emerge for different establishments to plug the gaps in ADAM (which at the time was missing a number of important facilities) with local solutions. The Hawaii Workshop consolidated these local extensions, adopting some and rejecting others. As a result, ADAM, as reviewed by this third workshop, was a much more complete and uniform system, and it was possible to

Adam and Bessie Arnet Residence, overall view from rocks above, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Adam and Bessie Arnet Residence, overall view from rocks above, looking southeast. - Adam & Bessie Arnet Homestead, Adam & Bessie Arnet Residence, 18 feet west of Generator House, Model, Las Animas County, CO

Conservation and divergence of ADAM family proteins in the Xenopus genome

PubMed Central

2010-01-01

Background Members of the disintegrin metalloproteinase (ADAM) family play important roles in cellular and developmental processes through their functions as proteases and/or binding partners for other proteins. The amphibian Xenopus has long been used as a model for early vertebrate development, but genome-wide analyses for large gene families were not possible until the recent completion of the X. tropicalis genome sequence and the availability of large scale expression sequence tag (EST) databases. In this study we carried out a systematic analysis of the X. tropicalis genome and uncovered several interesting features of ADAM genes in this species. Results Based on the X. tropicalis genome sequence and EST databases, we identified Xenopus orthologues of mammalian ADAMs and obtained full-length cDNA clones for these genes. The deduced protein sequences, synteny and exon-intron boundaries are conserved between most human and X. tropicalis orthologues. The alternative splicing patterns of certain Xenopus ADAM genes, such as adams 22 and 28, are similar to those of their mammalian orthologues. However, we were unable to identify an orthologue for ADAM7 or 8. The Xenopus orthologue of ADAM15, an active metalloproteinase in mammals, does not contain the conserved zinc-binding motif and is hence considered proteolytically inactive. We also found evidence for gain of ADAM genes in Xenopus as compared to other species. There is a homologue of ADAM10 in Xenopus that is missing in most mammals. Furthermore, a single scaffold of X. tropicalis genome contains four genes encoding ADAM28 homologues, suggesting genome duplication in this region. Conclusions Our genome-wide analysis of ADAM genes in X. tropicalis revealed both conservation and evolutionary divergence of these genes in this amphibian species. On the one hand, all ADAMs implicated in normal development and health in other species are conserved in X. tropicalis. On the other hand, some ADAM genes and ADAM protease

Neptune: towards understanding how Adams's upbringing enabled him to predict, then miss the discovery of the century

NASA Astrophysics Data System (ADS)

Sheen, B.

2013-03-01

The story of John Couch Adams the great Cornish astronomer of the nineteenth century is well known and this paper will not revisit old ground. However, many questions remain unanswered and in this paper I propose to indicate some of them as section headings, and seek to address them. In this way Adams's early life is examined, and its effect on his academic life during the time of the Neptune discovery. The row that followed discovery is high-lighted together with the equally contentious issue of the new planet's name. Although it is usually believed that Adams graciously accepted the failure of the Cambridge University Observatory to find his planet, examination of his later work which is often highly critical of French astronomers sheds a different light on that theory.

Adam and Bessie Arnet Residence, interior detail of jacal wall ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Adam and Bessie Arnet Residence, interior detail of jacal wall construction in west jacal room - Adam & Bessie Arnet Homestead, Adam & Bessie Arnet Residence, 18 feet west of Generator House, Model, Las Animas County, CO

ADAM10 regulates Notch function in intestinal stem cells of mice.

PubMed

Tsai, Yu-Hwai; VanDussen, Kelli L; Sawey, Eric T; Wade, Alex W; Kasper, Chelsea; Rakshit, Sabita; Bhatt, Riha G; Stoeck, Alex; Maillard, Ivan; Crawford, Howard C; Samuelson, Linda C; Dempsey, Peter J

2014-10-01

A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a cell surface sheddase that regulates physiologic processes, including Notch signaling. ADAM10 is expressed in all intestinal epithelial cell types, but the requirement for ADAM10 signaling in crypt homeostasis is not well defined. We analyzed intestinal tissues from mice with constitutive (Vil-Cre;Adam10(f/f) mice) and conditional (Vil-CreER;Adam10(f/f) and Leucine-rich repeat-containing GPCR5 [Lgr5]-CreER;Adam10(f/f) mice) deletion of ADAM10. We performed cell lineage-tracing experiments in mice that expressed a gain-of-function allele of Notch in the intestine (Rosa26(NICD)), or mice with intestine-specific disruption of Notch (Rosa26(DN-MAML)), to examine the effects of ADAM10 deletion on cell fate specification and intestinal stem cell maintenance. Loss of ADAM10 from developing and adult intestine caused lethality associated with altered intestinal morphology, reduced progenitor cell proliferation, and increased secretory cell differentiation. ADAM10 deletion led to the replacement of intestinal cell progenitors with 2 distinct, post-mitotic, secretory cell lineages: intermediate-like (Paneth/goblet) and enteroendocrine cells. Based on analysis of Rosa26(NICD) and Rosa26(DN-MAML) mice, we determined that ADAM10 controls these cell fate decisions by regulating Notch signaling. Cell lineage-tracing experiments showed that ADAM10 is required for survival of Lgr5(+) crypt-based columnar cells. Our findings indicate that Notch-activated stem cells have a competitive advantage for occupation of the stem cell niche. ADAM10 acts in a cell autonomous manner within the intestinal crypt compartment to regulate Notch signaling. This process is required for progenitor cell lineage specification and crypt-based columnar cell maintenance. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

ADAM10 Regulates Notch Function in Intestinal Stem Cells of Mice

PubMed Central

Tsai, Yu-Hwai; VanDussen, Kelli L.; Sawey, Eric T.; Wade, Alex W.; Kasper, Chelsea; Rakshit, Sabita; Bhatt, Riha G.; Stoeck, Alex; Maillard, Ivan; Crawford, Howard C.; Samuelson, Linda C.; Dempsey, Peter J.

2014-01-01

BACKGROUND & AIMS ADAM10 is a cell surface sheddase that regulates physiological processes including Notch signaling. ADAM10 is expressed in all intestinal epithelial cell types but the requirement for ADAM10 signaling in crypt homeostasis is not well defined. METHODS We analyzed intestinal tissues from mice with constitutive (Vil-Cre;Adam10f/f mice) and conditional (Vil-CreER;Adam10f/f and Lgr5-CreER;Adam10f/f mice) deletion of ADAM10. We performed cell lineage tracing experiments in mice that expressed a gain-of-function allele of Notch in the intestine (Rosa26NICD) or mice with intestine-specific disruption of Notch (Rosa26DN-MAML), to examine the effects of ADAM10 deletion on cell fate specification and intestinal stem cell maintenance. RESULTS Loss of ADAM10 from developing and adult intestine caused lethality associated with altered intestinal morphology, reduced progenitor cell proliferation, and increased secretory cell differentiation. ADAM10 deletion led to the replacement of intestinal cell progenitors with 2 distinct, post-mitotic, secretory cell lineages: intermediate-like (Paneth/goblet) and enteroendocrine cells. Based on analysis of Rosa26NICD and Rosa26DN-MAML mice, we determined that ADAM10 controls these cell fate decisions by regulating Notch signaling. Cell lineage tracing experiments showed that ADAM10 is required for survival of Lgr5+ crypt-based columnar cells. Our findings indicate that Notch-activated stem cells have a competitive advantage for occupation of the stem cell niche. CONCLUSIONS ADAM10 acts in a cell autonomous manner within the intestinal crypt compartment to regulate Notch signaling. This process is required for progenitor cell lineage specification and crypt-based columnar cell maintenance. PMID:25038433

Impulse fur Bibliotheken (Impulses for Libraries). Publications of Essen University Library 19.

ERIC Educational Resources Information Center

Helal, Ahmed H., Ed.

This collection of 12 papers commemorates the retirement of Bernhard Adams. Adams had a 30-year career at the Bochum University Library (Germany) and advocated innovation and automation in libraries. The papers are: (1) "Gemeinsame Wegstrecken: Bernhard Adams zur Ehre" ("Common Milestones: In Honor of Bernhard Adams") (Harro…

The induction of C/EBPβ contributes to vitamin D inhibition of ADAM17 expression and parathyroid hyperplasia in kidney disease.

PubMed

Arcidiacono, Maria Vittoria; Yang, Jing; Fernandez, Elvira; Dusso, Adriana

2015-03-01

In secondary hyperparathyroidism (SHPT), enhanced parathyroid levels of transforming growth factor-α (TGFα) increase EGF receptor (EGFR) activation causing parathyroid hyperplasia, high parathyroid hormone (PTH) and also reductions in vitamin D receptor (VDR) that limit vitamin D suppression of SHPT. Since anti-EGFR therapy is not an option in human SHPT, we evaluated ADAM17 as a therapeutic target to suppress parathyroid hyperplasia because ADAM17 is required to release mature TGFα, the most potent EGFR-activating ligand. Computer analysis of the ADAM17 promoter identified TGFα and C/EBPβ as potential regulators of the ADAM17 gene. Their regulation of ADAM17 expression, TGFα/EGFR-driven growth and parathyroid gland (PTG) enlargement were assessed in promoter-reporter assays in A431 cells and corroborated in rat and human SHPT, using erlotinib as anti-EGFR therapy to suppress TGFα signals, active vitamin D to induce C/EBPβ or the combination. While TGFα induced ADAM17-promoter activity by 2.2-fold exacerbating TGFα/EGFR-driven growth, ectopic C/EBPβ expression completely prevented this vicious synergy. Accordingly, in advanced human SHPT, parathyroid ADAM17 levels correlated directly with TGFα and inversely with C/EBPβ. Furthermore, combined erlotinib + calcitriol treatment suppressed TGFα/EGFR-cell growth and PTG enlargement more potently than erlotinib in part through calcitriol induction of C/EBPβ to inhibit ADAM17-promoter activity, mRNA and protein. Importantly, in rat SHPT, the correction of vitamin D deficiency effectively reversed the resistance to paricalcitol induction of C/EBPβ to suppress ADAM17 expression and PTG enlargement, reducing PTH by 50%. In SHPT, correction of vitamin D and calcitriol deficiency induces parathyroid C/EBPβ to efficaciously attenuate the severe ADAM17/TGFα synergy, which drives PTG enlargement and high PTH. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Disintegrin and metalloproteinases (ADAMs) expression in gastroesophageal reflux disease and in esophageal adenocarcinoma.

PubMed

Kauttu, T; Mustonen, H; Vainionpää, S; Krogerus, L; Ilonen, I; Räsänen, J; Salo, J; Puolakkainen, P

2017-01-01

Clinically useful marker molecules for the progression of gastroesophageal reflux disease and Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) are lacking. Many adenocarcinomas and inflammatory conditions exhibit increased expression of ADAMs, 'a disintegrin and metalloproteinases'. We assessed the expression of five ADAMs (9, 10, 12, 17, 19) in three esophageal cell lines (Het-1A, OE19, OE33) by RT-PCR and Western blotting, and in human samples of normal esophagus, esophagitis, BE, Barrett's dysplasia, and EAC by RT-PCR, and in selected samples by immunohistochemistry. EAC patients showed increased mRNA expression of ADAMs 9, 12, 17 and 19, as compared to controls. At immunohistochemistry, ADAM9 and ADAM10 proteins were increased in EAC. Patient samples also showed increased mRNA expression of ADAM12 in esophagitis, of ADAM9 in BE, and of ADAMs 9, 12 and 19 in Barrett's dysplasia, as compared to controls. Two EAC cell lines showed increased ADAM9 mRNA. ADAM9 expression is increased in EAC. Its predecessors show increased ADAM9 mRNA expression. The importance of the alterations in ADAM expression for the development of EAC, and their use as marker molecules, warrant further studies.

Poor interoperability of the Adams-Harbertson method for analysis of anthocyanins: comparison with AOAC pH differential method.

PubMed

Brooks, Larry M; Kuhlman, Benjamin J; McKesson, Doug W; McCloskey, Leo

2013-01-01

The poor interoperability of anthocyanin glycosides measurements by two pH differential methods is documented. Adams-Harbertson, which was proposed for commercial winemaking, was compared to AOAC Official Method 2005.02 for wine. California bottled wines (Pinot Noir, Merlot, and Cabernet Sauvignon) were assayed in a collaborative study (n=105), which found mean precision of Adams-Harbertson winery versus reference measurements to be 77 +/- 20%. Maximum error is expected to be 48% for Pinot Noir, 42% for Merlot, and 34% for Cabernet Sauvignon from reproducibility RSD. Range of measurements was actually 30 to 91% for Pinot Noir. An interoperability study (n=30) found Adams-Harbertson produces measurements that are nominally 150% of the AOAC pH differential method. Large analytical chemistry differences are: AOAC method uses Beer-Lambert equation and measures absorbance at pH 1.0 and 4.5, proposed a priori by Flueki and Francis; whereas Adams-Harbertson uses "universal" standard curve and measures absorbance ad hoc at pH 1.8 and 4.9 to reduce the effects of so-called co-pigmentation. Errors relative to AOAC are produced by Adams-Harbertson standard curve over Beer-Lambert and pH 1.8 over pH 1.0. The study recommends using AOAC Official Method 2005.02 for analysis of wine anthocyanin glycosides.

Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis.

PubMed

De Savi, Chris; Pape, Andrew; Sawyer, Yvonne; Milne, David; Davies, Chris; Cumming, John G; Ting, Attilla; Lamont, Scott; Smith, Peter D; Tart, Jonathon; Page, Ken; Moore, Peter

2011-06-01

A new achiral class of N-hydroxyformamide inhibitor of both ADAM-TS4 and ADAM-TS5, 2 has been discovered through modification of the complex P1 group present in historical inhibitors 1. This structural change improved the DMPK properties and greatly simplified the synthesis whilst maintaining excellent cross-MMP selectivity profiles. Investigation of structure-activity and structure-property relationships in the P1 group resulted in both ADAM-TS4 selective and mixed ADAM-TS4/5 inhibitors. This led to the identification of a pre-clinical candidate with excellent bioavailability across three species and predicting once daily dosing kinetics. Copyright © 2011 Elsevier Ltd. All rights reserved.

Adams National Historical Park expanded transit service evaluation

DOT National Transportation Integrated Search

2009-12-01

In 2005 and 2006, Adams National Historical Park piloted expanded shuttle service, with the aim of promoting car-free access for its visitors. This report evaluates the 2006 season of operation. Adams National Historical Park (NHP) is located approxi...

Roles of ADAM13-regulated Wnt activity in early Xenopus eye development

PubMed Central

Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; Nakayama, Takuya; Shah, Anoop; Grainger, Robert M.; White, Judith M.; DeSimone, Douglas W.

2012-01-01

Pericellular proteolysis by ADAM family metalloproteinases has been widely implicated in cell signaling and development. We recently found that Xenopus ADAM13, an ADAM metalloproteinase, is required for activation of canonical Wnt signaling during cranial neural crest (CNC) induction by regulating a novel crosstalk between Wnt and ephrin B (EfnB) signaling pathways (Wei et al., 2010b). In the present study we show that the metalloproteinase activity of ADAM13 also plays important roles in eye development in X. tropicalis. Knockdown of ADAM13 results in reduced expression of eye field markers pax6 and rx1, as well as that of the pan-neural marker sox2. Activation of canonical Wnt signaling or inhibition of forward EfnB signaling rescues the eye defects caused by loss of ADAM13, suggesting that ADAM13 functions through regulation of the EfnB-Wnt pathway interaction. Downstream of Wnt, the head inducer Cerberus was identified as an effector that mediates ADAM13 function in early eye field formation. Furthermore, ectopic expression of the Wnt target gene snail2 restores cerberus expression and rescues the eye defects caused by ADAM13 knockdown. Together these data suggest an important role of ADAM13-regulated Wnt activity in eye development in Xenopus. PMID:22227340

Marguerite Arnet Residence, exterior door detail, looking north. Adam ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Marguerite Arnet Residence, exterior door detail, looking north. - Adam & Bessie Arnet Homestead, Marguerite Arnet Residence, 560 feet northeast of Adam & Bessie Arnet Residence, Model, Las Animas County, CO

Marguerite Arnet Residence, exterior window detail, looking north. Adam ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Marguerite Arnet Residence, exterior window detail, looking north. - Adam & Bessie Arnet Homestead, Marguerite Arnet Residence, 560 feet northeast of Adam & Bessie Arnet Residence, Model, Las Animas County, CO

Selective Modulation of Integrin-mediated Cell Migration by Distinct ADAM Family MembersV⃞

PubMed Central

Huang, Jing; Bridges, Lance C.; White, Judith M.

2005-01-01

A disintegrin and a metalloprotease (ADAM) family members have been implicated in many biological processes. Although it is recognized that recombinant ADAM disintegrin domains can interact with integrins, little is known about ADAM-integrin interactions in cellular context. Here, we tested whether ADAMs can selectively regulate integrin-mediated cell migration. ADAMs were expressed in Chinese hamster ovary cells that express defined integrins (α4β1, α5β1, or both), and cell migration on full-length fibronectin or on its α4β1 or α5β1 binding fragments was studied. We found that ADAMs inhibit integrin-mediated cell migration in patterns dictated by the integrin binding profiles of their isolated disintegrin domains. ADAM12 inhibited cell migration mediated by the α4β1 but not the α5β1 integrin. ADAM17 had the reciprocal effect; it inhibited α5β1- but not α4β1-mediated cell migration. ADAM19 and ADAM33 inhibited migration mediated by both α4β1 and α5β1 integrins. A point mutation in the ADAM12 disintegrin loop partially reduced the inhibitory effect of ADAM12 on cell migration on the α4β1 binding fragment of fibronectin, whereas mutations that block metalloprotease activity had no effect. Our results indicate that distinct ADAMs can modulate cell migration mediated by specific integrins in a pattern dictated, at least in part, by their disintegrin domains. PMID:16079176

Identification of ADAM 31: a protein expressed in Leydig cells and specialized epithelia.

PubMed

Liu, L; Smith, J W

2000-06-01

A family of proteins containing a disintegrin and metalloproteinase domain (ADAMs) has been identified recently. Here, we report the identification of a novel member of the ADAM protein family from mouse. This protein is designated ADAM 31. The complementary DNA sequence of ADAM 31 predicts a transmembrane protein with metalloproteinase, disintegrin, cysteine-rich, and cytoplasmic domains. Messenger RNA encoding ADAM 31 was most abundant in testes, but was also detected in many other tissues. More significantly, the antibodies raised against ADAM 31 reveal that the protein has a unique and restricted expression pattern. ADAM 31 is expressed in Leydig cells of the testes, but unlike many other ADAMs, it is not found on developing sperm. Furthermore, ADAM 31 is highly expressed on four types of specialized epithelia: the cauda epididymidis, the vas deferens, the convoluted tubules of the kidney, and the parietal cells of the stomach.

The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity.

PubMed

Abbruzzese, Genevieve; Gorny, Anne-Kathrin; Kaufmann, Lilian T; Cousin, Hélène; Kleino, Iivari; Steinbeisser, Herbert; Alfandari, Dominique

2015-03-15

Cranial neural crest (CNC) cells are a transient population of stem cells that originate at the border of the neural plate and the epidermis, and migrate ventrally to contribute to most of the facial structures including bones, cartilage, muscles and ganglia. ADAM13 is a cell surface metalloprotease that is essential for CNC cell migration. Here, we show in Xenopus laevis embryos that the Wnt receptor Fz4 binds to the cysteine-rich domain of ADAM13 and negatively regulates its proteolytic activity in vivo. Gain of Fz4 function inhibits CNC cell migration and can be rescued by gain of ADAM13 function. Loss of Fz4 function also inhibits CNC cell migration and induces a reduction of mature ADAM13, together with an increase in the ADAM13 cytoplasmic fragment that is known to translocate into the nucleus to regulate gene expression. We propose that Fz4 associates with ADAM13 during its transport to the plasma membrane to regulate its proteolytic activity. © 2015. Published by The Company of Biologists Ltd.

The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity

PubMed Central

Abbruzzese, Genevieve; Gorny, Anne-Kathrin; Kaufmann, Lilian T.; Cousin, Hélène; Kleino, Iivari; Steinbeisser, Herbert; Alfandari, Dominique

2015-01-01

ABSTRACT Cranial neural crest (CNC) cells are a transient population of stem cells that originate at the border of the neural plate and the epidermis, and migrate ventrally to contribute to most of the facial structures including bones, cartilage, muscles and ganglia. ADAM13 is a cell surface metalloprotease that is essential for CNC cell migration. Here, we show in Xenopus laevis embryos that the Wnt receptor Fz4 binds to the cysteine-rich domain of ADAM13 and negatively regulates its proteolytic activity in vivo. Gain of Fz4 function inhibits CNC cell migration and can be rescued by gain of ADAM13 function. Loss of Fz4 function also inhibits CNC cell migration and induces a reduction of mature ADAM13, together with an increase in the ADAM13 cytoplasmic fragment that is known to translocate into the nucleus to regulate gene expression. We propose that Fz4 associates with ADAM13 during its transport to the plasma membrane to regulate its proteolytic activity. PMID:25616895

Characterization of a novel ADAM protease expressed by Pneumocystis carinii.

PubMed

Kennedy, Cassie C; Kottom, Theodore J; Limper, Andrew H

2009-08-01

Pneumocystis species are opportunistic fungal pathogens that cause severe pneumonia in immunocompromised hosts. Recent evidence has suggested that unidentified proteases are involved in Pneumocystis life cycle regulation. Proteolytically active ADAM (named for "a disintegrin and metalloprotease") family molecules have been identified in some fungal organisms, such as Aspergillus fumigatus and Schizosaccharomyces pombe, and some have been shown to participate in life cycle regulation. Accordingly, we sought to characterize ADAM-like molecules in the fungal opportunistic pathogen, Pneumocystis carinii (PcADAM). After an in silico search of the P. carinii genomic sequencing project identified a 329-bp partial sequence with homology to known ADAM proteins, the full-length PcADAM sequence was obtained by PCR extension cloning, yielding a final coding sequence of 1,650 bp. Sequence analysis detected the presence of a typical ADAM catalytic active site (HEXXHXXGXXHD). Expression of PcADAM over the Pneumocystis life cycle was analyzed by Northern blot. Southern and contour-clamped homogenous electronic field blot analysis demonstrated its presence in the P. carinii genome. Expression of PcADAM was observed to be increased in Pneumocystis cysts compared to trophic forms. The full-length gene was subsequently cloned and heterologously expressed in Saccharomyces cerevisiae. Purified PcADAMp protein was proteolytically active in casein zymography, requiring divalent zinc. Furthermore, native PcADAMp extracted directly from freshly isolated Pneumocystis organisms also exhibited protease activity. This is the first report of protease activity attributable to a specific, characterized protein in the clinically important opportunistic fungal pathogen Pneumocystis.

Altered cell-matrix associated ADAM proteins in Alzheimer disease.

PubMed

Gerst, J L; Raina, A K; Pirim, I; McShea, A; Harris, P L; Siedlak, S L; Takeda, A; Petersen, R B; Smith, M A

2000-03-01

Alterations in cell-matrix 'contact' are often related to a disruption of cell cycle regulation and, as such, occur variously in neoplasia. Given the recent findings showing cell cycle alterations in Alzheimer disease, we undertook a study of ADAM-1 and 2 (A Disintegrin And Metalloprotease), developmentally-regulated, integrin-binding, membrane-bound metalloproteases. Our results show that whereas ADAM-1 and 2 are found in susceptible hippocampal neurons in Alzheimer disease, these proteins were not generally increased in similar neuronal populations in younger or age-matched controls except in association with age-related neurofibrillary alterations. This increase in both ADAM-1 and 2 in cases of Alzheimer disease was verified by immunoblot analysis (P < 0.05). An ADAM-induced loss of matrix integration would effectively "reset" the mitotic clock and thereby stimulate re-entry into the cell cycle in neurons in Alzheimer disease. Furthermore, given the importance of integrins in maintaining short-term memory, alterations in ADAM proteins or their proteolytic activity could also play a proximal role in the clinico-pathological manifestations of Alzheimer disease. Copyright 2000 Wiley-Liss, Inc.

ADAMS executive and operating system

NASA Technical Reports Server (NTRS)

Pittman, W. D.

1981-01-01

The ADAMS Executive and Operating System, a multitasking environment under which a variety of data reduction, display and utility programs are executed, a system which provides a high level of isolation between programs allowing them to be developed and modified independently, is described. The Airborne Data Analysis/Monitor System (ADAMS) was developed to provide a real time data monitoring and analysis capability onboard Boeing commercial airplanes during flight testing. It inputs sensor data from an airplane performance data by applying transforms to the collected sensor data, and presents this data to test personnel via various display media. Current utilization and future development are addressed.

Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer’s Disease Treatment

PubMed Central

Peron, Rafaela; Vatanabe, Izabela Pereira; Manzine, Patricia Regina; Camins, Antoni

2018-01-01

ADAM (a disintegrin and metalloproteinase) is a family of widely expressed, transmembrane and secreted proteins of approximately 750 amino acids in length with functions in cell adhesion and proteolytic processing of the ectodomains of diverse cell-surface receptors and signaling molecules. ADAM10 is the main α-secretase that cleaves APP (amyloid precursor protein) in the non-amyloidogenic pathway inhibiting the formation of β-amyloid peptide, whose accumulation and aggregation leads to neuronal degeneration in Alzheimer’s disease (AD). ADAM10 is a membrane-anchored metalloprotease that sheds, besides APP, the ectodomain of a large variety of cell-surface proteins including cytokines, adhesion molecules and notch. APP cleavage by ADAM10 results in the production of an APP-derived fragment, sAPPα, which is neuroprotective. As increased ADAM10 activity protects the brain from β-amyloid deposition in AD, this strategy has been proved to be effective in treating neurodegenerative diseases, including AD. Here, we describe the physiological mechanisms regulating ADAM10 expression at different levels, aiming to propose strategies for AD treatment. We report in this review on the physiological regulation of ADAM10 at the transcriptional level, by epigenetic factors, miRNAs and/or translational and post-translational levels. In addition, we describe the conditions that can change ADAM10 expression in vitro and in vivo, and discuss how this knowledge may help in AD treatment. Regulation of ADAM10 is achieved by multiple mechanisms that include transcriptional, translational and post-translational strategies, which we will summarize in this review. PMID:29382156

Joseph Adams (1756-1818).

PubMed

Emery, A E

1989-02-01

Joseph Adams was eclectic in his interests and wrote on a variety of medical subjects. His last book published in 1814 was on hereditary disease and based on a lifetime's careful clinical observations. In it he distinguished between what would now be defined as dominant and recessive disorders; defined the term congenital; emphasised the role of inbreeding in producing clustering of certain inherited disorders; introduced concepts now known as founder effect, incomplete penetrance, and variable age at onset; emphasised the importance of environmental factors in precipitating disease in certain genetic disorders; and, finally, recommended the establishment of registers for the purpose of preventing genetic disease. But because he proposed no scientific explanation for these various ideas, they were largely ignored by his contemporaries. Nevertheless, it would seem right to regard Joseph Adams as perhaps the first clinical geneticist.

The enhanced susceptibility of ADAM-17 hypomorphic mice to DSS-induced colitis is not ameliorated by loss of RIPK3, revealing an unexpected function of ADAM-17 in necroptosis

PubMed Central

Luzius, Anne; Saggau, Carina; Ruder, Barbara; Bolik, Julia; Schmidt-Arras, Dirk; Linkermann, Andreas; Becker, Christoph; Rosenstiel, Philip; Rose-John, Stefan; Adam, Dieter

2018-01-01

The disintegrin metalloprotease ADAM17 has a critical role in intestinal inflammation and regeneration in mice, as illustrated by the dramatically increased susceptibility of ADAM17 hypomorphic (ADAM17ex/ex) mice to dextran sulfate sodium (DSS)-induced colitis. Similarly, necroptosis has been implicated in inflammatory responses in the intestine. In this study, we have investigated the contribution of necroptosis to ADAM17-regulated intestinal inflammation in vivo by crossing ADAM17ex/ex mice with mice that lack the necroptotic core protein RIPK3. Despite the loss of RIPK3, ADAM17ex/ex/RIPK3−/− mice showed the same increased susceptibility as ADAM17ex/ex mice in both acute and chronic models of DSS-induced colitis. Mice of both genotypes revealed comparable results with regard to weight loss, disease activity index and colitis-associated changes of inner organs. Histopathological analyses confirmed similar tissue destruction, loss of barrier integrity, immune cell infiltration, and cell death; serum analyses revealed similar levels of the pro-inflammatory cytokine KC. Resolving these unexpected findings, ADAM17ex/ex mice did not show phosphorylation of RIPK3 and its necroptotic interaction partner MLKL during DSS-induced colitis, although both proteins were clearly expressed. Consistent with these findings, murine embryonic fibroblasts derived from ADAM17ex/ex mice were protected from tumor necrosis factor (TNF)-induced necroptosis and failed to show phosphorylation of MLKL and RIPK3 after induction of necroptosis by TNF, revealing a novel, undescribed role of the protease ADAM17 in necroptosis. PMID:29560122

The enhanced susceptibility of ADAM-17 hypomorphic mice to DSS-induced colitis is not ameliorated by loss of RIPK3, revealing an unexpected function of ADAM-17 in necroptosis.

PubMed

Fuchslocher Chico, Johaiber; Falk-Paulsen, Maren; Luzius, Anne; Saggau, Carina; Ruder, Barbara; Bolik, Julia; Schmidt-Arras, Dirk; Linkermann, Andreas; Becker, Christoph; Rosenstiel, Philip; Rose-John, Stefan; Adam, Dieter

2018-02-27

The disintegrin metalloprotease ADAM17 has a critical role in intestinal inflammation and regeneration in mice, as illustrated by the dramatically increased susceptibility of ADAM17 hypomorphic (ADAM17 ex/ex ) mice to dextran sulfate sodium (DSS)-induced colitis. Similarly, necroptosis has been implicated in inflammatory responses in the intestine. In this study, we have investigated the contribution of necroptosis to ADAM17-regulated intestinal inflammation in vivo by crossing ADAM17 ex/ex mice with mice that lack the necroptotic core protein RIPK3. Despite the loss of RIPK3, ADAM17 ex/ex /RIPK3 -/- mice showed the same increased susceptibility as ADAM17 ex/ex mice in both acute and chronic models of DSS-induced colitis. Mice of both genotypes revealed comparable results with regard to weight loss, disease activity index and colitis-associated changes of inner organs. Histopathological analyses confirmed similar tissue destruction, loss of barrier integrity, immune cell infiltration, and cell death; serum analyses revealed similar levels of the pro-inflammatory cytokine KC. Resolving these unexpected findings, ADAM17 ex/ex mice did not show phosphorylation of RIPK3 and its necroptotic interaction partner MLKL during DSS-induced colitis, although both proteins were clearly expressed. Consistent with these findings, murine embryonic fibroblasts derived from ADAM17 ex/ex mice were protected from tumor necrosis factor (TNF)-induced necroptosis and failed to show phosphorylation of MLKL and RIPK3 after induction of necroptosis by TNF, revealing a novel, undescribed role of the protease ADAM17 in necroptosis.

Improved synthesis of ADAM10 inhibitor GI254023X.

PubMed

Hoettecke, Nicole; Ludwig, Andreas; Foro, Sabine; Schmidt, Boris

2010-01-01

The metalloproteinases ADAM10 and ADAM17 are involved in various diseases: neurodegeneration, cancer and inflammation. The inhibition of these proteases is a promising target in the treatment of inflammation and cancer. In this study, we present an improved synthesis of the ADAM10 reference inhibitor GI254023X with a higher overall yield, enhanced detection ability and increased acid stability, providing easier handling. This upscaled synthesis, free of diastereomeric intermediates, ensures single-batch identity, thus warranting its reproducibility in further biological investigations. 2010 S. Karger AG, Basel.

ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

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

Tan, Yu, E-mail: tanyu2048@163.com; Fu, Runqing, E-mail: furunqing@sjtu.edu.cn; Liu, Jiaqiang, E-mail: liujqmj@163.com

Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of themore » craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.« less

iRHOM2-dependent regulation of ADAM17 in cutaneous disease and epidermal barrier function.

PubMed

Brooke, Matthew A; Etheridge, Sarah L; Kaplan, Nihal; Simpson, Charlotte; O'Toole, Edel A; Ishida-Yamamoto, Akemi; Marches, Olivier; Getsios, Spiro; Kelsell, David P

2014-08-01

iRHOM2 is a highly conserved, catalytically inactive member of the Rhomboid family, which has recently been shown to regulate the maturation of the multi-substrate ectodomain sheddase enzyme ADAM17 (TACE) in macrophages. Dominant iRHOM2 mutations are the cause of the inherited cutaneous and oesophageal cancer-susceptibility syndrome tylosis with oesophageal cancer (TOC), suggesting a role for this protein in epithelial cells. Here, using tissues derived from TOC patients, we demonstrate that TOC-associated mutations in iRHOM2 cause an increase in the maturation and activity of ADAM17 in epidermal keratinocytes, resulting in significantly upregulated shedding of ADAM17 substrates, including EGF-family growth factors and pro-inflammatory cytokines. This activity is accompanied by increased EGFR activity, increased desmosome processing and the presence of immature epidermal desmosomes, upregulated epidermal transglutaminase activity and heightened resistance to Staphylococcal infection in TOC keratinocytes. Many of these features are consistent with the presence of a constitutive wound-healing-like phenotype in TOC epidermis, which may shed light on a novel pathway in skin repair, regeneration and inflammation. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

High ADAM8 expression is associated with poor prognosis in patients with hepatocellular carcinoma.

PubMed

Zhang, Yun; Tan, Yong-Fei; Jiang, Chao; Zhang, Kai; Zha, Tian-Zhou; Zhang, Miao

2013-01-01

In this study,we investigated the ADAM8 expression in hepatocellular carcinoma (HCC) and its correlation with clinicopathologic features,including the survival of patients with HCC. Furthermore,we examined the biological processes regulated by ADAM8 during the development of using HepG2 cell line as a model system. We used immunohistochemistry to compare ADAM8 protein expression in HCC and normal liver tissues and further analyze the ADAM8 protein expression in clinicopathologically characterized 105 HCC cases.We stably knocked down the endogenous expression level of ADAM8 in HepG2 cells with specific shRNA-expressing lentiviral vector. Following the successful establishment of stable cells,we examined in vitro cell growth by MTT assay,anchorage-independent growth by soft-agar colony formation assay and cell migration/invasion by transwell and boyden chamber assay. And in addition,we also investigated the in vivo tumor growth by xenograft transplantation of HepG2 cells into nude mice. Protein expression level of ADAM8 was markedly higher in HCC tissues than that in the normal liver tissues (P = 0.0058).In addition,high expression of ADAM8 protein was positively correlated with serum AFP elevation,tumor size,histological differentiation,tumor recurrence,tumor metastasis,and tumor stage. Patients with higher ADAM8 expression showed a significantly shorter overall survival time than patients with low ADAM8 expression. Multivariate analysis suggested that ADAM8 expression might be an independent prognostic indicator (p = 0.016) for the survival of patients with HCC. ADAM8-specific shRNA (shADAM8) successfully knocked down its endogenous expression in HepG2 cells. Compared to the parental and control shRNA-transfected (shCtrl) HepG2 cells,the shADAM8 cells exhibited significantly reduced in vitro cell growth,anchorage-independent growth,cell migration and invasion (p < 0.05).In vivo,the xenograft transplants from shADAM8 cells gave rise to much smaller

Taking Charge: Walter Sydney Adams and the Mount Wilson Observatory

NASA Astrophysics Data System (ADS)

Brashear, R.

2004-12-01

The growing preeminence of American observational astronomy in the first half of the 20th century is a well-known story and much credit is given to George Ellery Hale and his skill as an observatory-building entrepreneur. But a key figure who has yet to be discussed in great detail is Walter Sydney Adams (1876-1956), Hale's Assistant Director at Mount Wilson Observatory. Due to Hale's illnesses, Adams was Acting Director for much of Hale's tenure, and he became the second Director of Mount Wilson from 1923 to 1946. Behind his New England reserve Adams was instrumental in the growth of Mount Wilson and thus American astronomy in general. Adams was hand-picked by Hale to take charge of stellar spectroscopy work at Yerkes and Mount Wilson and the younger astronomer showed tremendous loyalty to Hale and Hale's vision throughout his career. As Adams assumed the leadership role at Mount Wilson he concentrated on making the observatory a place where researchers worked with great freedom but maintain a high level of cooperation. This paper will concentrate on Adams's early years and look at his growing relationship with Hale and how he came to be the central figure in the early history of Mount Wilson as both a solar and stellar observatory. His education, his years at Dartmouth and Yerkes (including his unfortunate encounter with epsilon Leonis), and his formative years on Mount Wilson are all important in learning how he shaped the direction of Mount Wilson and the development of American astronomy in the first half of the 20th century. This latter history cannot be complete until we bring Adams into better focus.

SAP97-mediated ADAM10 trafficking from Golgi outposts depends on PKC phosphorylation

PubMed Central

Saraceno, C; Marcello, E; Di Marino, D; Borroni, B; Claeysen, S; Perroy, J; Padovani, A; Tramontano, A; Gardoni, F; Di Luca, M

2014-01-01

A disintegrin and metalloproteinase 10 (ADAM10) is the major α-secretase that catalyzes the amyloid precursor protein (APP) ectodomain shedding in the brain and prevents amyloid formation. Its activity depends on correct intracellular trafficking and on synaptic membrane insertion. Here, we describe that in hippocampal neurons the synapse-associated protein-97 (SAP97), an excitatory synapse scaffolding element, governs ADAM10 trafficking from dendritic Golgi outposts to synaptic membranes. This process is mediated by a previously uncharacterized protein kinase C phosphosite in SAP97 SRC homology 3 domain that modulates SAP97 association with ADAM10. Such mechanism is essential for ADAM10 trafficking from the Golgi outposts to the synapse, but does not affect ADAM10 transport from the endoplasmic reticulum. Notably, this process is altered in Alzheimer's disease brains. These results help in understanding the mechanism responsible for the modulation of ADAM10 intracellular path, and can constitute an innovative therapeutic strategy to finely tune ADAM10 shedding activity towards APP. PMID:25429624

[The progress in the rehabilitation of dysarthria in Parkinson disease using LSVT (Lee Silverman Voice Treatment)].

PubMed

Kamińska, Ilona; Zebryk-Stopa, Anna; Pruszewicz, Antoni; Dziubalska-Kołaczyk, Katarzyna; Połczyńska-Fiszer, Monika; Pietrala, Dawid; Przedpelska-Ober, Elzbieta

2007-01-01

Parkison's disease causes damage to the central nervous system resulting in bradykinesia, muscle rigidity, rest tremor and dysarthric speech. In clinical terms dysarthria denotes the dysfunction of articulation, phonation and respiration. It is brought about by the impairment of neural paths innervating the speech apparatus, thus causing a decreased ability to communicate. The study was conducted by the Center for Speech and Language Processing (CSLP), Adam Mickiewicz University, Poznań and the Chair and Department of Phoniatrics and Audiology, the Medical University, Poznań within the interdisciplinary research project grant called "Speech and Language Virtual Therapist for Individuals with Parkinson's Disease". Apart from traditional voice and speech therapies, one of the ways of treating speech disturbances accompanying Parkinson's disease is an innovative Lee Silverman Voice Treatment (LSVT). The purpose of this innovative method introduced by dr L. Ramig and colleagues in 1987-1988, is to teach the patient to speak loud. As a result of co-operation between CLSP and the Center for Spoken Language Research (CSLR) at the University of Colorado, Boulder, USA, a Polish version of LSVT Virtual Therapist computer programme was created (LSVTVT). The programme is based on the principles of LSVT. The positive outcomes of the therapy give hope to Parkinson's disease patients with dysarthria, as well as to speech therapists.

ADAM-17 regulates endothelial cell morphology, proliferation, and in vitro angiogenesis

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

Goeoz, Pal; Goeoz, Monika; Baldys, Aleksander

2009-02-27

Modulation of angiogenesis is a promising approach for treating a wide variety of human diseases including ischemic heart disease and cancer. In this study, we show that ADAM-17 is an important regulator of several key steps during angiogenesis. Knocking down ADAM-17 expression using lentivirus-delivered siRNA in HUVECs inhibited cell proliferation and the ability of cells to form close contact in two-dimensional cultures. Similarly, ADAM-17 depletion inhibited the ability of HUVECs to form capillary-like networks on top of three-dimensional Matrigel as well as in co-culture with fibroblasts within a three-dimensional scaffold. In mechanistic studies, both baseline and VEGF-induced MMP-2 activation andmore » Matrigel invasion were inhibited by ADAM-17 depletion. Based on our findings we propose that ADAM-17 is part of a novel pro-angiogenic pathway leading to MMP-2 activation and vessel formation.« less

Adams-Based Rover Terramechanics and Mobility Simulator - ARTEMIS

NASA Technical Reports Server (NTRS)

Trease, Brian P.; Lindeman, Randel A.; Arvidson, Raymond E.; Bennett, Keith; VanDyke, Lauren P.; Zhou, Feng; Iagnemma, Karl; Senatore, Carmine

2013-01-01

The Mars Exploration Rovers (MERs), Spirit and Opportunity, far exceeded their original drive distance expectations and have traveled, at the time of this reporting, a combined 29 kilometers across the surface of Mars. The Rover Sequencing and Visualization Program (RSVP), the current program used to plan drives for MERs, is only a kinematic simulator of rover movement. Therefore, rover response to various terrains and soil types cannot be modeled. Although sandbox experiments attempt to model rover-terrain interaction, these experiments are time-intensive and costly, and they cannot be used within the tactical timeline of rover driving. Imaging techniques and hazard avoidance features on MER help to prevent the rover from traveling over dangerous terrains, but mobility issues have shown that these methods are not always sufficient. ARTEMIS, a dynamic modeling tool for MER, allows planned drives to be simulated before commands are sent to the rover. The deformable soils component of this model allows rover-terrain interactions to be simulated to determine if a particular drive path would take the rover over terrain that would induce hazardous levels of slip or sink. When used in the rover drive planning process, dynamic modeling reduces the likelihood of future mobility issues because high-risk areas could be identified before drive commands are sent to the rover, and drives planned over these areas could be rerouted. The ARTEMIS software consists of several components. These include a preprocessor, Digital Elevation Models (DEMs), Adams rover model, wheel and soil parameter files, MSC Adams GUI (commercial), MSC Adams dynamics solver (commercial), terramechanics subroutines (FORTRAN), a contact detection engine, a soil modification engine, and output DEMs of deformed soil. The preprocessor is used to define the terrain (from a DEM) and define the soil parameters for the terrain file. The Adams rover model is placed in this terrain. Wheel and soil parameter files

A Disintegrin and Metalloproteases (ADAMs) in Cardiovascular, Metabolic and Inflammatory Diseases: Aspects for Theranostic Approaches.

PubMed

van der Vorst, Emiel P C; Weber, Christian; Donners, Marjo M P C

2018-06-06

A disintegrin and metalloproteases (ADAMs) are membrane-bound enzymes responsible for the shedding or cleavage of various cell surface molecules, such as adhesion molecules, cytokines/chemokines and growth factors. This shedding can result in the release of soluble proteins that can exert agonistic or antagonistic functions. Additionally, ADAM-mediated cleavage can render these membrane proteins inactive. This review will describe the role and association of ADAMs in various pathologies with a main focus on ADAM10 and ADAM17 in atherosclerosis, including a brief overview of atherosclerosis-related ADAM substrates. Furthermore, ADAMs involvement in other metabolic and inflammatory diseases like diabetes, sepsis, Alzheimer's disease and rheumatoid arthritis will be highlighted. Subsequently, we will briefly discuss an interesting emerging field of research, i.e. the potential implications of ADAM expression in extracellular vesicles. Finally, several ADAM-based therapeutic and diagnostic (theranostic) opportunities will be discussed, while focusing on key questions about the required specificity and selectivity. Schattauer GmbH Stuttgart.

ADAM10 is essential for cranial neural crest-derived maxillofacial bone development.

PubMed

Tan, Yu; Fu, Runqing; Liu, Jiaqiang; Wu, Yong; Wang, Bo; Jiang, Ning; Nie, Ping; Cao, Haifeng; Yang, Zhi; Fang, Bing

2016-07-08

Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. Copyright © 2016 Elsevier Inc. All rights reserved.

Overview of graduate training program of John Adams Institute for Accelerator Science

NASA Astrophysics Data System (ADS)

Seryi, Andrei

The John Adams Institute for Accelerator Science is a center of excellence in the UK for advanced and novel accelerator technology, providing expertise, research, development and training in accelerator techniques, and promoting advanced accelerator applications in science and society. We work in JAI on design of novel light sources upgrades of 3-rd generation and novel FELs, on plasma acceleration and its application to industrial and medical fields, on novel energy recovery compact linacs and advanced beam diagnostics, and many other projects. The JAI is based on three universities - University of Oxford, Imperial College London and Royal Holloway University of London. Every year 6 to 10 accelerators science experts, trained via research on cutting edge projects, defend their PhD thesis in JAI partner universities. In this presentation we will overview the research and in particular the highly successful graduate training program in JAI.

ADAM10 Missense Mutations Potentiate β-Amyloid Accumulation by Impairing Prodomain Chaperone Function

PubMed Central

Suh, Jaehong; Choi, Se Hoon; Romano, Donna M.; Gannon, Moira A.; Lesinski, Andrea N.; Kim, Doo Yeon; Tanzi, Rudolph E.

2014-01-01

SUMMARY The generation of Aβ, the main component of senile plaques in Alzheimer’s disease (AD), is precluded by α-secretase cleavage within the Aβ domain of the amyloid precursor protein (APP). We identified two rare mutations (Q170H and R181G) in the prodomain of the metalloprotease, ADAM10, that co-segregate with late-onset AD (LOAD). Here, we addressed the pathogenicity of these mutations in transgenic mice expressing human ADAM10 in brain. In Tg2576 AD mice, both mutations attenuated α-secretase activity of ADAM10 and shifted APP processing toward β-secretase-mediated cleavage, while enhancing Aβ plaque load and reactive gliosis. We also demonstrated ADAM10 expression potentiates adult hippocampal neurogenesis, which is reduced by the LOAD mutations. Mechanistically, both LOAD mutations impaired the molecular chaperone activity of ADAM10 prodomain. Collectively, these findings suggest that diminished α-secretase activity, owing to LOAD ADAM10 prodomain mutations, leads to AD-related pathology, strongly supporting ADAM10 as a promising therapeutic target for this devastating disease. PMID:24055016

ADAM10 missense mutations potentiate β-amyloid accumulation by impairing prodomain chaperone function.

PubMed

Suh, Jaehong; Choi, Se Hoon; Romano, Donna M; Gannon, Moira A; Lesinski, Andrea N; Kim, Doo Yeon; Tanzi, Rudolph E

2013-10-16

The generation of Aβ, the main component of senile plaques in Alzheimer's disease (AD), is precluded by α-secretase cleavage within the Aβ domain of the amyloid precursor protein (APP). We identified two rare mutations (Q170H and R181G) in the prodomain of the metalloprotease, ADAM10, that cosegregate with late-onset AD (LOAD). Here, we addressed the pathogenicity of these mutations in transgenic mice expressing human ADAM10 in brain. In Tg2576 AD mice, both mutations attenuated α-secretase activity of ADAM10 and shifted APP processing toward β-secretase-mediated cleavage, while enhancing Aβ plaque load and reactive gliosis. We also demonstrated ADAM10 expression potentiates adult hippocampal neurogenesis, which is reduced by the LOAD mutations. Mechanistically, both LOAD mutations impaired the molecular chaperone activity of ADAM10 prodomain. Collectively, these findings suggest that diminished α-secretase activity, owing to LOAD ADAM10 prodomain mutations, leads to AD-related pathology, strongly supporting ADAM10 as a promising therapeutic target for this devastating disease. Copyright © 2013 Elsevier Inc. All rights reserved.

A Conversation with Adam Heller.

PubMed

Heller, Adam; Cairns, Elton J

2015-01-01

Adam Heller, Ernest Cockrell Sr. Chair in Engineering Emeritus of the John J. McKetta Department of Chemical Engineering at The University of Texas at Austin, recalls his childhood in the Holocaust and his contributions to science and technology that earned him the US National Medal of Technology and Innovation in a conversation with Elton J. Cairns, Professor of Chemical and Biomolecular Engineering at the University of California, Berkeley. Dr. Heller, born in 1933, describes the enslavement of his father by Hungarians in 1942; the confiscation of his family's home, business, and all its belongings in 1944; and his incarceration in a brick factory with 18,000 Jews who were shipped by the Hungarians to be gassed by Germans in Auschwitz. Dr. Heller and his immediate family survived the Holocaust and arrived in Israel in 1945. He studied under Ernst David Bergmann at the Hebrew University, and then worked at Bell Laboratories and GTE Laboratories, where he headed Bell Lab's Electronic Materials Research Department. At GTE Laboratories, he built in 1966 the first neodymium liquid lasers and in 1973 with Jim Auborn conceived and engineered the lithium thionyl chloride battery, one of the first to be manufactured lithium batteries, which is still in use. After joining the faculty of engineering of The University of Texas at Austin, he cofounded with his son Ephraim Heller TheraSense, now a major part of Abbott Diabetes Care, which produced a microcoulometer that made the monitoring of glucose painless by accurately measuring the blood glucose concentration in 300 nL of blood. He also describes the electrical wiring of enzymes, the basis for Abbott's state-of-the-art continuous glucose monitoring system. He discusses his perspective of reducing the risk of catastrophic global warming in a wealth-accumulating, more-energy-consuming world and provides advice for students entering careers in science or engineering.

Nuclear trafficking of the HIV-1 pre-integration complex depends on the ADAM10 intracellular domain

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

Endsley, Mark A., E-mail: maendsle@utmb.edu; Somasunderam, Anoma D., E-mail: asomasun@utmb.edu; Li, Guangyu, E-mail: LIG001@mail.etsu.edu

Previously, we showed that ADAM10 is necessary for HIV-1 replication in primary human macrophages and immortalized cell lines. Silencing ADAM10 expression interrupted the HIV-1 life cycle prior to nuclear translocation of viral cDNA. Furthermore, our data indicated that HIV-1 replication depends on the expression of ADAM15 and γ-secretase, which proteolytically processes ADAM10. Silencing ADAM15 or γ-secretase expression inhibits HIV-1 replication between reverse transcription and nuclear entry. Here, we show that ADAM10 expression also supports replication in CD4{sup +} T lymphocytes. The intracellular domain (ICD) of ADAM10 associates with the HIV-1 pre-integration complex (PIC) in the cytoplasm and immunoprecipitates and co-localizesmore » with HIV-1 integrase, a key component of PIC. Taken together, our data support a model whereby ADAM15/γ-secretase processing of ADAM10 releases the ICD, which then incorporates into HIV-1 PIC to facilitate nuclear trafficking. Thus, these studies suggest ADAM10 as a novel therapeutic target for inhibiting HIV-1 prior to nuclear entry. - Highlights: • Nuclear trafficking of the HIV-1 pre-integration complex depends on ADAM10. • ADAM10 associates with HIV-1 integrase in the pre-integration complex. • HIV-1 replication depends on the expression of ADAM15 and γ-secretase. • Silencing ADAM15 or γ-secretase expression inhibits nuclear import of viral cDNA. • ADAM10 is important for HIV-1 replication in human macrophages and CD4{sup +} T lymphocytes.« less

Erbb2 up-regulation of ADAM12 expression accelerates skin cancer progression.

PubMed

Rao, Velidi H; Vogel, Kristen; Yanagida, Jodi K; Marwaha, Nitin; Kandel, Amrit; Trempus, Carol; Repertinger, Susan K; Hansen, Laura A

2015-10-01

Solar ultraviolet (UV) radiation can cause severe damage to the skin and is the primary cause of most skin cancer. UV radiation causes DNA damage leading to mutations and also activates the Erbb2/HER2 receptor through indirect mechanisms involving reactive oxygen species. We hypothesized that Erbb2 activation accelerates the malignant progression of UV-induced skin cancer. Following the induction of benign squamous papillomas by UV exposure of v-ras(Ha) transgenic Tg.AC mice, mice were treated topically with the Erbb2 inhibitor AG825 and tumor progression monitored. AG825 treatment reduced tumor volume, increased tumor regression, and delayed the development of malignant squamous cell carcinoma (SCC). Progression to malignancy was associated with increased Erbb2 and ADAM12 (A Disintegin And Metalloproteinase 12) transcripts and protein, while inhibition of Erbb2 blocked the increase in ADAM12 message upon malignant progression. Similarly, human SCC and SCC cell lines had increased ADAM12 protein and transcripts when compared to normal controls. To determine whether Erbb2 up-regulation of ADAM12 contributed to malignant progression of skin cancer, Erbb2 expression was modulated in cultured SCC cells using forced over-expression or siRNA targeting, demonstrating up-regulation of ADAM12 by Erbb2. Furthermore, ADAM12 transfection or siRNA targeting revealed that ADAM12 increased both the migration and invasion of cutaneous SCC cells. Collectively, these results suggest Erbb2 up-regulation of ADAM12 as a novel mechanism contributing to the malignant progression of UV-induced skin cancer. Inhibition of Erbb2/HER2 reduced tumor burden, increased tumor regression, and delayed the progression of benign skin tumors to malignant SCC in UV-exposed mice. Inhibition of Erbb2 suppressed the increase in metalloproteinase ADAM12 expression in skin tumors, which in turn increased migration and tumor cell invasiveness. © 2014 Wiley Periodicals, Inc.

The expression of ADAM12 (meltrin alpha) in human giant cell tumours of bone.

PubMed

Tian, B L; Wen, J M; Zhang, M; Xie, D; Xu, R B; Luo, C J

2002-12-01

To examine the expression of ADAM12 (meltrin alpha), a member of the disintegrin and metalloprotease (ADAM) family, in human giant cell tumours of the bone, skeletal muscle tissue from human embryos, and human adult skeletal muscle tissue. ADAM12 mRNA was detected by reverse transcription polymerase chain reaction and in situ hybridisation. ADAM12 mRNA was detected in 14 of the 20 giant cell tumours of bone and in three of the six tumour cell cultures. The expression of ADAM12 in cells cultured from the tumour was linked to the presence of multinucleated giant cells. ADAM12 mRNA could not be detected in the five adult skeletal muscle tissue samples, although it was found in the two embryonic skeletal muscle tissue samples. ADAM12 mRNA was localised to the cytoplasm of multinucleated giant cells and some mononuclear stromal cells. These results indicate that multinucleated giant cells are formed by the cell fusion of mononuclear stromal cells in giant cell tumours of bone and that ADAM12 is involved in the cell fusion process.

The ADaptation and Anticipation Model (ADAM) of sensorimotor synchronization

PubMed Central

van der Steen, M. C. (Marieke); Keller, Peter E.

2013-01-01

A constantly changing environment requires precise yet flexible timing of movements. Sensorimotor synchronization (SMS)—the temporal coordination of an action with events in a predictable external rhythm—is a fundamental human skill that contributes to optimal sensory-motor control in daily life. A large body of research related to SMS has focused on adaptive error correction mechanisms that support the synchronization of periodic movements (e.g., finger taps) with events in regular pacing sequences. The results of recent studies additionally highlight the importance of anticipatory mechanisms that support temporal prediction in the context of SMS with sequences that contain tempo changes. To investigate the role of adaptation and anticipatory mechanisms in SMS we introduce ADAM: an ADaptation and Anticipation Model. ADAM combines reactive error correction processes (adaptation) with predictive temporal extrapolation processes (anticipation) inspired by the computational neuroscience concept of internal models. The combination of simulations and experimental manipulations based on ADAM creates a novel and promising approach for exploring adaptation and anticipation in SMS. The current paper describes the conceptual basis and architecture of ADAM. PMID:23772211

ADAM10 mediates trastuzumab resistance and is correlated with survival in HER2 positive breast cancer

PubMed Central

Feldinger, Katharina; Generali, Daniele; Kramer-Marek, Gabriela; Gijsen, Merel; Ng, Tzi Bun; Wong, Jack Ho; Strina, Carla; Cappelletti, Mariarosa; Andreis, Daniele; Li, Ji-Liang; Bridges, Esther; Turley, Helen; Leek, Russell; Roxanis, Ioannis; Capala, Jacek; Murphy, Gillian; Harris, Adrian L.; Kong, Anthony

2014-01-01

Trastuzumab prolongs survival in HER2 positive breast cancer patients. However, resistance remains a challenge. We have previously shown that ADAM17 plays a key role in maintaining HER2 phosphorylation during trastuzumab treatment. Beside ADAM17, ADAM10 is the other well characterized ADAM protease responsible for HER ligand shedding. Therefore, we studied the role of ADAM10 in relation to trastuzumab treatment and resistance in HER2 positive breast cancer. ADAM10 expression was assessed in HER2 positive breast cancer cell lines and xenograft mice treated with trastuzumab. Trastuzumab treatment increased ADAM10 levels in HER2 positive breast cancer cells (p≤0.001 in BT474; p≤0.01 in SKBR3) and in vivo (p≤0.0001) compared to control, correlating with a decrease in PKB phosphorylation. ADAM10 inhibition or knockdown enhanced trastuzumab response in naïve and trastuzumab resistant breast cancer cells. Trastuzumab monotherapy upregulated ADAM10 (p≤0.05); and higher pre-treatment ADAM10 levels correlated with decreased clinical response (p≤0.05) at day 21 in HER2 positive breast cancer patients undergoing a trastuzumab treatment window study. Higher ADAM10 levels correlated with poorer relapse-free survival (p≤0.01) in a cohort of HER2 positive breast cancer patients. Our studies implicate a role of ADAM10 in acquired resistance to trastuzumab and establish ADAM10 as a therapeutic target and a potential biomarker for HER2 positive breast cancer patients. PMID:24952873

Structural Basis for Regulated Proteolysis by the α-Secretase ADAM10.

PubMed

Seegar, Tom C M; Killingsworth, Lauren B; Saha, Nayanendu; Meyer, Peter A; Patra, Dhabaleswar; Zimmerman, Brandon; Janes, Peter W; Rubinstein, Eric; Nikolov, Dimitar B; Skiniotis, Georgios; Kruse, Andrew C; Blacklow, Stephen C

2017-12-14

Cleavage of membrane-anchored proteins by ADAM (a disintegrin and metalloproteinase) endopeptidases plays a key role in a wide variety of biological signal transduction and protein turnover processes. Among ADAM family members, ADAM10 stands out as particularly important because it is both responsible for regulated proteolysis of Notch receptors and catalyzes the non-amyloidogenic α-secretase cleavage of the Alzheimer's precursor protein (APP). We present here the X-ray crystal structure of the ADAM10 ectodomain, which, together with biochemical and cellular studies, reveals how access to the enzyme active site is regulated. The enzyme adopts an unanticipated architecture in which the C-terminal cysteine-rich domain partially occludes the enzyme active site, preventing unfettered substrate access. Binding of a modulatory antibody to the cysteine-rich domain liberates the catalytic domain from autoinhibition, enhancing enzymatic activity toward a peptide substrate. Together, these studies reveal a mechanism for regulation of ADAM activity and offer a roadmap for its modulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis and immunostimulating properties of novel adamant-1-yl tripeptides.

PubMed

Ribić, Rosana; Habjanec, Lidija; Vranešić, Branka; Frkanec, Ruža; Tomić, Srđanka

2012-04-01

The aim of this work was to prepare L- and D-(adamant-1-yl)-Gly-L-Ala-D-isoGln peptides in order to study their adjuvant (immunostimulating) activities. Adjuvant activity of adamant-1-yl tripeptides was tested in the mouse model using ovalbumin as an antigen and in comparison to the peptidoglycan monomer (PGM; β-D-GlcNAc-(1→4)-D-MurNAc-L-Ala-D-isoGln-mesoDAP(εNH(2) )-D-Ala-D-Ala) and structurally related adamant-2-yl tripeptides. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

Thioredoxin-1 Negatively Modulates ADAM17 Activity Through Direct Binding and Indirect Reductive Activity.

PubMed

Granato, Daniela C; E Costa, Rute A P; Kawahara, Rebeca; Yokoo, Sami; Aragão, Annelize Z; Domingues, Romênia R; Pauletti, Bianca A; Honorato, Rodrigo V; Fattori, Juliana; Figueira, Ana Carolina M; Oliveira, Paulo S L; Consonni, Silvio R; Fernandes, Denise; Laurindo, Francisco; Hansen, Hinrich P; Paes Leme, Adriana F

2018-02-27

A disintegrin and metalloprotease 17 (ADAM17) modulates signaling events by releasing surface protein ectodomains such as TNFa and the EGFR-ligands. We have previously characterized cytoplasmic thioredoxin-1 (Trx-1) as a partner of ADAM17 cytoplasmic domain. Still, the mechanism of ADAM17 regulation by Trx-1 is unknown, and it has become of paramount importance to assess the degree of influence that Trx-1 has on metalloproteinase ADAM17. Combining discovery and targeted proteomic approaches, we uncovered that Trx-1 negatively regulates ADAM17 by direct and indirect effect. We performed cell-based assays with synthetic peptides and site-directed mutagenesis, and we demonstrated that the interaction interface of Trx-1 and ADAM17 is important for the negative regulation of ADAM17 activity. However, both Trx-1 K72A and catalytic site mutant Trx-1 C32/35S rescued ADAM17 activity, although the interaction with Trx-1 C32/35S was unaffected, suggesting an indirect effect of Trx-1. We confirmed that the Trx-1 C32/35S mutant showed diminished reductive capacity, explaining this indirect effect on increasing ADAM17 activity through oxidant levels. Interestingly, Trx-1 K72A mutant showed similar oxidant levels to Trx-1 C32/35S , even though its catalytic site was preserved. We further demonstrated that the general reactive oxygen species inhibitor, Nacetylcysteine (NAC), maintained the regulation of ADAM17 dependent of Trx-1 reductase activity levels; whereas the electron transport chain modulator, rotenone, abolished Trx-1 effect on ADAM17 activity. We show for the first time that the mechanism of ADAM17 regulation, Trx-1 dependent, can be by direct interaction and indirect effect, bringing new insights into the cross-talk between isomerases and mammalian metalloproteinases. This unexpected Trx-1 K72A behavior was due to more dimer formation and, consequently, the reduction of its Trx-1 reductase activity, evaluated through dimer verification, by gel filtration and mass

The Failed Educations of John Stuart Mill and Henry Adams.

ERIC Educational Resources Information Center

Crossley, Robert

1979-01-01

Analyzes and contrasts Mill's "Autobiography" and Adams'"The Education of Henry Adams" in order to present two approaches to the nature of education and of failure. Maintains that their perspectives may serve as catalysts and cautions for contemporary theories of education and its utility and relevance. (CAM)

A new gene for asthma: would you ADAM and Eve it?

PubMed

Cookson, William

2003-04-01

Recently, a novel gene was reported to underlie asthma. Linkage to the short arm of chromosome 20 in a genome screen was followed by positive tests of association that centre on the gene for a membrane-anchored zinc-dependent metalloproteinase known as ADAM33. The domain structure of the ADAM33 protein gives capabilities of proteolysis, adhesion, cell fusion and intracellular signalling. Although its function is at present unknown, these potential actions of ADAM33 provide many possibilities for further research.

EMMPRIN and ADAM12 in prostate cancer: preliminary results of a prospective study.

