Keldysh formalism for multiple parallel worlds

International Nuclear Information System (INIS)

Ansari, M.; Nazarov, Y. V.

2016-01-01

We present a compact and self-contained review of the recently developed Keldysh formalism for multiple parallel worlds. The formalism has been applied to consistent quantum evaluation of the flows of informational quantities, in particular, to the evaluation of Renyi and Shannon entropy flows. We start with the formulation of the standard and extended Keldysh techniques in a single world in a form convenient for our presentation. We explain the use of Keldysh contours encompassing multiple parallel worlds. In the end, we briefly summarize the concrete results obtained with the method.

Keldysh formalism for multiple parallel worlds

Science.gov (United States)

Ansari, M.; Nazarov, Y. V.

2016-03-01

We present a compact and self-contained review of the recently developed Keldysh formalism for multiple parallel worlds. The formalism has been applied to consistent quantum evaluation of the flows of informational quantities, in particular, to the evaluation of Renyi and Shannon entropy flows. We start with the formulation of the standard and extended Keldysh techniques in a single world in a form convenient for our presentation. We explain the use of Keldysh contours encompassing multiple parallel worlds. In the end, we briefly summarize the concrete results obtained with the method.

Keldysh formalism for multiple parallel worlds

Energy Technology Data Exchange (ETDEWEB)

Ansari, M.; Nazarov, Y. V., E-mail: y.v.nazarov@tudelft.nl [Delft University of Technology, Kavli Institute of Nanoscience (Netherlands)

2016-03-15

We present a compact and self-contained review of the recently developed Keldysh formalism for multiple parallel worlds. The formalism has been applied to consistent quantum evaluation of the flows of informational quantities, in particular, to the evaluation of Renyi and Shannon entropy flows. We start with the formulation of the standard and extended Keldysh techniques in a single world in a form convenient for our presentation. We explain the use of Keldysh contours encompassing multiple parallel worlds. In the end, we briefly summarize the concrete results obtained with the method.

Allele-Specific DNA Methylation and Its Interplay with Repressive Histone Marks at Promoter-Mutant TERT Genes.

Science.gov (United States)

Stern, Josh Lewis; Paucek, Richard D; Huang, Franklin W; Ghandi, Mahmoud; Nwumeh, Ronald; Costello, James C; Cech, Thomas R

2017-12-26

A mutation in the promoter of the Telomerase Reverse Transcriptase (TERT) gene is the most frequent noncoding mutation in cancer. The mutation drives unusual monoallelic expression of TERT, allowing immortalization. Here, we find that DNA methylation of the TERT CpG island (CGI) is also allele-specific in multiple cancers. The expressed allele is hypomethylated, which is opposite to cancers without TERT promoter mutations. The continued presence of Polycomb repressive complex 2 (PRC2) on the inactive allele suggests that histone marks of repressed chromatin may be causally linked to high DNA methylation. Consistent with this hypothesis, TERT promoter DNA containing 5-methyl-CpG has much increased affinity for PRC2 in vitro. Thus, CpG methylation and histone marks appear to collaborate to maintain the two TERT alleles in different epigenetic states in TERT promoter mutant cancers. Finally, in several cancers, DNA methylation levels at the TERT CGI correlate with altered patient survival. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

SWAMP+: multiple subsequence alignment using associative massive parallelism

Energy Technology Data Exchange (ETDEWEB)

Steinfadt, Shannon Irene [Los Alamos National Laboratory; Baker, Johnnie W [KENT STATE UNIV.

2010-10-18

A new parallel algorithm SWAMP+ incorporates the Smith-Waterman sequence alignment on an associative parallel model known as ASC. It is a highly sensitive parallel approach that expands traditional pairwise sequence alignment. This is the first parallel algorithm to provide multiple non-overlapping, non-intersecting subsequence alignments with the accuracy of Smith-Waterman. The efficient algorithm provides multiple alignments similar to BLAST while creating a better workflow for the end users. The parallel portions of the code run in O(m+n) time using m processors. When m = n, the algorithmic analysis becomes O(n) with a coefficient of two, yielding a linear speedup. Implementation of the algorithm on the SIMD ClearSpeed CSX620 confirms this theoretical linear speedup with real timings.

Allele-specific characterization of alanine: glyoxylate aminotransferase variants associated with primary hyperoxaluria.

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Melissa D Lage

Full Text Available Primary Hyperoxaluria Type 1 (PH1 is a rare autosomal recessive kidney stone disease caused by deficiency of the peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT, which is involved in glyoxylate detoxification. Over 75 different missense mutations in AGT have been found associated with PH1. While some of the mutations have been found to affect enzyme activity, stability, and/or localization, approximately half of these mutations are completely uncharacterized. In this study, we sought to systematically characterize AGT missense mutations associated with PH1. To facilitate analysis, we used two high-throughput yeast-based assays: one that assesses AGT specific activity, and one that assesses protein stability. Approximately 30% of PH1-associated missense mutations are found in conjunction with a minor allele polymorphic variant, which can interact to elicit complex effects on protein stability and trafficking. To better understand this allele interaction, we functionally characterized each of 34 mutants on both the major (wild-type and minor allele backgrounds, identifying mutations that synergize with the minor allele. We classify these mutants into four distinct categories depending on activity/stability results in the different alleles. Twelve mutants were found to display reduced activity in combination with the minor allele, compared with the major allele background. When mapped on the AGT dimer structure, these mutants reveal localized regions of the protein that appear particularly sensitive to interactions with the minor allele variant. While the majority of the deleterious effects on activity in the minor allele can be attributed to synergistic interaction affecting protein stability, we identify one mutation, E274D, that appears to specifically affect activity when in combination with the minor allele.

Allelic inhibition of displacement activity: a simplified one tube allele-specific PCR for evaluation of ITPA polymorphisms.

Science.gov (United States)

Galmozzi, E; Facchetti, F; Degasperi, E; Aghemo, A; Lampertico, P

2013-02-01

Recently, genome-wide association studies (GWAS) in patients with chronic hepatitis C virus (HCV) infection have identified two functional single nucleotide polymorphisms (SNPs) in the inosine triphosphatase (ITPA) gene, that are associated strongly and independently with hemolytic anemia in patients exposed to pegylated-interferon (Peg-IFN) plus ribavirin (RBV) combined therapy. Here has been developed a simplified allele discrimination polymerase chain reaction (PCR) assay named allelic inhibition of displacement activity (AIDA) for evaluation of ITPA polymorphisms. AIDA system relies on three unlabeled primers only, two outer common primers and one inner primer with allele-specific 3' terminus mismatch. DNA samples from 192 patients with chronic HCV infection were used to validate the AIDA system and results were compared with the gold standard TaqMan(®) SNP genotyping assay. Concordant data were obtained for all samples, granting for high specificity of the method. In conclusion, AIDA is a practical one-tube method to reproducibly and to assess accurately rs7270101 and rs1127354 ITPA SNPs. Copyright © 2012 Elsevier B.V. All rights reserved.

Allele-Specific DNA Methylation Detection by Pyrosequencing®

DEFF Research Database (Denmark)

Kristensen, Lasse Sommer; Johansen, Jens Vilstrup; Grønbæk, Kirsten

2015-01-01

DNA methylation is an epigenetic modification that plays important roles in healthy as well as diseased cells, by influencing the transcription of genes. In spite the fact that human somatic cells are diploid, most of the currently available methods for the study of DNA methylation do not provide......-effective protocol for allele-specific DNA methylation detection based on Pyrosequencing(®) of methylation-specific PCR (MSP) products including a single nucleotide polymorphism (SNP) within the amplicon....

Efficient multitasking: parallel versus serial processing of multiple tasks.

Science.gov (United States)

Fischer, Rico; Plessow, Franziska

2015-01-01

In the context of performance optimizations in multitasking, a central debate has unfolded in multitasking research around whether cognitive processes related to different tasks proceed only sequentially (one at a time), or can operate in parallel (simultaneously). This review features a discussion of theoretical considerations and empirical evidence regarding parallel versus serial task processing in multitasking. In addition, we highlight how methodological differences and theoretical conceptions determine the extent to which parallel processing in multitasking can be detected, to guide their employment in future research. Parallel and serial processing of multiple tasks are not mutually exclusive. Therefore, questions focusing exclusively on either task-processing mode are too simplified. We review empirical evidence and demonstrate that shifting between more parallel and more serial task processing critically depends on the conditions under which multiple tasks are performed. We conclude that efficient multitasking is reflected by the ability of individuals to adjust multitasking performance to environmental demands by flexibly shifting between different processing strategies of multiple task-component scheduling.

Screening for SNPs with Allele-Specific Methylation based on Next-Generation Sequencing Data.

Science.gov (United States)

Hu, Bo; Ji, Yuan; Xu, Yaomin; Ting, Angela H

2013-05-01

Allele-specific methylation (ASM) has long been studied but mainly documented in the context of genomic imprinting and X chromosome inactivation. Taking advantage of the next-generation sequencing technology, we conduct a high-throughput sequencing experiment with four prostate cell lines to survey the whole genome and identify single nucleotide polymorphisms (SNPs) with ASM. A Bayesian approach is proposed to model the counts of short reads for each SNP conditional on its genotypes of multiple subjects, leading to a posterior probability of ASM. We flag SNPs with high posterior probabilities of ASM by accounting for multiple comparisons based on posterior false discovery rates. Applying the Bayesian approach to the in-house prostate cell line data, we identify 269 SNPs as candidates of ASM. A simulation study is carried out to demonstrate the quantitative performance of the proposed approach.

An efficient parallel algorithm for matrix-vector multiplication

Energy Technology Data Exchange (ETDEWEB)

Hendrickson, B.; Leland, R.; Plimpton, S.

1993-03-01

The multiplication of a vector by a matrix is the kernel computation of many algorithms in scientific computation. A fast parallel algorithm for this calculation is therefore necessary if one is to make full use of the new generation of parallel supercomputers. This paper presents a high performance, parallel matrix-vector multiplication algorithm that is particularly well suited to hypercube multiprocessors. For an n x n matrix on p processors, the communication cost of this algorithm is O(n/[radical]p + log(p)), independent of the matrix sparsity pattern. The performance of the algorithm is demonstrated by employing it as the kernel in the well-known NAS conjugate gradient benchmark, where a run time of 6.09 seconds was observed. This is the best published performance on this benchmark achieved to date using a massively parallel supercomputer.

Allele-specific cytokine responses at the HLA-C locus, implications for psoriasis

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Hundhausen, Christian; Bertoni, Anna; Mak, Rose K; Botti, Elisabetta; Di Meglio, Paola; Clop, Alex; Laggner, Ute; Chimenti, Sergio; Hayday, Adrian C; Barker, Jonathan N; Trembath, Richard C; Capon, Francesca; Nestle, Frank O

2011-01-01

Psoriasis is an inflammatory skin disorder that is inherited as a complex trait. Genetic studies have repeatedly highlighted HLA-C as the major determinant for psoriasis susceptibility, with the Cw*0602 allele conferring significant disease risk in a wide-range of populations. Despite the potential importance of HLA-C variation in psoriasis, either via an effect on peptide presentation or immuno-inhibitory activity, allele-specific expression patterns have not been investigated. Here, we used reporter assays to characterize two regulatory variants, which virtually abolished the response to TNF-α (rs2524094) and IFN-γ (rs10657191) in HLA-Cw*0602 and a cluster of related alleles. We validated these findings through the analysis of HLA-Cw*0602 expression in primary keratinocytes treated with TNF-α and IFN-γ. Finally, we showed that HLA-Cw*0602 transcripts are not increased in psoriatic skin lesions, despite highly elevated TNF-α levels. Thus, our findings demonstrate the presence of allele-specific differences in HLA-C expression and indicate that HLA-Cw*0602 is unresponsive to up-regulation by key pro-inflammatory cytokines in psoriasis. These data pave the way for functional studies into the pathogenic role of the major psoriasis susceptibility allele. PMID:22113476

Allele-specific cytokine responses at the HLA-C locus: implications for psoriasis.

