HLA-DR Alpha 2 Mediates Negative Signalling via Binding to Tirc7 Leading to Anti-Inflammatory and Apoptotic Effects in Lymphocytes In Vitro and In Vivo

Classically, HLA-DR expressed on antigen presenting cells (APC) initiates lymphocyte activation via presentation of peptides to TCR bearing CD4+ T-Cells. Here we demonstrate that HLA-DR alpha 2 domain (sHLA-DRα2) also induces negative signals by engaging TIRC7 on lymphocytes. This interaction inhibits proliferation and induces apoptosis in CD4+ and CD8+ T-cells via activation of the intrinsic pathway. Proliferation inhibition is associated with SHP-1 recruitment by TIRC7, decreased phosphorylation of STAT4, TCR-ζ chain & ZAP70, and inhibition of IFN-γ and FasL expression. HLA-DRα2 and TIRC7 co-localize at the APC-T cell interaction site. Triggering HLA-DR - TIRC7 pathway demonstrates that sHLA-DRα2 treatment inhibits proinflammatory-inflammatory cytokine expression in APC & T cells after lipopolysaccaride (LPS) stimulation in vitro and induces apoptosis in vivo. These results suggest a novel antiproliferative role for HLA-DR mediated via TIRC7, revise the notion of an exclusive stimulatory interaction of HLA-DR with CD4+ T cells and highlights a novel physiologically relevant regulatory pathway

Les Houches 2015: Physics at TeV Colliders Standard Model Working Group Report

This Report summarizes the proceedings of the 2015 Les Houches workshop on Physics at TeV Colliders. Session 1 dealt with (I) new developments relevant for high precision Standard Model calculations, (II) the new PDF4LHC parton distributions, (III) issues in the theoretical description of the production of Standard Model Higgs bosons and how to relate experimental measurements, (IV) a host of phenomenological studies essential for comparing LHC data from Run I with theoretical predictions and projections for future measurements in Run II, and (V) new developments in Monte Carlo event generators.Comment: Proceedings of the Standard Model Working Group of the 2015 Les Houches Workshop, Physics at TeV Colliders, Les Houches 1-19 June 2015. 227 page

Indirect study of 19Ne states near the 18F+p threshold

The early E < 511 keV gamma-ray emission from novae depends critically on the 18F(p,a)15O reaction. Unfortunately the reaction rate of the 18F(p,a)15O reaction is still largely uncertain due to the unknown strengths of low-lying proton resonances near the 18F+p threshold which play an important role in the nova temperature regime. We report here our last results concerning the study of the d(18F,p)19F(alpha)15N transfer reaction. We show in particular that these two low-lying resonances cannot be neglected. These results are then used to perform a careful study of the remaining uncertainties associated to the 18F(p,a)15O and 18F(p,g)19Ne reaction rates.Comment: 18 pages, 8 figures. Accepted in Nuclear Physics

Encephalopathy associated with autoimmune thyroid disease in patients with Graves' disease: clinical manifestations, follow-up, and outcomes

<p>Abstract</p> <p>Background</p> <p>The encephalopathy associated with autoimmune thyroid disease (EAATD) is characterized by neurological/psychiatric symptoms, high levels of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in patients with an autoimmune thyroid disease. Almost all EAATD patients are affected by Hashimoto's thyroiditis (HT), although fourteen EAATD patients with Graves' disease (GD) have been also reported.</p> <p>Methods</p> <p>We have recorded and analyzed the clinical, biological, radiological, and electrophysiological findings and the data on the therapeutic management of all GD patients with EAATD reported so far as well as the clinical outcomes in those followed-up in the long term.</p> <p>Results</p> <p>Twelve of the fourteen patients with EAATD and GD were women. The majority of GD patients with EAATD presented with mild hyperthyroidism at EAATD onset or shortly before it. Active anti-thyroid autoimmunity was detected in all cases. Most of the patients dramatically responded to corticosteroids. The long term clinical outcome was benign but EAATD can relapse, especially at the time of corticosteroid dose tapering or withdrawal. GD and HT patients with EAATD present with a similar clinical, biological, radiological, and electrophysiological picture and require an unaffected EAATD management.</p> <p>Conclusions</p> <p>GD and HT equally represent the possible background condition for the development of EAATD, which should be considered in the differential diagnosis of all patients with encephalopathy of unknown origin and an autoimmune thyroid disease, regardless of the nature of the underlying autoimmune thyroid disease.</p

Explaining the decline in coronary heart disease mortality in Turkey between 1995 and 2008.

BACKGROUND: Coronary heart disease (CHD) mortality rates have been decreasing in Turkey since the early 1990s. Our study aimed to determine how much of the CHD mortality decrease in Turkey between 1995 and 2008 could be attributed to temporal trends in major risk factors and how much to advances in medical and surgical treatments. METHODS: The validated IMPACT CHD mortality model was used to combine and analyse data on uptake and effectiveness of CHD treatments and risk factor trends in Turkey in adults aged 35-84 years between 1995 and 2008.Data sources were identified, searched and appraised on population, mortality and major CHD risk factors for adults those aged 35-84 years. Official statistics, electronic databases, national registers, surveys and published trials were screened from 1995 onwards. RESULTS: Between 1995 and 2008, coronary heart disease mortality rates in Turkey decreased by 34% in men and 28% in women 35 years and over. This resulted in 35,720 fewer deaths in 2008.Approximately 47% of this mortality decrease was attributed to treatments in individuals (including approximately 16% to secondary prevention, 3% angina treatments, 9% to heart failure treatments, 5% to initial treatments of acute myocardial infarction, and 5% to hypertension treatments) and approximately 42% was attributable to population risk factor reductions (notably blood pressure 29%; smoking 27%; and cholesterol 1%). Adverse trends were seen for obesity and diabetes (potentially increasing mortality by approximately 11% and 14% respectively). The model explained almost 90% of the mortality fall. CONCLUSION: Reduction in major cardiovascular risk factors explained approximately 42% and improvements in medical and surgical treatments explained some 47% of the CHD mortality fall. These findings emphasize the complimentary value of primary prevention and evidence-based medical treatments in controlling coronary heart disease

A Nonsimultaneous, Extended, Altruistic-Donor Chain

We report a chain of 10 kidney transplantations, initiated in July 2007 by a single altruistic donor (i.e., a donor without a designated recipient) and coordinated over a period of 8 months by two large paired-donation registries. These transplantations involved six transplantation centers in five states. In the case of five of the transplantations, the donors and their coregistered recipients underwent surgery simultaneously. In the other five cases, “bridge donors” continued the chain as many as 5 months after the coregistered recipients in their own pairs had received transplants. This report of a chain of paired kidney donations, in which the transplantations were not necessarily performed simultaneously, illustrates the potential of this strategy.Economic