PubMed

Bilgin Doğru, Elif; Dizdar, Yavuz; Akşit, Ece; Ural, Feyyaz; Şanlı, Öner; Yasasever, Vildan

2014-11-01

Extracellular metalloproteinase inducer (EMMPRIN) and a disintegrin and metalloproteinase (ADAM12) play a major role in cancer invasion and metastasis owing to the fact that they are directly related to the cell microenvironment and extracellular matrix (ECM) degradation. The aim of this study was to search for an answer to the question "whether the determination of EMMPRIN and ADAM12 values especially in urine may be helpful for the early diagnosis of prostate cancer without employing invasive methods" and also to check whether they may be useful for the determination of the patients with high metastasis risk. Peripheral blood and urine from 66 prostate cancer patients (40 local, 20 locally advanced, 6 metastatic) and 14 healthy controls were evaluated by enzyme-linked immunosorbent assay (ELISA) method. Serum EMMPRIN and ADAM12 values of the patients were seen to be statistically higher than the serum EMMPRIN and ADAM12 values of the healthy controls (p=0.01 and p=0.001, respectively). The urine ADAM12 levels were significantly higher in patients (p=0.013). No significant relationships were found between urine EMMPRIN values of the patients and the healthy controls (p>0.05). Positive correlation between urine EMMPRIN-urine ADAM12 tests was found in total patients group (r=0.683, p=0.001). Our preliminary results revealed that serum EMMPRIN and ADAM12 values and urine ADAM12 values may be useful markers in prostate cancer therapy. Due to the high correlation between these two tests, we are of the opinion that the use of urine ADAM12 in clinic may be sufficient and favorable together with prostate-specific antigen (PSA) for treatment.

The Role of ADAM9 in Tumor-Stromal Interactions in Breast Cancer

DTIC Science & Technology

2010-04-01

Tumor-Stromal Interactions in Breast Cancer PRINCIPAL INVESTIGATOR: Jessica L. Fry...The Role of ADAM9 in Tumor-Stromal Interactions in Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-06-1-0460 5c...ADAM9, the development of a model system to investigate the isoforms of ADAM-9 in breast cancer cell migration, and the use of this model system to

Adam10 Mediates the Choice between Principal Cells and Intercalated Cells in the Kidney

PubMed Central

Guo, Qiusha; Wang, Yinqiu; Tripathi, Piyush; Manda, Kalyan R.; Mukherjee, Malini; Chaklader, Malay; Austin, Paul F.

2015-01-01

A disintegrin and metalloproteinase domain 10 (Adam10), a member of the ADAM family of cell membrane–anchored proteins, has been linked to the regulation of the Notch, EGF, E-cadherin, and other signaling pathways. However, it is unclear what role Adam10 has in the kidney in vivo. In this study, we showed that Adam10 deficiency in ureteric bud (UB) derivatives leads to a decrease in urinary concentrating ability, polyuria, and hydronephrosis in mice. Furthermore, Adam10 deficiency led to a reduction in the percentage of aquaporin 2 (Aqp2)+ principal cells (PCs) in the collecting ducts that was accompanied by a proportional increase in the percentage of intercalated cells (ICs). This increase was more prominent in type A ICs than in type B ICs. Foxi1, a transcription factor important for the differentiation of ICs, was upregulated in the Adam10 mutants. The observed reduction of Notch activity in Adam10 mutant collecting duct epithelium and the similar reduction of PC/IC ratios in the collecting ducts in mice deficient for mindbomb E3 ubiquitin protein ligase 1, a key regulator of the Notch and Wnt/receptor-like tyrosine kinase signaling pathways, suggest that Adam10 regulates cell fate determination through the activation of Notch signaling, probably through the regulation of Foxi1 expression. However, phenotypic differences between the Adam10 mutants, the Mib1 mutants, and the Foxi1 mutants suggest that the functions of Adam10 in determining the fate of collecting duct cells are more complex than those of a simple upstream factor in a linear pathway involving Notch and Foxi1. PMID:24904084

ADAM disintegrin-like domain recognition by the lymphocyte integrins α4β1 and α4β7

PubMed Central

Bridges, Lance C.; Sheppard, Dean; Bowditch, Ron D.

2004-01-01

The ADAM (a disintegrin and metalloprotease) family of proteins possess both proteolytic and adhesive domains. We have established previously that the disintegrin domain of ADAM28, an ADAM expressed by human lymphocytes, is recognized by the integrin α4β1. The present study characterizes the integrin binding properties of the disintegrin-like domains of human ADAM7, ADAM28 and ADAM33 with the integrins α4β1, α4β7 and α9β1. Cell-adhesion assays demonstrated that, similar to ADAM28, the ADAM7 disintegrin domain supported α4β1-dependent Jurkat cell adhesion, whereas the ADAM33 disintegrin domain did not. The lymphocyte integrin α4β7 was also found to recognize both disintegrin domains of ADAM7 and ADAM28, but not of ADAM33. This is the first demonstration that mammalian disintegrins are capable of interacting with α4β7. All three disintegrin domains supported α9β1-dependent cell adhesion. Recognition by both α4β1 and α4β7 of ADAM7 and ADAM28 was activation-dependent, requiring either the presence of Mn2+ or an activating monoclonal antibody for cell attachment. Charge-to-alanine mutagenesis experiments revealed that the same residues within an individual ADAM disintegrin domain function in recognizing multiple integrins. However, the residues within a specific region of each ADAM disintegrin-like domain required for integrin binding were distinct. These results establish that ADAM7 and ADAM28 are recognized by the leucocyte integrins α4β1, α4β7 and α9β1. ADAM33 exclusively supported only α9β1-dependent adhesion. PMID:15504110

ADAM17 is associated with EMMPRIN and predicts poor prognosis in patients with uterine cervical carcinoma.

PubMed

Xu, Qin; Ying, Mingang; Chen, Guilin; Lin, Ang; Xie, Yunqing; Ohara, Noriyuki; Zhou, Dongmei

2014-08-01

Metalloproteinase activities of a disintegrin and metalloproteinase 17 (ADAM17), amphiregulin (AREG), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMPs) are involved in tumor biology. In patients with uterine cervical carcinoma, the expression and prognostic significance of ADAM17 remain to be fully elucidated. The expression of ADAM17, AREG, EMMPRIN, phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-regulated kinase (p-ERK), MMP-2, and MMP-9 was assessed by immunohistochemistry and/or Western blotting from cervical carcinoma cell lines, SiHa and HeLa cells, and cervical carcinoma tissues. AREG activity was measured by ELISA assay. The correlation of ADAM17, AREG, EMMPRIN, and MMP-9 expression with patients' survival rates was assessed by Kaplan-Meier and Cox regression analyses. RNA interference (RNAi) experiment was performed using small interfering mRNA to ADAM17 and EMMPRIN. ADAM17, EMMPRIN, and MMP-9 protein content was overexpressed in cervical carcinoma tissues compared with normal cervical tissues (P < 0.05). Strong expression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly associated with stages, lymph node metastasis, differentiation, and parametrium invasion (P < 0.05). Overexpression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly correlated with short progression-free survival and overall survival (P < 0.05). Multivariate analysis suggested that lymph node metastasis, parametrium invasion, and ADAM17 expression were independent prognostic indicators for cervical cancer. ADAM17 RNAi decreased EMMPRIN, p-EGFR, p-ERK, MMP-2, and MMP-9 proteins in SiHa and HeLa cells. ELISA assay revealed that AREG activity was stimulated by ADAM17 and was reversed by ADAM17 RNAi in SiHa and HeLa cells. Our data suggest that the increased expression of ADAM17 in cervical cancer is significantly associated with aggressive progression and poor prognosis. ADAM17 may be a

Dissecting the role of ADAM10 as a mediator of Staphylococcus aureus α-toxin action.

PubMed

von Hoven, Gisela; Rivas, Amable J; Neukirch, Claudia; Klein, Stefan; Hamm, Christian; Qin, Qianqian; Meyenburg, Martina; Füser, Sabine; Saftig, Paul; Hellmann, Nadja; Postina, Rolf; Husmann, Matthias

2016-07-01

Staphylococcus aureus is a leading cause of bacterial infections in humans, including life-threatening diseases such as pneumonia and sepsis. Its small membrane-pore-forming α-toxin is considered an important virulence factor. By destroying cell-cell contacts through cleavage of cadherins, the metalloproteinase ADAM10 (a disintegrin and metalloproteinase 10) critically contributes to α-toxin-dependent pathology of experimental S. aureus infections in mice. Moreover, ADAM10 was proposed to be a receptor for α-toxin. However, it is unclear whether the catalytic activity or specific domains of ADAM10 are involved in mediating binding and/or subsequent cytotoxicity of α-toxin. Also, it is not known how α-toxin triggers ADAM10's enzymatic activity, and whether ADAM10 is invariably required for all α-toxin action on cells. In the present study, we show that efficient cleavage of the ADAM10 substrate epithelial cadherin (E-cadherin) requires supra-cytotoxic concentrations of α-toxin, leading to significant increases in intracellular [Ca(2+)]; the fall in cellular ATP levels, typically following membrane perforation, became observable at far lower concentrations. Surprisingly, ADAM10 was dispensable for α-toxin-dependent xenophagic targeting of S. aureus, whereas a role for α-toxin attack on the plasma membrane was confirmed. The catalytic site of ADAM10, furin cleavage site, cysteine switch and intracellular domain of ADAM10 were not required for α-toxin binding and subsequent cytotoxicity. In contrast, an essential role for the disintegrin domain and the prodomain emerged. Thus, co-expression of the prodomain with prodomain-deficient ADAM10 reconstituted binding of α-toxin and susceptibility of ADAM10-deficient cells. The results of the present study may help to inform structural analyses of α-toxin-ADAM10 interactions and to design novel strategies to counteract S. aureus α-toxin action. © 2016 The Author(s). published by Portland Press Limited on behalf

From Adam Swift to Adam Smith: How the "Invisible Hand" Overcomes Middle Class Hypocrisy

ERIC Educational Resources Information Center

Tooley, James

2007-01-01

This paper challenges Richard Pring's suggestion that parents using private education may be undermining the desire for social justice and equality, using recent arguments of Adam Swift as a springboard. Swift's position on the banning of private schools, which uses a Rawlsian "veil of ignorance" argument, is explored, and it is suggested that, if…

Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function

PubMed Central

Kuhn, Peer-Hendrik; Colombo, Alessio Vittorio; Schusser, Benjamin; Dreymueller, Daniela; Wetzel, Sebastian; Schepers, Ute; Herber, Julia; Ludwig, Andreas; Kremmer, Elisabeth; Montag, Dirk; Müller, Ulrike; Schweizer, Michaela; Saftig, Paul; Bräse, Stefan; Lichtenthaler, Stefan F

2016-01-01

Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer's disease amyloid precursor protein. ADAM10 is also required for neuronal network functions in murine brain, but neuronal ADAM10 substrates are only partly known. With a proteomic analysis of Adam10-deficient neurons we identified 91, mostly novel ADAM10 substrate candidates, making ADAM10 a major protease for membrane proteins in the nervous system. Several novel substrates, including the neuronal cell adhesion protein NrCAM, are involved in brain development. Indeed, we detected mistargeted axons in the olfactory bulb of conditional ADAM10-/- mice, which correlate with reduced cleavage of NrCAM, NCAM and other ADAM10 substrates. In summary, the novel ADAM10 substrates provide a molecular basis for neuronal network dysfunctions in conditional ADAM10-/- mice and demonstrate a fundamental function of ADAM10 in the brain. DOI: http://dx.doi.org/10.7554/eLife.12748.001 PMID:26802628

John Adams's Montesquieuean Moment: Enlightened Historicism in the Discourses on Davila.

PubMed

Green, Jonathan

2016-01-01

At the outset of the French Revolution John Adams penned a series of Discourses of Davila, philosophical ruminations on the sixteenth-century French Wars of Religion. Recent historians have read these Discourses in terms of Adams's Machiavellianism-his conviction that men's passions lead to violence, if unrestrained. But this reading overlooks the extent to which Adams intended his Discourses as a particular investigation into the French nation's character, and into whether the revolutionaries could lay claim to a native, French tradition of mixed constitutional government. Situating the Discourses vis-à-vis Adams's contemporaneous reading of Montesquieu, this article argues for an underappreciated historicist dimension to his thought.

Identification of novel interaction between ADAM17 (a disintegrin and metalloprotease 17) and thioredoxin-1.

PubMed

Aragão, Annelize Z B; Nogueira, Maria Luiza C; Granato, Daniela C; Simabuco, Fernando M; Honorato, Rodrigo V; Hoffman, Zaira; Yokoo, Sami; Laurindo, Francisco R M; Squina, Fabio M; Zeri, Ana Carolina M; Oliveira, Paulo S L; Sherman, Nicholas E; Paes Leme, Adriana F

2012-12-14

ADAM17, which is also known as TNFα-converting enzyme, is the major sheddase for the EGF receptor ligands and is considered to be one of the main proteases responsible for the ectodomain shedding of surface proteins. How a membrane-anchored proteinase with an extracellular catalytic domain can be activated by inside-out regulation is not completely understood. We characterized thioredoxin-1 (Trx-1) as a partner of the ADAM17 cytoplasmic domain that could be involved in the regulation of ADAM17 activity. We induced the overexpression of the ADAM17 cytoplasmic domain in HEK293 cells, and ligands able to bind this domain were identified by MS after protein immunoprecipitation. Trx-1 was also validated as a ligand of the ADAM17 cytoplasmic domain and full-length ADAM17 recombinant proteins by immunoblotting, immunolocalization, and solid phase binding assay. In addition, using nuclear magnetic resonance, it was shown in vitro that the titration of the ADAM17 cytoplasmic domain promotes changes in the conformation of Trx-1. The MS analysis of the cross-linked complexes showed cross-linking between the two proteins by lysine residues. To further evaluate the functional role of Trx-1, we used a heparin-binding EGF shedding cell model and observed that the overexpression of Trx-1 in HEK293 cells could decrease the activity of ADAM17, activated by either phorbol 12-myristate 13-acetate or EGF. This study identifies Trx-1 as a novel interaction partner of the ADAM17 cytoplasmic domain and suggests that Trx-1 is a potential candidate that could be involved in ADAM17 activity regulation.

GSK3 and Polo-like kinase regulate ADAM13 function during cranial neural crest cell migration

PubMed Central

Abbruzzese, Genevieve; Cousin, Hélène; Salicioni, Ana Maria; Alfandari, Dominique

2014-01-01

ADAMs are cell surface metalloproteases that control multiple biological processes by cleaving signaling and adhesion molecules. ADAM13 controls cranial neural crest (CNC) cell migration both by cleaving cadherin-11 to release a promigratory extracellular fragment and by controlling expression of multiple genes via its cytoplasmic domain. The latter activity is regulated by γ-secretase cleavage and the translocation of the cytoplasmic domain into the nucleus. One of the genes regulated by ADAM13, the protease calpain8, is essential for CNC migration. Although the nuclear function of ADAM13 is evolutionarily conserved, it is unclear whether the transcriptional regulation is also performed by other ADAMs and how this process may be regulated. We show that ADAM13 function to promote CNC migration is regulated by two phosphorylation events involving GSK3 and Polo-like kinase (Plk). We further show that inhibition of either kinase blocks CNC migration and that the respective phosphomimetic forms of ADAM13 can rescue these inhibitions. However, these phosphorylations are not required for ADAM13 proteolysis of its substrates, γ-secretase cleavage, or nuclear translocation of its cytoplasmic domain. Of significance, migration of the CNC can be restored in the absence of Plk phosphorylation by expression of calpain-8a, pointing to impaired nuclear activity of ADAM13. PMID:25298404

Increased abundance of ADAM9 transcripts in the blood is associated with tissue damage

PubMed Central

Rinchai, Darawan; Kewcharoenwong, Chidchamai; Kessler, Bianca; Lertmemongkolchai, Ganjana; Chaussabel, Damien

2016-01-01

Background: Members of the ADAM (a disintegrin and metalloprotease domain) family have emerged as critical regulators of cell-cell signaling during development and homeostasis. ADAM9 is consistently overexpressed in various human cancers, and has been shown to play an important role in tumorigenesis. However, little is known about the involvement of ADAM9 during immune-mediated processes. Results: Mining of an extensive compendium of transcriptomic datasets identified important gaps in knowledge regarding the possible role of ADAM9 in immunological homeostasis and inflammation: 1) The abundance of ADAM9 transcripts in the blood was increased in patients with acute infection but, 2) changed very little after in vitro exposure to a wide range of pathogen-associated molecular patterns (PAMPs). 3) Furthermore it was found to increase significantly in subjects as a result of tissue injury or tissue remodeling, in absence of infectious processes. Conclusions: Our findings indicate that ADAM9 may constitute a valuable biomarker for the assessment of tissue damage, especially in clinical situations where other inflammatory markers are confounded by infectious processes. PMID:27990250

α-Lipoic acid reduces neurogenic hypertension by blunting oxidative stress-mediated increase in ADAM17

PubMed Central

de Queiroz, Thyago M.; Xia, Huijing; Filipeanu, Catalin M.; Braga, Valdir A.

2015-01-01

We previously reported that type 2 angiotensin-converting enzyme (ACE2) compensatory activity is impaired by the disintegrin and metalloprotease 17 (ADAM17), and lack of ACE2 is associated with oxidative stress in neurogenic hypertension. To investigate the relationship between ADAM17 and oxidative stress, Neuro2A cells were treated with ANG II (100 nM) 24 h after vehicle or α-lipoic acid (LA, 500 μM). ADAM17 expression was increased by ANG II (120.5 ± 9.1 vs. 100.2 ± 0.8%, P < 0.05) and decreased after LA (69.0 ± 0.3 vs. 120.5 ± 9.1%, P < 0.05). In another set of experiments, LA reduced ADAM17 (92.9 ± 5.3 vs. 100.0 ± 11.2%, P < 0.05) following its overexpression. Moreover, ADAM17 activity was reduced by LA in ADAM17-overexpressing cells [109.5 ± 19.8 vs. 158.0 ± 20.0 fluorescence units (FU)·min−1·μg protein−1, P < 0.05], in which ADAM17 overexpression increased oxidative stress (114.1 ± 2.5 vs. 101.0 ± 1.0%, P < 0.05). Conversely, LA-treated cells attenuated ADAM17 overexpression-induced oxidative stress (76.0 ± 9.1 vs. 114.1 ± 2.5%, P < 0.05). In deoxycorticosterone acetate (DOCA)-salt hypertensive mice, a model in which ADAM17 expression and activity are increased, hypertension was blunted by pretreatment with LA (119.0 ± 2.4 vs. 131.4 ± 2.2 mmHg, P < 0.05). In addition, LA improved dysautonomia and baroreflex sensitivity. Furthermore, LA blunted the increase in NADPH oxidase subunit expression, as well as the increase in ADAM17 and decrease in ACE2 activity in the hypothalamus of DOCA-salt hypertensive mice. Taken together, these data suggest that LA might preserve ACE2 compensatory activity by breaking the feedforward cycle between ADAM17 and oxidative stress, resulting in a reduction of neurogenic hypertension. PMID:26254330

Genetics Home Reference: Adams-Oliver syndrome

MedlinePlus

... Baveja R, Silva ES, Dixon J, Leon EL, Solomon BD, Glusman G, Niederhuber JE, Roach JC, Patel MS. Mutations in NOTCH1 cause Adams-Oliver syndrome. Am J Hum Genet. 2014 Sep 4;95(3):275-84. doi: 10.1016/j. ...

TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

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

Ebi, Masahide; Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp; Shimura, Takaya

2010-11-19

Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cellmore » growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to

Overexpression of soluble ADAM33 promotes a hypercontractile phenotype of the airway smooth muscle cell in rat

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

Duan, Yiyuan; Long, Jiaoyue; Chen, Jun

A disintegrin and metalloproteinase 33 (ADAM33) has been identified as a susceptibility gene for asthma, but details of the causality are not fully understood. We hypothesize that soluble ADAM33 (sADAM33) overexpression can alter the mechanical behaviors of airway smooth muscle cells (ASMCs) via regulation of the cell's contractile phenotype, and thus contributes to airway hyperresponsiveness (AHR) in asthma. To test this hypothesis, we either overexpressed or knocked down the sADAM33 in rat ASMCs by transfecting the cells with sADAM33 coding sequence or a small interfering RNA (siRNA) that specifically targets the ADAM33 disintegrin domain, and subsequently assessed the cells formore » stiffness, contractility and traction force, together with the expression level of contractile and proliferative phenotype markers. We also investigated whether these changes were dependent on Rho/ROCK pathway by culturing the ASMCs either in the absence or presence of ROCK inhibitor (H1152). The results showed that the ASMCs with sADAM33 overexpression were stiffer and more contractile, generated greater traction force, exhibited increased expression levels of contractile phenotype markers and markedly enhanced Rho activation. Furthermore these changes were largely attenuated when the cells were cultured in the presence of H-1152. However, the knock-down of ADAM33 seemed insufficient to influence majority of the mechanical behaviors of the ASMCs. Taken together, we demonstrated that sADAM33 overexpression altered the mechanical behaviors of ASMCs in vitro, which was most likely by promoting a hypercontractile phenotype transition of ASMCs through Rho/ROCK pathway. This revelation may establish the previously missing link between ADAM33 expression and AHR, and also provide useful insight for targeting sADAM33 in asthma prevention and therapy. - Highlights: • sADAM33 overexpression enhances the stiffness, traction force and contractility of ASMCs. • sADAM33 overexpression

Cardiomyocyte A Disintegrin And Metalloproteinase 17 (ADAM17) Is Essential in Post-Myocardial Infarction Repair by Regulating Angiogenesis.

PubMed

Fan, Dong; Takawale, Abhijit; Shen, Mengcheng; Wang, Wang; Wang, Xiuhua; Basu, Ratnadeep; Oudit, Gavin Y; Kassiri, Zamaneh

2015-09-01

A disintegrin and metalloproteinase 17 (ADAM17) is a membrane-bound enzyme that mediates shedding of many membrane-bound molecules, thereby regulating multiple cellular responses. We investigated the role of cardiomyocyte ADAM17 in myocardial infarction (MI). Cardiomyocyte-specific ADAM17 knockdown mice (ADAM17(flox/flox)/α-MHC-Cre; f/f/Cre) and parallel controls (ADAM17(flox/flox); f/f) were subjected to MI by ligation of the left anterior descending artery. Post MI, f/f/Cre mice showed compromised survival, higher rates of cardiac rupture, more severe left ventricular dilation, and suppressed ejection fraction compared with parallel f/f-MI mice. Ex vivo ischemic injury (isolated hearts) resulted in comparable recovery in both genotypes. Myocardial vascular density (fluorescent-labeled lectin perfusion and CD31 immunofluorescence staining) was significantly lower in the infarct areas of f/f/Cre-MI compared with f/f-MI mice. Activation of vascular endothelial growth factor receptor 2 (VEGFR2), its mRNA, and total protein levels were reduced in infarcted myocardium in ADAM17 knockdown mice. Transcriptional regulation of VEGFR2 by ADAM17 was confirmed in cocultured cardiomyocyte-fibroblast as ischemia-induced VEGFR2 expression was blocked by ADAM17-siRNA. Meanwhile, ADAM17-siRNA did not alter VEGFA bioavailability in the conditioned media. ADAM17 knockdown mice (f/f/Cre-MI) exhibited reduced nuclear factor-κB activation (DNA binding) in the infarcted myocardium, which could underlie the suppressed VEGFR2 expression in these hearts. Post MI, inflammatory response was not altered by ADAM17 downregulation. This study highlights the key role of cardiomyocyte ADAM17 in post-MI recovery by regulating VEGFR2 transcription and angiogenesis, thereby limiting left ventricular dilation and dysfunction. Therefore, ADAM17 upregulation, within the physiological range, could provide protective effects in ischemic cardiomyopathy. © 2015 American Heart Association, Inc.

Extraction and Separation Modeling of Orion Test Vehicles with ADAMS Simulation

NASA Technical Reports Server (NTRS)

Fraire, Usbaldo, Jr.; Anderson, Keith; Cuthbert, Peter A.

2013-01-01

The Capsule Parachute Assembly System (CPAS) project has increased efforts to demonstrate the performance of fully integrated parachute systems at both higher dynamic pressures and in the presence of wake fields using a Parachute Compartment Drop Test Vehicle (PCDTV) and a Parachute Test Vehicle (PTV), respectively. Modeling the extraction and separation events has proven challenging and an understanding of the physics is required to reduce the risk of separation malfunctions. The need for extraction and separation modeling is critical to a successful CPAS test campaign. Current PTV-alone simulations, such as Decelerator System Simulation (DSS), require accurate initial conditions (ICs) drawn from a separation model. Automatic Dynamic Analysis of Mechanical Systems (ADAMS), a Commercial off the Shelf (COTS) tool, was employed to provide insight into the multi-body six degree of freedom (DOF) interaction between parachute test hardware and external and internal forces. Components of the model include a composite extraction parachute, primary vehicle (PTV or PCDTV), platform cradle, a release mechanism, aircraft ramp, and a programmer parachute with attach points. Independent aerodynamic forces were applied to the mated test vehicle/platform cradle and the separated test vehicle and platform cradle. The aero coefficients were determined from real time lookup tables which were functions of both angle of attack ( ) and sideslip ( ). The atmospheric properties were also determined from a real time lookup table characteristic of the Yuma Proving Grounds (YPG) atmosphere relative to the planned test month. Representative geometries were constructed in ADAMS with measured mass properties generated for each independent vehicle. Derived smart separation parameters were included in ADAMS as sensors with defined pitch and pitch rate criteria used to refine inputs to analogous avionics systems for optimal separation conditions. Key design variables were dispersed in a Monte

Unconventional forms of popularization of science - festivals 'Science on Stage" in Poland.

NASA Astrophysics Data System (ADS)

Mika, Aneta

2010-05-01

Are natural sciences popular these days? There is no obvious and straight answer to this question. On the one hand, students discouraged with the effort which they must put into learning science, avoid choosing such subjects for matriculation exams and also are reluctant to choose courses related to these areas. On the other hand, a well-chosen activating method can infect plenty of students with enthusiasm for studying natural science. One of such method is the festival "Science on Stage", which has been periodically held at the Adam Mickiewicz University in Poznań, Department of Physics. By 2008 six such festivals were held. The first three of them were run under the name "Physics on Stage", and the other three as "Science on Stage". Every year the festivals were attended by over 200 teachers and students of all school types (from kindergartens to universities), until 2008, when the event attracted over 400 participants from all over the country. This shows an increasing popularity of such projects. Participants in the festival could present their ideas "on stage" in three basic categories which included: • Experiments such as "Water - a cycle of experiments", " Two elements - Smoke on the Water", Diffraction and fractals" ,"Light Amplification by Stimulated Emission of Radiation", " Wind-propelled vehicles moving against the wind". • Performances such as "The musical physics or the sounds around us", "The laws of physics and the human body", "The Piglet and the shadow or on the violation of the laws of physics in children stories" and "In the stream of light". • Multimedia presentations such as "Thermonuclear fusion - the energy of the future", "The phenomena on the Sky and Earth which the philosophers have not dreamed of", "Galvanic batteries - small electric power plants", "System PSR B1257 12", "Physics and Chemistry in the kitchen". The festivals were accompanied by photo and painting exhibitions covering the topic of natural sciences. The visitors

ADAM-17 is a poor prognostic indicator for patients with hilar cholangiocarcinoma and is regulated by FoxM1.

PubMed

Jiao, Xiaodong; Yu, Wenlong; Qian, Jianxin; Chen, Ying; Wei, Peilian; Fang, Wenzheng; Yu, Guanzhen

2018-05-18

A-disintegrin and metalloproteinases (ADAMs) are members of a family of multidomain transmembrane and secreted proteins. Specific ADAMs are upregulated in human cancers and correlated with tumor progression and poor outcome, but rarely studied in human hilar cholangiocarcinoma (HC). This study aimed to explore the expression profiles of ADAMs and their potential underlying mechanisms promoting cancer progression. mRNA expression of ADAM-9, - 10, - 11, - 12, - 15, - 17, - 28, and - 33 was analyzed in human hilar cholangiocarcinoma (HC) samples. Immunohistochemical (IHC) analysis was used to detect the expression of ADAM-10, - 17, - 28, and FoxM1 in HC. The regulation of ADAM-17 by FoxM1 and their functional study was investigated in vivo and in vitro. ADAM-10, - 17, and - 28 were upregulated in tumors compared with matched non-cancerous tissues. IHC analysis revealed increased expression of ADAM-10, - 17, and - 28 in HC cells, and ADAM17 seems to be an independent prognostic factor. ADAM-17 is regulated by FoxM1. A decrease in the expression of ADAM-17 by silencing FoxM1 led to an inhibition of cell proliferation, tumor growth, and the production of tumor necrosis factor α. IHC analysis showed co-expression of FoxM1 and ADAM-17 in HC specimens. The findings of the present study show an important role of the cross-talk among FoxM1, ADAM-17, and TNFa in HC development and progression.

ADAM17 limits the expression of CSF1R on murine hematopoietic progenitors

PubMed Central

Becker, Amy M.; Walcheck, Bruce; Bhattacharya, Deepta

2014-01-01

All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through post-transcriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of Csf1r transcripts than their upstream precursors, yet show limited cell surface protein expression of CSF1R. ALPs and other hematopoietic progenitors deficient in ADAM17, a metalloprotease that can cleave CSF1R, display elevated cell surface CSF1R expression. Adam17−/− ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, Adam17−/− ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of M-CSF. Mice with hematopoietic-specific deletion of Adam17 have grossly normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. PMID:25308957

DEVELOPMENT OF THE HUMAN LUNG MEASURED BY AEROSOL-DERIVED AIRWAY MORPHEMETRY (ADAM).

EPA Science Inventory

We measured, in vivo, the airspace calibers of the small airways and alveoli by ADAM in the lungs of children of ages 6 to 18 years and adults aged 18 to 80 years. ADAM utilizes the gravitational settling time of inhaled monodisperse particles to infer the vertical distance to th...

Association between ADAM metallopeptidase domain 33 gene polymorphism and risk of childhood asthma: a meta-analysis.

PubMed

Sun, F J; Zou, L Y; Tong, D M; Lu, X Y; Li, J; Deng, C B

2017-08-31

This study aimed to investigate the association between ADAM metallopeptidase domain 33 (ADAM33) gene polymorphisms and the risk of childhood asthma. The relevant studies about the relationship between ADAM33 gene polymorphisms and childhood asthma were searched from electronic databases and the deadline of retrieval was May 2016. The single nucleotide polymorphisms (SNPs) of ADAM33 (rs511898, rs2280092, rs3918396, rs528557, rs2853209, rs44707, rs2280091 and rs2280089) were analyzed based on several models including the allele, codominant, recessive and dominant models. The results showed that the ADAM33 rs2280091 polymorphism in all four genetic models was associated with an increased risk of childhood asthma. Positive associations were also found between the polymorphisms rs2280090, rs2787094, rs44707 and rs528557 and childhood asthma in some genetic models. This meta-analysis suggested that ADAM33 polymorphisms rs2280091, rs2280090, rs2787094, rs44707 and rs528557 were significantly associated with a high risk of childhood asthma.

77 FR 5291 - The Designation of Monir Chouka, also Known as Mounir Chouka, Also Known as Abu Adam, Also Known...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-02

... DEPARTMENT OF STATE [Public Notice: 7783] The Designation of Monir Chouka, also Known as Mounir Chouka, Also Known as Abu Adam, Also Known as Abu Adam From Germany, also Known as Abu Adam aus... Chouka, also known as Abu Adam from Germany, also known as Abu Adam aus Deutschland, committed, or poses...

ADAM10 as a therapeutic target for brain diseases: from developmental disorders to Alzheimer's disease.

PubMed

Marcello, Elena; Borroni, Barbara; Pelucchi, Silvia; Gardoni, Fabrizio; Di Luca, Monica

2017-11-01

In the central nervous system a disintegrin and metalloproteinase 10 (ADAM10) controls several functions such as neurodevelopment, synaptic plasticity and dendritic spine morphology thanks to its activity towards a high number of substrates, including the synaptic cell adhesion molecules as the Amyloid Precursor Protein, N-cadherin, Notch and Ephrins. In particular, ADAM10 plays a key role in the modulation of the molecular mechanisms responsible for dendritic spine formation, maturation and stabilization and in the regulation of the molecular organization of the glutamatergic synapse. Consequently, an alteration of ADAM10 activity is strictly correlated to the onset of different types of synaptopathies, ranging from neurodevelopmental disorders, i.e. autism spectrum disorders, to neurodegenerative diseases, i.e. Alzheimer's Disease. Areas covered: We describe the most recent discoveries in understanding of the role of ADAM10 activity at the glutamatergic excitatory synapse and its involvement in the onset of neurodevelopmental and neurodegenerative disorders. Expert opinion: A progress in the understanding of the molecular mechanisms driving ADAM10 activity at synapses and its alterations in brain disorders is the first step before designing a specific drug able to modulate ADAM10 activity.

Fidelia Adams Johnson: Ingenious Daughter of the Founder of Grambling State University. From Voices of Inspiration Series, an Oral History Project.

ERIC Educational Resources Information Center

Grambling State Univ., LA. Dept. of History and Philosophy.

In this brief oral history, the life of Fidelia Adams Johnson is recounted with sections devoted to her family background, formative years, college experience, working life and retirement years as a black woman of influence. Her grandfather helped establish Tuskegee Institute and her father founded Louisiana's Grambling State College. Fidelia…

The Adam language: Ada extended with support for multiway activities

NASA Technical Reports Server (NTRS)

Charlesworth, Arthur

1993-01-01

The Adam language is an extension of Ada that supports multiway activities, which are cooperative activities involving two or more processes. This support is provided by three new constructs: diva procedures, meet statements, and multiway accept statements. Diva procedures are recursive generic procedures having a particular restrictive syntax that facilitates translation for parallel computers. Meet statements and multiway accept statements provide two ways to express a multiway rendezvous, which is an n-way rendezvous generalizing Ada's 2-way rendezvous. While meet statements tend to have simpler rules than multiway accept statements, the latter approach is a more straightforward extension of Ada. The only nonnull statements permitted within meet statements and multiway accept statements are calls on instantiated diva procedures. A call on an instantiated diva procedure is also permitted outside a multiway rendezvous; thus sequential Adam programs using diva procedures can be written. Adam programs are translated into Ada programs appropriate for use on parallel computers.

The Adams formulas for numerical integration of differential equations from 1st to 20th order

NASA Technical Reports Server (NTRS)

Kirkpatrick, J. C.

1976-01-01

The Adams Bashforth predictor coefficients and the Adams Moulton corrector coefficients for the integration of differential equations are presented for methods of 1st to 20th order. The order of the method as presented refers to the highest order difference formula used in Newton's backward difference interpolation formula, on which the Adams method is based. The Adams method is a polynomial approximation method derived from Newton's backward difference interpolation formula. The Newton formula is derived and expanded to 20th order. The Adams predictor and corrector formulas are derived and expressed in terms of differences of the derivatives, as well as in terms of the derivatives themselves. All coefficients are given to 18 significant digits. For the difference formula only, the ratio coefficients are given to 10th order.

Serotoninergic antidepressants positively affect platelet ADAM10 expression in patients with Alzheimer's disease.

PubMed

Bianco, Otávio Augusto Fernandes Marques; Manzine, Patrícia Regina; Nascimento, Carla Manuela Crispim; Vale, Francisco Assis Carvalho; Pavarini, Sofia Cristina Iost; Cominetti, Márcia Regina

2016-06-01

Studies have demonstrated a decreased platelet ADAM10 expression in patients with Alzheimer's Disease (AD), classifying this protein as a blood-based AD biomarker. About 50% of the patients with AD are diagnosed with depression, which is commonly treated with tricyclic and tetracyclic antidepressants, monoaminoxidade (MAO) inhibitors and, more preferably, with selective serotonin reuptake inhibitors (SSRIs). Considering that a large proportion of patients with AD takes antidepressant medications during the course of the disease we investigated the influence of this medication on the expression of platelet ADAM10, which is considered the main α-secretase preventing beta-amyloid (βA) formation. Blood was collected for protein extraction from platelets. ADAM10 was analyzed by using western blotting and reactive bands were measured using β-actin as endogenous control. Platelet ADAM10 protein expression in patients with AD was positively influenced by serotoninergic medication. More studies on the positive effects of serotonergic antidepressants on ADAM10 platelet expression should be performed in order to understand its biological mechanisms and to verify whether these effects are reflected in the central nervous system. This work represents an important advance for the study of AD biomarkers, as well as for more effective pharmacological treatment of patients with AD and associated depression.

Insights on unconventional natural gas development from shale: an interview with Anthony R. Ingraffea by Adam Law.

PubMed

Ingraffea, Anthony R

2013-01-01

Adam Law, M.D., interviewed Anthony R. Ingraffea, Ph.D., P.E., as part of a series of interviews funded by the Heinz Endowment. Dr. Ingraffea is the Dwight C. Baum Professor of Engineering at Cornell University, and has taught structural mechanics, finite element methods, and fracture mechanics at Cornell for 33 years. He discusses issues related to hydraulic fracturing, including inherent risks, spatial intensity, and the importance of a multi-disciplinary organization in establishing a chain of evidence.

ADAM metalloproteases promote a developmental switch in responsiveness to the axonal repellant Sema3A.

PubMed

Romi, Erez; Gokhman, Irena; Wong, Eitan; Antonovsky, Niv; Ludwig, Andreas; Sagi, Irit; Saftig, Paul; Tessier-Lavigne, Marc; Yaron, Avraham

2014-06-05

During embryonic development, axons can gain and lose sensitivity to guidance cues, and this flexibility is essential for the correct wiring of the nervous system. Yet, the underlying molecular mechanisms are largely unknown. Here we show that receptor cleavage by ADAM (A Disintegrin And Metalloprotease) metalloproteases promotes murine sensory axons loss of responsiveness to the chemorepellant Sema3A. Genetic ablation of ADAM10 and ADAM17 disrupts the developmental downregulation of Neuropilin-1 (Nrp1), the receptor for Sema3A, in sensory axons. Moreover, this is correlated with gain of repulsive response to Sema3A. Overexpression of Nrp1 in neurons reverses axonal desensitization to Sema3A, but this is hampered in a mutant Nrp1 with high susceptibility to cleavage. Lastly, we detect guidance errors of proprioceptive axons in ADAM knockouts that are consistent with enhanced response to Sema3A. Our results provide the first evidence for involvement of ADAMs in regulating developmental switch in responsiveness to axonal guidance cues.

Selective arylsulfonamide inhibitors of ADAM-17: hit optimization and activity in ovarian cancer cell models.

PubMed

Nuti, Elisa; Casalini, Francesca; Santamaria, Salvatore; Fabbi, Marina; Carbotti, Grazia; Ferrini, Silvano; Marinelli, Luciana; La Pietra, Valeria; Novellino, Ettore; Camodeca, Caterina; Orlandini, Elisabetta; Nencetti, Susanna; Rossello, Armando

2013-10-24

Activated leukocyte cell adhesion molecule (ALCAM) is expressed at the surface of epithelial ovarian cancer (EOC) cells and is released in a soluble form (sALCAM) by ADAM-17-mediated shedding. This process is relevant to EOC cell motility and invasiveness, which is reduced by inhibitors of ADAM-17. In addition, ADAM-17 plays a key role in EGFR signaling and thus may represent a useful target in anticancer therapy. Herein we report our hit optimization effort to identify potent and selective ADAM-17 inhibitors, starting with previously identified inhibitor 1. A new series of secondary sulfonamido-based hydroxamates was designed and synthesized. The biological activity of the newly synthesized compounds was tested in vitro on isolated enzymes and human EOC cell lines. The optimization process led to compound 21, which showed an IC50 of 1.9 nM on ADAM-17 with greatly increased selectivity. This compound maintained good inhibitory properties on sALCAM shedding in several in vitro assays.

ADAM10 is essential for Notch2-dependent marginal zone B cell development and CD23 cleavage in vivo

PubMed Central

Gibb, David R.; El Shikh, Mohey; Kang, Dae-Joong; Rowe, Warren J.; El Sayed, Rania; Cichy, Joanna; Yagita, Hideo; Tew, John G.; Dempsey, Peter J.; Crawford, Howard C.

2010-01-01

The proteolytic activity of a disintegrin and metalloproteinase 10 (ADAM10) regulates cell-fate decisions in Drosophila and mouse embryos. However, in utero lethality of ADAM10−/− mice has prevented examination of ADAM10 cleavage events in lymphocytes. To investigate their role in B cell development, we generated B cell–specific ADAM10 knockout mice. Intriguingly, deletion of ADAM10 prevented development of the entire marginal zone B cell (MZB) lineage. Additionally, cleavage of the low affinity IgE receptor, CD23, was profoundly impaired, but subsequent experiments demonstrated that ADAM10 regulates CD23 cleavage and MZB development by independent mechanisms. Development of MZBs is dependent on Notch2 signaling, which requires proteolysis of the Notch2 receptor by a previously unidentified proteinase. Further experiments revealed that Notch2 signaling is severely impaired in ADAM10-null B cells. Thus, ADAM10 critically regulates MZB development by initiating Notch2 signaling. This study identifies ADAM10 as the in vivo CD23 sheddase and an important regulator of B cell development. Moreover, it has important implications for the treatment of numerous CD23- and Notch-mediated pathologies, ranging from allergy to cancer. PMID:20156974

Dr Adam Zamenhof (1888-1940) and his insight into ophthalmology.

PubMed

Wincewicz, Andrzej; Sulkowska, Mariola; Lieberman, E James; Bakunowicz-Lazarczyk, Alina; Sulkowski, Stanislaw

2009-02-01

Adam Zamenhof was greatly influenced by his father, Ludwik Zamenhof, who designed the international language Esperanto. Like his father, he became an ophthalmologist and joined the Esperanto movement. He published in the field of ophthalmology and was soon chosen as head of an ophthalmology department. He subsequently became Chief of the Orthodox Jewish Hospital at Czystem in Warsaw. He was active in the leadership of the Bialystok-Warsaw Chamber of Medical Doctors. He perished in the Nazi Holocaust (Shoah) but all Zamenhof's ideals that Adam served as a doctor and social activist remain still alive.

ADAM-12 as a Diagnostic Marker for the Proliferation, Migration and Invasion in Patients with Small Cell Lung Cancer

PubMed Central

Shao, Shuhong; Li, Zunling; Gao, Wei; Yu, Guohua; Liu, Dexiang; Pan, Fang

2014-01-01

Small cell lung cancer (SCLC) is highly aggressive and is characterized by malignant metastasis. Approximately 90% of patients die due to extensive metastasis. The extracellular matrix (ECM) is a natural barrier that can prevent cellular invasion and metastasis. Therefore, degradation of the ECM must take place in order for extensive metastasis to occur. A disintegrin and metalloprotease (ADAM) is a multi-domain protease that plays an important role in tumorigenesis, as well as tumor development, invasion and metastasis. However, there have been few reports on the expression and role of ADAMs in SCLC. In the current study, the expression and role of ADAMs in SCLC proliferation, invasion and metastasis was investigated. A total of 150 SCLC tissue samples were examined by immunohistochemistry for ADAMs expression. ADAM-12 was found to be abundantly expressed in 72.67% samples and other ADAMs were found to be expressed in 10% to 40% of samples. ADAM-12 levels in serum and urine, from 70 SCLC patients and 40 normal controls, were also measured using ELISA. ADAM-12 expression was significantly higher in SCLC patients than in healthy controls and in patients with extensive disease compared to those with more limited disease. Silencing the expression of ADAM-12 in H1688 cells through the use of specific siRNA significantly reduced cellular proliferation, invasion and metastasis. Supplementing the expression of ADAM-12-L or -S in H345 cells, significantly enhanced cellular proliferation, invasion and metastasis. Animal models with metastatic SCLC also exhibited increased expression of ADAM-12 along with enhanced invasion and metastasis. In brief, ADAM-12 is an independent prognostic factor and diagnostic marker, and is involved in the proliferation, invasion and metastasis of SCLC. PMID:24465799

ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis

PubMed Central

Lagares, David; Ghassemi-Kakroodi, Parisa; Tremblay, Caroline; Santos, Alba; Probst, Clemens K.; Franklin, Alicia; Santos, Daniela M.; Grasberger, Paula; Ahluwalia, Neil; Montesi, Sydney B.; Shea, Barry S.; Black, Katharine E.; Knipe, Rachel; Blati, Meryem; Baron, Murray; Wu, Brian; Fahmi, Hassan; Gandhi, Rajiv; Pardo, Annie; Selman, Moisés; Wu, Jiangping; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Tager, Andrew M.; Kapoor, Mohit

2017-01-01

Maladaptive wound healing responses to chronic tissue injury result in organ fibrosis. Fibrosis, which entails excessive extracellular matrix (ECM) deposition and tissue remodelling by activated myofibroblasts, leads to loss of proper tissue architecture and organ function; however the molecular mediators of myofibroblast activation remain to be fully identified. Here we identify soluble ephrin-B2 as a novel pro-fibrotic mediator in lung and skin fibrosis. We provide molecular, functional and translational evidence that the ectodomain of membrane-bound ephrin-B2 is shed from fibroblasts into the alveolar airspace after lung injury. Shedding of soluble ephrin-B2 (sEphrin-B2) promotes fibroblast chemotaxis and activation via EphB3/EphB4 receptor signaling. We found that mice lacking ephrin-B2 in fibroblasts are protected from skin and lung fibrosis and that a distintegrin and metalloproteinase 10 (ADAM10) is the major ephrin-B2 sheddase in fibroblasts. ADAM10 is induced by transforming growth factor-β1 (TGF-β1), and ADAM10-mediated sEphrin-B2 generation is required for TGF-β1–induced myofibroblast activation. Pharmacological inhibition of ADAM10 reduces sEphrin-B2 levels in bronchoalveolar lavage and prevents lung fibrosis in mice. Consistent with the mouse data, ADAM10/sEphrin-B2 signaling is upregulated in fibroblasts from human subjects with idiopathic pulmonary fibrosis. These results uncover a new molecular mechanism of tissue fibrogenesis and identify sEphrin-B2, its receptors Eph3/Eph4, and ADAM10 as potential therapeutic targets in the treatment of fibrotic diseases. PMID:29058717

ADAM12 induction by Twist1 promotes tumor invasion and metastasis via regulation of invadopodia and focal adhesions

PubMed Central

Eckert, Mark A.; Santiago-Medina, Miguel; Lwin, Thinzar M.; Kim, Jihoon; Courtneidge, Sara A.

2017-01-01

ABSTRACT The Twist1 transcription factor promotes tumor invasion and metastasis by inducing epithelial–mesenchymal transition (EMT) and invadopodia-mediated extracellular matrix (ECM) degradation. The critical transcription targets of Twist1 for mediating these events remain to be uncovered. Here, we report that Twist1 strongly induces expression of a disintegrin and metalloproteinase 12 (ADAM12). We observed that the expression levels of Twist1 mRNA and ADAM12 mRNA are tightly correlated in human breast tumors. Knocking down ADAM12 blocked cell invasion in a 3D mammary organoid culture. Suppression of ADAM12 also inhibited Twist1-induced tumor invasion and metastasis in human breast tumor xenografts, without affecting primary tumor formation. Mechanistically, knockdown of ADAM12 in breast cancer cells significantly reduced invadopodia formation and matrix degradation, and simultaneously increased overall cell adhesion to the ECM. Live-imaging analysis showed that knockdown of ADAM12 significantly inhibited focal adhesion turnover. Mechanistically, both the disintegrin and metalloproteinase domains of ADAM12 are required for its function at invadopodia, whereas the metalloproteinase domain is dispensable for its function at focal adhesions. Taken together, these data suggest that ADAM12 plays a crucial role in tumor invasion and metastasis by regulating both invadopodia and focal adhesions. PMID:28468988

An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth

PubMed Central

Saha, Nayanendu; Eissman, Moritz F.; Xu, Kai; Llerena, Carmen; Kusebauch, Ulrike; Ding, Bi-Sen; Cao, Zhongwei; Rafii, Shahin; Ernst, Matthias; Scott, Andrew M.; Nikolov, Dimitar B.; Lackmann, Martin

2016-01-01

The transmembrane metalloprotease ADAM10 sheds a range of cell surface proteins, including ligands and receptors of the Notch, Eph, and erbB families, thereby activating signaling pathways critical for tumor initiation and maintenance. ADAM10 is thus a promising therapeutic target. Although widely expressed, its activity is normally tightly regulated. We now report prevalence of an active form of ADAM10 in tumors compared with normal tissues, in mouse models and humans, identified by our conformation-specific antibody mAb 8C7. Structure/function experiments indicate mAb 8C7 binds an active conformation dependent on disulfide isomerization and oxidative conditions, common in tumors. Moreover, this active ADAM10 form marks cancer stem-like cells with active Notch signaling, known to mediate chemoresistance. Importantly, specific targeting of active ADAM10 with 8C7 inhibits Notch activity and tumor growth in mouse models, particularly regrowth after chemotherapy. Our results indicate targeted inhibition of active ADAM10 as a potential therapy for ADAM10-dependent tumor development and drug resistance. PMID:27503072

An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth.

PubMed

Atapattu, Lakmali; Saha, Nayanendu; Chheang, Chanly; Eissman, Moritz F; Xu, Kai; Vail, Mary E; Hii, Linda; Llerena, Carmen; Liu, Zhanqi; Horvay, Katja; Abud, Helen E; Kusebauch, Ulrike; Moritz, Robert L; Ding, Bi-Sen; Cao, Zhongwei; Rafii, Shahin; Ernst, Matthias; Scott, Andrew M; Nikolov, Dimitar B; Lackmann, Martin; Janes, Peter W

2016-08-22

The transmembrane metalloprotease ADAM10 sheds a range of cell surface proteins, including ligands and receptors of the Notch, Eph, and erbB families, thereby activating signaling pathways critical for tumor initiation and maintenance. ADAM10 is thus a promising therapeutic target. Although widely expressed, its activity is normally tightly regulated. We now report prevalence of an active form of ADAM10 in tumors compared with normal tissues, in mouse models and humans, identified by our conformation-specific antibody mAb 8C7. Structure/function experiments indicate mAb 8C7 binds an active conformation dependent on disulfide isomerization and oxidative conditions, common in tumors. Moreover, this active ADAM10 form marks cancer stem-like cells with active Notch signaling, known to mediate chemoresistance. Importantly, specific targeting of active ADAM10 with 8C7 inhibits Notch activity and tumor growth in mouse models, particularly regrowth after chemotherapy. Our results indicate targeted inhibition of active ADAM10 as a potential therapy for ADAM10-dependent tumor development and drug resistance. © 2016 Atapattu et al.

Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate {alpha}-secretase activity.

PubMed

Kim, Minji; Suh, Jaehong; Romano, Donna; Truong, Mimy H; Mullin, Kristina; Hooli, Basavaraj; Norton, David; Tesco, Giuseppina; Elliott, Kathy; Wagner, Steven L; Moir, Robert D; Becker, K David; Tanzi, Rudolph E

2009-10-15

ADAM10, a member of a disintegrin and metalloprotease family, is an alpha-secretase capable of anti-amyloidogenic proteolysis of the amyloid precursor protein. Here, we present evidence for genetic association of ADAM10 with Alzheimer's disease (AD) as well as two rare potentially disease-associated non-synonymous mutations, Q170H and R181G, in the ADAM10 prodomain. These mutations were found in 11 of 16 affected individuals (average onset age 69.5 years) from seven late-onset AD families. Each mutation was also found in one unaffected subject implying incomplete penetrance. Functionally, both mutations significantly attenuated alpha-secretase activity of ADAM10 (>70% decrease), and elevated Abeta levels (1.5-3.5-fold) in cell-based studies. In summary, we provide the first evidence of ADAM10 as a candidate AD susceptibility gene, and report two potentially pathogenic mutations with incomplete penetrance for late-onset familial AD.

MicroRNA-126 inhibits proliferation and metastasis in prostate cancer via regulation of ADAM9

PubMed Central

Hua, Yibo; Liang, Chao; Miao, Chenkui; Wang, Shangqian; Su, Shifeng; Shao, Pengfei; Liu, Bianjiang; Bao, Meiling; Zhu, Jundong; Xu, Aiming; Zhang, Jianzhong; Li, Jie; Wang, Zengjun

2018-01-01

The aberrant expression of microRNAs (miRs) has been identified to serve a crucial role in tumor progression. The present study aimed to evaluate the role of miR-126 in human prostate cancer (PCa). Firstly, miR-126 expression in prostate cancer tissues and cell lines was analyzed. A luciferase reporter assay and a rescue assay were performed, which identified ADAM metalloproteinase domain 9 (ADAM9) as the target gene of miR-126. Subsequently, Kaplan-Meier and log-rank analyses were used to investigate the association between ADAM9 expression and PCa prognosis. The results revealed that miR-126 expression was significantly downregulated in PCa tissues and cell lines. miR-126 overexpression was demonstrated to reduce PCa cell proliferation and metastasis, and to reverse the epithelial-mesenchymal transition process in vitro. In addition, as the target gene of miR-126, the upregulation of ADAM9 reestablished cell functions, including cell proliferation, migration and invasion. Patients with high ADAM9 expression levels exhibited a shorter biochemical recurrence-free survival time. In summary, miR-126 serves a role in the proliferation and metastasis of PCa cells, indicating that miR-126 and ADAM9 may represent potential biomarkers in the progression of advanced PCa, in addition to therapeutic targets. PMID:29805636

Characterization of Oxygen-Induced Retinopathy in Mice Carrying an Inactivating Point Mutation in the Catalytic Site of ADAM15

PubMed Central

Maretzky, Thorsten; Blobel, Carl P.; Guaiquil, Victor

2014-01-01

Purpose. Retinal neovascularization is found in diseases such as macular degeneration, diabetic retinopathy, or retinopathy of prematurity and is usually caused by alterations in oxygen supply. We have previously described that mice lacking the membrane-anchored metalloproteinase ADAM15 (a Disintegrin and Metalloprotease 15) have decreased pathological neovascularization of the retina in the oxygen-induced retinopathy (OIR) model. The main purpose of the present study was to determine the contribution of the catalytic activity of ADAM15 to OIR. Methods. To address this question, we generated knock-in mice carrying an inactivating Glutamate to Alanine (E>A) point mutation in the catalytic site of ADAM15 (Adam15E>A mice) and subjected these animals to the OIR model and a heterotopic tumor model. Moreover, we used cell-based assays to determine whether ADAM15 can process cell surface receptors involved in angiogenesis. Results. We found that pathological neovascularization in the OIR model in Adam15E>A mice was comparable to that observed in wild type mice, but tumor implantation by heterotopically injected melanoma cells was reduced. In cell-based assays, overexpressed ADAM15 could process the FGFR2iiib, but was unable to process several receptors with roles in angiogenesis. Conclusions. Collectively, these results suggest that the catalytic activity of ADAM15 is not crucial for its function in promoting pathological neovascularization in the mouse OIR model, most likely because of the very limited substrate repertoire of ADAM15. Instead, other noncatalytic functions of ADAM15 must be important for its role in the OIR model. PMID:25249606

Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate α-secretase activity

PubMed Central

Kim, Minji; Suh, Jaehong; Romano, Donna; Truong, Mimy H.; Mullin, Kristina; Hooli, Basavaraj; Norton, David; Tesco, Giuseppina; Elliott, Kathy; Wagner, Steven L.; Moir, Robert D.; Becker, K. David; Tanzi, Rudolph E.

2009-01-01

ADAM10, a member of a disintegrin and metalloprotease family, is an α-secretase capable of anti-amyloidogenic proteolysis of the amyloid precursor protein. Here, we present evidence for genetic association of ADAM10 with Alzheimer's disease (AD) as well as two rare potentially disease-associated non-synonymous mutations, Q170H and R181G, in the ADAM10 prodomain. These mutations were found in 11 of 16 affected individuals (average onset age 69.5 years) from seven late-onset AD families. Each mutation was also found in one unaffected subject implying incomplete penetrance. Functionally, both mutations significantly attenuated α-secretase activity of ADAM10 (>70% decrease), and elevated Aβ levels (1.5–3.5-fold) in cell-based studies. In summary, we provide the first evidence of ADAM10 as a candidate AD susceptibility gene, and report two potentially pathogenic mutations with incomplete penetrance for late-onset familial AD. PMID:19608551

ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling

PubMed Central

Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; White, Judith M.; DeSimone, Douglas W.

2010-01-01

SUMMARY The cranial neural crest (CNC) are multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identified as substrates for ADAM13. ADAM13 upregulates canonical Wnt signaling and early expression of the transcription factor snail2, whereas EfnB1 inhibits the canonical Wnt pathway and snail2 expression. We propose that by cleaving class B Efns, ADAM13 promotes canonical Wnt signaling and early CNC induction. PMID:20708595

Adam Smith, Religion, and Tuition Tax Credits.

ERIC Educational Resources Information Center

Alexander, Kern

1983-01-01

Examines tuition tax credit programs in framework of Adam Smith's ideas on the economic impact of established churches. Finds that tuition tax credits would amount to state expenditures to relieve the financial burden of parochial school parents and would allow churches to invest commercially to maintain their charitable functions. (JW)

Over-expression of two different forms of the alpha-secretase ADAM10 affects learning and memory in mice.

PubMed

Schmitt, Ulrich; Hiemke, Christoph; Fahrenholz, Falk; Schroeder, Anja

2006-12-15

Members of the ADAM family (adisintegrin and metalloprotease) are the main candidates for physiologically relevant alpha-secretases. The alpha-secretase cleaves in the non-amyloidogenic pathway the amyloid precursor protein within the region of the Abeta peptides preventing their aggregation in the brain. The increase of alpha-secretase activity in the brain provides a plausible strategy to prevent Abeta formation. Concerning this possibility two transgenic mouse lines (FVB/N) have been created: mice over-expressing the bovine form of the alpha-secretase (ADAM10) and mice over-expressing an inactive form of the alpha-secretase (ADAM10-E348A-HA; ADAM10-dn). For behavioral examination a F1 generation of transgenic mice (C57Bl/6 x FVB/N (tg)) was generated and compared to wild type F1 generation (C57Bl/6 x FVB/N). Behavior was characterized in the following tasks: standard open field, enriched open field, elevated plus-maze, and the Morris water maze hidden platform task. Concerning basal activity, exploration, and anxiety, transgenic mice behaved similar to controls. With respect to learning and memory both transgenic lines showed a significant deficit compared to controls. ADAM10 mice however, showed thigmotaxis with passive floating behavior in the Morris water maze indicating differences in motivation, whereas, ADAM10-dn mice displayed an inconspicuous but limited goal-directed search pattern. Thus variation of the enzymatic activity of alpha-secretase ADAM10 alters learning and memory differentially. Nevertheless, it could be concluded that both, ADAM10 and ADAM10-dn mice are suitable control mice for the assessment of alpha-secretase-related effects in animal models of Alzheimer's disease.

Upregulation of ADAM12 contributes to accelerated cell proliferation and cell adhesion-mediated drug resistance (CAM-DR) in Non-Hodgkin's Lymphoma.

PubMed

Yin, Haibing; Zhong, Fei; Ouyang, Yu; Wang, Qiru; Ding, Linlin; He, Song

2017-10-01

ADAM12 is a member of a disintegrin and metalloproteinase family and has been reported to participate in the development of variety of tumors. However, the role of ADAM12 in Non-Hodgkin Lymphoma (NHL) has not been investigated. The present study was undertaken to determine the expression and biologic function of ADAM12 in human NHL. First, we constructed a model of cell adhesion in NHL, the mRNA, and protein level of ADAM12 in suspension and the adhesion model was analyzed by RT-PCR and western blot. Then, flow cytometry assay and western blot were used to investigate the mechanism of ADAM12 in the proliferation of NHL cells. In vitro, after using siRNA interfering ADAM12 expression, we performed adhesion assay and cell viability assay to determine the effect of ADAM12 on adhesive rate and drug sensitivity. ADAM12 was lowly expressed in suspended cells and highly expressed in adherent NHL cells. In addition, ADAM12 was positively correlated with the proliferation and apoptosis of NHL cells by regulating the expression of p-AKT and p-GSK-3β. Furthermore, ADAM12 promoted cell adhesion-mediated drug resistance (CAM-DR) in DLBCL via AKT signaling pathway. Our data support a role for ADAM12 in NHL cell proliferation, adhesion, and drug resistance, and it may pave the way for a novel therapeutic approach for CAM-DR in NHL.

Adam Smith and the Rhetoric of Style.

ERIC Educational Resources Information Center

Moran, Michael G.

Historians of rhetoric have generally accepted the view that Adam Smith rejected the principles of classical rhetoric. However, while there can be no doubt that Smith greatly truncated the five classical arts of rhetoric (invention, arrangement, style, memory, and delivery) by reducing his concerns largely to style and arrangement, he did not…

Automatic Dynamic Aircraft Modeler (ADAM) for the Computer Program NASTRAN

NASA Technical Reports Server (NTRS)

Griffis, H.

1985-01-01

Large general purpose finite element programs require users to develop large quantities of input data. General purpose pre-processors are used to decrease the effort required to develop structural models. Further reduction of effort can be achieved by specific application pre-processors. Automatic Dynamic Aircraft Modeler (ADAM) is one such application specific pre-processor. General purpose pre-processors use points, lines and surfaces to describe geometric shapes. Specifying that ADAM is used only for aircraft structures allows generic structural sections, wing boxes and bodies, to be pre-defined. Hence with only gross dimensions, thicknesses, material properties and pre-defined boundary conditions a complete model of an aircraft can be created.

ADAM17 targets MMP-2 and MMP-9 via EGFR-MEK-ERK pathway activation to promote prostate cancer cell invasion.

PubMed

Xiao, Li-Jie; Lin, Ping; Lin, Feng; Liu, Xin; Qin, Wei; Zou, Hai-Feng; Guo, Liang; Liu, Wei; Wang, Shu-Juan; Yu, Xiao-Guang

2012-05-01

ADAM17, also known as tumor necrosis factor-α converting enzyme (TACE), is involved in proteolytic ectodomain shedding of cell surface molecules and cytokines. Although aberrant expression of ADAM17 has been shown in various malignancies, the function of ADAM17 in prostate cancer has not been clarified. In the present study, we sought to elucidate whether ADAM17 contributes to prostate cancer cell invasion, as well as the mechanism involved in the process. The expression pattern of ADAM17 was investigated in human prostate cancer cells. The results showed that ADAM17 expression levels are correlated with the invasive ability of androgen-independent prostate cancer cell lines. Further, ADAM17 was overexpressed in cells showing high invasion characteristics, activation of the EGFR-MEK-ERK pathway, up-regulation of MMP-2, MMP-9, and an increased TGF-α release into the supernatant. However, AG1478, PD98059 and antibody against TGF-α deactivating the EGFR-MEK-ERK signaling pathway, abolished up-regulation of MMP-2, MMP-9 and prevented cell invasion. In addition, cells with knockdown of ADAM17 by siRNA exhibited low invasive ability, deactivated EGFR-MEK-ERK signaling pathway, reduced TGF-α released and down-regulation of MMP-2, MMP-9. However, these effects could be reversed by simultaneous addition of TGF-α. These data demonstrated that ADAM17 contributes to androgen-independent prostate cancer cell invasion by shedding of EGFR ligand TGF-α, which subsequently activates the EGFR-MEK-ERK signaling pathway, leading finally to overexpression of MMP-2 and MMP-9. This study suggests that the ADAM17 expression level may be a new predictive biomarker of invasion and metastasis of prostate cancer, and ADAM17 could provide a target for treating metastatic PCa.