Science.gov (United States)

Hundhausen, Christian; Bertoni, Anna; Mak, Rose K; Botti, Elisabetta; Di Meglio, Paola; Clop, Alex; Laggner, Ute; Chimenti, Sergio; Hayday, Adrian C; Barker, Jonathan N; Trembath, Richard C; Capon, Francesca; Nestle, Frank O

2012-03-01

Psoriasis is an inflammatory skin disorder that is inherited as a complex trait. Genetic studies have repeatedly highlighted HLA-C as the major determinant for psoriasis susceptibility, with the Cw*0602 allele conferring significant disease risk in a wide range of populations. Despite the potential importance of HLA-C variation in psoriasis, either via an effect on peptide presentation or immuno-inhibitory activity, allele-specific expression patterns have not been investigated. Here, we used reporter assays to characterize two regulatory variants, which virtually abolished the response to tumor necrosis factor (TNF)-α (rs2524094) and IFN-γ (rs10657191) in HLA-Cw*0602 and a cluster of related alleles. We validated these findings through the analysis of HLA-Cw*0602 expression in primary keratinocytes treated with TNF-α and IFN-γ. Finally, we showed that HLA-Cw*0602 transcripts are not increased in psoriatic skin lesions, despite highly elevated TNF-α levels. Thus, our findings demonstrate the presence of allele-specific differences in HLA-C expression and indicate that HLA-Cw*0602 is unresponsive to upregulation by key proinflammatory cytokines in psoriasis. These data pave the way for functional studies into the pathogenic role of the major psoriasis susceptibility allele.

Allele-specific deletions in mouse tumors identify Fbxw7 as germline modifier of tumor susceptibility.

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Jesus Perez-Losada

Full Text Available Genome-wide association studies (GWAS have been successful in finding associations between specific genetic variants and cancer susceptibility in human populations. These studies have identified a range of highly statistically significant associations between single nucleotide polymorphisms (SNPs and susceptibility to development of a range of human tumors. However, the effect of each SNP in isolation is very small, and all of the SNPs combined only account for a relatively minor proportion of the total genetic risk (5-10%. There is therefore a major requirement for alternative routes to the discovery of genetic risk factors for cancer. We have previously shown using mouse models that chromosomal regions harboring susceptibility genes identified by linkage analysis frequently exhibit allele-specific genetic alterations in tumors. We demonstrate here that the Fbxw7 gene, a commonly mutated gene in a wide range of mouse and human cancers, shows allele-specific deletions in mouse lymphomas and skin tumors. Lymphomas from three different F1 hybrids show 100% allele-specificity in the patterns of allelic loss. Parental alleles from 129/Sv or Spretus/Gla mice are lost in tumors from F1 hybrids with C57BL/6 animals, due to the presence of a specific non-synonymous coding sequence polymorphism at the N-terminal portion of the gene. A specific genetic test of association between this SNP and lymphoma susceptibility in interspecific backcross mice showed a significant linkage (p = 0.001, but only in animals with a functional p53 gene. These data therefore identify Fbxw7 as a p53-dependent tumor susceptibility gene. Increased p53-dependent tumor susceptibility and allele-specific losses were also seen in a mouse skin model of skin tumor development. We propose that analysis of preferential allelic imbalances in tumors may provide an efficient means of uncovering genetic variants that affect mouse and human tumor susceptibility.

The Pleiotropic Phenotype of Apc Mutations in the Mouse: Allele Specificity and Effects of the Genetic Background

Science.gov (United States)

Halberg, Richard B.; Chen, Xiaodi; Amos-Landgraf, James M.; White, Alanna; Rasmussen, Kristin; Clipson, Linda; Pasch, Cheri; Sullivan, Ruth; Pitot, Henry C.; Dove, William F.

2008-01-01

Familial adenomatous polyposis (FAP) is a human cancer syndrome characterized by the development of hundreds to thousands of colonic polyps and extracolonic lesions including desmoid fibromas, osteomas, epidermoid cysts, and congenital hypertrophy of the pigmented retinal epithelium. Afflicted individuals are heterozygous for mutations in the APC gene. Detailed investigations of mice heterozygous for mutations in the ortholog Apc have shown that other genetic factors strongly influence the phenotype. Here we report qualitative and quantitative modifications of the phenotype of Apc mutants as a function of three genetic variables: Apc allele, p53 allele, and genetic background. We have found major differences between the Apc alleles Min and 1638N in multiplicity and regionality of intestinal tumors, as well as in incidence of extracolonic lesions. By contrast, Min mice homozygous for either of two different knockout alleles of p53 show similar phenotypic effects. These studies illustrate the classic principle that functional genetics is enriched by assessing penetrance and expressivity with allelic series. The mouse permits study of an allelic gene series on multiple genetic backgrounds, thereby leading to a better understanding of gene action in a range of biological processes. PMID:18723878

Parallel routes of human carcinoma development: implications of the age-specific incidence data.

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James P Brody

Full Text Available BACKGROUND: The multi-stage hypothesis suggests that cancers develop through a single defined series of genetic alterations. This hypothesis was first suggested over 50 years ago based upon age-specific incidence data. However, recent molecular studies of tumors indicate that multiple routes exist to the formation of cancer, not a single route. This parallel route hypothesis has not been tested with age-specific incidence data. METHODOLOGY/PRINCIPAL FINDINGS: To test the parallel route hypothesis, I formulated it in terms of a mathematical equation and then tested whether this equation was consistent with age-specific incidence data compiled by the Surveillance Epidemiology and End Results (SEER cancer registries since 1973. I used the chi-squared goodness of fit test to measure consistency. The age-specific incidence data from most human carcinomas, including those of the colon, lung, prostate, and breast were consistent with the parallel route hypothesis. However, this hypothesis is only consistent if an immune sub-population exists, one that will never develop carcinoma. Furthermore, breast carcinoma has two distinct forms of the disease, and one of these occurs at significantly different rates in different racial groups. CONCLUSIONS/SIGNIFICANCE: I conclude that the parallel route hypothesis is consistent with the age-specific incidence data only if carcinoma occurs in a distinct sub population, while the multi-stage hypothesis is inconsistent with this data.

Simultaneous SNP identification and assessment of allele-specific bias from ChIP-seq data

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Ni Yunyun

2012-09-01

Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs have been associated with many aspects of human development and disease, and many non-coding SNPs associated with disease risk are presumed to affect gene regulation. We have previously shown that SNPs within transcription factor binding sites can affect transcription factor binding in an allele-specific and heritable manner. However, such analysis has relied on prior whole-genome genotypes provided by large external projects such as HapMap and the 1000 Genomes Project. This requirement limits the study of allele-specific effects of SNPs in primary patient samples from diseases of interest, where complete genotypes are not readily available. Results In this study, we show that we are able to identify SNPs de novo and accurately from ChIP-seq data generated in the ENCODE Project. Our de novo identified SNPs from ChIP-seq data are highly concordant with published genotypes. Independent experimental verification of more than 100 sites estimates our false discovery rate at less than 5%. Analysis of transcription factor binding at de novo identified SNPs revealed widespread heritable allele-specific binding, confirming previous observations. SNPs identified from ChIP-seq datasets were significantly enriched for disease-associated variants, and we identified dozens of allele-specific binding events in non-coding regions that could distinguish between disease and normal haplotypes. Conclusions Our approach combines SNP discovery, genotyping and allele-specific analysis, but is selectively focused on functional regulatory elements occupied by transcription factors or epigenetic marks, and will therefore be valuable for identifying the functional regulatory consequences of non-coding SNPs in primary disease samples.

Allele-specific physical interactions regulate the heterotic traits in hybrids of Arabidopsis thaliana ecotypes

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Babita Singh

2017-10-01

Full Text Available Heterosis is an important phenomenon for the breeding in agricultural crops as it influences yield related traits such as biomass yield, seed number and weight, adaptive and reproductive traits. However, the level of heterosis greatly varies for different traits and different genotypes. The present study focuses on identification of physical interactions between alleles and their role in transcriptional regulation in heterotic plants. Here, we used two Arabidopsis ecotypes; Col-0 and C24 as parent for crosses. We performed crossing between these ecotypes and screened the F1 hybrids on the basis of different SSR markers. Further, we used Hi-C to capture intra- and inter-chromosomal physical interactions between alleles on genome-wide level. Then, we identified allele-specific chromatin interactions and constructed genome-wide allele-specific contact maps at different resolutions for the entire chromosome. We also performed RNA-seq of hybrids and their parents. RNA-seq analysis identified several differentially expressed genes and non-additively expressed genes in hybrids with respect to their parents. Further, to understand the biological significance of these chromatin interactions, we annotated these interactions and correlated with the transcriptome data. Thus, our study provides alleles-specific chromatin interactions in genome-wide fashion which play a crucial role in regulation of different genes that may be important for heterosis.

Sex-specific allelic transmission bias suggests sexual conflict at MC1R.

Science.gov (United States)

Ducret, Valérie; Gaigher, Arnaud; Simon, Céline; Goudet, Jérôme; Roulin, Alexandre

2016-09-01

Sexual conflict arises when selection in one sex causes the displacement of the other sex from its phenotypic optimum, leading to an inevitable tension within the genome - called intralocus sexual conflict. Although the autosomal melanocortin-1-receptor gene (MC1R) can generate colour variation in sexually dichromatic species, most previous studies have not considered the possibility that MC1R may be subject to sexual conflict. In the barn owl (Tyto alba), the allele MC1RWHITE is associated with whitish plumage coloration, typical of males, and the allele MC1RRUFOUS is associated with dark rufous coloration, typical of females, although each sex can express any phenotype. Because each colour variant is adapted to specific environmental conditions, the allele MC1RWHITE may be more strongly selected in males and the allele MC1RRUFOUS in females. We therefore investigated whether MC1R genotypes are in excess or deficit in male and female fledglings compared with the expected Hardy-Weinberg proportions. Our results show an overall deficit of 7.5% in the proportion of heterozygotes in males and of 12.9% in females. In males, interannual variation in assortative pairing with respect to MC1R explained the year-specific deviations from Hardy-Weinberg proportions, whereas in females, the deficit was better explained by the interannual variation in the probability of inheriting the MC1RWHITE or MC1RRUFOUS allele. Additionally, we observed that sons inherit the MC1RRUFOUS allele from their fathers on average slightly less often than expected under the first Mendelian law. Transmission ratio distortion may be adaptive in this sexually dichromatic species if males and females are, respectively, selected to display white and rufous plumages. © 2016 John Wiley & Sons Ltd.

A small asparagine-rich protein required for S-allele-specific pollen rejection in Nicotiana.

Science.gov (United States)

McClure, B; Mou, B; Canevascini, S; Bernatzky, R

1999-11-09

Although S-locus RNases (S-RNases) determine the specificity of pollen rejection in self-incompatible (SI) solanaceous plants, they alone are not sufficient to cause S-allele-specific pollen rejection. To identify non-S-RNase sequences that are required for pollen rejection, a Nicotiana alata cDNA library was screened by differential hybridization. One clone, designated HT, hybridized strongly to RNA from N. alata styles but not to RNA from Nicotiana plumbaginifolia, a species known to lack one or more factors necessary for S-allele-specific pollen rejection. Sequence analysis revealed a 101-residue ORF including a putative secretion signal and an asparagine-rich domain near the C terminus. RNA blot analysis showed that the HT-transcript accumulates in the stigma and style before anthesis. The timing of HT-expression lags slightly behind S(C10)-RNase in SI N. alata S(C10)S(C10) and is well correlated with the onset of S-allele-specific pollen rejection in the style. An antisense-HT construct was prepared to test for a role in pollen rejection. Transformed (N. plumbaginifolia x SI N. alata S(C10)S(C10)) hybrids with reduced levels of HT-protein continued to express S(C10)-RNase but failed to reject S(C10)-pollen. Control hybrids expressing both S(C10)-RNase and HT-protein showed a normal S-allele-specific pollen rejection response. We conclude that HT-protein is directly implicated in pollen rejection.

Tumor transcriptome sequencing reveals allelic expression imbalances associated with copy number alterations.

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Brian B Tuch

Full Text Available Due to growing throughput and shrinking cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide study of gene expression and copy number alterations in primary tumors. The sequencing of transcripts (RNA-Seq should offer several advantages over microarray-based methods, including the ability to detect somatic mutations and accurately measure allele-specific expression. To investigate these advantages we have applied a novel, strand-specific RNA-Seq method to tumors and matched normal tissue from three patients with oral squamous cell carcinomas. Additionally, to better understand the genomic determinants of the gene expression changes observed, we have sequenced the tumor and normal genomes of one of these patients. We demonstrate here that our RNA-Seq method accurately measures allelic imbalance and that measurement on the genome-wide scale yields novel insights into cancer etiology. As expected, the set of genes differentially expressed in the tumors is enriched for cell adhesion and differentiation functions, but, unexpectedly, the set of allelically imbalanced genes is also enriched for these same cancer-related functions. By comparing the transcriptomic perturbations observed in one patient to his underlying normal and tumor genomes, we find that allelic imbalance in the tumor is associated with copy number mutations and that copy number mutations are, in turn, strongly associated with changes in transcript abundance. These results support a model in which allele-specific deletions and duplications drive allele-specific changes in gene expression in the developing tumor.

