ePLAS Development for Jet Modeling and Applications

Plasma jets provide an alternate approach to the creation of high energy density laboratory plasmas (HEDLP). For the Plasma Liner Experiment (PLX), typically 30 partially ionized argon jets, produced with mini-rail guns, will be focused into a central volume for subsequent magnetic compression into high density plasma liners that can reach high (0.1 Mbar) peak pressures upon stagnation. The jets are typically 2.5 cm in radius traveling at Mach number 30. Ultimate success will require optimized tuning of the rail configurations, the nozzles injecting the gases, and the careful implementation of pre-ionization. The modeling of plasma jet transport is particularly challenging, due the large space (100 sq cm) and time scales (microseconds) involved. Even traditional implicit methods are insufficient, due to the usual need to track electrons explicitly on the mesh. Wall emission and chemistry must be managed, as must ionization of the jet plasma. Ions in the jets are best followed as particles to account properly for collisions upon jet merger. This Phase I Project developed the code ePLAS to attack and successfully surmount many of these challenges. It invented a new 'super implicit' electromagnetic scheme, using implicit electron moment currents that allowed for modeling of jets over multi-cm and multi-picoseconds on standard, single processor 2 GHz PCs. It enabled merger studies of two jets, in preparation for the multi-jet merger problem. The Project explored particle modeling for the ions, and prepared for the future addition of a grid-base jet ion collision model. Access was added to tabular equations of state for the study of ionization effects in merging jets. The improved code was discussed at the primary plasma meetings (IEEE and APS) during the Project period. Collaborations with National Laboratory and industrial partners were nurtured. Code improvements were made to facilitate code use. See: http://www.researchapplicationscorp.com. The ePLAS code enjoys EAR99 export control treatment, permitting distribution to most foreign countries without a license

The ePLAS Code for Ignition Studies

Inertial Confinement Fusion (ICF) presents unique opportunities for the extraction of clean energy from Fusion. Intense lasers and particle beams can create and interact with such plasmas, potentially yielding sufficient energy to satisfy all our national needs. However, few models are available to help aid the scientific community in the study and optimization of such interactions. This project enhanced and disseminated the computer code ePLAS for the early understanding and control of Ignition in ICF. ePLAS is a unique simulation code that tracks the transport of laser light to a target, the absorption of that light resulting in the generation and transport of hot electrons, and the heating and flow dynamics of the background plasma. It uses an implicit electromagnetic field-solving method to greatly reduce computing demands, so that useful target interaction studies can often be completed in 15 minutes on a portable 2.1 GHz PC. The code permits the rapid scoping of calculations for the optimization of laser target interactions aimed at fusion. Recent efforts have initiated the use of analytic equations of state (EOS), K-alpha image rendering graphics, allocatable memory for source-free usage, and adaption to the latest Mac and Linux Operating Systems. The speed and utility of ePLAS are unequaled in the ICF simulation community. This project evaluated the effects of its new EOSs on target heating, compared fluid and particle models for the ions, initiated the simultaneous use of both ion models in the code, and studied long time scale 500 ps hot electron deposition for shock ignition. ePLAS has been granted EAR99 export control status, permitting export without a license to most foreign countries. Beta-test versions of ePLAS have been granted to several Universities and Commercial users. The net Project was aimed at achieving early success in the laboratory ignition of thermonuclear targets and the mastery of controlled fusion power for the nation

Natural Progression of Biochemical Markers of Biliary Tract Obstruction in Patients with Gallstone Pancreatitis

The presenting pattern and natural progression of biochemical markers of biliary tract obstruction in patients with gallstone pancreatitis have not been elucidated. We analyzed serial values of bilirubin levels following admission to discharge in 143 patients. Ninety-four of patients demonstrated a Decrescendo (falling) pattern of bilirubin levels from admission until normalization at 21 hours (median). Forty-nine patients demonstrated a Crescendo-Decrescendo (initially rising) pattern with peak levels of bilirubin occurring at 39 hours after admission followed by a subsequent normalization after a median of 119 hours. Patients in the Decrescendo group were significantly younger (33 versus 41 years, P = .02) and more patients had experienced symptoms for greater than 48 hours (65% versus 47%, P = .05). Ten percent of patients in the Decrescendo group and 29% of patients in the Crescendo-Decrescendo group underwent ERCP (P = .02). Normalization of biochemical markers after ERCP was significantly delayed in both groups compared to no ERCP. Older patients present earlier, with higher bilirubin levels and normalize slower than younger patients, perhaps due to fibrosis of the ampulla and decreased compliance of the common bile duct. Patients who disobstruct spontaneously (90%) normalize quicker than patients undergoing ERCP

Prediction of Patients with Acute Cholecystitis Requiring Emergent Cholecystectomy: A Simple Score

The objective was to develop a score, to stratify patients with acute cholecystitis into high, intermediate, or low probability of gangrenous cholecystitis. The probability of gangrenous cholecystitis (score) was derived from a logistic regression of a clinical and pathological review of 245 patients undergoing urgent cholecystectomy. Sixty-eight patients had gangrenous inflammation, 132 acute, and 45 no inflammation. The score comprised of: age > 45 years (1 point), heart rate > 90 beats/min (1 point), male (2 points), Leucocytosis > 13,000/mm3 (1.5 points), and ultrasound gallbladder wall thickness > 4.5 mm (1 point). The prevalence of gangrenous cholecystitis was 13% in the low-probability (0–2 points), 33% in the intermediate-probability (2–4.5 points), and 87% in the high probability category (>4.5 points). A cutoff score of 2 identified 31 (69%) patients with no acute inflammation (PPV 90%). This scoring system can prioritize patients for emergent cholecystectomy based on their expected pathology