MiR-153 inhibits migration and invasion of human non-small-cell lung cancer by targeting ADAM19

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

Shan, Nianxi; Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan 410008; Shen, Liangfang

Highlights: • Decreased miR-153 and up-regulated ADAM19 are correlated with NSCLC pathology. • MiR-153 inhibits the proliferation and migration and invasion of NSCLC cells in vitro. • ADAM19 is a direct target of miR-153. • ADAM19 is involved in miR-153-suppressed migration and invasion of NSCLC cells. - Abstract: MiR-153 was reported to be dysregulated in some human cancers. However, the function and mechanism of miR-153 in lung cancer cells remains unknown. In this study, we investigated the role of miR-153 in human non-small-cell lung cancer (NSCLC). Using qRT-PCR, we demonstrated that miR-153 was significantly decreased in clinical NSCLC tissues andmore » cell lines, and downregulation of miR-153 was significantly correlated with lymph node status. We further found that ectopic expression of miR-153 significantly inhibited the proliferation and migration and invasion of NSCLC cells in vitro, suggesting that miR-153 may be a novel tumor suppressor in NSCLC. Further integrated analysis revealed that ADAM19 is as a direct and functional target of miR-153. Luciferase reporter assay demonstrated that miR-153 directly targeted 3′UTR of ADAM19, and correlation analysis revealed an inverse correlation between miR-153 and ADAM19 mRNA levels in clinical NSCLC tissues. Knockdown of ADAM19 inhibited migration and invasion of NSCLC cells which was similar with effects of overexpression of miR-153, while overexpression of ADAM19 attenuated the function of miR-153 in NSCLC cells. Taken together, our results highlight the significance of miR-153 and ADAM19 in the development and progression of NSCLC.« less

Soluble Axl Is Generated by ADAM10-Dependent Cleavage and Associates with Gas6 in Mouse Serum†

PubMed Central

Budagian, Vadim; Bulanova, Elena; Orinska, Zane; Duitman, Erwin; Brandt, Katja; Ludwig, Andreas; Hartmann, Dieter; Lemke, Greg; Saftig, Paul; Bulfone-Paus, Silvia

2005-01-01

Axl receptor tyrosine kinase exists as a transmembrane protein and as a soluble molecule. We show that constitutive and phorbol 12-myristate 13-acetate-induced generation of soluble Axl (sAxl) involves the activity of disintegrin-like metalloproteinase 10 (ADAM10). Spontaneous and inducible Axl cleavage was inhibited by the broad-spectrum metalloproteinase inhibitor GM6001 and by hydroxamate GW280264X, which is capable of blocking ADAM10 and ADAM17. Furthermore, murine fibroblasts deficient in ADAM10 expression exhibited a significant reduction in constitutive and inducible Axl shedding, whereas reconstitution of ADAM10 restored sAxl production, suggesting that ADAM10-mediated proteolysis constitutes a major mechanism for sAxl generation in mice. Partially overlapping 14-amino-acid stretch deletions in the membrane-proximal region of Axl dramatically affected sAxl generation, indicating that these regions are involved in regulating the access of the protease to the cleavage site. Importantly, relatively high circulating levels of sAxl are present in mouse sera in a heterocomplex with Axl ligand Gas6. Conversely, two other family members, Tyro3 and Mer, were not detected in mouse sera and conditioned medium. sAxl is constitutively released by murine primary cells such as dendritic and transformed cell lines. Upon immobilization, sAxl promoted cell migration and induced the phosphorylation of Axl and phosphatidylinositol 3-kinase. Thus, ADAM10-mediated generation of sAxl might play an important role in diverse biological processes. PMID:16227584

Inhibition of ADAM-17 more effectively down-regulates the Notch pathway than that of γ-secretase in renal carcinoma.

PubMed

Guo, Zhen; Jin, Xunbo; Jia, Haiyan

2013-05-09

Our study is to research the effect of inhibited ADAM-17 expression through the Notch pathway in renal carcinoma. Immunohistochemistry and western blot were used to examine the expression of ADAM-17 protein in renal cancer tissues. Proliferation and cell invasion of 786-o cells, as well as OS-RC-2 cells, after treatment with two different inhibitors of the Notch pathway, were examined by CCK-8 assay and Transwell assay, respectively. 786-o cell apoptosis was measured using the FCM test. ADAM-17 was highly expressed in RCC tissues. Compared with blocking γ-secretase, a known mechanism of impairing Notch, blockade of ADAM-17 more effectively down-regulated the expressions of Notch1 and HES-1 proteins. Similarly, we found that the ADAM-17 inhibitor, Marimastat, could more efficiently reduce renal cell proliferation and invasive capacity in comparison with the γ-secretase inhibitor DAPT when used at the same dose. Similar results were obtained when apoptosis of 786-o was measured. Compared with γ-secretase, inhibition of ADAM-17 expression more effectively inhibits Notch pathway-mediated renal cancer cell proliferation and invasion. ADAM-17 may be a new target for future treatment of renal carcinoma.

Lysophosphatidic acid-induced ADAM12 expression mediates human adipose tissue-derived mesenchymal stem cell-stimulated tumor growth.

PubMed

Do, Eun Kyoung; Kim, Young Mi; Heo, Soon Chul; Kwon, Yang Woo; Shin, Sang Hun; Suh, Dong-Soo; Kim, Ki-Hyung; Yoon, Man-Soo; Kim, Jae Ho

2012-11-01

Lysophosphatidic acid (LPA) is involved in mesenchymal stem cell-stimulated tumor growth in vivo. However, the molecular mechanism by which mesenchymal stem cells promote tumorigenesis remains elusive. In the present study, we demonstrate that conditioned medium from A549 human lung adenocarcinoma cells (A549 CM) induced the expression of ADAM12, a disintegrin and metalloproteases family member, in human adipose tissue-derived mesenchymal stem cells (hASCs). A549 CM-stimulated ADAM12 expression was abrogated by pretreatment of hASCs with the LPA receptor 1 inhibitor Ki16425 or by small interfering RNA-mediated silencing of LPA receptor 1, suggesting a key role for the LPA-LPA receptor 1 signaling axis in A549 CM-stimulated ADAM12 expression. Silencing of ADAM12 expression using small interfering RNA or short hairpin RNA abrogated LPA-induced expression of both α-smooth muscle actin, a marker of carcinoma-associated fibroblasts, and ADAM12 in hASCs. Using a xenograft transplantation model of A549 cells, we demonstrated that silencing of ADAM12 inhibited the hASC-stimulated in vivo growth of A549 xenograft tumors and the differentiation of transplanted hASCs to α-smooth muscle actin-positive carcinoma-associated fibroblasts. LPA-conditioned medium from hASCs induced the adhesion of A549 cells and silencing of ADAM12 inhibited LPA-induced expression of extracellular matrix proteins, periostin and βig-h3, in hASCs and LPA-conditioned medium-stimulated adhesion of A549 cells. These results suggest a pivotal role for LPA-stimulated ADAM12 expression in tumor growth and the differentiation of hASCs to carcinoma-associated fibroblasts expressing α-smooth muscle actin, periostin, and βig-h3. Copyright © 2012 Elsevier Ltd. All rights reserved.

Springs, streams, and gas vent on and near Mount Adams volcano, Washington

USGS Publications Warehouse

Nathenson, Manuel; Mariner, Robert H.

2013-01-01

Springs and some streams on Mount Adams volcano have been sampled for chemistry and light stable isotopes of water. Spring temperatures are generally cooler than air temperatures from weather stations at the same elevation. Spring chemistry generally reflects weathering of volcanic rock from dissolved carbon dioxide. Water in some springs and streams has either dissolved hydrothermal minerals or has reacted with them to add sulfate to the water. Some samples appear to have obtained their sulfate from dissolution of gypsum while some probably involve reaction with sulfide minerals such as pyrite. Light stable isotope data for water from springs follow a local meteoric water line, and the variation of isotopes with elevation indicate that some springs have very local recharge and others have water from elevations a few hundred meters higher. No evidence was found for thermal or slightly thermal springs on Mount Adams. A sample from a seeping gas vent on Mount Adams was at ambient temperature, but the gas is similar to that found on other Cascade volcanoes. Helium isotopes are 4.4 times the value in air, indicating that there is a significant component of mantle helium. The lack of fumaroles on Mount Adams and the ambient temperature of the gas indicates that the gas is from a hydrothermal system that is no longer active.

Comparison Virtual Landing Gear Drop Test for Commuter Aircraft Utilize MSC ADAMS And Solidworks Motion Analysis

NASA Astrophysics Data System (ADS)

Hidayat, Dony; Istiyanto, Jos; Agus Sumarsono, Danardono

2018-04-01

Loads at main landing gear while touchdown impact is function of aircraft weight and ground reaction load factor. In regulation states ground reaction load factor at Vsink = 3.05 m/s is below 3. Contact/impact force from simulation using MSC ADAMS is 94680 N, while using Solidworks Motion Analysis is 97691 N. The difference between MSC ADAMS and Solidworks Motion Analysis is 3.08%. The ground reaction load factor in MSC ADAMS is 2.78 while in Solidworks Motion Analysis is 2.87.

77 FR 60004 - Culturally Significant Object Imported for Exhibition Determinations: “Wtewael's Adam and Eve”

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-01

... Determinations: ``Wtewael's Adam and Eve'' SUMMARY: Notice is hereby given of the following determinations... April 15, 2003), I hereby determine that the object to be included in the exhibition ``Wtewael's Adam and Eve,'' imported from abroad for temporary exhibition within the United States, is of cultural...

Geologic map and geothermal assessment of the Mount Adams volcanic field, Cascade Range of southern Washington

USGS Publications Warehouse

Hildreth, Wes; Fierstein, Judy

1990-01-01

More than 60 Quaternary vents make up the basalt-to-rhyodacite Mount Adams volcanic field and have erupted scoriae and lavas with a total volume of >370 km3. The Mount Adams andesite-dacite stratocone itself is a compound edifice that includes the high cone above 2300 m (20-10 ka), remnants of at least two earlier andesite-dacite cones as old as 0.5 Ma, and 7 Holocene flank vents. Four other Holocene vents and tens of vents contemporaneous with Mount Adams are peripheral to the stratocone. All of these vents, including Mount Adams, lie within a N-S eruptive zone 55 km long and 5 km wide. The age of all known Mount Adams silicic products (>100 ka) and the heterogeneous mafic compositions of the summit cone and Holocene lavas make it unlikely that the stratocone is underlain by an upper-crustal reservoir. Rather, the stratocone at the focus is built up of fractionated hybrid magmas that rise from MASH zones (melting-assimilation-storage-homogenization). The pyroclastic core of breccia and scoria at Mount Adams has undergone acid-sulfate leaching and deposition of alunite, kaolinite, silica, gypsum, sulfur, and Fe-oxides and has been a constant source of avalanches and debris flows. Most heat supplied from depth to the fumarolically altered core is dispersed by the high precipitation rate and high permeability of the rubbly lava flows so that a hydrothermal convection pattern is not maintained. Summit-restricted fumaroles are weak and diffuse.

ADAM13 function is required in the 3 dimensional context of the embryo during cranial neural crest cell migration in Xenopus laevis

PubMed Central

Cousin, Hélène; Abbruzzese, Genevieve; McCusker, Catherine; Alfandari, Dominique

2012-01-01

The cranial neural crest (CNC) is a population of cells that arises from the lateral part of the developing brain, migrates ventrally and coordinates the entire craniofacial development of vertebrates. Many molecules are involved in CNC migration including the transmembrane metalloproteases ADAM13 and 19. We have previously shown that these ADAMs cleave a number of extracellular proteins and modify the transcription of a number of genes, and that both of these activities are important for cell migration. Here we show that the knock down of ADAM13 inhibits CNC migration in vivo but not in vitro, indicating that ADAM13 function is required in the 3-dimentional context of the embryo. We further show that the migration of CNC that do not express ADAM13 and ADAM19 can be rescued in vivo by co-grafting wild type CNC. Furthermore, the migration of CNC lacking ADAM13 can be rescued by mechanically separating the CNC from the surrounding ectoderm and mesoderm. Finally, we show that ADAM13 function is autonomous to CNC tissue, as the migration of morphant CNC can only be rescued by ADAM13 expression in the CNC and not the surrounding tissues. Together our results suggest that ADAM13 changes CNC interaction with the extracellular environment and that this change is necessary for their migration in vivo. PMID:22683825

Dr. Lytle Adams' incendiary "bat bomb" of World War II.

PubMed

Christen, Arden G; Christen, Joan A

2004-11-01

On December 7, 1941, a 60-year old dentist from Irwin, Pennsylvania, Dr. Lytle S. Adams, was driving home from a vacation at Carlsbad Caverns in New Mexico. Hours earlier, he had been gripped with amazement as he witnessed millions of bats exiting the caves of Carlsbad. Listening to his car radio on his return trip, he was shocked to hear that Japan had just attacked Pearl Harbor. Dr. Adams, outraged over this travesty, began to mentally construct a plan for U.S. retaliation. As his thoughts returned to the countless bats that had awed him, he formed a tentative plan: millions of these small, flying mammals could be connected to tiny, time-fused incendiary bombs, and then released to land on the flimsily constructed structures which dotted the cities of Japan. Within a few minutes, the bombs would explode and enflame the entire urban areas. He postulated that these immeasurable numbers of fires, spreading their devastation over such vast areas within Japanese cities would result in the enemy's speedy surrender. This article documents the futile efforts of Dr. Adams, his team and the U.S. government to develop and employ an effective, incendiary bat bomb. The recently developed atom bomb, a far more deadly weapon was used in its place.

ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death.

PubMed

Miyamae, Yuka; Mochizuki, Satsuki; Shimoda, Masayuki; Ohara, Kentaro; Abe, Hitoshi; Yamashita, Shuji; Kazuno, Saiko; Ohtsuka, Takashi; Ochiai, Hiroki; Kitagawa, Yuko; Okada, Yasunori

2016-05-01

ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells. © 2016 Federation of European Biochemical Societies.

In silico approaches and proportional odds model towards identifying selective ADAM17 inhibitors from anti-inflammatory natural molecules.

PubMed

Borah, Pallab Kumar; Chakraborty, Sourav; Jha, Anupam N; Rajkhowa, Sanchaita; Duary, Raj Kumar

2016-11-01

ADAM metallopeptidase domain 17 (ADAM17) is an attractive target for the development of new anti-inflammatory drugs. We aimed to identify selective inhibitors of ADAM17 against matrix metalloproteinase enzymes (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13, and MMP-16) which have substantial structural similarity. Target proteins were docked with 29 anti-inflammatory natural molecule ligands and a known selective inhibitor IK682. The ligands were screened based on Lipinski rules, interaction with the ADAM17 active site cavity, and then ranked using the proportional odds model multinomial logistic regression. Silymarin was the most selective inhibitor of ADAM17 exhibiting H-bonding with Glu 406, Gly 349, Glu 398, Asn 447, Tyr 433, and Lys 432. Molecular dynamics simulations were carried out for 10ns. The root mean square deviation (RMSD), root mean squared fluctuations (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), and H-bonding indicated the induced metastability. A comparison of the principal component analysis revealed that the silymarin complex also explored lesser region compared to IK682 complex. A control study on ADAM17 protein (2OI0) is included. These observations present silymarin (widely present in plants such as milk thistle (Silybum maianum), wild artichokes (Cynara cardunculus), turmeric (Curcuma longa) roots, coriander (Coriandrum sativum) seeds, etc.) as a promising natural template for development of ADAM17 selective drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

ADAM-17 and TIMP3 protein and mRNA expression in spinal cord white matter of rats with acute experimental autoimmune encephalomyelitis.

PubMed

Plumb, Jonnie; Cross, Alison K; Surr, Jessica; Haddock, Gail; Smith, Terence; Bunning, Rowena A D; Woodroofe, M Nicola

2005-07-01

Tumour necrosis factor (TNF) is a major immunomodulatory and proinflammatory cytokine implicated in the pathogenesis of multiple sclerosis (MS) and the animal model experimental autoimmune encephalomyelitis (EAE). ADAM-17 cleaves membrane-bound TNF into its soluble form. The distribution and level of ADAM-17 expression within spinal cords of Lewis rats with EAE was investigated. ADAM-17 was associated with endothelial cells in the naïve and pre-disease spinal cords. In peak disease astrocytic and inflammatory cells expressed ADAM-17. Upregulation of ADAM-17 mRNA expression was coupled with a decrease in mRNA levels of its inhibitor TIMP3 suggesting a role for ADAM-17 in EAE pathogenesis.

[The importance of ADAM family proteins in malignant tumors].

PubMed

Walkiewicz, Katarzyna; Gętek, Monika; Muc-Wierzgoń, Małgorzata; Kokot, Teresa; Nowakowska-Zajdel, Ewa

2016-02-11

Increasing numbers of reports about the role of adamalysins (ADAM) in malignant tumors are being published. To date, more than 30 representatives of this group, out of which about 20 occur in humans, have been described. The ADAM family is a homogeneous group of proteins which regulate, from the stage of embryogenesis, a series of processes such as cell migration, adhesion, and cell fusion. Half of them have proteolytic activity and are involved in the degradation of the extracellular matrix and the disintegration of certain protein complexes, thereby regulating the bioavailability of various growth factors. Many of these functions have a direct role in the processes of carcinogenesis and promoting the growth of tumor, which affect some signaling pathways, including those related to insulin-like growth factors (IGF1, IGF2), vascular growth factor (VEGF), tumor necrosis factor α (TNFα) and the EGFR/HER pathway. Another branch of studies is the evaluation of the possibility of using members of ADAM family proteins in the diagnosis, especially in breast, colon and non- small cell lung cancer. The detection of concentrations of adamalysin in serum, urine and pleural aspirates might contribute to the development of methods of early diagnosis of cancer and monitoring the therapy. However, both the role of adamalysins in the development and progression of tumors and their importance as a diagnostic and predictive further research still need to be checked on large groups of patients.

Isotopic and trace element constraints on the petrogenesis of lavas from the Mount Adams volcanic field, Washington

USGS Publications Warehouse

Jicha, B.R.; Hart, G.L.; Johnson, C.M.; Hildreth, Wes; Beard, B.L.; Shirey, S.B.; Valley, J.W.

2009-01-01

Strontium, Nd, Pb, Hf, Os, and O isotope compositions for 30 Quaternary lava flows from the Mount Adams stratovolcano and its basaltic periphery in the Cascade arc, southern Washington, USA indicate a major component from intraplate mantle sources, a relatively small subduction component, and interaction with young mafic crust at depth. Major- and trace-element patterns for Mount Adams lavas are distinct from the rear-arc Simcoe volcanic field and other nearby volcanic centers in the Cascade arc such as Mount St. Helens. Radiogenic isotope (Sr, Nd, Pb, and Hf) compositions do not correlate with geochemical indicators of slab-fluids such as (Sr/P)n and Ba/Nb. Mass-balance modeling calculations, coupled with trace-element and isotopic data, indicate that although the mantle source for the calc-alkaline Adams basalts has been modified with a fluid derived from subducted sediment, the extent of modification is significantly less than what is documented in the southern Cascades. The isotopic and trace-element compositions of most Mount Adams lavas require the presence of enriched and depleted mantle sources, and based on volume-weighted chemical and isotopic compositions for Mount Adams lavas through time, an intraplate mantle source contributed the major magmatic mass of the system. Generation of basaltic andesites to dacites at Mount Adams occurred by assimilation and fractional crystallization in the lower crust, but wholesale crustal melting did not occur. Most lavas have Tb/Yb ratios that are significantly higher than those of MORB, which is consistent with partial melting of the mantle in the presence of residual garnet. ??18O values for olivine phenocrysts in Mount Adams lavas are within the range of typical upper mantle peridotites, precluding involvement of upper crustal sedimentary material or accreted terrane during magma ascent. The restricted Nd and Hf isotope compositions of Mount Adams lavas indicate that these isotope systems are insensitive to crustal

Adam Smith and the Teaching of English Literature.

ERIC Educational Resources Information Center

Court, Franklin E.

1985-01-01

Adam Smith used selections from English literature in his classroom during the eighteenth century because he believed that vernacular literature could provide a ready context for the teaching of ideological, social, and moral lessons. He believed that higher education should prepare students for the real business of the real world. (RM)

The TspanC8 Subgroup of Tetraspanins Interacts with A Disintegrin and Metalloprotease 10 (ADAM10) and Regulates Its Maturation and Cell Surface Expression*

PubMed Central

Haining, Elizabeth J.; Yang, Jing; Bailey, Rebecca L.; Khan, Kabir; Collier, Richard; Tsai, Schickwann; Watson, Steve P.; Frampton, Jon; Garcia, Paloma; Tomlinson, Michael G.

2012-01-01

A disintegrin and metalloprotease 10 (ADAM10) is a ubiquitous transmembrane metalloprotease that cleaves the extracellular regions from over 40 different transmembrane target proteins, including Notch and amyloid precursor protein. ADAM10 is essential for embryonic development and is also important in inflammation, cancer, and Alzheimer disease. However, ADAM10 regulation remains poorly understood. ADAM10 is compartmentalized into membrane microdomains formed by tetraspanins, which are a superfamily of 33 transmembrane proteins in humans that regulate clustering and trafficking of certain other transmembrane “partner” proteins. This is achieved by specific tetraspanin-partner interactions, but it is not clear which tetraspanins specifically interact with ADAM10. The aims of this study were to identify which tetraspanins interact with ADAM10 and how they regulate this metalloprotease. Co-immunoprecipitation identified specific ADAM10 interactions with Tspan5, Tspan10, Tspan14, Tspan15, Tspan17, and Tspan33/Penumbra. These are members of the largely unstudied TspanC8 subgroup of tetraspanins, all six of which promoted ADAM10 maturation. Different cell types express distinct repertoires of TspanC8 tetraspanins. Human umbilical vein endothelial cells express relatively high levels of Tspan14, the knockdown of which reduced ADAM10 surface expression and activity. Mouse erythrocytes express predominantly Tspan33, and ADAM10 expression was substantially reduced in the absence of this tetraspanin. In contrast, ADAM10 expression was normal on Tspan33-deficient mouse platelets in which Tspan14 is the major TspanC8 tetraspanin. These results define TspanC8 tetraspanins as essential regulators of ADAM10 maturation and trafficking to the cell surface. This finding has therapeutic implications because focusing on specific TspanC8-ADAM10 complexes may allow cell type- and/or substrate-specific ADAM10 targeting. PMID:23035126

George Adams Junior and his 1789 book An essay on vision.

PubMed

Goss, David A

2009-04-01

English instrument maker George Adams Junior (1750-1795) published An Essay on Vision in 1789, with a second edition appearing in 1792. The 153 page book (157 pages in the second edition) presented material on structure of the eye and the basic nature of vision and vision conditions, with an emphasis on the proper use and choice of spectacles for the "long sighted" and the "short-sighted." A brief biographical sketch of Adams is given, and the contents of the book are discussed, with presentation of excerpts relating to general optometric principles. The excerpts can serve to illustrate the state of optometric knowledge in the late eighteenth century.

A score including ADAM17 substrates correlates to recurring cardiovascular event in subjects with atherosclerosis.

PubMed

Rizza, Stefano; Copetti, Massimiliano; Cardellini, Marina; Menghini, Rossella; Pecchioli, Chiara; Luzi, Alessio; Di Cola, Giovanni; Porzio, Ottavia; Ippoliti, Arnaldo; Romeo, Franco; Pellegrini, Fabio; Federici, Massimo

2015-04-01

Atherosclerosis disease is a leading cause for mortality and morbidity. The narrowing/rupture of a vulnerable atherosclerotic plaque is accountable for acute cardiovascular events. However, despite of an intensive research, a reliable clinical method which may disclose a vulnerable patient is still unavailable. We tested the association of ADAM17 (A Disintegrin and Metallo Protease Domain 17) circulating substrates (sICAM-1, sVCAM-1, sIL6R and sTNFR1) with a second major cardiovascular events [MACEs] (cardiovascular death, peripheral artery surgeries, non-fatal myocardial infarction and non-fatal stroke) in 298 patients belonging to the Vascular Diabetes (AVD) study. To evaluate ADAM17 activity we create ADAM17 score through a RECPAM model. Finally we tested the discrimination ability and the reclassification of clinical models. At follow-up (mean 47 months, range 1-118 months), 55 MACEs occurred (14 nonfatal MI, 14 nonfatal strokes, 17 peripheral artery procedures and 10 cardiovascular deaths) (incidence = 7.8% person-years). An increased risk for incident events was observed among the high ADAM17 score individuals both in univariable (HR 19.20, 95% CI 15.82-63.36, p < 0.001) and multivariable analysis (HR 3.42, 95% CI 1.55-7.54, p < 0.001). Finally we found that ADAM17 score significantly increases the prediction accuracy of the Framingham Recurring-Coronary-Heart-Disease-Score, with a significant improvement in discrimination (integrated discrimination improvement = 9%, p = 0.012) and correctly reclassifying 10% of events and 41% of non-events resulting in a cNRI = 0.51 (p = 0.005). We demonstrated a positive role of ADAM17 activity to predicting CV events. We think that an approach that targets strategies beyond classic cardiovascular risk factors control is necessary in individuals with an established vascular atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A Mechanism of Male Germ Cell Apoptosis Induced by Bisphenol-A and Nonylphenol Involving ADAM17 and p38 MAPK Activation

PubMed Central

Moreno, Ricardo D.

2014-01-01

Germ cell apoptosis regulation is pivotal in order to maintain proper daily sperm production. Several reports have shown that endocrine disruptors such as Bisphenol-A (BPA) and Nonylphenol (NP) induce germ cell apoptosis along with a decrease in sperm production. Given their ubiquitous distribution in plastic products used by humans it is important to clarify their mechanism of action. TACE/ADAM17 is a widely distributed extracellular metalloprotease and participates in the physiological apoptosis of germ cells during spermatogenesis. The aims of this work were: 1) to determine whether BPA and NP induce ADAM17 activation; and 2) to study whether ADAM17 and/or ADAM10 are involved in germ cell apoptosis induced by BPA and NP in the pubertal rat testis. A single dose of BPA or NP (50 mg/kg) induces germ cell apoptosis in 21-day-old male rats, which was prevented by a pharmacological inhibitor of ADAM17, but not by an inhibitor of ADAM10. In vitro, we showed that BPA and NP, at similar concentrations to those found in human samples, induce the shedding of exogenous and endogenous (TNF-α) ADAM17 substrates in primary rat Sertoli cell cultures and TM4 cell line. In addition, pharmacological inhibitors of metalloproteases and genetic silencing of ADAM17 prevent the shedding induced in vitro by BPA and NP. Finally, we showed that in vivo BPA and NP induced early activation (phosphorylation) of p38 MAPK and translocation of ADAM17 to the cell surface. Interestingly, the inhibition of p38 MAPK prevents germ cell apoptosis and translocation of ADAM17 to the cell surface. These results show for the first time that xenoestrogens can induce activation of ADAM17 at concentrations similar to those found in human samples, suggesting a mechanism by which they could imbalance para/juxtacrine cell-to-cell-communication and induce germ cell apoptosis. PMID:25474107

Adams National Historic Park Trolley Vehicle Replacement Selection Analysis

DOT National Transportation Integrated Search

2017-12-01

Adams NHP owns three trolley vehicles that were purchased in the early 2000s and, while their accrued mileage remains low, they have reached the end of their useful lives due in large part to vehicle parts becoming unavailable. Both the original trol...

IL-5-stimulated eosinophils adherent to periostin undergo stereotypic morphological changes and ADAM8-dependent migration.

PubMed

Johansson, M W; Khanna, M; Bortnov, V; Annis, D S; Nguyen, C L; Mosher, D F

2017-10-01

IL-5 causes suspended eosinophils to polarize with filamentous (F)-actin and granules at one pole and the nucleus in a specialized uropod, the "nucleopod," which is capped with P-selectin glycoprotein ligand-1 (PSGL-1). IL-5 enhances eosinophil adhesion and migration on periostin, an extracellular matrix protein upregulated in asthma by type 2 immunity mediators. Determine how the polarized morphology evolves to foster migration of IL-5-stimulated eosinophils on a surface coated with periostin. Blood eosinophils adhering to adsorbed periostin were imaged at different time points by fluorescent microscopy, and migration of eosinophils on periostin was assayed. After 10 minutes in the presence of IL-5, adherent eosinophils were polarized with PSGL-1 at the nucleopod tip and F-actin distributed diffusely at the opposite end. After 30-60 minutes, the nucleopod had dissipated such that PSGL-1 was localized in a crescent or ring away from the cell periphery, and F-actin was found in podosome-like structures. The periostin layer, detected with monoclonal antibody Stiny-1, shown here to recognize the FAS1 4 module, was cleared in wide areas around adherent eosinophils. Clearance was attenuated by metalloproteinase inhibitors or antibodies to disintegrin metalloproteinase 8 (ADAM8), a major eosinophil metalloproteinase previously implicated in asthma pathogenesis. ADAM8 was not found in podosome-like structures, which are associated with proteolytic activity in other cell types. Instead, immunoblotting demonstrated proteoforms of ADAM8 that lack the cytoplasmic tail in the supernatant. Anti-ADAM8 inhibited migration of IL-5-stimulated eosinophils on periostin. Migrating IL-5-activated eosinophils on periostin exhibit loss of nucleopodal features and appearance of prominent podosomes along with clearance of the Stiny-1 periostin epitope. Migration and epitope clearance are both attenuated by inhibitors of ADAM8. We propose, therefore, that eosinophils remodel and migrate

Henry Adams’s Life of George Cabot Lodge: A Portrait of the Artist as an Alienated Man

DTIC Science & Technology

1994-07-20

literary tradition, especially as had been handed down from Adams’s Puritan forebears. My aim is to present the most complete critical study of this...several critics have pointed to this book as evidence of Adams’s diminished talents--when a careful study of the book in fact demonstrates otherwise...critical studies have given more than cursory attention to the Life of Lodge: J. C. Levenson, The Mind and Art of Henry Adams (1957); George Hochfield

Targeting ADAM17 inhibits human colorectal adenocarcinoma progression and tumor-initiating cell frequency.

PubMed

Dosch, Joseph; Ziemke, Elizabeth; Wan, Shanshan; Luker, Kathryn; Welling, Theodore; Hardiman, Karin; Fearon, Eric; Thomas, Suneetha; Flynn, Matthew; Rios-Doria, Jonathan; Hollingsworth, Robert; Herbst, Ronald; Hurt, Elaine; Sebolt-Leopold, Judith

2017-09-12

ADAM17 (a disintegrin and metalloproteinase 17)/TACE (TNFα converting enzyme) has emerged as a potential therapeutic target in colorectal cancer (CRC) and other cancers, due in part to its role in regulating various tumor cell surface proteins and growth factors and cytokines in the tumor microenvironment. The emergence of MEDI3622, a highly potent and specific antibody-based ADAM17 inhibitor, has allowed testing of the concept that targeting ADAM17 may be an important new therapeutic approach for CRC patients. We demonstrate that MEDI3622 is highly efficacious on tumor growth in multiple human CRC PDX models, resulting in improved survival of animals bearing tumor xenografts. MEDI3622 was further found to impact Notch pathway activity and tumor-initiating cells. The promising preclinical activity seen here supports further clinical investigation of this treatment approach to improve therapeutic outcome for patients diagnosed with metastatic CRC, including patients with KRAS-mutant tumors for whom other therapeutic options are currently limited.

7. Historic American Buildings Survey, C. C. Adams, Photographer August ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. Historic American Buildings Survey, C. C. Adams, Photographer August 1931, SEED PACKING ROOM, Gift of New York State Department of Education. - Shaker North Family Washhouse (first), Shaker Road, New Lebanon, Columbia County, NY

ADAM: An Axisymmetric Duct Aeroacoustic Modeling system. [aircraft turbofan engines

NASA Technical Reports Server (NTRS)

Abrahamson, A. L.

1983-01-01

An interconnected system of computer programs for analyzing the propagation and attenuation of sound in aeroengine ducts containing realistic compressible subsonic mean flows, ADAM was developed primarily for research directed towards the reduction of noise emitted from turbofan aircraft engines. The two basic components are a streamtube curvature program for determination of the mean flow, and a finite element code for solution of the acoustic propagation problem. The system, which has been specifically tailored for ease of use, is presently installed at NASA Langley Reseach Center on a Control Data Cyber 175 Computer under the NOS Operating system employing a Tektronix terminal for interactive graphics. The scope and organization of the ADAM system is described. A users guide, examples of input data, and results for selected cases are included.

System Verification of MSL Skycrane Using an Integrated ADAMS Simulation

NASA Technical Reports Server (NTRS)

White, Christopher; Antoun, George; Brugarolas, Paul; Lih, Shyh-Shiuh; Peng, Chia-Yen; Phan, Linh; San Martin, Alejandro; Sell, Steven

2012-01-01

Mars Science Laboratory (MSL) will use the Skycrane architecture to execute final descent and landing maneuvers. The Skycrane phase uses closed-loop feedback control throughout the entire phase, starting with rover separation, through mobility deploy, and through touchdown, ending only when the bridles have completely slacked. The integrated ADAMS simulation described in this paper couples complex dynamical models created by the mechanical subsystem with actual GNC flight software algorithms that have been compiled and linked into ADAMS. These integrated simulations provide the project with the best means to verify key Skycrane requirements which have a tightly coupled GNC-Mechanical aspect to them. It also provides the best opportunity to validate the design of the algorithm that determines when to cut the bridles. The results of the simulations show the excellent performance of the Skycrane system.

Ectodomain Shedding by ADAM17: Its Role in Neutrophil Recruitment and the Impairment of This Process during Sepsis.

PubMed

Mishra, Hemant K; Ma, Jing; Walcheck, Bruce

2017-01-01

Neutrophils are specialized at killing bacteria and are recruited from the blood in a rapid and robust manner during infection. A cascade of adhesion events direct their attachment to the vascular endothelium and migration into the underlying tissue. A disintegrin and metalloproteinase 17 (ADAM17) functions in the cell membrane of neutrophils and endothelial cells by cleaving its substrates, typically in a cis manner, at an extracellular site proximal to the cell membrane. This process is referred to as ectodomain shedding and it results in the downregulation of various adhesion molecules and receptors, and the release of immune regulating factors. ADAM17 sheddase activity is induced upon cell activation and rapidly modulates intravascular adhesion events in response to diverse environmental stimuli. During sepsis, an excessive systemic inflammatory response against infection, neutrophil migration becomes severely impaired. This involves ADAM17 as indicated by increased levels of its cleaved substrates in the blood of septic patients, and that ADAM17 inactivation improves neutrophil recruitment and bacterial clearance in animal models of sepsis. Excessive ADAM17 sheddase activity during sepsis thus appears to undermine in a direct and indirect manner the necessary balance between intravascular adhesion and de-adhesion events that regulate neutrophil migration into sites of infection. This review provides an overview of ADAM17 function and regulation and its potential contribution to neutrophil dysfunction during sepsis.

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma.

PubMed

Rooprai, Harcharan K; Martin, Andrew J; King, Andrew; Appadu, Usha D; Jones, Huw; Selway, Richard P; Gullan, Richard W; Pilkington, Geoffrey J

2016-12-01

MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) are implicated in invasion and angiogenesis: both are tissue remodeling processes involving regulated proteolysis of the extracellular matrix, growth factors and their receptors. The expression of these three groups and their correlations with clinical behaviour has been reported in gliomas but a similar comprehensive study in meningiomas is lacking. In this study, we aimed to evaluate the patterns of expression of 23 MMPs, 4 TIMPs, 8 ADAMs, selective growth factors and their receptors in 17 benign meningiomas using a quantitative real-time polymerase chain reaction (qPCR). Results indicated very high gene expression of 13 proteases, inhibitors and growth factors studied: MMP2 and MMP14, TIMP-1, -2 and -3, ADAM9, 10, 12, 15 and 17, EGF-R, EMMPRIN and VEGF-A, in almost every meningioma. Expression pattern analysis showed several positive correlations between MMPs, ADAMs, TIMPs and growth factors. Furthermore, our findings suggest that expression of MMP14, ADAM9, 10, 12, 15 and 17, TIMP-2, EGF-R and EMMPRIN reflects histological subtype of meningioma such that fibroblastic subtype had the highest mRNA expression, transitional subtype was intermediate and meningothelial type had the lowest expression. In conclusion, this is the first comprehensive study characterizing gene expression of 8 ADAMs in meningiomas. These neoplasms, although by histological definition benign, have invasive potential. Taken together, the selected elevated gene expression pattern may serve to identify targets for therapeutic intervention or indicators of biological progression and recurrence.

Lightweight robotic mobility: template-based modeling for dynamics and controls using ADAMS/car and MATLAB

NASA Astrophysics Data System (ADS)

Adamczyk, Peter G.; Gorsich, David J.; Hudas, Greg R.; Overholt, James

2003-09-01

The U.S. Army is seeking to develop autonomous off-road mobile robots to perform tasks in the field such as supply delivery and reconnaissance in dangerous territory. A key problem to be solved with these robots is off-road mobility, to ensure that the robots can accomplish their tasks without loss or damage. We have developed a computer model of one such concept robot, the small-scale "T-1" omnidirectional vehicle (ODV), to study the effects of different control strategies on the robot's mobility in off-road settings. We built the dynamic model in ADAMS/Car and the control system in Matlab/Simulink. This paper presents the template-based method used to construct the ADAMS model of the T-1 ODV. It discusses the strengths and weaknesses of ADAMS/Car software in such an application, and describes the benefits and challenges of the approach as a whole. The paper also addresses effective linking of ADAMS/Car and Matlab for complete control system development. Finally, this paper includes a section describing the extension of the T-1 templates to other similar ODV concepts for rapid development.

ADAM15 is involved in MICB shedding and mediates the effects of gemcitabine on MICB shedding in PANC-1 pancreatic cancer cells.

PubMed

Duan, Xiaohui; Mao, Xianhai; Sun, Weijia

2013-03-01

The aim of this study was to investigate the role of ADAM15 in MHC class I polypeptide-related sequence B (MICB) protein ectodomain shedding and observe whether or not gemcitabine affects MICB shedding from PANC-1 cells. In this study, immunohistochemistry of MICB and ADAM15 were performed on tumor samples obtained from 93 patients with pancreatic ductal adenocarcinoma (PDAC). The expression of MICB and ADAM15 in the PDAC tissues was significantly higher compared with that in the normal tissues of the pancreas. Statistical analysis showed a significant correlation between the expression of MICB and certain classic clinicopathological characteristics (i.e., histological grade and TNM stage). ADAM15 expression was found to correlate with lymph node metastasis and TNM stage. The Spearman's rank test suggested that the expression of MICB was inversely correlated with that of ADAM15 in PDAC tissues. Knockdown of ADAM15 in PANC-1 cells clearly upregulated MICB expression on the cellular surface and downregulated soluble MICB (sMICB) levels in the culture supernatants. A non-toxic dose of 0.5 µmol/l gemcitabine suppresses ADAM15 expression leading, at the same time, to an increase in MICB expression and a decrease in sMICB production in PANC-1 cells. The mRNA levels of MICB did not change following PANC-1 exposure to gemcitabine. Further study suggests that the suppressive effect of gemcitabine on MICB shedding in PANC-1 cells is mediated by ADAM15 downregulation. In conclusion, the results of the present study support the hypothesis that ADAM15 is involved in MICB shedding of PANC-1 cells and that gemcitabine inhibits MICB ectodomain shedding through the suppression of ADAM15.

Cytoskeletal confinement of CX3CL1 limits its susceptibility to proteolytic cleavage by ADAM10

PubMed Central

Wong, Harikesh S.; Jaumouillé, Valentin; Heit, Bryan; Doodnauth, Sasha A.; Patel, Sajedabanu; Huang, Yi-Wei; Grinstein, Sergio; Robinson, Lisa A.

2014-01-01

CX3CL1 is a unique chemokine that acts both as a transmembrane endothelial adhesion molecule and, upon proteolytic cleavage, a soluble chemoattractant for circulating leukocytes. The constitutive release of soluble CX3CL1 requires the interaction of its transmembrane species with the integral membrane metalloprotease ADAM10, yet the mechanisms governing this process remain elusive. Using single-particle tracking and subdiffraction imaging, we studied how ADAM10 interacts with CX3CL1. We observed that the majority of cell surface CX3CL1 diffused within restricted confinement regions structured by the cortical actin cytoskeleton. These confinement regions sequestered CX3CL1 from ADAM10, precluding their association. Disruption of the actin cytoskeleton reduced CX3CL1 confinement and increased CX3CL1–ADAM10 interactions, promoting the release of soluble chemokine. Our results demonstrate a novel role for the cytoskeleton in limiting membrane protein proteolysis, thereby regulating both cell surface levels and the release of soluble ligand. PMID:25253723

GLASS VISCOSITY AS A FUNCTION OF TEMPERATURE AND COMPOSITION: A MODEL BASED ON ADAM-GIBBS EQUATION

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

Hrma, Pavel R.

2008-07-01

Within the temperature range and composition region of processing and product forming, the viscosity of commercial and waste glasses spans over 12 orders of magnitude. This paper shows that a generalized Adam-Gibbs relationship reasonably approximates the real behavior of glasses with four temperature-independent parameters of which two are linear functions of the composition vector. The equation is subjected to two constraints, one requiring that the viscosity-temperature relationship approaches the Arrhenius function at high temperatures with a composition-independent pre-exponential factor and the other that the viscosity value is independent of composition at the glass-transition temperature. Several sets of constant coefficients weremore » obtained by fitting the generalized Adam-Gibbs equation to data of two glass families: float glass and Hanford waste glass. Other equations (the Vogel-Fulcher-Tammann equation, original and modified, the Avramov equation, and the Douglass-Doremus equation) were fitted to float glass data series and compared with the Adam-Gibbs equation, showing that Adam-Gibbs glass appears an excellent approximation of real glasses even as compared with other candidate constitutive relations.« less

EGF promotes the shedding of soluble E-cadherin in an ADAM10-dependent manner in prostate epithelial cells.

PubMed

Grabowska, Magdalena M; Sandhu, Brindar; Day, Mark L

2012-02-01

During the progression of prostate cancer, the epithelial adhesion molecule E-cadherin is cleaved from the cell surface by ADAM15 proteolytic processing, generating an extracellular 80kDa fragment referred to as soluble E-cadherin (sE-cad). Contrary to observations in cancer, the generation of sE-cad appears to correlate with ADAM10 activity in benign prostatic epithelium. The ADAM10-specific inhibitor INCB8765 and the ADAM10 prodomain inhibit the generation of sE-cad, as well as downstream signaling and cell proliferation. Addition of EGF or amphiregulin (AREG) to these untransformed cell lines increases the amount of sE-cad shed into the conditioned media, as well as sE-cad bound to EGFR. EGF-associated shedding appears to be mediated by ADAM10 as shRNA knockdown of ADAM10 results in reduced shedding of sE-cad. To examine the physiologic role of sE-cad on benign prostatic epithelium, we treated BPH-1 and large T immortalized prostate epithelial cells (PrEC) with an sE-cad chimera comprised of the human Fc domain of IgG(1), fused to the extracellular domains of E-cadherin (Fc-Ecad). The treatment of untransformed prostate epithelial cells with Fc-Ecad resulted in phosphorylation of EGFR and downstream signaling through ERK and increased cell proliferation. Pre-treating BPH-1 and PrEC cells with cetuximab, a therapeutic monoclonal antibody against EGFR, decreased the ability of Fc-Ecad to induce EGFR phosphorylation, downstream signaling, and proliferation. These data suggest that ADAM10-generated sE-cad may have a role in EGFR signaling independent of traditional EGFR ligands. Copyright © 2011 Elsevier Inc. All rights reserved.

Ectodomain shedding of Limbic System-Associated Membrane Protein (LSAMP) by ADAM Metallopeptidases promotes neurite outgrowth in DRG neurons.

PubMed

Sanz, Ricardo L; Ferraro, Gino B; Girouard, Marie-Pier; Fournier, Alyson E

2017-08-11

IgLONs are members of the immunoglobulin superfamily of cell adhesion proteins implicated in the process of neuronal outgrowth, cell adhesion and subdomain target recognition. IgLONs form homophilic and heterophilic complexes on the cell surface that repress or promote growth depending on the neuronal population, the developmental stage and surface repertoire of IgLON family members. In the present study, we identified a metalloproteinase-dependent mechanism necessary to promote growth in embryonic dorsal root ganglion cells (DRGs). Treatment of embryonic DRG neurons with pan-metalloproteinase inhibitors, tissue inhibitor of metalloproteinase-3, or an inhibitor of ADAM Metallopeptidase Domain 10 (ADAM10) reduces outgrowth from DRG neurons indicating that metalloproteinase activity is important for outgrowth. The IgLON family members Neurotrimin (NTM) and Limbic System-Associated Membrane Protein (LSAMP) were identified as ADAM10 substrates that are shed from the cell surface of DRG neurons. Overexpression of LSAMP and NTM suppresses outgrowth from DRG neurons. Furthermore, LSAMP loss of function decreases the outgrowth sensitivity to an ADAM10 inhibitor. Together our findings support a role for ADAM-dependent shedding of cell surface LSAMP in promoting outgrowth from DRG neurons.

ADAM binding protein Eve-1 is required for ectodomain shedding of epidermal growth factor receptor ligands.

PubMed

Tanaka, Motonari; Nanba, Daisuke; Mori, Seiji; Shiba, Fumio; Ishiguro, Hiroshi; Yoshino, Koichiro; Matsuura, Nariaki; Higashiyama, Shigeki

2004-10-01

A disintegrin and metalloproteases (ADAMs) are implicated in the ectodomain shedding of epidermal growth factor receptor (EGFR) ligands in EGFR transactivation. However, the activation mechanisms of ADAMs remain elusive. To analyze the regulatory mechanisms of ADAM activation, we performed yeast two-hybrid screening using the cytoplasmic domain of ADAM12 as bait, and identified a protein that we designated Eve-1. Two cDNAs were cloned and characterized. They encode alternatively spliced isoforms of Eve-1, called Eve-1a and Eve-1b, that have four and five tandem Src homology 3 (SH3) domains in the carboxyl-terminal region, respectively, and seven proline-rich SH3 domain binding motifs in the amino-terminal region. The short forms of Eve-1, Eve-1c and Eve-1d, translated at Met-371 are human counterparts of mouse Sh3d19. Northern blot analysis demonstrated that Eve-1 is abundantly expressed in skeletal muscle and heart. Western blot analysis revealed the dominant production of Eve-1c in human cancer cell lines. Knockdown of Eve-1 by small interfering RNA in HT1080 cells reduced the shedding of proHB-EGF induced by angiotensin II and 12-O-tetradecanoylphorbol-13-acetate, as well as the shedding of pro-transforming growth factor-alpha, promphiregulin, and proepiregulin by 12-O-tetradecanoylphorbol-13-acetate, suggesting that Eve-1 plays a role in positively regulating the activity of ADAMs in the signaling of EGFR-ligand shedding.

Trestle #1, deck from above. Note Adams Ranch and Thiokol ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Trestle #1, deck from above. Note Adams Ranch and Thiokol (upper right). View to northeast - Promontory Route Railroad Trestles, S.P. Trestle 779.91, One mile southwest of junction of State Highway 83 and Blue Creek, Corinne, Box Elder County, UT

An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin.

PubMed

Lo Sardo, Valentina; Zuccato, Chiara; Gaudenzi, Germano; Vitali, Barbara; Ramos, Catarina; Tartari, Marzia; Myre, Michael A; Walker, James A; Pistocchi, Anna; Conti, Luciano; Valenza, Marta; Drung, Binia; Schmidt, Boris; Gusella, James; Zeitlin, Scott; Cotelli, Franco; Cattaneo, Elena

2012-05-01

The Huntington's disease gene product, huntingtin, is indispensable for neural tube formation, but its role is obscure. We studied neurulation in htt-null embryonic stem cells and htt-morpholino zebrafish embryos and found a previously unknown, evolutionarily recent function for this ancient protein. We found that htt was essential for homotypic interactions between neuroepithelial cells; it permitted neurulation and rosette formation by regulating metalloprotease ADAM10 activity and Ncadherin cleavage. This function was embedded in the N terminus of htt and was phenocopied by treatment of htt knockdown zebrafish with an ADAM10 inhibitor. Notably, in htt-null cells, reversion of the rosetteless phenotype occurred only with expression of evolutionarily recent htt heterologues from deuterostome organisms. Conversely, all of the heterologues that we tested, including htt from Drosophila melanogaster and Dictyostelium discoideum, exhibited anti-apoptotic activity. Thus, anti-apoptosis may have been one of htt’s ancestral function(s), but, in deuterostomes, htt evolved to acquire a unique regulatory activity for controlling neural adhesion via ADAM10-Ncadherin, with implications for brain evolution and development.

Toward Understanding Trust: A Response to Adams and Miskell

ERIC Educational Resources Information Center

Romero, Lisa S.; Mitchell, Douglas E.

2018-01-01

Purpose: Trust is a key component of successful schools. Although scholars widely agree that trust is multifaceted, there is less agreement about the number and nature of these factors. In the October 2016 issue of "Educational Administration Quarterly," C. M. Adams and Miskell (see EJ1112413) argued that their Teacher Trust of District…

The Retention of Minorities in Colorado Public Institutions of Higher Education: Fort Lewis and Adams State Colleges.

ERIC Educational Resources Information Center

Colorado State Advisory Committee to the U.S. Commission on Civil Rights, Denver.

Based on background research, interviews, and a public hearing held in Durango (Colorado) in March 1993, this report addresses issues regarding minority retention at Fort Lewis College in Durango and, to a lesser extent, at Adams State College in Alamosa. Due to limited information about Adams State College, none of the recommendations address…

Adam M. Reid: APA/APAGS Award for Distinguished Graduate Student in Professional Psychology.

PubMed

2015-11-01

The APA/APAGS Award for Distinguished Graduate Student in Professional Psychology is awarded on an annual basis by the APA Board of Professional Affairs (BPA) and the American Psychological Association of Graduate Students (APAGS) to a graduate student who has demonstrated outstanding practice and application of psychology. One of the 2015 award winners is Adam M. Reid, who received this award "for his community service, in which he has integrated the highest standards of professional psychological clinical practice and science." Adam's award citation, biography, and a selected bibliography are presented here. (c) 2015 APA, all rights reserved).

Empathy's purity, sympathy's complexities; De Waal, Darwin and Adam Smith.

PubMed

van der Weele, Cor

2011-07-01

Frans de Waal's view that empathy is at the basis of morality directly seems to build on Darwin, who considered sympathy as the crucial instinct. Yet when we look closer, their understanding of the central social instinct differs considerably. De Waal sees our deeply ingrained tendency to sympathize (or rather: empathize) with others as the good side of our morally dualistic nature. For Darwin, sympathizing was not the whole story of the "workings of sympathy"; the (selfish) need to receive sympathy played just as central a role in the complex roads from sympathy to morality. Darwin's understanding of sympathy stems from Adam Smith, who argued that the presence of morally impure motives should not be a reason for cynicism about morality. I suggest that De Waal's approach could benefit from a more thorough alignment with the analysis of the workings of sympathy in the work of Darwin and Adam Smith.

ADAM: analysis of discrete models of biological systems using computer algebra.

PubMed

Hinkelmann, Franziska; Brandon, Madison; Guang, Bonny; McNeill, Rustin; Blekherman, Grigoriy; Veliz-Cuba, Alan; Laubenbacher, Reinhard

2011-07-20

Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on mathematical algorithms as a web

ADAM: Analysis of Discrete Models of Biological Systems Using Computer Algebra

PubMed Central

2011-01-01

Background Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. Results We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Conclusions Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on

Decks of Trestle #2 (foreground) and Trestle #1. Note Adams ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Decks of Trestle #2 (foreground) and Trestle #1. Note Adams Ranch and Thiokol (upper right). View to northeast - Promontory Route Railroad Trestles, S.P. Trestle 779.91, One mile southwest of junction of State Highway 83 and Blue Creek, Corinne, Box Elder County, UT

Translocation of the cytoplasmic domain of ADAM13 to the nucleus is essential for Calpain-8 expression and cranial neural crest cell migration

PubMed Central

Cousin, Hélène; Abbruzzese, Genevieve; Kerdavid, Erin; Gaultier, Alban; Alfandari, Dominique

2011-01-01

Summary ADAMs are transmembrane metalloproteases that control cell behavior by cleaving both cell adhesion and signaling molecules. The cytoplasmic domain of ADAMs can regulate the proteolytic activity by controlling the subcellular localization and/or the activation of the protease domain. Here we show that the cytoplasmic domain of ADAM13 is cleaved and translocates into the nucleus. Preventing this translocation renders the protein incapable of promoting cranial neural crest (CNC) cell migration in vivo, without affecting its proteolytic activity. In addition, the cytoplasmic domain of ADAM13 regulates the expression of multiple genes in CNC, including the protease Calpain8-a. Restoring the expression of Calpain8-a is sufficient to rescue CNC migration in the absence of the ADAM13 cytoplasmic domain. This study shows that the cytoplasmic domain of ADAM metalloproteases can perform essential functions in the nucleus of cells and may contribute substantially to the overall function of the protein. PMID:21316592

Sensitization of cerebral tissue in nude mice with photodynamic therapy induces ADAM17/TACE and promotes glioma cell invasion

PubMed Central

Zheng, Xuguang; Jiang, Feng; Katakowski, Mark; Zhang, Xuepeng; Jiang, Hao; Zhang, Zheng Gang; Chopp, Michael

2008-01-01

In the present study, we tested the hypothesis that a mild cerebral tissue injury promotes subsequent glioma invasion via activation of the ADAM17-EGFR-PI3K-Akt pathway. Mild injury was induced by Photodynamic therapy (PDT), which employs tissue-penetrating laser light exposure following systemic administration of a tumor-localizing photosensitizer. Athymic nude mice were treated with sublethal PDT (80J/cm2 with 2mg/kg Photofrin). Hypoxic stress and ADAM17-EGFR-PI3K-Akt were measured using Western blot and immunostaining. Additional groups with/without pro-sublethal PDT were subsequently implanted with U87 glioma tumor cell. Tumor invasion and ADAM17-EGFR-PI3K-Akt pathway in tumor area were measured. After a sublethal dose of PDT, HIF-1α expression was increased by a factor of three in PDT-treated normal brain tissue compared to contralateral control brain tissue. PDT-treated brain tissue exhibited a significant increase in ADAM17, p-EGFR, p-Akt expression compared to non-treated tissue. ADAM17 positive area significantly increased from 1.78% to 10.89%. The percentage of p-EGFR and p-Akt positive cells significantly increased from 9.50% and 14.50% to 21.31% and 32.29%,respectively, PDT treatment significantly increased subsequent implanted U87 glioma cell invasion by 3.68-fold and increased ADAM17, EGFR, p-EGFR, Akt, p-Akt expression by 178%, 43.9%,152.7%, 89.6%,and 164.2%, respectively, compared to control group. Our data showed that a sublethal sensitization of cerebral tissue with PDT significantly increased U87 cell invasion in nude mice, and that glioma cell invasion is highly correlated with activation of the ADAM17-EGFR-PI3K-Akt pathway (r=0.928, 0.775, 0.870, 0.872, and 0.883, respectively), most likely via HIF-1α. PMID:18358600

Problems with McAdams and Pals's (2006) Proposal of a Framework for an Integrative Theory of Personality

ERIC Educational Resources Information Center

Epstein, Seymour

2007-01-01

Comments on the original article "A New Big Five: Fundamental Principles for an Integrative Science of Personality," by Dan P. McAdams and Jennifer L. Pals (see record 2006-03947-002). Here, the current author begins with a critique of McAdams and Pals's (April 2006) five principles for a framework for an integrative theory of personality. The…

An ADAM12 and FAK positive feedback loop amplifies the interaction signal of tumor cells with extracellular matrix to promote esophageal cancer metastasis.

PubMed

Luo, Man-Li; Zhou, Zhuan; Sun, Lichao; Yu, Long; Sun, Lixin; Liu, Jun; Yang, Zhihua; Ran, Yuliang; Yao, Yandan; Hu, Hai

2018-05-28

Esophageal squamous cell carcinomas (ESCCs) have a poor prognosis mostly due to early metastasis. To explore the early event of metastasis in ESCC, we established an in vitro selection model to mimic the interaction of tumor cells with extracellular matrix, through which a sub-line of ESCC cells with high invasive ability was generated. By comparing the gene expression profile of the highly invasive sub-line to that of the parental cells, ADAM12-L was identified as a candidate gene promoting ESCC cell invasion. Immunohistochemistry revealed that the ADAM12-L was overexpressed in human ESCC tissues, especially at cancer invasive edge, and ADAM12-L overexpression tightly correlated with increased metastasis and poor outcome of ESCC patients. Indeed, ADAM12-L knockdown reduced the invasion and metastasis of ESCC cells both in vitro and in vivo. Furthermore, we demonstrated that ADAM12-L participated in focal adhesion turnover and promoted the activation of focal adhesion kinase (FAK), which in turn increased ADAM12-L transcription through FAK/JNK/c-Jun axis. Therefore, a loop initiated from the cancer cell upon the engagement with extracellular matrix through FAK and c-Jun to enhance ADAM12-L expression is established, leading to the positive feedback of further FAK activation and prompting metastasis. Our study indicates that overexpression of ADAM12-L can serve as a precision marker to determine the activation of this loop. Targeting ADAM12-L to disrupt this positive feedback loop represents a promising strategy to treat the metastasis of esophageal cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

Branding campaign: Emory Healthcare, Adam Arkin, promote hospital as destination.

PubMed

2006-01-01

Popular actor Adam Arkin (Chicago Hope, Commander in Chief) teamed up with Emory Healthcare-an 800-bed, three-hospital health system located in Atlanta-to promote the hospital's cardiology and oncology services, and to brand the facility as a destination hospital that's free of stress and hassle.

Endothelial deletion of ADAM17 in mice results in defective remodeling of the semilunar valves and cardiac dysfunction in adults.

PubMed

Wilson, Carole L; Gough, Peter J; Chang, Cindy A; Chan, Christina K; Frey, Jeremy M; Liu, Yonggang; Braun, Kathleen R; Chin, Michael T; Wight, Thomas N; Raines, Elaine W

2013-01-01

Global inactivation of the metalloproteinase ADAM17 during mouse development results in perinatal lethality and abnormalities of the heart, including late embryonic cardiomegaly and thickened semilunar and atrioventricular valves. These defects have been attributed in part to a lack of ADAM17-mediated processing of HB-EGF, as absence of soluble HB-EGF results in similar phenotypes. Because valvular mesenchymal cells are largely derived from cardiac endothelial cells, we generated mice with a floxed Adam17 allele and crossed these animals with Tie2-Cre transgenics to focus on the role of endothelial ADAM17 in valvulogenesis. We find that although hearts from late-stage embryos with ablation of endothelial ADAM17 appear normal, an increase in valve size and cell number is evident, but only in the semilunar cusps. Unlike Hbegf(-/-) valves, ADAM17-null semilunar valves do not differ from controls in acute cell proliferation at embryonic day 14.5 (E14.5), suggesting compensatory processing of HB-EGF. However, levels of the proteoglycan versican are significantly reduced in mutant hearts early in valve remodeling (E12.5). After birth, aortic valve cusps from mutants are not only hyperplastic but also show expansion of the glycosaminoglycan-rich component, with the majority of adults exhibiting aberrant compartmentalization of versican and increased deposition of collagen. The inability of mutant outflow valve precursors to transition into fully mature cusps is associated with decreased postnatal viability, progressive cardiomegaly, and systolic dysfunction. Together, our data indicate that ADAM17 is required in valvular endothelial cells for regulating cell content as well as extracellular matrix composition and organization in semilunar valve remodeling and homeostasis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Application of the ADAMS program to deployable space truss structures

NASA Technical Reports Server (NTRS)

Calleson, R. E.

1985-01-01

The need for a computer program to perform kinematic and dynamic analyses of large truss structures while deploying from a packaged configuration in space led to the evaluation of several existing programs. ADAMS (automatic dynamic analysis of mechanical systems), a generalized program from performing the dynamic simulation of mechanical systems undergoing large displacements, is applied to two concepts of deployable space antenna units. One concept is a one cube folding unit of Martin Marietta's Box Truss Antenna and the other is a tetrahedral truss unit of a Tetrahedral Truss Antenna. Adequate evaluation of dynamic forces during member latch-up into the deployed configuration is not yet available from the present version of ADAMS since it is limited to the assembly of rigid bodies. Included is a method for estimating the maximum bending stress in a surface member at latch-up. Results include member displacement and velocity responses during extension and an example of member bending stresses at latch-up.

3. Aerial view southeast, State Route 92 bottom left, Adams ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. Aerial view southeast, State Route 92 bottom left, Adams Dam Road center, Brandywine Creek State Park and J. Chandler Farm in center left, duck pond bottom right and reservoir bottom left. - Winterthur Farms, Intersection State Routes 92 & 100, Intersection State Routes 92 & 100, Winterthur, New Castle County, DE

Cost-effectiveness of Project ADAM: a project to prevent sudden cardiac death in high school students.

PubMed

Berger, S; Whitstone, B N; Frisbee, S J; Miner, J T; Dhala, A; Pirrallo, R G; Utech, L M; Sachdeva, R C

2004-01-01

Public access defibrillation (PAD) in the adult population is thought to be both efficacious and cost-effective. Similar programs aimed at children and adolescents have not been evaluated for their cost-effectiveness. This study evaluates the potential cost-effectiveness of implementing Project ADAM, a program targeting children and adolescents in high schools in the Milwaukee Public School System. Project ADAM provides education about cardiopulmonary resuscitation (CPR) and the warning signs of sudden cardiac death (SCD) and training in the use and placement of automated external defibrillators (AEDs) in high schools. We developed decision analysis models to evaluate the cost-effectiveness of the decision to implement Project ADAM in public high schools in Milwaukee. We examined clinical model and public policy applications. Data on costs included estimates of hospital-based charges derived from a pediatric medical center where a series of patients were treated for SCD, educational programming, and the direct costs of one AED and training for 15 personnel per school. We performed sensitivity analyses to assess the variation in outputs with respect to changes to input data. The main outcome measures were Life years saved and incremental cost-effectiveness ratios. At an arbitrary societal willingness to pay $100,000 per life year saved, the policy to implement Project ADAM in schools is a cost-effective strategy at a threshold of approximately 5 patients over 5 years for the clinical model and approximately 8 patients over 5 years for the public policy model. Implementation of Project ADAM in high schools in the United States is potentially associated with an incremental cost-effectiveness ratio that is favorable.

Deficiency of a Disintegrin and Metalloproteinase 10 (ADAM10) on dendritic cells prevents the development of type 2 immunity and IgE production

USDA-ARS?s Scientific Manuscript database

Mice in which dendritic cells (DCs)lack ADAM10 (ADAM10DC-/-) were found to have a dramatic decrease in TH2 immunity and IgE production, as measured by both lung inflammation to house dust mite (HDM) and active systemic anaphylaxis models (ASA). With HDM, the ADAM10DC-/- had significantly less airway...

Skin cancer patients profile at faculty of medicine university of North Sumatera pathology anatomy laboratory and Haji Adam Malik general hospital in the year of 2012-2015

NASA Astrophysics Data System (ADS)

Sembiring, E. K.; Delyuzar; Soekimin

2018-03-01

The most common types of skin cancer found worldwide are basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. In America, about 800,000 people suffer from skin cancer every year and 75% are basal cell carcinoma. According to WHO, around 160,000 people suffer from malignant melanoma every year and 48,000 deaths were reported every year. In Jakarta, in 2000-2009, dr. CiptoMangunkusumo Hospital (RSCM) reported 261 cases of basal cell carcinoma, followed by 69 cases of squamous cell carcinoma and 22 cases of malignant melanoma.This study was descriptive study with retrospective design and consecutive sampling method. Data consisted of age, gender, tumor location, occupation and histopathology subtype which were taken from skin cancer patients’ medical record at Faculty of Medicine University of North Sumatera Pathology Anatomy Laboratory and Haji Adam Malik General Hospital Medan in 2012-2015. Data were analyzed using SPSS program and classified based on WHO. From 92 study subjects, squamous cell carcinoma is the most common form of skin cancer which is 59 cases (64.13%), found in 48 women (52.2%), and often found between 45-47 years old (30.4%).

AVS as a GUI for ADAM

NASA Astrophysics Data System (ADS)

Terrett, D. L.

The basis of this report is 2 days spent with an AVS expert from DEC's CERN project office attempting to convert an ADAM application into an AVS module. The experiment was successful in that we succeeded in running a KAPPA application (ADD) as a module in an AVS network without modifying the applications program code in any way. We took many short cuts and it became clear that doing the job properly would be a major exercise, but we learned enough to know that the job is feasible and gained a clear idea of what the final system would look like and what it would be capable of.

