55 research outputs found

    Many-task computing on many-core architectures

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    Many-Task Computing (MTC) is a common scenario for multiple parallel systems, such as cluster, grids, cloud and supercomputers, but it is not so popular in shared memory parallel processors. In this sense and given the spectacular growth in performance and in number of cores integrated in many-core architectures, the study of MTC on such architectures is becoming more and more relevant. In this paper, authors present what are those programming mechanisms to take advantages of such massively parallel features for the particular target of MTC. Also, the hardware features of the two dominant many-core platforms (NVIDIA's GPUs and Intel Xeon Phi) are also analyzed for our specific framework. Given the important differences in terms of hardware and software in our two many-core platforms, we have considered different strategies based on CUDA (for GPUs) and OpenMP (for Intel Xeon Phi). We carried out several test cases based on an appropriate and widely studied problem for benchmarking as matrix multiplication. Essentially, this study consisted of comparing the time consumed for computing in parallel several tasks one by one (the whole computational resources are used just to compute one task at a time) with the time consumed for computing in parallel the same set of tasks simultaneously (the whole computational resources are used for computing the set of tasks at very same time). Finally, we compared both software-hardware scenarios to identify the most relevant computer features in each of our many-core architectures

    Hemodynamic latency is associated with reduced intelligence across the lifespan: an fMRI DCM study of aging, cerebrovascular integrity, and cognitive ability

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    Changes in neurovascular coupling are associated with both Alzheimer’s disease and vascular dementia in later life, but this may be confounded by cerebrovascular risk. We hypothesized that hemodynamic latency would be associated with reduced cognitive functioning across the lifespan, holding constant demographic and cerebrovascular risk. In 387 adults aged 18–85 (mean = 48.82), dynamic causal modeling was used to estimate the hemodynamic response function in the left and right V1 and V3-ventral regions of the visual cortex in response to a simple checkerboard block design stimulus with minimal cognitive demands. The hemodynamic latency (transit time) in the visual cortex was used to predict general cognitive ability (Full-Scale IQ), controlling for demographic variables (age, race, education, socioeconomic status) and cerebrovascular risk factors (hypertension, alcohol use, smoking, high cholesterol, BMI, type 2 diabetes, cardiac disorders). Increased hemodynamic latency in the visual cortex predicted reduced cognitive function (p < 0.05), holding constant demographic and cerebrovascular risk. Increased alcohol use was associated with reduced overall cognitive function (Full Scale IQ 2.8 pts, p < 0.05), while cardiac disorders (Full Scale IQ 3.3 IQ pts; p < 0.05), high cholesterol (Full Scale IQ 3.9 pts; p < 0.05), and years of education (2 IQ pts/year; p < 0.001) were associated with higher general cognitive ability. Increased hemodynamic latency was associated with reduced executive functioning (p < 0.05) as well as reductions in verbal concept formation (p < 0.05) and the ability to synthesize and analyze abstract visual information (p < 0.01). Hemodynamic latency is associated with reduced cognitive ability across the lifespan, independently of other demographic and cerebrovascular risk factors. Vascular health may predict cognitive ability long before the onset of dementias

    Lst4, the yeast Fnip1/2 orthologue, is a DENN-family protein.

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    The folliculin/Fnip complex has been demonstrated to play a crucial role in the mechanisms underlying Birt-Hogg-Dubé (BHD) syndrome, a rare inherited cancer syndrome. Lst4 has been previously proposed to be the Fnip1/2 orthologue in yeast and therefore a member of the DENN family. In order to confirm this, we solved the crystal structure of the N-terminal region of Lst4 from Kluyveromyces lactis and show it contains a longin domain, the first domain of the full DENN module. Furthermore, we demonstrate that Lst4 through its DENN domain interacts with Lst7, the yeast folliculin orthologue. Like its human counterpart, the Lst7/Lst4 complex relocates to the vacuolar membrane in response to nutrient starvation, most notably in carbon starvation. Finally, we express and purify the recombinant Lst7/Lst4 complex and show that it exists as a 1 : 1 heterodimer in solution. This work confirms the membership of Lst4 and the Fnip proteins in the DENN family, and provides a basis for using the Lst7/Lst4 complex to understand the molecular function of folliculin and its role in the pathogenesis of BHD syndrome.AP, BKB and RKN were supported by the Myrovlytis Trust. DBA was supported by a NHMRC CJ Martin Fellowship (APP1072476). LHW was supported by Medical Research Council (MRC) studentship, MR/J006580/1 and TPL by University College London. SD was supported by Fondation de France, La Ligue National contre le Cancer (Comité de Paris / Ile-de-France and Comité de l’Oise); TLB and NZ thank the University of Cambridge and The Wellcome Trust for facilities and support.This is the final version of the article. It was first available from Royal Society Publishing via http://dx.doi.org/10.1098/rsob.15017

    Stelleninhaber geht – Wissen bleibt!

