Accelerating Network Communication and I/O in Scientific High Performance Computing Environments

High performance computing has become one of the major drivers behind technology inventions and science discoveries. Originally driven through the increase of operating frequencies and technology scaling, a recent slowdown in this evolution has led to the development of multi-core architectures, which are supported by accelerator devices such as graphics processing units (GPUs). With the upcoming exascale era, the overall power consumption and the gap between compute capabilities and I/O bandwidth have become major challenges. Nowadays, the system performance is dominated by the time spent in communication and I/O, which highly depends on the capabilities of the network interface. In order to cope with the extreme concurrency and heterogeneity of future systems, the software ecosystem of the interconnect needs to be carefully tuned to excel in reliability, programmability, and usability. This work identifies and addresses three major gaps in today's interconnect software systems. The I/O gap describes the disparity in operating speeds between the computing capabilities and second storage tiers. The communication gap is introduced through the communication overhead needed to synchronize distributed large-scale applications and the mixed workload. The last gap is the so called concurrency gap, which is introduced through the extreme concurrency and the inflicted learning curve posed to scientific application developers to exploit the hardware capabilities. The first contribution is the introduction of the network-attached accelerator approach, which moves accelerators into a "stand-alone" cluster connected through the Extoll interconnect. The novel communication architecture enables the direct accelerators communication without any host interactions and an optimal application-to-compute-resources mapping. The effectiveness of this approach is evaluated for two classes of accelerators: Intel Xeon Phi coprocessors and NVIDIA GPUs. The next contribution comprises the design, implementation, and evaluation of the support of legacy codes and protocols over the Extoll interconnect technology. By providing TCP/IP protocol support over Extoll, it is shown that the performance benefits of the interconnect can be fully leveraged by a broader range of applications, including the seamless support of legacy codes. The third contribution is twofold. First, a comprehensive analysis of the Lustre networking protocol semantics and interfaces is presented. Afterwards, these insights are utilized to map the LNET protocol semantics onto the Extoll networking technology. The result is a fully functional Lustre network driver for Extoll. An initial performance evaluation demonstrates promising bandwidth and message rate results. The last contribution comprises the design, implementation, and evaluation of two easy-to-use load balancing frameworks, which transparently distribute the I/O workload across all available storage system components. The solutions maximize the parallelization and throughput of file I/O. The frameworks are evaluated on the Titan supercomputing systems for three I/O interfaces. For example for large-scale application runs, POSIX I/O and MPI-IO can be improved by up to 50% on a per job basis, while HDF5 shows performance improvements of up to 32%

VEB-1 in Achromobacter xylosoxidans from Cystic Fibrosis Patient, France

Multidrug-resistant Achromobacter xylosoxidans was recovered from the sputum of a patient with cystic fibrosis. The VEB-1 extended-spectrum β-lactamase was detected on a class 1 integron. This first report of a VEB-1–producing isolate in this population requires further investigation to determine its distribution

Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting.

BACKGROUND: Asthma is the most prevalent chronic disease of childhood. Recently, we identified a critical window early in the life of both mice and Canadian infants during which gut microbial changes (dysbiosis) affect asthma development. Given geographic differences in human gut microbiota worldwide, we studied the effects of gut microbial dysbiosis on atopic wheeze in a population living in a distinct developing world environment. OBJECTIVE: We sought to determine whether microbial alterations in early infancy are associated with the development of atopic wheeze in a nonindustrialized setting. METHODS: We conducted a case-control study nested within a birth cohort from rural Ecuador in which we identified 27 children with atopic wheeze and 70 healthy control subjects at 5 years of age. We analyzed bacterial and eukaryotic gut microbiota in stool samples collected at 3 months of age using 16S and 18S sequencing. Bacterial metagenomes were predicted from 16S rRNA data by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and categorized by function with Kyoto Encyclopedia of Genes and Genomes ontology. Concentrations of fecal short-chain fatty acids were determined by using gas chromatography. RESULTS: As previously observed in Canadian infants, microbial dysbiosis at 3 months of age was associated with later development of atopic wheeze. However, the dysbiosis in Ecuadorian babies involved different bacterial taxa, was more pronounced, and also involved several fungal taxa. Predicted metagenomic analysis emphasized significant dysbiosis-associated differences in genes involved in carbohydrate and taurine metabolism. Levels of the fecal short-chain fatty acids acetate and caproate were reduced and increased, respectively, in the 3-month stool samples of children who went on to have atopic wheeze. CONCLUSIONS: Our findings support the importance of fungal and bacterial microbiota during the first 100 days of life on the development of atopic wheeze and provide additional support for considering modulation of the gut microbiome as a primary asthma prevention strategy