Parallel object-oriented specification language

NARCIS (Netherlands)

Florescu, O.; Voeten, J.P.M.; Theelen, B.D.; Geilen, M.C.W.; Corporaal, H.; Burns, Alan

2008-01-01

The Parallel Object-Oriented Specification Language (POOSL) is an expressive modelling language for hardware/software systems [10]. It was originally defined in [7] as an object-oriented extension of process algebra CCS [6], supporting (conditional) synchronous message passing between

Parallel Beam-Beam Simulation Incorporating Multiple Bunches and Multiple Interaction Regions

CERN Document Server

Jones, F W; Pieloni, T

2007-01-01

The simulation code COMBI has been developed to enable the study of coherent beam-beam effects in the full collision scenario of the LHC, with multiple bunches interacting at multiple crossing points over many turns. The program structure and input are conceived in a general way which allows arbitrary numbers and placements of bunches and interaction points (IP's), together with procedural options for head-on and parasitic collisions (in the strong-strong sense), beam transport, statistics gathering, harmonic analysis, and periodic output of simulation data. The scale of this problem, once we go beyond the simplest case of a pair of bunches interacting once per turn, quickly escalates into the parallel computing arena, and herein we will describe the construction of an MPI-based version of COMBI able to utilize arbitrary numbers of processors to support efficient calculation of multi-bunch multi-IP interactions and transport. Implementing the parallel version did not require extensive disruption of the basic ...

Typing for HLA-DPB1*03 and HLA-DPB1*06 using allele-specific DNA in vitro amplification and allele-specific oligonucleotide probes. Detection of "new" DPB1*06 variants

DEFF Research Database (Denmark)

Fugger, L; Morling, N; Ryder, L P

1989-01-01

DP gene typing using in vitro DNA amplification combined with sequence-specific oligonucleotide probes has recently been reported. The resulting DNA amplification was specific for the HLA-DPB locus. Typing for the individual DPB alleles was exclusively dependent on the hybridizations of the probe...

Allele-specific gene expression in a wild nonhuman primate population

Science.gov (United States)

Tung, J.; Akinyi, M. Y.; Mutura, S.; Altmann, J.; Wray, G. A.; Alberts, S. C.

2015-01-01

Natural populations hold enormous potential for evolutionary genetic studies, especially when phenotypic, genetic and environmental data are all available on the same individuals. However, untangling the genotype-phenotype relationship in natural populations remains a major challenge. Here, we describe results of an investigation of one class of phenotype, allele-specific gene expression (ASGE), in the well-studied natural population of baboons of the Amboseli basin, Kenya. ASGE measurements identify cases in which one allele of a gene is overexpressed relative to the alternative allele of the same gene, within individuals, thus providing a control for background genetic and environmental effects. Here, we characterize the incidence of ASGE in the Amboseli baboon population, focusing on the genetic and environmental contributions to ASGE in a set of eleven genes involved in immunity and defence. Within this set, we identify evidence for common ASGE in four genes. We also present examples of two relationships between cis-regulatory genetic variants and the ASGE phenotype. Finally, we identify one case in which this relationship is influenced by a novel gene-environment interaction. Specifically, the dominance rank of an individual’s mother during its early life (an aspect of that individual’s social environment) influences the expression of the gene CCL5 via an interaction with cis-regulatory genetic variation. These results illustrate how environmental and ecological data can be integrated into evolutionary genetic studies of functional variation in natural populations. They also highlight the potential importance of early life environmental variation in shaping the genetic architecture of complex traits in wild mammals. PMID:21226779

Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations.

Science.gov (United States)

Jeselsohn, Rinath; Bergholz, Johann S; Pun, Matthew; Cornwell, MacIntosh; Liu, Weihan; Nardone, Agostina; Xiao, Tengfei; Li, Wei; Qiu, Xintao; Buchwalter, Gilles; Feiglin, Ariel; Abell-Hart, Kayley; Fei, Teng; Rao, Prakash; Long, Henry; Kwiatkowski, Nicholas; Zhang, Tinghu; Gray, Nathanael; Melchers, Diane; Houtman, Rene; Liu, X Shirley; Cohen, Ofir; Wagle, Nikhil; Winer, Eric P; Zhao, Jean; Brown, Myles

2018-02-12

Estrogen receptor α (ER) ligand-binding domain (LBD) mutations are found in a substantial number of endocrine treatment-resistant metastatic ER-positive (ER + ) breast cancers. We investigated the chromatin recruitment, transcriptional network, and genetic vulnerabilities in breast cancer models harboring the clinically relevant ER mutations. These mutants exhibit both ligand-independent functions that mimic estradiol-bound wild-type ER as well as allele-specific neomorphic properties that promote a pro-metastatic phenotype. Analysis of the genome-wide ER binding sites identified mutant ER unique recruitment mediating the allele-specific transcriptional program. Genetic screens identified genes that are essential for the ligand-independent growth driven by the mutants. These studies provide insights into the mechanism of endocrine therapy resistance engendered by ER mutations and potential therapeutic targets. Copyright © 2018 Elsevier Inc. All rights reserved.

Multiple Independent File Parallel I/O with HDF5

Energy Technology Data Exchange (ETDEWEB)

Miller, M. C.

2016-07-13

The HDF5 library has supported the I/O requirements of HPC codes at Lawrence Livermore National Labs (LLNL) since the late 90’s. In particular, HDF5 used in the Multiple Independent File (MIF) parallel I/O paradigm has supported LLNL code’s scalable I/O requirements and has recently been gainfully used at scales as large as O(10⁶) parallel tasks.

Functional PMS2 hybrid alleles containing a pseudogene-specific missense variant trace back to a single ancient intrachromosomal recombination event.

Science.gov (United States)

Ganster, Christina; Wernstedt, Annekatrin; Kehrer-Sawatzki, Hildegard; Messiaen, Ludwine; Schmidt, Konrad; Rahner, Nils; Heinimann, Karl; Fonatsch, Christa; Zschocke, Johannes; Wimmer, Katharina

2010-05-01

Sequence exchange between PMS2 and its pseudogene PMS2CL, embedded in an inverted duplication on chromosome 7p22, has been reported to be an ongoing process that leads to functional PMS2 hybrid alleles containing PMS2- and PMS2CL-specific sequence variants at the 5'-and the 3'-end, respectively. The frequency of PMS2 hybrid alleles, their biological significance, and the mechanisms underlying their formation are largely unknown. Here we show that overall hybrid alleles account for one-third of 384 PMS2 alleles analyzed in individuals of different ethnic backgrounds. Depending on the population, 14-60% of hybrid alleles carry PMS2CL-specific sequences in exons 13-15, the remainder only in exon 15. We show that exons 13-15 hybrid alleles, named H1 hybrid alleles, constitute different haplotypes but trace back to a single ancient intrachromosomal recombination event with crossover. Taking advantage of an ancestral sequence variant specific for all H1 alleles we developed a simple gDNA-based polymerase chain reaction (PCR) assay that can be used to identify H1-allele carriers with high sensitivity and specificity (100 and 99%, respectively). Because H1 hybrid alleles harbor missense variant p.N775S of so far unknown functional significance, we assessed the H1-carrier frequency in 164 colorectal cancer patients. So far, we found no indication that the variant plays a major role with regard to cancer susceptibility. (c) 2010 Wiley-Liss, Inc.

Impact of pre-existing MSP142-allele specific immunity on potency of an erythrocytic Plasmodium falciparum vaccine

Directory of Open Access Journals (Sweden)

Bergmann-Leitner Elke S

2012-09-01

Full Text Available Abstract Background MSP1 is the major surface protein on merozoites and a prime candidate for a blood stage malaria vaccine. Preclinical and seroepidemiological studies have implicated antibodies to MSP1 in protection against blood stage parasitaemia and/or reduced parasite densities, respectively. Malaria endemic areas have multiple strains of Plasmodium falciparum circulating at any given time, giving rise to complex immune responses, an issue which is generally not addressed in clinical trials conducted in non-endemic areas. A lack of understanding of the effect of pre-existing immunity to heterologous parasite strains may significantly contribute to vaccine failure in the field. The purpose of this study was to model the effect of pre-existing immunity to MSP142 on the immunogenicity of blood-stage malaria vaccines based on alternative MSP1 alleles. Methods Inbred and outbred mice were immunized with various recombinant P. falciparum MSP142 proteins that represent the two major alleles of MSP142, MAD20 (3D7 and Wellcome (K1, FVO. Humoral immune responses were analysed by ELISA and LuminexTM, and functional activity of induced MSP142-specific antibodies was assessed by growth inhibition assays. T-cell responses were characterized using ex vivo ELISpot assays. Results Analysis of the immune responses induced by various immunization regimens demonstrated a strong allele-specific response at the T cell level in both inbred and outbred mice. The success of heterologous regimens depended on the degree of homology of the N-terminal p33 portion of the MSP142, likely due to the fact that most T cell epitopes reside in this part of the molecule. Analysis of humoral immune responses revealed a marked cross-reactivity between the alleles. Functional analyses showed that some of the heterologous regimens induced antibodies with improved growth inhibitory activities. Conclusion The development of a more broadly efficacious MSP1 based vaccine may be

High-specificity detection of rare alleles with Paired-End Low Error Sequencing (PELE-Seq).

Science.gov (United States)

Preston, Jessica L; Royall, Ariel E; Randel, Melissa A; Sikkink, Kristin L; Phillips, Patrick C; Johnson, Eric A

2016-06-14

Polymorphic loci exist throughout the genomes of a population and provide the raw genetic material needed for a species to adapt to changes in the environment. The minor allele frequencies of rare Single Nucleotide Polymorphisms (SNPs) within a population have been difficult to track with Next-Generation Sequencing (NGS), due to the high error rate of standard methods such as Illumina sequencing. We have developed a wet-lab protocol and variant-calling method that identifies both sequencing and PCR errors, called Paired-End Low Error Sequencing (PELE-Seq). To test the specificity and sensitivity of the PELE-Seq method, we sequenced control E. coli DNA libraries containing known rare alleles present at frequencies ranging from 0.2-0.4 % of the total reads. PELE-Seq had higher specificity and sensitivity than standard libraries. We then used PELE-Seq to characterize rare alleles in a Caenorhabditis remanei nematode worm population before and after laboratory adaptation, and found that minor and rare alleles can undergo large changes in frequency during lab-adaptation. We have developed a method of rare allele detection that mitigates both sequencing and PCR errors, called PELE-Seq. PELE-Seq was evaluated using control E. coli populations and was then used to compare a wild C. remanei population to a lab-adapted population. The PELE-Seq method is ideal for investigating the dynamics of rare alleles in a broad range of reduced-representation sequencing methods, including targeted amplicon sequencing, RAD-Seq, ddRAD, and GBS. PELE-Seq is also well-suited for whole genome sequencing of mitochondria and viruses, and for high-throughput rare mutation screens.

Hierarchical Parallel Matrix Multiplication on Large-Scale Distributed Memory Platforms

KAUST Repository

Quintin, Jean-Noel

2013-10-01

Matrix multiplication is a very important computation kernel both in its own right as a building block of many scientific applications and as a popular representative for other scientific applications. Cannon\\'s algorithm which dates back to 1969 was the first efficient algorithm for parallel matrix multiplication providing theoretically optimal communication cost. However this algorithm requires a square number of processors. In the mid-1990s, the SUMMA algorithm was introduced. SUMMA overcomes the shortcomings of Cannon\\'s algorithm as it can be used on a nonsquare number of processors as well. Since then the number of processors in HPC platforms has increased by two orders of magnitude making the contribution of communication in the overall execution time more significant. Therefore, the state of the art parallel matrix multiplication algorithms should be revisited to reduce the communication cost further. This paper introduces a new parallel matrix multiplication algorithm, Hierarchical SUMMA (HSUMMA), which is a redesign of SUMMA. Our algorithm reduces the communication cost of SUMMA by introducing a two-level virtual hierarchy into the two-dimensional arrangement of processors. Experiments on an IBM BlueGene/P demonstrate the reduction of communication cost up to 2.08 times on 2048 cores and up to 5.89 times on 16384 cores. © 2013 IEEE.

