Institution
Research Triangle Park
Nonprofit•Durham, North Carolina, United States•
About: Research Triangle Park is a nonprofit organization based out in Durham, North Carolina, United States. It is known for research contribution in the topics: Population & Environmental exposure. The organization has 24961 authors who have published 35800 publications receiving 1684504 citations. The organization is also known as: RTP.
Topics: Population, Environmental exposure, Receptor, Poison control, Agonist
Papers published on a yearly basis
Papers
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University of California, San Diego1, BC Cancer Research Centre2, University of Arkansas for Medical Sciences3, Oregon Health & Science University4, Drexel University5, University of Maryland, Baltimore6, Thermo Fisher Scientific7, Simon Fraser University8, Vrije Universiteit Brussel9, Stanford University10, Research Triangle Park11, National Institutes of Health12, Royal Society of Chemistry13, University of Oxford14, University of Michigan15, University at Buffalo16, Newcastle University17, European Bioinformatics Institute18, University of Pennsylvania19, Southern Methodist University20, University of Manchester21, La Jolla Institute for Allergy and Immunology22, J. Craig Venter Institute23, Leibniz Association24, Brunel University London25, Georgia State University26
TL;DR: The state of OBI and several applications that are using it are described, such as adding semantic expressivity to existing databases, building data entry forms, and enabling interoperability between knowledge resources.
Abstract: The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource (http://obi-ontology.org) providing details on the people, policies, and issues being addressed in association with OBI. The current release of OBI is available at http://purl.obolibrary.org/obo/obi.owl.
265 citations
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TL;DR: NA inhibition of inducible mouse macrophage NOS (iNOS) was weaker (Ki = 4.4 microM) and rapidly reversible and NA was a 300-fold more potent inhibitor of bovine brain cNOS than mousemacrophage iNOS.
Abstract: L-NG-Nitroarginine (NA) inhibited both the L-arginine oxidation and the L-arginine-independent NADPH oxidation reactions catalyzed by the calcium/calmodulin-dependent constitutive nitric oxide synthase (cNOS) from bovine brain. NA binding did not require calmodulin, calcium, or NADPH. The onset of inhibition was slow with a second-order association rate constant (k(on) of 4.4 x 10(4) M-1 s-1. The dissociation rate constant (k(off) was 6.5 x 10(-4) s-1. The Kd value (k(off)/k(on)) of bovine brain cNOS for NA was 15 nM. L-Arginine was a competitive inhibitor of NA binding with a Ks value of 0.8 microM. The Km for L-arginine in the cNOS reaction was 1.2 microM. The NA binding sites of cNOS were titrated with NA, which enabled a kcat of 0.7 s-1, for the oxidation of L-arginine, to be calculated. Finally, a brain cNOS-(3H)NA complex was isolated. In contrast to the potent and slow onset of NA inhibition of brain cNOS, NA inhibition of inducible mouse macrophage NOS (iNOS) was weaker (Ki = 4.4 microM) and rapidly reversible. Thus, NA was a 300-fold more potent inhibitor of bovine brain cNOS than mouse macrophage iNOS.
265 citations
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TL;DR: It is reported that contactin colocalizes and forms a cis complex with Caspr in the paranodes and juxtamesaxon, suggesting that a preformed complex of Caspr and contactin is targeted to the paranodal junctions via extracellular interactions with myelinating glia.
Abstract: Specialized paranodal junctions form between the axon and the closely apposed paranodal loops of myelinating glia. They are interposed between sodium channels at the nodes of Ranvier and potassium channels in the juxtaparanodal regions; their precise function and molecular composition have been elusive. We previously reported that Caspr (contactin-associated protein) is a major axonal constituent of these junctions (Einheber et al., 1997). We now report that contactin colocalizes and forms a cis complex with Caspr in the paranodes and juxtamesaxon. These proteins coextract and coprecipitate from neurons, myelinating cultures, and myelin preparations enriched in junctional markers; they fractionate on sucrose gradients as a high-molecular-weight complex, suggesting that other proteins may also be associated with this complex. Neurons express two contactin isoforms that differ in their extent of glycosylation: a lower-molecular-weight phosphatidylinositol phospholipase C (PI-PLC)-resistant form is associated specifically with Caspr in the paranodes, whereas a higher-molecular-weight form of contactin, not associated with Caspr, is present in central nodes of Ranvier. These results suggest that the targeting of contactin to different axonal domains may be determined, in part, via its association with Caspr. Treatment of myelinating cocultures of Schwann cells and neurons with RPTPβ–Fc, a soluble construct containing the carbonic anhydrase domain of the receptor protein tyrosine phosphatase β (RPTPβ), a potential glial receptor for contactin, blocks the localization of the Caspr/contactin complex to the paranodes. These results strongly suggest that a preformed complex of Caspr and contactin is targeted to the paranodal junctions via extracellular interactions with myelinating glia.