[Adam hammer (1818 - 1878) - remarks on a forgotten pioneer of ether anaesthesia in obstetrics].

PubMed

Goerig, M; Streckfuss, W

2004-05-01

Adam Hammer, born in 1818, and working as a doctor for the poor since 1847 in Mannheim, was the first person in the German speaking world to use ether for pain relief during labor on February 18th 1847. He took part in the abortive April 1848 Revolution in Mannheim - a pinnacle of German liberalism and later of political radicalism, which attented to abolish the Monarchy and introduce a democratic Republic. After the revolution was put down, Hammer emigrated to the United States and settled down in St. Louis, Missouri. Remaining politically active, he joined the Republican Party, founded in 1854 and served as a military surgeon in the Union Army during the American Civil War. Even before the war, he was engaged in efforts to improve the level of medical training in America and was involved with the foundation of High Schools which offered training courses along the lines of German universities. His ideas and innovations were not introduced immediately, but had a significant impact on medical training methology later on in the US. During a visit in Europe in 1876, he was the first to diagnose a coronary thombosis as the cause of a heart attack on a live patient. The diagnosis was later confirmed by post-morten autopsy on the patient. In 1877 he returned to Germany and died one year later. The biography of Adam Hammer mirrows that of many other German-Americans whose emigration proved to be a gain for America but a loss for Germany. This story was destinated to be repeated in terrible circumstances some decades later.

"Adam of the Road" by Elizabeth Janet Gray. Literature Unit.

ERIC Educational Resources Information Center

Robbins, Mari Lu

Intended as an aid to classroom teachers, this 48-page handbook presents a literature unit based on the children's book, "Adam of the Road" by Elizabeth Janet Gray. It begins with sample lesson plans, pre-reading activities, author information, a book summary, and vocabulary lists and suggested vocabulary activities. Next, chapters of…

5. Aerial view west, Adams Dam Road bottom center, State ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. Aerial view west, Adams Dam Road bottom center, State Route 100 center, duck pond and reservoir center, State Route 100 center right, State Route 92 below center right, Brandywine Creek State Park center bottom. - Winterthur Farms, Intersection State Routes 92 & 100, Intersection State Routes 92 & 100, Winterthur, New Castle County, DE

Maternal serum ADAM12s as a marker of rare aneuploidies in the first or second trimester of pregnancy.

PubMed

Spencer, Kevin; Cowans, Nicholas J; Stamatopoulou, Anastasia

2007-12-01

To assess whether the maternal serum ADAM12s concentrations are altered in the first and second trimester of pregnancies complicated by rare aneuploides. ADAM12s was measured by a semi-automated time-resolved immunofluorometric assay in a series of 60 first-trimester cases with trisomy 13, 78 first-trimester cases with Turner's syndrome, 38 first-trimester cases with triploidy and 24 first-trimester cases with sex aneuploidy-the cases were compared with the data from 389 first-trimester controls. In the second trimester, a smaller number of 6, 7, 2 and 13 cases, respectively, were compared with the data from 341 controls. All data were expressed as multiple of the median (MoM) and corrected for maternal weight. Correlation with previously analysed markers (PAPP-A, free beta-hCG and delta NT) was performed. The first-trimester median MoM ADAM12s was significantly lower than 1.0 in all types of rare aneuploidy with the possible exception of triploidy type II. A significant positive correlation with gestational age was reported for trisomy 13 and Turner's syndrome. ADAM12s was not significantly correlated with any other first-trimester marker. In the second trimester, ADAM12s values were marginally increased in these rare aneuploidies. ADAM12s has already been shown to be a possible early first- and second-trimester marker of trisomies 21 and 18. Our data also show the possibility of levels of this marker being altered in the first and second trimester of pregnancies with rare aneuploidies. This may be a useful addition to screening strategies in the future. Copyright (c) 2007 John Wiley & Sons, Ltd.

Adam M. Grant: Award for Distinguished Scientific Early Career Contributions to Psychology.

PubMed

2011-11-01

Presents Adam M. Grant, the 2011 winner of the American Psychological Association Award for Distinguished Scientific Early Career Contributions to Psychology. "For extensive, elegant, and programmatic research on the power of relational job design in enhancing employee motivation, productivity, and satisfaction; for creative and rigorous studies documenting the profound and surprising effects of connecting employees to their impact on others; for highlighting prosocial motivation, not only extrinsic and intrinsic motivations, as a key force behind employee behavior; and for demonstrating by example the feasibility and benefits of conducting field experiments, yielding studies rich in internal validity, external validity, and practical impact. In addition to his accomplishments, Adam M. Grant is known for his generosity as a scholar, teacher, and colleague." (PsycINFO Database Record (c) 2011 APA, all rights reserved). 2011 APA, all rights reserved

Two Rival Conceptions of Vocational Education: Adam Smith and Friedrich List.

ERIC Educational Resources Information Center

Winch, Christopher

1998-01-01

Examines and discusses two views of political economy: (1) the classical model of Adam Smith; and (2) the social capitalist model associated with Friedrich List. Explores two varieties of vocational education and training that emerge from a comparison of Smith's and List's ideas. (CMK)

EGFR and ADAMs Cooperate to Regulate Shedding and Endocytic Trafficking of the Desmosomal Cadherin Desmoglein 2

PubMed Central

Klessner, Jodi L.; Desai, Bhushan V.; Amargo, Evangeline V.; Getsios, Spiro

2009-01-01

Regulation of classic cadherins plays a critical role in tissue remodeling during development and cancer; however, less attention has been paid to the importance of desmosomal cadherins. We previously showed that EGFR inhibition results in accumulation of the desmosomal cadherin, desmoglein 2 (Dsg2), at cell–cell interfaces accompanied by inhibition of matrix metalloprotease (MMP)-dependent shedding of the Dsg2 ectodomain and tyrosine phosphorylation of its cytoplasmic domain. Here, we show that EGFR inhibition stabilizes Dsg2 at intercellular junctions by interfering with its accumulation in an internalized cytoplasmic pool. Furthermore, MMP inhibition and ADAM17 RNAi, blocked shedding and depleted internalized Dsg2, but less so E-cadherin, in highly invasive SCC68 cells. ADAM9 and 15 silencing also impaired Dsg2 processing, supporting the idea that this desmosomal cadherin can be regulated by multiple ADAM family members. In contrast, ADAM10 siRNA enhanced accumulation of a 100-kDa Dsg2 cleavage product and internalized pool of Dsg2. Although both MMP and EGFR inhibition increased intercellular adhesive strength in control cells, the response to MMP-inhibition was Dsg2-dependent. These data support a role for endocytic trafficking in regulating desmosomal cadherin turnover and function and raise the possibility that internalization and regulation of desmosomal and classic cadherin function can be uncoupled mechanistically. PMID:18987342

Cytoskeletal confinement of CX3CL1 limits its susceptibility to proteolytic cleavage by ADAM10.

PubMed

Wong, Harikesh S; Jaumouillé, Valentin; Heit, Bryan; Doodnauth, Sasha A; Patel, Sajedabanu; Huang, Yi-Wei; Grinstein, Sergio; Robinson, Lisa A

2014-12-01

CX3CL1 is a unique chemokine that acts both as a transmembrane endothelial adhesion molecule and, upon proteolytic cleavage, a soluble chemoattractant for circulating leukocytes. The constitutive release of soluble CX3CL1 requires the interaction of its transmembrane species with the integral membrane metalloprotease ADAM10, yet the mechanisms governing this process remain elusive. Using single-particle tracking and subdiffraction imaging, we studied how ADAM10 interacts with CX3CL1. We observed that the majority of cell surface CX3CL1 diffused within restricted confinement regions structured by the cortical actin cytoskeleton. These confinement regions sequestered CX3CL1 from ADAM10, precluding their association. Disruption of the actin cytoskeleton reduced CX3CL1 confinement and increased CX3CL1-ADAM10 interactions, promoting the release of soluble chemokine. Our results demonstrate a novel role for the cytoskeleton in limiting membrane protein proteolysis, thereby regulating both cell surface levels and the release of soluble ligand. © 2014 Wong et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

4. Aerial view southwest, Adams Dam Road bottom left, State ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. Aerial view southwest, Adams Dam Road bottom left, State Route 100 center, back gates to Winterthur and Wilmington Country Club upper center, duck pond and reservoir bottom right and center, and State Route 92 center bottom. - Winterthur Farms, Intersection State Routes 92 & 100, Intersection State Routes 92 & 100, Winterthur, New Castle County, DE

Life, the Universe, and everything—42 fundamental questions

NASA Astrophysics Data System (ADS)

Allen, Roland E.; Lidström, Suzy

2017-01-01

In The Hitchhiker’s Guide to the Galaxy, by Douglas Adams, the Answer to the Ultimate Question of Life, the Universe, and Everything is found to be 42—but the meaning of this is left open to interpretation. We take it to mean that there are 42 fundamental questions which must be answered on the road to full enlightenment, and we attempt a first draft (or personal selection) of these ultimate questions, on topics ranging from the cosmological constant and origin of the Universe to the origin of life and consciousness.

Adam Huber of Riesenpach (1545-1613) and his Translation of the Book on Regimen within the Context of the Prague Medical Milieu.

PubMed

Zemla, Martin

2016-02-01

This paper outlines the life, work, and views of Adam Huber of Riesenpach (1545-1613). Huber was one of the personal physicians to Rudolf ii in Prague, a pharmacist, translator, pedagogue, progressive academic and chancellor at Prague University, aiming to re-establish its medical faculty. Here, I will first appraise Huber as a distinguished translator of medical books published by the prominent Prague printer Daniel Adam of Veleslavin (1546-1599) and as a scholar who helped establish Czech medical terminology, most notably through his new translation of the great Herbal of Pietro Andrea Mattioli (1501-1577), which he reworked and expanded. In the second part, the article focuses on a popular book on regimen, the De conservanda valetudine (1576) by the German humanist author and politician Heinrich Rantzau (1526-1598), translated into Czech by Huber in 1587. The text and its translation are analysed against the backdrop of the new, more specifically Paracelsian, approaches in medicine. The author's views are compared with Huber's own ideas expressed in his foreword and in several of his other texts. His distinctive emphases and views are analysed, particularly in relation to Paracelsian medicine, Renaissance (and notably Piconian) concepts of man, and astrology.

iRHOM2-dependent regulation of ADAM17 in cutaneous disease and epidermal barrier function

PubMed Central

Brooke, Matthew A.; Etheridge, Sarah L.; Kaplan, Nihal; Simpson, Charlotte; O'Toole, Edel A.; Ishida-Yamamoto, Akemi; Marches, Olivier; Getsios, Spiro; Kelsell, David P.

2014-01-01

iRHOM2 is a highly conserved, catalytically inactive member of the Rhomboid family, which has recently been shown to regulate the maturation of the multi-substrate ectodomain sheddase enzyme ADAM17 (TACE) in macrophages. Dominant iRHOM2 mutations are the cause of the inherited cutaneous and oesophageal cancer-susceptibility syndrome tylosis with oesophageal cancer (TOC), suggesting a role for this protein in epithelial cells. Here, using tissues derived from TOC patients, we demonstrate that TOC-associated mutations in iRHOM2 cause an increase in the maturation and activity of ADAM17 in epidermal keratinocytes, resulting in significantly upregulated shedding of ADAM17 substrates, including EGF-family growth factors and pro-inflammatory cytokines. This activity is accompanied by increased EGFR activity, increased desmosome processing and the presence of immature epidermal desmosomes, upregulated epidermal transglutaminase activity and heightened resistance to Staphylococcal infection in TOC keratinocytes. Many of these features are consistent with the presence of a constitutive wound-healing-like phenotype in TOC epidermis, which may shed light on a novel pathway in skin repair, regeneration and inflammation. PMID:24643277

Father Knows Best: Using Adam Smith to Teach Transactions Costs

ERIC Educational Resources Information Center

Dupont, Brandon

2014-01-01

Adam Smith's moral philosophy can be used to introduce economics students to the important idea of transactions costs. The author provides a brief background in this article to Smith's moral philosophy and connects it to the costs of transacting in a way that fits easily into the standard principles of microeconomics classroom. By doing…

SuperADAM: Upgraded polarized neutron reflectometer at the Institut Laue-Langevin

NASA Astrophysics Data System (ADS)

Devishvili, A.; Zhernenkov, K.; Dennison, A. J. C.; Toperverg, B. P.; Wolff, M.; Hjörvarsson, B.; Zabel, H.

2013-02-01

A new neutron reflectometer SuperADAM has recently been built and commissioned at the Institut Laue-Langevin, Grenoble, France. It replaces the previous neutron reflectometer ADAM. The new instrument uses a solid state polarizer/wavelength filter providing a highly polarized (up to 98.6%) monochromatic neutron flux of 8 × 104 n cm-2 s-1 with monochromatization Δλ/λ = 0.7% and angular divergence Δα = 0.2 mrad. The instrument includes both single and position sensitive detectors. The position sensitive detector allows simultaneous measurement of specular reflection and off-specular scattering. Polarization analysis for both specular reflection and off-specular scattering is achieved using either mirror analyzers or a 3He spin filter cell. High efficiency detectors, low background, and high flux provides a dynamic range of up to seven decades in reflectivity. Detailed specifications and the instrument capabilities are illustrated with examples of recently collected data in the fields of thin film magnetism and thin polymer films.

Influence of mannosylation on immunostimulating activity of adamant-1-yl tripeptide.

PubMed

Ribić, Rosana; Habjanec, Lidija; Frkanec, Ruža; Vranešić, Branka; Tomić, Srđanka

2012-07-01

The mannosylated derivative of adamant-1-yl tripeptide (D-(Ad-1-yl)Gly-L-Ala-D-isoGln) was prepared to study the effects of mannosylation on adjuvant (immunostimulating) activity. Mannosylated adamant-1-yl tripeptide (Man-OCH(2) CH(Me)CO-D-(Ad-1-yl)Gly-L-Ala-D-isoGln) is a non-pyrogenic, H(2) O-soluble, and non-toxic compound. Adjuvant activity of mannosylated adamantyl tripeptide was tested in the mouse model with ovalbumin as an antigen and in comparison to the parent tripeptide and peptidoglycan monomer (PGM, β-D-GlcNAc-(1→4)-D-MurNAc-L-Ala-D-isoGln-mesoDAP(εNH(2) )-D-Ala-D-Ala), a well-known effective adjuvant. The mannosylation of adamantyl tripeptide caused the amplification of its immunostimulating activity in such a way that it was comparable to that of PGM. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

SuperADAM: upgraded polarized neutron reflectometer at the Institut Laue-Langevin.

PubMed

Devishvili, A; Zhernenkov, K; Dennison, A J C; Toperverg, B P; Wolff, M; Hjörvarsson, B; Zabel, H

2013-02-01

A new neutron reflectometer SuperADAM has recently been built and commissioned at the Institut Laue-Langevin, Grenoble, France. It replaces the previous neutron reflectometer ADAM. The new instrument uses a solid state polarizer/wavelength filter providing a highly polarized (up to 98.6%) monochromatic neutron flux of 8 × 10(4) n cm(-2) s(-1) with monochromatization Δλ∕λ = 0.7% and angular divergence Δα = 0.2 mrad. The instrument includes both single and position sensitive detectors. The position sensitive detector allows simultaneous measurement of specular reflection and off-specular scattering. Polarization analysis for both specular reflection and off-specular scattering is achieved using either mirror analyzers or a (3)He spin filter cell. High efficiency detectors, low background, and high flux provides a dynamic range of up to seven decades in reflectivity. Detailed specifications and the instrument capabilities are illustrated with examples of recently collected data in the fields of thin film magnetism and thin polymer films.

Elevated serum CXCL16 is an independent predictor of poor survival in ovarian cancer and may reflect pro-metastatic ADAM protease activity

PubMed Central

Gooden, M J M; Wiersma, V R; Boerma, A; Leffers, N; Boezen, H M; ten Hoor, K A; Hollema, H; Walenkamp, A M E; Daemen, T; Nijman, H W; Bremer, E

2014-01-01

Background: In certain cancers, expression of CXCL16 and its receptor CXCR6 associate with lymphocyte infiltration, possibly aiding anti-tumour immune response. In other cancers, CXCL16 and CXCR6 associate with pro-metastatic activity. In the current study, we aimed to characterise the role of CXCL16, sCXCL16, and CXCR6 in ovarian cancer (OC). Methods: CXCL16/CXCR6 expression was analysed on tissue microarray containing 306 OC patient samples. Pre-treatment serum sCXCL16 was determined in 118 patients using ELISA. In vitro, (primary) OC cells were treated with an ADAM-10/ADAM-17 inhibitor (TAPI-2) and an ADAM-10-specific inhibitor (GI254023x), whereupon CXCL16 levels were evaluated on the cell membrane (immunofluorescent analysis, western blots) and in culture supernatants (ELISA). In addition, cell migration was assessed using scratch assays. Results: sCXCL16 independently predicted for poor survival (hazard ratio=2.28, 95% confidence interval=1.29–4.02, P=0.005), whereas neither CXCL16 nor CXCR6 expression correlated with survival. Further, CXCL16/CXCR6 expression and serum sCXCL16 levels did not associate with lymphocyte infiltration. In vitro inhibition of both ADAM-17 and ADAM-10, but especially the latter, decreased CXCL16 membrane shedding and strongly reduced cell migration of A2780 and cultured primary OC-derived malignant cells. Conclusions: High serum sCXCL16 is a prognostic marker for poor survival of OC patients, possibly reflecting ADAM-10 and ADAM-17 pro-metastatic activity. Therefore, serum sCXCL16 levels may be a pseudomarker that identifies patients with highly metastatic tumours. PMID:24518602

Comparing Adam Smith's Wealth of Nations to James Madison's Federalist #10.

ERIC Educational Resources Information Center

Mundell, Jean

1987-01-01

Presents a lesson which calls upon students to compare Adam Smith's WEALTH OF NATIONS to James Madison's FEDERALIST #10 to see how the ancient concept of individual rights and liberties was used to describe both economic and governmental systems. Presents questions to provide the basis for comparison. (GEA)

Autophagy regulates cisplatin-induced stemness and chemoresistance via the upregulation of CD44, ABCB1 and ADAM17 in oral squamous cell carcinoma.

PubMed

Naik, Prajna Paramita; Mukhopadhyay, Subhadip; Panda, Prashanta Kumar; Sinha, Niharika; Das, Chandan Kanta; Mishra, Rajakishore; Patil, Shankargouda; Bhutia, Sujit Kumar

2018-02-01

We inspected the relevance of CD44, ABCB1 and ADAM17 in OSCC stemness and deciphered the role of autophagy/mitophagy in regulating stemness and chemoresistance. A retrospective analysis of CD44, ABCB1 and ADAM17 with respect to the various clinico-pathological factors and their correlation was analysed in sixty OSCC samples. Furthermore, the stemness and chemoresistance were studied in resistant oral cancer cells using sphere formation assay, flow cytometry and florescence microscopy. The role of autophagy/mitophagy was investigated by transient transfection of siATG14, GFP-LC3, tF-LC3, mKeima-Red-Mito7 and Western blot analysis of autophagic and mitochondrial proteins. In OSCC, high CD44, ABCB1 and ADAM17 expressions were correlated with higher tumour grades and poor differentiation and show significant correlation in their co-expression. In vitro and OSCC tissue double labelling confirmed that CD44 + cells co-expresses ABCB1 and ADAM17. Further, cisplatin (CDDP)-resistant FaDu cells displayed stem-like features and higher CD44, ABCB1 and ADAM17 expression. Higher autophagic flux and mitophagy were observed in resistant FaDu cells as compared to parental cells, and inhibition of autophagy led to the decrease in stemness, restoration of mitochondrial proteins and reduced expression of CD44, ABCB1 and ADAM17. The CD44 + /ABCB1 + /ADAM17 + expression in OSCC is associated with stemness and chemoresistance. Further, this study highlights the involvement of mitophagy in chemoresistance and autophagic regulation of stemness in OSCC. © 2017 John Wiley & Sons Ltd.

ADAM33 polymorphisms are associated with asthma and a distinctive palm dermatoglyphic pattern

PubMed Central

XUE, WEILIN; HAN, WEI; ZHOU, ZHAO-SHAN

2013-01-01

A close correlation between asthma and palm dermatoglyphic patterns has been observed in previous studies, but the underlying genetic mechanisms have not been investigated. A disintegrin and metalloprotein-33 (ADAM33) polymorphisms are important in the development of asthma and other atopic diseases. To investigate the underlying mechanisms of the association between asthma and distinctive palm dermatoglyphic patterns, thirteen ADAM33 single-nucleotide polymorphisms (SNPs) were analyzed for the association between asthma and palm dermatoglyphic patterns in a population of 400 asthmatic patients and 200 healthy controls. Based on the results, five SNPs, rs44707 (codominant model, P=0.031; log-additive model, P=0.0084), rs2787094 (overdominant model, P=0.049), rs678881 (codominant model, P=0.028; overdominant model, P=0.0083), rs677044 (codominant model, P=0.013; log-additive model, P=0.0033) and rs512625 (dominant model, P=0.033), were associated with asthma in this population. Two SNPs, rs44707 (dominant model, P=0.042) and rs2787094 (codominant model, P=0.014; recessive model, P=0.0038), were observed in the asthma patients with the distinctive palm pattern. As rs44707 and rs2787094 are associated with asthma and a distinctive palm pattern, the data suggest that ADAM33 polymorphisms are correlated with asthma and may be the underlying genetic basis of the association between asthma and palm dermatoglyphic patterns. PMID:24141861

Expression of ADAM10, Fas, FasL and Soluble FasL in Patients with Oral Squamous Cell Carcinoma (OSCC) and their Association with Clinical-Pathological Parameters.

PubMed

Zepeda-Nuño, José Sergio; Guerrero-Velázquez, Celia; Del Toro-Arreola, Susana; Vega-Magaña, Natali; Ángeles-Sánchez, Julián; Haramati, Jesse; Pereira-Suárez, Ana L; Bueno-Topete, Miriam R

2017-04-01

ADAM10 has been implicated in the progression of various solid tumors. ADAM10 regulates the cleavage of the FasL ectodomain from the plasma membrane of different cell types, generating the soluble FasL fragment (sFasL). Currently, there are few studies in oral squamous cell carcinoma (OSCC) that correlate levels of ADAM10 and FasL in the tumor microenvironment with clinical parameters of the disease. To determine the expression of ADAM10, Fas, FasL and sFasL in patients with OSCC and its association with TNM stage. Twenty-five patients with OSCC and 25 healthy controls were included. Biopsies of tumor tissue from patients with OSCC and buccal mucosa in controls were obtained. ADAM10, Fas, and FasL were analyzed by Western blotting. sFasL was quantified by ELISA. ADAM10 and Fas decreased significantly in OSCC compared with controls. Relatedly, within the OSCC group, Fas and ADAM10 decreased in accordance with tumor disease stage; in stages I/II, as well as in tumors of smaller diameter (T1-T2), ADAM10 showed higher levels when compared to patients with T3-T4 tumors and in stage III-IV. FasL in the tumor microenvironment and serum FasL showed no significant differences between both groups. Levels of complete FasL and cleaved FasL were positively correlated in controls; this correlation is preserved in patients with tumors in early stages (I-II), but is lost in later stage (III-IV). The dysregulation of ADAM10, Fas and FasL could be useful indicators of the progression and severity of OSCC.

Extraction-Separation Performance and Dynamic Modeling of Orion Test Vehicles with Adams Simulation: 3rd Edition

NASA Technical Reports Server (NTRS)

Varela, Jose G.; Reddy, Satish; Moeller, Enrique; Anderson, Keith

2017-01-01

NASA's Orion Capsule Parachute Assembly System (CPAS) Project is now in the qualification phase of testing, and the Adams simulation has continued to evolve to model the complex dynamics experienced during the test article extraction and separation phases of flight. The ability to initiate tests near the upper altitude limit of the Orion parachute deployment envelope requires extractions from the aircraft at 35,000 ft-MSL. Engineering development phase testing of the Parachute Test Vehicle (PTV) carried by the Carriage Platform Separation System (CPSS) at altitude resulted in test support equipment hardware failures due to increased energy caused by higher true airspeeds. As a result, hardware modifications became a necessity requiring ground static testing of the textile components to be conducted and a new ground dynamic test of the extraction system to be devised. Force-displacement curves from static tests were incorporated into the Adams simulations, allowing prediction of loads, velocities and margins encountered during both flight and ground dynamic tests. The Adams simulation was then further refined by fine tuning the damping terms to match the peak loads recorded in the ground dynamic tests. The failure observed in flight testing was successfully replicated in ground testing and true safety margins of the textile components were revealed. A multi-loop energy modulator was then incorporated into the system level Adams simulation model and the effect on improving test margins be properly evaluated leading to high confidence ground verification testing of the final design solution.

Music for Elementary Teachers, Competency-Based Approach. Adams State College.

ERIC Educational Resources Information Center

Stokes, Cloyce; And Others

This is one of a series of eight Teacher Education Modules developed by Adams State College Teacher Corps Program. The goals of this module package are listed as follows: a) to introduce the intern to music for elementary school children; b) to enable interns to develop knowledge and skills of an elementary level in music; c) to enable interns to…

Back to Beginnings: Credentialism, Productivity, and Adam Smith's Division of Labour.

ERIC Educational Resources Information Center

Davis, Denis J.

1981-01-01

The foundation of factional pressures for upgrading educational credentials in the labor market is examined through a review of human capital and screening theories. The writings of Adam Smith are referenced to show that the claims of the beneficial effects of educational upgrading have been questioned for 200 years. (Author/MLW)

Helicopter magnetic and electromagnetic surveys at Mounts Adams, Baker and Rainier, Washington: implications for debris flow hazards and volcano hydrology

USGS Publications Warehouse

Finn, Carol A.; Deszcz-Pan, Maria

2011-01-01

High‐resolution helicopter magnetic and electromagnetic (HEM) data flown over the rugged, ice‐covered Mt. Adams, Mt. Baker and Mt. Rainier volcanoes (Washington), reveal the distribution of alteration, water and ice thickness essential to evaluating volcanic landslide hazards. These data, combined with geological mapping and rock property measurements, indicate the presence of appreciable thicknesses (>500 m) of water‐saturated hydrothermally altered rock west of the modern summit of Mount Rainier in the Sunset Amphitheater region and in the central core of Mount Adams north of the summit. Alteration at Mount Baker is restricted to thinner (<300 m) zones beneath Sherman Crater and the Dorr Fumarole Fields. The EM data identified water‐saturated rocks from the surface to the detection limit (100–200 m) in discreet zones at Mt. Rainier and Mt Adams and over the entire summit region at Mt. Baker. The best estimates for ice thickness are obtained over relatively low resistivity (<800 ohm‐m) ground for the main ice cap on Mt. Adams and over most of the summit of Mt. Baker. The modeled distribution of alteration, pore fluids and partial ice volumes on the volcanoes helps identify likely sources for future alteration‐related debris flows, including the Sunset Amphitheater region at Mt. Rainier, steep cliffs at the western edge of the central altered zone at Mount Adams and eastern flanks of Mt. Baker.

Development of an advanced system identification technique for comparing ADAMS analytical results with modal test data for a MICON 65/13 wind turbine

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

Bialasiewicz, J.T.

1995-07-01

This work uses the theory developed in NREL/TP--442-7110 to analyze simulated data from an ADAMS (Automated Dynamic Analysis of Mechanical Systems) model of the MICON 65/13 wind turbine. The Observer/Kalman Filter identification approach is expanded to use input-output time histories from ADAMS simulations or structural test data. A step by step outline is offered on how the tools developed in this research, can be used for validation of the ADAMS model.

[11C]SMe-ADAM, an imaging agent for the brain serotonin transporter: synthesis, pharmacological characterization and microPET studies in rats.

PubMed

Zessin, Jörg; Deuther-Conrad, Winnie; Kretzschmar, Marion; Wüst, Frank; Pawelke, Beate; Brust, Peter; Steinbach, Jörg; Bergmann, Ralf

2006-01-01

N,N-Dimethyl-2-(2-amino-4-methylthiophenylthio)benzylamine (SMe-ADAM, 1) is a highly potent and selective inhibitor of the serotonin transporter (SERT). This compound was labeled with carbon-11 by methylation of the S-desmethyl precursor 10 with [(11)C]methyl iodide to obtain the potential positron emission tomography (PET) radioligand [(11)C]SMe-ADAM. The radiochemical yield was 27 +/- 5%, and the specific radioactivity was 26-40 GBq/micromol at the end of synthesis. Ex vivo and in vivo biodistribution experiments in rats demonstrated a rapid accumulation of the radiotracer in brain regions known to be rich in SERT, such as the thalamus/hypothalamus region (3.59 +/- 0.41%ID/g at 5 min after injection). The specific uptake reached a thalamus to cerebellum ratio of 6.74 +/- 0.95 at 60 min postinjection. The [(11)C]SMe-ADAM uptake in the thalamus was significantly decreased by pretreatment with fluoxetine to 38 +/- 11% of the control value. Furthermore, no metabolites of [(11)C]SMe-ADAM could be detected in the SERT-rich regions of the rat brain. It is concluded that [(11)C]SMe-ADAM may be a suitable PET ligand for SERT imaging in the living brain.

Development of a High Fidelity Dynamic Module of the Advanced Resistive Exercise Device (ARED) Using Adams

NASA Technical Reports Server (NTRS)

Humphreys, B. T.; Thompson, W. K.; Lewandowski, B. E.; Cadwell, E. E.; Newby, N. J.; Fincke, R. S.; Sheehan, C.; Mulugeta, L.

2012-01-01

NASA's Digital Astronaut Project (DAP) implements well-vetted computational models to predict and assess spaceflight health and performance risks, and enhance countermeasure development. DAP provides expertise and computation tools to its research customers for model development, integration, or analysis. DAP is currently supporting the NASA Exercise Physiology and Countermeasures (ExPC) project by integrating their biomechanical models of specific exercise movements with dynamic models of the devices on which the exercises were performed. This presentation focuses on the development of a high fidelity dynamic module of the Advanced Resistive Exercise Device (ARED) on board the ISS. The ARED module, illustrated in the figure below, was developed using the Adams (MSC Santa Ana, California) simulation package. The Adams package provides the capabilities to perform multi rigid body, flexible body, and mixed dynamic analyses of complex mechanisms. These capabilities were applied to accurately simulate: Inertial and mass properties of the device such as the vibration isolation system (VIS) effects and other ARED components, Non-linear joint friction effects, The gas law dynamics of the vacuum cylinders and VIS components using custom written differential state equations, The ARED flywheel dynamics, including torque limiting clutch. Design data from the JSC ARED Engineering team was utilized in developing the model. This included solid modeling geometry files, component/system specifications, engineering reports and available data sets. The Adams ARED module is importable into LifeMOD (Life Modeler, Inc., San Clemente, CA) for biomechanical analyses of different resistive exercises such as squat and dead-lift. Using motion capture data from ground test subjects, the ExPC developed biomechanical exercise models in LifeMOD. The Adams ARED device module was then integrated with the exercise subject model into one integrated dynamic model. This presentation will describe the

Reliability evaluation of I-123 ADAM SPECT imaging using SPM software and AAL ROI methods

NASA Astrophysics Data System (ADS)

Yang, Bang-Hung; Tsai, Sung-Yi; Wang, Shyh-Jen; Su, Tung-Ping; Chou, Yuan-Hwa; Chen, Chia-Chieh; Chen, Jyh-Cheng

2011-08-01

The level of serotonin was regulated by serotonin transporter (SERT), which is a decisive protein in regulation of serotonin neurotransmission system. Many psychiatric disorders and therapies were also related to concentration of cerebral serotonin. I-123 ADAM was the novel radiopharmaceutical to image SERT in brain. The aim of this study was to measure reliability of SERT densities of healthy volunteers by automated anatomical labeling (AAL) method. Furthermore, we also used statistic parametric mapping (SPM) on a voxel by voxel analysis to find difference of cortex between test and retest of I-123 ADAM single photon emission computed tomography (SPECT) images.Twenty-one healthy volunteers were scanned twice with SPECT at 4 h after intravenous administration of 185 MBq of 123I-ADAM. The image matrix size was 128×128 and pixel size was 3.9 mm. All images were obtained through filtered back-projection (FBP) reconstruction algorithm. Region of interest (ROI) definition was performed based on the AAL brain template in PMOD version 2.95 software package. ROI demarcations were placed on midbrain, pons, striatum, and cerebellum. All images were spatially normalized to the SPECT MNI (Montreal Neurological Institute) templates supplied with SPM2. And each image was transformed into standard stereotactic space, which was matched to the Talairach and Tournoux atlas. Then differences across scans were statistically estimated on a voxel by voxel analysis using paired t-test (population main effect: 2 cond's, 1 scan/cond.), which was applied to compare concentration of SERT between the test and retest cerebral scans.The average of specific uptake ratio (SUR: target/cerebellum-1) of 123I-ADAM binding to SERT in midbrain was 1.78±0.27, pons was 1.21±0.53, and striatum was 0.79±0.13. The cronbach's α of intra-class correlation coefficient (ICC) was 0.92. Besides, there was also no significant statistical finding in cerebral area using SPM2 analysis. This finding might help us

ADAM: An Accident Diagnostic,Analysis and Management System - Applications to Severe Accident Simulation and Management

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

Zavisca, M.J.; Khatib-Rahbar, M.; Esmaili, H.

2002-07-01

The Accident Diagnostic, Analysis and Management (ADAM) computer code has been developed as a tool for on-line applications to accident diagnostics, simulation, management and training. ADAM's severe accident simulation capabilities incorporate a balance of mechanistic, phenomenologically based models with simple parametric approaches for elements including (but not limited to) thermal hydraulics; heat transfer; fuel heatup, meltdown, and relocation; fission product release and transport; combustible gas generation and combustion; and core-concrete interaction. The overall model is defined by a relatively coarse spatial nodalization of the reactor coolant and containment systems and is advanced explicitly in time. The result is to enablemore » much faster than real time (i.e., 100 to 1000 times faster than real time on a personal computer) applications to on-line investigations and/or accident management training. Other features of the simulation module include provision for activation of water injection, including the Engineered Safety Features, as well as other mechanisms for the assessment of accident management and recovery strategies and the evaluation of PSA success criteria. The accident diagnostics module of ADAM uses on-line access to selected plant parameters (as measured by plant sensors) to compute the thermodynamic state of the plant, and to predict various margins to safety (e.g., times to pressure vessel saturation and steam generator dryout). Rule-based logic is employed to classify the measured data as belonging to one of a number of likely scenarios based on symptoms, and a number of 'alarms' are generated to signal the state of the reactor and containment. This paper will address the features and limitations of ADAM with particular focus on accident simulation and management. (authors)« less

ADAM10 controls collagen signaling and cell migration on collagen by shedding the ectodomain of discoidin domain receptor 1 (DDR1)

PubMed Central

Shitomi, Yasuyuki; Thøgersen, Ida B.; Ito, Noriko; Leitinger, Birgit; Enghild, Jan J.; Itoh, Yoshifumi

2015-01-01

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and transmits signals from various collagens in epithelial cells. However, how DDR1–dependent signaling is regulated has not been understood. Here we report that collagen binding induces ADAM10-dependent ectodomain shedding of DDR1. DDR1 shedding is not a result of an activation of its signaling pathway, since DDR1 mutants defective in signaling were shed in an efficient manner. DDR1 and ADAM10 were found to be in a complex on the cell surface, but shedding did not occur unless collagen bound to DDR1. Using a shedding-resistant DDR1 mutant, we found that ADAM10-dependent DDR1 shedding regulates the half-life of collagen-induced phosphorylation of the receptor. Our data also revealed that ADAM10 plays an important role in regulating DDR1-mediated cell adhesion to achieve efficient cell migration on collagen matrices. PMID:25540428

The Adam Williams initiative: collaborating with community resources to improve care for traumatic brain injury.

PubMed

Bader, Mary Kay; Stutzman, Sonja E; Palmer, Sylvain; Nwagwu, Chiedozie I; Goodman, Gary; Whittaker, Margie; Olson, Daiwai M

2014-12-01

The Brain Trauma Foundation has developed treatment guidelines for the care of patients with acute traumatic brain injury. However, a method to provide broad acceptance and application of these guidelines has not been published. To describe methods for the development, funding, and continued educational efforts of the Adam Williams Initiative; the experiences from the first 10 years may serve as a template for hospitals and nurses that seek to engage in long-term quality improvement collaborations with foundations and/or industry. In 2004, the nonprofit Adam Williams Initiative was established with the goal of providing education and resources that would encourage hospitals across the United States to incorporate the Brain Trauma Foundation's guidelines into practice. Between 2004 and 2014, 37 hospitals have been funded by the Adam Williams Initiative and have had staff members participate in an immersion experience at Mission Hospital (Mission Viejo, California) during which team members received both didactic and hands-on education in the care of traumatic brain injury. Carefully cultivated relationships and relentless teamwork have contributed to successful implementation of the Brain Trauma Foundation's guidelines in US hospitals. ©2014 American Association of Critical-Care Nurses.

Deletion of admB gene encoding a fungal ADAM affects cell wall construction in Aspergillus oryzae.

PubMed

Kobayashi, Takuji; Maeda, Hiroshi; Takeuchi, Michio; Yamagata, Youhei

2017-05-01

Mammals possess a unique signaling system based on the proteolytic mechanism of a disintegrin and metalloproteinases (ADAMs) on the cell surface. We found two genes encoding ADAMs in Aspergillus oryzae and named them admA and admB. We produced admA and admB deletion strains to elucidate their biological function and clarify whether fungal ADAMs play a similar role as in mammals. The ∆admA∆admB and ∆admB strains were sensitive to cell wall-perturbing agents, congo red, and calcofluor white. Moreover, the two strains showed significantly increased weights of total alkali-soluble fractions from the mycelial cell wall compared to the control strain. Furthermore, ∆admB showed MpkA phosphorylation at lower concentration of congo red stimulation than the control strain. However, the MpkA phosphorylation level was not different between ∆admB and the control strain without the stimulation. The results indicated that A. oryzae AdmB involved in the cell wall integrity without going through the MpkA pathway.

Fractalkine shedding is mediated by p38 and the ADAM10 protease under pro-inflammatory conditions in human astrocytes.

PubMed

O'Sullivan, Sinead A; Gasparini, Fabrizio; Mir, Anis K; Dev, Kumlesh K

2016-08-22

The fractalkine (CX3CR1) ligand is expressed in astrocytes and reported to be neuroprotective. When cleaved from the membrane, soluble fractalkine (sCX3CL1) activates the receptor CX3CR1. Although somewhat controversial, CX3CR1 is reported to be expressed in neurons and microglia. The membrane-bound form of CX3CL1 additionally acts as an adhesion molecule for microglia and infiltrating white blood cells. Much research has been done on the role of fractalkine in neuronal cells; however, little is known about the regulation of the CX3CL1 ligand in astrocytes. The mechanisms involved in the up-regulation and cleavage of CX3CL1 from human astrocytes were investigated using immunocytochemistry, Q-PCR and ELISA. All statistical analysis was performed using GraphPad Prism 5. A combination of ADAM17 (TACE) and ADAM10 protease inhibitors was found to attenuate IL-1β-, TNF-α- and IFN-γ-induced sCX3CL1 levels in astrocytes. A specific ADAM10 (but not ADAM17) inhibitor also attenuated these effects, suggesting ADAM10 proteases induce release of sCX3CL1 from stimulated human astrocytes. A p38 MAPK inhibitor also attenuated the levels of sCX3CL1 upon treatment with IL-1β, TNF-α or IFN-γ. In addition, an IKKβ inhibitor significantly reduced the levels of sCX3CL1 induced by IL-1β or TNF-α in a concentration-dependent manner, suggesting a role for the NF-kB pathway. In conclusion, this study shows that the release of soluble astrocytic fractalkine is regulated by ADAM10 proteases with p38 MAPK also playing a role in the fractalkine shedding event. These findings are important for understanding the role of CX3CL1 in healthy and stimulated astrocytes and may benefit our understanding of this pathway in neuro-inflammatory and neurodegenerative diseases.

SuperADAM: Upgraded polarized neutron reflectometer at the Institut Laue-Langevin

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

Devishvili, A.; Zhernenkov, K.; Institut Laue-Langevin, BP 156, 38042 Grenoble

2013-02-15

A new neutron reflectometer SuperADAM has recently been built and commissioned at the Institut Laue-Langevin, Grenoble, France. It replaces the previous neutron reflectometer ADAM. The new instrument uses a solid state polarizer/wavelength filter providing a highly polarized (up to 98.6%) monochromatic neutron flux of 8 Multiplication-Sign 10{sup 4} n cm{sup -2} s{sup -1} with monochromatization {Delta}{lambda}/{lambda}= 0.7% and angular divergence {Delta}{alpha}= 0.2 mrad. The instrument includes both single and position sensitive detectors. The position sensitive detector allows simultaneous measurement of specular reflection and off-specular scattering. Polarization analysis for both specular reflection and off-specular scattering is achieved using either mirror analyzersmore » or a {sup 3}He spin filter cell. High efficiency detectors, low background, and high flux provides a dynamic range of up to seven decades in reflectivity. Detailed specifications and the instrument capabilities are illustrated with examples of recently collected data in the fields of thin film magnetism and thin polymer films.« less

Award for Distinguished Scientific Early Career Contributions to Psychology: Adam K. Anderson

ERIC Educational Resources Information Center

American Psychologist, 2009

2009-01-01

Adam K. Anderson, recipient of the Award for Distinguished Scientific Early Career Contributions to Psychology, is cited for his outstanding contribution to understanding the representation of emotion and its influence on cognition. By combining psychological and neuroscience techniques with rigorous and creative experimental designs, Anderson has…

Adam Smith and the Educative Critique: A Response to My Commentators

ERIC Educational Resources Information Center

Weinstein, Jack Russell

2015-01-01

This paper is both a response to the four reviewers in a special symposium on my book Adam Smith's Pluralism and a substantive discussion of philosophy of education. In it, I introduce what I call "the educative critique," a mode of analysis similar to Marxist, feminist, or postcolonial critiques, but focusing on the educative role of a…

First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system.

PubMed

Cowans, Nicholas J; Spencer, Kevin

2007-03-01

PAPP-A is a marker used as part of the most effective method of screening for chromosomal anomalies in the first trimester. ADAM12 is a recently discovered pregnancy associated member of the ADAM (a multidomain glycoprotein metalloprotease) family. Recently, ADAM12 has been shown as a potential marker for early screening for chromosomal anomalies. Both PAPP-A and ADAM12 have been identified as proteases to insulin-like growth factor binding proteins. In this role, they may have a regulatory function in controlling the amount of free bioactive insulin-like growth factor (IGF). We therefore wish to examine if the levels of either of these proteases are related to various growth related adverse pregnancy outcomes. PAPP-A and ADAM12 were measured in a subset of samples collected at 11 to 14 weeks as part of an OSCAR clinic screening for chromosomal anomalies. Follow-up of pregnancies screened between September 1999 and August 2003 identified 1705 pregnancies with an outcome of intrauterine fetal demise on or after 24 weeks, preterm delivery at 24-34 weeks or 35-36 weeks, very low birthweight (<1.5 kg), low birthweight (<2.5 kg), large birthweight (>4.5 kg), and birth weight below the 3rd or 5th or 10th centile for gestation. A series of 414 normal outcome pregnancies constituted the control group. Marker levels were adjusted for gestation and maternal weight and the log MoM of the markers were compared using t-test of unequal variance between the control group and the various adverse outcome groups. ADAM12 and PAPP-A concentrations were reduced in low for gestational age birth weights and in all births with weights below 2.5 kg. There was a linear relationship between the severity of the IUGR and the decrease in PAPP-A and ADAM12. In the larger babies, only ADAM12 was found to be significantly increased in babies above the 90th centile of weight for gestation. The results of our study are compatible with the proposed role of ADAM12 and PAPP-A in promoting growth and

Estrogen upregulates MICA/B expression in human non-small cell lung cancer through the regulation of ADAM17.

PubMed

Ren, Jing; Nie, Yunzhong; Lv, Mingming; Shen, Sunan; Tang, Ruijing; Xu, Yujun; Hou, Yayi; Zhao, Shuli; Wang, Tingting

2015-11-01

Estrogen is involved in promoting lung cancer cell division and metastasis. MICA and MICB function as ligands for NKG2D, an important immunoreceptor expressed on natural killer (NK) cells. However, whether estrogen regulates MICA/B expression and affects tumor immune escape remains unknown. In this study, we measured the mRNA levels of MICA, MICB and ADAM17in non-small cell lung cancer (NSCLC) cell lines treated with estrogen. Surface expression of MICA/B on LTEP-a2 and A549 was detected using flow cytometry. We demonstrate that both mRNA and secretory protein levels of MICA/B in lung adenocarcinoma cell lines were upregulated by estradiol. Estradiol enhanced the expression of ADAM17, which was associated with the secretion of MICA/B. This secretion of MICA/B downregulated the NKG2D receptor on the surface of NK92 cells and impaired the cytotoxic activity of NK cells. Estradiol enhanced the expression of ADAM17, which was associated with the secretion of MICA/B. Furthermore, a significant correlation between the concentration of estradiol and the expression of MICA was found in tumor tissues of NSCLC patients. Therefore, we conclude that estrogen can regulate the expression and secretion of MICA/B through ADAM17, which helps lung cancer cells escape NKG2D-mediated immune surveillance.

The Efficiency of First-Trimester Uterine Artery Doppler, ADAM12, PAPP-A and Maternal Characteristics in the Prediction of Pre-Eclampsia

PubMed Central

GOETZINGER, Katherine R.; ZHONG, Yan; CAHILL, Alison G.; ODIBO, Linda; MACONES, George A.; ODIBO, Anthony O.

2014-01-01

Objective To estimate the efficiency of first-trimester uterine artery Doppler, A-disintegrin and metalloprotease 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A) and maternal characteristics in the prediction of pre-eclampsia. Methods This is a prospective cohort study of patients presenting for first-trimester aneuploidy screening between 11-14 weeks’ gestation. Maternal serum ADAM12 and PAPP-A levels were measured by immunoassay, and mean uterine artery Doppler pulsatility indices (PI) were calculated. Outcomes of interest included pre-eclampsia, early pre-eclampsia, defined as requiring delivery at <34 weeks’ gestation, and gestational hypertension. Logistic regression analysis was used to model the prediction of pre-eclampsia using ADAM12 multiples of the median (MoM), PAPP-A MoM, and uterine artery Doppler PI MoM, either individually or in combination. Sensitivity, specificity, and area under the receiver-operating characteristic curves (AUC) were used to compare the screening efficiency of the models using non-parametric U-statistics. Results Of 578 patients with complete outcome data, there were 54 (9.3%) cases of preeclampsia and 13 (2.2%) cases of early pre-eclampsia. Median ADAM12 levels were significantly lower in patients who developed pre-eclampsia compared to those who did not. (0.81 v. 1.01 MoMs; p<0.04) For a fixed false positive rate (FPR) of 10%, ADAM12, PAPP-A, and uterine artery Doppler in combination with maternal characteristics identified 50%, 48%, and 52% of patients who developed pre-eclampsia, respectively. Combining these first-trimester parameters did not improve the predictive efficiency of the models. Conclusion First-trimester ADAM12, PAPP-A, and uterine artery Doppler are not sufficiently predictive of pre-eclampsia. Combinations of these parameters do not further improve their screening efficiency. PMID:23980220

[Future psychologists' attitudes toward lesbians raising children together in the situation of child focused intervention].

PubMed

Wycisk, Jowita; Kleka, Pawel

2014-01-01

The aim of paper was to explore the attitudes of Polish psychology students towards lesbian mothers whose children undergo psychological intervention, in an imaginary situation of providing professional support to the child. The authors found 3 types of psychologist behaviour: contact omission (withdrawal from the intervention, mother's partner exclusion), apparent appreciation of mother's partner and authentic appreciation of mother's partner (with women comparable participation). The authors explored an interaction between these attitudes and the support for gay and lesbian rights, the origin of the child (from a previous heterosexual relationship or present, homosexual one) and demographic variables. 97 students of psychology were examined at the Adam Mickiewicz University in Poznan, using the custom survey. Respondents were most likely to include mother's partner to intervention, and the least - to avoid contact. Based on cluster analysis we found three types of attitude: unconditional acceptance, conditional acceptance, dependent on whether the child was born due in heterosexual or lesbian relationship and avoidance / rejection. The attitude of participants was associated with the declared support for gay rights, there was no correlation with gender and age. Due to the significant level of social prejudice against gays and lesbians in Poland, the issue of homosexual parenting and social functioning of gay and lesbians' children should become an area of research and scientific debate. There is a necessity ofthe introduction of this issue to the curricula of higher education and the implementation of formal, systematic training on sexual diversity for the professionals supporting families.

The design and synthesis of novel N-hydroxyformamide inhibitors of ADAM-TS4 for the treatment of osteoarthritis.

PubMed

De Savi, Chris; Pape, Andrew; Cumming, John G; Ting, Attilla; Smith, Peter D; Burrows, Jeremy N; Mills, Mark; Davies, Chris; Lamont, Scott; Milne, David; Cook, Calum; Moore, Peter; Sawyer, Yvonne; Gerhardt, Stefan

2011-03-01

Two series of N-hydroxyformamide inhibitors of ADAM-TS4 were identified from screening compounds previously synthesised as inhibitors of matrix metalloproteinase-13 (collagenase-3). Understanding of the binding mode of this class of compound using ADAM-TS1 as a structural surrogate has led to the discovery of potent and very selective inhibitors with favourable DMPK properties. Synthesis, structure-activity relationships, and strategies to improve selectivity and lower in vivo metabolic clearance are described. Copyright © 2011 Elsevier Ltd. All rights reserved.

PAR -- Interface to the ADAM Parameter System

NASA Astrophysics Data System (ADS)

Currie, Malcolm J.; Chipperfield, Alan J.

PAR is a library of Fortran subroutines that provides convenient mechanisms for applications to exchange information with the outside world, through input-output channels called parameters. Parameters enable a user to control an application's behaviour. PAR supports numeric, character, and logical parameters, and is currently implemented only on top of the ADAM parameter system. The PAR library permits parameter values to be obtained, without or with a variety of constraints. Results may be put into parameters to be passed onto other applications. Other facilities include setting a prompt string, and suggested defaults. This document also introduces a preliminary C interface for the PAR library -- this may be subject to change in the light of experience.

Adam Smith and dependency.

PubMed

Ozler, Sule

2012-06-01

The focus of this paper is the works and life of Adam Smith, who is widely recognized as the father and founder of contemporary economics. Latent content analysis is applied to his seminal text in economics, An Inquiry into the Nature and Causes of the Wealth of Nations (1776). The results reveal that Smith considers dependence on others a problem and sees the solution to this problem in impersonalized interdependence. In addition, his views on social dependency and personal dependency, reflected in his Lectures on Jurisprudence (1963) and The Theory of Moral Sentiments (1759), are analyzed. This analysis suggests a central tension between dependence and independence in Smith's writings. The personal dependency patterns he exhibited in his life, which also suggest a tension between dependence and independence, are identified through a reading of his biographies. Based on insights from psychoanalytic literature, this paper proposes that developing the ideas in the Wealth of Nations was part of Smith's creative solution to this tension. In particular, his solution to one individual's dependence on another was through a system of impersonalized interdependence. In other words, Smith defended against his personal dependence through his economic theorizing.

Adam Smith on population.

PubMed

Spengler, J J

1970-11-01

Abstract Adam Smith dealt with questions of population mainly in his Wealth of Nations. His discussion falls roughly under five heads and reflects in considerable measure his image of the English economy. (1) A country's population capacity, given the average level of consumption, was conditioned by the stock of land, the skill with which it was cultivated, and the degree to which division of labour could be increased and thereby augment output for domestic use and sale in external markets. (2) Growth of population was essentially in response to growth of the demand for labour and served to increase division of labour. (3) The social mechanisms underlying elevation of the scale of living are touched upon, and in an optimistic spirit. (4) The distribution of a country's population responded to its progress in opulence, with the rate of this progress conditioned by the degree to which inappropriate (e.g. mercantilist) policies were avoided. (5) Smith dealt briefly with such matters as colonies, education, size of economy, environmental influences, and public policy, all of which he recognized as significant for the quantity and quality of a country's numbers.

Serendipity in the Theater: Maude Adams as James M. Barrie's American Muse.

ERIC Educational Resources Information Center

Diaz de Chumaceiro, Cora L.

2003-01-01

This essay discusses how Maude Adams influenced James M. Barrie's creative process and became his inspiration. Set change theory is underscored as a cognitive explanation for Barrie's illumination. The psychoanalytic theory of transference is proposed as an underlying mechanism for facilitating the change of mental set during the incubation stage.…

[Improvement and the mechanism of cardiac function by knockdown of ADAM10 in adriamycin-induced cardiomyopathy rats].

PubMed

Li, Xiaoou; Xie, Lili; He, Bing; Huang, Wei

2018-01-01

Objective To study the role of a disintegrin and metalloproteinase10 (ADAM10) in shedding neural cadherin (N-cadherin) and develop an approach to interfere the process of ventricular remodeling in adriamycin-induced cardiomyopathy (ACM) rats. Methods In a rat model of ACM, the effects of intraperitoneal injection of the lentiviral RNAi vector of ADAM10 on the morphology of cardiomyocytes and contractile function were observed by HE staining and color Doppler echocardiography. The expressions of N-cadherin and C-terminal fragment 1 (CTF1) were detected by Western blotting and immunohistochemistry. Results In the in vivo experiment, a large amount of fluorescence was seen in the isolated primary cardiomyocytes, which indicated that the transfection in the rat model was successful. In the treatment group, the morphology of cardiomyocytes and function of the heart were evidently improved, N-cadherin protein expression was remarkably up-regulated and CTF1 protein was obviously down-regulated compared with the model group. Conclusion Knock-down of ADAM10 increases N-cadherin expression and decreases CTF1 expression, thus improves cardiac function in the rat model of ACM.

The Adam and Eve Robot Scientists for the Automated Discovery of Scientific Knowledge

NASA Astrophysics Data System (ADS)

King, Ross

A Robot Scientist is a physically implemented robotic system that applies techniques from artificial intelligence to execute cycles of automated scientific experimentation. A Robot Scientist can automatically execute cycles of hypothesis formation, selection of efficient experiments to discriminate between hypotheses, execution of experiments using laboratory automation equipment, and analysis of results. The motivation for developing Robot Scientists is to better understand science, and to make scientific research more efficient. The Robot Scientist `Adam' was the first machine to autonomously discover scientific knowledge: both form and experimentally confirm novel hypotheses. Adam worked in the domain of yeast functional genomics. The Robot Scientist `Eve' was originally developed to automate early-stage drug development, with specific application to neglected tropical disease such as malaria, African sleeping sickness, etc. We are now adapting Eve to work with on cancer. We are also teaching Eve to autonomously extract information from the scientific literature.

Evaluation of ADAM/1 model for advanced coal extraction concepts

NASA Technical Reports Server (NTRS)

Deshpande, G. K.; Gangal, M. D.

1982-01-01

Several existing computer programs for estimating life cycle cost of mining systems were evaluated. A commercially available program, ADAM/1 was found to be satisfactory in relation to the needs of the advanced coal extraction project. Two test cases were run to confirm the ability of the program to handle nonconventional mining equipment and procedures. The results were satisfactory. The model, therefore, is recommended to the project team for evaluation of their conceptual designs.

The Moral Dignity of Inductive Method and the Reconciliation of Science and Faith in Adam Sedgwick's Discourse

NASA Astrophysics Data System (ADS)

Bellon, Richard

2012-07-01

Science's inductive method required patient, humble and self-controlled behavior; Christian revelation demanded the same virtues. The discoveries of science and the truths of scripture would always harmonize as long as both men of science and men of faith conducted themselves in scrupulous accordance with their duty. So ran a central argument in A Discourse on the studies of the university (1833; 5th ed, 1850) by Adam Sedgwick (1785-1873), the longtime professor of geology at the University of Cambridge. This sanctification of the inductive method provided the foundation for a theistic science which (in theory) did not subordinate scientific theory to religious doctrine. This vision provided the foundation for Sedgwick's lifelong crusade against all forms of evolutionary theory. Evolution's impiety, he insisted, resulted from (and exacerbated) a failure to behave inductively. The fact that Sedgwick (in principle if not always in practice) elevated norms of behavior above systems of belief had an important and paradoxical consequence. Even though his personal hatred of evolution never cooled, his Discourse nonetheless provided a dominant model for younger theists to reconcile faith with Charles Darwin's evolutionary theory.

Towards the "Informed Use" of Information and Communication Technology in Education: A Response to Adams' "Powerpoint, Habits of Mind, and Classroom Culture"

ERIC Educational Resources Information Center

Vallance, Michael; Towndrow, Phillip A.

2007-01-01

PowerPoint, the widely-used slide-show software package, is finding increasing currency in lecture halls and classrooms as the preferred method of communicating and presenting information. But, as Adams [Adams, C. (2006) "PowerPoint, habits of mind, and classroom culture." "Journal of Curriculum Studies," 38(4), 389-411] attempts to show, users…

Rhetorical Studies: A Reassessment of Adam Smith's Lectures on Rhetoric and Belles Lettres.

ERIC Educational Resources Information Center

Purcell, William M.

1986-01-01

Offers a dissenting interpretation of Adam Smith's Lectures on Rhetoric and Belles Lettres and a more conservative perspective on Smith's significance to the history of rhetorical theory. Views the lectures as an historical commentary on literature and rhetoric from the perspective of an eighteenth-century lecturer. (JD)

Genetic variants of ADAM33 are associated with asthma susceptibility in the Punjabi population of Pakistan.

PubMed

Sabar, Muhammad Farooq; Ghani, Muhammad Usman; Shahid, Mariam; Sumrin, Aleena; Ali, Amjad; Akram, Muhammad; Tariq, Muhammad Akram; Bano, Iqbal

2016-01-01

A disintegrin and metalloproteinase 33 (ADAM33) gene has been considered as an asthma susceptibility gene due to its possible role in airway remodeling, abnormal cell proliferation, and differentiation. Association of this gene with asthma has been reported in several genetic studies on various populations. The current study aims to evaluate the association of ADAM33 gene polymorphisms with the risk of asthma in the Punjabi population of Pakistan. A total of 101 asthma patients and 102 age-matched healthy controls from Lahore, a city in Punjab, were recruited. ADAM33 single nucleotide polymorphisms (SNPs) T + 1[rs2280089], T2[rs2280090], T1[rs2280091], ST + 5[rs597980], ST + 4[rs44707], S2[rs528557], Q - 1[rs612709], and F + 1[rs511898] were genotyped in both patients and controls using single base extension and capillary electrophoresis-based genetic analyzer. The basic allelic and genotypic model was analyzed for association of the SNPs with asthma using SHEsis software. Haploview software was used to calculate pairwise linkage disequilibrium (LD) among six of the genotyped SNPs. Of the 8 SNPs genotyped, only S2[rs528557] showed significant association with asthma (Allele p = 0.0189, Genotype p = 0.021). SNPs T + 1[rs2280089], T2[rs2280090], T1[rs2280091], ST + 4[rs44707], S2[rs528557], and Q - 1[rs612709] were found to be in moderate to strong LD. The significantly higher frequency of haplotype "AAGTCG" in healthy controls suggests a protective effect against asthma risk in the studied population (p = 0.0059). These findings suggest that genetic variants of ADAM33 gene may play important roles in asthma susceptibility in the Punjabi population of Pakistan.

Modeled inundation limits of potential lahars from Mount Adams in the White Salmon River Valley, Washington

USGS Publications Warehouse

Griswold, Julia P.; Pierson, Thomas C.; Bard, Joseph A.

2018-05-09

Lahars large enough to reach populated areas are a hazard at Mount Adams, a massive volcano in the southern Cascade Range of Washington State (fig. 1). It is considered to be still active and has the potential to erupt again. By definition, lahars are gravity-driven flows of water-saturated mixtures of mud and rock (plus or minus ice, wood, and other debris), which originate from volcanoes and have a variety of potential triggering mechanisms (Vallance, 2000; Vallance and Iverson, 2015). Flowing mixtures can range in fluid consistency from something like a milkshake to something more like wet concrete, and they behave like flash floods, in that they can appear suddenly in river channels with little warning and commonly have boulder- or log-choked flow fronts. Lahars are hazardous because they can flow rapidly in confined valleys (commonly 20–35 miles per hour [mph] or 9–16 meters per second [m/s]), can travel more than 100 miles (mi) (161 kilometers [km]) from a source volcano, and can move with incredible destructive force, carrying multi-ton boulders and logs that can act as battering rams (Pierson, 1998). The biggest threats from lahars to downstream communities are present during eruptive activity, and impacts to communities can be dire. For example, a very large eruption-triggered lahar in Colombia in 1985 surprised and killed more than 20,000 people in a large town located about 45 mi (72 km) downstream and out of sight of the volcano that produced it (Pierson and others, 1990).Mount Adams, one of the largest volcanoes in the Cascade Range, is a composite stratocone composed primarily of andesite lava flows. It has been the most continuously active volcano within the 480-mi2 Mount Adams volcanic field—a region covering parts of Klickitat, Skamania, Yakima, andLewis Counties and part of the Yakama Nation Reservation in Washington State (Hildreth and Fierstein,1995, 1997). About 500,000 years in age, Mount Adams reached its present size by about 15

Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis.

PubMed

Gavert, Nancy; Sheffer, Michal; Raveh, Shani; Spaderna, Simone; Shtutman, Michael; Brabletz, Thomas; Barany, Francis; Paty, Phillip; Notterman, Daniel; Domany, Eytan; Ben-Ze'ev, Avri

2007-08-15

L1-CAM, a neuronal cell adhesion receptor, is also expressed in a variety of cancer cells. Recent studies identified L1-CAM as a target gene of beta-catenin-T-cell factor (TCF) signaling expressed at the invasive front of human colon cancer tissue. We found that L1-CAM expression in colon cancer cells lacking L1-CAM confers metastatic capacity, and mice injected in their spleen with such cells form liver metastases. We identified ADAM10, a metalloproteinase that cleaves the L1-CAM extracellular domain, as a novel target gene of beta-catenin-TCF signaling. ADAM10 overexpression in colon cancer cells displaying endogenous L1-CAM enhanced L1-CAM cleavage and induced liver metastasis, and ADAM10 also enhanced metastasis in colon cancer cells stably transfected with L1-CAM. DNA microarray analysis of genes induced by L1-CAM in colon cancer cells identified a cluster of genes also elevated in a large set of human colon carcinoma tissue samples. Expression of these genes in normal colon epithelium was low. These results indicate that there is a gene program induced by L1-CAM in colon cancer cells that is also present in colorectal cancer tissue and suggest that L1-CAM can serve as target for colon cancer therapy.

Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand–dependent terminal keratinocyte differentiation

PubMed Central

Cobzaru, Cristina; Triantafyllopoulou, Antigoni; Löffek, Stefanie; Horiuchi, Keisuke; Threadgill, David W.; Kurz, Thomas; van Rooijen, Nico; Bruckner-Tuderman, Leena

2012-01-01

ADAM17 (a disintegrin and metalloproteinase 17) is ubiquitously expressed and cleaves membrane proteins, such as epidermal growth factor receptor (EGFR) ligands, l-selectin, and TNF, from the cell surface, thus regulating responses to tissue injury and inflammation. However, little is currently known about its role in skin homeostasis. We show that mice lacking ADAM17 in keratinocytes (A17ΔKC) have a normal epidermal barrier and skin architecture at birth but develop pronounced defects in epidermal barrier integrity soon after birth and develop chronic dermatitis as adults. The dysregulated expression of epidermal differentiation proteins becomes evident 2 d after birth, followed by reduced transglutaminase (TGM) activity, transepidermal water loss, up-regulation of the proinflammatory cytokine IL-36α, and inflammatory immune cell infiltration. Activation of the EGFR was strongly reduced in A17ΔKC skin, and topical treatment of A17ΔKC mice with recombinant TGF-α significantly improved TGM activity and decreased skin inflammation. Finally, we show that mice lacking the EGFR in keratinocytes (EgfrΔKC) closely resembled A17ΔKC mice. Collectively, these results identify a previously unappreciated critical role of the ADAM17–EGFR signaling axis in maintaining the homeostasis of the postnatal epidermal barrier and suggest that this pathway could represent a good target for treatment of epidermal barrier defects. PMID:22565824

Music for Elementary Teachers; Self-Help Guide (MUS 370). Adams State College.

