79 research outputs found

    Autoantibodies against type I IFNs in patients with life-threatening COVID-19

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    Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

    On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

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    A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

    New insights into the genetic etiology of Alzheimer's disease and related dementias

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    Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE Δ4 allele

    Regulation of intracellular free arachidonic acid in Aplysia nervous system

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    We have studied the regulation of arachidonic acid (AA) uptake, metabolism, and release in Aplysia nervous system. Following uptake of [ 3 H]AA, the distribution of radioactivity in intracellular and extracellular lipid pools was measured as a function of time in the presence or absence of exogenous AA. The greatest amount of AA was esterified into phosphatidylinositol (relative to pool size). We found that the intracellular free AA pool underwent rapid turnover, and that radioactive free AA and eicosanoids were released at a rapid rate into the extracellular medium, both in the presence and absence of exogenous AA. Most of the released radioactivity originated from phosphatidylinositol.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48020/1/232_2005_Article_BF01868464.pd

    Overview of the JET results in support to ITER

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    First end‐to‐end PQC protected DPU‐to‐DPU communications

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    Abstract The appearance of quantum computing in the short foreseeable future and its capability to break conventional cryptographic algorithms forces to change the paradigm of secure real‐time communications. Thus, government organizations, data centers, and enterprises among others are migrating their public key infrastructure towards using post‐quantum cryptography (PQC) algorithms in order to mitigate the security threats posed by quantum computers. This letter presents the first quantum resilient secure end‐to‐end communication link based on PQC algorithms operating between two data‐processing units DPU. Both data‐processing units employ on‐board ARM processors to perform the computationally expensive cryptographic building blocks—in that case CRYSTALS‐Kyber as a key encapsulation mechanism and CRYSTALS‐Dilithium for digital signature scheme in combination with advanced encryption standard with 256‐bit key

    A review of the impact of climate change on future nitrate concentrations in groundwater of the UK

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    This paper reviews the potential impacts of climate change on nitrate concentrations in groundwater of the UK using a Source–Pathway–Receptor framework. Changes in temperature, precipitation quantity and distribution, and atmospheric carbon dioxide concentrations will affect the agricultural nitrate source term through changes in both soil processes and agricultural productivity. Non-agricultural source terms, such as urban areas and atmospheric deposition, are also expected to be affected. The implications for the rate of nitrate leaching to groundwater as a result of these changes are not yet fully understood but predictions suggest that leaching rate may increase under future climate scenarios. Climate change will affect the hydrological cycle with changes to recharge, groundwater levels and resources and flow processes. These changes will impact on concentrations of nitrate in abstracted water and other receptors, such as surface water and groundwater-fed wetlands. The implications for nitrate leaching to groundwater as a result of climate changes are not yet well enough understood to be able to make useful predictions without more site-specific data. The few studies which address the whole cycle show likely changes in nitrate leaching ranging from limited increases to a possible doubling of aquifer concentrations by 2100. These changes may be masked by nitrate reductions from improved agricultural practices, but a range of adaption measures need to be identified. Future impact may also be driven by economic responses to climate change
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