43 research outputs found

    Application of a floating well concept to a latch-up-free, low-cost, smart power high-side switch technology

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    The aim of this brief is to present an original design methodology that permits implementing latch-up-free smart power circuits on a very simple, cost-effective technology. The basic concept used for this purpose is letting float the wells of the MOS transistors most susceptible to initiate latch-up

    Global assessment of dengue Virus-Specific CD4+ T cell responses in Dengue-Endemic areas

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    Background: Dengue is a major public health problem worldwide. Assessment of adaptive immunity is important to understanding immunopathology and to define correlates of protection against dengue virus (DENV). To enable global assessment of CD4+ T cell responses, we mapped HLA-DRB1-restricted DENV-specific CD4+ T cell epitopes in individuals previously exposed to DENV in the general population of the dengue-endemic region of Managua, Nicaragua. Methods: HLA class II epitopes in the population of Managua were identified by an in vitro IFNγ ELISPOT assay. CD4+ T cells purified by magnetic bead negative selection were stimulated with HLA-matched epitope pools in the presence of autologous antigen-presenting cells, followed by pool deconvolution to identify specific epitopes. The epitopes identified in this study were combined with those previously identified in the DENV endemic region of Sri Lanka, to generate a “megapool” (MP) consisting of 180 peptides specifically designed to achieve balanced HLA and DENV serotype coverage. The DENV CD4MP180 was validated by intracellular cytokine staining assays. Results: We detected responses directed against a total of 431 epitopes, representing all 4 DENV serotypes, restricted by 15 different HLA-DRB1 alleles. The responses were associated with a similar pattern of protein immunodominance, overall higher magnitude of responses, as compared to what was observed previously in the Sri Lanka region. Based on these epitope mapping studies, we designed a DENV CD4 MP180 with higher and more consistent coverage, which allowed the detection of CD4+ T cell DENV responses ex vivo in various cohorts of DENV exposed donors worldwide, including donors from Nicaragua, Brazil, Singapore, Sri Lanka, and U.S. domestic flavivirus-naïve subjects immunized with Tetravalent Dengue Live-Attenuated Vaccine (TV005). This broad reactivity reflects that the 21 HLA-DRB1 alleles analyzed in this and previous studies account for more than 80% of alleles present with a phenotypic frequency ≥5% worldwide, corresponding to 92% phenotypic coverage of the general population (i.e., 92% of individuals express at least one of these alleles). Conclusion: The DENV CD4 MP180 can be utilized to measure ex vivo responses to DENV irrespective of geographical location

    A CD8+ T cell transcription signature predicts prognosis in autoimmune disease.

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    Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of potentially toxic immunosuppressive therapy. Gene expression-based biomarkers facilitating such tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into clinical practice. We show that transcriptional profiling of purified CD8(+) T cells, which avoids the confounding influences of unseparated cells, identifies two distinct subject subgroups predicting long-term prognosis in two autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a chronic, severe disease characterized by inflammation of medium-sized and small blood vessels, and systemic lupus erythematosus (SLE), characterized by autoantibodies, immune complex deposition and diverse clinical manifestations ranging from glomerulonephritis to neurological dysfunction. We show that the subset of genes defining the poor prognostic group is enriched for genes involved in the interleukin-7 receptor (IL-7R) pathway and T cell receptor (TCR) signaling and those expressed by memory T cells. Furthermore, the poor prognostic group is associated with an expanded CD8(+) T cell memory population. These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest new potential therapeutic targets in autoimmunity

    La qualité des eaux de surface sur le bassin versant d’Auradé. Évaluation des risques agroenvironnementaux et mesures analytiques

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    National audienceLe Bassin versant expérimental d'Auradé (320 ha), à quelques kms de la station de pompage et de traitement des eaux de la ville de L'Isle Jourdain est situé dans une zone de production agricole dont les pratiques intensives impactent fortement la qualité des eaux de surface (fertilisants, phytosanitaires, rotations très simplifiées). Ce BVE fait l'objet d'un suivi analytique de la qualité des eaux de surface du ruisseau Le Montoussé depuis le début des années 1980 (Sté Grande Paroisse, ex AZF pour le suivi des NO3), puis par EcoLab depuis 2006 qui contrôle également la concentration en produits phytosanitaires. Des bonnes pratiques environnementales (BPEs) ont été mises en ½uvre le long du cours d'eau depuis la création de l'Association des Agriculteurs d'Auradé (AAA) en 1992. Une méthode d'évaluation des risques de contamination des eaux du Montoussé a été développée par Irstea (Bordeaux) en tenant compte des BPEs, avec comparaison par rapport aux résultats analytiques

    Fcγ receptor biology and systemic lupus erythematosus

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    10.1111/j.1756-185X.2009.01426.xInternational Journal of Rheumatic Diseases124293-29
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