ERIC Educational Resources Information Center

Stokes, Cloyce

This self-help guide for the music teacher is one of a series of eight Teacher Education Modules developed by Adams State College Teacher Corps Program. The guide itself consists of 11 modules, the first five of which focus on the mathematical and scientific aspects of music--pitch, tempo, furation, time, and key. These five modules are…

Sequence-specific interaction between the disintegrin domain of mouse ADAM 3 and murine eggs: role of beta1 integrin-associated proteins CD9, CD81, and CD98.

PubMed

Takahashi, Y; Bigler, D; Ito, Y; White, J M

2001-04-01

ADAM 3 is a sperm surface glycoprotein that has been implicated in sperm-egg adhesion. Because little is known about the adhesive activity of ADAMs, we investigated the interaction of ADAM 3 disintegrin domains, made in bacteria and in insect cells, with murine eggs. Both recombinant proteins inhibited sperm-egg binding and fusion with potencies similar to that which we recently reported for the ADAM 2 disintegrin domain. Alanine scanning mutagenesis revealed a critical importance for the glutamine at position 7 of the disintegrin loop. Fluorescent beads coated with the ADAM 3 disintegrin domain bound to the egg surface. Bead binding was inhibited by an authentic, but not by a scrambled, peptide analog of the disintegrin loop. Bead binding was also inhibited by the function-blocking anti-alpha6 monoclonal antibody (mAb) GoH3, but not by a nonfunction blocking anti-alpha6 mAb, or by mAbs against either the alphav or beta3 integrin subunits. We also present evidence that in addition to the tetraspanin CD9, two other beta1-integrin-associated proteins, the tetraspanin CD81 as well as the single pass transmembrane protein CD98 are expressed on murine eggs. Antibodies to CD9 and CD98 inhibited in vitro fertilization and binding of the ADAM 3 disintegrin domain. Our findings are discussed in terms of the involvement of multiple sperm ADAMs and multiple egg beta1 integrin-associated proteins in sperm-egg binding and fusion. We propose that an egg surface "tetraspan web" facilitates fertilization and that it may do so by fostering ADAM-integrin interactions.

ADAM10 and γ-secretase regulate sensory regeneration in the avian vestibular organs.

PubMed

Warchol, Mark E; Stone, Jennifer; Barton, Matthew; Ku, Jeffrey; Veile, Rose; Daudet, Nicolas; Lovett, Michael

2017-08-01

The loss of sensory hair cells from the inner ear is a leading cause of hearing and balance disorders. The mammalian ear has a very limited ability to replace lost hair cells, but the inner ears of non-mammalian vertebrates can spontaneously regenerate hair cells after injury. Prior studies have shown that replacement hair cells are derived from epithelial supporting cells and that the differentiation of new hair cells is regulated by the Notch signaling pathway. The present study examined molecular influences on regeneration in the avian utricle, which has a particularly robust regenerative ability. Chicken utricles were placed in organotypic culture and hair cells were lesioned by application of the ototoxic antibiotic streptomycin. Cultures were then allowed to regenerate in vitro for seven days. Some specimens were treated with small molecule inhibitors of γ-secretase or ADAM10, proteases which are essential for transmission of Notch signaling. As expected, treatment with both inhibitors led to increased numbers of replacement hair cells. However, we also found that inhibition of both proteases resulted in increased regenerative proliferation. Subsequent experiments showed that inhibition of γ-secretase or ADAM10 could also trigger proliferation in undamaged utricles. To better understand these phenomena, we used RNA-Seq profiling to characterize changes in gene expression following γ-secretase inhibition. We observed expression patterns that were consistent with Notch pathway inhibition, but we also found that the utricular sensory epithelium contains numerous γ-secretase substrates that might regulate cell cycle entry and possibly supporting cell-to-hair cell conversion. Together, our data suggest multiple roles for γ-secretase and ADAM10 in vestibular hair cell regeneration. Copyright © 2017. Published by Elsevier Inc.

The LGI1–ADAM22 protein complex directs synapse maturation through regulation of PSD-95 function

PubMed Central

Lovero, Kathryn L.; Fukata, Yuko; Granger, Adam J.; Fukata, Masaki; Nicoll, Roger A.

2015-01-01

Synapse development is coordinated by a number of transmembrane and secreted proteins that come together to form synaptic organizing complexes. Whereas a variety of synaptogenic proteins have been characterized, much less is understood about the molecular networks that support the maintenance and functional maturation of nascent synapses. Here, we demonstrate that leucine-rich, glioma-inactivated protein 1 (LGI1), a secreted protein previously shown to modulate synaptic AMPA receptors, is a paracrine signal released from pre- and postsynaptic neurons that acts specifically through a disintegrin and metalloproteinase protein 22 (ADAM22) to set postsynaptic strength. We go on to describe a novel role for ADAM22 in maintaining excitatory synapses through PSD-95/Dlg1/zo-1 (PDZ) domain interactions. Finally, we show that in the absence of LGI1, the mature synapse scaffolding protein PSD-95, but not the immature synapse scaffolding protein SAP102, is unable to modulate synaptic transmission. These results indicate that LGI1 and ADAM22 form an essential synaptic organizing complex that coordinates the maturation of excitatory synapses by regulating the functional incorporation of PSD-95. PMID:26178195

[Professor Adam Nowosławski (1925-2012)--founder of the Polish School of Immunopathology].

PubMed

Madaliński, Kazimierz

2012-01-01

Professor dr med. Adam Nowosławski, has died at age of 87, on February 3, 2012, the founder of the Polish school of immunopathology, member of Polish Academy of Sciences and of Polish Academy of Art and Sciences. Professor was born on April 30, 1925 in Rzeszów (SE Poland). During the Second World War he took part in the anti-nazi resistance movement; he was the soldier of the 'Baszta' regiment of the Home Army. Subsequently, he was imprisoned in the Pawiak and concentration camps: Majdanek and Buchenwald. The medical studies he has completed at Warsaw Medical Academy between 1946-1951. The degree of doctor of medicine Prof. Adam Nowosławski has obtained in 1963, habilitation degree in the field of immunopathology--in 1966; the title of Professor he has obtained in 1980. His scientific achievements consist of 170 publications, including 101 original papers. His publications were quoted in several American books for students and physicians. Topics of his early papers concerned the immunopatogenesis ofPneumocystis carinii--induced pneumonia in premature babies, immunopatogenesis of rheumatoid arthritis, and the origin of rheumatoid factor. The enormous role in the field of hepatology played research on the virus of hepatitis B. These studies dealt with the discovery of HB core antigen which had the cellular localization different from HB surface antigen and with the parameters of the immune response to infection. Papers published on this topic were the mostly quoted in the literature and earned him national awards. The activity of Prof. Adam Nowosławski in the field of HIV/AIDS prevention was honored by the special prize of the Minister of Health. Professor was the honorary member of the two Societies: Polish Society of Pathologists and Polish Society of Hepatology. He was also the member of International Association for the Study of the Liver and International Academy of Pathology. Prof. Adam Nowosławski received the national medals: Polonia Restituta Crosses

N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)-benzylamine (4-(18)F-ADAM): an improved PET radioligand for serotonin transporters.

PubMed

Shiue, Grace G; Choi, Seok-Rye; Fang, Ping; Hou, Catherine; Acton, Paul D; Cardi, Chris; Saffer, Janet R; Greenberg, Joel H; Karp, Joel S; Kung, Hank F; Shiue, Chyng-Yann

2003-12-01

There has been considerable interest in the development of PET radioligands that are useful for imaging serotonin transporter (SERT) in the living human brain. For the last decade, (11)C-(+)McN5652 has been the most promising PET agent for studying SERT in humans. However, this agent has some limitations. Recently, a new promising SERT PET radioligand, 3-(11)C-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile, has been reported. We recently reported the synthesis of a new (18)F-labeled SERT PET radioligand, N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)benzylamine (4-(18)F-ADAM), which may have advantages over (11)C-labeled radioligands. The purpose of this study was to evaluate this newly developed (18)F-labeled PET radioligand as a promising agent for studying SERT in the living human brain. This agent was evaluated by studying its in vitro binding to different monoamine transporters, its in vivo biodistributions in rats, its integrity and pharmacologic profiles in rat brain, and its distribution in a female baboon brain. In vitro binding assays showed that 4-F-ADAM displayed high affinity to SERT sites (inhibition constant = 0.081 nmol/L, using membrane preparations of LLC-PK1 cells expressing the specific transporter) and showed more than 1,000- and 28,000-fold selectivity for SERT over norepinephrine transporter and dopamine transporter, respectively. Biodistribution of 4-(18)F-ADAM in rats showed a high initial uptake and slow clearance in the brain (2.13%, 1.90%, and 0.95% injected dose per organ at 2, 30, and 60 min after intravenous injection, respectively), with the specific binding peaking at 2 h after injection (hypothalamus/cerebellum = 12.49). The uptake in blood, muscle, lung, kidney, and liver was also initially high but cleared rapidly. The radioactivity in the femur increases with time for 4-(18)F-ADAM, indicating that in vivo defluorination may occur. In vivo metabolism studies in rats showed that 4-(18)F-ADAM was not metabolized in

TACE/ADAM17 is essential for oligodendrocyte development and CNS myelination.

PubMed

Palazuelos, Javier; Crawford, Howard C; Klingener, Michael; Sun, Bingru; Karelis, Jason; Raines, Elaine W; Aguirre, Adan

2014-09-03

Several studies have elucidated the significance of a disintegrin and metalloproteinase proteins (ADAMs) in PNS myelination, but there is no evidence if they also play a role in oligodendrogenesis and CNS myelination. Our study identifies ADAM17, also called tumor necrosis factor-α converting enzyme (TACE), as a novel key modulator of oligodendrocyte (OL) development and CNS myelination. Genetic deletion of TACE in oligodendrocyte progenitor cells (OPs) induces premature cell cycle exit and reduces OL cell survival during postnatal myelination of the subcortical white matter (SCWM). These cellular and molecular changes lead to deficits in SCWM myelination and motor behavior. Mechanistically, TACE regulates oligodendrogenesis by modulating the shedding of EGFR ligands TGFα and HB-EGF and, consequently, EGFR signaling activation in OL lineage cells. Constitutive TACE depletion in OPs in vivo leads to similar alterations in CNS myelination and motor behavior as to what is observed in the EGFR hypofunctional mouse line EgfrWa2. EGFR overexpression in TACE-deficient OPs restores OL survival and development. Our study reveals an essential function of TACE in oligodendrogenesis, and demonstrates how this molecule modulates EGFR signaling activation to regulate postnatal CNS myelination. Copyright © 2014 the authors 0270-6474/14/3411884-13$15.00/0.

Rival ecologies of global commerce: Adam Smith and the natural historians.

PubMed

Jonsson, Fredrik Albritton

2010-01-01

This essay explores how the defense of global commerce pioneered in the Enlightenment was tied to the improvement of the natural order. Two rival ecologies, one made by natural historians and the other developed by Adam Smith and his liberal successors, vied for intellectual precedence as well as for practical application in the metropole and the colonies. Together they constitute the beginnings of an ongoing quarrel over the environmental foundation of capitalism.

Detrital zircon geochronology of the Adams Argillite and Nation River Formation, east-central Alaska, U.S.A

USGS Publications Warehouse

Gehrels, G.E.; Johnsson, M.J.; Howell, D.G.

1999-01-01

The Cambrian Adams Argillite and the Devonian Nation River Formation are two sandstone-bearing units within a remarkably complete Paleozoic stratigraphic section in east-central Alaska. These strata, now foreshortened and fault-bounded, were originally contiguous with miogeoclinal strata to the east that formed as a passive-margin sequence along the northwestern margin of the North American continent. Seventy-five detrital zircon grains from the Adams Argillite and the Nation River Formation were analyzed in an effort to provide constraints on the original sources of the grains, and to generate a detrital zircon reference for miogeoclinal strata in the northern Cordillera. Thirty-five single zircon grains from a quartzite in the Adams Argillite yield dominant age clusters of 1047-1094 (n = 6), 1801-1868 (n = 10), and 2564-2687 (n = 5) Ma. Forty zircons extracted from a sandstone in the Nation River Formation yield clusters primarily of 424-434 (n = 6), 1815-1838 (n = 6), 1874-1921 (n = 7), and 2653-2771 (n = 4) Ma. The Early Proterozoic and Archean grains in both units probably originated in basement rocks in a broad region of the Canadian Shield. In contrast, the original igneous sources for mid-Protcrozoic grains in the Adams Argillite and ??? 430 Ma grains in the Nation River Formation are more difficult to identify. Possible original sources for the mid-Proterozoic grains include: (1) the Grenville Province of eastern Laurentia, (2) the Pearya terrane along the Arctic margin, and (3) mid-Proterozoic igneous rocks that may have been widespread along or outboard of the Cordilleran margin. The ??? 430 Ma grains may have originated in: (1) arc-type sources along the Cordilleran margin, (2) the Caledonian orogen, or (3) a landmass, such as Pearya, Siberia, or crustal fragments now in northern Asia, that resided outboard of the Innuitian orogen during mid-Paleozoic time. Copyright ?? 1999, SEPM (Society for Sedimentary Geology).

Mt, St. Helens, Mt. Adams, and Mt. Rainier, WA, USA

NASA Technical Reports Server (NTRS)

1992-01-01

This view of Mt. St. Helens (46.5N, 122.0W), taken 12 years after the volcanic eruption on 18 May 1980, in which the top 1300 ft. of the 9,677 ft. mountain was blown away, shows the rapid vegetation recovery within the blast area. Many fir trees have grown to heights of 20 ft. within the 150 square mile devastated area. Mt. Adams, an extinct volcano is just to the west and Mt. Rainier is to the north. Checkerboard logging can be seen throughout.

Mid-trimester maternal ADAM12 levels differ according to fetal gender in pregnancies complicated by preeclampsia.

PubMed

Myers, Jenny E; Thomas, Grégoire; Tuytten, Robin; Van Herrewege, Yven; Djiokep, Raoul O; Roberts, Claire T; Kenny, Louise C; Simpson, Nigel A B; North, Robyn A; Baker, Philip N

2015-02-01

An overrepresentation of adverse pregnancy outcomes has been observed in pregnancies associated with a male fetus. We investigated the association between fetal gender and candidate biomarkers for preeclampsia. Proteins were quantified in samples taken at 20 weeks from women recruited to the SCreening fOr Pregnancy Endpoints (SCOPE) study (preeclampsia n = 150; no preeclampsia n = 450). In contrast to placental growth factor, soluble endoglin, and insulin-like growth factor acid labile subunit, levels of metallopeptidase domain 12 (ADAM12) at 20 weeks were dependent on fetal gender in pregnancies complicated by preeclampsia, for male (n = 73) fetuses the multiples of the median (MoM; interquartile range [IQR] 1.1-1.5) was 1.3, whereas for female fetuses (n = 75) MoM was 1.1 (1.0-1.3); P < .01. Prediction of preeclampsia using ADAM12 levels was improved for pregnancies associated with a male fetus (area under receiver-operator curve [AUC] 0.73 [95% confidence interval [CI] 0.67-0.80]) than that of a female fetus (AUC 0.62 [0.55-0.70]); P = .03. The data presented here fit a contemporary hypothesis that there is a difference between the genders in response to an adverse maternal environment and suggest that an alteration in ADAM12 may reflect an altered placental response in pregnancies subsequently complicated by preeclampsia. © The Author(s) 2014.

Cocaine use and syphilis trends: findings from the arrestee drug abuse monitoring (ADAM) program and syphilis epidemiology in Houston.

PubMed

Ross, Michael W; Risser, Jan; Peters, Ronald J; Johnson, Regina J

2006-01-01

There has been speculation that trends in syphilis have been fueled by crack cocaine use. This study examined the data on syphilis notifications and arrestee drug abuse monitoring (ADAM) to ascertain the relationships between syphilis and cocaine use trends in three racial/ethnic groups. Syphilis notifications and data from the ADAM project were compared in Houston/Harris County, Texas, from 1991-1998 using a linear regression equation. Data indicated significant relationships between the data for cocaine use and syphilis in African Americans but not Hispanics or non-Hispanic whites. For African Americans, 58% of the variance between cocaine use and syphilis was explained. When data limited to jail syphilis notifications and ADAM cocaine in African Americans were examined, the association was stronger for males than for females. For African Americans, cocaine (probably crack cocaine) use trends were significantly associated with syphilis trends in this population. These data suggest that control of crack cocaine may have an impact on syphilis rates and that there may be close relationships between some STDs and drug abuse.

Critical Role of the Disintegrin Metalloprotease ADAM-like Decysin-1 [ADAMDEC1] for Intestinal Immunity and Inflammation.

PubMed

O'Shea, Nuala R; Chew, Thean S; Dunne, Jenny; Marnane, Rebecca; Nedjat-Shokouhi, Bahman; Smith, Philip J; Bloom, Stuart L; Smith, Andrew M; Segal, Anthony W

2016-12-01

ADAM [A Disintegrin And Metalloproteinase] is a family of peptidase proteins which have diverse roles in tissue homeostasis and immunity. Here, we study ADAM-like DECysin-1 [ADAMDEC1] a unique member of the ADAM family. ADAMDEC1 expression is restricted to the macrophage/dendritic cell populations of the gastrointestinal tract and secondary lymphoid tissue. The biological function of ADAMDEC1 is unknown but it has been hypothesised to play a role in immunity. The identification of reduced ADAMDEC1 expression in Crohn's disease patients has provided evidence of a potential role in bowel inflammation. Adamdec1 -/- mice were exposed to dextran sodium sulphate or infected orally with Citrobacter rodentium or Salmonella typhimurium. The clinical response was monitored. The loss of Adamdec1 rendered mice more susceptible to the induction of bacterial and chemical induced colitis, as evidenced by increased neutrophil infiltration, greater IL-6 and IL-1β secretion, more weight loss and increased mortality. In the absence of Adamdec1, greater numbers of Citrobacter rodentium were found in the spleen, suggestive of a breakdown in mucosal immunity which resulted in bacteraemia. In summary, ADAMDEC1 protects the bowel from chemical and bacterial insults, failure of which may predispose to Crohn's disease. © European Crohn’s and Colitis Organisation 2016.

The futility of utility: how market dynamics marginalize Adam Smith

NASA Astrophysics Data System (ADS)

McCauley, Joseph L.

2000-10-01

Economic theorizing is based on the postulated, nonempiric notion of utility. Economists assume that prices, dynamics, and market equilibria are supposed to be derived from utility. The results are supposed to represent mathematically the stabilizing action of Adam Smith's invisible hand. In deterministic excess demand dynamics I show the following. A utility function generally does not exist mathematically due to nonintegrable dynamics when production/investment are accounted for, resolving Mirowski's thesis. Price as a function of demand does not exist mathematically either. All equilibria are unstable. I then explain how deterministic chaos can be distinguished from random noise at short times. In the generalization to liquid markets and finance theory described by stochastic excess demand dynamics, I also show the following. Market price distributions cannot be rescaled to describe price movements as ‘equilibrium’ fluctuations about a systematic drift in price. Utility maximization does not describe equilibrium. Maximization of the Gibbs entropy of the observed price distribution of an asset would describe equilibrium, if equilibrium could be achieved, but equilibrium does not describe real, liquid markets (stocks, bonds, foreign exchange). There are three inconsistent definitions of equilibrium used in economics and finance, only one of which is correct. Prices in unregulated free markets are unstable against both noise and rising or falling expectations: Adam Smith's stabilizing invisible hand does not exist, either in mathematical models of liquid market data, or in real market data.

The substrate degradome of meprin metalloproteases reveals an unexpected proteolytic link between meprin β and ADAM10.

PubMed

Jefferson, Tamara; Auf dem Keller, Ulrich; Bellac, Caroline; Metz, Verena V; Broder, Claudia; Hedrich, Jana; Ohler, Anke; Maier, Wladislaw; Magdolen, Viktor; Sterchi, Erwin; Bond, Judith S; Jayakumar, Arumugam; Traupe, Heiko; Chalaris, Athena; Rose-John, Stefan; Pietrzik, Claus U; Postina, Rolf; Overall, Christopher M; Becker-Pauly, Christoph

2013-01-01

The in vivo roles of meprin metalloproteases in pathophysiological conditions remain elusive. Substrates define protease roles. Therefore, to identify natural substrates for human meprin α and β we employed TAILS (terminal amine isotopic labeling of substrates), a proteomics approach that enriches for N-terminal peptides of proteins and cleavage fragments. Of the 151 new extracellular substrates we identified, it was notable that ADAM10 (a disintegrin and metalloprotease domain-containing protein 10)-the constitutive α-secretase-is activated by meprin β through cleavage of the propeptide. To validate this cleavage event, we expressed recombinant proADAM10 and after preincubation with meprin β, this resulted in significantly elevated ADAM10 activity. Cellular expression in murine primary fibroblasts confirmed activation. Other novel substrates including extracellular matrix proteins, growth factors and inhibitors were validated by western analyses and enzyme activity assays with Edman sequencing confirming the exact cleavage sites identified by TAILS. Cleavages in vivo were confirmed by comparing wild-type and meprin(-/-) mice. Our finding of cystatin C, elafin and fetuin-A as substrates and natural inhibitors for meprins reveal new mechanisms in the regulation of protease activity important for understanding pathophysiological processes.

Working for the People? Mrs Bridges Adams and the London School Board, 1897-1904.

ERIC Educational Resources Information Center

Martin, Jane

2000-01-01

Focuses on Mrs. Bridges Adams who was a supporter of state maintenance committed to educational opportunity for workers' children. Focuses on her political recruitment, her contribution to the work of the London School Board (England), and her role in the struggle to save the school board system. (CMK)

Sequence-Specific Interaction between the Disintegrin Domain of Mouse ADAM 3 and Murine Eggs: Role of β1 Integrin-associated Proteins CD9, CD81, and CD98

PubMed Central

Takahashi, Yuji; Bigler, Dora; Ito, Yasuhiko; White, Judith M.

2001-01-01

ADAM 3 is a sperm surface glycoprotein that has been implicated in sperm-egg adhesion. Because little is known about the adhesive activity of ADAMs, we investigated the interaction of ADAM 3 disintegrin domains, made in bacteria and in insect cells, with murine eggs. Both recombinant proteins inhibited sperm-egg binding and fusion with potencies similar to that which we recently reported for the ADAM 2 disintegrin domain. Alanine scanning mutagenesis revealed a critical importance for the glutamine at position 7 of the disintegrin loop. Fluorescent beads coated with the ADAM 3 disintegrin domain bound to the egg surface. Bead binding was inhibited by an authentic, but not by a scrambled, peptide analog of the disintegrin loop. Bead binding was also inhibited by the function-blocking anti-α6 monoclonal antibody (mAb) GoH3, but not by a nonfunction blocking anti-α6 mAb, or by mAbs against either the αv or β3 integrin subunits. We also present evidence that in addition to the tetraspanin CD9, two other β1-integrin-associated proteins, the tetraspanin CD81 as well as the single pass transmembrane protein CD98 are expressed on murine eggs. Antibodies to CD9 and CD98 inhibited in vitro fertilization and binding of the ADAM 3 disintegrin domain. Our findings are discussed in terms of the involvement of multiple sperm ADAMs and multiple egg β1 integrin-associated proteins in sperm-egg binding and fusion. We propose that an egg surface “tetraspan web” facilitates fertilization and that it may do so by fostering ADAM–integrin interactions. PMID:11294888

Functional and molecular evidence for expression of the renin angiotensin system and ADAM17-mediated ACE2 shedding in COS7 cells

PubMed Central

Grobe, Nadja; Di Fulvio, Mauricio; Kashkari, Nada; Chodavarapu, Harshita; Somineni, Hari K.; Singh, Richa

2015-01-01

The renin angiotensin system (RAS) plays a vital role in the regulation of the cardiovascular and renal functions. COS7 is a robust and easily transfectable cell line derived from the kidney of the African green monkey, Cercopithecus aethiops. The aims of this study were to 1) demonstrate the presence of an endogenous and functional RAS in COS7, and 2) investigate the role of a disintegrin and metalloproteinase-17 (ADAM17) in the ectodomain shedding of angiotensin converting enzyme-2 (ACE2). Reverse transcription coupled to gene-specific polymerase chain reaction demonstrated expression of ACE, ACE2, angiotensin II type 1 receptor (AT1R), and renin at the transcript levels in total RNA cell extracts. Western blot and immunohistochemistry identified ACE (60 kDa), ACE2 (75 kDa), AT1R (43 kDa), renin (41 kDa), and ADAM17 (130 kDa) in COS7. At the functional level, a sensitive and selective mass spectrometric approach detected endogenous renin, ACE, and ACE2 activities. ANG-(1–7) formation (m/z 899) from the natural substrate ANG II (m/z 1,046) was detected in lysates and media. COS7 cells stably expressing shRNA constructs directed against endogenous ADAM17 showed reduced ACE2 shedding into the media. This is the first study demonstrating endogenous expression of the RAS and ADAM17 in the widely used COS7 cell line and its utility to study ectodomain shedding of ACE2 mediated by ADAM17 in vitro. The transfectable nature of this cell line makes it an attractive cell model for studying the molecular, functional, and pharmacological properties of the renal RAS. PMID:25740155

Dynamics of Natural and Artificial Celestial Bodies

NASA Astrophysics Data System (ADS)

Pretka-Ziomek, Halina; Wnuk, Edwin; Seidelmann, P. Kenneth; Richardson, David.

2002-01-01

This volume contains papers presented at the US/European Celestial Mechanics Workshop organized by the Astronomical Observatory of Adam Mickiewicz University in Poznan, Poland and held in Poznan, from 3 to 7 July 2000. The purpose of the workshop was to identify future research in celestial mechanics and astrometry and encourage collaboration among scientists from eastern and western countries. Also an emphasis was placed on attracting young members of the fields from around the world and encouraging them to undertake new research efforts needed for advancements in those fields. There was a full program of invited and contributed presentations on selected subjects and each day ended with a discussion period on a general subject in celestial mechanics. The discussion topics and the leaders were: Resonances and Chaos -- A. Morbidelli; Artificial Satellite Orbits -- K.T. Alfriend; Near Earth Objects -- K. Muinonen; Small Solar System Bodies -- I. Williams; and Summary -- P.K. Seidelmann. The goal of the discussions was to identify what we did not know and how we might further our knowledge. It was felt, in addition, that Poznan, Poland, with a core of scientists covering a range of ages, would provide an example of how a research and educational group could be developed elsewhere. Also, Poznan is a central location convenient to eastern and western countries. Thus, the gathering of people and the papers presented are to be the bases for building the future of astrometry and celestial mechanics. Link: http://www.wkap.nl/prod/b/1-4020-0115-0

Making Socialists: Mary Bridges Adams and the Fight for Knowledge and Power, 1855-1939

ERIC Educational Resources Information Center

Weiler, Kathleen

2012-01-01

This article presents a review of "Making socialists: Mary Bridges Adams and the fight for knowledge and power, 1855-1939," by Jane Martin. Jane Martin has explored the history of late-nineteenth-century and early-twentieth century-British women educational activists in numerous publications over the past two decades. Her first book,…

An overview of Airborne Data for Assessing Models (ADAM): a web development effort to effectively disseminate airborne data products

NASA Astrophysics Data System (ADS)

Mangosing, D. C.; Chen, G.; Kusterer, J.; Rinsland, P.; Perez, J.; Sorlie, S.; Parker, L.

2011-12-01

One of the objectives of the NASA Langley Research Center's MEaSURES project, "Creating a Unified Airborne Database for Model Assessment", is the development of airborne Earth System Data Records (ESDR) for the regional and global model assessment and validation activities performed by the tropospheric chemistry and climate modeling communities. The ongoing development of ADAM, a web site designed to access a unified, standardized and relational ESDR database, meets this objective. The ESDR database is derived from publically available data sets, from NASA airborne field studies to airborne and in-situ studies sponsored by NOAA, NSF, and numerous international partners. The ADAM web development activities provide an opportunity to highlight a growing synergy between the Airborne Science Data for Atmospheric Composition (ASD-AC) group at NASA Langley and the NASA Langley's Atmospheric Sciences Data Center (ASDC). These teams will collaborate on the ADAM web application by leveraging the state-of-the-art service and message-oriented data distribution architecture developed and implemented by ASDC and using a web-based tool provided by the ASD-AC group whose user interface accommodates the nuanced perspective of science users in the atmospheric chemistry and composition and climate modeling communities.

Neptune's Discovery: Le Verrier, Adams, and the Assignment of Credit

NASA Astrophysics Data System (ADS)

Sheehan, William

2011-01-01

As one of the most significant achievements of 19th century astronomy, the discovery of Neptune has been the subject of a vast literature. A large part of this literature--beginning with the period immediately after the optical discovery in Berlin--has been the obsession with assigning credit to the two men who attempted to calculate the planet's position (and initially this played out against the international rivalry between France and England). Le Verrier and Adams occupied much different positions in the Scientific Establishments of their respective countries; had markedly different personalities; and approached the investigation using different methods. A psychiatrist and historian of astronomy tries to provide some new contexts to the familiar story of the discovery of Neptune, and argues that the personalities of these two men played crucial roles in their approaches to the problem they set themselves and the way others reacted to their stimuli. Adams had features of high-functioning autism, while Le Verrier's domineering, obsessive, orderly personality--though it allowed him to be immensely productive--eventually led to serious difficulties with his peers (and an outright revolt). Though it took extraordinary smarts to calculate the position of Neptune, the discovery required social skills that these men lacked--and thus the process to discovery was more bumbling and adventitious than it might have been. The discovery of Neptune occurred at a moment when astronomy was changing from that of heroic individuals to team collaborations involving multiple experts, and remains an object lesson in the sociological aspects of scientific endeavor.

"ADAM' or "EVE'?--a toxicological conundrum.

PubMed

Cox, D E; Williams, K R

1996-01-12

The 3,4-methylenedioxy ring-substituted amphetamines, including "ADAM' and "EVE', are currently popular drugs of abuse. Adverse reactions are reported in the clinical literature but few fatal cases are documented and little toxicological data is available to guide those determining the cause or manner of death in such cases. We report two deaths presenting in a similar manner and with similar clinical features. Various body fluid samples were analysed for amphetamines by gas chromatography/mass spectrometry. In one case, amphetamine alone was detected at levels of 1.54 mg/l and 1.47 mg/l in postmortem blood and admission serum, respectively. The other involved several 3,4-methylenedioxy ring-substituted amphetamines, namely MDA, MDMA and MDEA, at levels of 0.25 mg/l, 0.43 mg/l and 0.3 mg/l, respectively in postmortem femoral blood and 0.24 mg/l, 0.55 mg/l and 0.49 mg/l in admission blood. The interpretation of these toxicological results and some novel legal issues are discussed.

Big huckleberry abundance as related to environment and associated vegetation near Mount Adams, Washington.

Treesearch

Don Minore; Michael E. Dubrasich

1978-01-01

Big huckleberry abundance was correlated with associated vegetation and soil pH in a 625-square-kilometer (241-square-mile) area southwest of Mount Adams, Washington. Annual berry production appeared to be influenced by weather more than by site factors in this area. Douglas-fir site index was not correlated with either Vaccinium membranaceum...

A Global Education Program for the High Schools of Adams County, Ohio. Applied Project.

ERIC Educational Resources Information Center

Yunker, Jonel Jones

This project sought to develop a global education curriculum at the secondary level by developing a rationale and support for a global education curriculum; surveying teachers at North Adams High School as to what they would like to include in the course of study that related to global education; contacting various state departments of education…

T1 polymorphism in a disintegrin and metalloproteinase 33 (ADAM33) gene may contribute to the risk of childhood asthma in Asians.

PubMed

Deng, Rui; Zhao, Fengyan; Zhong, Xiaoyun

2017-05-01

Polymorphisms in ADAM33 gene have been implicated in susceptibility to the risk of childhood asthma. However, the results remain controversial. We performed meta-analyses to clarify the relationship between them. Relevant articles were searched in PubMed, Embase, Wanfang, and China National Knowledge Infrastructure. The Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the associations. Fourteen studies with five ADAM33 polymorphisms (F + 1, T1, T2, S2, and V4) were identified, involving 2687 cases and 2996 controls. ADAM33 F + 1, T2, and T1 polymorphisms showed significant associations with asthma risks in the overall and Caucasian children, Asian children, and Caucasian and Chinese children, respectively; however, these significant results were unstable in sensitivity analysis. T1 revealed significant and stable associations with asthma risks among Asian children in the dominant (OR = 2.00, 95% CI = 1.40-2.87, P = 0.0002) and codominant (OR = 3.06, 95% CI = 1.71-5.50, P = 0.0002) models; in cumulative meta-analyses, these significant results were robust. Concerning S2 or V4 polymorphism, no significant associations were observed. These findings demonstrate that ADAM33 T1 polymorphism might be a potential susceptible predictor of asthma for Asian children. Further functional studies between this polymorphism and asthma risks are warranted.

Areca nut components stimulate ADAM17, IL-1α, PGE2 and 8-isoprostane production in oral keratinocyte: role of reactive oxygen species, EGF and JAK signaling.

PubMed

Chang, Mei-Chi; Chan, Chiu-Po; Chen, Yi-Jane; Hsien, Hsiang-Chi; Chang, Ya-Ching; Yeung, Sin-Yuet; Jeng, Po-Yuan; Cheng, Ru-Hsiu; Hahn, Liang-Jiunn; Jeng, Jiiang-Huei

2016-03-29

Betel quid (BQ) chewing is an etiologic factor of oral submucous fibrosis (OSF) and oral cancer. There are 600 million BQ chewers worldwide. The mechanisms for the toxic and inflammatory responses of BQ are unclear. In this study, both areca nut (AN) extract (ANE) and arecoline stimulated epidermal growth factor (EGF) and interleukin-1α (IL-1α) production of gingival keratinocytes (GKs), whereas only ANE can stimulate a disintegrin and metalloproteinase 17 (ADAM17), prostaglandin E2 (PGE2) and 8-isoprostane production. ANE-induced EGF production was inhibited by catalase. Addition of anti-EGF neutralizing antibody attenuated ANE-induced cyclooxygenase-2 (COX-2), mature ADAM9 expression and PGE2 and 8-isoprostane production. ANE-induced IL-1α production was inhibited by catalase, anti-EGF antibody, PD153035 (EGF receptor antagonist) and U0126 (MEK inhibitor) but not by α-naphthoflavone (cytochrome p450-1A1 inhibitor). ANE-induced ADAM17 production was inhibited by pp2 (Src inhibitor), U0126, α-naphthoflavone and aspirin. AG490 (JAK inhibitor) prevented ANE-stimulated ADAM17, IL-1α, PGE2 production, COX-2 expression, ADAM9 maturation, and the ANE-induced decline in keratin 5 and 14, but showed little effect on cdc2 expression and EGF production. Moreover, ANE-induced 8-isoprostane production by GKs was inhibited by catalase, anti-EGF antibody, AG490, pp2, U0126, α-naphthoflavone, Zinc protoporphyrin (ZnPP) and aspirin. These results indicate that AN components may involve in BQ-induced oral cancer by induction of reactive oxygen species, EGF/EGFR, IL-1α, ADAMs, JAK, Src, MEK/ERK, CYP1A1, and COX signaling pathways, and the aberration of cell cycle and differentiation. Various blockers against ROS, EGF, IL-1α, ADAM, JAK, Src, MEK, CYP1A1, and COX can be used for prevention or treatment of BQ chewing-related diseases.

ADAM17_i33708A>G polymorphism interacts with dietary n-6 polyunsaturated fatty acids to modulate obesity risk in the Genetics of Lipid Lowering Drugs and Diet Network study

PubMed Central

Junyent, Mireia; Parnell, Laurence D.; Lai, Chao-Qiang; Arnett, Donna K.; Tsai, Michael Y.; Kabagambe, Edmond K.; Straka, Robert J.; Province, Michael; An, Ping; Smith, Caren E.; Lee, Yu-Chi; Borecki, Ingrid; Ordovás, Jose M.

2015-01-01

Background and aims The disintegrin and metalloproteinase ADAM17, also known as tumor necrosis factor alpha converting enzyme, is expressed in adipocytes. Importantly, elevated levels of ADAM17 expression have been linked to obesity and insulin resistance. Therefore, the aim of this study was to evaluate the association of six ADAM17 single nucleotide polymorphisms (SNPs) (m1254A>G, i14121C>A, i33708A>G, i48827A>C, i53440C>T, and i62781G>T) with insulin-resistance phenotypes and obesity risk, and their potential interactions with dietary polyunsaturated fatty acids (PUFA). Methods and results ADAM17 SNPs were genotyped in 936 subjects (448 men/488 women) who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Anthropometrical and biochemical measurements were determined by standard procedures. PUFA intake was estimated using a validated questionnaire. G allele carriers at the ADAM17_m1254A>G polymorphism exhibited significantly higher risk of obesity (P=0.003), were shorter (P=0.017), had higher insulin (P=0.016), and lower HDL-C concentrations (P=0.027) than AA subjects. For the ADAM17_i33708A>G SNP, homozygotes for the A allele displayed higher risk of obesity (P=0.001), were heavier (P=0.011), had higher BMI (P=0.005), and higher waist measurements (P=0.023) than GG subjects. A significant gene-diet interaction was found (P=0.030), in which the deleterious association of the i33708A allele with obesity was observed in subjects with low intakes from (n-6) PUFA (P<0.001), whereas no differences in obesity risk were seen among subjects with high (n-6) PUFA intake (P>0.5) Conclusion These findings support that ADAM17 (m1254A>G and i33708A>G) SNPs may contribute to obesity risk. For the ADAM17_i33708A>G SNP, this risk may be further modulated by (n-6) PUFA intake. PMID:19819120

ADAM17_i33708A>G polymorphism interacts with dietary n-6 polyunsaturated fatty acids to modulate obesity risk in the Genetics of Lipid Lowering Drugs and Diet Network study.

PubMed

Junyent, M; Parnell, L D; Lai, C-Q; Arnett, D K; Tsai, M Y; Kabagambe, E K; Straka, R J; Province, M; An, P; Smith, C E; Lee, Y-C; Borecki, I; Ordovás, J M

2010-12-01

The disintegrin and metalloproteinase ADAM17, also known as tumor necrosis factor alpha converting enzyme, is expressed in adipocytes. Importantly, elevated levels of ADAM17 expression have been linked to obesity and insulin resistance. Therefore, the aim of this study was to evaluate the association of six ADAM17 single nucleotide polymorphisms (SNPs) (m1254A>G, i14121C>A, i33708A>G, i48827A>C, i53440C>T, and i62781G>T) with insulin-resistance phenotypes and obesity risk, and their potential interactions with dietary polyunsaturated fatty acids (PUFA). ADAM17 SNPs were genotyped in 936 subjects (448 men/488 women) who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Anthropometrical and biochemical measurements were determined by standard procedures. PUFA intake was estimated using a validated questionnaire. G allele carriers at the ADAM17_m1254A>G polymorphism exhibited significantly higher risk of obesity (P=0.003), were shorter (P=0.017), had higher insulin (P=0.016), and lower HDL-C concentrations (P=0.027) than AA subjects. For the ADAM17_i33708A>G SNP, homozygotes for the A allele displayed higher risk of obesity (P=0.001), were heavier (P=0.011), had higher BMI (P=0.005), and higher waist measurements (P=0.023) than GG subjects. A significant gene-diet interaction was found (P=0.030), in which the deleterious association of the i33708A allele with obesity was observed in subjects with low intakes from (n-6) PUFA (P<0.001), whereas no differences in obesity risk were seen among subjects with high (n-6) PUFA intake (P>0.5) These findings support that ADAM17 (m1254A>G and i33708A>G) SNPs may contribute to obesity risk. For the ADAM17_i33708A>G SNP, this risk may be further modulated by (n-6) PUFA intake. Copyright © 2009 Elsevier B.V. All rights reserved.

Blood-induced bone loss in murine hemophilic arthropathy is prevented by blocking the iRhom2/ADAM17/TNFα pathway.

PubMed

Haxaire, Coline; Hakobyan, Narine; Pannellini, Tania; Carballo, Camila; McIlwain, David; Mak, Tak W; Rodeo, Scott; Acharya, Suchitra; Li, Daniel; Szymonifka, Jackie; Song, Xiangqian; Monette, Sébastien; Srivastava, Alok; Salmon, Jane E; Blobel, Carl P

2018-05-18

Hemophilic arthropathy (HA) is a debilitating degenerative joint disease that is a major manifestation of the bleeding disorder Hemophilia A. HA typically begins with hemophilic synovitis (HS) that resembles inflammatory arthritides such as rheumatoid arthritis (RA) and frequently results in bone loss in patients. A major cause of RA is inappropriate release of the pro-inflammatory cytokine tumor necrosis factor α (TNFα) by the TNFα convertase (TACE, also referred to as ADAM17) and its regulator, iRhom2. Therefore, we hypothesized that iRhom2/ADAM17-dependent shedding of TNFα also has a pivotal role in mediating HA. Here, we show that addition of blood or its components to macrophages activates iRhom2/ADAM17-dependent TNFα shedding, providing the premise to study the activation of this pathway by blood in the joint in vivo. For this, we turned to hemophilic FVIII-deficient mice (F8-/- mice), which develop a hemarthrosis following needle puncture injury with synovial inflammation and significant osteopenia adjacent to the affected joint. We found that needle puncture-induced bleeding leads to increased TNFα levels in the affected joint of F8-/- mice. Moreover, inactivation of TNFα or iRhom2 in F8-/- mice reduced the osteopenia and synovial inflammation that develops in this mouse model for HA. Taken together, our results suggest that blood entering the joint activates the iRhom2/ADAM17/TNFα pathway, thereby contributing to osteopenia and synovitis in mice. Therefore, this pro-inflammatory signaling pathway could emerge as an attractive new target to prevent osteoporosis and joint damage in HA patients. Copyright © 2018 American Society of Hematology.

Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a.

PubMed

Khedgikar, Vikram; Abbruzzese, Genevieve; Mathavan, Ketan; Szydlo, Hannah; Cousin, Helene; Alfandari, Dominique

2017-08-22

Adam13/33 is a cell surface metalloprotease critical for cranial neural crest (CNC) cell migration. It can cleave multiple substrates including itself, fibronectin, ephrinB, cadherin-11, pcdh8 and pcdh8l (this work). Cleavage of cadherin-11 produces an extracellular fragment that promotes CNC migration. In addition, the adam13 cytoplasmic domain is cleaved by gamma secretase, translocates into the nucleus and regulates multiple genes. Here, we show that adam13 interacts with the arid3a/dril1/Bright transcription factor. This interaction promotes a proteolytic cleavage of arid3a and its translocation to the nucleus where it regulates another transcription factor: tfap2α. Tfap2α in turn activates multiple genes including the protocadherin pcdh8l (PCNS). The proteolytic activity of adam13 is critical for the release of arid3a from the plasma membrane while the cytoplasmic domain appears critical for the cleavage of arid3a. In addition to this transcriptional control of pcdh8l, adam13 cleaves pcdh8l generating an extracellular fragment that also regulates cell migration.

Fisetin suppresses ADAM9 expression and inhibits invasion of glioma cancer cells through increased phosphorylation of ERK1/2.

PubMed

Chen, Chien-Min; Hsieh, Yi-Hsien; Hwang, Jin-Ming; Jan, Hsun-Jin; Hsieh, Shu-Ching; Lin, Shin-Huey; Lai, Chung-Yu

2015-05-01

Fisetin (3,3',4',7-tetrahydroxyflavone) is a naturally occurring flavonoid which is widely distributed in plants. It has been reported to possess some anticancer and anti-invasive capabilities. We set out to explore the effects of fisetin on antimetastatic and its mechanism of action in GBM8401 cells. The results indicated that fisetin exhibited effective inhibition of cell migration and inhibited the invasion of GBM8401 cells under non-cytotoxic concentrations. To identify the potential targets of fisetin, human proteinase antibody array analysis was performed, and the results indicated that the fisetin treatment inhibited the expression of ADAM9 protein and mRNA, which are known to contribute to the progression of glioma cancer. Our results showed that fisetin phosphorylated ERK1/2 in a sustained way that contributed to the inhibited ADAM9 protein and mRNA expression determined by Western blot and RT-PCR. Moreover, inhibition of ERK1/2 by U0126 or transfection with the siERK plasmid significantly abolished the fisetin-inhibited migration and invasion through activation of the ERK1/2 pathway. In summary, our results suggest that fisetin might be a potential therapeutic agent against human glioma cells based on its capacity to activate ERK1/2 and to inhibit ADAM9 expression.

Tuberculous spondylitis in Haji Adam Malik hospital, Medan

NASA Astrophysics Data System (ADS)

Dharmajaya, R.

2018-03-01

Ankylosing tuberculosis is an infection caused by Mycobacterium tuberculosis in one or more components of the vertebrae; it is Pott disease or tuberculous spondylitis. It might become a potential cause of morbidity, including neurological deficits and permanent deformity of the spine. Management of TB Spondylitis, in general, is chemotherapy with antituberculosis drugs (ATG), immobilization, and spine surgical interventions. A retrospective study was conducted to analyze the patients of TB Spondylitis who had undergone surgery at Haji Adam Malik hospital from June 2015 to June 2017. The most common location is thoracal (10%), lumbal (3%), and thoracolumbal junction (3%). Decompression laminectomy with fusion (18%) is the most suitable option for surgical management. The majority, pre- operation ASIA scale is D (8%), and post operation is E (8%). It means that surgical plays an important role in themanagement of tuberculous spondylitis.

The "delivery" of Adam: a medical interpretation of Michelangelo.

PubMed

Di Bella, Stefano; Taglietti, Fabrizio; Iacobuzio, Andrea; Johnson, Emma; Baiocchini, Andrea; Petrosillo, Nicola

2015-04-01

This article describes what we believe to be the key to interpreting the concept represented by Michelangelo's painting the Creation of Adam. This fresco, one of his most famous masterpieces, is situated in the heart of the Sistine Chapel and is viewed by millions of people every year. A man of many talents, Michelangelo's proficiency in anatomical dissection is reflected in his artwork. As such, analyses of hidden meanings in this fresco have been ascribed, including the concept of the "Brain-God." However, we see a postpartum uterus and adjacent anatomy, justifying our interpretation that Michelangelo was depicting something far more fundamental: the birth of mankind. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Modeling and analysis of dynamic characteristics of carrier system of machining center in MSC.Adams

NASA Astrophysics Data System (ADS)

Grinek, A. V.; Rybina, A. V.; Boychuk, I. P.; Dantsevich, I. M.; Hurtasenko, A. V.

2018-03-01

The simulation model with the help of vibration analysis was developed in MSC.Adams/Vibration and experimental research of the dynamic characteristics of a five-axis machining center was carried out. The amplitude-frequency characteristics, resonant frequencies in various directions are investigated. Dynamic and static rigidity, damping intensity and the coefficient of dynamism of the center are determined.

Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a

PubMed Central

Khedgikar, Vikram; Abbruzzese, Genevieve; Mathavan, Ketan; Szydlo, Hannah; Cousin, Helene

2017-01-01

Adam13/33 is a cell surface metalloprotease critical for cranial neural crest (CNC) cell migration. It can cleave multiple substrates including itself, fibronectin, ephrinB, cadherin-11, pcdh8 and pcdh8l (this work). Cleavage of cadherin-11 produces an extracellular fragment that promotes CNC migration. In addition, the adam13 cytoplasmic domain is cleaved by gamma secretase, translocates into the nucleus and regulates multiple genes. Here, we show that adam13 interacts with the arid3a/dril1/Bright transcription factor. This interaction promotes a proteolytic cleavage of arid3a and its translocation to the nucleus where it regulates another transcription factor: tfap2α. Tfap2α in turn activates multiple genes including the protocadherin pcdh8l (PCNS). The proteolytic activity of adam13 is critical for the release of arid3a from the plasma membrane while the cytoplasmic domain appears critical for the cleavage of arid3a. In addition to this transcriptional control of pcdh8l, adam13 cleaves pcdh8l generating an extracellular fragment that also regulates cell migration. PMID:28829038

Paricalcitol modulates ACE2 shedding and renal ADAM17 in NOD mice beyond proteinuria.

PubMed

Riera, Marta; Anguiano, Lidia; Clotet, Sergi; Roca-Ho, Heleia; Rebull, Marta; Pascual, Julio; Soler, Maria Jose

2016-03-15

Circulating and renal activity of angiotensin-converting enzyme 2 (ACE2) is increased in non-obese diabetic (NOD) mice. Because paricalcitol has been reported to protect against diabetic nephropathy, we investigated the role of paricalcitol in modulating ACE2 in these mice. In addition, renal ADAM17, a metalloprotease implied in ACE2 shedding, was assessed. NOD female and non-diabetic control mice were studied for 21 days after diabetes onset and divided into various treatment groups. Diabetic animals received either vehicle; 0.4 or 0.8 μg/kg paricalcitol, aliskiren, or a combination of paricalcitol and aliskiren. We then studied the effect of paricalcitol on ACE2 expression in proximal tubular epithelial cells. Paricalcitol alone or in combination with aliskiren resulted in significantly reduced circulating ACE2 activity in NOD mice but there were no changes in urinary albumin excretion. Serum renin activity was significantly decreased in mice that received aliskiren but no effect was found when paricalcitol was used alone. Renal content of ADAM17 was significantly decreased in animals that received a high dose of paricalcitol. Renal and circulating oxidative stress (quantified by plasma H2O2 levels and immunolocalization of nitrotyrosine) were reduced in high-dose paricalcitol-treated mice compared with non-treated diabetic mice. In culture, paricalcitol incubation resulted in a significant increase in ACE2 expression compared with nontreated cells. In NOD mice with type 1 diabetes, paricalcitol modulates ACE2 activity, ADAM17, and oxidative stress renal content independently from the glycemic profile and urinary albumin excretion. In tubular cells, paricalcitol may modulate ACE2 by blocking its shedding. In the early stage of diabetic nephropathy, paricalcitol treatment counterbalances the effect of diabetes on circulating ACE2 activity. Our results suggest that additional use of paricalcitol may be beneficial in treating patients with diabetes under standard

Human colonic myocytes are involved in postischemic inflammation through ADAM17-dependent TNFα production

PubMed Central

Jarry, Anne; Bach-Ngohou, Kalyane; Masson, Damien; Dejoie, Thomas; Lehur, Paul-Antoine; Mosnier, Jean-François; Denis, Marc G; Laboisse, Christian L

2005-01-01

The aim of this study was to identify human colonic resident cells able to initiate an inflammatory response in postischemic injury. Postischemic colonic injury, a condition relevant to various clinical settings, involves an inflammatory cascade in intestinal tissues through the recruitment of circulating inflammatory cells. However, there is no information on the nature of resident cells of the different intestinal layers able to initiate a postischemic inflammatory response. It is however an important issue in the context of a pharmacological approach of the early phase of intestinal ischemia. We reasoned that maintaining the different colonic layers as explant cultures in an oxygenated medium immediately after colonic resection, that is, after an ischemic period, would allow one to identify the resident cells able to initiate an inflammatory cascade, without interference of recruited inflammatory/immune cells. To this end, we designed an explant culture system that operationally defines three compartments in surgical specimens of the human colon, based on the microdissected layers, that is, mucosa, submucosa (containing muscularis mucosae) and muscularis propria. To validate the results obtained in explant cultures in the clinical setting of ischemic colitis, eight cases of sigmoid volvulus were examined. Only the myocytes-containing explants produced tumor necrosis factor alpha (TNFα), via an ADAM17 (a disintegrin and metalloproteinase-17)-dependent pathway, as shown by the abrogation of TNFα production by the inhibitor Tapi-2. Immunofluorescence studies identified nonvascular and vascular myocytes as resident cells coexpressing TNFα and ADAM17, both in our postischemic explant system and in surgical specimens from ischemic colitis patients. Finally, time-course experiments on explanted tissues showed that TNFα production by myocytes was an early event triggered by a postischemic oxidative stress involving nuclear factor kappa B (NF-κB). In conclusion

Division Viii: Galaxies and the Universe

NASA Astrophysics Data System (ADS)

Sadler, Elaine M.; Combes, Françoise; Okamura, Sadanori; Davies, Roger L.; Gallagher, John S.; Padmanabhan, Thanu; Schmidt, Brian P.

2012-04-01

The fields of extragalactic research and cosmology have continued to progress rapidly over the past three years, as detailed in the reports of the Commission Presidents, and we are pleased to acknowledge the award of the 2011 Nobel Prize in Physics to Saul Perlmutter, Brian P. Schmidt and Adam G. Riess for ``the discovery of the accelerating expansion of the Universe through observations of distant supernovae''. The Gruber Cosmology Prize was awarded in 2009 to Wendy L. Freedman, Robert C. Kennicutt and Jeremy Mould for their leadership of the Hubble Space Telescope Key Project on the Extragalactic Distance Scale, in 2010 to Charles Steidel for the identification and study of galaxies in the very distant universe, and in 2011 to Marc Davis, George Efstathiou, Carlos Frenk and Simon D.M. White for pioneering the use of numerical simulations as a tool to model and interpret the large-scale distribution of galaxies and dark matter.

ADAM17_i33780A>G polymorphism interacts with dietary n-6 polyunsaturated fatty acids to modulate obesity risk in the genetics of lipid lowering drugs and diet network study

USDA-ARS?s Scientific Manuscript database

The disintegrin and metalloproteinase ADAM17, also known as tumor necrosis factor alpha converting enzyme, is expressed in adipocytes, and elevated levels of expression have been linked to obesity and insulin resistance. This study evaluated the association of six ADAM17 single nucleotide polymorphi...

Econophysical visualization of Adam Smith’s invisible hand

NASA Astrophysics Data System (ADS)

Cohen, Morrel H.; Eliazar, Iddo I.

2013-02-01

Consider a complex system whose macrostate is statistically observable, but yet whose operating mechanism is an unknown black-box. In this paper we address the problem of inferring, from the system’s macrostate statistics, the system’s intrinsic force yielding the observed statistics. The inference is established via two diametrically opposite approaches which result in the very same intrinsic force: a top-down approach based on the notion of entropy, and a bottom-up approach based on the notion of Langevin dynamics. The general results established are applied to the problem of visualizing the intrinsic socioeconomic force-Adam Smith’s invisible hand-shaping the distribution of wealth in human societies. Our analysis yields quantitative econophysical representations of figurative socioeconomic forces, quantitative definitions of “poor” and “rich”, and a quantitative characterization of the “poor-get-poorer” and the “rich-get-richer” phenomena.

Oligodendrocyte Regeneration and CNS Remyelination Require TACE/ADAM17.

PubMed

Palazuelos, Javier; Klingener, Michael; Raines, Elaine W; Crawford, Howard C; Aguirre, Adan

2015-09-02

The identification of the molecular network that supports oligodendrocyte (OL) regeneration under demyelinating conditions has been a primary goal for regenerative medicine in demyelinating disorders. We recently described an essential function for TACE/ADAM17 in regulating oligodendrogenesis during postnatal myelination, but it is unknown whether this protein also plays a role in OL regeneration and remyelination under demyelinating conditions. By using genetic mouse models to achieve selective gain- or loss-of-function of TACE or EGFR in OL lineage cells in vivo, we found that TACE is critical for EGFR activation in OLs following demyelination, and therefore, for sustaining OL regeneration and CNS remyelination. TACE deficiency in oligodendrocyte progenitor cells following demyelination disturbs OL lineage cell expansion and survival, leading to a delay in the remyelination process. EGFR overexpression in TACE deficient OLs in vivo restores OL development and postnatal CNS myelination, but also OL regeneration and CNS remyelination following demyelination. Our study reveals an essential function of TACE in supporting OL regeneration and CNS remyelination that may contribute to the design of new strategies for therapeutic intervention in demyelinating disorders by promoting oligodendrocyte regeneration and myelin repair. Oligodendrocyte (OL) regeneration has emerged as a promising new approach for the treatment of demyelinating disorders. By using genetic mouse models to selectively delete TACE expression in oligodendrocyte progenitors cells (OPs), we found that TACE/ADAM17 is required for supporting OL regeneration following demyelination. TACE genetic depletion in OPs abrogates EGFR activation in OL lineage cells, and perturbs cell expansion and survival, blunting the process of CNS remyelination. Moreover, EGFR overexpression in TACE-deficient OPs in vivo overcomes the defects in OL development during postnatal development but also OL regeneration during CNS

TACE (ADAM17) inhibits Schwann cell myelination

PubMed Central

Marca, Rosa La; Cerri, Federica; Horiuchi, Keisuke; Bachi, Angela; Feltri, M Laura; Wrabetz, Lawrence; Blobel, Carl P; Quattrini, Angelo; Salzer, James L; Taveggia, Carla

2012-01-01

Tumor necrosis factor-α–converting enzyme (TACE; also known as ADAM17) is a proteolytic sheddase that is responsible for the cleavage of several membrane-bound molecules. We report that TACE cleaves neuregulin-1 (NRG1) type III in the epidermal growth factor domain, probably inactivating it (as assessed by deficient activation of the phosphatidylinositol-3-OH kinase pathway), and thereby negatively regulating peripheral nervous system (PNS) myelination. Lentivirus-mediated knockdown of TACE in vitro in dorsal root ganglia neurons accelerates the onset of myelination and results in hypermyelination. In agreement, motor neurons of conditional knockout mice lacking TACE specifically in these cells are significantly hypermyelinated, and small-caliber fibers are aberrantly myelinated. Further, reduced TACE activity rescues hypomyelination in NRG1 type III haploinsufficient mice in vivo. We also show that the inhibitory effect of TACE is neuron-autonomous, as Schwann cells lacking TACE elaborate myelin of normal thickness. Thus, TACE is a modulator of NRG1 type III activity and is a negative regulator of myelination in the PNS. PMID:21666671

Museum Quality: A New Museum and Recharged College Bring Creative Energy to North Adams, Massachusetts

ERIC Educational Resources Information Center

Grant, Mary

2005-01-01

Nestled in the valley between the Berkshire hills and the Taconic range, North Adams, Massachusetts, in many ways is typical of old New England mill towns working hard to create a new identity in the global economy. When Sprague Electric left town in 1985, the city of 16,000 reeled from the loss of 4,000 blue-collar jobs. This article describes…

An ADAM33 polymorphism associates with progression of preschool wheeze into childhood asthma: a prospective case-control study with replication in a birth cohort study.

PubMed

Klaassen, Ester M M; Penders, John; Jöbsis, Quirijn; van de Kant, Kim D G; Thijs, Carel; Mommers, Monique; van Schayck, Constant P; van Eys, Guillaume; Koppelman, Gerard H; Dompeling, Edward

2015-01-01

The influence of asthma candidate genes on the development from wheeze to asthma in young children still needs to be defined. To link genetic variants in asthma candidate genes to progression of wheeze to persistent wheeze into childhood asthma. In a prospective study, children with recurrent wheeze from the ADEM (Asthma DEtection and Monitoring) study were followed until the age of six. At that age a classification (transient wheeze or asthma) was based on symptoms, lung function and medication use. In 198 children the relationship between this classification and 30 polymorphisms in 16 asthma candidate genes was assessed by logistic regression. In case of an association based on a p<0.10, replication analysis was performed in an independent birth cohort study (KOALA study, n = 248 included for the present analysis). In the ADEM study, the minor alleles of ADAM33 rs511898 and rs528557 and the ORMDL3/GSDMB rs7216389 polymorphisms were negatively associated, whereas the minor alleles of IL4 rs2243250 and rs2070874 polymorphisms were positively associated with childhood asthma. When replicated in the KOALA study, ADAM33 rs528557 showed a negative association of the CG/GG-genotype with progression of recurrent wheeze into childhood asthma (0.50 (0.26-0.97) p = 0.04) and no association with preschool wheeze. Polymorphisms in ADAM33, ORMDL3/GSDMB and IL4 were associated with childhood asthma in a group of children with recurrent wheeze. The replication of the negative association of the CG/GG-genotype of rs528557 ADAM33 with childhood asthma in an independent birth cohort study confirms that a compromised ADAM33 gene may be implicated in the progression of wheeze into childhood asthma.

An ADAM33 Polymorphism Associates with Progression of Preschool Wheeze into Childhood Asthma: A Prospective Case-Control Study with Replication in a Birth Cohort Study

PubMed Central

Klaassen, Ester M. M.; Penders, John; Jöbsis, Quirijn; van de Kant, Kim D. G.; Thijs, Carel; Mommers, Monique; van Schayck, Constant P.; van Eys, Guillaume; Koppelman, Gerard H.; Dompeling, Edward

2015-01-01

Background The influence of asthma candidate genes on the development from wheeze to asthma in young children still needs to be defined. Objective To link genetic variants in asthma candidate genes to progression of wheeze to persistent wheeze into childhood asthma. Materials and Methods In a prospective study, children with recurrent wheeze from the ADEM (Asthma DEtection and Monitoring) study were followed until the age of six. At that age a classification (transient wheeze or asthma) was based on symptoms, lung function and medication use. In 198 children the relationship between this classification and 30 polymorphisms in 16 asthma candidate genes was assessed by logistic regression. In case of an association based on a p<0.10, replication analysis was performed in an independent birth cohort study (KOALA study, n = 248 included for the present analysis). Results In the ADEM study, the minor alleles of ADAM33 rs511898 and rs528557 and the ORMDL3/GSDMB rs7216389 polymorphisms were negatively associated, whereas the minor alleles of IL4 rs2243250 and rs2070874 polymorphisms were positively associated with childhood asthma. When replicated in the KOALA study, ADAM33 rs528557 showed a negative association of the CG/GG-genotype with progression of recurrent wheeze into childhood asthma (0.50 (0.26-0.97) p = 0.04) and no association with preschool wheeze. Conclusion Polymorphisms in ADAM33, ORMDL3/GSDMB and IL4 were associated with childhood asthma in a group of children with recurrent wheeze. The replication of the negative association of the CG/GG-genotype of rs528557 ADAM33 with childhood asthma in an independent birth cohort study confirms that a compromised ADAM33 gene may be implicated in the progression of wheeze into childhood asthma. PMID:25768087

Loss of tumor suppressor miR-126 contributes to the development of hepatitis B virus-related hepatocellular carcinoma metastasis through the upregulation of ADAM9.

PubMed

Xiang, Le-Yang; Ou, Huo-Hui; Liu, Xin-Cheng; Chen, Zhan-Jun; Li, Xiang-Hong; Huang, Yu; Yang, Ding-Hua

2017-06-01

Hepatocellular carcinoma is the most common histological type of primary liver cancer, which represents the second leading cause of cancer-related mortality. MiR-126 was reported to be downregulated in hepatocellular carcinoma tissues, compared with its levels in noncancerous tissues. However, baseline miR-126 expression levels in hepatitis B virus-related hepatocellular carcinoma patients who did not undergo pre-operational treatment remains unknown since hepatitis B virus infection and pre-operational transcatheter arterial chemoembolization were shown to upregulate miR-126 expression. Here, we demonstrated that miR-126 is generally downregulated in a homogeneous population of pre-operational treatment-naïve hepatitis B virus-related hepatocellular carcinoma patients (84.0%, 84/100), and its expression is significantly associated with pre-operational alpha-fetoprotein levels ( p < 0.05), microvascular invasion ( p < 0.05), tumor metastasis ( p < 0.05), as well as early recurrence (12 months after surgery; p < 0.01). Furthermore, the results of our study revealed that miR-126 is negatively correlated with ADAM9 expression in hepatitis B virus-related hepatocellular carcinoma patients. Overexpression of miR-126 was shown to attenuate ADAM9 expression in hepatocellular carcinoma cells, which subsequently inhibits cell migration and invasion in vitro. In addition, Cox proportional hazards regression model analysis showed that ADAM9 levels, tumor number, microvascular invasion, and tumor metastasis rate represent independent prognostic factors for shorter recurrence-free survival. In conclusion, we demonstrated that the loss of tumor suppressor miR-126 in hepatitis B virus-related hepatocellular carcinoma cells contributes to the development of metastases through the upregulated expression of its target gene, ADAM9. MiR-126-ADAM9 pathway-based therapeutic targeting may represent a novel approach for the inhibition of hepatitis B virus

A dual inhibitor of matrix metalloproteinases and a disintegrin and metalloproteinases, [¹⁸F]FB-ML5, as a molecular probe for non-invasive MMP/ADAM-targeted imaging.

