861 research outputs found

    Simulation System for the Wendelstein 7-X Safety Control System

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    The Wendelstein 7-X (W7-X) Safety Instrumented System (SIS) ensures personal safety and investment protection. The development and implementation of the SIS are based on the international safety standard for the process industry sector, IEC 61511. The SIS exhibits a distributed and hierarchical organized architecture consisting of a central Safety System (cSS) on the top and many local Safety Systems (lSS) at the bottom. Each technical component or diagnostic system potentially hazardous for the staff or for the device is equipped with an lSS. The cSS is part of the central control system of W7-X. Whereas the lSSs are responsible for the safety of each individual component, the cSS ensures safety of the whole W7-X device. For every operation phase of the W7-X experiment hard- and software updates for the SIS are mandatory. New components with additional lSS functionality and additional safety signals have to be integrated. Already established safety functions must be adapted and new safety functions have to be integrated into the cSS. Finally, the safety programs of the central and local safety systems have to be verified for every development stage and validated against the safety requirement specification. This contribution focuses on the application of a model based simulation system for the whole SIS of W7-X. A brief introduction into the development process of the SIS and its technical realization will be give followed by a description of the design and implementation of the SIS simulation system using the framework SIMIT (Siemens). Finally, first application experiences of this simulation system for the preparation of the SIS for the upcoming operation phase OP 1.2b of W7-X will be discussed

    Dysregulated NK cell PLCγ2 signaling and activity in juvenile dermatomyositis

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    Juvenile dermatomyositis (JDM) is a debilitating pediatric autoimmune disease manifesting with characteristic rash and muscle weakness. To delineate signaling abnormalities in JDM, mass cytometry was performed with PBMCs from treatment-naive JDM patients and controls. NK cell percentages were lower while frequencies of naive B cells and naive CD4+ T cells were higher in JDM patients than in controls. These cell frequency differences were attenuated with cessation of active disease. A large number of signaling differences were identified in treatment-naive JDM patients compared with controls. Classification models incorporating feature selection demonstrated that differences in phospholipase Cγ2 (PLCγ2) phosphorylation comprised 10 of 12 features (i.e., phosphoprotein in a specific immune cell subset) distinguishing the 2 groups. Because NK cells represented 5 of these 12 features, further studies focused on the PLCγ2 pathway in NK cells, which is responsible for stimulating calcium flux and cytotoxic granule movement. No differences were detected in upstream signaling or total PLCγ2 protein levels. Hypophosphorylation of PLCγ2 and downstream mitogen-activated protein kinase-activated protein kinase 2 were partially attenuated with cessation of active disease. PLCγ2 hypophosphorylation in treatment-naive JDM patients resulted in decreased calcium flux. The identification of dysregulation of PLCγ2 phosphorylation and decreased calcium flux in NK cells provides potential mechanistic insight into JDM pathogenesis

    Continuous engagement of a self-specific activation receptor induces NK cell tolerance

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    Natural killer (NK) cell tolerance mechanisms are incompletely understood. One possibility is that they possess self-specific activation receptors that result in hyporesponsiveness unless modulated by self–major histocompatability complex (MHC)–specific inhibitory receptors. As putative self-specific activation receptors have not been well characterized, we studied a transgenic C57BL/6 mouse that ubiquitously expresses m157 (m157-Tg), which is the murine cytomegalovirus (MCMV)–encoded ligand for the Ly49H NK cell activation receptor. The transgenic mice were more susceptible to MCMV infection and were unable to reject m157-Tg bone marrow, suggesting defects in Ly49H+ NK cells. There was a reversible hyporesponsiveness of Ly49H+ NK cells that extended to Ly49H-independent stimuli. Continuous Ly49H–m157 interaction was necessary for the functional defects. Interestingly, functional defects occurred when mature wild-type NK cells were adoptively transferred to m157-Tg mice, suggesting that mature NK cells may acquire hyporesponsiveness. Importantly, NK cell tolerance caused by Ly49H–m157 interaction was similar in NK cells regardless of expression of Ly49C, an inhibitory receptor specific for a self-MHC allele in C57BL/6 mice. Thus, engagement of self-specific activation receptors in vivo induces an NK cell tolerance effect that is not affected by self-MHC–specific inhibitory receptors