Regional climate information for risk management: capabilities

A comprehensive review of regional capabilities to produce climate information for risk management around the world is done. Data access, quality control and the potential use of regional reanalyses is explained. Progress on seasonal forecast techniques, the increasing skill of statistical and dynamical methods and the challenges on dynamical downscaling and spatial resolution is presented. A comprehensive review of the progress of Regional Climate Outlook Forums around the world is done explaining the mutual learning process among providers and sectoral users, the opportunities created to develop better climate services for the disaster prevention and planning sectors, the lessons learnt and best practices. The potential of Regional Climate Centres (RCCs) to improve climate services is revised considering the experience of the formal RCCs and other centres working in different regions although not formally recognized as RCCs. Finally a detailed set of recommendations to enhance regional capabilities is listed

A Transcription Factor Map as Revealed by a Genome-Wide Gene Expression Analysis of Whole-Blood mRNA Transcriptome in Multiple Sclerosis

Background: Several lines of evidence suggest that transcription factors are involved in the pathogenesis of Multiple Sclerosis (MS) but complete mapping of the whole network has been elusive. One of the reasons is that there are several clinical subtypes of MS and transcription factors that may be involved in one subtype may not be in others. We investigate the possibility that this network could be mapped using microarray technologies and contemporary bioinformatics methods on a dataset derived from whole blood in 99 untreated MS patients (36 Relapse Remitting MS, 43 Primary Progressive MS, and 20 Secondary Progressive MS) and 45 age-matched healthy controls. Methodology/Principal Findings: We have used two different analytical methodologies: a non-standard differential expression analysis and a differential co-expression analysis, which have converged on a significant number of regulatory motifs that are statistically overrepresented in genes that are either differentially expressed (or differentially co-expressed) in cases and controls (e.g., V$KROX_Q6, p-value ,3.31E-6; V$CREBP1_Q2, p-value ,9.93E-6, V$YY1_02, p-value ,1.65E-5). Conclusions/Significance: Our analysis uncovered a network of transcription factors that potentially dysregulate several genes in MS or one or more of its disease subtypes. The most significant transcription factor motifs were for the Early Growth Response EGR/KROX family, ATF2, YY1 (Yin and Yang 1), E2F-1/DP-1 and E2F-4/DP-2 heterodimers, SOX5, and CREB and ATF families. These transcription factors are involved in early T-lymphocyte specification and commitment as well as in oligodendrocyte dedifferentiation and development, both pathways that have significant biological plausibility in MS causation

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Comparing genotyping algorithms for Illumina's Infinium whole-genome SNP BeadChips

The Brassica napus 60K Illumina Infinium™ SNP array has had huge international uptake in the rapeseed community due to the revolutionary speed of acquisition and ease of analysis of this high-throughput genotyping data, particularly when coupled with the newly available reference genome sequence. However, further utilization of this valuable resource can be optimized by better understanding the promises and pitfalls of SNP arrays. We outline how best to analyze Brassica SNP marker array data for diverse applications, including linkage and association mapping, genetic diversity and genomic introgression studies. We present data on which SNPs are locus-specific in winter, semi-winter and spring B. napus germplasm pools, rather than amplifying both an A-genome and a C-genome locus or multiple loci. Common issues that arise when analyzing array data will be discussed, particularly those unique to SNP markers and how to deal with these for practical applications in Brassica breeding applications

Soft windowing application to improve analysis of high-throughput phenotyping data.

MOTIVATION: High-throughput phenomic projects generate complex data from small treatment and large control groups that increase the power of the analyses but introduce variation over time. A method is needed to utlize a set of temporally local controls that maximizes analytic power while minimizing noise from unspecified environmental factors. RESULTS: Here we introduce \u27soft windowing\u27, a methodological approach that selects a window of time that includes the most appropriate controls for analysis. Using phenotype data from the International Mouse Phenotyping Consortium (IMPC), adaptive windows were applied such that control data collected proximally to mutants were assigned the maximal weight, while data collected earlier or later had less weight. We applied this method to IMPC data and compared the results with those obtained from a standard non-windowed approach. Validation was performed using a resampling approach in which we demonstrate a 10% reduction of false positives from 2.5 million analyses. We applied the method to our production analysis pipeline that establishes genotype-phenotype associations by comparing mutant versus control data. We report an increase of 30% in significant P-values, as well as linkage to 106 versus 99 disease models via phenotype overlap with the soft-windowed and non-windowed approaches, respectively, from a set of 2082 mutant mouse lines. Our method is generalizable and can benefit large-scale human phenomic projects such as the UK Biobank and the All of Us resources. AVAILABILITY AND IMPLEMENTATION: The method is freely available in the R package SmoothWin, available on CRAN http://CRAN.R-project.org/package=SmoothWin. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online