Hierarchical Parallel Matrix Multiplication on Large-Scale Distributed Memory Platforms

KAUST Repository

Quintin, Jean-Noel; Hasanov, Khalid; Lastovetsky, Alexey

2013-01-01

Matrix multiplication is a very important computation kernel both in its own right as a building block of many scientific applications and as a popular representative for other scientific applications. Cannon's algorithm which dates back to 1969 was the first efficient algorithm for parallel matrix multiplication providing theoretically optimal communication cost. However this algorithm requires a square number of processors. In the mid-1990s, the SUMMA algorithm was introduced. SUMMA overcomes the shortcomings of Cannon's algorithm as it can be used on a nonsquare number of processors as well. Since then the number of processors in HPC platforms has increased by two orders of magnitude making the contribution of communication in the overall execution time more significant. Therefore, the state of the art parallel matrix multiplication algorithms should be revisited to reduce the communication cost further. This paper introduces a new parallel matrix multiplication algorithm, Hierarchical SUMMA (HSUMMA), which is a redesign of SUMMA. Our algorithm reduces the communication cost of SUMMA by introducing a two-level virtual hierarchy into the two-dimensional arrangement of processors. Experiments on an IBM BlueGene/P demonstrate the reduction of communication cost up to 2.08 times on 2048 cores and up to 5.89 times on 16384 cores. © 2013 IEEE.

Detection of MPL mutations by a novel allele-specific PCR-based strategy.

Science.gov (United States)

Furtado, Larissa V; Weigelin, Helmut C; Elenitoba-Johnson, Kojo S J; Betz, Bryan L

2013-11-01

MPL mutation testing is recommended in patients with suspected primary myelofibrosis or essential thrombocythemia who lack the JAK2 V617F mutation. MPL mutations can occur at allelic levels below 15%, which may escape detection by commonly used mutation screening methods such as Sanger sequencing. We developed a novel multiplexed allele-specific PCR assay capable of detecting most recurrent MPL exon 10 mutations associated with primary myelofibrosis and essential thrombocythemia (W515L, W515K, W515A, and S505N) down to a sensitivity of 2.5% mutant allele. Test results were reviewed from 15 reference cases and 1380 consecutive specimens referred to our laboratory for testing. Assay performance was compared to Sanger sequencing across a series of 58 specimens with MPL mutations. Positive cases consisted of 45 with W515L, 6 with S505N, 5 with W515K, 1 with W515A, and 1 with both W515L and S505N. Seven cases had mutations below 5% that were undetected by Sanger sequencing. Ten additional cases had mutation levels between 5% and 15% that were not consistently detected by sequencing. All results were easily interpreted in the allele-specific test. This assay offers a sensitive and reliable solution for MPL mutation testing. Sanger sequencing appears insufficiently sensitive for robust MPL mutation detection. Our data also suggest the relative frequency of S505N mutations may be underestimated, highlighting the necessity for inclusion of this mutation in MPL test platforms. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Allele-Specific Alternative mRNA processing (ASARP) | Informatics Technology for Cancer Research (ITCR)

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A software pipeline for prediction of allele-specific alternative RNA processing events using single RNA-seq data. The current version focuses on prediction of alternative splicing and alternative polyadenylation modulated by genetic variants.

Use of allele-specific FAIRE to determine functional regulatory polymorphism using large-scale genotyping arrays.

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Andrew J P Smith

Full Text Available Following the widespread use of genome-wide association studies (GWAS, focus is turning towards identification of causal variants rather than simply genetic markers of diseases and traits. As a step towards a high-throughput method to identify genome-wide, non-coding, functional regulatory variants, we describe the technique of allele-specific FAIRE, utilising large-scale genotyping technology (FAIRE-gen to determine allelic effects on chromatin accessibility and regulatory potential. FAIRE-gen was explored using lymphoblastoid cells and the 50,000 SNP Illumina CVD BeadChip. The technique identified an allele-specific regulatory polymorphism within NR1H3 (coding for LXR-α, rs7120118, coinciding with a previously GWAS-identified SNP for HDL-C levels. This finding was confirmed using FAIRE-gen with the 200,000 SNP Illumina Metabochip and verified with the established method of TaqMan allelic discrimination. Examination of this SNP in two prospective Caucasian cohorts comprising 15,000 individuals confirmed the association with HDL-C levels (combined beta = 0.016; p = 0.0006, and analysis of gene expression identified an allelic association with LXR-α expression in heart tissue. Using increasingly comprehensive genotyping chips and distinct tissues for examination, FAIRE-gen has the potential to aid the identification of many causal SNPs associated with disease from GWAS.

An informational view of accession rarity and allele specificity in germplasm banks for management and conservation.

Science.gov (United States)

Reyes-Valdés, M Humberto; Burgueño, Juan; Singh, Sukhwinder; Martínez, Octavio; Sansaloni, Carolina Paola

2018-01-01

Germplasm banks are growing in their importance, number of accessions and amount of characterization data, with a large emphasis on molecular genetic markers. In this work, we offer an integrated view of accessions and marker data in an information theory framework. The basis of this development is the mutual information between accessions and allele frequencies for molecular marker loci, which can be decomposed in allele specificities, as well as in rarity and divergence of accessions. In this way, formulas are provided to calculate the specificity of the different marker alleles with reference to their distribution across accessions, accession rarity, defined as the weighted average of the specificity of its alleles, and divergence, defined by the Kullback-Leibler formula. Albeit being different measures, it is demonstrated that average rarity and divergence are equal for any collection. These parameters can contribute to the knowledge of the structure of a germplasm collection and to make decisions about the preservation of rare variants. The concepts herein developed served as the basis for a strategy for core subset selection called HCore, implemented in a publicly available R script. As a proof of concept, the mathematical view and tools developed in this research were applied to a large collection of Mexican wheat accessions, widely characterized by SNP markers. The most specific alleles were found to be private of a single accession, and the distribution of this parameter had its highest frequencies at low levels of specificity. Accession rarity and divergence had largely symmetrical distributions, and had a positive, albeit non-strictly linear relationship. Comparison of the HCore approach for core subset selection, with three state-of-the-art methods, showed it to be superior for average divergence and rarity, mean genetic distance and diversity. The proposed approach can be used for knowledge extraction and decision making in germplasm collections of

Parallel magnetotransport in multiple quantum well structures

International Nuclear Information System (INIS)

Sheregii, E.M.; Ploch, D.; Marchewka, M.; Tomaka, G.; Kolek, A.; Stadler, A.; Mleczko, K.; Strupinski, W.; Jasik, A.; Jakiela, R.

2004-01-01

The results of investigations of parallel magnetotransport in AlGaAs/GaAs and InGaAs/InAlAs/InP multiple quantum wells structures (MQW's) are presented in this paper. The MQW's were obtained by metalorganic vapour phase epitaxy with different shapes of QW, numbers of QW and levels of doping. The magnetotransport measurements were performed in wide region of temperatures (0.5-300 K) and at high magnetic fields up to 30 T (B is perpendicular and current is parallel to the plane of the QW). Three types of observed effects are analyzed: quantum Hall effect and Shubnikov-de Haas oscillations at low temperatures (0.5-6 K) as well as magnetophonon resonance at higher temperatures (77-300 K)

High-throughput analysis of candidate imprinted genes and allele-specific gene expression in the human term placenta

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Clark Taane G

2010-04-01

Full Text Available Abstract Background Imprinted genes show expression from one parental allele only and are important for development and behaviour. This extreme mode of allelic imbalance has been described for approximately 56 human genes. Imprinting status is often disrupted in cancer and dysmorphic syndromes. More subtle variation of gene expression, that is not parent-of-origin specific, termed 'allele-specific gene expression' (ASE is more common and may give rise to milder phenotypic differences. Using two allele-specific high-throughput technologies alongside bioinformatics predictions, normal term human placenta was screened to find new imprinted genes and to ascertain the extent of ASE in this tissue. Results Twenty-three family trios of placental cDNA, placental genomic DNA (gDNA and gDNA from both parents were tested for 130 candidate genes with the Sequenom MassArray system. Six genes were found differentially expressed but none imprinted. The Illumina ASE BeadArray platform was then used to test 1536 SNPs in 932 genes. The array was enriched for the human orthologues of 124 mouse candidate genes from bioinformatics predictions and 10 human candidate imprinted genes from EST database mining. After quality control pruning, a total of 261 informative SNPs (214 genes remained for analysis. Imprinting with maternal expression was demonstrated for the lymphocyte imprinted gene ZNF331 in human placenta. Two potential differentially methylated regions (DMRs were found in the vicinity of ZNF331. None of the bioinformatically predicted candidates tested showed imprinting except for a skewed allelic expression in a parent-specific manner observed for PHACTR2, a neighbour of the imprinted PLAGL1 gene. ASE was detected for two or more individuals in 39 candidate genes (18%. Conclusions Both Sequenom and Illumina assays were sensitive enough to study imprinting and strong allelic bias. Previous bioinformatics approaches were not predictive of new imprinted genes

GenPlay Multi-Genome, a tool to compare and analyze multiple human genomes in a graphical interface.

Science.gov (United States)

Lajugie, Julien; Fourel, Nicolas; Bouhassira, Eric E

2015-01-01

Parallel visualization of multiple individual human genomes is a complex endeavor that is rapidly gaining importance with the increasing number of personal, phased and cancer genomes that are being generated. It requires the display of variants such as SNPs, indels and structural variants that are unique to specific genomes and the introduction of multiple overlapping gaps in the reference sequence. Here, we describe GenPlay Multi-Genome, an application specifically written to visualize and analyze multiple human genomes in parallel. GenPlay Multi-Genome is ideally suited for the comparison of allele-specific expression and functional genomic data obtained from multiple phased genomes in a graphical interface with access to multiple-track operation. It also allows the analysis of data that have been aligned to custom genomes rather than to a standard reference and can be used as a variant calling format file browser and as a tool to compare different genome assembly, such as hg19 and hg38. GenPlay is available under the GNU public license (GPL-3) from http://genplay.einstein.yu.edu. The source code is available at https://github.com/JulienLajugie/GenPlay. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Interactions Between SNP Alleles at Multiple Loci and Variation in Skin Pigmentation in 122 Caucasians

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Sumiko Anno

2007-01-01

Full Text Available This study was undertaken to clarify the molecular basis for human skin color variation and the environmental adaptability to ultraviolet irradiation, with the ultimate goal of predicting the impact of changes in future environments on human health risk. One hundred twenty-two Caucasians living in Toledo, Ohio participated. Back and cheek skin were assayed for melanin as a quantitative trait marker. Buccal cell samples were collected and used for DNA extraction. DNA was used for SNP genotyping using the Masscode™ system, which entails two-step PCR amplification and a platform chemistry which allows cleavable mass spectrometry tags. The results show gene-gene interaction between SNP alleles at multiple loci (not necessarily on the same chromosome contributes to inter-individual skin color variation while suggesting a high probability of linkage disequilibrium. Confirmation of these findings requires further study with other ethic groups to analyze the associations between SNP alleles at multiple loci and human skin color variation. Our overarching goal is to use remote sensing data to clarify the interaction between atmospheric environments and SNP allelic frequency and investigate human adaptability to ultraviolet irradiation. Such information should greatly assist in the prediction of the health effects of future environmental changes such as ozone depletion and increased ultraviolet exposure. If such health effects are to some extent predictable, it might be possible to prepare for such changes in advance and thus reduce the extent of their impact.

The specificity of learned parallelism in dual-memory retrieval.

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Strobach, Tilo; Schubert, Torsten; Pashler, Harold; Rickard, Timothy

2014-05-01

Retrieval of two responses from one visually presented cue occurs sequentially at the outset of dual-retrieval practice. Exclusively for subjects who adopt a mode of grouping (i.e., synchronizing) their response execution, however, reaction times after dual-retrieval practice indicate a shift to learned retrieval parallelism (e.g., Nino & Rickard, in Journal of Experimental Psychology: Learning, Memory, and Cognition, 29, 373-388, 2003). In the present study, we investigated how this learned parallelism is achieved and why it appears to occur only for subjects who group their responses. Two main accounts were considered: a task-level versus a cue-level account. The task-level account assumes that learned retrieval parallelism occurs at the level of the task as a whole and is not limited to practiced cues. Grouping response execution may thus promote a general shift to parallel retrieval following practice. The cue-level account states that learned retrieval parallelism is specific to practiced cues. This type of parallelism may result from cue-specific response chunking that occurs uniquely as a consequence of grouped response execution. The results of two experiments favored the second account and were best interpreted in terms of a structural bottleneck model.

