24 research outputs found

    Transition radiation of fast electrons as a broadband vacuum-ultraviolet radiation source

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    The characteristics of a possible radiation source in the vacuum ultraviolet and soft X ray range based on the transition radiation of electrons with an energy of about 100 keV are calculated. The possibilities of enhancing the radiation yield in the geometry of the glancing interaction of electrons with a target are ana lyzed. The possibility of creating a source with a yield on the order of 10–5 photon/(eV sr) per electron is dem onstratedyesBelgorod State National Research Universit

    Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

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    Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis

    ANCA-associated vasculitis.

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    The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA+ or ANCA-, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients

    Immunity of human epithelial ovarian carcinoma: the paradigm of immune suppression in cancer

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    Transition radiation of fast electrons as a broadband vacuum-ultraviolet radiation source

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    yesThe characteristics of a possible radiation source in the vacuum ultraviolet and soft X ray range based on the transition radiation of electrons with an energy of about 100 keV are calculated. The possibilities of enhancing the radiation yield in the geometry of the glancing interaction of electrons with a target are ana lyzed. The possibility of creating a source with a yield on the order of 10–5 photon/(eV sr) per electron is dem onstratedBelgorod State National Research Universit

    Analysis of FoxP3+ T-regulatory cells and CD8+ T-cells in ovarian carcinoma: location and tumor infiltration patterns are key prognostic markers.

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    Tumor infiltrating CD4+CD25+FoxP3+ regulatory immune cells (Treg) have been associated with impaired anti-tumor immune response and unfavorable prognosis for patients affected by ovarian carcinoma, whereas CD8+ T-cells have been found to positively influence survival rates in a large panel of solid tumors. Recently, density, location and tumor infiltration patterns of the respective immune cell subtypes have been identified as key prognostic factors for different types of tumors.We stained 210 human ovarian carcinoma samples immunhistochemically for FoxP3 and CD8 to identify the impact different immune cell patterns have on generally accepted prognostic variables as well as on overall survival.We found that FoxP3+ cells located within lymphoid aggregates surrounding the tumor were strongly associated with reduced survival time (P = 0.007). Central accumulation of CD8+ effector cells within the tumor bed shows a positive effect on survival (P = 0,001).The distribution pattern of immune cells within the tumor environment strongly influences prognosis and overall survival time of patients with ovarian carcinoma
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