PubMed

Matusiak, Nathalie; Castelli, Riccardo; Tuin, Adriaan W; Overkleeft, Herman S; Wisastra, Rosalina; Dekker, Frank J; Prély, Laurette M; Bischoff, Rainer; Bischoff, Rainer P M; van Waarde, Aren; Dierckx, Rudi A J O; Elsinga, Philip H

2015-01-01

Numerous clinical studies have shown a correlation between increased matrix metalloproteinase (MMP)/a disintegrin and metalloproteinase (ADAM) activity and poor outcome of cancer. Various MMP inhibitors (MMPIs) have been developed for therapeutic purposes in oncology. In addition, molecular imaging of MMP/ADAM levels in vivo would allow the diagnosis of tumors. We selected the dual inhibitor of MMPs and ADAMs, ML5, which is a hydroxamate-based inhibitor with affinities for many MMPs and ADAMs. ML5 was radiolabelled with (18)F and the newly obtained radiolabelled inhibitor was evaluated in vitro and in vivo. ML5 was radiolabelled by direct acylation with N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB) for PET (positron emission tomography). The resulting radiotracer [(18)F]FB-ML5 was evaluated in vitro in human bronchial epithelium 16HBE cells and breast cancer MCF-7 cells. The non-radioactive probe FB-ML5 and native ML5 were tested in a fluorogenic inhibition assay against MMP-2, -9, -12 and ADAM-17. The in vivo kinetics of [(18)F]FB-ML5 were examined in a HT1080 tumor-bearing mouse model. Specificity of probe binding was examined by co-injection of 0 or 2.5mg/kg ML5. ML5 and FB-ML5 showed high affinity for MMP-2, -9, -12 and ADAM-17; indeed IC50 values were respectively 7.4 ± 2.0, 19.5 ± 2.8, 2.0 ± 0.2 and 5.7 ± 2.2 nM and 12.5 ± 3.1, 31.5 ± 13.7, 138.0 ± 10.9 and 24.7 ± 2.8 nM. Radiochemical yield of HPLC-purified [(18)F]FB-ML5 was 13-16% (corrected for decay). Cellular binding of [(18)F]FB-ML5 was reduced by 36.6% and 27.5% in MCF-7 and 16 HBE cells, respectively, after co-incubation with 10 μM of ML5. In microPET scans, HT1080 tumors exhibited a low and homogeneous uptake of the tracer. Tumors of mice injected with [(18)F]FB-ML5 showed a SUVmean of 0.145 ± 0.064 (n=6) which decreased to 0.041 ± 0.027 (n=6) after target blocking (p<0.05). Ex vivo biodistribution showed a rapid excretion through the kidneys and the liver. Metabolite assays

Microarray identifies ADAM family members as key responders to TGF-beta1 in alveolar epithelial cells.

PubMed

Keating, Dominic T; Sadlier, Denise M; Patricelli, Andrea; Smith, Sinead M; Walls, Dermot; Egan, Jim J; Doran, Peter P

2006-09-01

The molecular mechanisms of Idiopathic Pulmonary Fibrosis (IPF) remain elusive. Transforming Growth Factor beta 1(TGF-beta1) is a key effector cytokine in the development of lung fibrosis. We used microarray and computational biology strategies to identify genes whose expression is significantly altered in alveolar epithelial cells (A549) in response to TGF-beta1, IL-4 and IL-13 and Epstein Barr virus. A549 cells were exposed to 10 ng/ml TGF-beta1, IL-4 and IL-13 at serial time points. Total RNA was used for hybridisation to Affymetrix Human Genome U133A microarrays. Each in vitro time-point was studied in duplicate and an average RMA value computed. Expression data for each time point was compared to control and a signal log ratio of 0.6 or greater taken to identify significant differential regulation. Using normalised RMA values and unsupervised Average Linkage Hierarchical Cluster Analysis, a list of 312 extracellular matrix (ECM) proteins or modulators of matrix turnover was curated via Onto-Compare and Gene-Ontology (GO) databases for baited cluster analysis of ECM associated genes. Interrogation of the dataset using ontological classification focused cluster analysis revealed coordinate differential expression of a large cohort of extracellular matrix associated genes. Of this grouping members of the ADAM (A disintegrin and Metalloproteinase domain containing) family of genes were differentially expressed. ADAM gene expression was also identified in EBV infected A549 cells as well as IL-13 and IL-4 stimulated cells. We probed pathologenomic activities (activation and functional activity) of ADAM19 and ADAMTS9 using siRNA and collagen assays. Knockdown of these genes resulted in diminished production of collagen in A549 cells exposed to TGF-beta1, suggesting a potential role for these molecules in ECM accumulation in IPF.

Frailty profile for geriatric patients in outpatient clinic of RSUP H. Adam Malik Medan

NASA Astrophysics Data System (ADS)

Permatasari, T. D.; Sihombing, B.; Arianto, P.

2018-03-01

Frailty is a circumstance of increased vulnerability to bad resolution of homeostasis after a stressor occasion, which increases the risk of adverse outcomes. Early detection of frailty in elderly patients is a must but is rarely in the Geriatric Outpatient settings. We conducted a study to see the frailty profile for geriatric patients in the outpatient clinic of RSUP H. Adam Malik Medan. A cross-sectional research with a descriptive method was in the Geriatric Outpatient Clinic of Adam Malik Hospital from July-September 2016. The population of this study was patients from the Geriatric Outpatient Clinic, and sampling was by using consecutive methods. Samples were by questionnaires assessing (FRAIL Scale).This study was140 patients. Based on age, the age group of 81-90 years was dominantly frail (53.8%). Most of the subjects worked as government employees (109 subjects), and most of them were robust (42.2%). Based on income, both groups were dominated by robust (38.3% and 41.3%, respectively). Based on BMI, most were robust with underweight 33.5%, normoweight 37.8%, and obese 44.7%. Among the 140 patients, frailty was in the 27.1% of the subjects and the contributing factors were Age, Gender, and Obesity.

The Adam and Eve story as exemplar of an early-life variant of the oedipus complex.

PubMed

Osman, M P

2000-01-01

The Adam and Eve story is construed as having an organizing function that facilitates the analytic understanding of certain patients. In this interpretation, the story epitomizes a psychodynamic in which progressive growth, with separation and individuation, of the young is experienced as perilous--not only to them, but also correspondingly to their procreators. In the myth, the increasing psychic and physical maturation of Adam and Eve produced a crisis. Not only was divine authority flouted, but also apprehensions were aroused that God might be humbled or diminished. This threatened him, evoking his wrath and leading to the punishment by abandonment of his youthful wards. It is suggested that the story depicts an emotional complex of widespread application and is an archaic version of the oedipus complex, continuous with the oedipus complex proper, but from an earlier stage of development. This archaic complex is delineated with clinical vignettes, and a clinical explication of its various components is provided. Clinical management is considered, particularly with reference to the challenge that a closed-system perspective (Fairbairn 1958) presents to a patient's development.

Geochemical survey of the Adams Gap and Shinbone Creek Roadless Areas, Clay County, Alabama

USGS Publications Warehouse

Robinson, G.R.; Klein, T.L.; Lesure, F.G.; Hanley, J.T.

1984-01-01

Reports covering the mineral resources of Clay County and vicinity include Brewer (1896) and Adams (1930) on gold, Prouty (1923) on graphite, and Heinrich and Olson (1953) on mica. The mineral resources of the Talladega National Forest were evaluated by Gilbert and Smith (1973). The mineral resource potential of the two roadless areas is detailed in Robinson and others (1983) and an accompanying geologic report is given in Robinson and others (in press).

Performance evaluation of the Arkray Adams HA-8160 HbA1c analyser.

PubMed

Thevarajah, T Malathi; Nani, Nordin; Chew, Y Y

2008-12-01

HbA1c measurement is currently routinely used to predict long term outcome of diabetes, thus playing a fundamental role in the management of diabetes. The relationship between HbA1c value and long term diabetic complications has been established by a randomised control Diabetes Control and Complications Trial (DCCT) which used high performance liquid chromatography (HPLC) as a reference method for HbA1c assay. To ensure that HbA1c results from a variety HbA1c assay methods are similar to the DCCT values, the American Diabetes Association (ADA) recommended that all laboratories should use methods certified by the National Glycohemoglobin Standardization Programme (NGSP) with interassay coefficient variation (CV) of < 5% (ideally < 3%). The International Federation of Clinical Chemistry (IFCC) working group on HbA1c standardisation has set a CV < 2.5% as a criteria for its reference laboratories. To evaluate the performance of Arkray Adams HA-8160 HbA1c analyser which uses a cation exchange HPLC method and its correlation to HbA1c assay on Cobas Integra 800 which is an immunoturbidimetric method. For the imprecision study, patient samples and control material of two levels were analysed on HA-8160 analyser 20 times in a single run (within-run imprecision) and twice a day on five consecutive days (between-run imprecision). For the recovery study, two samples each with high and low values were selected and mixed in ratios of 1:3, 1:1 and 3:1, and were analysed by HA-8160. Sixty samples were analysed by both Cobas Integra 800 and HA-8160 for method comparison study. Ten uraemic samples and ten thalassaemic samples were assayed on Cobas Integra 800 and HA 8160 for interference study. Within-run CVs were 0.6% and 0.7% for medium and high value samples respectively, 0.6% and 0.7% for low and high level controls respectively. Between-run CVs were 0.5% and 0.4% for medium and high value samples respectively, 0.5% and 0.6% for low and high level controls respectively. The

78 FR 37791 - In the Matter of: Jose Guadalupe Reyes-Martinez, Inmate Number #85993-279, CI Adams County...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-24

... DEPARTMENT OF COMMERCE Bureau of Industry and Security In the Matter of: Jose Guadalupe Reyes-Martinez, Inmate Number 85993-279, CI Adams County, Correctional Institution, P.O. Box 1600, Washington, MS 39190; Order Denying Export Privileges On November 21, 2011, in the U.S. District Court, Southern...

ADAM17 and EGFR regulate IL-6 receptor and amphiregulin mRNA expression and release in cigarette smoke-exposed primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD).

PubMed

Stolarczyk, Marta; Amatngalim, Gimano D; Yu, Xiao; Veltman, Mieke; Hiemstra, Pieter S; Scholte, Bob J

2016-08-01

Aberrant activity of a disintegrin and metalloprotease 17 (ADAM17), also known as TACE, and epidermal growth factor receptor (EGFR) has been suggested to contribute to chronic obstructive pulmonary disease (COPD) development and progression. The aim of this study was to investigate the role of these proteins in activation of primary bronchial epithelial cells differentiated at the air-liquid interface (ALI-PBEC) by whole cigarette smoke (CS), comparing cells from COPD patients with non-COPD CS exposure of ALI-PBEC enhanced ADAM17-mediated shedding of the IL-6 receptor (IL6R) and the EGFR agonist amphiregulin (AREG) toward the basolateral compartment, which was more pronounced in cells from COPD patients than in non-COPD controls. CS transiently increased IL6R and AREG mRNA in ALI-PBEC to a similar extent in cultures from both groups, suggesting that posttranslational events determine differential shedding between COPD and non-COPD cultures. We show for the first time by in situ proximity ligation (PLA) that CS strongly enhances interactions of phosphorylated ADAM17 with AREG and IL-6R in an intracellular compartment, suggesting that CS-induced intracellular trafficking events precede shedding to the extracellular compartment. Both EGFR and ADAM17 activity contribute to CS-induced IL-6R and AREG protein shedding and to mRNA expression, as demonstrated using selective inhibitors (AG1478 and TMI-2). Our data are consistent with an autocrine-positive feedback mechanism in which CS triggers shedding of EGFR agonists evoking EGFR activation, in ADAM17-dependent manner, and subsequently transduce paracrine signaling toward myeloid cells and connective tissue. Reducing ADAM17 and EGFR activity could therefore be a therapeutic approach for the tissue remodeling and inflammation observed in COPD. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Protein levels of ADAM10, BACE1, and PSEN1 in platelets and leukocytes of Alzheimer's disease patients.

PubMed

Bram, Jessyka Maria de França; Talib, Leda Leme; Joaquim, Helena Passarelli Giroud; Sarno, Tamires Alves; Gattaz, Wagner Farid; Forlenza, Orestes Vicente

2018-05-29

The clinical diagnosis of Alzheimer's disease (AD) is a probabilistic formulation that may lack accuracy particularly at early stages of the dementing process. Abnormalities in amyloid-beta precursor protein (APP) metabolism and in the level of APP secretases have been demonstrated in platelets, and to a lesser extent in leukocytes, of AD patients, with conflicting results. The aim of the present study was to compare the protein level of the APP secretases A-disintegrin and metalloprotease 10 (ADAM10), Beta-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PSEN1) in platelets and leukocytes from 20 non-medicated older adults with AD and 20 healthy elders, and to determine the potential use of these biomarkers to discriminate cases of AD from controls. The protein levels of all APP secretases were significantly higher in platelets compared to leukocytes. We found statistically a significant decrease in ADAM10 (52.5%, p < 0.0001) and PSEN1 (32%, p = 0.02) in platelets from AD patients compared to controls, but not in leukocytes. Combining all three secretases to generate receiver-operating characteristic (ROC) curves, we found a good discriminatory effect (AD vs. controls) when using platelets (the area under the curve-AUC-0.90, sensitivity 88.9%, specificity 66.7%, p = 0.003), but not in leukocytes (AUC 0.65, sensitivity 77.8%, specificity 50.0%, p = 0.2). Our findings indicate that platelets represent a better biological matrix than leukocytes to address the peripheral level of APP secretases. In addition, combining the protein level of ADAM10, BACE1, and PSEN1 in platelets, yielded a good accuracy to discriminate AD from controls.

ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site.

PubMed

Abbruzzese, Genevieve; Becker, Sarah F; Kashef, Jubin; Alfandari, Dominique

2016-07-15

The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell-cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. Copyright © 2015. Published by Elsevier Inc.

ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site

PubMed Central

Kashef, Jubin; Alfandari, Dominique

2015-01-01

The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell–cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. PMID:26206614

The Elsevier Trophoblast Research Award Lecture: Importance of metzincin proteases in trophoblast biology and placental development: a focus on ADAM12.

PubMed

Aghababaei, Mahroo; Beristain, Alexander G

2015-04-01

Placental development is a highly regulated process requiring signals from both fetal and maternal uterine compartments. Within this complex system, trophoblasts, placental cells of epithelial lineage, form the maternal-fetal interface controlling nutrient, gas and waste exchange. The commitment of progenitor villous cytotrophoblasts to differentiate into diverse trophoblast subsets is a fundamental process in placental development. Differentiation of trophoblasts into invasive stromal- and vascular-remodeling subtypes is essential for uterine arterial remodeling and placental function. Inadequate placentation, characterized by defects in trophoblast differentiation, may underlie the earliest cellular events driving pregnancy disorders such as preeclampsia and fetal growth restriction. Molecularly, invasive trophoblasts acquire characteristics defined by profound alterations in cell-cell and cell-matrix adhesion, cytoskeletal reorganization and production of proteolytic factors. To date, most studies have investigated the importance of the matrix metalloproteinases (MMPs) and their ability to efficiently remodel components of the extracellular matrix (ECM). However, it is now becoming clear that besides MMPs, other related proteases regulate trophoblast invasion via mechanisms other than ECM turnover. In this review, we will summarize the current knowledge on the regulation of trophoblast invasion by members of the metzincin family of metalloproteinases. Specifically, we will discuss the emerging roles that A Disintegrin and Metalloproteinases (ADAMs) play in placental development, with a particular focus on the ADAM subtype, ADAM12. Copyright © 2015 Elsevier Ltd. All rights reserved.

Model Compound Studies of Rigid Rod Aromatic Heterocyclic Polymer Systems, the X-Ray Crystal Structure of 2,6-Diphenylbenzo (1,2-d; 5,4-d’) Diimidazole Tetrahydrate, C2OH14N4. 4H2O, a Model System for the Study of Polymer-Water Interaction in Polybenzimidazoles.

DTIC Science & Technology

1983-07-01

Marilyn Hunsaker and W. Wade Adams Polyimer Branch Nonmetallic Division Albert V. Fratini University of Dayton Research Institute 300 College Park...U. CONTRACT OR GRANT NUMUER(e) M. Hunsaker, and W. W. Adams , Air Force Wright I atudrcnrc Aeronautical Laboratories, Materials Laboratory F33615-81-C...Scientist. Co-authors were Marilyn Hunsaker and W. W. Adams , Materials Laboratory (AFWAL/MLHP); and Dr. Albert V. Fratini, University of Dayton Research

Hydroquinone-induced FOXP3-ADAM17-Lyn-Akt-p21 signaling axis promotes malignant progression of human leukemia U937 cells.

PubMed

Chen, Ying-Jung; Liu, Wen-Hsin; Chang, Long-Sen

2017-02-01

Hydroquinone (1,4-benzenediol; HQ), a major marrow metabolite of the leukemogen benzene, has been proven to evoke benzene-related hematological disorders and myelotoxicity in vitro and in vivo. The goal of the present study was to explore the role of FOXP3 in HQ-induced malignant progression of U937 human leukemia cells. U937 cells were treated with 5 μM HQ for 24 h, and the cells were re-suspended in serum-containing medium without HQ for 2 days. The same procedure was repeated three times, and the resulting U937/HQ cells were maintained in cultured medium containing 5 μM HQ. Proliferation and colony formation of U937/HQ cells were notably higher than those of U937 cells. Ten-eleven translocation methylcytosine dioxygenase-mediated demethylation of the Treg-specific demethylated region in FOXP3 gene resulted in higher FOXP3 expression in U937/HQ cells than in U937 cells. FOXP3-induced miR-183 expression reduced β-TrCP mRNA stability and suppressed β-TrCP-mediated Sp1 degradation, leading to up-regulation of Sp1 expression in U937/HQ cells. Sp1 up-regulation further increased ADAM17 and Lyn expression, and ADAM17 up-regulation stimulated Lyn activation in U937/HQ cells. Moreover, U937/HQ cells showed higher Lyn-mediated Akt activation and cytoplasmic p21 expression than U937 cells did. Abolishment of Akt activation decreased cytoplasmic p21 expression in U937/HQ cells. Suppression of FOXP3, ADAM17, and Lyn expression, as well as Akt inactivation, repressed proliferation and clonogenicity of U937/HQ cells. Together with the finding that cytoplasmic p21 shows anti-apoptotic and oncogenic activities in cancer cells, the present data suggest a role of FOXP3/ADAM17/Lyn/Akt/p21 signaling axis in HQ-induced hematological disorders.

The Co-simulation of Humanoid Robot Based on Solidworks, ADAMS and Simulink

NASA Astrophysics Data System (ADS)

Song, Dalei; Zheng, Lidan; Wang, Li; Qi, Weiwei; Li, Yanli

A simulation method of adaptive controller is proposed for the humanoid robot system based on co-simulation of Solidworks, ADAMS and Simulink. A complex mathematical modeling process is avoided by this method, and the real time dynamic simulating function of Simulink would be exerted adequately. This method could be generalized to other complicated control system. This method is adopted to build and analyse the model of humanoid robot. The trajectory tracking and adaptive controller design also proceed based on it. The effect of trajectory tracking is evaluated by fitting-curve theory of least squares method. The anti-interference capability of the robot is improved a lot through comparative analysis.

A.D.A.M. test (Antibiofilm Dressing's Activity Measurement) - Simple method for evaluating anti-biofilm activity of drug-saturated dressings against wound pathogens.

PubMed

Junka, Adam F; Żywicka, Anna; Szymczyk, Patrycja; Dziadas, Mariusz; Bartoszewicz, Marzena; Fijałkowski, Karol

2017-12-01

In the present article, we propose a simple Antibiofilm Dressing's Activity Measurement (A.D.A.M.) test that allows to check in vitro a dressing's suitability against biofilm-related wound infections. To perform the test, three agar discs are covered with biofilm formed by the tested pathogen after which they are assembled one over another in the form of an agar plug and placed in the well of a 24-well plate. The top disc is covered with the analyzed dressing and the entire set is incubated for 24h. During this time, the investigated antimicrobial substance is released from the dressing and penetrates to subsequent biofilm-covered agar discs. Biofilm reduction is measured using 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) spectrometric assay and the results are compared to untreated control samples (agar plug covered with biofilm and without the dressing/or with a passive dressing placed on the top disc). Furthermore, in order to standardize the differences in penetrability of the drugs released from active dressings the results can be expressed as a dimensionless value referred to as the Penetrability Index. In summary, A.D.A.M. test is simple, cheap, can be performed practically in every clinical laboratory and takes no more time than routine microbiological diagnostics. Apart from measuring the released drug's activity, the A.D.A.M. test allows to assess drug penetrability (across three agar discs), reflecting real wound conditions, where microbes are frequently hidden under the necrotic tissue or cloth. In conclusion, the A.D.A.M. test produces a high volume of data that, when analyzed, can provide a researcher with a valuable hint concerning the applicability of active dressings against specific biofilm pathogens in a particular setting. Copyright © 2017 Elsevier B.V. All rights reserved.

Apixaban and dalteparin in active malignancy associated venous thromboembolism. The ADAM VTE Trial.

PubMed

McBane Ii, Robert; Loprinzi, Charles L; Ashrani, Aneel; Perez-Botero, Juliana; Leon Ferre, Roberto A; Henkin, Stanislav; Lenz, Charles J; Le-Rademacher, Jennifer G; Wysokinski, Waldemar E

2017-10-05

Currently, low molecular weight heparin (LMWH) is the guideline endorsed treatment of patients with cancer associated venous thromboembolism (VTE). While apixaban is approved for the treatment of acute VTE, there are limited data supporting its use in cancer patients. The rationale and design of this investigator initiated Phase IV, multicenter, randomized, open label, superiority trial assessing the safety of apixaban versus dalteparin for cancer associated VTE is provided (ADAM-VTE; NCT02585713). The main aim of the ADAM-VTE trial is to test the hypothesis that apixaban is associated with a significantly lower rate of major bleeding compared to dalteparin in the treatment of cancer patients with acute VTE. The primary safety outcome is rate of major bleeding. Secondary efficacy objective is to assess the rates of recurrent VTE or arterial thromboembolism. Cancer patients with acute VTE (n=300) are randomized to receive apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily thereafter) or dalteparin (200 IU/Kg daily for 30 days followed by 150 IU/kg daily thereafter) for 6 months. Stratification factors used for randomization include cancer stage and cancer specific risk of venous thromboembolism using the Khorana score. Participating centers are chosen from the Academic and Community Cancer Research United (ACCRU) consortium comprised of 90 oncology practices in the United States and Canada. Based on the hypothesis to be tested, we anticipate that these trial results will provide evidence supporting apixaban as an effective treatment of cancer associated VTE at lower rates of major bleeding compared to LMWH.

Defenses and morality: Adam Smith, Sigmund Freud, and contemporary psychoanalysis.

PubMed

Gabrinetti, Paul A; Özler, Sule

2014-10-01

In this paper we follow the development and transmission of moral learning from Adam Smith's impartial spectator to Sigmund Freud's superego and then to contemporary psychoanalysis. We argue that defenses are an integral component in the acquisition of any moral system. Elaborating on this argument, we assert that there is a progression from defensive systems that are "closed" to defensive systems that are "open," as defined in a recent work by Novick and Novick. The former system is "static, avoids reality, and is characterized by power dynamics, sadomasochism, and omnipotent defense." The latter, on the other hand, is a system that allows for "joy, creativity, spontaneity, love and it is attuned to reality." Furthermore, while Smith and Freud's systems are more one-person systems of defense, contemporary psychoanalysis has moved to more of a two-person system.

Suppression of Akt/Foxp3-mediated miR-183 expression blocks Sp1-mediated ADAM17 expression and TNFα-mediated NFκB activation in piceatannol-treated human leukemia U937 cells.

PubMed

Liu, Wen-Hsin; Chang, Long-Sen

2012-09-01

To address the mechanism of piceatannol in inhibiting TNFα-mediated pathway, studies on piceatannol-treated human leukemia U937 cells were conducted. Piceatannol treatment reduced TNFα shedding and NFκB activation and decreased the release of soluble TNFα into the culture medium of U937 cells. Moreover, ADAM17 expression was down-regulated in piceatannol-treated cells. Over-expression of ADAM17 abrogated the ability of piceatannol to suppress TNFα-mediated NFκB activation. Piceatannol-evoked β-TrCP up-regulation promoted Sp1 degradation, thus reducing transcriptional level of ADAM17 gene in U937 cells. Piceatannol treatment induced p38 MAPK phosphorylation but inactivation of Akt and ERK. In contrast to p38 MAPK inhibitor or restoration of ERK activation, transfection of constitutive active Akt abolished the effect of piceatannol on β-TrCP, Sp1 and ADAM17 expression. Piceatannol-elicited down-regulation of miR-183 expression was found to cause β-TrCP up-regulation. Inactivation of Akt resulted in Foxp3 down-regulation and reduced miR-183 expression in piceatannol-treated cells. Knock-down of Foxp3 and chromatin immunoprecipitating revealed that Foxp3 genetically regulated transcription of miR-183 gene. Taken together, our data indicate that suppression of Akt/Foxp3-mediated miR-183 expression blocks Sp1-mediated ADAM17 expression in piceatannol-treated U937 cells. Consequently, piceatannol suppresses TNFα shedding, leading to inhibition of TNFα/NFκB pathway. Copyright © 2012 Elsevier Inc. All rights reserved.

ADAM, a hands‐on patient simulator for teaching principles of drug disposition and compartmental pharmacokinetics

PubMed Central

Zuna, Ines

2017-01-01

Aims To design, construct and validate a pharmacokinetics simulator that offers students hands‐on opportunities to participate in the design, administration and analysis of oral and intravenous dosing regimens. Methods The Alberta Drug Administration Modeller (ADAM) is a mechanical patient in which peristaltic circulation of water through a network of silicone tubing and glass bottles creates a representation of the outcomes of drug absorption, distribution, metabolism and elimination. Changing peristaltic pump rates and volumes in bottles allows values for pharmacokinetic constants to be varied, thereby simulating differences in drug properties and in patient physiologies and pathologies. Following administration of methylene blue dye by oral or intravenous routes, plasma and/or urine samples are collected and drug concentrations are determined spectrophotometrically. The effectiveness of the simulator in enhancing student competence and confidence was assessed in two undergraduate laboratory classes. Results The simulator effectively models one‐ and two‐compartment drug behaviour in a mathematically‐robust and realistic manner. Data allow calculation of numerous pharmacokinetic constants, by traditional graphing methods or with curve‐fitting software. Students' competence in solving pharmacokinetic problems involving calculations and graphing improved significantly, while an increase in confidence and understanding was reported. Conclusions The ADAM is relatively inexpensive and straightforward to construct, and offers a realistic, hands‐on pharmacokinetics learning opportunity for students that effectively complements didactic lectures. PMID:28666308

Adams' Closed-Loop Concept of Learning and Motor Performance: It's Application in Behavioural Kinesiology and Patients Education in Rehabilitation.

ERIC Educational Resources Information Center

Olaogun, Matthew O. B.

1986-01-01

J. Adams' application of the closed-loop theory (involving feedback and correction) on human learning and motor performance is described. The theory's applicability to behavioral kinesiology (the science of human movement) is discussed in the context of physical therapy, stressing the importance of knowledge of results as a motivating factor.…

Modeling and simulation research on electromagnetic and energy-recycled damper based on Adams

NASA Astrophysics Data System (ADS)

Zhou, C. F.; Zhang, K.; Zhang, Pengfei

2018-05-01

In order to study the voltage and power output characteristics of the electromagnetic and energy-recycled damper which consists of gear, rack and generator, the Adams model of this damper and the Simulink model of generator are established, and the co-simulation is accomplished with these two models. The output indexes such as the gear speed and power of generator are obtained by the simulation, and the simulation results demonstrate that the voltage peak of the damper is 25 V; the maximum output power of the damper is 8 W. The above research provides a basis for the prototype development of electromagnetic and energy-recycled damper with gear and rack.

[Kurschmann-Steinert myotonic dystrophia and Adams-Stoke attacks. Successful treatment of arrhythmia by means of pacemaker implantation].

PubMed

Bieler, M; Sefidpar, M; Engel, U R; Reutter, F W

1976-11-20

The case is reported of a 39-year-old male with Steinert's dystrophia myotonica complicated by cardiac arrhythmias manifested by high-degree a-v block with Stokes-Adams attacks. Implantation of a demand-type cardiac pacemaker brought prompt relief from cardiac symptoms and the patient was able to resume work. The pathologico-anatomical findings in dystrophia myotonica are discussed, together with their possible connection with the type of arrhythmias described.

ADAM, a hands-on patient simulator for teaching principles of drug disposition and compartmental pharmacokinetics.

PubMed

Zuna, Ines; Holt, Andrew

2017-11-01

To design, construct and validate a pharmacokinetics simulator that offers students hands-on opportunities to participate in the design, administration and analysis of oral and intravenous dosing regimens. The Alberta Drug Administration Modeller (ADAM) is a mechanical patient in which peristaltic circulation of water through a network of silicone tubing and glass bottles creates a representation of the outcomes of drug absorption, distribution, metabolism and elimination. Changing peristaltic pump rates and volumes in bottles allows values for pharmacokinetic constants to be varied, thereby simulating differences in drug properties and in patient physiologies and pathologies. Following administration of methylene blue dye by oral or intravenous routes, plasma and/or urine samples are collected and drug concentrations are determined spectrophotometrically. The effectiveness of the simulator in enhancing student competence and confidence was assessed in two undergraduate laboratory classes. The simulator effectively models one- and two-compartment drug behaviour in a mathematically-robust and realistic manner. Data allow calculation of numerous pharmacokinetic constants, by traditional graphing methods or with curve-fitting software. Students' competence in solving pharmacokinetic problems involving calculations and graphing improved significantly, while an increase in confidence and understanding was reported. The ADAM is relatively inexpensive and straightforward to construct, and offers a realistic, hands-on pharmacokinetics learning opportunity for students that effectively complements didactic lectures. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Formononetin protects neurons against hypoxia-induced cytotoxicity through upregulation of ADAM10 and sAβPPα.

PubMed

Sun, Miao; Zhou, Ting; Zhou, Liang; Chen, Qiang; Yu, Yan; Yang, Huan; Zhong, Kaiyin; Zhang, Ximeng; Xu, Feng; Cai, Shaoqing; Yu, Albert; Zhang, Hui; Xiao, Ruizhong; Xiao, Dongsheng; Chui, Dehua

2012-01-01

Formononetin, an active constituent of the Chinese herb Astragali Radix, has been reported to have beneficial effects for Alzheimer's disease (AD). Yet the mechanism of this effect remains to be elucidated. The present study shows that formononetin increases soluble-AβPPα (sAβPPα) secretion and thus protects human-AβPP Swedish mutation cell (N2a-AβPP cell) from hypoxia-induced apoptosis. Using hypoxic N2a-AβPP cell as an in vitro model of AD-like pathology, we confirmed that regular treatment with formononetin could have neuroprotective effects, followed respectively by reduced caspase 3 activity and increased cell viability. Strikingly, our data revealed that the caspase 3-blocking effect of formononetin was largely mediated by stimulation of α-secretase cleavage of AβPP, and increasing the secretion of its soluble form, sAβPPα. Moreover, the protective effect of formononetin was totally inhibited by TAPI-2, an α-secretase complex inhibitor, suggesting the role of the sAβPPα pathway in the neuroprotective response to formononetin. We also found that the stimulative effect of formononetin on α-secretase activity was mainly conducted by upregulating ADAM10 expression at the transcriptional level. Altogether, our study provides novel insights into how formononetin mediates stimulation of the ADAM10-sAβPPα pathway and exerts a neuronal protective effect.

Activation of microRNA-494-targeting Bmi1 and ADAM10 by silibinin ablates cancer stemness and predicts favourable prognostic value in head and neck squamous cell carcinomas

PubMed Central

Chang, Yu-Chao; Lai, Yu-Chi; Hu, Fang-Wei; Yu, Cheng-Chia

2015-01-01

Tumor initiating cells (TICs) possessing cancer stemness were shown to be enriched after therapy, resulting in the relapse and metastasis of head and neck squamous cell carcinomas (HNC). An effective therapeutic approach suppressing the HNC-TICs would be a potential method to improve the treatments for HNC. We observed that the treatment of silibinin (SB) dose dependently down-regulated the ALDH1 activity, CD133 positivity, stemness signatures expression, self-renewal property, and chemoresistance in ALDH1+CD44+ HNC-TICs. Using miRNA-microarray and mechanistic studies, SB increased the expression of microRNA-494 (miR-494) and both Bmi1 and ADAM10 were identified as the novel targets of miR-494. Moreover, overexpression of miR-494 results in a reduction in cancer stemness. However, knockdown of miR-494 in CD44−ALDH1−non-HNC-TICs enhanced cancer stemness and oncogenicity, while co-knockdown of Bmi1 and ADAM10 effectively reversed these phenomena. Mice model showed that SB treatment by oral gavage to xenograft tumors reduced tumor growth and prolonged the survival time of tumor-bearing mice by activation of miR-494-inhibiting Bmi1/ADAM10 expression. Survival analysis indicated that a miR494highBmi1lowADAM10low phenotype predicted a favourable clinical outcome. We conclude that the inhibition of tumor aggressiveness in HNC-TICs by SB was mediated by up-regulation miR-494, suggesting that SB would be a valuable anti-cancer drug for treatment of HNC. PMID:26090866

Role of tumour necrosis factor alpha converting enzyme (TACE/ADAM17) and associated proteins in coronary artery disease and cardiac events.

PubMed

Chemaly, Melody; McGilligan, Victoria; Gibson, Mark; Clauss, Matthias; Watterson, Steven; Alexander, H Denis; Bjourson, Anthony John; Peace, Aaron

2017-12-01

Tumour necrosis factor alpha converting enzyme (TACE/ADAM17) is a member of the A disintegrin and metalloproteinase (ADAM) family of ectodomain shedding proteinases. It regulates many inflammatory processes by cleaving several transmembrane proteins, including tumour necrosis factor alpha (TNFα) and its receptors tumour necrosis factor alpha receptor 1 and tumour necrosis factor alpha receptor 2. There is evidence that TACE is involved in several inflammatory diseases, such as ischaemia, heart failure, arthritis, atherosclerosis, diabetes and cancer as well as neurological and immune diseases. This review summarizes the latest discoveries regarding the mechanism of action and regulation of TACE. It also focuses on the role of TACE in atherosclerosis and coronary artery disease (CAD), highlighting clinical studies that have investigated its expression and protein activity. The multitude of substrates cleaved by TACE make this enzyme an attractive target for therapy and a candidate for biomarker research and development in CAD. Crown Copyright © 2017. Published by Elsevier Masson SAS. All rights reserved.

78 FR 11688 - Notice of Issuance of Amendment to Facility License R-77 Incorporating a Decommissioning Plan for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-19

... Reactor at the State University of New York at Buffalo AGENCY: Nuclear Regulatory Commission. ACTION... University of New York at Buffalo (UB) decommissioning plan (DP) by amendment to the Facility License R-77... in the NRC Library at http://www.nrc.gov/reading-rm/adams.html . To begin the search, select ``ADAMS...

Robust Algorithms for on Minor-Free Graphs Based on the Sherali-Adams Hierarchy

NASA Astrophysics Data System (ADS)

Magen, Avner; Moharrami, Mohammad

This work provides a Linear Programming-based Polynomial Time Approximation Scheme (PTAS) for two classical NP-hard problems on graphs when the input graph is guaranteed to be planar, or more generally Minor Free. The algorithm applies a sufficiently large number (some function of when approximation is required) of rounds of the so-called Sherali-Adams Lift-and-Project system. needed to obtain a -approximation, where f is some function that depends only on the graph that should be avoided as a minor. The problem we discuss are the well-studied problems, the and problems. An curious fact we expose is that in the world of minor-free graph, the is harder in some sense than the.

Adam Warren | NREL

Science.gov Websites

, 2014 Wind Power Opportunities in St. Thomas, USVI: A Site-Specific Evaluation and Analysis. NREL , Canada B.S., Chemical Engineering, Texas A&M University, College Station, Texas Featured Publications Low Carbon Desalination: Status and Research, Development, and Demonstration Needs. Report of a

Primary and secondary coronary heart disease prevention using statins: is targeting Adam or Eve equally effective?

PubMed

Kakafika, Anna I; Athyros, Vasilios G; Tziomalos, Konstantinos; Karagiannis, Asterios; Mikhailidis, Dimitri P

2008-06-01

Women differ from men in terms of their cardiovascular disease risk. The existing data suggest that primary cardiovascular disease prevention treatment with a statin could be cost effective for women and men with a high cardiovascular disease risk. In secondary cardiovascular disease prevention both men and women seem to benefit equally from statin treatment. However, the relatively small number of women included in several statin trials has limited the evidence available. With regard to the question of whether Eve is becoming Adam, the answer is not yet: we need more evidence!

The correlation of pain intensity and quality of life in chronic LBP patients in Adam Malik general hospital

NASA Astrophysics Data System (ADS)

Nasution, I. K.; Lubis, N. D. A.; Amelia, S.; Hocin, K.

2018-03-01

Low back pain (LBP) is a world health problems and a major cause of disability. The study is to determine the correlation between pain intensity and quality of life (QoL) in patients with chronic LBP. This study was a descriptive, analytical research with the cross sectional design. Twenty-nine chronic LBP outpatients that have visited the Neurology Clinic of Adam Malik General Hospital Medan. Patients from July to November 2015 were selected by consecutive sampling. A questionnaire and interview are asking the information about subjects’ characteristics, diagnosis, medical history, pain intensity and quality of life-based on WHO QoL criteria were used to collect the data. Using Spearman correlation test, we found correlation among VAS and physical function (p<0.001, r=-0.606), limitations due to physical problems (p<0.001, r=-0.837), limitations due to emotional problems (p=0.007, r=-0,477), vitality (p=0.021, r=-0.380), social function (p=0.015, r=-0.403), the feeling of pain (p=0.003, r=-0.499) and general health (p=0.040, r=-0.330). On the other hand, there was no correlation between VAS and mental health (p=0.110, r=-0.235). We concluded that pain intensity in outpatients with chronic LBP in the Neurology Clinic at Adam Malik General Hospital Medan correlates with the patients’ quality of life.

Wired enzyme electrodes--a retroperspective story about an exciting time at University of Texas at Austin and its impact on my scientific career.

PubMed

Lindquist, Sten-Eric

2013-07-22

The present paper features an exciting time in the late 1980s when I, as a visiting scientist, had the privilege to participate in the early and very exciting development of the in vivo redox-polymer-wired glucose sensor in Professor Adam Heller's laboratory at the Department of Chemical Engineering at University of Texas at Austin. This story is followed by an overview of the research my visit initiated at Uppsala University. In collaboration with Swedish colleagues, we explored a few of the many possibilities to form new biosensors by utilizing Prof. Heller's concept of cross-linked redox-polymer/redox-enzyme electrodes. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dynamic analysis of a bio-inspired climbing robot using ADAMS-Simulink co-simulation

NASA Astrophysics Data System (ADS)

Chattopadhyay, P.; Dikshit, H.; Majumder, A.; Ghoshal, S.; Maity, A.

2018-04-01

Climbing robot has been an area of interest since the demand of inspection of pipeline, nuclear power plant, and various big structure is growing up rapidly. This paper represents the development of a bio-inspired modular robot which mimics inchworm locomotion during climbing. In the present paper, the climbing motion is achieved only on a flat vertical plane by magnetic adhesion principle. The robot is modelled as a 4-link planar mechanism with three revolute joints actuated by DC servo motors. Sinusoidal gait pattern is used to approximate the motion of an inchworm. The dynamics of the robot is presented by using ADAMS/MATLAB co-simulation methodology. The simulation result gives the maximum value of joint torque during one complete cycle of motion. This torque value is used for the selection of servo motor specifications required to build the prototype.

Extraction-Separation Performance and Dynamic Modeling of Orion Test Vehicles with Adams Simulation: 2nd Edition

NASA Technical Reports Server (NTRS)

Fraire, Usbaldo, Jr.; Anderson, Keith; Varela, Jose G.; Bernatovich, Michael A.

2015-01-01

NASA's Orion Capsule Parachute Assembly System (CPAS) project has advanced into the third generation of its parachute test campaign and requires technically comprehensive modeling capabilities to simulate multi-body dynamics (MBD) of test articles released from a C-17. Safely extracting a 30,000 lbm mated test article from a C-17 and performing stable mid-air separation maneuvers requires an understanding of the interaction between elements in the test configuration and how they are influenced by extraction parachute performance, aircraft dynamics, aerodynamics, separation dynamics, and kinetic energy experienced by the system. During the real-time extraction and deployment sequences, these influences can be highly unsteady and difficult to bound. An avionics logic window based on time, pitch, and pitch rate is used to account for these effects and target a favorable separation state in real time. The Adams simulation has been employed to fine-tune this window, as well as predict and reconstruct the coupled dynamics of the Parachute Test Vehicle (PTV) and Cradle Platform Separation System (CPSS) from aircraft extraction through the mid-air separation event. The test-technique for the extraction of CPAS test articles has evolved with increased complexity and requires new modeling concepts to ensure the test article is delivered to a stable test condition for the programmer phase. Prompted by unexpected dynamics and hardware malfunctions in drop tests, these modeling improvements provide a more accurate loads prediction by incorporating a spring-damper line-model derived from the material properties. The qualification phase of CPAS testing is on the horizon and modeling increasingly complex test-techniques with Adams is vital to successfully qualify the Orion parachute system for human spaceflight.

The Earliest Reference to ADHD in the Medical Literature? Melchior Adam Weikard's Description in 1775 of "Attention Deficit" (Mangel der Aufmerksamkeit, Attentio Volubilis)

ERIC Educational Resources Information Center

Barkley, Russell A.; Peters, Helmut

2012-01-01

Objective: The present article reports on the discovery and translation of a chapter in a 1775 medical textbook by the German physician, Melchior Adam Weikard, which describes attention disorders. This article is believed to be the earliest reference to the syndrome that today is known as attention deficit hyperactivity disorder, or ADHD. Method:…

Historical Notes on the Expanding Universe

NASA Technical Reports Server (NTRS)

Way, Michael J.; Belenkyi, Ari; Nussbaumer, Harry; Peacock, John

2014-01-01

The article Measuring the Hubble constant by Mario Livio and Adam Riess (Physics Today, October 2013, page 41) reviewed studies of the expanding universe from the 1920s to the present. Although the history of the subject underwent considerable compression to fit the length of a magazine article, we think it may leave a misleading impression of some of the key steps to our current understanding. We therefore offer the following clarifications. Most significantly, papers by Arthur Eddington and by Willem de Sitter in 1930, who successfully promoted Georges Lematres 1927 article for the Scientific Society of Brussels, effected a paradigm shift in interpretation of extragalactic redshifts in 1930. Before then, the astronomical community was generally unaware of the existence of nonstatic cosmological solutions and did not broadly appreciate that redshifts could be thought of locally as Doppler shifts in an expanding matter distribution. Certainly, in 1929 Edwin Hubble referred only to the de Sitter solution of 1917. At the time, the relation between distance and redshift predicted in that model was generally seen purely as a manifestation of static spacetime curvature.

On the temperature dependence of the Adam-Gibbs equation around the crossover region in the glass transition

NASA Astrophysics Data System (ADS)

Duque, Michel; Andraca, Adriana; Goldstein, Patricia; del Castillo, Luis Felipe

2018-04-01

The Adam-Gibbs equation has been used for more than five decades, and still a question remains unanswered on the temperature dependence of the chemical potential it includes. Nowadays, it is a well-known fact that in fragile glass formers, actually the behavior of the system depends on the temperature region it is being studied. Transport coefficients change due to the appearance of heterogeneity in the liquid as it is supercooled. Using the different forms for the logarithmic shift factor and the form of the configurational entropy, we evaluate this temperature dependence and present a discussion on our results.

Adam Smith's invisible hand is unstable: physics and dynamics reasoning applied to economic theorizing

NASA Astrophysics Data System (ADS)

McCauley, Joseph L.

2002-11-01

Neo-classical economic theory is based on the postulated, nonempiric notion of utility. Neo-classical economists assume that prices, dynamics, and market equilibria are supposed to be derived from utility. The results are supposed to represent mathematically the stabilizing action of Adam Smith's invisible hand. In deterministic excess demand dynamics, however, a utility function generally does not exist mathematically due to nonintegrability. Price as a function of demand does not exist and all equilibria are unstable. Qualitatively, and empirically, the neo-classical prediction of price as a function of demand describes neither consumer nor trader demand. We also discuss five inconsistent definitions of equilibrium used in economics and finance, only one of which is correct, and then explain the fallacy in the economists’ notion of ‘temporary price equilibria’.

Adams-Oliver Syndrome with Unusual Central Nervous System Findings and an Extrahepatic Portosystemic Shunt

PubMed Central

Pérez-García, Carlos; Martín, Yolanda Ruíz; del Hoyo, Alejandra Aguado; Rodríguez, Carlos Marín; Domínguez, Minia Campos

2017-01-01

We report a case of a premature neonate girl with scalp and skull defects and brachydactyly of the feet consistent with an Adams-Oliver syndrome (AOS). The patient had central nervous system abnormalities, such as periventricular calcifications, hypoplastic corpus callosum, and bilateral hemispheric corticosubcortical hemorrhagic lesions. A muscular ventricular septal defect and a portosystemic shunt were diagnosed. To our knowledge, this is the first report of congenital supratentorial grey-white matter junction lesions without dural sinus thrombosis in association with AOS. Some of these lesions may be secondary to birth trauma (given the skull defect) whilst others have a watershed location, perhaps as further evidence of vascular disruption and decreased perfusion during critical periods of fetal brain development as the previously proposed pathogenesis of this syndrome. PMID:28706620

Body Size Changes of Royal Australian Air Force Aircrew: 1971 - 2005

DTIC Science & Technology

2009-08-01

International Airport (2004). Adam completed his Physiotherapy Degree in 2008 at the University of South Australia. Adam currently works as a physiotherapist...Australia (UniSA) School of Health Sciences student pool and personal contacts (e.g. friends, family and work colleagues). All subjects were fully informed

Gaia-GOSA: An interactive service for coordination of asteroid observation campaigns

NASA Astrophysics Data System (ADS)

Santana-Ros, Toni; Bartczak, Przemyslaw; Michalowski, Tadeusz; Marciniak, Anna; Butkiewicz-Bak, Magda; Dudziński, Grzegorz

2016-10-01

We describe the Gaia-Ground-based Observational Service for Asteroids (www.gaiagosa.eu), which is a website aiming to facilitate asteroid observers in contributing to the Gaia mission by gathering lightcurves of selected targets.There are many asteroids which lightcurves cannot be covered during one observing run, like slow rotators,with periods longer than 12 hours. There are also targets with periods commensurate with the Earth's day, sotheir lightcurves cannot be covered by observing from one site only. There are also targets of special interest,like binary objects, where a large amount of data is needed. For all targets like those mentioned above, acoordination of observers is needed, also to avoid unnecessary duplication of data gathering.To that end we have created Gaia-GOSA, a web service which allows coordination between observers, focuseson interesting targets and may avoid observers to unnecessary gather data of the same object at the sametime. Furthermore, it is not necessary to be an advanced observer to contribute to the project. The websiteprepares the observing plan, providing all the necessary information to point your telescope. Thesubscription is free and observers with any level of experience are welcome.All the data gathered by Gaia-GOSA users will be reduced and analyzed by astronomers from the Astronomical Observatory of Adam Mickiewicz University in Poznan (AO AMU). The resulting catalogue, containing all the lightcurves obtained, will be used to enhance the results of the Gaia (cornerstone European Space Agency's mission) inversion algorithm.The project has been developed under funding from the European Space Agency (ESA) and initially was only devoted to help users in planning photometric observations of asteroids. However, in this poster we also present an extended version of the website, which also aims to publish predictions of stellar occultations for selected targets. This work has been done in the framework of the Small Bodies: Near

Evidence that Distinct States of the Integrin α6β1 Interact with Laminin and an ADAM

PubMed Central

Chen, M.S.; Almeida, E.A.C.; Huovila, A.-P.J.; Takahashi, Y.; Shaw, L.M.; Mercurio, A.M.; White, J.M.

1999-01-01

Integrins can exist in different functional states with low or high binding capacity for particular ligands. We previously provided evidence that the integrin α6β1, on mouse eggs and on α6-transfected cells, interacted with the disintegrin domain of the sperm surface protein ADAM 2 (fertilin β). In the present study we tested the hypothesis that different states of α6β1 interact with fertilin and laminin, an extracellular matrix ligand for α6β1. Using α6-transfected cells we found that treatments (e.g., with phorbol myristate acetate or MnCl2) that increased adhesion to laminin inhibited sperm binding. Conversely, treatments that inhibited laminin adhesion increased sperm binding. Next, we compared the ability of fluorescent beads coated with either fertilin β or with the laminin E8 fragment to bind to eggs. In Ca2+-containing media, fertilin β beads bound to eggs via an interaction mediated by the disintegrin loop of fertilin β and by the α6 integrin subunit. In Ca2+-containing media, laminin E8 beads did not bind to eggs. Treatment of eggs with phorbol myristate acetate or with the actin disrupting agent, latrunculin A, inhibited fertilin bead binding, but did not induce laminin E8 bead binding. Treatment of eggs with Mn2+ dramatically increased laminin E8 bead binding, and inhibited fertilin bead binding. Our results provide the first evidence that different states of an integrin (α6β1) can interact with an extracellular matrix ligand (laminin) or a membrane-anchored cell surface ligand (ADAM 2). PMID:9971748

Higher serotonin transporter occupancy after multiple dose administration of escitalopram compared to citalopram: an [123I]ADAM SPECT study.

PubMed

Klein, Nikolas; Sacher, Julia; Geiss-Granadia, Thomas; Mossaheb, Nilufar; Attarbaschi, Trawat; Lanzenberger, Rupert; Spindelegger, Christoph; Holik, Alexander; Asenbaum, Susanne; Dudczak, Robert; Tauscher, Johannes; Kasper, Siegfried

2007-04-01

Previous studies have investigated the occupancy of the serotonin reuptake transporter (SERT) after clinical doses of citalopram and other selective serotonin reuptake inhibitors. In the present study, the occupancies of SERT after multiple doses of escitalopram and citalopram were compared using the radioligand [(123)I]ADAM and single photon emission computed tomography (SPECT). Fifteen healthy subjects received escitalopram 10 mg/day (n = 6) or citalopram 20 mg/day (n = 9) for a total of 10 days. SERT occupancies in midbrain were determined with SPECT and [(123)I]ADAM at three different time points: at baseline (no medication) and at 6 and 54 h after last drug intake. At 6 h after the last dose, mean SERT occupancies were 81.5 +/- 5.4% (mean+/-SD) for escitalopram and 64.0 +/- 12.7% for citalopram (p < 0.01). At 54 h after the last dose, mean SERT occupancies were 63.3 +/- 12.1% for escitalopram and 49.0 +/- 11.7% for citalopram (p < 0.05). The plasma concentrations of the S-enantiomer were of the same magnitude in both substances. For both drugs, the elimination rate of the S-enantiomer in plasma was markedly higher than the occupancy decline rate in the midbrain. The significantly higher occupancy of SERT after multiple doses of escitalopram compared to citalopram indicates an increased inhibition of SERT by escitalopram. The results can also be explained by an attenuating effect of R-citalopram on the occupancy of S-citalopram at the SERT.

Three-dimensional geophysical mapping of rock alteration and water content at Mount Adams, Washington: Implications for lahar hazards

USGS Publications Warehouse

Finn, C.A.; Deszcz-Pan, M.; Anderson, E.D.; John, D.A.

2007-01-01

Hydrothermally altered rocks, particularly if water saturated, can weaken stratovolcanoes, thereby increasing the potential for catastrophic sector collapses that can lead to far-traveled, destructive debris flows. Evaluating the hazards associated with such alteration is difficult because alteration has been mapped on few active volcanoes and the distribution and intensity of subsurface alteration are largely unknown on any active volcano. At Mount Adams, some Holocene debris flows contain abundant hydrothermal minerals derived from collapse of the altered, edifice. Intense hydrothermal alteration significantly reduces the resistivity and magnetization of volcanic rock, and therefore hydrothermally altered rocks can be identified with helicopter electromagnetic and magnetic measurements. Electromagnetic and magnetic data, combined with geological mapping and rock property measurements, indicate the presence of appreciable thicknesses of hydrothermally altered rock in the central core of Mount Adams north of the summit. We identify steep cliffs at the western edge of this zone as the likely source for future large debris flows. In addition, the electromagnetic data identified water in the brecciated core of the upper 100-200 m of the volcano. Water helps alter the rocks, reduces the effective stress, thereby increasing the potential for slope failure, and acts, with entrained melting ice, as a lubricant to transform debris avalanches into lahars. Therefore knowing the distribution of water is also important for hazard assessments. Our results demonstrate that high-resolution geophysical and geological observations can yield unprecedented views of the three-dimensional distribution of altered rock and shallow pore water aiding evaluation of the debris avalanche hazard.

[Effects of piracetam therapy in a case of Lance-Adams syndrome].

PubMed

Hoshino, Ai; Kumada, Satoko; Yokochi, Fusako; Hachiya, Yasuo; Hanafusa, Yukiko; Tomita, Sunao; Okiyama, Ryoich; Kurihara, Eiji

2009-09-01

We report a 17-year-old female patient with Lance-Adams syndrome caused by anoxic encephalopathy during a severe attack of bronchial asthma. She had difficulty in writing because of action myoclonus in her arms. She also exhibited freezing gait and was unable to walk without cane. Although her gait disturbance resembled those seen in patients with parkinsonism secondary to anoxic encephalopathy, surface electromyography revealed that it was caused by action myoclonus in her legs. The presence of giant somatosensory evoked potentials and enhanced cortical reflexes in response to the electrical stimulation to her posterior tibial nerves supported our diagnosis. A combined therapy with valproate sodium, clonazepam and piracetam (15 g/day) was not effective. However, her freezing gait remarkably improved and she was able to walk without help, after the treatment with sufficient dose of piracetam (21 g/day). Cortical hyperexcitability as revealed by electrophysiological examination also improved. We concluded that the combined therapy with antiepileptic drugs and piracetam was effective in the treatment for action myoclonus. However, because the effects seemed dose-related, the dosage of piracetam needed to be increased until the optimum effects were obtained.

Children and grief

MedlinePlus

... Clinical Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle, WA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team. Related MedlinePlus Health Topics Bereavement Child Mental Health Browse the Encyclopedia A.D.A.M., ...

Application of the thermorheologically complex nonlinear Adam-Gibbs model for the glass transition to molecular motion in hydrated proteins.

PubMed

Hodge, Ian M

2006-08-01

The nonlinear thermorheologically complex Adam Gibbs (extended "Scherer-Hodge") model for the glass transition is applied to enthalpy relaxation data reported by Sartor, Mayer, and Johari for hydrated methemoglobin. A sensible range in values for the average localized activation energy is obtained (100-200 kJ mol(-1)). The standard deviation in the inferred Gaussian distribution of activation energies, computed from the reported KWW beta-parameter, is approximately 30% of the average, consistent with the suggestion that some relaxation processes in hydrated proteins have exceptionally low activation energies.

Differentiation-induced skin cancer suppression by FOS, p53, and TACE/ADAM17

PubMed Central

Guinea-Viniegra, Juan; Zenz, Rainer; Scheuch, Harald; Jiménez, María; Bakiri, Latifa; Petzelbauer, Peter; Wagner, Erwin F.

2012-01-01

Squamous cell carcinomas (SCCs) are heterogeneous and aggressive skin tumors for which innovative, targeted therapies are needed. Here, we identify a p53/TACE pathway that is negatively regulated by FOS and show that the FOS/p53/TACE axis suppresses SCC by inducing differentiation. We found that epidermal Fos deletion in mouse tumor models or pharmacological FOS/AP-1 inhibition in human SCC cell lines induced p53 expression. Epidermal cell differentiation and skin tumor suppression were caused by a p53-dependent transcriptional activation of the metalloprotease TACE/ADAM17 (TNF-α–converting enzyme), a previously unknown p53 target gene that was required for NOTCH1 activation. Although half of cutaneous human SCCs display p53-inactivating mutations, restoring p53/TACE activity in mouse and human skin SCCs induced tumor cell differentiation independently of the p53 status. We propose FOS/AP-1 inhibition or p53/TACE reactivating strategies as differentiation-inducing therapies for SCCs. PMID:22772468

Evidence that a functional fertilin-like ADAM plays a role in human sperm-oolemmal interactions.

PubMed

Bronson, R A; Fusi, F M; Calzi, F; Doldi, N; Ferrari, A

1999-05-01

Fertilin is a protein initially identified in guinea pig spermatozoa; it is the prototype of a larger family of conserved, proteins designated as a disintegrin and a metalloproteinase (ADAM). These heterodimers which consist of alpha and beta subunits, containing metalloproteinase-like and disintegrin-like domains, appear to play a role in mammalian fertilization. Peptides derived from the disintegrin domains of two ADAMs, fertilin and cyritestin, interfere with gamete adhesion and sperm-egg membrane fusion in non-human species. It has been suggested that fertilin-beta binds to an oolemmal integrin, and it is proposed that the tripeptide FEE (Phe-Glu-Glu) is the integrin recognition sequence in human fertilin-beta. We evaluated whether fertilin beta plays a role in human fertilization by studying the effects of a linear octapeptide containing the FEE sequence, SFEECDLP, and a scrambled octapeptide with the same amino acids, SFPCEDEL, on the incorporation of human spermatozoa by human zona-free eggs. The effects of G4120, a potent RGD-containing (Arg-Gly-Asp) thioether-bridged cyclic peptide which blocks both fibronectin and vitronectin receptors, and the relationship between FEE- and RGD-receptor interactions on sperm-egg interactions were also studied. The FEE-containing peptide, but not the scrampled peptide, inhibited sperm adhesion to oocytes and their penetration, over the range 1-5 microM. The inhibition induced by SFEECDLP was reversible and occurred only in the presence of peptide itself. The G4120 peptide exhibited 10-fold less inhibitory effects on sperm adhesion and penetration than did SFEECDLP. When combined, SFEECDLP and G4120 exhibited strong inhibition of both adhesion and penetration at concentrations that individually had been ineffective, suggesting co-operation between the two receptor-ligand interactions during fertilization. We propose that a fertilin-like molecule is functionally active on human spermatozoa and that its interaction with an

Testimony of Gina Adams, Senior Fellow, Urban Institute. Before the Early Childhood, Elementary, and Secondary Education Subcommittee Hearing on "Improving Early Childhood Development Policies and Practices"

ERIC Educational Resources Information Center

Adams, Gina

2009-01-01

This paper presents the testimony of Gina Adams before the Early Childhood, Elementary, and Secondary Education Subcommittee Hearing on "Improving Early Childhood Development Policies and Practices." This testimony was presented to the House Committee on Education and Labor, U.S. House of Representatives last March 19, 2009. She talks about how…

More than a neuroanatomical representation in The Creation of Adam by Michelangelo Buonarroti, a representation of the Golden Ratio.

PubMed

de Campos, Deivis; Malysz, Tais; Bonatto-Costa, João Antonio; Jotz, Geraldo Pereira; de Oliveira Junior, Lino Pinto; da Rocha, Andrea Oxley

2015-09-01

Michelangelo Buonarroti (1475-1564) was a master anatomist as well as an artistic genius. He dissected numerous cadavers and developed a profound understanding of human anatomy. Among his best-known artworks are the frescoes painted on the ceiling of the Sistine Chapel (1508-1512), in Rome. Currently, there is some debate over whether the frescoes merely represent the teachings of the Catholic Church at the time or if there are other meanings hidden in the images. In addition, there is speculation regarding the image of the brain embedded in the fresco known as "The Creation of Adam," which contains anatomic features of the midsagittal and lateral surfaces of the brain. Within this context, we report our use of Image Pro Plus Software 6.0 to demonstrate mathematical evidence that Michelangelo painted "The Creation of Adam" using the Divine Proportion/Golden Ratio (GR) (1.6). The GR is classically associated with greater structural efficiency and is found in biological structures and works of art by renowned artists. Thus, according to the evidence shown in this article, we can suppose that the beauty and harmony recognized in all Michelangelo's works may not be based solely on his knowledge of human anatomical proportions, but that the artist also probably knew anatomical structures that conform to the GR display greater structural efficiency. It is hoped that this report will at least stimulate further scientific and scholarly contributions to this fascinating topic, as the study of these works of art is essential for the knowledge of the history of Anatomy. © 2015 Wiley Periodicals, Inc.

Geographic information system datasets of regolith-thickness data, regolith-thickness contours, raster-based regolith thickness, and aquifer-test and specific-capacity data for the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado

USGS Publications Warehouse

Arnold, L. Rick

2010-01-01

These datasets were compiled in support of U.S. Geological Survey Scientific-Investigations Report 2010-5082-Hydrogeology and Steady-State Numerical Simulation of Groundwater Flow in the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado. The datasets were developed by the U.S. Geological Survey in cooperation with the Lost Creek Ground Water Management District and the Colorado Geological Survey. The four datasets are described as follows and methods used to develop the datasets are further described in Scientific-Investigations Report 2010-5082: (1) ds507_regolith_data: This point dataset contains geologic information concerning regolith (unconsolidated sediment) thickness and top-of-bedrock altitude at selected well and test-hole locations in and near the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado. Data were compiled from published reports, consultant reports, and from lithologic logs of wells and test holes on file with the U.S. Geological Survey Colorado Water Science Center and the Colorado Division of Water Resources. (2) ds507_regthick_contours: This dataset consists of contours showing generalized lines of equal regolith thickness overlying bedrock in the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado. Regolith thickness was contoured manually on the basis of information provided in the dataset ds507_regolith_data. (3) ds507_regthick_grid: This dataset consists of raster-based generalized thickness of regolith overlying bedrock in the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado. Regolith thickness in this dataset was derived from contours presented in the dataset ds507_regthick_contours. (4) ds507_welltest_data: This point dataset contains estimates of aquifer transmissivity and hydraulic conductivity at selected well locations in the Lost Creek Designated Ground Water Basin, Weld, Adams, and

"Mitochondrial Eve", "Y Chromosome Adam", testosterone, and human evolution.