The level 1 and 2 specification for parallel benchmark and a benchmark test of scalar-parallel computer SP2 based on the specifications

International Nuclear Information System (INIS)

Orii, Shigeo

1998-06-01

A benchmark specification for performance evaluation of parallel computers for numerical analysis is proposed. Level 1 benchmark, which is a conventional type benchmark using processing time, measures performance of computers running a code. Level 2 benchmark proposed in this report is to give the reason of the performance. As an example, scalar-parallel computer SP2 is evaluated with this benchmark specification in case of a molecular dynamics code. As a result, the main causes to suppress the parallel performance are maximum band width and start-up time of communication between nodes. Especially the start-up time is proportional not only to the number of processors but also to the number of particles. (author)

On coding genotypes for genetic markers with multiple alleles in genetic association study of quantitative traits

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Wang Tao

2011-09-01

Full Text Available Abstract Background In genetic association study of quantitative traits using F∞ models, how to code the marker genotypes and interpret the model parameters appropriately is important for constructing hypothesis tests and making statistical inferences. Currently, the coding of marker genotypes in building F∞ models has mainly focused on the biallelic case. A thorough work on the coding of marker genotypes and interpretation of model parameters for F∞ models is needed especially for genetic markers with multiple alleles. Results In this study, we will formulate F∞ genetic models under various regression model frameworks and introduce three genotype coding schemes for genetic markers with multiple alleles. Starting from an allele-based modeling strategy, we first describe a regression framework to model the expected genotypic values at given markers. Then, as extension from the biallelic case, we introduce three coding schemes for constructing fully parameterized one-locus F∞ models and discuss the relationships between the model parameters and the expected genotypic values. Next, under a simplified modeling framework for the expected genotypic values, we consider several reduced one-locus F∞ models from the three coding schemes on the estimability and interpretation of their model parameters. Finally, we explore some extensions of the one-locus F∞ models to two loci. Several fully parameterized as well as reduced two-locus F∞ models are addressed. Conclusions The genotype coding schemes provide different ways to construct F∞ models for association testing of multi-allele genetic markers with quantitative traits. Which coding scheme should be applied depends on how convenient it can provide the statistical inferences on the parameters of our research interests. Based on these F∞ models, the standard regression model fitting tools can be used to estimate and test for various genetic effects through statistical contrasts with the

Deducing the pathogenic contribution of recessive ABCA4 alleles in an outbred population.

Science.gov (United States)

Schindler, Emily I; Nylen, Erik L; Ko, Audrey C; Affatigato, Louisa M; Heggen, Andrew C; Wang, Kai; Sheffield, Val C; Stone, Edwin M

2010-10-01

Accurate prediction of the pathogenic effects of specific genotypes is important for the design and execution of clinical trials as well as for meaningful counseling of individual patients. However, for many autosomal recessive diseases, it can be difficult to deduce the relative pathogenic contribution of individual alleles because relatively few affected individuals share the same two disease-causing variations. In this study, we used multiple regression analysis to estimate the pathogenicity of specific alleles of ABCA4 in patients with retinal phenotypes ranging from Stargardt disease to retinitis pigmentosa. This analysis revealed quantitative allelic effects on two aspects of the visual phenotype, visual acuity (P disease and will also aid in the optimal selection of subjects for clinical trials of new therapies.

Hybrid parallel execution model for logic-based specification languages

CERN Document Server

Tsai, Jeffrey J P

2001-01-01

Parallel processing is a very important technique for improving the performance of various software development and maintenance activities. The purpose of this book is to introduce important techniques for parallel executation of high-level specifications of software systems. These techniques are very useful for the construction, analysis, and transformation of reliable large-scale and complex software systems. Contents: Current Approaches; Overview of the New Approach; FRORL Requirements Specification Language and Its Decomposition; Rewriting and Data Dependency, Control Flow Analysis of a Lo

Rapid ABO genotyping by high-speed droplet allele-specific PCR using crude samples.

Science.gov (United States)

Taira, Chiaki; Matsuda, Kazuyuki; Takeichi, Naoya; Furukawa, Satomi; Sugano, Mitsutoshi; Uehara, Takeshi; Okumura, Nobuo; Honda, Takayuki

2018-01-01

ABO genotyping has common tools for personal identification of forensic and transplantation field. We developed a new method based on a droplet allele-specific PCR (droplet-AS-PCR) that enabled rapid PCR amplification. We attempted rapid ABO genotyping using crude DNA isolated from dried blood and buccal cells. We designed allele-specific primers for three SNPs (at nucleotides 261, 526, and 803) in exons 6 and 7 of the ABO gene. We pretreated dried blood and buccal cells with proteinase K, and obtained crude DNAs without DNA purification. Droplet-AS-PCR allowed specific amplification of the SNPs at the three loci using crude DNA, with results similar to those for DNA extracted from fresh peripheral blood. The sensitivity of the methods was 5%-10%. The genotyping of extracted DNA and crude DNA were completed within 8 and 9 minutes, respectively. The genotypes determined by the droplet-AS-PCR method were always consistent with those obtained by direct sequencing. The droplet-AS-PCR method enabled rapid and specific amplification of three SNPs of the ABO gene from crude DNA treated with proteinase K. ABO genotyping by the droplet-AS-PCR has the potential to be applied to various fields including a forensic medicine and transplantation medical care. © 2017 Wiley Periodicals, Inc.

SAAS-CNV: A Joint Segmentation Approach on Aggregated and Allele Specific Signals for the Identification of Somatic Copy Number Alterations with Next-Generation Sequencing Data.

Science.gov (United States)

Zhang, Zhongyang; Hao, Ke

2015-11-01

Cancer genomes exhibit profound somatic copy number alterations (SCNAs). Studying tumor SCNAs using massively parallel sequencing provides unprecedented resolution and meanwhile gives rise to new challenges in data analysis, complicated by tumor aneuploidy and heterogeneity as well as normal cell contamination. While the majority of read depth based methods utilize total sequencing depth alone for SCNA inference, the allele specific signals are undervalued. We proposed a joint segmentation and inference approach using both signals to meet some of the challenges. Our method consists of four major steps: 1) extracting read depth supporting reference and alternative alleles at each SNP/Indel locus and comparing the total read depth and alternative allele proportion between tumor and matched normal sample; 2) performing joint segmentation on the two signal dimensions; 3) correcting the copy number baseline from which the SCNA state is determined; 4) calling SCNA state for each segment based on both signal dimensions. The method is applicable to whole exome/genome sequencing (WES/WGS) as well as SNP array data in a tumor-control study. We applied the method to a dataset containing no SCNAs to test the specificity, created by pairing sequencing replicates of a single HapMap sample as normal/tumor pairs, as well as a large-scale WGS dataset consisting of 88 liver tumors along with adjacent normal tissues. Compared with representative methods, our method demonstrated improved accuracy, scalability to large cancer studies, capability in handling both sequencing and SNP array data, and the potential to improve the estimation of tumor ploidy and purity.

Harmonic resonance assessment of multiple paralleled grid-connected inverters system

DEFF Research Database (Denmark)

Wang, Yanbo; Wang, Xiongfei; Blaabjerg, Frede

2017-01-01

This paper presents an eigenvalue-based impedance stability analytical method of multiple paralleled grid-connected inverter system. Different from the conventional impedance-based stability criterion, this work first built the state-space model of paralleled grid-connected inverters. On the basis...... of this, a bridge between the state-space-based modelling and impedance-based stability criterion is presented. The proposed method is able to perform stability assessment locally at the connection points of the component. Meanwhile, the eigenvalue-based sensitivity analysis is adopted to identify...

Consequences for diversity when animals are prioritized for conservation of the whole genome or of one specific allele

NARCIS (Netherlands)

Engelsma, K.A.; Veerkamp, R.F.; Calus, M.P.L.; Windig, J.J.

2014-01-01

When animals are selected for one specific allele, for example for inclusion in a gene bank, this may result in the loss of diversity in other parts of the genome. The aim of this study was to quantify the risk of losing diversity across the genome when targeting a single allele for conservation

Allele-specific expression at the androgen receptor alpha gene in a hybrid unisexual fish, the Amazon molly (Poecilia formosa.

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Fangjun Zhu

Full Text Available The all-female Amazon molly (Poecilia formosa is the result of a hybridization of the Atlantic molly (P. mexicana and the sailfin molly (P. latipinna approximately 120,000 years ago. As a gynogenetic species, P. formosa needs to copulate with heterospecific males including males from one of its bisexual ancestral species. However, the sperm only triggers embryogenesis of the diploid eggs. The genetic information of the sperm donor typically will not contribute to the next generation of P. formosa. Hence, P. formosa possesses generally one allele from each of its ancestral species at any genetic locus. This raises the question whether both ancestral alleles are equally expressed in P. formosa. Allele-specific expression (ASE has been previously assessed in various organisms, e.g., human and fish, and ASE was found to be important in the context of phenotypic variability and disease. In this study, we utilized Real-Time PCR techniques to estimate ASE of the androgen receptor alpha (arα gene in several distinct tissues of Amazon mollies. We found an allelic bias favoring the maternal ancestor (P. mexicana allele in ovarian tissue. This allelic bias was not observed in the gill or the brain tissue. Sequencing of the promoter regions of both alleles revealed an association between an Indel in a known CpG island and differential expression. Future studies may reveal whether our observed cis-regulatory divergence is caused by an ovary-specific trans-regulatory element, preferentially activating the allele of the maternal ancestor.

SPEEDES - A multiple-synchronization environment for parallel discrete-event simulation

Science.gov (United States)

Steinman, Jeff S.

1992-01-01

Synchronous Parallel Environment for Emulation and Discrete-Event Simulation (SPEEDES) is a unified parallel simulation environment. It supports multiple-synchronization protocols without requiring users to recompile their code. When a SPEEDES simulation runs on one node, all the extra parallel overhead is removed automatically at run time. When the same executable runs in parallel, the user preselects the synchronization algorithm from a list of options. SPEEDES currently runs on UNIX networks and on the California Institute of Technology/Jet Propulsion Laboratory Mark III Hypercube. SPEEDES also supports interactive simulations. Featured in the SPEEDES environment is a new parallel synchronization approach called Breathing Time Buckets. This algorithm uses some of the conservative techniques found in Time Bucket synchronization, along with the optimism that characterizes the Time Warp approach. A mathematical model derived from first principles predicts the performance of Breathing Time Buckets. Along with the Breathing Time Buckets algorithm, this paper discusses the rules for processing events in SPEEDES, describes the implementation of various other synchronization protocols supported by SPEEDES, describes some new ones for the future, discusses interactive simulations, and then gives some performance results.

Somatic mutations, allele loss, and DNA methylation of the Cub and Sushi Multiple Domains 1 (CSMD1 gene reveals association with early age of diagnosis in colorectal cancer patients.

