Chiminey: Reliable Computing and Data Management Platform in the Cloud

The enabling of scientific experiments that are embarrassingly parallel, long running and data-intensive into a cloud-based execution environment is a desirable, though complex undertaking for many researchers. The management of such virtual environments is cumbersome and not necessarily within the core skill set for scientists and engineers. We present here Chiminey, a software platform that enables researchers to (i) run applications on both traditional high-performance computing and cloud-based computing infrastructures, (ii) handle failure during execution, (iii) curate and visualise execution outputs, (iv) share such data with collaborators or the public, and (v) search for publicly available data.Comment: Preprint, ICSE 201

The evolution of the ISOLDE control system

The ISOLDE on-line mass separator facility is operating on a Personal Computer based control system since spring 1992. Front End Computers accessing the hardware are controlled from consoles running Microsoft WindowsTM through a Novell NetWare4TM local area network. The control system is transparently integrated in the CERN wide office network and makes heavy use of the CERN standard office application programs to control and to document the running of the ISOLDE isotope separators. This paper recalls the architecture of the control system, shows its recent developments and gives some examples of its graphical user interface

The SMILE Soft X-ray Imager (SXI) CCD design and development

SMILE, the Solar wind Magnetosphere Ionosphere Link Explorer, is a joint science mission between the European Space Agency and the Chinese Academy of Sciences. The spacecraft will be uniquely equipped to study the interaction between the Earth’s magnetosphere-ionosphere system and the solar wind on a global scale. SMILE’s instruments will explore this science through imaging of the solar wind charge exchange soft X-ray emission from the dayside magnetosheath, simultaneous imaging of the UV northern aurora and in-situ monitoring of the solar wind and magnetosheath plasma and magnetic field conditions. The Soft X-ray Imager (SXI) is the instrument being designed to observe X-ray photons emitted by the solar wind charge exchange process at photon energies between 200 eV and 2000 eV. X-rays will be collected using a focal plane array of two custom-designed CCDs, each consisting of 18 µm square pixels in a 4510 by 4510 array. SMILE will be placed in a highly elliptical polar orbit, passing in and out of the Earth’s radiation belts every 48 hours. Radiation damage accumulated in the CCDs during the mission’s nominal 3-year lifetime will degrade their performance (such as through decreases in charge transfer efficiency), negatively impacting the instrument’s ability to detect low energy X-rays incident on the regions of the CCD image area furthest from the detector outputs. The design of the SMILE-SXI CCDs is presented here, including features and operating methods for mitigating the effects of radiation damage and expected end of life CCD performance. Measurements with a PLATO device that has not been designed for soft X-ray signal levels indicate a temperature-dependent transfer efficiency performance varying between 5 × 10−5 and 9 × 10−4 at expected End of Life for 5.9 keV photons, giving an initial set of measurements from which to extrapolate the performance of the SXI CCDs

Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice.

Background: P. aeruginosa is one of the top three causes of opportunistic human bacterial infections. The remarkable variability in the clinical outcomes of this infection is thought to be associated with genetic predisposition. However, the genes underlying host susceptibility to P. aeruginosa infection are still largely unknown. Results: As a step towards mapping these genes, we applied a genome wide linkage analysis approach to a mouse model. A large F2 intercross population, obtained by mating P. aeruginosa-resistant C3H/HeOuJ, and susceptible A/J mice, was used for quantitative trait locus (QTL) mapping. The F2 progenies were challenged with a P. aeruginosa clinical strain and monitored for the survival time up to 7 days post-infection, as a disease phenotype associated trait. Selected phenotypic extremes of the F2 distribution were genotyped with high-density single nucleotide polymorphic (SNP) markers, and subsequently QTL analysis was performed. A significant locus was mapped on chromosome 6 and was named P. aeruginosa infection resistance locus 1 (Pairl1). The most promising candidate genes, including Dok1, Tacr1, Cd207, Clec4f, Gp9, Gata2, Foxp1, are related to pathogen sensing, neutrophils and macrophages recruitment and inflammatory processes. Conclusions: We propose a set of genes involved in the pathogenesis of P. aeruginosa infection that may be explored to complement human studie

Mechanical thrombectomy in acute basilar artery stroke: a systematic review and Meta-analysis of randomized controlled trials

