36 research outputs found

    StreamFlow: cross-breeding cloud with HPC

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    Workflows are among the most commonly used tools in a variety of execution environments. Many of them target a specific environment; few of them make it possible to execute an entire workflow in different environments, e.g. Kubernetes and batch clusters. We present a novel approach to workflow execution, called StreamFlow, that complements the workflow graph with the declarative description of potentially complex execution environments, and that makes it possible the execution onto multiple sites not sharing a common data space. StreamFlow is then exemplified on a novel bioinformatics pipeline for single-cell transcriptomic data analysis workflow.Comment: 30 pages - 2020 IEEE Transactions on Emerging Topics in Computin

    Bringing AI pipelines onto cloud-HPC: setting a baseline for accuracy of COVID-19 diagnosis

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    HPC is an enabling platform for AI. The introduction of AI workloads in the HPC applications basket has non-trivial consequences both on the way of designing AI applications and on the way of providing HPC computing. This is the leitmotif of the convergence between HPC and AI. The formalized definition of AI pipelines is one of the milestones of HPC-AI convergence. If well conducted, it allows, on the one hand, to obtain portable and scalable applications. On the other hand, it is crucial for the reproducibility of scientific pipelines. In this work, we advocate the StreamFlow Workflow Management System as a crucial ingredient to define a parametric pipeline, called ‚ÄúCLAIRE COVID-19 Universal Pipeline‚ÄĚ, which is able to explore the optimization space of methods to classify COVID-19 lung lesions from CT scans, compare them for accuracy, and therefore set a performance baseline. The universal pipeline automatizes the training of many different Deep Neural Networks (DNNs) and many different hyperparameters. It, therefore, requires a massive computing power, which is found in traditional HPC infrastructure thanks to the portability-by-design of pipelines designed with StreamFlow. Using the universal pipeline, we identified a DNN reaching over 90% accuracy in detecting COVID-19 lesions in CT scans

    HYPOXIC STRESS, HEPATOCYTES AND CACO-2 VIABILITY AND SUSCEPTIBILITY TO Shigella flexneri INVASION

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    SUMMARY Inflammation due to Shigella flexneri can cause damage to the colonic mucosa and cell death by necrosis and apoptosis. This bacteria can reach the bloodstream in this way, and the liver through portal veins. Hypoxia is a condition present in many human diseases, and it may induce bacterial translocation from intestinal lumen. We studied the ability of S. flexneri to invade rat hepatocytes and Caco-2 cells both in normoxic and hypoxic microenvironments, as well as morphological and physiological alterations in these cells after infection under hypoxia. We used the primary culture of rat hepatocytes as a model of study. We analyzed the following parameters in normoxic and hypoxic conditions: morphology, cell viability, bacterial recovery and lactate dehydrogenase (LDH) released. The results showed that there were fewer bacteria within the Caco-2 cells than in hepatocytes in normoxic and hypoxic conditions. We observed that the higher the multiplicity of infection (MOI) the greater the bacterial recovery in hepatocytes. The hypoxic condition decreased the bacterial recovery in hepatocytes. The cytotoxicity evaluated by LDH released by cells was significantly higher in cells submitted to hypoxia than normoxia. Caco-2 cells in normoxia released 63% more LDH than hepatocytes. LDH increased 164% when hepatocytes were submitted to hypoxia and just 21% when Caco-2 cells were in the same condition. The apoptosis evaluated by Tunel was significantly higher in cells submitted to hypoxia than normoxia. When comparing hypoxic cells, we obtained more apoptotic hepatocytes than apoptotic Caco-2 cells. Concluding our results contribute to a better knowledge of interactions between studied cells and Shigella flexneri. These data may be useful in the future to define strategies to combat this virulent pathogen.RESUMO A inflama√ß√£o causada por Shigella flexneri pode causar danos √† mucosa do c√≥lon e morte celular por necrose e apoptose. Esta bact√©ria pode atingir a corrente sangu√≠nea por esta via e o f√≠gado atrav√©s da veia porta. A hip√≥xia √© uma condi√ß√£o presente em muitas doen√ßas humanas, podendo induzir a transloca√ß√£o bacteriana a partir do l√ļmen intestinal. N√≥s estudamos a capacidade de S. flexneri invadir hepat√≥citos de rato e c√©lulas Caco-2 nos microambientes de norm√≥xia e hip√≥xia, bem como as altera√ß√Ķes morfol√≥gicas e fisiol√≥gicas dessas c√©lulas ap√≥s a infec√ß√£o sob hip√≥xia. Utilizamos a cultura prim√°ria de hepat√≥citos de ratos como modelo de estudo. N√≥s analisamos os seguintes par√Ęmetros em condi√ß√Ķes de norm√≥xia e hip√≥xia: morfologia, viabilidade celular, recupera√ß√£o bacteriana e libera√ß√£o de lactato desidrogenase (LDH). Os resultados mostraram menor quantidade de bact√©rias dentro das c√©lulas Caco-2 do que em hepat√≥citos em condi√ß√Ķes de norm√≥xia e hip√≥xia. N√≥s observamos que quanto maior foi a multiplicidade de infec√ß√£o (MOI), maior tamb√©m foi a recupera√ß√£o bacteriana em hepat√≥citos. A condi√ß√£o hip√≥xica foi capaz de diminuir a recupera√ß√£o de bact√©rias dos hepat√≥citos. A citotoxicidade avaliada pela libera√ß√£o de LDH foi significativamente maior em c√©lulas submetidas √† hip√≥xia do que norm√≥xia. As c√©lulas Caco-2 em norm√≥xia produziram 63% mais LDH do que os hepat√≥citos. O LDH aumentou 164% quando os hepat√≥citos foram submetidos √† hipoxia e apenas 21% quando as c√©lulas Caco-2 estavam na mesma condi√ß√£o. A apoptose avaliada por TUNEL foi significativamente maior em c√©lulas submetidas √† hip√≥xia que norm√≥xia. Quando comparamos c√©lulas hip√≥xicas houve mais apoptose entre hepat√≥citos do que nas c√©lulas Caco-2. Concluindo, nossos resultados contribuem para um melhor conhecimento das intera√ß√Ķes entre as c√©lulas estudadas e S. flexneri. Estes dados podem ser √ļteis no futuro, para definir estrat√©gias de combate a este pat√≥geno virulento

    Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19

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    The established risk factors of coronavirus disease 2019 (COVID-19) are advanced age, male sex and comorbidities, but they do not fully explain the wide spectrum of disease manifestations. Genetic factors implicated in the host antiviral response provide for novel insights into its pathogenesis. We performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data, including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from the COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms within TMPRSS2 and near MX1 gene show associations with severe COVID-19. The minor alleles of the five SNPs correlated with a reduced risk of developing severe COVID-19 and high level of MX1 expression in blood. Our findings demonstrate that host genetic factors can influence the different clinical presentations of COVID-19 and that MX1 could be a potential therapeutic target

    Cystathionine ő≤-synthase-derived hydrogen sulfide is involved in human malignant hyperthermia

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    Hydrogen sulfide is an endogenous gasotransmitter and its mechanism of action involves activation of ATP-sensitive K(+) channels and phosphodiesterase inhibition. As both mechanisms are potentially involved in malignant hyperthermia (MH), in the present study we addressed the involvement of the L-cysteine/hydrogen sulfide pathway in MH. Skeletal muscle biopsies obtained from 25 MH-susceptible (MHS) and 56 MH-negative (MHN) individuals have been used to perform the in¬†vitro contracture test (IVCT). Quantitative real-time PCR (qPCR) and Western blotting studies have also been performed. Hydrogen sulfide levels are measured in both tissue samples and plasma. In MHS biopsies an increase in cystathionine ő≤-synthase (CBS) occurs, as both mRNA and protein expression compared with MHN biopsies. Hydrogen sulfide biosynthesis is increased in MHS biopsies (0.128¬Ī0.12 compared with 0.943¬Ī0.13 nmol/mg of protein per min for MHN and MHS biopsies, respectively; P<0.01). Addition of sodium hydrosulfide (NaHS) to MHS samples evokes a response similar, in the IVCT, to that elicited by either caffeine or halothane. Incubation of MHN biopsies with NaHS, before caffeine or halothane challenge, switches an MHN to an MHS response. In conclusion we demonstrate the involvement of the L-cysteine/hydrogen sulfide pathway in MH, giving new insight into MH molecular mechanisms. This finding has potential implications for clinical care and could help to define less invasive diagnostic procedures
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