Staphylococcus aureus infective endocarditis versus bacteremia strains: Subtle genetic differences at stake

AbstractInfective endocarditis (IE)(1) is a severe condition complicating 10–25% of Staphylococcus aureus bacteremia. Although host-related IE risk factors have been identified, the involvement of bacterial features in IE complication is still unclear. We characterized strictly defined IE and bacteremia isolates and searched for discriminant features. S. aureus isolates causing community-acquired, definite native-valve IE (n=72) and bacteremia (n=54) were collected prospectively as part of a French multicenter cohort. Phenotypic traits previously reported or hypothesized to be involved in staphylococcal IE pathogenesis were tested. In parallel, the genotypic profiles of all isolates, obtained by microarray, were analyzed by discriminant analysis of principal components (DAPC)(2). No significant difference was observed between IE and bacteremia strains, regarding either phenotypic or genotypic univariate analyses. However, the multivariate statistical tool DAPC, applied on microarray data, segregated IE and bacteremia isolates: IE isolates were correctly reassigned as such in 80.6% of the cases (C-statistic 0.83, P<0.001). The performance of this model was confirmed with an independent French collection IE and bacteremia isolates (78.8% reassignment, C-statistic 0.65, P<0.01). Finally, a simple linear discriminant function based on a subset of 8 genetic markers retained valuable performance both in study collection (86.1%, P<0.001) and in the independent validation collection (81.8%, P<0.01). We here show that community-acquired IE and bacteremia S. aureus isolates are genetically distinct based on subtle combinations of genetic markers. This finding provides the proof of concept that bacterial characteristics may contribute to the occurrence of IE in patients with S. aureus bacteremia

ROCK-ALS: Protocol for a Randomized, Placebo-Controlled, Double-Blind Phase IIa Trial of Safety, Tolerability and Efficacy of the Rho Kinase (ROCK) Inhibitor Fasudil in Amyotrophic Lateral Sclerosis

Objectives: Disease-modifying therapies for amyotrophic lateral sclerosis (ALS) are still not satisfactory. The Rho kinase (ROCK) inhibitor fasudil has demonstrated beneficial effects in cell culture and animal models of ALS. For many years, fasudil has been approved in Japan for the treatment of vasospasm in patients with subarachnoid hemorrhage with a favorable safety profile. Here we describe a clinical trial protocol to repurpose fasudil as a disease-modifying therapy for ALS patients.Methods: ROCK-ALS is a multicenter, double-blind, randomized, placebo-controlled phase IIa trial of fasudil in ALS patients (EudraCT: 2017-003676-31, NCT: 03792490). Safety and tolerability are the primary endpoints. Efficacy is a secondary endpoint and will be assessed by the change in ALSFRS-R, ALSAQ-5, slow vital capacity (SVC), ECAS, and the motor unit number index (MUNIX), as well as survival. Efficacy measures will be assessed before (baseline) and immediately after the infusion therapy as well as on days 90 and 180. Patients will receive a daily dose of either 30 or 60 mg fasudil, or placebo in two intravenous applications for a total of 20 days. Regular assessments of safety will be performed throughout the treatment period, and in the follow-up period until day 180. Additionally, we will collect biological fluids to assess target engagement and evaluate potential biomarkers for disease progression. A total of 120 patients with probable or definite ALS (revised El Escorial criteria) and within 6–18 months of the onset of weakness shall be included in 16 centers in Germany, Switzerland and France.Results and conclusions: The ROCK-ALS trial is a phase IIa trial to evaluate the ROCK-inhibitor fasudil in early-stage ALS-patients that started patient recruitment in 2019

Etude de la résistance à la lévofloxacine d'une souche clinique de streptococcus mitis

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Etude de la résistance à la lévofloxacine d'une souche clinique de streptococcus mitis

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

A ProScale case study on indoor wall paint

ProScale is a method to assess toxicity potentials for products in a life cycle perspective, in its current version covering direct human exposure related toxicity potential. It is designed to be useful on its own or alongside other impact categories in life cycle assessment (LCA). The study reported herein was conducted by examination of the ProScale model in a case study on indoor wall paint. The reason for choosing indoor wall paint was that the EU commission has paint as one of their pilots for Product Environmental Footprint (PEF), and a particular purpose of the case study was to showcase the applicability of ProScale in PEF. The ProScale assessment on indoor wall paint was simplified due to time limitation in scope.

One New LEN Enzyme and Two New OKP Enzymes in Klebsiella pneumoniae Clinical Isolates and Proposed Nomenclature for Chromosomal β-Lactamases of This Species

International audienc