265 citations
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TL;DR: Significant antitumor effects were observed in nude mice bearing tumors derived from WiDr/CD cells when these animals were given 500 mg FCyt/kg i.p. for 10 consecutive days, and positive data support the continued development of a gene therapy approach to colorectal carcinoma involving the selective expression of CD.
Abstract: A human colorectal carcinoma cell line, WiDr, was genetically engineered to express the nonmammalian enzyme, cytosine deaminase (CD) Expression of CD in WiDr cells (WiDr/CD) did not alter the growth rate of these cells when grown in vitro or as solid tumor xenografts in nude mice However, expression of CD did increase the sensitivity of these cells to the nontoxic prodrug, 5-fluorocytosine (FCyt), decreasing the 50% inhibitory concentration for FCyt from 26,000 µm in parental WiDr cells to 27 µm in WiDr/CD cells The increase in sensitivity to FCyt in WiDr/CD cells was the result of the CD-mediated conversion of FCyt to 5-fluorouracil (FUra) and subsequent FUra anabolites The half-life of the prodrug, FCyt, was determined to be approximately 40 min in nude mice A single ip injection of 500 mg FCyt/kg body weight resulted in a transient FCyt plasma level of approximately 4000 µm while osmotic minipumps or constant tail vein infusions of FCyt achieved continual FCyt plasma levels of 5 µm and 50 µm, respectively, with no overt signs of toxicity Significant antitumor effects were observed in nude mice bearing tumors derived from WiDr/CD cells when these animals were given 500 mg FCyt/kg ip for 10 consecutive days These antitumor effects were demonstrated by decreases in tumor growth rate, tumor size, tumor weight, and thymidine incorporation into tumor DNA This antitumor effect was significant but less profound if FCyt was administered by constant tail vein infusion WiDr and WiDr/CD cells were very sensitive to FUra in vitro (50% inhibitory concentration approximately 5 /am) However, no significant antitumor effects were observed in nude mice bearing tumors derived from either WiDr or WiDr/CD cells when these animals were treated with various doses of FUra Taken collectively, these data indicate that nontoxic plasma levels of FCyt can be attained which can produce profound antitumor effects on tumors engineered to express CD and that these antitumor effects are significantly better than those that can be achieved using FUra These positive data support the continued development of a gene therapy approach to colorectal carcinoma involving the selective expression of CD in colorectal tumors with subsequent administration of FCyt
264 citations
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University of Colorado Boulder1, Lawrence Berkeley National Laboratory2, Joint BioEnergy Institute3, Cooperative Institute for Research in Environmental Sciences4, Argonne National Laboratory5, University of Southern California6, University of Queensland7, Research Triangle Park8, University of Chicago9, Washington University in St. Louis10, VU University Amsterdam11
TL;DR: Improvements in comparability of data will facilitate the study of biotechnologically relevant processes, such as bioprospecting for new glycoside hydrolases or identifying novel energy sources.
Abstract: Metagenomics holds enormous promise for discovering novel enzymes and organisms that are biomarkers or drivers of processes relevant to disease, industry and the environment. In the past two years, we have seen a paradigm shift in metagenomics to the application of cross-sectional and longitudinal studies enabled by advances in DNA sequencing and high-performance computing. These technologies now make it possible to broadly assess microbial diversity and function, allowing systematic investigation of the largely unexplored frontier of microbial life. To achieve this aim, the global scientific community must collaborate and agree upon common objectives and data standards to enable comparative research across the Earth's microbiome. Improvements in comparability of data will facilitate the study of biotechnologically relevant processes, such as bioprospecting for new glycoside hydrolases or identifying novel energy sources.
264 citations
Authors
Showing all 25006 results
Name | H-index | Papers | Citations |
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Douglas G. Altman | 253 | 1001 | 680344 |
Lewis C. Cantley | 196 | 748 | 169037 |
Ronald Klein | 194 | 1305 | 149140 |
Daniel J. Jacob | 162 | 656 | 76530 |
Christopher P. Cannon | 151 | 1118 | 108906 |
James B. Meigs | 147 | 574 | 115899 |
Lawrence Corey | 146 | 773 | 78105 |
Jeremy K. Nicholson | 141 | 773 | 80275 |
Paul M. Matthews | 140 | 617 | 88802 |
Herbert Y. Meltzer | 137 | 1148 | 81371 |
Charles J. Yeo | 136 | 672 | 76424 |
Benjamin F. Cravatt | 131 | 666 | 61932 |
Timothy R. Billiar | 131 | 838 | 66133 |
Peter Brown | 129 | 908 | 68853 |
King K. Holmes | 124 | 606 | 56192 |