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Austin Y Shull

Full Text Available The Cub and Sushi Multiple Domains 1 (CSMD1 gene, located on the short arm of chromosome 8, codes for a type I transmembrane protein whose function is currently unknown. CSMD1 expression is frequently lost in many epithelial cancers. Our goal was to characterize the relationships between CSMD1 somatic mutations, allele imbalance, DNA methylation, and the clinical characteristics in colorectal cancer patients.We sequenced the CSMD1 coding regions in 54 colorectal tumors using the 454FLX pyrosequencing platform to interrogate 72 amplicons covering the entire coding sequence. We used heterozygous SNP allele ratios at multiple CSMD1 loci to determine allelic balance and infer loss of heterozygosity. Finally, we performed methylation-specific PCR on 76 colorectal tumors to determine DNA methylation status for CSMD1 and known methylation targets ALX4, RUNX3, NEUROG1, and CDKN2A.Using 454FLX sequencing and confirming with Sanger sequencing, 16 CSMD1 somatic mutations were identified in 6 of the 54 colorectal tumors (11%. The nonsynonymous to synonymous mutation ratio of the 16 somatic mutations was 15:1, a ratio significantly higher than the expected 2:1 ratio (p = 0.014. This ratio indicates a presence of positive selection for mutations in the CSMD1 protein sequence. CSMD1 allelic imbalance was present in 19 of 37 informative cases (56%. Patients with allelic imbalance and CSMD1 mutations were significantly younger (average age, 41 years than those without somatic mutations (average age, 68 years. The majority of tumors were methylated at one or more CpG loci within the CSMD1 coding sequence, and CSMD1 methylation significantly correlated with two known methylation targets ALX4 and RUNX3. C:G>T:A substitutions were significantly overrepresented (47%, suggesting extensive cytosine methylation predisposing to somatic mutations.Deep amplicon sequencing and methylation-specific PCR reveal that CSMD1 alterations can correlate with earlier clinical

Aberrant allele-specific replication, independent of parental origin, in blood cells of cancer patients

International Nuclear Information System (INIS)

Dotan, Zohar A; Dotan, Aviva; Ramon, Jacob; Avivi, Lydia

2008-01-01

Allelic counterparts of biallelically expressed genes display an epigenetic symmetry normally manifested by synchronous replication, different from genes subjected to monoallelic expression, which normally are characterized by an asynchronous mode of replication (well exemplified by the SNRPN imprinted locus). Malignancy was documented to be associated with gross modifications in the inherent replication-timing coordination between allelic counterparts of imprinted genes as well as of biallelically expressed loci. The cancer-related allelic replication timing aberrations are non-disease specific and appear in peripheral blood cells of cancer patients, including those with solid tumors. As such they offer potential blood markers for non-invasive cancer test. The present study was aimed to gain some insight into the mechanism leading to the replication timing alterations of genes in blood lymphocytes of cancer patients. Peripheral blood samples derived from patients with prostate cancer were chosen to represent the cancerous status, and samples taken from patients with no cancer but with benign prostate hyperplasia were used to portray the normal status. Fluorescence In Situ Hybridization (FISH) replication assay, applied to phytohemagglutinin (PHA)-stimulated blood lymphocytes, was used to evaluate the temporal order (either synchronous or asynchronous) of genes in the patients' cells. We demonstrated that: (i) the aberrant epigenetic profile, as delineated by the cancer status, is a reversible modification, evidenced by our ability to restore the normal patterns of replication in three unrelated loci (CEN15, SNRPN and RB1) by introducing an archetypical demethylating agent, 5-azacytidine; (ii) following the rehabilitating effect of demethylation, an imprinted gene (SNRPN) retains its original parental imprint; and (iii) the choice of an allele between early or late replication in the aberrant asynchronous replication, delineated by the cancer status, is not

Design of multiple sequence alignment algorithms on parallel, distributed memory supercomputers.

Science.gov (United States)

Church, Philip C; Goscinski, Andrzej; Holt, Kathryn; Inouye, Michael; Ghoting, Amol; Makarychev, Konstantin; Reumann, Matthias

2011-01-01

The challenge of comparing two or more genomes that have undergone recombination and substantial amounts of segmental loss and gain has recently been addressed for small numbers of genomes. However, datasets of hundreds of genomes are now common and their sizes will only increase in the future. Multiple sequence alignment of hundreds of genomes remains an intractable problem due to quadratic increases in compute time and memory footprint. To date, most alignment algorithms are designed for commodity clusters without parallelism. Hence, we propose the design of a multiple sequence alignment algorithm on massively parallel, distributed memory supercomputers to enable research into comparative genomics on large data sets. Following the methodology of the sequential progressiveMauve algorithm, we design data structures including sequences and sorted k-mer lists on the IBM Blue Gene/P supercomputer (BG/P). Preliminary results show that we can reduce the memory footprint so that we can potentially align over 250 bacterial genomes on a single BG/P compute node. We verify our results on a dataset of E.coli, Shigella and S.pneumoniae genomes. Our implementation returns results matching those of the original algorithm but in 1/2 the time and with 1/4 the memory footprint for scaffold building. In this study, we have laid the basis for multiple sequence alignment of large-scale datasets on a massively parallel, distributed memory supercomputer, thus enabling comparison of hundreds instead of a few genome sequences within reasonable time.

Allele-specific Gene Silencing of Mutant mRNA Restores Cellular Function in Ullrich Congenital Muscular Dystrophy Fibroblasts

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Satoru Noguchi

2014-01-01

Full Text Available Ullrich congenital muscular dystrophy (UCMD is an inherited muscle disorder characterized clinically by muscle weakness, distal joint hyperlaxity, and proximal joint contractures. Sporadic and recessive mutations in the three collagen VI genes, COL6A1, COL6A2, and COL6A3, are reported to be causative. In the sporadic forms, a heterozygous point mutation causing glycine substitution in the triple helical domain has been identified in higher rate. In this study, we examined the efficacy of siRNAs, which target point mutation site, on specific knockdown toward transcripts from mutant allele and evaluated consequent cellular phenotype of UCMD fibroblasts. We evaluated the effect of siRNAs targeted to silence-specific COL6A1 alleles in UCMD fibroblasts, where simultaneous expression of both wild-type and mutant collagen VI resulted in defective collagen localization. Addition of mutant-specific siRNAs allowed normal extracellular localization of collagen VI surrounding fibroblasts, suggesting selective inhibition of mutant collagen VI. Targeting the single-nucleotide COL6A1 c.850G>A (p.G284R mutation responsible a sporadic autosomal dominant form of UCMD can potently and selectively block expression of mutant collagen VI. These results suggest that allele-specific knockdown of the mutant mRNA can potentially be considered as a therapeutic procedure in UCMD due to COL6A1 point mutations.

Identification and Genetic Diversity of Etambutol Resistant Strains of Mycobacterium Tuberculosis by Allelic-Specific PCR and Spologiotyping

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Zahra Derakhshani Nezhad

2012-09-01

Full Text Available Background & Objectives: Ethambutol is one of the four main drugs in treatment of tuberculosis. The most common mutation associated with this drug resistance usually occurs in codon 306 of embB. The aim of this study was to detect ethambutol resistance using Allele-Specific PCR and Spoligotyping in various subtypes of Mycobacterium tuberculosis.   Methods : 140 sputum specimens were collected from suspected TB patients. They were digested and decontaminated using Pettrof method before culturing them on LJ medium. Drug susceptibility testing was performed on 106 culture positive specimens using proportional method. DNA was extracted from the isolated organisms and subsequently subjected to Allele-Specific PCR to detect any mutationin embB306. Spoligotyping was then used to determine the subtypes.   Results: Out of 106 cultures positive samples, 36 samples (33.9% showed resistance to ethambutol using proportional method. Allele-Specific PCR assay identified 93 as sensitive and 13 (27.6% as resistant strains. The results of PCR were in agreement with result of proportional method. The PCR method revealed that 61.5% of mutation occurred in the first and 38.5% in third nucleotides. Spoligotyping differentiated Mycobacterium tuberculosis strains into Beijing (10 9.4%, Bovis (2 1.8%, CAS (24 22.6%, EAI (1 0.9%, Haarlem (27 25.4%, LAM (5 4.7%, Manu (5 4.7%, T (27 25.4% and U( 2 1,8% families. The high frequency of mutation in embB gene was belonged to Haarlem, CAS and T subfamilies.   Conclusion: Based on results current study, mutations in the genes other than embB might have occurred in the resistant strains that gave negative result in Allele-Specific PCR assay. Therefore other mechanisms of resistance to this antibiotic should be investigated.

Allelic diversity of the Plasmodium falciparum erythrocyte membrane protein 1 entails variant-specific red cell surface epitopes.

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Inès Vigan-Womas

Full Text Available The clonally variant Plasmodium falciparum PfEMP1 adhesin is a virulence factor and a prime target of humoral immunity. It is encoded by a repertoire of functionally differentiated var genes, which display architectural diversity and allelic polymorphism. Their serological relationship is key to understanding the evolutionary constraints on this gene family and rational vaccine design. Here, we investigated the Palo Alto/VarO and IT4/R29 and 3D7/PF13_003 parasites lines. VarO and R29 form rosettes with uninfected erythrocytes, a phenotype associated with severe malaria. They express an allelic Cys2/group A NTS-DBL1α(1 PfEMP1 domain implicated in rosetting, whose 3D7 ortholog is encoded by PF13_0003. Using these three recombinant NTS-DBL1α(1 domains, we elicited antibodies in mice that were used to develop monovariant cultures by panning selection. The 3D7/PF13_0003 parasites formed rosettes, revealing a correlation between sequence identity and virulence phenotype. The antibodies cross-reacted with the allelic domains in ELISA but only minimally with the Cys4/group B/C PFL1955w NTS-DBL1α. By contrast, they were variant-specific in surface seroreactivity of the monovariant-infected red cells by FACS analysis and in rosette-disruption assays. Thus, while ELISA can differentiate serogroups, surface reactivity assays define the more restrictive serotypes. Irrespective of cumulated exposure to infection, antibodies acquired by humans living in a malaria-endemic area also displayed a variant-specific surface reactivity. Although seroprevalence exceeded 90% for each rosetting line, the kinetics of acquisition of surface-reactive antibodies differed in the younger age groups. These data indicate that humans acquire an antibody repertoire to non-overlapping serotypes within a serogroup, consistent with an antibody-driven diversification pressure at the population level. In addition, the data provide important information for vaccine design, as

Dyslexia risk variant rs600753 is linked with dyslexia-specific differential allelic expression of DYX1C1

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Bent Müller

2018-02-01

Full Text Available Abstract An increasing number of genetic variants involved in dyslexia development were discovered during the last years, yet little is known about the molecular functional mechanisms of these SNPs. In this study we investigated whether dyslexia candidate SNPs have a direct, disease-specific effect on local expression levels of the assumed target gene by using a differential allelic expression assay. In total, 12 SNPs previously associated with dyslexia and related phenotypes were suitable for analysis. Transcripts corresponding to four SNPs were sufficiently expressed in 28 cell lines originating from controls and a family affected by dyslexia. We observed a significant effect of rs600753 on expression levels of DYX1C1 in forward and reverse sequencing approaches. The expression level of the rs600753 risk allele was increased in the respective seven cell lines from members of the dyslexia family which might be due to a disturbed transcription factor binding sites. When considering our results in the context of neuroanatomical dyslexia-specific findings, we speculate that this mechanism may be part of the pathomechanisms underlying the dyslexia-specific brain phenotype. Our results suggest that allele-specific DYX1C1 expression levels depend on genetic variants of rs600753 and contribute to dyslexia. However, these results are preliminary and need replication.

Hierarchical approach to optimization of parallel matrix multiplication on large-scale platforms

KAUST Repository

Hasanov, Khalid

2014-03-04

© 2014, Springer Science+Business Media New York. Many state-of-the-art parallel algorithms, which are widely used in scientific applications executed on high-end computing systems, were designed in the twentieth century with relatively small-scale parallelism in mind. Indeed, while in 1990s a system with few hundred cores was considered a powerful supercomputer, modern top supercomputers have millions of cores. In this paper, we present a hierarchical approach to optimization of message-passing parallel algorithms for execution on large-scale distributed-memory systems. The idea is to reduce the communication cost by introducing hierarchy and hence more parallelism in the communication scheme. We apply this approach to SUMMA, the state-of-the-art parallel algorithm for matrix–matrix multiplication, and demonstrate both theoretically and experimentally that the modified Hierarchical SUMMA significantly improves the communication cost and the overall performance on large-scale platforms.

TumorBoost: Normalization of allele-specific tumor copy numbers from a single pair of tumor-normal genotyping microarrays

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Neuvial Pierre

2010-05-01

Full Text Available Abstract Background High-throughput genotyping microarrays assess both total DNA copy number and allelic composition, which makes them a tool of choice for copy number studies in cancer, including total copy number and loss of heterozygosity (LOH analyses. Even after state of the art preprocessing methods, allelic signal estimates from genotyping arrays still suffer from systematic effects that make them difficult to use effectively for such downstream analyses. Results We propose a method, TumorBoost, for normalizing allelic estimates of one tumor sample based on estimates from a single matched normal. The method applies to any paired tumor-normal estimates from any microarray-based technology, combined with any preprocessing method. We demonstrate that it increases the signal-to-noise ratio of allelic signals, making it significantly easier to detect allelic imbalances. Conclusions TumorBoost increases the power to detect somatic copy-number events (including copy-neutral LOH in the tumor from allelic signals of Affymetrix or Illumina origin. We also conclude that high-precision allelic estimates can be obtained from a single pair of tumor-normal hybridizations, if TumorBoost is combined with single-array preprocessing methods such as (allele-specific CRMA v2 for Affymetrix or BeadStudio's (proprietary XY-normalization method for Illumina. A bounded-memory implementation is available in the open-source and cross-platform R package aroma.cn, which is part of the Aroma Project (http://www.aroma-project.org/.

