Teaching the Grid: Learning Distributed Computing with the M-grid Framework

A classic challenge within Computer Science is to distribute data and processes so as to take advantage of multiple computers tackling a single problem in a simultaneous and coordinated way. This situation arises in a number of different scenarios, including Grid computing which is a secure, service-based architecture for tackling massively parallel problems and creating virtual organizations. Although the Grid seems destined to be an important part of the future computing landscape, it is very difficult to learn how to use as real Grid software requires extensive setting up and complex security processes. M-grid mimics the core features of the Grid, in a much simpler way, enabling the rapid prototyping of distributed applications. We describe m-grid and explore how it may be used to teach foundation Grid computing skills at the Higher Education level and report some of our experiences of deploying it as an exercise within a programming course

Lactadherin Inhibits Secretory Phospholipase A2 Activity on Pre-Apoptotic Leukemia Cells

Secretory phospholipase A2 (sPLA2) is a critical component of insect and snake venoms and is secreted by mammalian leukocytes during inflammation. Elevated secretory PLA2 concentrations are associated with autoimmune diseases and septic shock. Many sPLA2’s do not bind to plasma membranes of quiescent cells but bind and digest phospholipids on the membranes of stimulated or apoptotic cells. The capacity of these phospholipases to digest membranes of stimulated or apoptotic cells correlates to the exposure of phosphatidylserine. In the present study, the ability of the phosphatidyl-L-serine-binding protein, lactadherin to inhibit phospholipase enzyme activity has been assessed. Inhibition of human secretory phospholipase A2-V on phospholipid vesicles exceeded 90%, whereas inhibition of Naja mossambica sPLA2 plateaued at 50–60%. Lactadherin inhibited 45% of activity of Naja mossambica sPLA2 and >70% of human secretory phospholipase A2-V on the membranes of human NB4 leukemia cells treated with calcium ionophore A23187. The data indicate that lactadherin may decrease inflammation by inhibiting sPLA2

Safety, Immunogenicity, and Efficacy of Intramuscular and Oral Delivery of ERA-G333 Recombinant Rabies Virus Vaccine to Big Brown Bats (\u3ci\u3eEptesicus fuscus\u3c/i\u3e)

Attenuated strains of rabies virus (RABV) have been used for oral vaccination of wild carnivores in Europe and North America. However, some RABV vaccines caused clinical rabies in target animals. To improve the safety of attenuated RABV as an oral vaccine for field use, strategies using selection of escape mutants under monoclonal antibody neutralization pressure and reverse genetics–defined mutations have been used. We tested the safety, immunogenicity, and efficacy of one RABV construct, ERA-g333, developed with reverse genetics by intramuscular (IM) or oral (PO) routes in big brown bats (Eptesicus fuscus). Twenty-five bats received 5×106 mouse intracerebral median lethal doses (MICLD50) of ERA-g333 by IM route, 10 received 5×106 MICLD50 of ERA-g333 by PO route, and 22 bats served as unvaccinated controls. Twenty-one days after vaccination, 44 bats were infected by IM route with 102.9 MICLD50 of E. fuscus RABV. We report both the immunogenicity and efficacy of ERA-g333 delivered by the IM route; no induction of humoral immunity was detected in bats vaccinated by the PO route. Two subsets of bats vaccinated IM (n=5) and PO (n=3) were not challenged, and none developed clinical rabies from ERA-g333. Scarce reports exist on the evaluation of oral rabies vaccines in insectivorous bats, although the strategy evaluated here may be feasible for future application to these important RABV reservoirs

Impact of Age and Estimated Glomerular Filtration Rate on the Glycemic Efficacy and Safety of Canagliflozin: A Pooled Analysis of Clinical Studies.

