110 research outputs found

    Influence of melt feeding scheme and casting parameters during direct-chill casting on microstructure of an AA7050 billet

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    © The Minerals, Metals & Materials Society and ASM International 2012Direct-chill (DC) casting billets of an AA7050 alloy produced with different melt feeding schemes and casting speeds were examined in order to reveal the effect of these factors on the evolution of microstructure. Experimental results show that grain size is strongly influenced by the casting speed. In addition, the distribution of grain sizes across the billet diameter is mostly determined by melt feeding scheme. Grains tend to coarsen towards the center of a billet cast with the semi-horizontal melt feeding, while upon vertical melt feeding the minimum grain size was observed in the center of the billet. Computer simulations were preformed to reveal sump profiles and flow patterns during casting under different melt feeding schemes and casting speeds. The results show that solidification front and velocity distribution of the melt in the liquid and slurry zones are very different under different melt feeding scheme. The final grain structure and the grain size distribution in a DC casting billet is a result of a combination of fragmentation effects in the slurry zone and the cooling rate in the solidification range

    Muon Spin Rotation study of the (TMTSF)2ClO4(TMTSF)_2ClO_4 system

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    We report a study of the organic compound (TMTSF)2ClO4(TMTSF)_2 ClO_4 in both a sample cooled very slowly through the anion ordering temperature (relaxed state) and a sample cooled more rapidly (intermediate state). For the relaxed state the entire sample is observed to be superconducting below about T_c ~ 1.2 K. The second moment of the internal field distribution was measured for the relaxed state yielding an in-plane penetration depth of ~ 12000 Angstroms. The intermediate state sample entered a mixed phase state, characterized by coexisting macroscopic sized regions of superconducting and spin density wave (SDW) regions, below T_c ~ 0.87 K. These data were analyzed using a back-to-back cutoff exponential function, allowing the extraction of the first three moments of the magnetic field distribution. Formation of a vortex lattice is observed below 0.87 K as evidenced by the diamagnetic shift for the two fields in which we took intermediate state data.Comment: 6 pages, 3 figures, to be submitted to Physica

    Immunology of multiple sclerosis

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    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) leading to demyelination, axonal damage, and progressive neurologic disability. The development of MS is influenced by environmental factors, particularly the Epstein-Barr virus (EBV), and genetic factors, which include specific HLA types, particularly DRB1*1501-DQA1*0102-DQB1*0602, and a predisposition to autoimmunity in general. MS patients have increased circulating T-cell and antibody reactivity to myelin proteins and gangliosides. It is proposed that the role of EBV is to infect autoreactive B cells that then seed the CNS and promote the survival of autoreactive T cells there. It is also proposed that the clinical attacks of relapsing-remitting MS are orchestrated by myelin-reactive T cells entering the white matter of the CNS from the blood, and that the progressive disability in primary and secondary progressive MS is caused by the action of autoantibodies produced in the CNS by ­meningeal lymphoid follicles with germinal centers

    Cyber risk assessment in cloud provider environments: Current models and future needs

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    Traditional frameworks for risk assessment do not work well for cloud computing. While recent work has often focussed on the risks faced by firms adopting or selecting cloud services, there has been little research on how cloud providers might assess their own services. In this paper, we use an in-depth review of the extant literature to highlight the weaknesses of traditional risk assessment frameworks for this task. Using examples, we then describe a new risk assessment model (CSCCRA) and compare this against three established approaches. For each approach, we consider its goals, the risk assessment process, decisions, the scope of the assessment and the way in which risk is conceptualised. This evaluation points to the need for dynamic models specifically designed to evaluate cloud risk. Our suggestions for future research are aimed at improving the identification, assessment, and mitigation of inter-dependent cloud risks inherent in a defined supply chain

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Highly-parallelized simulation of a pixelated LArTPC on a GPU

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    The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype

    Prevalence of the post-thrombotic syndrome in young women with previous venous thromboembolism

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    The prevalence of mild, moderate and severe post‐thrombotic syndrome (PTS) among 43 young women with a previous single episode of deep vein thrombosis (DVT) was 67%, 7% and 0% respectively. Subjects were assessed at a mean 51 months after the event. Moderate PTS was more common in women with recurrent (n = 9) DVT (44%, P < 0.001). Chronic venous insufficiency, assessed by light reflection rheography (LRR), was significantly (P < 0.05) more prevalent in women with single previous DVT (n = 40), recurrent DVT (n = 9) and isolated pulmonary embolism (PE) (n = 19) compared with healthy age‐matched controls (odds ratios 10.9, 52.4 and 3.8 respectively). LRR findings correlated with moderate, but not mild, PTS. There was no correlation between development of PTS and body mass index

    Hyperpolarization-activated cyclic nucleotide-gated channels in olfactory sensory neurons regulate axon extension and glomerular formation

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    Mechanisms influencing the development of olfactory bulb glomeruli are poorly understood. While odor receptors (ORs) play an important role in olfactory sensory neuron (OSN) axon targeting/coalescence (Mombaerts et al., 1996; Wang et al., 1998; Feinstein and Mombaerts, 2004), recent work showed that G protein activation alone is sufficient to induce OSN axon coalescence (Imai et al., 2006; Chesler et al., 2007), suggesting an activity-dependent mechanism in glomerular development. Consistent with these data, OSN axon projections and convergence are perturbed in mice deficient for adenylyl cyclase III, which is downstream from the OR and catalyzes the conversion of ATP to cAMP. However, in cyclic nucleotide-gated (CNG) channel knock-out mice OSN axons are only transiently perturbed (Lin et al., 2000), suggesting that the CNG channel may not be the sole target of cAMP. This prompted us to investigate an alternative channel, the hyperpolarization-activated, cyclic nucleotide-gated cation channel (HCN), as a potential developmental target of cAMP in OSNs. Here, we demonstrate that HCN channels are developmentally precocious in OSNs and therefore are plausible candidates for affecting OSN axon development. Inhibition of HCN channels in dissociated OSNs significantly reduced neurite outgrowth. Moreover, in HCN1 knock-out mice the formation of glomeruli was delayed in parallel with perturbations of axon organization in the olfactory nerve. These data support the hypothesis that the outgrowth and coalescence of OSN axons is, at least in part, subject to activity-dependent mechanisms mediated via HCN channels
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