The immunogenetics of multiple sclerosis. The frequency of HLA-alleles class 1 and 2 is lower in Southern Brazil than in the European population.

Science.gov (United States)

Werneck, Lineu Cesar; Lorenzoni, Paulo José; Arndt, Raquel Cristina; Kay, Cláudia Suemi Kamoi; Scola, Rosana Herminia

2016-08-01

To study the HLA of class 1and 2 in a multiple sclerosis (MS) population to verify the susceptibility for the disease in the Southern Brazil. We analyzed patients with MS and controls, by direct sequencing of the genes related to HLA DRB1, DQB1, DPB1, A, B and C alleles with high resolution techniques. We found a lower frequency of all HLA alleles class 1 and 2 in MS and controls comparing to the European population. Several alleles had statistical correlation, but after Bonferroni correction, the only allele with significance was the HLA-DQB1*02:03, which has a positive association with MS. Our data have different frequency of HLA-alleles than the previous published papers in the Southeast Brazil and European population, possible due to several ethnic backgrounds.

Further exploration of antimicrobial ketodihydronicotinic acid derivatives by multiple parallel syntheses

DEFF Research Database (Denmark)

Laursen, Jane B.; Nielsen, Janne; Haack, T.

2006-01-01

A synthetic reexamination of a series of ketodihydronicotinic acid class antibacterial agents was undertaken in an attempt to improve their therapeutic potential. A convenient new synthesis was developed involving hetero Diels-Alder chemistry producing 74 new analogs in a multiple parallel synthe...

Enhanced specificity of TPMT*2 genotyping using unidirectional wild-type and mutant allele-specific scorpion primers in a single tube.

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Dong Chen

Full Text Available Genotyping of thiopurine S-methyltransferase (TPMT is recommended for predicting the adverse drug response of thiopurines. In the current study, a novel version of allele-specific PCR (AS-PCR, termed competitive real-time fluorescent AS-PCR (CRAS-PCR was developed to analyze the TPMT*2 genotype in ethnic Chinese. This technique simultaneously uses wild-type and mutant allele-specific scorpion primers in a single reaction. To determine the optimal conditions for both traditional AS-PCR and CRAS-PCR, we used the Taguchi method, an engineering optimization process that balances the concentrations of all components using an orthogonal array rather than a factorial array. Instead of running up to 264 experiments with the conventional factorial method, the Taguchi method achieved the same optimization using only 16 experiments. The optimized CRAS-PCR system completely avoided non-specific amplification occurring in traditional AS-PCR and could be performed at much more relaxed reaction conditions at 1% sensitivity, similar to traditional AS-PCR. TPMT*2 genotyping of 240 clinical samples was consistent with published data. In conclusion, CRAS-PCR is a novel and robust genotyping method, and the Taguchi method is an effective tool for the optimization of molecular analysis techniques.

Allelic Imbalance Is a Prevalent and Tissue-Specific Feature of the Mouse Transcriptome

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Pinter, Stefan F.; Colognori, David; Beliveau, Brian J.; Sadreyev, Ruslan I.; Payer, Bernhard; Yildirim, Eda; Wu, Chao-ting; Lee, Jeannie T.

2015-01-01

In mammals, several classes of monoallelic genes have been identified, including those subject to X-chromosome inactivation (XCI), genomic imprinting, and random monoallelic expression (RMAE). However, the extent to which these epigenetic phenomena are influenced by underlying genetic variation is unknown. Here we perform a systematic classification of allelic imbalance in mouse hybrids derived from reciprocal crosses of divergent strains. We observe that deviation from balanced biallelic expression is common, occurring in ∼20% of the mouse transcriptome in a given tissue. Allelic imbalance attributed to genotypic variation is by far the most prevalent class and typically is tissue-specific. However, some genotype-based imbalance is maintained across tissues and is associated with greater genetic variation, especially in 5′ and 3′ termini of transcripts. We further identify novel random monoallelic and imprinted genes and find that genotype can modify penetrance of parental origin even in the setting of large imprinted regions. Examination of nascent transcripts in single cells from inbred parental strains reveals that genes showing genotype-based imbalance in hybrids can also exhibit monoallelic expression in isogenic backgrounds. This surprising observation may suggest a competition between alleles and/or reflect the combined impact of cis- and trans-acting variation on expression of a given gene. Our findings provide novel insights into gene regulation and may be relevant to human genetic variation and disease. PMID:25858912

DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status

DEFF Research Database (Denmark)

Weiner Lachmi, Karin; Lin, Ling; Kornum, Birgitte Rahbek

2012-01-01

The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression...

Screening for SNPs with Allele-Specific Methylation based on Next-Generation Sequencing Data

OpenAIRE

Hu, Bo; Ji, Yuan; Xu, Yaomin; Ting, Angela H

2013-01-01

Allele-specific methylation (ASM) has long been studied but mainly documented in the context of genomic imprinting and X chromosome inactivation. Taking advantage of the next-generation sequencing technology, we conduct a high-throughput sequencing experiment with four prostate cell lines to survey the whole genome and identify single nucleotide polymorphisms (SNPs) with ASM. A Bayesian approach is proposed to model the counts of short reads for each SNP conditional on its genotypes of multip...

Conceptual design of multiple parallel switching controller

International Nuclear Information System (INIS)

Ugolini, D.; Yoshikawa, S.; Ozawa, K.

1996-01-01

This paper discusses the conceptual design and the development of a preliminary model of a multiple parallel switching (MPS) controller. The introduction of several advanced controllers has widened and improved the control capability of nonlinear dynamical systems. However, it is not possible to uniquely define a controller that always outperforms the others, and, in many situations, the controller providing the best control action depends on the operating conditions and on the intrinsic properties and behavior of the controlled dynamical system. The desire to combine the control action of several controllers with the purpose to continuously attain the best control action has motivated the development of the MPS controller. The MPS controller consists of a number of single controllers acting in parallel and of an artificial intelligence (AI) based selecting mechanism. The AI selecting mechanism analyzes the output of each controller and implements the one providing the best control performance. An inherent property of the MPS controller is the possibility to discard unreliable controllers while still being able to perform the control action. To demonstrate the feasibility and the capability of the MPS controller the simulation of the on-line operation control of a fast breeder reactor (FBR) evaporator is presented. (author)

Correlation of geographic distributions of haptoglobin alleles with prevalence of multiple sclerosis (MS) - a narrative literature review.

Science.gov (United States)

Bamm, Vladimir V; Geist, Arielle M; Harauz, George

2017-02-01

We have proposed that the myelin damage observed in multiple sclerosis (MS) may be partly mediated through the long-term release and degradation of extracellular hemoglobin (Hb) and the products of its oxidative degradation [Cellular and Molecular Life Sciences, 71, 1789-1798, 2014]. The protein haptoglobin (Hpt) binds extracellular Hb as a first line of defense, and can serve as a vascular antioxidant. Humans have two different Hpt alleles: Hpt1 and Hpt2, giving either homozygous Hpt1-1 or Hpt2-2 phenotypes, or a heterozygous Hpt1-2 phenotype. We questioned whether those geographic regions with higher frequency of the Hpt2 allele (conversely, lower frequency of Hpt1 allele) would correlate with an increased incidence of MS, because different Hpt phenotypes will have variable anti-oxidative potentials in protecting myelin from damage inflicted by extracellular Hb and its degradation products. To test this hypothesis, we undertook a systematic analysis of the literature on reported geographic distributions of Hpt alleles to compare them with data reported in the World Health Organization Atlas of worldwide MS prevalence. We found the frequency of the Hpt1 allele to be low in European and North American countries with a high prevalence of MS, consistent with our hypothesis. However, this correlation was not observed in China and India, countries with the lowest Hpt1 frequencies, yet low reported prevalence of MS. Nevertheless, this work shows the need for continued refinement of geographic patterns of MS prevalence, including data on ethnic or racial origin, and for new clinical studies to probe the observed correlation and evaluate Hpt phenotype as a predictor of disease variability and progression, severity, and/or comorbidity with cardiovascular disorders.

Frequency Specific Effects of ApoE ε4 Allele on Resting-State Networks in Nondemented Elders

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Ying Liang

2017-01-01

Full Text Available We applied resting-state functional magnetic resonance imaging (fMRI to examine the Apolipoprotein E (ApoE ε4 allele effects on functional connectivity of the default mode network (DMN and the salience network (SN. Considering the frequency specific effects of functional connectivity, we decomposed the brain network time courses into two bands: 0.01–0.027 Hz and 0.027–0.08 Hz. All scans were acquired by the Alzheimer’s Disease Neuroscience Initiative (ADNI. Thirty-two nondemented subjects were divided into two groups based on the presence (n=16 or absence (n=16 of the ApoE ε4 allele. We explored the frequency specific effects of ApoE ε4 allele on the default mode network (DMN and the salience network (SN functional connectivity. Compared to ε4 noncarriers, the DMN functional connectivity of ε4 carriers was significantly decreased while the SN functional connectivity of ε4 carriers was significantly increased. Many functional connectivities showed significant differences at the lower frequency band of 0.01–0.027 Hz or the higher frequency band of 0.027–0.08 Hz instead of the typical range of 0.01–0.08 Hz. The results indicated a frequency dependent effect of resting-state signals when investigating RSNs functional connectivity.

Ultrascalable petaflop parallel supercomputer

Science.gov (United States)

Blumrich, Matthias A [Ridgefield, CT; Chen, Dong [Croton On Hudson, NY; Chiu, George [Cross River, NY; Cipolla, Thomas M [Katonah, NY; Coteus, Paul W [Yorktown Heights, NY; Gara, Alan G [Mount Kisco, NY; Giampapa, Mark E [Irvington, NY; Hall, Shawn [Pleasantville, NY; Haring, Rudolf A [Cortlandt Manor, NY; Heidelberger, Philip [Cortlandt Manor, NY; Kopcsay, Gerard V [Yorktown Heights, NY; Ohmacht, Martin [Yorktown Heights, NY; Salapura, Valentina [Chappaqua, NY; Sugavanam, Krishnan [Mahopac, NY; Takken, Todd [Brewster, NY

2010-07-20

A massively parallel supercomputer of petaOPS-scale includes node architectures based upon System-On-a-Chip technology, where each processing node comprises a single Application Specific Integrated Circuit (ASIC) having up to four processing elements. The ASIC nodes are interconnected by multiple independent networks that optimally maximize the throughput of packet communications between nodes with minimal latency. The multiple networks may include three high-speed networks for parallel algorithm message passing including a Torus, collective network, and a Global Asynchronous network that provides global barrier and notification functions. These multiple independent networks may be collaboratively or independently utilized according to the needs or phases of an algorithm for optimizing algorithm processing performance. The use of a DMA engine is provided to facilitate message passing among the nodes without the expenditure of processing resources at the node.

ABO alleles are linked with haplotypes of an erythroid cell-specific regulatory element in intron 1 with a few exceptions attributable to genetic recombination.

Science.gov (United States)

Nakajima, T; Sano, R; Takahashi, Y; Watanabe, K; Kubo, R; Kobayashi, M; Takahashi, K; Takeshita, H; Kominato, Y

2016-01-01

Recent investigation of transcriptional regulation of the ABO genes has identified a candidate erythroid cell-specific regulatory element, named the +5·8-kb site, in the first intron of ABO. Six haplotypes of the site have been reported previously. The present genetic population study demonstrated that each haplotype was mostly linked with specific ABO alleles with a few exceptions, possibly as a result of hybrid formation between common ABO alleles. Thus, investigation of these haplotypes could provide a clue to further elucidation of ABO alleles. © 2015 International Society of Blood Transfusion.

Sensory-specific clock components and memory mechanisms: investigation with parallel timing.