PubMed

Howard, James Michael

2002-01-01

I suggest primate evolution began as a consequence of increased testosterone in males which increased aggression and sexuality, therefore, reproduction and success. With time, negative effects of excessive testosterone reduced spermatogenesis and started a decline of the group. Approximately 30-40 million years ago, the gene DAZ (Deleted in AZoospermia) appeared on the Y chromosome, increased spermatogenesis, and rescued the early primates from extinction. (Note: DAZ is considered by some to specifically, positively affect spermatogenesis; others suggest it has no effect on spermatogenesis.) Hominid evolution continued with increasing testosterone. The advent of increased testosterone in females of Homo erectus (or Homo ergaster) increased the female-to-male body size ratio, and eventually produced another era of excessive testosterone. Excessive testosterone caused a reduction in population size (bottleneck) that produced the "Mitochondrial Eve" (ME) mechanism. (Only certain females continued during the bottleneck to transmit their mitochondrial DNA.) That is, the ME mechanism culminated, again, in excessive testosterone and reduced spermatogenesis in the hominid line. Approximately 50,000 to 200,000 years ago, a "doubling" of the DAZ gene occurred on the Y chromosome in hominid males which rescued the hominid line with increased spermatogenesis in certain males. This produced the "Y Chromosome Adam" event. The doubling of DAZ allowed further increases in testosterone in hominids that resulted in the increased size and development of the brain. Modern humans periodically fluctuate between the positive and negative consequences of increased levels of testosterone, currently identifiable as the secular trend, increased infections, and reduced spermatogenesis.

National Program for Inspection of Non-Federal Dams. Notch Reservoir Dam (MA 00283), Hoosic River Basin, North Adams, Massachusetts. Phase I Inspection Report.

DTIC Science & Technology

1979-06-01

floodwaters. About 600 feet downstream of the dam, West Mountain Road would be overtopped; 600 feet further downstream Reservoir Road would be overtopped for...removed and the surface coated to protect the pipes. . d. Reservoir Area- Notch Reservoir, as the name implies, is in a mountain notch. The area is...Brook which connects Notch Reservoir to the Hoosic River in the City of North Adams, Massachusetts, flows on a steep gradient down a mountain notch

Comparison of brain serotonin transporter using [I-123]-ADAM between obese and non-obese young adults without an eating disorder

PubMed Central

Wu, Chih-Hsing; Chang, Chin-Sung; Yang, Yen Kuang; Shen, Lie-Hang; Yao, Wei-Jen

2017-01-01

Cerebral serotonin metabolism has an important but controversial role in obesity. However, it is not given enough attention in morbidly obese young adults. We used single photon emission computed tomography (SPECT) with [I-123]-labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) to investigate changes in serotonin transporter (SERT) availability in 10 morbidly obese young adults without an eating disorder (M/F = 5/5, body mass index (BMI): 40.3 ± 4.1 kg/m2, percentage of body fat (BF%): 46.0 ± 3.9%) and 10 age- and sex-matched non-obese controls (BMI: 20.3 ± 1.2 kg/m2, BF%: 20.6 ± 8.9%). All participants underwent SPECT at 10 min and 6 h after an injection of 200 MBq of [I-123]-ADAM. The SERT binding site (midbrain) was drawn with cerebellum normalization. The BF% and fat distribution were measured using dual-energy X-ray absorptiometry. The midbrain/cerebellum SERT binding ratios (2.49 ± 0.46 vs. 2.47 ± 0.47; p = 0.912) at 6 h were not significantly different between groups, nor was the distribution of the summed images at 10 min (1.36 ± 0.14 vs. 1.35 ± 0.11; p = 0.853). There were no significant correlations between midbrain/cerebellum SERT binding ratio and age, BMI, BF%, or fat distribution. No significant difference in SERT availability in the midbrain between morbidly obese and non-obese young adults without an eating disorder indicates an unmet need for investigating the role of cerebral serotonin in obesity. PMID:28182708

Adams, Walter Sydney (1876-1956)

NASA Astrophysics Data System (ADS)

Murdin, P.

2000-11-01

Born in Antioch, Syria, to American missionary parents, he worked under GEORGE HALE at Yerkes Observatory at the University of Chicago, accompanying Hale to California to set up the Mount Wilson Observatory, and becoming its director on Hale's retirement. He helped design the 200 in telescope for Mount Palomar Observatory. His method of spectroscopic parallaxes, a technique using spectra to give ...

The Adam Walsh Act: An Examination of Sex Offender Risk Classification Systems.

PubMed

Zgoba, Kristen M; Miner, Michael; Levenson, Jill; Knight, Raymond; Letourneau, Elizabeth; Thornton, David

2016-12-01

This study was designed to compare the Adam Walsh Act (AWA) classification tiers with actuarial risk assessment instruments and existing state classification schemes in their respective abilities to identify sex offenders at high risk to re-offend. Data from 1,789 adult sex offenders released from prison in four states were collected (Minnesota, New Jersey, Florida, and South Carolina). On average, the sexual recidivism rate was approximately 5% at 5 years and 10% at 10 years. AWA Tier 2 offenders had higher Static-99R scores and higher recidivism rates than Tier 3 offenders, and in Florida, these inverse correlations were statistically significant. Actuarial measures and existing state tier systems, in contrast, did a better job of identifying high-risk offenders and recidivists. As well, we examined the distribution of risk assessment scores within and across tier categories, finding that a majority of sex offenders fall into AWA Tier 3, but more than half score low or moderately low on the Static-99R. The results indicate that the AWA sex offender classification scheme is a poor indicator of relative risk and is likely to result in a system that is less effective in protecting the public than those currently implemented in the states studied. © The Author(s) 2015.

Spiro K. Antiochos Receives 2013 John Adam Fleming Medal: Citation

NASA Astrophysics Data System (ADS)

Klimchuk, James A.

2014-01-01

The John Adam Fleming Medal is awarded for "original research and technical leadership in geomagnetism, atmospheric electricity, aeronomy, space physics, and related sciences." Originality and technical leadership are exactly the characteristics that distinguish the research of Spiro K. Antiochos. Spiro possesses a truly unique combination of physical insight, creativity, and mastery of the concepts and mathematical and numerical tools of space physics. These talents have allowed him to develop completely original theories for major observational problems and to test and refine those theories using sophisticated numerical simulation codes that he himself helped to develop. Spiro's physical insight is especially impressive. He has an uncanny ability to identify the fundamental aspects of complex problems and to see physical connections where others do not. This can sometimes involve ideas that may initially seem counterintuitive to those with less creativity. Many of Spiro's revolutionary advances have opened up whole new areas of study and shaped the course of space physics. Examples include the breakout model for coronal mass ejections (CMEs), the S-web model for the slow solar wind, and the thermal nonequilibrium model for solar prominences. The breakout model is of special significance to AGU as it strives to promote science for the betterment of humanity. CMEs are enormous explosions on the Sun that can have major "space weather" impacts here on Earth. They affect technologies ranging from communication and navigation systems to electrical power grids. Breakout is the leading theory for why CMEs occur and may one day be the foundation for more accurate space weather forecasting.

Understanding Influence within the Context of Nursing: Development of the Adams Influence Model Using Practice, Research, and Theory.

PubMed

Adams, Jeffrey M; Natarajan, Sudha

2016-01-01

Acquiring influence, and knowing how to use it, is a required competency for nurse leaders, yet the concept of influence and how it works is not well described in the nursing literature. In this article, the authors examine what is known about influence and present an influence model specific to nurse leaders. The Adams Influence Model was developed through an iterative process and is based on a comprehensive review of the influence literature, expert commentary, multiple pilot studies, evaluation of nursing theories, and validation by an external data source. Rather than defining "how to" influence, the model serves as a guide for personal reflection, helping nurse leaders understand and reflect on the influence process and factors, tactics, and strategies they can use when seeking to influence others.

Predictive use of routine 24-hour electrocardiography in suspected Adams-Stokes syndrome. Comparison with cardiac rhythm during symptoms.

PubMed Central

Abdon, N J; Johansson, B W; Lessem, J

1982-01-01

Using strictly defined criteria of significant arrhythmias, long term electrocardiographic recording has been evaluated for confirmation of arrhythmias as the cause of cerebral symptoms in 81 patients with suspected Adams-Stokes syndrome. Extension of long term electrocardiographic recording for more than 24 hours gives marginal additional information at a high cost. Among 43 patients monitored until symptoms appeared, non cardiogenic causes were confirmed in 20 of 22 patients because the recording showed normal rhythm during symptoms. Fifteen of 21 patients with a significant arrhythmia during an asymptomatic 24 hour recording later had the same arrhythmia during symptoms. Of 38 patients who failed to develop symptoms, 21 had a significant arrhythmia detectable within 24 hours and 23 when 48 hours of recording were analysed. PMID:7082502

Number of discernible colors for color-deficient observers estimated from the MacAdam limits.

PubMed

Perales, Esther; Martínez-Verdú, Francisco Miguel; Linhares, João Manuel Maciel; Nascimento, Sérgio Miguel Cardoso

2010-10-01

We estimated the number of colors perceived by color normal and color-deficient observers when looking at the theoretic limits of object-color stimuli. These limits, the optimal color stimuli, were computed for a color normal observer and CIE standard illuminant D65, and the resultant colors were expressed in the CIELAB and DIN99d color spaces. The corresponding color volumes for abnormal color vision were computed using models simulating for normal trichromatic observers the appearance for dichromats and anomalous trichomats. The number of colors perceived in each case was then computed from the color volumes enclosed by the optimal colors also known as MacAdam limits. It was estimated that dichromats perceive less than 1% of the colors perceived by normal trichromats and that anomalous trichromats perceive 50%-60% for anomalies in the medium-wavelength-sensitive and 60%-70% for anomalies in the long-wavelength-sensitive cones. Complementary estimates obtained similarly for the spectral locus of monochromatic stimuli suggest less impairment for color-deficient observers, a fact that is explained by the two-dimensional nature of the locus.

Analysis of Survivor Benefit Plan - Acceptance and Comparison with Private Sector

DTIC Science & Technology

1989-01-01

I COPY AIU WAR COLLEGE ,.SEARCH REPORT ,YSIS OF SURVIVOR BENEFIT PLAN-__CCEPTANCE ’-U AND COMPARISON WITH PRIVATE SECTOR LIEUENNT COLONEL JOHN R...AAA AIR WAR COLLEGE AIR UNIVERSITY ANALYSIS OF SURVIVOR BENEFIT PLAN--ACCEPTANCE AND COMPARISON WITH PRIVATE SECTOR by John R. Adams Lieutenant...Survivor Benefit Plan (SBP)--Acceptance and Comparison With Private Sector . AUTHORS: John R. Adams, Lieutenant Colonel, USAF; Daniel 3. Kohn

Wind turbine design codes: A comparison of the structural response

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

Buhl, M.L. Jr.; Wright, A.D.; Pierce, K.G.

2000-03-01

The National Wind Technology Center (NWTC) of the National Renewable Energy Laboratory is continuing a comparison of several computer codes used in the design and analysis of wind turbines. The second part of this comparison determined how well the programs predict the structural response of wind turbines. In this paper, the authors compare the structural response for four programs: ADAMS, BLADED, FAST{_}AD, and YawDyn. ADAMS is a commercial, multibody-dynamics code from Mechanical Dynamics, Inc. BLADED is a commercial, performance and structural-response code from Garrad Hassan and Partners Limited. FAST{_}AD is a structural-response code developed by Oregon State University and themore » University of Utah for the NWTC. YawDyn is a structural-response code developed by the University of Utah for the NWTC. ADAMS, FAST{_}AD, and YawDyn use the University of Utah's AeroDyn subroutine package for calculating aerodynamic forces. Although errors were found in all the codes during this study, once they were fixed, the codes agreed surprisingly well for most of the cases and configurations that were evaluated. One unresolved discrepancy between BLADED and the AeroDyn-based codes was when there was blade and/or teeter motion in addition to a large yaw error.« less

CSUNSat-1 Team working on their CubeSat at California State University Northridge

NASA Image and Video Library

2015-03-02

CSUNSat-1 Team (Adam Kaplan, James Flynn, Donald Eckels) working on their CubeSat at California State University Northridge. The primary mission of CSUNSat1 is to space test an innovative low temperature capable energy storage system developed by the Jet Propulsion Laboratory, raising its TRL level to 7 from 4 to 5. The success of this energy storage system will enable future missions, especially those in deep space to do more science while requiring less energy, mass and volume. This CubeSat was designed, built, programmed, and tested by a team of over 70 engineering and computer science students at CSUN.  The primary source of funding for CSUNSat1 comes from NASA’s Smallest Technology Partnership program. Launched by NASA’s CubeSat Launch Initiative NET April 18, 2017 ELaNa XVII mission on the seventh Orbital-ATK Cygnus Commercial Resupply Services (OA-7) to the International Space Station and deployed on tbd.

Changes in the cardiac muscle electric activity as a result of Coronary Artery Bypass Graft operation

NASA Astrophysics Data System (ADS)

Grajek, Magdalena; Krzyminiewski, Ryszard; Kalawski, Ryszard; Kulczak, Mariusz

2008-01-01

Many bioelectric signals have a complex internal structure that can be a rich source of information on the tissue or cell processes. The structure of such signals can be analysed in detail by applying digital methods of signal processing. Therefore, of substantial use in diagnosis of the coronary arterial disease is the method of digital enhancement of increasing signal resolution ECG (NURSE-ECG), permitting detection of temporary changes in the electric potentials in the cardiac muscle in the process of depolarisation. Thanks to the application of NURSE-ECG it has become possible to detect relatively small changes in the electric activity of particular fragments of the cardiac muscle undetectable by the standard ECG method, caused by ischemia, the effect of a drug or infarct. The aim of this study was to identify and analyse changes in the electric activity of the cardiac muscle as a result of the Coronary Artery Bypass Graft (CABG) operation. In this study the method of NURSE-ECG has been applied in order to identify and analyse changes in the electric activity of the cardiac muscle as a result of the CABG operation. In the study performed in cooperation of the Institute of Physics Adam Mickiewicz University and the Strus Hospital, Cardiac Surgery Ward, 37 patients with advanced coronary arterial disease were asked to participate. The patients were examined prior to the operation, on the day after the operation and two months after the operation and a year after the operation. The ECG recordings were subjected to a numerical procedure of resolution enhancement by a NURSE-ECG program to reveal the tentative changes in the electric potential of the cardiac muscle on its depolarisation. Results of the study have shown that the NURSE ECG method can be applied to monitor changes in the electric activity of the cardiac muscle occurring as a result of CABG operation. One the second day after the operation in the majority of patients (70%) a rapid decrease of the total

Distribution of melt beneath Mount St Helens and Mount Adams inferred from magnetotelluric data

NASA Astrophysics Data System (ADS)

Hill, Graham J.; Caldwell, T. Grant; Heise, Wiebke; Chertkoff, Darren G.; Bibby, Hugh M.; Burgess, Matt K.; Cull, James P.; Cas, Ray A. F.

2009-11-01

Three prominent volcanoes that form part of the Cascade mountain range in Washington State (USA)-Mounts St Helens, Adams and Rainier-are located on the margins of a mid-crustal zone of high electrical conductivity. Interconnected melt can increase the bulk conductivity of the region containing the melt, which leads us to propose that the anomalous conductivity in this region is due to partial melt associated with the volcanism. Here we test this hypothesis by using magnetotelluric data recorded at a network of 85 locations in the area of the high-conductivity anomaly. Our data reveal that a localized zone of high conductivity beneath this volcano extends downwards to join the mid-crustal conductor. As our measurements were made during the recent period of lava extrusion at Mount St Helens, we infer that the conductivity anomaly associated with the localized zone, and by extension with the mid-crustal conductor, is caused by the presence of partial melt. Our interpretation is consistent with the crustal origin of silicic magmas erupting from Mount St Helens, and explains the distribution of seismicity observed at the time of the catastrophic eruption in 1980 (refs 9, 10).

Exemplar Models as a Mechanism for Performing Bayesian Inference

DTIC Science & Technology

2010-01-01

Feldman Department of Cognitive and Linguistic Sciences Brown University Adam N. Sanborn Gatsby Computational Neuroscience Unit University College London...problem. As noted above, particle filters are another instance of a rational process model, but the great diversity of efficient approximation algorithms

Analysis of mixed model in gear transmission based on ADAMS

NASA Astrophysics Data System (ADS)

Li, Xiufeng; Wang, Yabin

2012-09-01

The traditional method of mechanical gear driving simulation includes gear pair method and solid to solid contact method. The former has higher solving efficiency but lower results accuracy; the latter usually obtains higher precision of results while the calculation process is complex, also it is not easy to converge. Currently, most of the researches are focused on the description of geometric models and the definition of boundary conditions. However, none of them can solve the problems fundamentally. To improve the simulation efficiency while ensure the results with high accuracy, a mixed model method which uses gear tooth profiles to take the place of the solid gear to simulate gear movement is presented under these circumstances. In the process of modeling, build the solid models of the mechanism in the SolidWorks firstly; Then collect the point coordinates of outline curves of the gear using SolidWorks API and create fit curves in Adams based on the point coordinates; Next, adjust the position of those fitting curves according to the position of the contact area; Finally, define the loading conditions, boundary conditions and simulation parameters. The method provides gear shape information by tooth profile curves; simulates the mesh process through tooth profile curve to curve contact and offer mass as well as inertia data via solid gear models. This simulation process combines the two models to complete the gear driving analysis. In order to verify the validity of the method presented, both theoretical derivation and numerical simulation on a runaway escapement are conducted. The results show that the computational efficiency of the mixed model method is 1.4 times over the traditional method which contains solid to solid contact. Meanwhile, the simulation results are more closely to theoretical calculations. Consequently, mixed model method has a high application value regarding to the study of the dynamics of gear mechanism.

HABS drawing field team at east entrance to Cyclorama Building. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

HABS drawing field team at east entrance to Cyclorama Building. Front, left to right: Robyn Chrabascz (Roger Williams University), Brian Carnahan (University of Arkansas), Noelle McManus (Edinburgh College of Art, ICOMOS/Great Britian), Amanda Loughlin (Kansas State University). Standing: Steven Utz, Field Supervisor. - Cyclorama Building, 125 Taneytown Road, Gettysburg, Adams County, PA

Airborne Magnetic and Electromagnetic Data map Rock Alteration and Water Content at Mount Adams, Mount Baker and Mount Rainier, Washington: Implications for Lahar Hazards and Hydrothermal Systems

NASA Astrophysics Data System (ADS)

Finn, C. A.; Deszcz-Pan, M.; Horton, R.; Breit, G.; John, D.

2007-12-01

High resolution helicopter-borne magnetic and electromagnetic (EM) data flown over the rugged, ice-covered, highly magnetic and mostly resistive volcanoes of Mount Rainier, Mount Adams and Mount Baker, along with rock property measurements, reveal the distribution of alteration, water and hydrothermal fluids that are essential to evaluating volcanic landslide hazards and understanding hydrothermal systems. Hydrothermally altered rocks, particularly if water saturated, can weaken stratovolcanoes, thereby increasing the potential for catastrophic sector collapses that can lead to far-traveled, destructive debris flows. Intense hydrothermal alteration significantly reduces the magnetization and resistivity of volcanic rock resulting in clear recognition of altered rock by helicopter magnetic and EM measurements. Magnetic and EM data, combined with geological mapping and rock property measurements, indicate the presence of appreciable thicknesses of hydrothermally altered rock west of the modern summit of Mount Rainier in the Sunset Amphitheater region, in the central core of Mount Adams north of the summit, and in much of the central cone of Mount Baker. We identify the Sunset Amphitheater region and steep cliffs at the western edge of the central altered zone at Mount Adams as likely sources for future debris flows. In addition, the EM data identified water-saturated rocks in the upper 100-200 m of the three volcanoes. The water-saturated zone could extend deeper, but is beyond the detection limits of the EM data. Water in hydrothermal fluids reacts with the volcanic rock to produce clay minerals. The formation of clay minerals and presence of free water reduces the effective stress, thereby increasing the potential for slope failure, and acts, with entrained melting ice, as a lubricant to transform debris avalanches into lahars. Therefore, knowing the distribution of water is also important for hazard assessments. Finally, modeling requires extremely low

A Method for Soft Body Armor Evaluation: Medical Assessment

DTIC Science & Technology

1975-01-01

the invstigators adhered to the "Guide for the Care and Use of Laboratory Animals ," as promulgated by the Committee on Revision of the Guide for...Laboratory Animal Facilities and Care of the Institute of Laboratory Animal Resources - National Research Council. The use of trade names in this report...Messrs Carlyle Uilly, Russell Prather, James Lewis, and Alexander Mickiewicz, who helped conduct all animal experiments; Mr. John Janeson for target

Factors related to successful treatment of drug-resistance tuberculosis in H. Adam Malik hospital, Medan, Indonesia

NASA Astrophysics Data System (ADS)

Manurung, M. P. F.; Siagian, P.; Sinaga, B. Y. M.; Mutiara, E.

2018-03-01

The number of drug-resistant TB cases keeps increasing for over the years. Drug-resistant TB is adifficult case because of the treatment, many side effects, more expensive, and less satisfactory results. This study is a retrospective cohort design aimed to determine the factors influencing the success of TB drug resistance treatment at H. Adam Malik Hospital during 2012–2015. The number of confirmed patients with drug-resistant TB was 223 people, 153 male, and 70 female. Two factors have been found to affect the treatment outcomes significantly, age and resistance pattern (P<0.05). Patients aged <50 years old have 2.73 times greater chance of recovery than patients aged ≥50 years old. Based on resistance pattern, patients with rifampicin resistant or poly-resistant would be 6.4 times more likely to recover compared with pre-XDR patients. There was no significant difference in the success rate of treatment among MDR patients compared with rifampicin resistant or poly-resistant cases. Age and resistance pattern has been proved to influence the success of drug-resistant TB treatment.

Volumes and bulk densities of forty asteroids from ADAM shape modeling

NASA Astrophysics Data System (ADS)

Hanuš, J.; Viikinkoski, M.; Marchis, F.; Ďurech, J.; Kaasalainen, M.; Delbo', M.; Herald, D.; Frappa, E.; Hayamizu, T.; Kerr, S.; Preston, S.; Timerson, B.; Dunham, D.; Talbot, J.

2017-05-01

Context. Disk-integrated photometric data of asteroids do not contain accurate information on shape details or size scale. Additional data such as disk-resolved images or stellar occultation measurements further constrain asteroid shapes and allow size estimates. Aims: We aim to use all the available disk-resolved images of approximately forty asteroids obtained by the Near-InfraRed Camera (Nirc2) mounted on the W.M. Keck II telescope together with the disk-integrated photometry and stellar occultation measurements to determine their volumes. We can then use the volume, in combination with the known mass, to derive the bulk density. Methods: We downloaded and processed all the asteroid disk-resolved images obtained by the Nirc2 that are available in the Keck Observatory Archive (KOA). We combined optical disk-integrated data and stellar occultation profiles with the disk-resolved images and use the All-Data Asteroid Modeling (ADAM) algorithm for the shape and size modeling. Our approach provides constraints on the expected uncertainty in the volume and size as well. Results: We present shape models and volume for 41 asteroids. For 35 of these asteroids, the knowledge of their mass estimates from the literature allowed us to derive their bulk densities. We see a clear trend of lower bulk densities for primitive objects (C-complex) and higher bulk densities for S-complex asteroids. The range of densities in the X-complex is large, suggesting various compositions. We also identified a few objects with rather peculiar bulk densities, which is likely a hint of their poor mass estimates. Asteroid masses determined from the Gaia astrometric observations should further refine most of the density estimates.

Distribution of melt beneath Mount St Helens and Mount Adams inferred from magnetotelluric data

USGS Publications Warehouse

Hill, G.J.; Caldwell, T.G.; Heise, W.; Chertkoff, D.G.; Bibby, H.M.; Burgess, M.K.; Cull, J.P.; Cas, Ray A.F.

2009-01-01

Three prominent volcanoes that form part of the Cascade mountain range in Washington State (USA)Mounts StHelens, Adams and Rainierare located on the margins of a mid-crustal zone of high electrical conductivity1,5. Interconnected melt can increase the bulk conductivity of the region containing the melt6,7, which leads us to propose that the anomalous conductivity in this region is due to partial melt associated with the volcanism. Here we test this hypothesis by using magnetotelluric data recorded at a network of 85 locations in the area of the high-conductivity anomaly. Our data reveal that a localized zone of high conductivity beneath thisvolcano extends downwards to join the mid-crustal conductor. As our measurements were made during the recent period of lava extrusion at Mount St Helens, we infer that the conductivity anomaly associated with the localized zone, and by extension with the mid-crustal conductor, is caused by the presence of partial melt. Our interpretation is consistent with the crustal origin of silicic magmas erupting from Mount St Helens8, and explains the distribution of seismicity observed at the time of the catastrophic eruption in 1980 (refs9, 10). ?? 2009 Macmillan Publishers Limited. All rights reserved.

The Adam family metalloprotease Kuzbanian regulates the cleavage of the roundabout receptor to control axon repulsion at the midline

PubMed Central

Coleman, Hope A.; Labrador, Juan-Pablo; Chance, Rebecca K.; Bashaw, Greg J.

2010-01-01

Slits and their Roundabout (Robo) receptors mediate repulsive axon guidance at the Drosophila ventral midline and in the vertebrate spinal cord. Slit is cleaved to produce fragments with distinct signaling properties. In a screen for genes involved in Slit-Robo repulsion, we have identified the Adam family metalloprotease Kuzbanian (Kuz). Kuz does not regulate midline repulsion through cleavage of Slit, nor is Slit cleavage essential for repulsion. Instead, Kuz acts in neurons to regulate repulsion and Kuz can cleave the Robo extracellular domain in Drosophila cells. Genetic rescue experiments using an uncleavable form of Robo show that this receptor does not maintain normal repellent activity. Finally, Kuz activity is required for Robo to recruit its downstream signaling partner, Son of sevenless (Sos). These observations support the model that Kuz-directed cleavage is important for Robo receptor activation. PMID:20570941

78 FR 57604 - Endangered and Threatened Wildlife and Plants; Proposed Endangered Status for Gunnison Sage...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-19

... likely impacts of climate change on the Gunnison sage-grouse and proposed critical habitat. (11) With... draft economic analysis, or the draft environmental assessment by mail from the Western Colorado Field... public hearing will be held at Western State Colorado University, University Center, 600 N. Adams Street...

Morphology and phylogenetic analysis of two oxytrichid soil ciliates from China, Oxytricha paragranulifera n. sp. and Oxytricha granulifera Foissner and Adam, 1983 (Protista, Ciliophora, Hypotrichia).

PubMed

Shao, Chen; Lv, Zhao; Pan, Ying; Al-Rasheid, Khaled A S; Yi, Zhenzhen

2014-09-01

The morphology and infraciliature of two hypotrichous ciliates, Oxytricha paragranulifera n. sp. and Oxytricha granulifera Foissner and Adam, 1983, collected respectively from the surface of a sandy soil in the Huguang mangrove forest, Zhanjiang, China, and the surface of soil in a forest beside Ziwu Road, Xian, north-west China, were examined. O. paragranulifera n. sp. is characterized by an elongate body with slightly tapered anterior end, two macronuclear nodules and two micronuclei, paroral and endoral in Stylonychia-pattern, colourless cortical granules distributed in clusters or irregular short rows, adoral zone occupying 37 % of the body length, marginal rows almost confluent posteriorly, six dorsal kineties and three caudal cirri, caudal cirri and dorsal bristles almost indistinguishable when viewed in vivo. The well-known O. granulifera Foissner and Adam, 1983 was also redescribed and can be separated from the novel species by having cortical granules arranged along dorsal kineties and marginal rows on both sides (vs grouped in clusters as well as in short irregular rows), paroral and endoral in Oxytricha-pattern (vs in Stylonychia-pattern), macronuclear nodules obviously detached (vs adjacent) and a non-saline terrestrial habitat (vs saline terrestrial). The separation of these two taxa is also firmly supported by the molecular data, which show a significant difference between the two in their SSU rRNA gene sequences (similarity 97.1 %). Phylogenetic analyses based on SSU rRNA gene sequence data suggest a close relationship within the Oxytrichidae assemblage between O. paragranulifera n. sp. and O. granulifera. © 2014 IUMS.

Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity.

PubMed

Misemer, Benjamin S; Skubitz, Amy P N; Carlos Manivel, J; Schmechel, Stephen C; Cheng, Edward Y; Henriksen, Jonathan C; Koopmeiners, Joseph S; Corless, Christopher L; Skubitz, Keith M

2014-02-01

Aggressive fibromatosis (AF) represents a group of tumors with a variable and unpredictable clinical course, characterized by a monoclonal proliferation of myofibroblastic cells. The optimal treatment for AF remains unclear. Identification and validation of genes whose expression patterns are associated with AF may elucidate biological mechanisms in AF, and aid treatment selection. This study was designed to examine the protein expression by immunohistochemistry (IHC) of four genes, ADAM12, FAP, SOX11, and WISP1, that were found in an earlier study to be uniquely overexpressed in AF compared with normal tissues. Digital image analysis was performed to evaluate inter- and intratumor heterogeneity, and correlate protein expression with histologic features, including a histopathologic assessment of tumor activity, defined by nuclear chromatin density ratio (CDR). AF tumors exhibited marked inter- and intratumor histologic heterogeneity. Pathologic assessment of tumor activity and digital assessment of average nuclear size and CDR were all significantly correlated. IHC revealed protein expression of all four genes. IHC staining for ADAM12, FAP, and WISP1 correlated with CDR and was higher, whereas SOX11 staining was lower in tumors with earlier recurrence following excision. All four proteins were expressed, and the regional variation in tumor activity within and among AF cases was demonstrated. A spatial correlation between protein expression and nuclear morphology was observed. IHC also correlated with the probability of recurrence following excision. These proteins may be involved in AF pathogenesis and the corresponding pathways could serve as potential targets of therapy. © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Multicultural Education: Strategies for Implementation in Colleges and Universities. Volume 4.

ERIC Educational Resources Information Center

Adams, J. Q., Ed.; Welsch, Janice R., Ed.

The 21 essays of this book discuss strategies for implementing multicultural education at the higher education level, especially in Illinois. Following a statement on multicultural education by former Senator Carol Moseley-Braun and an introduction by the text's editors (J. Q. Adams and Janice R. Welsch), the papers are: "Multicultural…

In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram.

PubMed

Klein, N; Sacher, J; Geiss-Granadia, T; Attarbaschi, T; Mossaheb, N; Lanzenberger, R; Pötzi, C; Holik, A; Spindelegger, C; Asenbaum, S; Dudczak, R; Tauscher, J; Kasper, S

2006-10-01

Escitalopram is a dual serotonin reuptake inhibitor (SSRI) approved for the treatment of depression and anxiety disorders. It is the S-enantiomer of citalopram, and is responsible for the serotonin reuptake activity, and thus for its pharmacological effects. Previous studies pointed out that clinically efficacious doses of other SSRIs produce an occupancy of the serotonin reuptake transporter (SERT) of about 80% or more. The novel radioligand [123I]ADAM and single photon emission computer tomography (SPECT) were used to measure midbrain SERT occupancies for different doses of escitalopram and citalopram. Twenty-five healthy subjects received a single dose of escitalopram [5 mg (n=5), 10 mg (n=5), and 20 mg (n=5)] or citalopram [(10 mg (n=5) and 20 mg (n=5)]. Midbrain SERT binding was measured with [(123)I]ADAM and SPECT on two study days, once without study drug and once 6 h after single dose administration of the study drug. The ratio of midbrain-cerebellum/cerebellum was the outcome measure (V3") for specific binding to SERT in midbrain. Subsequently, SERT occupancy levels were calculated using the untreated baseline level for each subject. An Emax model was used to describe the relationship between S-citalopram concentrations and SERT occupancy values. Additionally, four subjects received placebo to determine test-retest variability. Single doses of 5, 10, or 20 mg escitalopram led to a mean SERT occupancy of 60+/-6, 64+/-6, and 75+/-5%, respectively. SERT occupancies for subjects treated with single doses of 10 and 20 mg citalopram were 65+/-10 and 70+/-6%, respectively. A statistically significant difference was found between SERT occupancies after application of 10 and 20 mg escitalopram, but not for 10 and 20 mg citalopram. There was no statistically significant difference between the SERT occupancies of either 10 mg citalopram or 10 mg escitalopram, or between 20 mg citalopram and 20 mg escitalopram. Emax was slightly higher after administration of

Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort.

PubMed

Meester, Josephina A N; Sukalo, Maja; Schröder, Kim C; Schanze, Denny; Baynam, Gareth; Borck, Guntram; Bramswig, Nuria C; Duman, Duygu; Gilbert-Dussardier, Brigitte; Holder-Espinasse, Muriel; Itin, Peter; Johnson, Diana S; Joss, Shelagh; Koillinen, Hannele; McKenzie, Fiona; Morton, Jenny; Nelle, Heike; Reardon, Willie; Roll, Claudia; Salih, Mustafa A; Savarirayan, Ravi; Scurr, Ingrid; Splitt, Miranda; Thompson, Elizabeth; Titheradge, Hannah; Travers, Colm P; Van Maldergem, Lionel; Whiteford, Margo; Wieczorek, Dagmar; Vandeweyer, Geert; Trembath, Richard; Van Laer, Lut; Loeys, Bart L; Zenker, Martin; Southgate, Laura; Wuyts, Wim

2018-06-20

Adams-Oliver syndrome (AOS) is a rare developmental disorder, characterized by scalp aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). Autosomal dominant forms of AOS are linked to mutations in ARHGAP31, DLL4, NOTCH1 or RBPJ, while DOCK6 and EOGT underlie autosomal recessive inheritance. Data on the frequency and distribution of mutations in large cohorts is currently limited. The purpose of this study was therefore to comprehensively examine the genetic architecture of AOS in an extensive cohort. Molecular diagnostic screening of 194 AOS/ACC/TTLD probands/families was conducted using next-generation and/or capillary sequencing analyses. In total, we identified 63 (likely) pathogenic mutations, comprising 56 distinct and 22 novel mutations, providing a molecular diagnosis in 30% of patients. Taken together with previous reports, these findings bring the total number of reported disease variants to 63, with a diagnostic yield of 36% in familial cases. NOTCH1 is the major contributor, underlying 10% of AOS/ACC/TTLD cases, with DLL4 (6%), DOCK6 (6%), ARHGAP31 (3%), EOGT (3%), and RBPJ (2%) representing additional causality in this cohort. We confirm the relevance of genetic screening across the AOS/ACC/TTLD spectrum, highlighting preliminary but important genotype-phenotype correlations. This cohort offers potential for further gene identification to address missing heritability. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The Ansel Adams zone system: HDR capture and range compression by chemical processing

NASA Astrophysics Data System (ADS)

McCann, John J.

2010-02-01

We tend to think of digital imaging and the tools of PhotoshopTM as a new phenomenon in imaging. We are also familiar with multiple-exposure HDR techniques intended to capture a wider range of scene information, than conventional film photography. We know about tone-scale adjustments to make better pictures. We tend to think of everyday, consumer, silver-halide photography as a fixed window of scene capture with a limited, standard range of response. This description of photography is certainly true, between 1950 and 2000, for instant films and negatives processed at the drugstore. These systems had fixed dynamic range and fixed tone-scale response to light. All pixels in the film have the same response to light, so the same light exposure from different pixels was rendered as the same film density. Ansel Adams, along with Fred Archer, formulated the Zone System, staring in 1940. It was earlier than the trillions of consumer photos in the second half of the 20th century, yet it was much more sophisticated than today's digital techniques. This talk will describe the chemical mechanisms of the zone system in the parlance of digital image processing. It will describe the Zone System's chemical techniques for image synthesis. It also discusses dodging and burning techniques to fit the HDR scene into the LDR print. Although current HDR imaging shares some of the Zone System's achievements, it usually does not achieve all of them.

Selective Inhibition of ADAM17 Efficiently Mediates Glycoprotein Ibα Retention During Ex Vivo Generation of Human Induced Pluripotent Stem Cell‐Derived Platelets

PubMed Central

Hirata, Shinji; Murata, Takahiko; Suzuki, Daisuke; Nakamura, Sou; Jono‐Ohnishi, Ryoko; Hirose, Hidenori; Sawaguchi, Akira; Nishimura, Satoshi; Sugimoto, Naoshi

2016-01-01

Abstract Donor‐independent platelet concentrates for transfusion can be produced in vitro from induced pluripotent stem cells (iPSCs). However, culture at 37°C induces ectodomain shedding on platelets of glycoprotein Ibα (GPIbα), the von Willebrand factor receptor critical for adhesive function and platelet lifetime in vivo, through temperature‐dependent activation of a disintegrin and metalloproteinase 17 (ADAM17). The shedding can be suppressed by using inhibitors of panmetalloproteinases and possibly of the upstream regulator p38 mitogen‐activated protein kinase (p38 MAPK), but residues of these inhibitors in the final platelet products may be accompanied by harmful risks that prevent clinical application. Here, we optimized the culture conditions for generating human iPSC‐derived GPIbα+ platelets, focusing on culture temperature and additives, by comparing a new and safe selective ADAM17 inhibitor, KP‐457, with previous inhibitors. Because cultivation at 24°C (at which conventional platelet concentrates are stored) markedly diminished the yield of platelets with high expression of platelet receptors, 37°C was requisite for normal platelet production from iPSCs. KP‐457 blocked GPIbα shedding from iPSC platelets at a lower half‐maximal inhibitory concentration than panmetalloproteinase inhibitor GM‐6001, whereas p38 MAPK inhibitors did not. iPSC platelets generated in the presence of KP‐457 exhibited improved GPIbα‐dependent aggregation not inferior to human fresh platelets. A thrombus formation model using immunodeficient mice after platelet transfusion revealed that iPSC platelets generated with KP‐457 exerted better hemostatic function in vivo. Our findings suggest that KP‐457, unlike GM‐6001 or p38 MAPK inhibitors, effectively enhances the production of functional human iPSC‐derived platelets at 37°C, which is an important step toward their clinical application. Stem Cells Translational Medicine 2017;6:720–730 PMID

'Nothing is so soon forgot as pain': Reading Agony in Adam Smith's The Theory of Moral Sentiments.

PubMed

Franson, Craig

2014-01-01

Giving a rigorous philosophical explanation to the imagination's role in sympathy, Adam Smith's The Theory of Moral Sentiments became a central text in Romantic aesthetics. It not only justified the age's vogue for making suffering an object of artistic pleasure, it treated suffering's affectivity as the very foundation of society. Depicting agony as a spectacle to be read by others, Smith transformed morality into rhetoric, making human subjects into readers of a sentimentalised, textual world. Yet Smith's work restricted the bonds of sympathy, too, following established distinctions between mind and body that helped him to exclude physical pain from sympathetic response. This essay looks to Smith's context in the overlapping philosophical and medical discourses of the Scottish Enlightenment, exploring his moral theory's resonance with the nerve theories of Robert Whytt and William Cullen, then the leading figures in Scotland's rising medical community. Deepening our understanding of Smith's probable sources, it reframes Smith's intellectual and ideological legacy, foregrounding some of the ambivalent cultural and political implications of Smith's troubling censure of physical pain.

Race Unknown

ERIC Educational Resources Information Center

Gray, Katti

2011-01-01

Bryan Lee, a senior at the University of California, Irvine, has noticed that some of his classmates adamantly declare their multiracial heritage while others choose not to identify themselves as being any particular ethnicity. The half-Korean, half-White biomedical engineering major is co-president of the university's Mixed Students Organization…

The Library as Search Engine

ERIC Educational Resources Information Center

Chronicle of Higher Education, 2007

2007-01-01

This article presents a Technology Forum that focuses on online archives and their role in academe. The forum brought together Daniel Greenstein, associate vice provost for scholarly information and university librarian at the California Digital Library of the University of California; Adam Smith, group business-product manager for the Google Book…

Uterine artery embolization - discharge

MedlinePlus

... Kauh C. Complications of gynecological procedures, abortion, and assisted reproductive technology. In: Adams JG, ed. ... of Obstetrics and Gynecology, Loma Linda University School of Medicine, Loma Linda Center for Fertility, Loma ...

The level of depression in lower back pain patient at outpatient of neurology Haji Adam Malik hospital Medan (RS HAM

NASA Astrophysics Data System (ADS)

Pardosi, M. C.; Loebis’, B.; Husada, M. S.

2018-03-01

The incidence of Lower Back Pain (LBP) in Indonesia is unclear. Various data in some developing countries stated that the LBP incidence is approximately 15% - 20% of the population. Because there is the unclear incidence of psychological symptoms such as depression on LBP, the researchers were interested in doing this research. A descriptive study was conducted to know the level of depression of patients with LBP in outpatient of neurology RS HAM Medan. Patients with LBP (n=78) in outpatient were examined BDI-II. The minimum depression was 47.44% (n=37), mild depression was 21.79% (n=17), moderate depression was 21.79% (n=17), severe depression was 8.98% (n=7). In conclusion, the level of depression in lower back pain patient at outpatient of neurology Haji Adam Malik Hospital Medan is higher at minimum depression.

SIVA/DIVA- INITIAL VALUE ORDINARY DIFFERENTIAL EQUATION SOLUTION VIA A VARIABLE ORDER ADAMS METHOD

NASA Technical Reports Server (NTRS)

Krogh, F. T.

1994-01-01

The SIVA/DIVA package is a collection of subroutines for the solution of ordinary differential equations. There are versions for single precision and double precision arithmetic. These solutions are applicable to stiff or nonstiff differential equations of first or second order. SIVA/DIVA requires fewer evaluations of derivatives than other variable order Adams predictor-corrector methods. There is an option for the direct integration of second order equations which can make integration of trajectory problems significantly more efficient. Other capabilities of SIVA/DIVA include: monitoring a user supplied function which can be separate from the derivative; dynamically controlling the step size; displaying or not displaying output at initial, final, and step size change points; saving the estimated local error; and reverse communication where subroutines return to the user for output or computation of derivatives instead of automatically performing calculations. The user must supply SIVA/DIVA with: 1) the number of equations; 2) initial values for the dependent and independent variables, integration stepsize, error tolerance, etc.; and 3) the driver program and operational parameters necessary for subroutine execution. SIVA/DIVA contains an extensive diagnostic message library should errors occur during execution. SIVA/DIVA is written in FORTRAN 77 for batch execution and is machine independent. It has a central memory requirement of approximately 120K of 8 bit bytes. This program was developed in 1983 and last updated in 1987.

Antibiotic sensitivity pattern of bacteria from diabetic foot infections Haji Adam Malik central general hospital

NASA Astrophysics Data System (ADS)

Bulolo, B. A.; Pase, M. A.; Ginting, F.

2018-03-01

Increasing rate of Diabetic Foot Infections (DFIs) caused by multi-drug-resistance pathogens plays a huge role in the duration of hospitalization, morbidity, and mortality of diabetic patients. The aim of the study is to assess the antibiotic sensitivity pattern of bacteria in DFIs and causative microorganisms. Using cross-sectional retrospective study, data were collected from medical records of DFIs patients previously hospitalized atHaji Adam Malik Hospital, Medan from January to July 2017. 33 patients met the criteria and got enrolled in the study. The classification of DFIs was evaluated according to Wagner’s Classification. Evaluation of antibiotic sensitivity and identification of causative microorganisms were performed in standard microbiologic methods. The most common grade of DFIs was Grade-4 (48.5%), followed by Grade-3 (39.4%) and Grade-5 (9.1%). A total of 12 pathogens were identified. The most common infecting microorganism isolated on pus cultures was Klebsiella pneumonia (33.3%), followed by Escherichia coli (24.2%), Acinetobacter baumanni (12.1%), and Staphylococcus aureus (9.1%). Frequent susceptible antibiotics were Amikacin (88.8%), Imipenem (87%), Meropenem (84.6%), Erythromycin (75%), and Cefoperazone/Sulbactam (68.9%). DFIs are polymicrobial infections in this study K. pneumonia was the most common cause microorganism.

Pessimism vs. Existentialism

ERIC Educational Resources Information Center

Solomon, Robert C.

2007-01-01

So opined Adam Cohen recently in the "International Herald Tribune", and so, too, according to a recent book by Joshua Foa Dienstag, a political scientist at the University of California at Los Angeles, "Pessimism: Philosophy, Ethic, Spirit "(Princeton University Press, 2006). In his defense of pessimism as an appropriate and realistic philosophy,…

HEALing Higher Education: An Innovative Approach to Preparing HSI Leaders

ERIC Educational Resources Information Center

Freeman, Melissa L.

2015-01-01

This chapter is a case study of the Higher Education Administration and Leadership (HEAL) program at Adams State University. HEAL focuses on preparing the next generation of leaders at the nation's Hispanic-serving institutions.

Discriminating assimilants and decoupling deep- vs. shallow-level crystal records at Mount Adams using 238U-230Th disequilibria and Os isotopes

USGS Publications Warehouse

Jicha, B.R.; Johnson, C.M.; Hildreth, W.; Beard, B.L.; Hart, G.L.; Shirey, S.B.; Singer, B.S.

2009-01-01

A suite of 23 basaltic to dacitic lavas erupted over the last 350??kyr from the Mount Adams volcanic field has been analyzed for U-Th isotope compositions to evaluate the roles of mantle versus crustal components during magma genesis. All of the lavas have (230Th/238U) > 1 and span a large range in (230Th/232Th) ratios, and most basalts have higher (230Th/232Th) ratios than andesites and dacites. Several of the lavas contain antecrysts (crystals of pre-existing material), yet internal U-Th mineral isochrons from six of seven lavas are indistinguishable from their eruption ages. This indicates a relatively brief period of time between crystal growth and eruption for most of the phenocrysts (olivine, clinopyroxene, plagioclase, magnetite) prior to eruption. One isochron gave a crystallization age that is ~ 20-25??ka older than its corresponding eruptive age, and is interpreted to reflect mixing of older and juvenile crystals or a protracted period of magma storage in the crust. Much of the eruptive volume since 350??ka consists of lavas that have small to moderate 230Th excesses (2-16%), which are likely inherited from melting of a garnet-bearing intraplate ("OIB-like") mantle source. Following melt generation and subsequent migration through the upper mantle, most Mt. Adams magmas interacted with young, mafic lower crust, as indicated by 187Os/188Os ratios that are substantially more radiogenic than the mantle or those expected via mixing of subducted material and the mantle wedge. Moreover, Os-Th isotope variations suggest that unusually large 230Th excesses (25-48%) and high 187Os/188Os ratios in some peripheral lavas reflect assimilation of small degree partial melts of pre-Quaternary basement that had residual garnet or Al-rich clinopyroxene. Despite the isotopic evidence for lower crustal assimilation, these processes are not generally recorded in the erupted phenocrysts, indicating that the crystal record of the deep-level 'cryptic' processes has been

Better Nutrition Every Day: How to Make Healthier Food Choices

MedlinePlus

... Issues Subscribe September 2015 Print this issue Better Nutrition Every Day How to Make Healthier Food Choices ... cook at home,” says Dr. Adam Drewnowski, a nutrition expert at the University of Washington in Seattle. ...

Evaluation of brain SERT occupancy by resveratrol against MDMA-induced neurobiological and behavioral changes in rats: A 4-[¹⁸F]-ADAM/small-animal PET study.

PubMed

Shih, Jui-Hu; Ma, Kuo-Hsing; Chen, Chien-Fu F; Cheng, Cheng-Yi; Pao, Li-Heng; Weng, Shao-Ju; Huang, Yuahn-Sieh; Shiue, Chyng-Yann; Yeh, Ming-Kung; Li, I-Hsun

2016-01-01

The misuse of 3,4-methylenedioxymethamphetamine (MDMA) has drawn a growing concern worldwide for its psychophysiological impacts on humans. MDMA abusers are often accompanied by long-term serotonergic neurotoxicity, which is associated with reduced density of cerebral serotonin transporters (SERT) and depressive disorders. Resveratrol (RSV) is a natural polyphenolic phytoalexin that has been known for its antidepressant and neuroprotective effects. However, biological targets of RSV as well as its neuroprotective effects against MDMA remained largely unknown. In this study, we examined binding potency of RSV and MDMA to SERT using small-animal positron emission tomography (PET) with the SERT radioligand, N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM) and investigated the protection of RSV against the acute and long-term adverse effects of MDMA. We found that RSV exhibit binding potentials to SERT in vivo in a dose-dependent manner with variation among brain regions. When the MDMA-treated rats (10mg/kg, s.c.) were co-injected with RSV (20mg/kg, i.p.) twice daily for 4 consecutive days, MDMA-induced acute elevation in plasma corticosterone was significantly reduced. Further, 4-[(18)F]-ADAM PET imaging revealed that RSV protected against the MDMA-induced decrease in SERT availability in the midbrain and the thalamus 2 weeks following the co-treatment. The PET data were comparable to the observation from the forced swim test that RSV sufficiently ameliorated the depressive-like behaviors of the MDMA-treated rats. Together, these findings suggest that RSV is a potential antidepressant and may confer protection against neurobiological and behavioral changes induced by MDMA. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

The Marriage of Alma Mater to Adam Smith.

ERIC Educational Resources Information Center

Buescher, John B.

1987-01-01

Businesses and universities must be encouraged to act from their traditional positions of strength, based on the longest view and the broadest interests. They must examine carefully their potential sources of conflict as well as opportunities for benefit before engaging in alliances that may become complex and difficult to manage. (MSE)

Desperately seeking social approval: Adam Smith, Thorstein Veblen and the moral limits of capitalist culture.

PubMed

Watson, Matthew

2012-09-01

Adam Smith and Thorstein Veblen shared much in matters of economic ontology. Both dismissed the very notion of an autonomous economic self and instead investigated the processes through which self and other are mutually constituted under changing cultural traditions of individual aspiration. Their strikingly similar critiques of status-oriented consumption and concern for the moral basis of the market economy are established in this manner. However, the political implications of their analyses point in different directions, with Veblen being the more radical. The Smithian individual can always use spectatorial insights to assert through genuinely praiseworthy behaviour personal moral distance from social norms of status-oriented consumption. The Veblenian individual, by contrast, has no such capacity for elevating abstract moral principles above socially-situated conduct, as mind and environment co-evolve in line with changing material circumstances of life. For Veblen, the rise of status-oriented consumption itself acted as a form of moral self-education that more deeply entrenched the social norms of ownership out of which it arose, thus the impossibility of an autonomous economic self was matched by the impossibility of an autonomous moral self. To his way of thinking, moral degradation in conspicuous consumption was irredeemably inscribed into the whole cultural structure of capitalism. © London School of Economics and Political Science 2012.

Inductive Microenvironment for Improved Osseous Integration

DTIC Science & Technology

2012-10-01

PRINCIPAL INVESTIGATOR: Lakshmi S. Nair CONTRACTING ORGANIZATION: University of...Integration 5b. GRANT NUMBER W81WXH-10-1-0653 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Lakshmi S,.Nair ,David Rowe, Peter Maye ,Douglas Adams 5d

Argonne HEP Lunch Seminars

Science.gov Websites

reactor neutrino experiment July 29, 2008 August 5, 2008 Adam Clark (Rockhurst University) and Teng Jian August 12, 2008 Peter de Maagt THz Technology August 19, 2008 Razmick Mirzoyan Recent Developments on Low

Incongruent reduction of serotonin transporter associated with suicide attempts in patients with major depressive disorder: a positron emission tomography study with 4-[18F]-ADAM.

PubMed

Yeh, Yi-Wei; Ho, Pei-Shen; Chen, Chun-Yen; Kuo, Shin-Chang; Liang, Chih-Sung; Ma, Kuo-Hsing; Shiue, Chyng-Yann; Huang, Wen-Sheng; Cheng, Cheng-Yi; Wang, Tzu-Yun; Lu, Ru-Band; Huang, San-Yuan

2014-10-31

Much evidence supports the role of the serotonin transporter (SERT) in the pathophysiology and pharmacotherapy of major depressive disorder (MDD) and suicidal behaviors. In this study, we recruited 17 antidepressant-naïve patients with MDD and 17 age- and gender-matched healthy controls. SERT availability was measured in vivo with N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM) positron emission tomography (PET) imaging. The 21-item Hamilton Depression Rating Scale (HDRS) and Beck Scale for Suicide Ideation were used to assess the severity of depression and the intent of suicide ideation prior to PET imaging. All subjects with MDD were in a current state of depression with HDRS scores ≧18. Subjects who attempted suicide within two weeks of the study onset were recruited in the depressed suicidal group (n = 8). Subjects with MDD who denied any prior suicide attempt were recruited into the depressed non-suicidal group (n = 9). A significant reduction of SERT availability in the midbrain, thalamus, and striatum was noted in the MDD group relative to the control group (Bonferroni-adjusted p-value < 0.05). Moreover, this effect was more pronounced in the depressed suicidal group compared to the control group (Bonferroni-adjusted p-value < 0.01). Relative to both the depressed non-suicidal and control groups, the depressed suicidal group showed an increased prefrontal cortex (PFC)/midbrain SERT binding ratio (Bonferroni-adjusted p-value < 0.01). This study suggests an incongruent reduction of PFC SERT binding relative to the midbrain might discriminate between depressed suicide attempters and non-attempters in patients with MDD and may be involved in the pathophysiology of suicide behaviors. © The Author 2015. Published by Oxford University Press on behalf of CINP.

The Relationship of Dynamical Heterogeneity to the Adam-Gibbs and Random First-Order Transition Theories of Glass Formation

NASA Astrophysics Data System (ADS)

Starr, Francis; Douglas, Jack; Sastry, Srikanth

2013-03-01

We examine measures of dynamical heterogeneity for a bead-spring polymer melt and test how these scales compare with the scales hypothesized by the Adam and Gibbs (AG) and random first-order transition (RFOT) theories. We show that the time scale of the high-mobility clusters and strings is associated with a diffusive time scale, while the low-mobility particles' time scale relates to a structural relaxation time. The difference of the characteristic times naturally explains the decoupling of diffusion and structural relaxation time scales. We examine the appropriateness of identifying the size scales of mobile particle clusters or strings with the size of cooperatively rearranging regions (CRR) in the AG and RFOT theories. We find that the string size appears to be the most consistent measure of CRR for both the AG and RFOT models. Identifying strings or clusters with the``mosaic'' length of the RFOT model relaxes the conventional assumption that the``entropic droplet'' are compact. We also confirm the validity of the entropy formulation of the AG theory, constraining the exponent values of the RFOT theory. This constraint, together with the analysis of size scales, enables us to estimate the characteristic exponents of RFOT.

Upper airway biopsy

MedlinePlus

... Otolaryngology – Head and Neck Surgery, The University of Texas Medical School at Houston, Houston, TX. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team. Biopsy Read more Cancer Read more ...

Tracheitis

MedlinePlus

... Otolaryngology – Head and Neck Surgery, The University of Texas Medical School at Houston, Houston, TX. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team. team. Staphylococcal Infections Read more Tracheal ...

Distance Learning and the Information Highway [and] Comments on Burgstahler.

ERIC Educational Resources Information Center

Burgstahler, Sheryl; And Others

1995-01-01

Two University of Washington programs that demonstrate the use of the Internet for distance learning in rehabilitation are described: Project DO-IT (Disabilities, Opportunities, Internetworking, and Technology) and an adaptive computer technology course. Comments by Oestreich and Adams follow the article. (SK)

77 FR 53248 - Culturally Significant Objects Imported for Exhibition Determinations: “Swiss Treasures: From...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-31

... United States, are of cultural significance. The objects are imported pursuant to loan agreements with... objects at The University of Chicago Library, Special Collections Research Center in Chicago, Illinois.... J. Adam Ereli, Principal Deputy Assistant Secretary, Bureau of Educational and Cultural Affairs...

PREFACE: 10th Summer School on Theoretical Physics 'Symmetry and Structural Properties of Condensed Matter'

NASA Astrophysics Data System (ADS)

Lulek, Tadeusz; Wal, Andrzej; Lulek, Barbara

2010-03-01

This volume contains the Proceedings of the Tenth Summer School on Theoretical Physics under the banner title 'Symmetry and Structural Properties of Condensed Matter' (SSPCM 2009). The School was organized by Rzeszow University of Technology, Poland, in cooperation with AGH University of Science and Technology, Cracow, Poland, and took place on 2-9 September 2009 in Myczkowce, Poland. With this meeting we have reached the round number ten of the series of biannual SSPCM schools, which started in 1990 and were focused on some advanced mathematical methods of condensed matter physics. The first five meetings were held in Zajaczkowo near Poznan, under the auspices of The Institute of Physics of Adam Mickiewicz University, and the last five in Myczkowce near Rzeszów, in the south-eastern part of Poland. Within these two decades several young workers who started at kindergarten lectures at SSPCM, have now reached their PhD degrees, professorships and authority. Proceedings of the first seven SSPCM meetings were published as separate volumes by World Scientific, and the last two as volumes 30 and 104 of Journal of Physics: Conference Series. The present meeting is also the third of the last schools which put the emphasis on quantum informatics. The main topics of our jubilee SSPCM'09 are the following: Information processing, entanglement, and tensor calculus, Integrable models and unitary symmetry, Finite systems and nanophysics. The Proceedings are divided into three parts accordingly. The school gathered together 55 participants from seven countries and several scientific centers in Poland, accommodating again advanced research with young collaborators and students. Acknowledgements The Organizing Committee would like to express its gratitude to all participants for their many activities during the School and for creating a friendly and inspiring atmosphere within our SSPCM society. Special thanks are due to all lecturers for preparing and presenting their talks and

Culture Wars: Air Force Culture and Civil-Military Relations

DTIC Science & Technology

2010-06-01

Builder, The Masks of War: American Military Styles in Strategy and Analysis (Baltimore: Johns Hopkins University Press, 1989 ). 9 Adam Stulberg and...University Press, 1989 ), 3. 49 Charles Dunlap, Understanding Airmen: A Primer for Soldiers, Military Review (2007), 128. 21 heuristic of organizational...James Q. Wilson, Bureaucracy: What Government Agencies Do and Why They Do it (New York: Basic Books, 1989 ), 91. The idea of organizational

Comparison of microbial pattern in early and late onset neonatal sepsis in referral center Haji Adam Malik hospital Medan Indonesia

NASA Astrophysics Data System (ADS)

Hasibuan, B. S.

2018-03-01

Neonatal sepsis contributes a significant rate of infants mortality and morbidity. The pathogens are diverse from region to another and change time to time even in the same place. To analyze the microbial pattern in early and late onset neonatal sepsis andthe pattern of antibiotic resistance of the causative microbes at one of referral center hospital in Indonesia, Haji Adam Malik Hospital, a cross-sectional descriptive study was conducted on neonates with sepsis diagnosis proven with positive blood culture within one year period (2015-2016). Among 626 neonates admitted to perinatology unit, the total of 154 neonates was proven to have neonatal sepsis with positive blood culture with the incidence rate 24.6%. Seventy-nine (51.3%) neonates were diagnosed with early onset sepsis while 75 (48,7%) neonates had late-onset sepsis. Klebsiella pneumonia was the most commonly isolated organism in both early and late onset sepsis, encompassing 19.5% of cases. Periodic surveillance of the causative agents of neonatal sepsis is needed to implement the rational, empirical choice of antibiotic prescription while waiting for blood culture result to come out.

Stereotypic movement disorder

MedlinePlus

... Clinical Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle, WA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team. Child Mental Health Read more NIH MedlinePlus Magazine Read more Health ...

ULTRAVIOLET RADIATION DOSE AND AMPHIBIAN DISTRIBUTIONS IN NATIONAL PARKS

EPA Science Inventory

Ultraviolet Radiation Dose and Amphibian Distributions in National Parks. Diamond, S. A., Detenbeck, N. E., USEPA, Duluth, MN, USA, Bradford, D. F., USEPA, Las Vegas, NV, USA, Trenham, P. C., University of California, Davis, CA., USA, Adams, M. J., Corn, P. S., Hossack, B., USGS,...

Ear surgery - slideshow

MedlinePlus

... Otolaryngology – Head and Neck Surgery, The University of Texas Medical School at Houston, Houston, TX. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team. Related MedlinePlus Health Topics Ear Disorders ...

Facelift - slideshow

MedlinePlus

... Otolaryngology – Head and Neck Surgery, The University of Texas Medical School at Houston, Houston, TX. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team. Related MedlinePlus Health Topics Plastic and ...

A Center of Excellence in the Mathematical Sciences - at Cornell University

DTIC Science & Technology

1992-03-01

of my recent efforts go in two directions. 1. Cellular Automata. The Greenberg Hastings model is a simple system that models the behavior of an... Greenberg -Hastings Model. We also obtained results concerning the crucial value for a threshold voter model. This resulted in the papers "Some Rigorous...Results for the Greenberg - Hastings Model" and "Fixation Results for Threshold Voter Systems." Together with Scot Adams, I wrote "An Application of the

Adapting the ADAM Manikin Technology for Injury Probability Assessment

DTIC Science & Technology

1992-02-19

Benson, J.B., Holstein , G.L., Melvin, J.W. Whole Body Response Research Program. Ann Arbor, MI, University of Michigan, Highway Safety Research...Liver Laceration I Fatal 25 227 9. UNKNOWN - COW ’ Aassiou" Ntoobor of 14my~ PAft Irni Type [ rid Ca ry Rados Neck tam 2nd D•s"* I Minimwl 4 Neck

Summary of hydrogeologic and ground-water-quality data and hydrogeologic framework at selected well sites, Adams County, Pennsylvania

USGS Publications Warehouse

Low, Dennis J.; Dugas, Diana L.

1999-01-01

Rapid population growth in Adams County has increased the demand for ground water and led Adams County planning officials to undertake an effort to evaluate the capabilities of existing community water systems to meet future, projected growth and to begin wellhead-protection programs for public-supply wells. As part of this effort, this report summarizes ground-water data on a countywide scale and provides hydrogeologic information needed to delineate wellheadprotection areas in three hydrogeologic units (Gettysburg Lowland, Blue Ridge, and Piedmont Lowland).Reported yields, specific capacities, well depths, and reported overburden thickness can vary by hydrogeologic unit, geologic formation, water use (domestic and nondomestic), and topographic setting. The reported yields of domestic wells drilled in the Gettysburg Lowland (median reported yield of 10 gallons per minute) are significantly greater than the reported yields from the Blue Ridge, Piedmont Lowland, and Piedmont Upland (median reported yields of 7.0, 8.0, and 7.0 gallons per minute, respectively). Reported yields of domestic wells completed in the diabase and the New Oxford Formation of the Gettysburg Lowland, and in the metarhyolite and metabasalt of the Blue Ridge, are significantly lower than reported yields of wells completed in the Gettysburg Formation. For nondomestic wells, reported yields from the Conestoga Formation of the Piedmont Lowland are significantly greater than in the diabase. Reported yields of nondomestic wells drilled in the Gettysburg, New Oxford, and Conestoga Formations, and the metarhyolite are significantly greater than those for domestic wells drilled in the respective geologic formations. Specific capacities of nondomestic wells in the Conestoga and Gettysburg Formations are significantly greater than their domestic counterparts. Specific capacities of nondomestic wells in the Conestoga Formation are significantly greater than the specific capacities of nondomestic wells in

Center of Excellence in Space Data and Information Sciences Annual Report, Year 9

DTIC Science & Technology

1997-06-01

faculty at INSEAD in Paris, France, THESEUS in Sophia, Antibe, and the London Business School. Gave an invited presentation and chaired a panel at...the conference on digital cash held at THESEUS . Visited the Department of Computer Science at Johns Hopkins University with Nabil Adam (Rutgers

OCCUPATIONS IN COLORADO. PART I, OUTLOOK BY INDUSTRIES.

ERIC Educational Resources Information Center

1966

CURRENT AND PROJECTED EMPLOYMENT STATISTICS ARE GIVEN FOR THE STATE AND FOR THE DENVER STANDARD METROPOLITAN STATISTICAL AREA WHICH INCLUDES ADAMS, ARAPAHOE, BOULDER, DENVER, AND JEFFERSON COUNTIES. DATA WERE OBTAINED FROM THE COLORADO DEPARTMENT OF EMPLOYMENT, DENVER RESEARCH INSTITUTE, U.S. CENSUS, UNIVERSITY OF COLORADO, MOUNTAIN STATES…

Hydrogeology and analysis of ground-water withdrawal from the Catahoula aquifer system in the Natchez area, Adams County, Mississippi

USGS Publications Warehouse

Strom, E.W.; Burt, D.E.; Oakley, W.T.

