26 research outputs found

    Microfield Fluctuations and Spectral Line Shapes in Strongly Coupled Two-Component Plasmas

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    The spectral line shapes for hydrogen-like heavy ion emitters embedded in strongly correlated two-component electron-ion plasmas are investigated with numerical simulations. For that purpose the microfield fluctuations are calculated by molecular dynamics simulations where short range quantum effects are taken into account by using a regularized Coulomb potential for the electron-ion interaction. The microfield fluctuations are used as input in a numerical solution of the time-dependent Schroedinger equation for the radiating electron. In distinction to the standard impact and quasistatic approximations the method presented here allows to account for the correlations between plasma ions and electrons. The shapes of the Ly-alpha line in Al are investigated in the intermediate regime. The calculations are in good agreement with experiments on the Ly-alpha line in laser generated plasmas.Comment: 5 figure

    Somatic mTOR mutation in clonally expanded T lymphocytes associated with chronic graft versus host disease

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    Graft versus host disease (GvHD) is the main complication of allogeneic hematopoietic stem cell transplantation (HSCT). Here we report studies of a patient with chronic GvHD (cGvHD) carrying persistent CD4(+) T cell clonal expansion harboring somatic mTOR, NFKB2, and TLR2 mutations. In the screening cohort (n=134), we detect the mTOR P2229R kinase domain mutation in two additional cGvHD patients, but not in healthy or HSCT patients without cGvHD. Functional analyses of the mTOR mutation indicate a gain-of-function alteration and activation of both mTORC1 and mTORC2 signaling pathways, leading to increased cell proliferation and decreased apoptosis. Single-cell RNA sequencing and real-time impedance measurements support increased cytotoxicity of mutated CD4(+) T cells. High throughput drug-sensitivity testing suggests that mutations induce resistance to mTOR inhibitors, but increase sensitivity for HSP90 inhibitors. Our findings imply that somatic mutations may contribute to aberrant T cell proliferations and persistent immune activation in cGvHD, thereby paving the way for targeted therapies. Chronic graft versus host disease (cGvHD) is a major cause of morbidity and mortality in allogeneic bone marrow transplantation. Here the authors identify a recurrent activating mTOR mutation in expanded donor T-cell clones of 3 cGvHD patients, which suggests somatic mutations may contribute to GvHD pathogenesis and opens avenues to targeted therapies.Peer reviewe

    CMV antigenemia and quantitative viral load assessments in hematopoietic stem cell transplant recipients

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    BACKGROUND: Sensitive and reliable diagnostic tests are essential for the prevention of cytomegalovirus (CMV) disease after hematopoietic stem cell transplantation (HSCT). pp65 antigenemia and polymerase chain reaction (PCR) assays are commonly used to monitor CMV in HSCT recipients. However, there is considerable intra- and inter-laboratory variability in the results, which impact comparability and clinical practice. OBJECTIVES/STUDY DESIGN: Using 380 samples from 135 HSCT recipients, we compared the new FDA approved quantitative PCR assay, COBAS((R)) AmpliPrep/COBAS((R)) TaqMan((R)) CMV test (CAP/CTM CMV test) developed and standardized using the 1st WHO International Standard for CMV with pp65 antigenemia and COBAS((R)) AMPLICOR MONITOR CMV tests. RESULTS: The median time between transplantation and testing samples was 57 days (range, 0-207 days). The median CMV load (log(10)) was 3.17 IU/mL (3.21 copies/mL). Among samples with detectable CMV load, 52% were negative by pp65 antigenemia. CMV loads were higher in pp65 antigenemia-positive than in negative samples. One pp65-antigenemia-positive cell per 100,000 leukocytes corresponded to a median CMV load of 1200 IU/mL. CMV loads determined by the CAP/CTM CMV test were slightly lower than the ones by the AMPLICOR MONITOR CMV test (-0.15 [95% CI, -0.18 to -0.13] copies/mL), but slope differences indicated only limited co-linearity. CONCLUSIONS: The CAP/CTM CMV test is more sensitive than pp65 antigenemia and the AMPLICOR MONITOR CMV test in HSCT recipients. The lower limit of quantification and co-linearity with the international WHO standard renders the CAP/CTM CMV test suitable for future clinical trials defining viral load thresholds of CMV therapy
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