Background: The evidence for mechanical thrombectomy in acute basilar artery occlusion has until now remained inconclusive with basilar artery strokes associated with high rates of death and disability. This systematic review and meta-analysis will summarize the available evidence for the effectiveness of mechanical thrombectomy in acute basilar artery occlusion compared to best medical therapy. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials using Embase, Medline and the Cochrane Central Register of Controlled Trials (CENTRAL). We calculated risk ratios (RRs) and 95% confidence intervals (CIs) to summarize the effect estimates for each outcome. Results: We performed a random effects (Mantel-Haenszel) meta-analysis of the four included randomized controlled trials comprising a total of 988 participants. We found a statistically significant improvement in the rates of those with a good functional outcome (mRS 0–3, RR 1.54, 1.16–2.06, p = 0.003) and functional independence (mRS 0–2, RR 1.69, 1.05–2.71, p = 0.03) in those who were treated with thrombectomy when compared to best medical therapy alone. Thrombectomy was associated with a higher level of sICH (RR 7.12, 2.16–23.54, p = 0.001) but this was not reflected in a higher mortality rate, conversely the mortality rate was significantly lower in the intervention group (RR 0.76, 0.65–0.89, p = 0.0004). Conclusions: Our meta-analysis of the recently presented randomized controlled studies is the first to confirm the disability and mortality benefit of mechanical thrombectomy in basilar artery stroke

An association study on contrasting cystic fibrosis endophenotypes recognizes KRT8 but not KRT18 as a modifier of cystic fibrosis disease severity and CFTR mediated residual chloride secretion

<p>Abstract</p> <p>Background</p> <p>F508del-CFTR, the most frequent disease-causing mutation among Caucasian cystic fibrosis (CF) patients, has been characterised as a mutant defective in protein folding, processing and trafficking. We have investigated the two neighbouring cytokeratin genes <it>KRT8 </it>and <it>KRT18 </it>in a candidate gene approach to ask whether variants in <it>KRT8 </it>and/or <it>KRT18 </it>modify the impaired ion conductance known as the CF basic defect, and whether they are associated with correct trafficking of mutant CFTR and disease severity of CF.</p> <p>Methods</p> <p>We have selected contrasting F508del-<it>CFTR </it>homozygous patient subpopulations stratified for disease severity, comparing 13 concordant mildly affected sib pairs vs. 12 concordant severely affected sib pairs, or manifestation of the CF basic defect in intestinal epithelium, comparing 22 individuals who exhibit CFTR-mediated residual chloride secretion vs. 14 individuals who do not express any chloride secretion, for an association. The <it>KRT8</it>/<it>KRT18 </it>locus was initially interrogated with one informative microsatellite marker. Subsequently, a low density SNP map with four SNPs in KRT8 and two SNPs in KRT18, each selected for high polymorphism content, was used to localize the association signal.</p> <p>Results</p> <p><it>KRT8</it>, but not <it>KRT18</it>, showed an association with CF disease severity (P_best= 0.00131; P_corr= 0.0185) and CFTR mediated residual chloride secretion (P_best= 0.0004; P_corr= 0.0069). Two major four-marker-haplotypes spanning 13 kb including the entire <it>KRT8 </it>gene accounted for 90% of chromosomes, demonstrating strong linkage disequilibrium at that locus. Absence of chloride secretion was associated with the recessive haplotype 1122 at rs1907671, rs4300473, rs2035878 and rs2035875. The contrasting haplotype 2211 was dominant for the presence of CFTR mediated residual chloride secretion. In consistency, the <it>KRT8 </it>haplotype 2211 was associated with mild CF disease while 1122 was observed as risk haplotype. Analysis of microsatellite allele distributions on the SNP background suggests that the mild <it>KRT8 </it>haplotype 2211 is phylogenetically older than its severe counterpart.</p> <p>Conclusions</p> <p>The two opposing <it>KRT8 </it>alleles which have been identified as a benign and as a risk allele in this work are likely effective in the context of epithelial cell differentiation. As the mild <it>KRT8 </it>allele is associated with CFTR mediated residual chloride secretion among F508del-<it>CFTR </it>homozygotes, the KRT8/KRT18 heterodimeric intermediary filaments of the cytoskeleton apparently are an essential component for the proper targeting of CFTR to the apical membrane in epithelial cells.</p