AbstractObjectiveReduced efficacy has been reported in the elderly; it may be a consequence of an age-dependent decline in estimated glomerular filtration rate (eGFR) rather than ageing per se. We sought to determine the impact of these 2 parameters, as well as sex and baseline body mass index (BMI), on the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in people with type 2 diabetes.MethodsData were pooled from 6 randomized, double-blind, placebo-controlled studies (18 or 26 weeks; N=4053). Changes in glycated hemoglobin (A1C) and systolic blood pressure (BP) from baseline with canagliflozin 100 mg and 300 mg and placebo were evaluated in subgroups by sex, baseline BMI, baseline age and baseline eGFR. Safety was assessed by reports of adverse events.ResultsPlacebo-subtracted reductions in A1C with canagliflozin 100 mg and 300 mg were similar in men and women. A1C reductions with canagliflozin were seen across BMI subgroups and in participants aged <65 years and ≥65 years. Significantly greater placebo-subtracted reductions in A1C were seen with both canagliflozin doses in participants with higher baseline eGFR (≥90 mL/min/1.73 m2). Reductions in systolic BP were seen with canagliflozin across subgroups of sex, BMI, age and eGFR. A1C reductions with canagliflozin were similar for participants aged <65 or ≥65 years who had baseline eGFR ≥60 mL/min/1.73 m2 and were smaller in older than in younger participants with baseline eGFR 45 to <60 mL/min/1.73 m2. The overall incidence of adverse events was similar across treatment groups regardless of sex, baseline BMI, baseline age or baseline eGFR.ConclusionsCanagliflozin improved glycemic control, reduced BP and was generally well tolerated in people with type 2 diabetes across a range of ages, BMIs and renal functions

Selecting social work students:lessons from research in Scotland

The issue of selection of students to social work programmes is one that remains highly contested. While it is clear that there is no single way of choosing the next generation of social work students, nevertheless, there are a number of strongly held beliefs about what ‘best practice’ means in this fraught field. These can be difficult to challenge, and even harder to shift, in spite of contrary evidence. This paper presents research conducted in Scotland in 2016 as part of the Scottish Government-sponsored Review of Social Work Education. The research set out to consider what selection processes were being used in Scotland and why; more fundamentally, it sought to explore the views of those involved in social work education alongside evidence about the outcomes of the selection processes (that is, data on student retention and success). The article concludes that while there is little evidence that one method of selection to social work programmes is intrinsically better than another, issues of fairness and transparency in selection, as well as diversity, remain pressing

Specific sequences within arginine–glycine-rich domains affect mRNA-binding protein function

The discovery of roles for arginine methylation in intracellular transport and mRNA splicing has focused attention on the methylated arginine–glycine (RG)-rich domains found in many eukaryotic RNA-binding proteins. Sequence similarity among these highly repetitive RG domains, combined with interactions between RG-rich proteins, raises the question of whether these regions are general interaction motifs or whether there is specificity within these domains. Using the essential Saccharomyces cerevisiae mRNA-binding protein Npl3 (ScNpl3) as a model system, we first tested the importance of the RG domain for protein function. While Npl3 lacking the RG domain could not support growth of cells lacking Npl3, surprisingly, expression of the RG domain alone supported partial growth of these cells. To address the specificity of this domain, we created chimeric forms of ScNpl3 with RG-rich domains of S. cerevisiae nucleolar proteins, Gar1 and Nop1 (ScGar1, ScNop1), or of the Candida albicans Npl3 ortholog (CaNpl3). Whereas the CaNpl3 RG chimeric protein retained nearly wild-type function in S. cerevisiae, the ScGar1 and ScNop1 RG domains significantly reduced Npl3 function and self-association, indicating RG domain specificity. Nuclear localization of Npl3 also requires specific RG sequences, yet heterologous RG domains allow similar modulation of Npl3 transport by arginine methylation

Calibrating CHIME, A New Radio Interferometer to Probe Dark Energy

The Canadian Hydrogen Intensity Mapping Experiment (CHIME) is a transit interferometer currently being built at the Dominion Radio Astrophysical Observatory (DRAO) in Penticton, BC, Canada. We will use CHIME to map neutral hydrogen in the frequency range 400 -- 800\,MHz over half of the sky, producing a measurement of baryon acoustic oscillations (BAO) at redshifts between 0.8 -- 2.5 to probe dark energy. We have deployed a pathfinder version of CHIME that will yield constraints on the BAO power spectrum and provide a test-bed for our calibration scheme. I will discuss the CHIME calibration requirements and describe instrumentation we are developing to meet these requirements