    Physico-chemical foundations underpinning microarray and next-generation sequencing experiments

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    Hybridization of nucleic acids on solid surfaces is a key process involved in high-throughput technologies such as microarrays and, in some cases, next-generation sequencing (NGS). A physical understanding of the hybridization process helps to determine the accuracy of these technologies. The goal of a widespread research program is to develop reliable transformations between the raw signals reported by the technologies and individual molecular concentrations from an ensemble of nucleic acids. This research has inputs from many areas, from bioinformatics and biostatistics, to theoretical and experimental biochemistry and biophysics, to computer simulations. A group of leading researchers met in Ploen Germany in 2011 to discuss present knowledge and limitations of our physico-chemical understanding of high-throughput nucleic acid technologies. This meeting inspired us to write this summary, which provides an overview of the state-of-the-art approaches based on physico-chemical foundation to modeling of the nucleic acids hybridization process on solid surfaces. In addition, practical application of current knowledge is emphasized

    The GALFA-HI Compact Cloud Catalog

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    We present a catalog of 1964 isolated, compact neutral hydrogen clouds from the Galactic Arecibo L-Band Feed Array Survey Data Release One (GALFA-HI DR1). The clouds were identified by a custom machine-vision algorithm utilizing Difference of Gaussian kernels to search for clouds smaller than 20'. The clouds have velocities typically between |VLSR| = 20-400 km/s, linewidths of 2.5-35 km/s, and column densities ranging from 1 - 35 x 10^18 cm^-2. The distances to the clouds in this catalog may cover several orders of magnitude, so the masses may range from less than a Solar mass for clouds within the Galactic disc, to greater than 10^4 Solar Masses for HVCs at the tip of the Magellanic Stream. To search for trends, we separate the catalog into five populations based on position, velocity, and linewidth: high velocity clouds (HVCs); galaxy candidates; cold low velocity clouds (LVCs); warm, low positive-velocity clouds in the third Galactic Quadrant; and the remaining warm LVCs. The observed HVCs are found to be associated with previously-identified HVC complexes. We do not observe a large population of isolated clouds at high velocities as some models predict. We see evidence for distinct histories at low velocities in detecting populations of clouds corotating with the Galactic disc and a set of clouds that is not corotating.Comment: 34 Pages, 9 Figures, published in ApJ (2012, ApJ, 758, 44), this version has the corrected fluxes and corresponding flux histogram and masse

    Circumgalactic Gas at Its Extreme : Tidal Gas Streams around the Whale Galaxy NGC 4631 Explored with HST/COS

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    We present a detailed analysis of the absorption properties of one of the tidal gas streams around the "Whale" galaxy NGC 4631 in the direction of the quasar 2MASS J12421031+3214268. Our study is based on ultraviolet spectral data obtained with the Cosmic Origins Spectrograph (COS) on board the Hubble Space Telescope (HST) and 21cm-data from the HALOGAS project and the Green Bank Telescope (GBT). We detect strong H I Ly alpha absorption in the velocity range +550 to +800 km s(-1) related to gas from a NGC 4631 tidal stream known as Spur 2. We measure a column density of log (N(H I/cm(-2))) = 18.68 +/- 0.15, indicating that the quasar sightline traces the outer boundary of Spur 2 as seen in the 21 cm data. Metal absorption in Spur 2 is detected in the lines of O I, C II, Si II, and Si III in a complex absorption pattern that reflects the multiphase nature of the gas. We find that the average neutral gas fraction in Spur 2 toward 2MASS J12421031+3214268 is only 14%. This implies that ionized gas dominates the total mass of Spur 2, which then may comprise more than 10(9)M(circle dot). No significant depletion of Si is observed, showing that Spur 2 does not contain significant amounts of dust. From the measured O I/H I column density ratio, we determine an alpha abundance in Spur 2 of 0.131(-0.05)(+0.07) solar ([alpha/H] = -0.90 +/- 0.16), which is substantially lower than what is observed in the NGC 4631 disk. The low metallicity and low dust content suggest that Spur 2 represents metal-deficient gas stripped off a gas-rich satellite galaxy during a recent encounter with NGC 4631.Peer reviewe
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