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Following antigenic challenge, MHC-restricted T cell responses are directed against a few dominant antigenic epitopes. Here, evidence is provided demonstrating the importance of APC in modulating the hierarchy of MHC class II-restricted T cell responses. Biochemical analysis of class II:peptide complexes in B cells revealed the presentation of a hierarchy(More)
Inhibition of the biosynthesis of proinflammatory cytokines such as tumor necrosis factor and interleukin-1 via p38 has been an approach toward the development of a disease modifying agent for the treatment of chronic inflammation and autoimmune diseases. The development of a new core structure of p38 inhibitors,(More)
The human immunodeficiency, type II bare lymphocyte syndrome (BLS), has been attributed to a defect in the transcription of class II histocompatibility genes. Immunocompetence, as assessed by functional exogenous antigen presentation, was not restored in immortalized B cells, derived from a BLS patient, after transfection with HLA-DR class II structural(More)
BACKGROUND Human pancreatic islet structure poses challenges to investigations that require specific modulation of gene expression. Yet dissociation of islets into individual cells destroys cellular interactions important to islet physiology. Approaches that improve transient targeting of gene expression in intact human islets are needed in order to(More)
Peptides derived from endogenous and exogenous antigens compete for binding and presentation via class II molecules. Studies with mutant B cell lines defective in exogenous antigen presentation suggest that HLA-DM molecules facilitate the interaction of foreign peptides and class II molecules. In contrast, presentation of self antigens is not strictly(More)
For years we have recognized that using genetics to target the right medicines to the right patients at the right time could improve health care; however, technical and financial constraints have prevented researchers from conducting the comprehensive, whole-genome association studies required to make such advances. Now, Perlegen and its collaborators are(More)
A novel class of highly selective inhibitors of p38 MAP kinase was discovered from high throughput screening. The synthesis and optimization of a series of 5-amino-N-phenyl-1H-pyrazol-4-yl-3-phenylmethanones is described. An X-ray crystal structure of this series bound in the ATP binding pocket of unphosphorylated p38alpha established the presence of a(More)
For years we have recognized that using genetics to target the right medicines to the right patients at the right time could improve healthcare; however, technical and financial constraints have prevented researchers from conducting the comprehensive, whole-genome association studies required to make such advances. Now, Perlegen and its collaborators are(More)
Article history: Received 18 May 2015 Received in revised form 17 November 2015 Accepted 30 November 2015 Available online xxxx In this work, a methodology based on the E-model for the reliability projection of a thick (N20 nm) SiO2 gate oxide on a vertical trenchpowerMOSFET, is presented. Experimental results suggest that a Logic Level (LL) trench(More)
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