Canadian Hydrogen Intensity Mapping Experiment (CHIME) Pathfinder

A pathfinder version of CHIME (the Canadian Hydrogen Intensity Mapping Experiment) is currently being commissioned at the Dominion Radio Astrophysical Observatory (DRAO) in Penticton, BC. The instrument is a hybrid cylindrical interferometer designed to measure the large scale neutral hydrogen power spectrum across the redshift range 0.8 to 2.5. The power spectrum will be used to measure the baryon acoustic oscillation (BAO) scale across this poorly probed redshift range where dark energy becomes a significant contributor to the evolution of the Universe. The instrument revives the cylinder design in radio astronomy with a wide field survey as a primary goal. Modern low-noise amplifiers and digital processing remove the necessity for the analog beamforming that characterized previous designs. The Pathfinder consists of two cylinders 37\,m long by 20\,m wide oriented north-south for a total collecting area of 1,500 square meters. The cylinders are stationary with no moving parts, and form a transit instrument with an instantaneous field of view of $\sim$100\,degrees by 1-2\,degrees. Each CHIME Pathfinder cylinder has a feedline with 64 dual polarization feeds placed every $\sim$30\,cm which Nyquist sample the north-south sky over much of the frequency band. The signals from each dual-polarization feed are independently amplified, filtered to 400-800\,MHz, and directly sampled at 800\,MSps using 8 bits. The correlator is an FX design, where the Fourier transform channelization is performed in FPGAs, which are interfaced to a set of GPUs that compute the correlation matrix. The CHIME Pathfinder is a 1/10th scale prototype version of CHIME and is designed to detect the BAO feature and constrain the distance-redshift relation.Comment: 20 pages, 12 figures. submitted to Proc. SPIE, Astronomical Telescopes + Instrumentation (2014

Stability Constraints on Classical de Sitter Vacua

We present further no-go theorems for classical de Sitter vacua in Type II string theory, i.e., de Sitter constructions that do not invoke non-perturbative effects or explicit supersymmetry breaking localized sources. By analyzing the stability of the 4D potential arising from compactification on manfiolds with curvature, fluxes, and orientifold planes, we found that additional ingredients, beyond the minimal ones presented so far, are necessary to avoid the presence of unstable modes. We enumerate the minimal setups for (meta)stable de Sitter vacua to arise in this context.Comment: 18 pages; v2: argument improved, references adde

Kinome Profiling Identifies Druggable Targets for Novel Human Cytomegalovirus (HCMV) Antivirals

Human cytomegalovirus (HCMV) is a significant cause of disease in immune-compromised adults and immune naïve newborns. No vaccine exists to prevent HCMV infection, and current antiviral therapies have toxic side effects that limit the duration and intensity of their use. There is thus an urgent need for new strategies to treat HCMV infection. Repurposing existing drugs as antivirals is an attractive approach to limit the time and cost of new antiviral drug development. Virus-induced changes in infected cells are often driven by changes in cellular kinase activity, which led us to hypothesize that defining the complement of kinases (the kinome), whose abundance or expression is altered during infection would identify existing kinase inhibitors that could be repurposed as new antivirals. To this end, we applied a kinase capture technique, multiplexed kinase inhibitor bead-mass spectrometry (MIB-MS) kinome, to quantitatively measure perturbations in >240 cellular kinases simultaneously in cells infected with a laboratory-adapted (AD169) or clinical (TB40E) HCMV strain. MIB-MS profiling identified time-dependent increases and decreases in MIB binding of multiple kinases including cell cycle kinases, receptor tyrosine kinases, and mitotic kinases. Based on the kinome data, we tested the antiviral effects of kinase inhibitors and other compounds, several of which are in clinical use or development. Using a novel flow cytometry-based assay and a fluorescent reporter virus we identified three compounds that inhibited HCMV replication with IC 50 values of 3 log decrease in virus replication. These results show the utility of MIB-MS kinome profiling for identifying existing kinase inhibitors that can potentially be repurposed as novel antiviral drugs