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    In Deutschland nimmt der Anteil älterer Arbeitnehmerinnen und Arbeitnehmer tendenziell zu. Deshalb muss sich die Bibliotheksleitung verstärkt auf das altersbedingte Ausscheiden älterer Arbeitnehmer einstellen. Eine langjährige Fachkraft verfügt über spezielles Erfahrungswissen im direkten Aufgabenfeld. Die Bibliotheksleitung muss den Transfer allen relevanten Wissens, dazu gehört das Erfahrungswissen, vom Stelleninhaber auf seinen Nachfolger ermöglichen und unterstützen. Am Beispiel der Universitätsbibliothek der Bergakademie Freiberg wird untersucht, wie das Wissensmanagement im Rahmen eines Stellenwechsels derzeit geregelt ist. Das geschieht mit Hilfe von Tiefeninterviews in verschiedenen Abteilungen. Die Auswertung der Interviews bildet die Basis für ein Konzept für das Wissensmanagement beim Stellenwechsel an der UB Freiberg. Das Konzept benennt u. a. Maßnahmen zur Identifikation des stellenbezogenen Wissens, Maßnahmen zur Dokumentation des relevanten Wissens und Instrumente zur Wissensweitergabe beim Stellenwechsel

    Mixed Th1 and Th2 Mycobacterium tuberculosis-specific CD4 T cell responses in patients with active pulmonary tuberculosis from Tanzania.

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    Mycobacterium tuberculosis (Mtb) and helminth infections elicit antagonistic immune effector functions and are co-endemic in several regions of the world. We therefore hypothesized that helminth infection may influence Mtb-specific T-cell immune responses. We evaluated the cytokine profile of Mtb-specific T cells in 72 individuals with pulmonary TB disease recruited from two Sub-Saharan regions with high and moderate helminth burden i.e. 55 from Tanzania (TZ) and 17 from South Africa (SA), respectively. We showed that Mtb-specific CD4 T-cell functional profile of TB patients from Tanzania are primarily composed of polyfunctional Th1 and Th2 cells, associated with increased expression of Gata-3 and reduced expression of T-bet in memory CD4 T cells. In contrast, the cytokine profile of Mtb-specific CD4 T cells of TB patients from SA was dominated by single IFN-γ and dual IFN-γ/TNF-α and associated with TB-induced systemic inflammation and elevated serum levels of type I IFNs. Of note, the proportion of patients with Mtb-specific CD8 T cells was significantly reduced in Mtb/helminth co-infected patients from TZ. It is likely that the underlying helminth infection and possibly genetic and other unknown environmental factors may have caused the induction of mixed Th1/Th2 Mtb-specific CD4 T cell responses in patients from TZ. Taken together, these results indicate that the generation of Mtb-specific CD4 and CD8 T cell responses may be substantially influenced by environmental factors in vivo. These observations may have major impact in the identification of immune biomarkers of disease status and correlates of protection

    Enhanced Pro-Inflammatory Cytokine Responses following Toll-Like-Receptor Ligation in Schistosoma haematobium-Infected Schoolchildren from Rural Gabon

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    BACKGROUND: Schistosoma infection is thought to lead to down-regulation of the host's immune response. This has been shown for adaptive immune responses, but the effect on innate immunity, that initiates and shapes the adaptive response, has not been extensively studied. In a first study to characterize these responses, we investigated the effect of Schistosoma haematobium infection on cytokine responses of Gabonese schoolchildren to a number of Toll-like receptor (TLR) ligands. METHODOLOGY: Peripheral blood mononuclear cells (PBMCs) were collected from S. haematobium-infected and uninfected schoolchildren from the rural area of Zile in Gabon. PBMCs were incubated for 24 h and 72 h with various TLR ligands, as well as schistosomal egg antigen (SEA) and adult worm antigen (AWA). Pro-inflammatory TNF-alpha and anti-inflammatory/regulatory IL-10 cytokine concentrations were determined in culture supernatants. PRINCIPAL FINDINGS: Infected children produced higher adaptive IL-10 responses than uninfected children against schistosomal antigens (72 h incubation). On the other hand, infected children had higher TNF-alpha responses than uninfected children and significantly higher TNF-alpha to IL-10 ratios in response to FSL-1 and Pam3, ligands of TLR2/6 and TLR2/1 respectively. A similar trend was observed for the TLR4 ligand LPS while Poly(I:C) (Mda5/TLR3 ligand) did not induce substantial cytokine responses (24 h incubation). CONCLUSIONS: This pilot study shows that Schistosoma-infected children develop a more pro-inflammatory TLR2-mediated response in the face of a more anti-inflammatory adaptive immune response. This suggests that S. haematobium infection does not suppress the host's innate immune system in the context of single TLR ligation

    Impact of early life exposures to geohelminth infections on the development of vaccine immunity, allergic sensitization, and allergic inflammatory diseases in children living in tropical Ecuador: the ECUAVIDA birth cohort study.