1995-01-01

The city of Natchez, located in Adams County, Mississippi, relies on ground water for public supply and industrial needs. Most public supply and industrial wells are developed in Catahoula Formation sands of Miocene age. In 1991, an investigation began to describe the hydrogeology, analyze the effects of ground-water withdrawal from currently pumped wells, and project the possible effects of increased ground-water withdrawals on water levels in the Catahoula aquifer system within the Natchez area. The study area covers about 80 square miles in Adams County, southwestern Mississippi. The study area contains several aquifers; however, the most important aquifers in terms of water supply are the Mississippi River alluvial aquifer and the Catahoula aquifer system. In the Natchez area, the Catahoula aquifer system consists of three main sand intervals that form the upper, middle, and lower Catahoula aquifers. Ground-water withdrawal from the Catahoula aquifer system in the study area currently (March 1995) is from 24 wells screened in the three aquifers. The current daily rate of withdrawal is about 9.2 million gallons of water per day. Analysis of the effect of ground-water withdrawal from these wells was made using the Theis nonequilibrium equation and applying the principle of superposition. The calculated drawdown surfaces under current conditions indicate cones of depression surrounding the principal wells. In the upper Catahoula sand, most of the drawdown is concentrated about 1 mile east of the downtown Natchez area, where a maximum drawdown of 95x11 feet was calculated. Most of the drawdown in the middle Catahoula sand occurred in the same general vicinity as in the upper sand, with a maximum calculated drawdown of about 113 feet. Drawdown in the lower Catahoula sand was concentrated about 4x11 miles northeast of downtown Natchez, with a maximum calculated drawdown of about 31 feet. Drawdown-surface maps were made using calculations based on current pumping

The Other Club Scene

ERIC Educational Resources Information Center

Davis, Noah

2007-01-01

At colleges nationwide, students from diverse racial, cultural and socioeconomic backgrounds meet and befriend each other under the auspices of club sports. Adam Pruett, the recreational sports coordinator at the University of California, Los Angeles, says any cultural uneasiness is overcome by the students' shared passion for the particular…

Genetics Home Reference: cranioectodermal dysplasia

MedlinePlus

... CRANIOECTODERMAL DYSPLASIA 4 Sources for This Page Arts H, Knoers N. Cranioectodermal Dysplasia. 2013 Sep 12. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Fong CT, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of ...

The Effects of Speech and Language Therapy Intervention on Children with Pragmatic Language Impairments in Mainstream School

ERIC Educational Resources Information Center

Adams, Catherine; Lloyd, Julian

2007-01-01

In this article, Catherine Adams, clinical senior lecturer in speech and language therapy at the University of Manchester, and Julian Lloyd, senior lecturer in psychology at Newman College, Birmingham, describe the implementation and effects of an intensive programme of speech and language therapy for children who have pragmatic language…

Bayesian Computational Sensor Networks for Aircraft Structural Health Monitoring

DTIC Science & Technology

2016-02-02

LAKE CITY Final Report 02/02/2016 DISTRIBUTION A: Distribution approved for public release. AF Office Of Scientific Research (AFOSR)/ RTA2 Arlington...Adams Grant Number: FA9550-12-1-0291 AFOSR PI: Dr. Frederica Darema 25 January 2016 University of Utah, Salt lake City UT 84112 Executive Summary...Boonsirisumpun, Kyle Luthy and Edward Grant, University of Utah Technical Report, UUCS-13-003, Salt Lake City, UT, May 2013. [5] ``Robot Cognition using

MAX meets ADAM: a dosimetric comparison between a voxel-based and a mathematical model for external exposure to photons

NASA Astrophysics Data System (ADS)

Kramer, R.; Vieira, J. W.; Khoury, H. J.; Lima, F. de Andrade

2004-03-01

The International Commission on Radiological Protection intends to revise the organ and tissue equivalent dose conversion coefficients published in various reports. For this purpose the mathematical human medical internal radiation dose (MIRD) phantoms, actually in use, have to be replaced by recently developed voxel-based phantoms. This study investigates the dosimetric consequences, especially with respect to the effective male dose, if not only a MIRD phantom is replaced by a voxel phantom, but also if the tissue compositions and the radiation transport codes are changed. This task will be resolved by systematically replacing in the mathematical ADAM/GSF exposure model, first the radiation transport code, then the tissue composition and finally the phantom anatomy, in order to arrive at the voxel-based MAX/EGS4 exposure model. The results show that the combined effect of these replacements can decrease the effective male dose by up to 25% for external exposures to photons for incident energies above 30 keV for different field geometries, mainly because of increased shielding by a heterogeneous skeleton and by the overlying adipose and muscle tissue, and also because of the positions internal organs have in a realistically designed human body compared to their positions in the mathematically constructed phantom.

ADAM-C score: New risk score for predicting diagnostic yield of transesophageal echocardiography after cerebral ischemia.

PubMed

Charbonnel, Clément; Jego, Christophe; Jourda, François; Vinsonneau, Ulric; Garçon, Philippe; Turlotte, Guillaume; Rivière, Jean François; Maurin, Marion; Lubret, Rémy; Meimoun, Patrick; Akret, Chrystelle; Cournot, Maxime; Sokic, Charles; Michel, Laurent; Lescure, Maryse; Kenizou, David; Melay, Marie; Fayard, Maxime; Gallet, Bruno; Fouche, Rémi; Janin-Manificat, Luc; Dijoux, Nicolas; Martin, Anne Céline; Tho-Agostini, Aurélia; Mann, Hubert; Ricard, Cécile; Pico, Fernando; Georges, Jean Louis; Belle, Loïc; Jourdain, Patrick

2018-05-14

The clinical utility of transesophageal echocardiography (TEE) after brain ischemia (BI) remains a matter of debate. We aimed to evaluate the clinical impact of TEE and to build a score that could help physicians to identify which patients should better benefit from TEE. This prospective, multicenter, observational study included patients over 18 years old, hospitalized for BI. TEE findings were judged discriminant if the results showed important information leading to major changes in the management of patients. Most patients with patent foramen ovale were excluded. Variables independently associated with a discriminant TEE were used to build the prediction model. Of the entire population (1479 patients), 255 patients (17%) were classified in the discriminant TEE group. Five parameters were selected as predictors of a discriminant TEE. Accordingly, the ADAM-C score could be calculated as follows: Score = 4 (if age ≥60) + 2 (if diabetes) + 2 (if aortic stenosis from any degrees) + 1 (if multi-territory stroke) + 2 (if history of coronary artery disease). At a threshold lower than 3, the sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of detecting discriminant TEE were 88% (95% CI 85-90), 44% (95% CI 41-47), 21% (95% CI 19-27), and 95% (95% CI 94-97), respectively. A simple score based on clinical and transthoracic echocardiographic parameters can help physicians to identify patients who might not benefit from TEE. Indeed, a score lower than 3 has an interesting NPV of 95% (95% CI 94-97). © 2018 Wiley Periodicals, Inc.

Comparison of lipid profile between degrees of severity of hepatic cirrhosis in Haji Adam Malik general hospital Medan

NASA Astrophysics Data System (ADS)

Siregar, G. A.; Tampubolon, S. E.

2018-03-01

Lipid metabolism disorders usually occurred in chronic liver disease. A cross- sectional study was conducted in liver cirrhosis (LC) patients who came to Central Hospital Haji Adam Malik, Medan on July-December 2016 to evaluatethe comparison of total cholesterol, LDL, HDL, triglyceride in Child-Pugh class. Inclusions criteria were apatient diagnosed with LC from anamnesis, physic diagnostic, laboratory, and imaging. The patientswere being evaluated with Child-Pugh (CP). P-value was calculated by using univariate and bivariate analysis of variance test (ANOVA). There were 80 subjects which included 45 men (56.3%) and 35 women (43.8%). Mean age was 51.36±12.6 years. There were 40% with HBsAg(+) and 12.5% with Anti-HCV (+). There was 60% patient with CP-C, 21.3% CP-B, and 18.8% CP-A. There were significant differences between LDL and HDL level among LC patient grade in CP-A, B, and C (p<0.05). HDL and LDL level significantly lower in CP-C compared with CP-A. There were significantly differences between LDL and HDL level among LC patient grade in CP-A, B, and C (p<0.05). HDL and LDL level significantly lower in CP-C compared with CP-A. There weren’t any statistically difference between total cholesterol and triglyceride level in LC patients with CP- A, B, and C.

DigitSeis: A New Digitization Software and its Application to the Harvard-Adam Dziewoński Observatory Collection

NASA Astrophysics Data System (ADS)

Bogiatzis, P.; Altoé, I. L.; Karamitrou, A.; Ishii, M.; Ishii, H.

2015-12-01

DigitSeis is a new open-source, interactive digitization software written in MATLAB that converts digital, raster images of analog seismograms to readily usable, discretized time series using image processing algorithms. DigitSeis automatically identifies and corrects for various geometrical distortions of seismogram images that are acquired through the original recording, storage, and scanning procedures. With human supervision, the software further identifies and classifies important features such as time marks and notes, corrects time-mark offsets from the main trace, and digitizes the combined trace with an analysis to obtain as accurate timing as possible. Although a large effort has been made to minimize the human input, DigitSeis provides interactive tools for challenging situations such as trace crossings and stains in the paper. The effectiveness of the software is demonstrated with the digitization of seismograms that are over half a century old from the Harvard-Adam Dziewoński observatory that is still in operation as a part of the Global Seismographic Network (station code HRV and network code IU). The spectral analysis of the digitized time series shows no spurious features that may be related to the occurrence of minute and hour marks. They also display signals associated with significant earthquakes, and a comparison of the spectrograms with modern recordings reveals similarities in the background noise.

Example evaluation of a permit application for a proposed hazardous-waste landfill in eastern Adams County, Colorado

USGS Publications Warehouse

Banta, E.R.

1986-01-01

A project was undertaken by the U.S. Geological Survey in cooperation with the U. S. Environmental Protection Agency to demonstrate methods by which RCRA (Resources Conservation and Recovery Act of 1976) Part B permit applications might be evaluated. The purpose of the project was to prepare a report that would supplement a series of case studies to be made available to permit writers in the U.S. Environmental Protection Agency. Four sites in the United States were chosen for their potential applicability to geologically similar sites. The Adams County, Colorado, site was chosen to be representative of sites in the Upper Cretaceous Pierre Shale. The intent of this report is to provide an example of how available earth-science information might be used in evaluating an application and not to evaluate the acceptability of the site. Because this study is an evaluation of a permit application, the data used are limited to the data supplied in the application and in published reports. Of the five criteria required by the U.S. Environmental Protection Agency to be addressed in the permit application considered in the case study, the application was evaluated to be inadequate in addressing three criteria: (1) Site characterization, (2) ability to monitor the location, and (3) flow paths and 100-foot time of travel. Details of the inadequacies and a description of the information needed to eliminate the inadequacies are included in the report. (USGS)

Diamond Anniversary Lecture Series.

ERIC Educational Resources Information Center

Adams, Dewey A.; And Others

This document contains the texts of four lectures that were presented as part of a series commemorating the 75th anniversary of Ohio State University's Department of Agricultural Education. The first lecture, "The Conceptualization Process and Vocational Education Management," (Dewey A. Adams) discusses a five-step management behavior approach for…

Photographic copy of photograph (ca. 1934, original print located in ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photographic copy of photograph (ca. 1934, original print located in Margaret Long Collection, Box 20, Folder 2, Western History Collections, Norlin Library, University of Colorado at Boulder). VIEW OF THE SITE OF BOX ELDER STATION - Box Elder Road, Between 104th & 112th Avenues, Hudson & Watkins Roads, Watkins, Adams County, CO

Eventos de Julio (July Events).

ERIC Educational Resources Information Center

Pla, Myrna; Toro, Leonor

Written in Spanish, this booklet contains brief information on 10 July events celebrated by Puerto Ricans: United States Declaration of Independence; the birthdays of P.T. Barnum, Elias Howe, John Quincy Adams, Luis Munoz Rivera, and Simon Bolivar; Marisol Malaret (first puerto Rican to be "Miss Universe"); Puerto Rican Constitution; Las…

Transportation Research Fueled by Academia | News | NREL

Science.gov Websites

. Interested in furthering their research and education with the vast resources available at NREL, university researchers who are currently teaching include Senior Research Engineer Adam Duran, who has a senior capstone more transportation researchers-Yi Hou, Clement Rames, and Josh Sperling-are currently teaching an

Female condoms

MedlinePlus

... of Gynecology and Obstetrics at Johns Hopkins University School of Medicine, Baltimore, MD. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team. Birth Control Read more NIH MedlinePlus Magazine Read more Health ...

Birth control pills - overview

MedlinePlus

... of Gynecology and Obstetrics at Johns Hopkins University School of Medicine, Baltimore, MD. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team. Birth Control Read more NIH MedlinePlus Magazine Read more Health ...

The Relationship between Undergraduate Attendance and Performance Revisited: Alignment of Student and Instructor Goals

ERIC Educational Resources Information Center

Westerman, James W.; Perez-Batres, Luis A.; Coffey, Betty S.; Pouder, Richard W.

2011-01-01

We revisit the relationship between attendance and performance in the undergraduate university setting and apply agency theory in the instructor-student context. Building on agency theory propositions in the educational setting advanced by Smith, Zsidisin, and Adams (2005), we propose that the student and instructor must align goals to promote the…

Characteristics of SUN Learners (First Five Offerings). Statistical Summary No. 4.

ERIC Educational Resources Information Center

Bryan, Donna; Forman, David C.

Based on a period of two and one-half years, during which the State University of Nebraska (SUN) has offered 15 multimedia courses to Nebraska learners, this report offers a statistical summary of student characteristics. The courses offered include: Accounting I, Accounting II, Adams Chronicles, American Economy, Anyone for Tennyson, Classic…

Using Literacy Integration for Communicating Scientifically: Research Results on Teacher Efficacy and Student Achievement.

ERIC Educational Resources Information Center

Fortino, Carol; Gerretson, Helen; Button, Linda J.; Johnson, Sharon

The professional development program Using Literacy Integration for Communicating Scientifically (ULINCS) is a joint program of the University of Northern Colorado and Adams Twelve Five Star School District. It had been noted that the increased emphasis on literacy skills was leading educators to place less emphasis on science. The ULINCS project…

Diversifying Pedagogy

ERIC Educational Resources Information Center

Pember, Mary Annette

2008-01-01

Indigenous or native ways of knowing, indigenous knowledge, indigenous science, traditional ecological knowledge are terms that have been making their way out of tribal colleges and into mainstream universities in recent years. According to Dr. Dawn Adrian Adams, Choctaw, founder of Tapestry Institute, these terms refer to two separate, yet…

Nex-Gen Space Observatory

NASA Image and Video Library

2011-10-26

Adam Reiss, recipient of the 2011 Nobel Prize in Physics and professor of astronomy and physics at Johns Hopkins University speaks at the presentation of the permanent exhibit of the James Webb Space Telescope at the Maryland Science Center on Wednesday, Oct. 26, 2011 in Baltimore. Photo Credit: (NASA/Carla Cioffi)

Understanding Community Effects on Information Diffusion

DTIC Science & Technology

2015-05-22

Science, University of Illinois at Chicago, Chicago, IL, USA slin38@uic.edu 2 Institute for Data Science, Tsinghua University , Beijing, China 3 LinkedIn...Generally, we select vit by maximizing ∑ C∈C n t−1 c qit→C , where nt−1c = n t−2 c − nt−2c qit−1→C . 6 Experiment 6.1 Experiment Setup We use the DBLP...Award, and the Pinnacle Lab at Singa- pore Management University . References 1. Bakshy, E., Rosenn, I., Marlow, C., Adamic, L.: The role of social

Odzwierciedlenie zmian klimatycznych w przebiegu fenologicznych pór roku. w Poznaniu w latach 1958-2009

NASA Astrophysics Data System (ADS)

Górska-Zajączkowska, Maria; Wójtowicz, Wanda

2011-01-01

The term "phenology" is derived from the Greek word phainomenon. It combines indications of changes in climate, plants and animals. The interrelationship is close enough to determine phonological seasons on the basis of plant phases of development (foliage, flowering, seed dispersal, leaf shedding) of certain species of plants taken as indicator species. They act as "measurement devices" of sorts in a domain known as climate phenology. The Botanical Garden in Poznań has been conducting Adam Mickiewicz Uniwersity (UAM) phenological observations and phenological season analyses since 1958, with regard to A. Łukasiewicz's 1967 slight revision of the selection of indicator species. Using the obtained data start dates and duration of subsequent phenological seasons have been determined. Phenological season analysis in successive years is performed by comparing meteorological data from the IMiGW (Institute of Meteorology and Water Economy) weather station at Poznań Ławica, and since 2006 data from the UAM Botanical Garden's own weather station. Among the five decades of observations, the last one is characterized by a distinctly higher average temperature. During this decade, the pre-spring vegetation period in plants started earlier than in the previous forty years. The onset of spring and early summer was also accelerated, whereas summer, autumn, and late autumn were delayed. The average duration of successive phenological seasons, compared to the data from 1958-1997 was as follows: prespring, early summer and all autumn seasons lasted longer, the average length of early spring and spring was the same, while summer was slightly shorter in this ten-year period. Winter, defined using meteorological criteria, was an unstable season often starting only in the new calendar year. The difference between the average duration of this season in the periods under consideration was very significant, with 89 days in the 40-year period and 67 days in the last

The variability of expiration peak flow of workers employed in the washing installation (laundry) of Haji Adam Malik general hospital Medan

NASA Astrophysics Data System (ADS)

Saragih, W.; Tarigan, A. P.; Nainggolan, N.; Eyanoer, P. C.

2018-03-01

Laundress in hospitals is very susceptible to respiratory disorders, especially occupational asthma. To investigate the occurrence of an obstruction, the daily Expiration Peak Flow (EPF) examination was carried to compare the EPF, before and after work. It is a descriptive study conducted in November 2016. The samplewas 24 workers in Haji Adam Malik General Hospital Medan Laundry Installation, without any exclusion criteria, where all workers have been working for more than one year. Sampling was by distributing daily questionnaires and EPF examination for 14 days. From the results of EPF examinations that have been conducted, there were nine persons were indicated to experience a decreased in lung function. Based on the most sex category, men were 5 people (55.6%), age ≥ 40 years were 2 people (22.2%), working duration ≥10 years were 3 people (33.3%), with the smoking habit were 5 people (55.6%), total dust ≥0.2 micron were 6 people (66.7), total exposure of bacterium ≥500 were 3 people (33.3%), poor APD usage was 3 people (33.3%). In conclusion, there was a decrease in lung function by ≥ 3.1% found in 9 workers.

Genetics Home Reference: ankyloblepharon-ectodermal defects-cleft lip/palate syndrome

MedlinePlus

... 32791. Citation on PubMed Sutton VR, van Bokhoven H. TP63-Related Disorders. 2010 Jun 8 [updated 2015 Aug 6]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of ...

Genetics Home Reference: cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy

MedlinePlus

... Nov 6. Citation on PubMed Onodera O, Nozaki H, Fukutake T. CARASIL. 2010 Apr 27 [updated 2014 Sep 11]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of ...

Why Science?

ERIC Educational Resources Information Center

Primary Science Review, 2006

2006-01-01

This article presents people from many walks of life, including some well-known names, who share their views about science. Adam Hart-Davis, who studied chemistry at university and is now an author, photographer, historian and broadcaster, explains why science cannot start too soon. Lis Nairn, Manager, Stratigraphy, with Fugro Robertson Ltd (Oil…

A Google Official Stresses the Positive

ERIC Educational Resources Information Center

Chronicle of Higher Education, 2005

2005-01-01

What will Google do next? Representatives of the company divulge few details of their projects -- a policy that, in the case of its partnerships with university libraries, probably only fuels the buzz. In this interview, Adam M. Smith, a senior business-product manager, discusses Google's work with publishers and libraries on expanding its…

[Figures of first laureates of the Wiktor Dega medal (XXXVII Jubilee Congress of Polish Orthopaedic and Traumatologic Society, 10-13 September 2008)].

PubMed

Nowakowski, Andrzej; Rapała, Kazimierz

2008-01-01

of the Society. Professor Malawski is undoubtedly a great successor to the active way of surgical thinking introduced by professor Adam Gruca. Professor Jerzy Król is among the greatest Polish orthopedic surgeons. He was born on 21st February 1926 in Baranowice (Nowogródek woiwodship). He graduated from high school in the underground schooling system during the Second World War, receiving his maturity exam in 1945 from the Konarski High Scool School of the Western Lands in Czestochowa. In 1945 the professor started his medical studies at Adam Mickiewicz University of Poznan, where he graduated in 1949. In 1950 he started his medical career in in Orthopedic Department of Poznan head by professor Wiktor Dega. Professor Król is the author of over 100 medical papers printed in national and international journals. His key fields of interest are congenital dislocation of the hip, hip arthroplasty, scoliosis and rehabilitaton and prosthesis problems. In 1968 he performed the first scoliosis correction with the Harrington rod in Poland as well as the implantation of the first McKee-Ferara hip prosthesis. He is the co-author of the text-book Orthopedics and Rehabilitation, Medical Rehabilitation and a number of WHO text books: Community Health Worker and Guide for prevention of Deformities in Poliomyelitis. He also took part in the publishing of the WHO text-book Rehabilitation Surgery, for which he received the Ministry of Health Award. He overlooked 7 Ph.D thesis and 4 papers qualifying for assistant professor. Between 1972 and 1995 professor Król worked as a WHO expert, as member of the Expert Committee for Rehabilitation. Between 1986-1987 head was the director of the Orthopedics and Rehabilitation Institute in Poznan. He resigned from this function due to his work with WHO in Madagaskar. After his return he was the head of the Orthopedic Department in Poznan University of Medical Sciennces until October 1996 when he retired.

Bigger eyes in a wider universe: The American understanding of Earth in outer space, 1893--1941

NASA Astrophysics Data System (ADS)

Prosser, Jodicus Wayne

Between 1893 and 1941, the understanding of the Milky Way galaxy within the American culture changed from a sphere to a spiral and Earth's location within it changed from the center to the periphery. These changes were based primarily upon scientific theories developed at Mount Wilson Observatory near Pasadena, California. This dissertation is an "astrosophy" that traces the history of changing depictions of the Milky Way in selected published sources and identifies key individuals, theories and technologies involved. It also demonstrates why the accepted depictions of the universe envisioned at Mount Wilson were cultural-scientific products created, in part, as the result of place. Southern California became the hearth of a culture that justified its superiority based upon its unique climate. Clear skies, remarkable visibility, and a perceived existence of intense natural light became the basis for the promotion of Mount Wilson as the premier location for astronomical observations. Conservation, en plein air paintings, and the concept of pays age moralisé are Southern Californian cultural products of the early 1900s that promoted an idealized society capable of exceptional intellectual endeavors and scientific accomplishments. The efforts of astronomers Hale, Shapley, Adams, Hubble and Ritchey resulted in the changing American understanding of the universe. This dissertation reveals how the diverse social interactions of these astronomers intersected Arroyo Seco meetings, women's organizations, the Valley Hunt Club elites, and philanthropic groups that comprised the schizophrenic culture of Pasadena. Their astronomical theories are compared to other aspects of the Southern Californian culture revealed in the writings of Raymond Chandler, Nathanael West and John Fante. The desire of astronomers to gain prestige from their discoveries is compared to competition in the creative processes of Hollywood. The theories created by astronomers and the films of the motion

Preface

NASA Astrophysics Data System (ADS)

Kowalska, Magdalena; Błaszczak, Zdzislaw

2017-11-01

It is with great pleasure that we are presenting the subsequent volume of the International Poznan Workshop proceedings. The conferences of this cycle have been since the beginning devoted to laser light interaction with atomic nuclei and since more recently also to the applications of ion-storage devices. The first edition entitled "Laser Spectroscopy of Atomic Nuclei" took place in Dubna in December 1990, and since then the subsequent conferences have been held every two to three years in Poznan, where they have been jointly organized by the Faculty of Physics at the Adam Mickiewicz University (Poznan) and the Flerov Laboratory of Nuclear Reactions at the Joint Institute of Nuclear Research (Dubna). The conferences have enjoyed increasing popularity and have attracted increasing numbers of specialists from a number of research institutions engaged in laser spectroscopy of radioactive and other exotic (e.g. anti-) atomic nuclei and related instruments. Over the years the workshops have gained a reputation of presenting research of a high scientific level and having impact on the directions of future studies. The 2016 workshop on the Application of Lasers and Storage Devices in Atomic Nuclei Research has been already the 10th edition and it was a pleasure to see that the event was thriving and the participants were enjoying it in all fronts. Around 100 scientists met on May 16 -19 in Poznan for the 4-day event. They were even more international than in the previous edition, representing institutes in Europe, North America, Japan, and even Australia. Many have returned to Poznan, but there were also new faces, especially among the younger participants. It was great to see the leaders in their topics discussing physics, but not only, with PhD students and starting post-docs. More than sixty talks were delivered, reflecting well the state-of-the art in the covered fields which were all related to the techniques, experimental results and theory connected to lasers and

Substance P activates ADAM9 mRNA expression and induces α-secretase-mediated amyloid precursor protein cleavage.

PubMed

Marolda, R; Ciotti, M T; Matrone, C; Possenti, R; Calissano, P; Cavallaro, S; Severini, C

2012-04-01

Altered levels of Substance P (SP), a neuropeptide endowed with neuroprotective and anti-apoptotic properties, were found in brain areas and spinal fluid of Alzheimer's disease (AD) patients. One of the hallmarks of AD is the abnormal extracellular deposition of neurotoxic beta amyloid (Aβ) peptides, derived from the proteolytic processing of amyloid precursor protein (APP). In the present study, we confirmed, the neurotrophic action of SP in cultured rat cerebellar granule cells (CGCs) and investigated its effects on APP metabolism. Incubation with low (5 mM) potassium induced apoptotic cell death of CGCs and amyloidogenic processing of APP, whereas treatment with SP (200 nM) reverted these effects via NK1 receptors. The non-amyloidogenic effect of SP consisted of reduction of Aβ(1-42), increase of sAPPα and enhanced α-secretase activity, without a significant change in steady-state levels of cellular APP. The intracellular mechanisms whereby SP alters APP metabolism were further investigated by measuring mRNA and/or steady-state protein levels of key enzymes involved with α-, β- and γ-secretase activity. Among them, Adam9, both at the mRNA and protein level, was the only enzyme to be significantly down-regulated following the induction of apoptosis (K5) and up-regulated after SP treatment. In addition to its neuroprotective properties, this study shows that SP is able to stimulate non-amyloidogenic APP processing, thereby reducing the possibility of generation of toxic Aβ peptides in brain. Copyright © 2011 Elsevier Ltd. All rights reserved.

Analyzing Value Content in Television Programs.

ERIC Educational Resources Information Center

Jensen, Larry; Zelig, Mark

Four prime time television programs--"Charlie's Angels,""Little House on the Prairie,""Grizzly Adams," and "Lou Grant" --were rated by university students for their portrayal of moral reasoning and values. Data were obtained from three episodes of each program by randomly assigning raters to one of two viewing groups, both of which used an…

The Big Sky inside

ERIC Educational Resources Information Center

Adams, Earle; Ward, Tony J.; Vanek, Diana; Marra, Nancy; Hester, Carolyn; Knuth, Randy; Spangler, Todd; Jones, David; Henthorn, Melissa; Hammill, Brock; Smith, Paul; Salisbury, Rob; Reckin, Gene; Boulafentis, Johna

2009-01-01

The University of Montana (UM)-Missoula has implemented a problem-based program in which students perform scientific research focused on indoor air pollution. The Air Toxics Under the Big Sky program (Jones et al. 2007; Adams et al. 2008; Ward et al. 2008) provides a community-based framework for understanding the complex relationship between poor…

Cosmic Christ in a Quantum Universe.

NASA Astrophysics Data System (ADS)

Kohli, Mary Ann

This study examines the figure of the second American Adam--the cosmic Christ archetype--in terms of a possible shift in the focus of Western consciousness. As science moves closer to religion and as Newtonian dualism gives way to a more holistic theory (in which observer, observed, and process of observation are all intricately interlinked), the cosmic Christ emerges as a symbol in contemporary American fiction of a potentially unified awareness which could reconnect post-Christian man to God, to the world, and to the self. Such a rebirth of unity would be contingent upon the death of a consciousness reliant upon the rational, linear, masculine, left-brained thinking associated with the old Newtonian paradigm. The resurrected consciousness would consolidate Eastern and Western religion by acknowledging the God within man through the Western symbology of the Christ prototype. It would also balance the intuitional with the rational, the cyclical with the linear, the feminine with the masculine, and the right brain with the left. In other words, the repressed elements of the collective Western psyche would be allowed to come to awareness and be integrated into the mind at large. This integrating process is implicit in the cosmic Christ imagery. The novels which are considered are all concerned with the role of consciousness in the postmodern world and the part that science and religion play in determining the nature of that role. In such varied works as Thomas Pynchon's Gravity's Rainbow, John Updike's Roger's Version, Saul Bellow's Herzog, Joan Didion's A Book of Common Prayer, and William Vollmann's The Ice-Shirt, a cosmic Christ figure invariably appears. The success of this figure, however, is ambiguous and uncertain. At best, the transition of consciousness that is achieved is individual rather than communal. Nevertheless, as chaos theory has demonstrated, small changes can bring about major effects. Consequently, both the science of today and the rapid growth

Recapturing the Universal in the University

ERIC Educational Resources Information Center

Barnett, Ronald

2005-01-01

The idea of "the university" has stood for universal themes--of knowing, of truthfulness, of learning, of human development, and of critical reason. Through its affirming and sustaining of such themes, the university came itself to stand for universality in at least two senses: the university was neither partial (in its truth criteria) nor local…

Unstable Behavior of Lasers and Other Optical Systems.

DTIC Science & Technology

1987-11-27

Isaacs, R.S. Gioggia, S.P. Adams, L.M. Narducci, L.A. Lugiato, Optical Instabilities, R.W. Boyd, M.G. Raymer , L.M. Narducci, Eds. (Cambridge...Instabilities, R.W. Boyd, M.G. Raymer , L.M. Narducci, Eds. (Cambridge University" Press, Cambridge, 1986), p. 34. "The Effect of Modulation in a Bistable System...Books "* " "OPTICAL INSTABILITIES", edited by R.W. Boyd, M.G. Raymer , and L.M. Narducci, Cambridge University Press, Cambridge, 1986. S P.-• 58

Adaptation of Economy Attitude Scale to Turkish Culture: Validity and Reliability Study

ERIC Educational Resources Information Center

Alagoz, Bullent

2015-01-01

Economics affects us no matter what role we play in social life. Its foundation as a science was laid by the studies of Adam Smith, and since history it has become one of the disciplines accepted in university curriculums. Scarcity, opportunity costs and abandoning something in order to obtain another one are the core concepts of this discipline.…

26th National Neurotrauma Symposium

DTIC Science & Technology

2008-12-31

Sanchez Alvaro I., Puyana Juan C., Fabio Anthony, Adelson P. David 81 COMPARATIVE NEUROPROTECTIVE EFFECTS OF CYCLOSPORIN A AND NIM811, A NON...Xiangbai, Fabio Anthony, Yuan Zhifang, Niyonkuru Christian, Wagner Amy 99 ACTIVATION OF MITOCHONDRIAL UNCOUPLING PROTEINS BY POLYUNSATURATED FATTY...Metabolism/Physiological Assessments TBI Mitchell Cohen University of California, San Francisco Ferguson Adam, Cohen Mitchell, Morabito Diane

Responses from the Field

ERIC Educational Resources Information Center

Moreau, Lori; Weaver, Roberta; Adams, Shauna M.; Landers, Mary F.; Owen, Mary Jane

2006-01-01

This article offers responses from Lori Moreau, a principal, Roberta Weaver, associate dean, Shauna M. Adams, associate professor, Mary F. Landers of University of Dayton, and Mary Jane Owen, a founding director, to the article "The State of Special Education in Catholic Schools," by L. DeFiore (2006). Jesus, the master teacher, reached out to the…

The UHURU X-ray instrument.

NASA Technical Reports Server (NTRS)

Jagoda, N.; Austin, G.; Mickiewicz, S.; Goddard, R.

1972-01-01

On Dec. 12, 1970, the UHURU X-ray observatory was launched into equatorial orbit with the prime mission of conducting an all-sky survey of astronomical X-ray sources with intensities of 0.00005 Sco-X1 or greater. The X-ray detection system contains 12 gas-filled proportional counters, 6 behind each collimator. The aspect system is discussed together with the structure, the pulse height analyzer, the command system, the calibration system, and the power distribution system. Pulse shape discrimination circuits used on UHURU use the same technique that was used on the system originally developed for large area proportional counters described by Gorenstein and Mickiewicz (1968).

Therapeutic impact of rHuEPO on abnormal platelet APP, BACE 1, presenilin 1, ADAM 10 and Aβ expressions in chronic kidney disease patients with cognitive dysfunction like Alzheimer's disease: A pilot study.

PubMed

G, Vinothkumar; S, Krishnakumar; Sureshkumar; G, Shivashekar; S, Sreedhar; Preethikrishnan; S, Dinesh; A, Sundaram; D, Balakrishnan; Riya; P, Venkataraman

2018-08-01

Cognitive dysfunction is reported to be a major cause of morbidity in chronic kidney disease (CKD). The senile plaques (SPs) in the brain are one of the most pathophysiological characteristics of cognitive dysfunction and its major constituent amyloid β (Aβ) released from amyloid precursor protein (APP) by β (BACE1) and γ (presenilin 1) secretases . Platelets contain more than 95% of the circulating APP and implicate as a candidate biomarker for cognitive decline. Recombinant human erythropoietin (rHuEPO) is a standard therapy for anemia in CKD and also acts as a neuroprotective agent. The aim of the study is to determine the impact of rHuEPO therapy on platelet APP processing in CKD with Cognitive Dysfunction. A total of 60 subjects comprising of 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction based on neuropsychological assessment. APP, BACE1, Presenilin 1, ADAM 10 (α secretase) and Aβ expressions in platelets were determined by western blotting and lipid peroxidation (LPO) in platelet rich plasma (PRP) was done by spectrophotometrically. The parameters were statistically compared with Alzheimer's disease (AD), Normocytic normochromic anemic and healthy subjects. Significantly (p < 0.05) decreased APP, ADAM 10 while increased BACE1, Presenilin 1, Aβ and LPO were observed in CKD with cognitive dysfunction like AD subjects compared to other groups. The parameters were reassessed in CKD with cognitive dysfunction subjects after rHuEPO (100 IU/ kg, weekly twice, 6 months) therapy. All the parameters were retrieved significantly (p < 0.05) along with improved neuropsychological tests scoring after rHuEPO therapy. This study demonstrated that rHuEPO is an effective neuroprotective agent in the context of CKD associated cognitive dysfunction and proved its clinical usefulness. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The California Central Coast Research Partnership: Building Relationships, Partnerships, and Paradigms for University-Industry Research Collaboration

DTIC Science & Technology

2010-03-08

on the Cell Cycle and Development of Sea Urchins NATIONAL SCIENCE FOUNDATION (RUI) Lab Technician TBD Adams, Nikki 04-144 08/01/04-07/31/09...376,678 Mass spectroscopy analysis of effects of ultraviolet radiation on the proteome of sea urchin embryos CSUPERB: CSU FACULTY-STUDENT COLLABORATIVE...Development of Sea Urchins NATIONAL SCIENCE FOUNDATION (REU) 07-250 06/01/07-07/31/08 $6,000 CHRISTOPHER CLARK Clark, Christopher Moline, Mark Personnel

Detecting Potential Insider Threats Through Email Datamining

DTIC Science & Technology

2006-03-01

enron.com..................... Gracie S. Presas.... 0.000406706548263 9 83584 adam.giannone@enron.com................. Adam Giannone ...enron.com................ .................... 0.000380934354936 47 83584 adam.giannone@enron.com................. Adam Giannone

Brain Imaging and rTMS Studies of Individual Differences in Cognitive Processing

DTIC Science & Technology

2013-08-09

Institution: Address: Phone: Fax: Email : Web Page: Contract: Project Title: Program Officer: Dr. Marcel Adam Just Carnegie Mellon University...and multitasking ) are included in the progress report using well established sets of materials. In the sentence and discourse tasks, participants...compensatory partnerships and the re-emergence of the primary regions. 3. Cortical reorganization induced by rTMS during multitasking (listening to

Photographic copy of photograph (ca. 1934, original print located in ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photographic copy of photograph (ca. 1934, original print located in Margaret Long Collection, Box 20, Folder 2, Western History Collections, Norlin Library, University of Colorado at Boulder). VIEW OF ROUTE OF SMOKY HILL TRAIL NORTH NEAR JUNCTION WITH BOX ELDER ROAD, VICINITY OF WATKINS, COLORADO - Box Elder Road, Between 104th & 112th Avenues, Hudson & Watkins Roads, Watkins, Adams County, CO

Numerical Investigation of Laminar-Turbulent Transition in a Flat Plate Wake

DTIC Science & Technology

1990-03-02

Difference Methods , Oxford University Press. 3 Swarztrauber, P. N. (1977). "The Methods of Cyclic Reduction, Fourier Analysis and The FACR Algorithm for...streamwise and trans- verse directions. For the temporal discretion, a combination of ADI, Crank-Nicolson,Iand Adams-Rashforth methods is employed. The...41 U 5. NUMERICAL METHOD ...... .................... .. 50 3 5.1 Spanwise Spectral Approximation ... .............. ... 50 5.1.1 Fourier

Risk factor for preterm labor in Haji Adam Malik General Hospital, Pirngadi General hospital and satellite hospitals in Medan from January 2014 to December 2016

NASA Astrophysics Data System (ADS)

Sukatendel, K.; Hasibuan, C. L.; Pasaribu, H. P.; Sihite, H.; Ardyansah, E.; Situmorang, M. F.

2018-03-01

In 2010, Indonesia was ranked fifth in the world for the number of premature birth. Prematurity is a multifactorial problem. Preterm Labor (PTL) can occur spontaneously without a clear cause. Preventing PTL, its associated risk factors must be recognized first. To analyze risk factors associated with the incidence of PTL. It is a cross sectional study using secondary data obtained from medical records in Haji Adam Malik general hospital, Pirngadi general hospital and satellite hospitals in Medan from January 2014 to December 2016. Data were analyzed using chi-square method and logistic regression test. 148 cases for each group of preterm labor and obtained term laborin this study. Using the logistic regression test, three factors with astrong association to the incidence of identifiedpreterm labor. Antenatal Care frequency (OR 2,326; CI 95%), leucorrhea (OR 6,291; 95%), and premature rupture of membrane (OR 9,755; CI 95%). In conclusion, antenatal care frequency, leucorrhea, and history of premature rupture of themembrane may increase the incidence of Preterm Labor (PTL).

New Openings in University-Industry Cooperation: Aalto University as the Forerunner of European University Reform

ERIC Educational Resources Information Center

Markkula, Markku; Lappalainen, Pia

2009-01-01

The Innovation University (IU)--to be called the Aalto University after Alvav Aalto, a famous Finnish architect and MIT professor--is a new university which will be created through a merger of three existing universities: the Helsinki University of Technology (TKK), the Helsinki School of Economics (HSE) and the University of Art and Design…

The First Modern University: The University of Birmingham

ERIC Educational Resources Information Center

Arthur, James

2017-01-01

The University of Birmingham was planned, advanced and established with both national and German models of a University in mind. Civic reasons for the planning of the University need to be viewed within a broader motivational context. Even with a strong sense of civic place, the University was conceived as a modern University with multiple…

The University-Industry Relations of an Entrepreneurial University: The Case of the University of Twente.

ERIC Educational Resources Information Center

Schutte, Frits

1999-01-01

Describes the development of the University of Twente from a regional teaching university to a national research university, the "entrepreneurial university" of the Netherlands. Focuses on spinoffs from the university, an incubator in a business and science park and the generation of venture capital. Estimates the regional impact of such…

Experimental Methods to Characterize Nonlinear Vibration of Flapping Wing Micro Air Vehicles

DTIC Science & Technology

2007-03-01

EXPERIMENTAL METHODS TO CHARACTERIZE NONLINEAR VIBRATION OF FLAPPING WING MICRO AIR VEHICLES THESIS Adam P. Tobias, Captain, USAF...AFIT/GAE/ENY/07-M23 DEPARTMENT OF THE AIR FORCE AIR UNIVERSITY AIR FORCE INSTITUTE OF TECHNOLOGY Wright-Patterson Air Force Base, Ohio...author and do not reflect the official policy or position of the United States Air Force, Department of Defense, or the United States Government

Economic Development in Afghanistan during the Soviet Period, 1979-1989: Lessons Learned from the Soviet Experience in Afghanistan

DTIC Science & Technology

2007-08-01

edited by Harold Shukman; Adam B. Ulam, The Bolsheviks: The Intellectual and Political History of the Triumph of Communism in Russia ( New York...Fredericton, NB E3B 5A3 Professor Hugh White, Head Strategic and Defence Studies Centre Australian National University Coombs Building # 9...International Crisis Group Brussels Office 149 avenue Louise Level 24 B-1050 Brussels Belgium Mr. Robert Barrett Chief, International

RELEVANCE OF RELIGIOUS LEADER ENGAGEMENT FOR THE AIR FORCE CHAPLAIN CORPS

DTIC Science & Technology

2015-12-01

organizations. They are ordained religious leaders who have been set them aside to do sacred works. Furthermore, as Navy Chaplain George Adams writes...AU/ACSC/CHAE, C/AY16 AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY RELEVANCE OF RELIGIOUS LEADER ENGAGEMENT FOR THE...agent of Religious Leader Engagement on deployments in an informal manner. As the nature of warfare continues to evolve toward a non-traditional

Suicidal ideation modulates the reduction in serotonin transporter availability in male military conscripts with major depression: A 4-[18F]-ADAM PET study.

PubMed

Yeh, Yi-Wei; Ho, Pei-Shen; Chen, Chun-Yen; Kuo, Shin-Chang; Liang, Chih-Sung; Yen, Che-Hung; Huang, Chang-Chih; Shiue, Chyng-Yann; Huang, Wen-Sheng; Ma, Kuo-Hsing; Lu, Ru-Band; Huang, San-Yuan

2015-10-01

Suicide is an important issue in the military service, since it can influence military morale and create dangerous situations for other personnel. The serotonin transporter (SERT) has been suggested to be involved in the pathophysiology of depression and suicidal behaviours. The aims of this study were to examine whether the brain SERT availability differs between military conscripts with depression and control subjects, and whether suicidal ideation is correlated with SERT availability. We used N,N-dimethyl-2-(2-amino-4-[(18)F]-fluorophenylthio)benzylamine (4-[(18)F]-ADAM) as a radioligand for positron emission tomography (PET) imaging. All participants completed the Hamilton Depression Rating Scale and Beck Scale for Suicide Ideation (BSS) prior to PET imaging. The effect of major depression and BSS scores had an interaction on SERT availability. After adjusting for the BSS score, subjects with depression had lower SERT availability than control subjects (F1,17 = 23.85, P < 0.001). A positive correlation between SERT availability and BSS scores was observed in the depression group (F1,8 = 30.67, P = 0.001). The status of depression and intensity of suicidal ideation exert opposite effects on SERT availability. The extent of suicidal ideation may moderate the reduction effect in SERT binding observed in major depression in male military conscripts.

A disintegrin and metalloproteinase 17 regulates TNF and TNFR1 levels in inflammation and liver regeneration in mice

PubMed Central

McMahan, Ryan S.; Riehle, Kimberly J.; Fausto, Nelson

2013-01-01

A disintegrin and metalloproteinase 17 (ADAM17), or tumor necrosis factor (TNF)-α-converting enzyme, is a key metalloproteinase and physiological convertase for a number of putative targets that play critical roles in cytokine and growth factor signaling. These interdependent pathways are essential components of the signaling network that links liver function with the compensatory growth that occurs during liver regeneration following 2/3 partial hepatectomy (PH) or chemically induced hepatotoxicity. Despite identification of many soluble factors needed for efficient liver regeneration, very little is known about how such ligands are regulated in the liver. To directly study the role of ADAM17 in the liver, we employed two cell-specific ADAM17 knockout (KO) mouse models. Using lipopolysaccharide (LPS) as a robust stimulus for TNF release, we found attenuated levels of circulating TNF in myeloid-specific ADAM17 KO mice (ADAM17 m-KO) and, unexpectedly, in mice with hepatocyte-specific ADAM17 deletion (ADAM17 h-KO), indicating that ADAM17 expression in both cell types plays a role in TNF shedding. After 2/3 PH, induction of TNF, TNFR1, and amphiregulin (AR) was significantly attenuated in ADAM17 h-KO mice, implicating ADAM17 as the primary sheddase for these factors in the liver. Surprisingly, the extent and timing of hepatocyte proliferation were not affected after PH or carbon tetrachloride injection in ADAM17 h-KO or ADAM17 m-KO mice. We conclude that ADAM17 regulates TNF, TNFR1, and AR in the liver, and its expression in both hepatocytes and myeloid cells is important for TNF regulation after LPS injury or 2/3 PH, but is not required for liver regeneration. PMID:23639813

Inducible expression of A Disintegrin and Metalloproteinase 8 in chronic periodontitis and gingival epithelial cells.

PubMed

Aung, W P P; Chotjumlong, P; Pata, S; Montreekachon, P; Supanchart, C; Khongkhunthian, S; Sastraruji, T; Krisanaprakornkit, S

2017-06-01

The expression of A Disintegrin and Metalloproteinase 8 (ADAM8) is associated with several inflammatory diseases. Elevated ADAM8 levels have been shown in gingival crevicular fluid of patients with chronic periodontitis. The objective of this study was to investigate ADAM8 expression in chronic periodontitis tissues compared with that in normal tissues. ADAM8 expression and its inductive mechanism were examined in human gingival epithelial cells (HGECs) and human gingival fibroblasts. Total RNA and protein were extracted from gingival biopsies of 33 patients with chronic periodontitis and those of 23 healthy volunteers. ADAM8 mRNA and protein expression was analyzed by real-time polymerase chain reaction, immunoblotting and immunohistochemistry. ADAM8 expression in control and stimulated cells in the presence or absence of specific inhibitors for mitogen-activated protein kinase pathways was assayed by real-time polymerase chain reaction, immunoblotting, flow cytometry and immunofluorescence. ADAM8 mRNA and protein expression in chronic periodontitis tissues was significantly greater than that in normal tissues (p < 0.01). Significantly increased ADAM8 expression was detected in the gingival epithelium of chronic periodontitis tissues (p < 0.001). ADAM8 mRNA expression in HGECs, but not in human gingival fibroblasts, was significantly induced by stimulation with Fusobacterium nucleatum (p < 0.05), partially via the p44/42 mitogen-activated protein kinase pathway. ADAM8 expression in the cell lysates and on the surface of HGECs was induced by stimulation with F. nucleatum. ADAM8 expression is increased in inflamed chronic periodontitis tissues and localized within gingival epithelium, consistent with an upregulation of ADAM8 expression in F. nucleatum-stimulated HGECs, suggesting a possible role of ADAM8 in innate immunity of periodontal tissue. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Universities, Knowledge and Pedagogical Configurations: Glimpsing the Complex University

ERIC Educational Resources Information Center

Guzmán-Valenzuela, Carolina

2018-01-01

This paper elaborates a typology of universities in which each university is characteristically associated with (i) diverse missions, (ii) different ways of producing knowledge and (iii) contrasting pedagogical configurations. Four university forms are identified, analysed and illustrated, namely the expert university, the non-elite university,…

"Computers: Cure-All or Snake Oil?" Proceedings from the Spring Meeting of the Nebraska Library Association, College and University Section (Bellevue, Nebraska, April 20, 1984).

ERIC Educational Resources Information Center

Krzywkowski, Valerie I., Ed.

The 15 papers in this collection discuss various aspects of computer use in libraries and several other aspects of library service not directly related to computers. Following an introduction and a list of officers, the papers are: (1) "Criminal Justice and Related Databases" (Kate E. Adams); (2) "Software and Hard Thought:…

78 FR 70964 - Luminant Generation Company, LLC

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-27

... search for Docket ID NRC-2008-0594. Address questions about NRC dockets to Carol Gallagher; telephone... at http://www.nrc.gov/reading-rm/adams.html . To begin the search, select ``ADAMS Public Documents'' and then select ``Begin Web- based ADAMS Search.'' For problems with ADAMS, please contact the NRC's...

77 FR 50541 - STP Nuclear Operating Company, South Texas Project, Units 1 and 2; Application for Amendment to...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-21

... any of the following methods: Federal Rulemaking Web Site: Go to http://www.regulations.gov and search.../reading-rm/adams.html . To begin the search, select ``ADAMS Public Documents'' and then select ``Begin Web- based ADAMS Search.'' For problems with ADAMS, please contact the NRC's Public Document Room (PDR...

78 FR 68100 - Luminant Generation Company, LLC

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-13

... following methods: Federal Rulemaking Web site: Go to http://www.regulations.gov and search for Docket ID.../adams.html . To begin the search, select ``ADAMS Public Documents'' and then select ``Begin Web- based ADAMS Search.'' For problems with ADAMS, please contact the NRC's Public Document Room (PDR) reference...

78 FR 49305 - Luminant Generation Company LLC, Comanche Peak Nuclear Power Plant, Unit Nos. 1 and 2...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-13

... http://www.regulations.gov and search for Docket ID NRC-2013-0182. Address questions about NRC dockets... NRC Library at http://www.nrc.gov/reading-rm/adams.html . To begin the search, select ``ADAMS Public Documents'' and then select ``Begin Web- based ADAMS Search.'' For problems with ADAMS, please contact the...

77 FR 56238 - Wolf Creek Nuclear Operating Corporation, Wolf Creek Generating Station; Application for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-12

....regulations.gov and search for Docket ID NRC-2012-0212. Address questions about NRC dockets to Carol Gallagher....gov/reading-rm/adams.html . To begin the search, select ``ADAMS Public Documents'' and then select ``Begin Web- based ADAMS Search.'' For problems with ADAMS, please contact the NRC's Public Document Room...

Selling University Reform: The University of Melbourne and the Press

ERIC Educational Resources Information Center

Potts, Anthony

2012-01-01

Since the advent of the "Times Higher Education Supplement World University Rankings" and the "Academic Rankings of World Universities" by Shanghai Jiao Tong University, some Australian universities have become especially concerned with being ranked among the 100 leading universities. The University of Melbourne, Australia's…

EphA2/Ephrin-A1 Mediate Corneal Epithelial Cell Compartmentalization via ADAM10 Regulation of EGFR Signaling

PubMed Central

Kaplan, Nihal; Ventrella, Rosa; Peng, Han; Pal-Ghosh, Sonali; Arvanitis, Constadina; Rappoport, Joshua Z.; Mitchell, Brian J.; Stepp, Mary Ann; Lavker, Robert M.

2018-01-01

Purpose Progenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal–corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal pattern led us to assess the role of ephrin-A1 and EphA2 in limbal–corneal epithelial boundary organization. Methods EphA2-expressing corneal epithelial cells engineered to express ephrin-A1 were used to study boundary formation in vitro in a manner that mimicked the relative abundance of these juxtamembrane signaling proteins in the limbal and corneal epithelium in vivo. Interaction of these two distinct cell populations following initial seeding into discrete culture compartments was assessed by live cell imaging. Immunofluoresence and immunoblotting was used to evaluate the contribution of downstream growth factor signaling and cell–cell adhesion systems to boundary formation at sites of heterotypic contact between ephrin-A1 and EphA2 expressing cells. Results Ephrin-A1–expressing cells impeded and reversed the migration of EphA2-expressing corneal epithelial cells upon heterotypic contact formation leading to coordinated migration of the two cell populations in the direction of an ephrin-A1–expressing leading front. Genetic silencing and pharmacologic inhibitor studies demonstrated that the ability of ephrin-A1 to direct migration of EphA2-expressing cells depended on an a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and epidermal growth factor receptor (EGFR) signaling pathway that limited E-cadherin–mediated adhesion at heterotypic boundaries. Conclusions Ephrin-A1/EphA2 signaling complexes play a key role in limbal–corneal epithelial compartmentalization and the response of these tissues to injury. PMID:29351356

EphA2/Ephrin-A1 Mediate Corneal Epithelial Cell Compartmentalization via ADAM10 Regulation of EGFR Signaling.

PubMed

Kaplan, Nihal; Ventrella, Rosa; Peng, Han; Pal-Ghosh, Sonali; Arvanitis, Constadina; Rappoport, Joshua Z; Mitchell, Brian J; Stepp, Mary Ann; Lavker, Robert M; Getsios, Spiro

2018-01-01

Progenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal-corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal pattern led us to assess the role of ephrin-A1 and EphA2 in limbal-corneal epithelial boundary organization. EphA2-expressing corneal epithelial cells engineered to express ephrin-A1 were used to study boundary formation in vitro in a manner that mimicked the relative abundance of these juxtamembrane signaling proteins in the limbal and corneal epithelium in vivo. Interaction of these two distinct cell populations following initial seeding into discrete culture compartments was assessed by live cell imaging. Immunofluoresence and immunoblotting was used to evaluate the contribution of downstream growth factor signaling and cell-cell adhesion systems to boundary formation at sites of heterotypic contact between ephrin-A1 and EphA2 expressing cells. Ephrin-A1-expressing cells impeded and reversed the migration of EphA2-expressing corneal epithelial cells upon heterotypic contact formation leading to coordinated migration of the two cell populations in the direction of an ephrin-A1-expressing leading front. Genetic silencing and pharmacologic inhibitor studies demonstrated that the ability of ephrin-A1 to direct migration of EphA2-expressing cells depended on an a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and epidermal growth factor receptor (EGFR) signaling pathway that limited E-cadherin-mediated adhesion at heterotypic boundaries. Ephrin-A1/EphA2 signaling complexes play a key role in limbal-corneal epithelial compartmentalization and the response of these tissues to injury.

77 FR 26316 - Progress Energy Florida; Final Environmental Impact Statement for Combined Licenses for Levy...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-03

..., Rockville, Maryland, 20852 or from NRC's Agencywide Documents Access and Management System (ADAMS). ADAMS is accessible from the NRC's Web site at www.nrc.gov/reading-rm/adams.html . The ADAMS accession numbers for the... . In addition, the following four public libraries have agreed to make the final EIS available to the...

Overexpression and knock-down studies highlight that a disintegrin and metalloproteinase 28 controls proliferation and migration in human prostate cancer.

PubMed

Rudnicka, Caroline; Mochizuki, Satsuki; Okada, Yasunori; McLaughlin, Claire; Leedman, Peter J; Stuart, Lisa; Epis, Michael; Hoyne, Gerard; Boulos, Sherif; Johnson, Liam; Schlaich, Markus; Matthews, Vance

2016-10-01

Prostate cancer is one of the most prevalent cancers in men. It is critical to identify and characterize oncogenes that drive the pathogenesis of human prostate cancer. The current study builds upon previous research showing that a disintegrin and metallproteinase (ADAM)28 is involved in the pathogenesis of numerous cancers. Our novel study used overexpression, pharmacological, and molecular approaches to investigate the biological function of ADAM28 in human prostate cancer cells, with a focus on cell proliferation and migration. The results of this study provide important insights into the role of metalloproteinases in human prostate cancer.The expression of ADAM28 protein levels was assessed within human prostate tumors and normal adjacent tissue by immunohistochemistry. Immunocytochemistry and western blotting were used to assess ADAM28 protein expression in human prostate cancer cell lines. Functional assays were conducted to assess proliferation and migration in human prostate cancer cells in which ADAM28 protein expression or activity had been altered by overexpression, pharmacological inhibition, or by siRNA gene knockdown.The membrane bound ADAM28 was increased in human tumor biopsies and prostate cancer cell lines. Pharmacological inhibition of ADAM28 activity and/or knockdown of ADAM28 significantly reduced proliferation and migration of human prostate cancer cells, while overexpression of ADAM28 significantly increased proliferation and migration.ADAM28 is overexpressed in primary human prostate tumor biopsies, and it promotes human prostate cancer cell proliferation and migration. This study supports the notion that inhibition of ADAM28 may be a potential novel therapeutic strategy for human prostate cancer.

Dome: Distributed Object Migration Environment

DTIC Science & Technology

1994-05-01

Best Available Copy AD-A281 134 Computer Science Dome: Distributed object migration environment Adam Beguelin Erik Seligman Michael Starkey May 1994...Beguelin Erik Seligman Michael Starkey May 1994 CMU-CS-94-153 School of Computer Science Carnegie Mellon University Pittsburgh, PA 15213 Abstract Dome... Linda [4], Isis [2], and Express [6] allow a pro- grammer to treat a heterogeneous network of computers as a parallel machine. These tools allow the

Validation of Automated Prediction of Blood Product Needs Algorithm Processing Continuous Non Invasive Vital Signs Streams (ONPOINT4)

DTIC Science & Technology

2018-01-25

ORGANIZATION NAME(S) AND ADDRESS(ES) University of Maryland, Baltimore 22 S. Greene St. R Adams Cowley Shock Trauma Center, T5R46 Baltimore, MD 21201 8...the revised trauma score, shock index (= heart rate/systolic blood pressure), and assessment of blood consumption, our M2 (bleeding risk index...11 4.2 Transfusion Prediction Model Evaluation in Special Subsets (Model Stress Test) ....... 15 4.3 Feature Sets and Model Stability

Countering Radicalization: Refocusing Responses to Violent Extremism Within the United States

DTIC Science & Technology

2011-12-01

obsessed with religion.38 His initial goals were laudable; according to his brother, “He said he just wanted to do good. He wanted to go to heaven...time Samir arrived in North Carolina he was completely obsessed with extremist ideology. A friend, Adam Azad related that during their first...volunteer activities. Efforts can be tailored to specific areas such as university campuses, coffee shops, or community centers. Each effort

Understanding the Islamic Movement of Uzbekistan Through Social Movement Theory, and Analyzing and Evaluating Its Potential Threat to Kazakhstan

DTIC Science & Technology

2014-12-01

ORGANIZATION REPORT NUMBER 9. SPONSORING /MONITORING AGENCY NAME(S) AND ADDRESS(ES) N /A 10. SPONSORING/MONITORING AGENCY REPORT NUMBER...Insurgency, 1930‒1970 (Chicago: University of Chicago Press, 1982), 18. 36 Doug McAdam, John D. McCarthy, and Mayer N . Zald, Comparative Perspectives on...Portrait,” Central Asia and the Caucasus, http://cyberleninka.ru/article/ n /the-islamic-movement-of-uzbekistan-lines-to- complete-the-portrait. 27

Antimony-Based Type-II Superlattice Photodetectors

DTIC Science & Technology

2010-09-06

photodetectors, antimony-based mid- infrared detectors Shun L. Chuang, Russell D. Dupuis University of Illinois - Urbana Grants and Contracts Office...Q. Yang, Interband Cascade Detectors , US Patent #7,282,777, October 16, 2007. Graduate Students PERCENT_SUPPORTEDNAME Shin Mou 0.25 Adam Petschke...DD882) Inventions (DD882) Interband Cascade Detectors Patent Filed in US? (5d-1) Y NPatent Filed in Foreign Countries? (5d-2) Was the assignment

International Workshop on Detection, Classification and Localization of Marine Mammals Using Passive Acoustics (4th). International Workshop on Density Estimation of Marine Mammals Using Passive Acoustics (1st)

DTIC Science & Technology

2009-09-13

University of Singapore) Olivier Adam (NAMC, Univ. of Paris , France) Len Thomas (Univ St Andrews, Scotland; convenor of the DE workshop...Hervé, Paris Sébastien 90 3 - The Continuous Development for Passive Acoustic Monitoring in Offshore Commercial Industry A. Cucknell and N. Clark...encourage researchers to work on a common dataset, to focus on the same problems, to find original solutions, and to present and compare them at the

University-Community Engagement: Case Study of University Social Responsibility

ERIC Educational Resources Information Center

Chile, Love M.; Black, Xavier M.

2015-01-01

Corporatisation of universities has drawn parallels between contemporary universities and business corporations, and extended analysis of corporate social responsibility to universities. This article reports on a case study of university-community engagement with schools and school communities through youth engagement programmes to enhance…

[The "Anatomic Charts" (1722) of Johann Adam Kulmus (1689-1745). A textbook for (wound)physician education in the German language countries and in Japan].

PubMed

Sachs, Michael

2002-01-01

Although we can not find new disclosures or new ways of describing anatomical structures in the "Anatomischen Tabellen", a text-book written by Johann Adam Kulmus (1689-1745), it has had it's influence in the development of medicine, not only in Germany but in Japan. The "Anatomischen Tabellen" has been one of the most published anatomical text-books of the 18th century. This book was concepted by the medical doctor Kulmus, who was born in the German town Breslau and who was living in Danzig, especially to educate the apprentices and fellows of surgeons in German language. Therefore the book was equiped with several copper-plates for illustration. During the years from 1722 to 1814 23 different editions were found, from those were 14 in German, 5 in Latin and one each in French and Netherland. Not one other anatomical textbooks of the 18th century has had such an abundance of editions. The disadvantage of the former used oversized anatomical atlases was their being published in latin and therefore they have been without any use and much too expensive for educational purposes for young surgeons. The "Anatomischen Tabellen" has been the first occidental text-book of anatomy to be translated into japanese to be published in 1774, supplied with numerous wooden engravings.

1988-91 Agreement between Oakland University and the Oakland University Chapter, American Association of University Professors.

ERIC Educational Resources Information Center

American Association of Univ. Professors, Washington, DC.

This document presents the 1988-91 agreement between Oakland University (Michigan) and the Oakland University Chapter of the American Association of University Professors. The following 32 articles are detailed: definitions; recognition; work of the bargaining unit; academic titles; association rights; University management; faculty employment,…

Adam's Dream

ERIC Educational Resources Information Center

Piacenti, Alexandria

2011-01-01

Growing up as a young girl, summer camp was a typical affair. Packed lunches kept cold with frozen freezer packs, seemingly endless slip n' slides, activities, games, contests. Every morning, the author was eager to wake up and head off to hours and hours of fun with friends and counselors. However, one may think the camping experience could not…

Agreement between Oakland University and the Oakland University Chapter, American Association of University Professors, 1985-88.

ERIC Educational Resources Information Center

American Association of Univ. Professors, Washington, DC.

The collective bargaining agreement between Oakland University and the University's chapter (370 members) of the American Association of University Professors (AAUP) covering the period 1985-1988 is presented. Items covered in the agreement include: definitions and recognition of AAUP, academic titles, AAUP rights, university management,…

Is this the right time to come out? Case study.

PubMed

Williamson, A D; Woods, J D; Conley, J M; O'Barr, W M; Losey, M R; Colbert, C; Wofford, J; McNamara, E

1993-01-01

In this fictional case study, Adam Lawson is a promising young associate at Kirkham McDowell Securities, a St. Louis underwriting and financial advisory firm. Recently, Adam helped to bring in an extremely lucrative deal, and soon he and a few other associates will be honored for their efforts at the firm's silver anniversary dinner. George Campbell, vice president in mergers and acquisitions, is caught unprepared when Adam tells him that, after serious reflection, he has decided to bring his partner, Robert Collins, to the banquet. George is one of Adam's biggest supporters at the firm, and he personally has no problem with Adam being gay. But it is one thing for Adam to come out of the closet at the office. It is quite another to do so at a public company-client event. After all, Kirkham McDowell's client roster includes some very conservative companies--one of the country's largest defense contractors, for example. George is concerned with how Adam's openness about his sexual orientation will play with their clients and, as a result, how senior management will react. Adam has not come to George for permission to bring Robert to the dinner. But clearly Adam wants some sort of response. George has never faced sexual diversity issues in the workplace before, and there is no company policy to guide him. Just how negative an effect could Robert have on Adam's career with the firm and the firm's relationship with its clients? Isn't it possible that even the firm's most conservative clients will simply decide that Adam's choice of guest is a personal matter--not a business one?(ABSTRACT TRUNCATED AT 250 WORDS)