Concert/C: A language for distributed programming

Concert/C is a new language for distributed C programming that extends ANSI C to support distribution and process dynamics. Concert/C provides the ability to create and terminate processes, connect them together, and communicate among them. It supports transparent remote function calls (RPC) and asynchronous messages. Interprocess communications interfaces are typed in Concert/C, and type correctness is checked at compile time wherever possible, otherwise at runtime. All C data types, including complex data structures containing pointers and aliases, can be transmitted in RPCs. Concert/C programs run on a heterogeneous set of machine architectures and operating systems and communicate over multiple RPC and messaging protocols. The current Concert/C implementation runs on AIX 3.2 1, SunOS 4.1, Solaris 2.2 and OS/2 2.1, and communicates over Sun RPC, OSF/DCE and UDP multicast. Several groups inside and outside IBM are actively using Concert/C, and it is available via anonymous ftp from software.watson.ibm.com:/pub/concert.

Reduction in Urinary Arsenic with Bottled-water Intervention

The study was conducted to measure the effectiveness of providing bottled water in reducing arsenic exposure. Urine, tap-water and toenail samples were collected from non-smoking adults residing in Ajo (n=40) and Tucson (n=33), Arizona, USA. The Ajo subjects were provided bottled water for 12 months prior to re-sampling. The mean total arsenic (μg/L) in tap-water was 20.3±3.7 in Ajo and 4.0±2.3 in Tucson. Baseline urinary total inorganic arsenic (μg/L) was significantly higher among the Ajo subjects (n=40, 29.1±20.4) than among the Tucson subjects (n=32, 11.0±12.0, p<0.001), as was creatinine-adjusted urinary total inorganic arsenic (μg/g) (35.5±25.2 vs 13.2±9.3, p<0.001). Baseline concentrations of arsenic (μg/g) in toenails were also higher among the Ajo subjects (0.51±0.72) than among the Tucson subjects (0.17±0.21) (p<0.001). After the intervention, the mean urinary total inorganic arsenic in Ajo (n=36) dropped by 21%, from 29.4±21.1 to 23.2±23.2 (p=0.026). The creatinine-adjusted urinary total inorganic arsenic and toenail arsenic levels did not differ significantly with the intervention. Provision of arsenic-free bottled water resulted in a modest reduction in urinary total inorganic arsenic

Evaluation of a Hybrid Boltzmann-Continuum Method for High Speed Nonequilibrium Flows

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83556/1/AIAA-2010-1569-683.pd

Efficient Rijndael Encryption Implementation with Composite Field Arithmetic

Abstract. We explore the use of subfield arithmetic for efficient imple-mentations of Galois Field arithmetic especially in the context of the Rijndael block cipher. Our technique involves mapping field elements to a composite field representation. We describe how to select a represen-tation which minimizes the computation cost of the relevant arithmetic, taking into account the cost of the mapping as well. Our method results in a very compact and fast gate circuit for Rijndael encryption. In conjunction with bit-slicing techniques applied to newly proposed par-allelizable modes of operation, our circuit leads to a high-performance software implementation for Rijndael encryption which offers significant speedup compared to previously reported implementations

Swimming dynamics of a micro-organism in a couple stress fluid : a rheological model of embryological hydrodynamic propulsion

Mathematical simulations of embryological fluid dynamics are fundamental to improving clinical understanding of the intricate mechanisms underlying sperm locomotion. The strongly rheological nature of reproductive fluids has been established for a number of decades. Complimentary to clinical studies, mathematical models of reproductive hydrodynamics provide a deeper understanding of the intricate mechanisms involved in spermatozoa locomotion which can be of immense benefit in clarifying fertilization processes. Although numerous non-Newtonian studies of spermatozoa swimming dynamics in non-Newtonian media have been communicated, very few have addressed the micro-structural characteristics of embryological media. This family of micro-continuum models include Eringen’s micro-stretch theory, Eringen’s microfluid and micropolar constructs and V.K. Stokes’ couple-stress fluid model, all developed in the 1960s. In the present paper we implement the last of these models to examine the problem of micro-organism (spermatozoa) swimming at low Reynolds number in a homogenous embryological fluid medium with couple stress effects. The micro-organism is modeled as with Taylor’s classical approach, as an infinite flexible sheet on whose surface waves of lateral displacement are propagated. The swimming speed of the sheet and rate of work done by it are determined as function of the parameters of orbit and the couple stress fluid parameter (α). The perturbation solutions are validated with a Nakamura finite difference algorithm. The perturbation solutions reveal that the normal beat pattern is effective for both couple stress and Newtonian fluids only when the amplitude of stretching wave is small. The swimming speed is observed to decrease with couple stress fluid parameter tending to its Newtonian limit as alpha tends to infinity. However the rate of work done by the sheet decreases with α and approaches asymptotically to its Newtonian value. The present solutions also provide a good benchmark for more advanced numerical simulations of micro-organism swimming in couple-stress rheological biofluids

Excessive Biologic Response to IFNβ Is Associated with Poor Treatment Response in Patients with Multiple Sclerosis

Interferon-beta (IFNβ) is used to inhibit disease activity in multiple sclerosis (MS), but its mechanisms of action are incompletely understood, individual treatment response varies, and biological markers predicting response to treatment have yet to be identified.he relationship between the molecular response to IFNβ and treatment response was determined in 85 patients using a longitudinal design in which treatment effect was categorized by brain magnetic resonance imaging as good (n = 70) or poor response (n = 15). Molecular response was quantified using a customized cDNA macroarray assay for 166 IFN-regulated genes (IRGs).The molecular response to IFNβ differed significantly between patients in the pattern and number of regulated genes. The molecular response was strikingly stable for individuals for as long as 24 months, however, suggesting an individual ‘IFN response fingerprint’. Unexpectedly, patients with poor response showed an exaggerated molecular response. IRG induction ratios demonstrated an exaggerated molecular response at both the first and 6-month IFNβ injections.MS patients exhibit individually unique but temporally stable biological responses to IFNβ. Poor treatment response is not explained by the duration of biological effects or the specific genes induced. Rather, individuals with poor treatment response have a generally exaggerated biological response to type 1 IFN injections. We hypothesize that the molecular response to type I IFN identifies a pathogenetically distinct subset of MS patients whose disease is driven in part by innate immunity. The findings suggest a strategy for biologically based, rational use of IFNβ for individual MS patients

Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

Published online: 24 February 2021Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.Puya Gharahkhani ... Robert J. Casson (ANZRAG consortium) ... et al

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Variant annotation was supported by software resources provided via the Caché Campus program of the InterSystems GmbH to Alexander Teumer