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    Background Geohelminth infections are highly prevalent infectious diseases of childhood in many regions of the Tropics, and are associated with significant morbidity especially among pre-school and school-age children. There is growing concern that geohelminth infections, particularly exposures occurring during early life in utero through maternal infections or during infancy, may affect vaccine immunogenicity in populations among whom these infections are endemic. Further, the low prevalence of allergic disease in the rural Tropics has been attributed to the immune modulatory effects of these infections and there is concern that widespread use of anthelmintic treatment in high-risk groups may be associated with an increase in the prevalence of allergic diseases. Because the most widely used vaccines are administered during the first year of life and the antecedents of allergic disease are considered to occur in early childhood, the present study has been designed to investigate the impact of early exposures to geohelminths on the development of protective immunity to vaccines, allergic sensitization, and allergic disease. Methods/Design A cohort of 2,403 neonates followed up to 8 years of age. Primary exposures are infections with geohelminth parasites during the last trimester of pregnancy and the first 2 years of life. Primary study outcomes are the development of protective immunity to common childhood vaccines (i.e. rotavirus, Haemophilus influenzae type B, Hepatitis B, tetanus toxoid, and oral poliovirus type 3) during the first 5 years of life, the development of eczema by 3 years of age, the development of allergen skin test reactivity at 5 years of age, and the development of asthma at 5 and 8 years of age. Potential immunological mechanisms by which geohelminth infections may affect the study outcomes will be investigated also. Discussion The study will provide information on the potential effects of early exposures to geohelminths (during pregnancy and the first 2 years of life) on the development of vaccine immunity and allergy. The data will inform an ongoing debate of potential effects of geohelminths on child health and will contribute to policy decisions on new interventions designed to improve vaccine immunogenicity and protect against the development of allergic diseases

    Beam test performance of a prototype module with Short Strip ASICs for the CMS HL-LHC tracker upgrade

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    The Short Strip ASIC (SSA) is one of the four front-end chips designed for the upgrade of the CMS Outer Tracker for the High Luminosity LHC. Together with the Macro-Pixel ASIC (MPA) it will instrument modules containing a strip and a macro-pixel sensor stacked on top of each other. The SSA provides both full readout of the strip hit information when triggered, and, together with the MPA, correlated clusters called stubs from the two sensors for use by the CMS Level-1 (L1) trigger system. Results from the first prototype module consisting of a sensor and two SSA chips are presented. The prototype module has been characterized at the Fermilab Test Beam Facility using a 120 GeV proton beam

    Structure of the heterodimeric core primase.

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    Primases are DNA-dependent RNA polymerases that synthesize the oligoribonucleotide primers essential to DNA replication. In archaeal and eukaryotic organisms, the core primase is a heterodimeric enzyme composed of a small and a large subunit. Here we report a crystallographic and biochemical analysis of the core primase from the archaeon Sulfolobus solfataricus. The structure provides the first three-dimensional description of the large subunit and its interaction with the small subunit. The evolutionary conservation of amino acids at the protein-protein interface implies that the observed mode of subunit association is conserved among archaeal and eukaryotic primases. The orientation of the large subunit in the core primase probably excludes its direct involvement in catalysis. Modeling of a DNA-RNA helix together with structure-based site-directed mutagenesis provides insight into the mechanism of template DNA binding and RNA primer synthesis

    Synthesis, characterization and evaluation of antimicrobial efficacy and brine shrimp lethality assay of Alstonia scholaris stem bark extract mediated ZnONPs

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    Alstonia scholaris is one of the most important medicinal plants and herein, we present the synthesis of zinc oxide nanoparticles using the bark extract of Alstonia scholaris, and evaluation of their antimicrobial efficacy. Stable ZnO nanoparticles were formed by treating 90 mL of 1 mM zinc nitrate aqueous solution with 10 mL of 10% bark extract. The formation of Alstonia scholaris bark extract mediated zinc oxide nanoparticles was confirmed by UV–visible spectroscopic analysis and recorded the localized surface plasmon resonance (LSPR) at 430 nm. Fourier transform infrared spectroscopic (FT-IR) analysis revealed that primary and secondary amine groups in combination with the proteins present in the bark extract is responsible for the reduction and stabilization of the ZnONPs. The crystalline phase of the nanocrystals was determined by XRD analysis and morphology was studied using transmission electron microscopy (TEM). The hydrodynamic diameter (26.2 nm) and a positive zeta potential (43.0 mV) were measured using the dynamic light scattering technique. The antimicrobial activity of Alstonia scholaris ZnONPs was evaluated (in-vitro) using disc diffusion method against fungi, Gram-negative and Gram-positive bacteria which were isolated from the biofilm formed in drinking water PVC pipelines. The results obtained suggested that ZnO nanoparticles exhibit a good anti-fungal activity than bactericidal effect towards all pathogens tested in in-vitro disc diffusion method (170 ppm, 100 ppm and 50 ppm). Further, the toxicity of biosynthesized ZnONPs was tested against Alstonia scholaris to evaluate the cytotoxic effect that displayed LC50 value of 95% confidence intervals
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