Science.gov (United States)

Gamache, Pierre-Luc; Grondin, Simon

2010-05-01

A challenge for researchers in the time-perception field is to determine whether temporal processing is governed by a central mechanism or by multiple mechanisms working in concert. Behavioral studies of parallel timing offer interesting insights into the question, although the conclusions fail to converge. Most of these studies focus on the number-of-clocks issue, but the commonality of memory mechanisms involved in time processing is often neglected. The present experiment aims to address a straightforward question: do signals from different modalities marking time intervals share the same clock and/or the same memory resources? To this end, an interval reproduction task involving the parallel timing of two sensory signals presented either in the same modality or in different modalities was conducted. The memory component was tested by manipulating the delay separating the presentation of the target intervals and the moment when the reproduction of one of these began. Results show that there is more variance when only visually marked intervals are presented, and this effect is exacerbated with longer retention delays. Finally, when there is only one interval to process, encoding the interval with signals delivered from two modalities helps to reduce variance. Taken together, these results suggest that the hypothesis stating that there are sensory-specific clock components and memory mechanisms is viable.

Allele-specific expression in the germline of patients with familial pancreatic cancer: An unbiased approach to cancer gene discovery

OpenAIRE

Tan, Aik Choon; Fan, Jian-Bing; Karikari, Collins; Bibikova, Marina; Garcia, Eliza Wickham; Zhou, Lixin; Barker, David; Serre, David; Feldmann, Georg; Hruban, Ralph H.; Klein, Alison P.; Goggins, Michael; Couch, Fergus J.; Hudson, Thomas J.; Winslow, Raimond L.

2007-01-01

Physiologic allele-specific expression (ASE) in germline tissues occurs during random X-chromosome inactivation1 and in genomic imprinting,2 wherein the two alleles of a gene in a heterozygous individual are not expressed equally. Recent studies have confirmed the existence of ASE in apparently non-imprinted autosomal genes;3–14 however, the extent of ASE in the human genome is unknown. We explored ASE in lymphoblastoid cell lines of 145 individuals using an oligonucleotide array based assay....

DIALIGN P: Fast pair-wise and multiple sequence alignment using parallel processors

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Kaufmann Michael

2004-09-01

Full Text Available Abstract Background Parallel computing is frequently used to speed up computationally expensive tasks in Bioinformatics. Results Herein, a parallel version of the multi-alignment program DIALIGN is introduced. We propose two ways of dividing the program into independent sub-routines that can be run on different processors: (a pair-wise sequence alignments that are used as a first step to multiple alignment account for most of the CPU time in DIALIGN. Since alignments of different sequence pairs are completely independent of each other, they can be distributed to multiple processors without any effect on the resulting output alignments. (b For alignments of large genomic sequences, we use a heuristics by splitting up sequences into sub-sequences based on a previously introduced anchored alignment procedure. For our test sequences, this combined approach reduces the program running time of DIALIGN by up to 97%. Conclusions By distributing sub-routines to multiple processors, the running time of DIALIGN can be crucially improved. With these improvements, it is possible to apply the program in large-scale genomics and proteomics projects that were previously beyond its scope.

Parallel computing of physical maps--a comparative study in SIMD and MIMD parallelism.

Science.gov (United States)

Bhandarkar, S M; Chirravuri, S; Arnold, J

1996-01-01

Ordering clones from a genomic library into physical maps of whole chromosomes presents a central computational problem in genetics. Chromosome reconstruction via clone ordering is usually isomorphic to the NP-complete Optimal Linear Arrangement problem. Parallel SIMD and MIMD algorithms for simulated annealing based on Markov chain distribution are proposed and applied to the problem of chromosome reconstruction via clone ordering. Perturbation methods and problem-specific annealing heuristics are proposed and described. The SIMD algorithms are implemented on a 2048 processor MasPar MP-2 system which is an SIMD 2-D toroidal mesh architecture whereas the MIMD algorithms are implemented on an 8 processor Intel iPSC/860 which is an MIMD hypercube architecture. A comparative analysis of the various SIMD and MIMD algorithms is presented in which the convergence, speedup, and scalability characteristics of the various algorithms are analyzed and discussed. On a fine-grained, massively parallel SIMD architecture with a low synchronization overhead such as the MasPar MP-2, a parallel simulated annealing algorithm based on multiple periodically interacting searches performs the best. For a coarse-grained MIMD architecture with high synchronization overhead such as the Intel iPSC/860, a parallel simulated annealing algorithm based on multiple independent searches yields the best results. In either case, distribution of clonal data across multiple processors is shown to exacerbate the tendency of the parallel simulated annealing algorithm to get trapped in a local optimum.

Parallel encoders for pixel detectors

International Nuclear Information System (INIS)

Nikityuk, N.M.

1991-01-01

A new method of fast encoding and determining the multiplicity and coordinates of fired pixels is described. A specific example construction of parallel encodes and MCC for n=49 and t=2 is given. 16 refs.; 6 figs.; 2 tabs

A scalable parallel algorithm for multiple objective linear programs

Science.gov (United States)

Wiecek, Malgorzata M.; Zhang, Hong

1994-01-01

This paper presents an ADBASE-based parallel algorithm for solving multiple objective linear programs (MOLP's). Job balance, speedup and scalability are of primary interest in evaluating efficiency of the new algorithm. Implementation results on Intel iPSC/2 and Paragon multiprocessors show that the algorithm significantly speeds up the process of solving MOLP's, which is understood as generating all or some efficient extreme points and unbounded efficient edges. The algorithm gives specially good results for large and very large problems. Motivation and justification for solving such large MOLP's are also included.

Mutant Allele-Specific Uncoupling of PENETRATION3 Functions Reveals Engagement of the ATP-Binding Cassette Transporter in Distinct Tryptophan Metabolic Pathways1[OPEN

Science.gov (United States)

Lu, Xunli; Dittgen, Jan; Piślewska-Bednarek, Mariola; Molina, Antonio; Schneider, Bernd; Doubský, Jan; Schneeberger, Korbinian; Schulze-Lefert, Paul

2015-01-01

Arabidopsis (Arabidopsis thaliana) PENETRATION (PEN) genes quantitatively contribute to the execution of different forms of plant immunity upon challenge with diverse leaf pathogens. PEN3 encodes a plasma membrane-resident pleiotropic drug resistance-type ATP-binding cassette transporter and is thought to act in a pathogen-inducible and PEN2 myrosinase-dependent metabolic pathway in extracellular defense. This metabolic pathway directs the intracellular biosynthesis and activation of tryptophan-derived indole glucosinolates for subsequent PEN3-mediated efflux across the plasma membrane at pathogen contact sites. However, PEN3 also functions in abiotic stress responses to cadmium and indole-3-butyric acid (IBA)-mediated auxin homeostasis in roots, raising the possibility that PEN3 exports multiple functionally unrelated substrates. Here, we describe the isolation of a pen3 allele, designated pen3-5, that encodes a dysfunctional protein that accumulates in planta like wild-type PEN3. The specific mutation in pen3-5 uncouples PEN3 functions in IBA-stimulated root growth modulation, callose deposition induced with a conserved peptide epitope of bacterial flagellin (flg22), and pathogen-inducible salicylic acid accumulation from PEN3 activity in extracellular defense, indicating the engagement of multiple PEN3 substrates in different PEN3-dependent biological processes. We identified 4-O-β-d-glucosyl-indol-3-yl formamide (4OGlcI3F) as a pathogen-inducible, tryptophan-derived compound that overaccumulates in pen3 leaf tissue and has biosynthesis that is dependent on an intact PEN2 metabolic pathway. We propose that a precursor of 4OGlcI3F is the PEN3 substrate in extracellular pathogen defense. These precursors, the shared indole core present in IBA and 4OGlcI3F, and allele-specific uncoupling of a subset of PEN3 functions suggest that PEN3 transports distinct indole-type metabolites in distinct biological processes. PMID:26023163

AllelicImbalance: An R/ bioconductor package for detecting, managing, and visualizing allele expression imbalance data from RNA sequencing

DEFF Research Database (Denmark)

Gådin, Jesper R.; van't Hooft, Ferdinand M.; Eriksson, Per

2015-01-01

the possible biases. Results: We present AllelicImblance, a software program that is designed to detect, manage, and visualize allelic imbalances comprehensively. The purpose of this software is to allow users to pose genetic questions in any RNA sequencing experiment quickly, enhancing the general utility...... of RNA sequencing. The visualization features can reveal notable, non-trivial allelic imbalance behavior over specific regions, such as exons. Conclusions: The software provides a complete framework to perform allelic imbalance analyses of aligned RNA sequencing data, from detection to visualization...

Bamgineer: Introduction of simulated allele-specific copy number variants into exome and targeted sequence data sets.

Science.gov (United States)

Samadian, Soroush; Bruce, Jeff P; Pugh, Trevor J

2018-03-01

Somatic copy number variations (CNVs) play a crucial role in development of many human cancers. The broad availability of next-generation sequencing data has enabled the development of algorithms to computationally infer CNV profiles from a variety of data types including exome and targeted sequence data; currently the most prevalent types of cancer genomics data. However, systemic evaluation and comparison of these tools remains challenging due to a lack of ground truth reference sets. To address this need, we have developed Bamgineer, a tool written in Python to introduce user-defined haplotype-phased allele-specific copy number events into an existing Binary Alignment Mapping (BAM) file, with a focus on targeted and exome sequencing experiments. As input, this tool requires a read alignment file (BAM format), lists of non-overlapping genome coordinates for introduction of gains and losses (bed file), and an optional file defining known haplotypes (vcf format). To improve runtime performance, Bamgineer introduces the desired CNVs in parallel using queuing and parallel processing on a local machine or on a high-performance computing cluster. As proof-of-principle, we applied Bamgineer to a single high-coverage (mean: 220X) exome sequence file from a blood sample to simulate copy number profiles of 3 exemplar tumors from each of 10 tumor types at 5 tumor cellularity levels (20-100%, 150 BAM files in total). To demonstrate feasibility beyond exome data, we introduced read alignments to a targeted 5-gene cell-free DNA sequencing library to simulate EGFR amplifications at frequencies consistent with circulating tumor DNA (10, 1, 0.1 and 0.01%) while retaining the multimodal insert size distribution of the original data. We expect Bamgineer to be of use for development and systematic benchmarking of CNV calling algorithms by users using locally-generated data for a variety of applications. The source code is freely available at http://github.com/pughlab/bamgineer.

Bamgineer: Introduction of simulated allele-specific copy number variants into exome and targeted sequence data sets.

Directory of Open Access Journals (Sweden)

Soroush Samadian

2018-03-01

Full Text Available Somatic copy number variations (CNVs play a crucial role in development of many human cancers. The broad availability of next-generation sequencing data has enabled the development of algorithms to computationally infer CNV profiles from a variety of data types including exome and targeted sequence data; currently the most prevalent types of cancer genomics data. However, systemic evaluation and comparison of these tools remains challenging due to a lack of ground truth reference sets. To address this need, we have developed Bamgineer, a tool written in Python to introduce user-defined haplotype-phased allele-specific copy number events into an existing Binary Alignment Mapping (BAM file, with a focus on targeted and exome sequencing experiments. As input, this tool requires a read alignment file (BAM format, lists of non-overlapping genome coordinates for introduction of gains and losses (bed file, and an optional file defining known haplotypes (vcf format. To improve runtime performance, Bamgineer introduces the desired CNVs in parallel using queuing and parallel processing on a local machine or on a high-performance computing cluster. As proof-of-principle, we applied Bamgineer to a single high-coverage (mean: 220X exome sequence file from a blood sample to simulate copy number profiles of 3 exemplar tumors from each of 10 tumor types at 5 tumor cellularity levels (20-100%, 150 BAM files in total. To demonstrate feasibility beyond exome data, we introduced read alignments to a targeted 5-gene cell-free DNA sequencing library to simulate EGFR amplifications at frequencies consistent with circulating tumor DNA (10, 1, 0.1 and 0.01% while retaining the multimodal insert size distribution of the original data. We expect Bamgineer to be of use for development and systematic benchmarking of CNV calling algorithms by users using locally-generated data for a variety of applications. The source code is freely available at http://github.com/pughlab/bamgineer.

Dynamics of leaf and spikelet primordia initiation in wheat as affected by Ppd-1a alleles under field conditions.

Science.gov (United States)

Ochagavía, Helga; Prieto, Paula; Savin, Roxana; Griffiths, Simon; Slafer, GustavoA

2018-04-27

Wheat adaptation is affected by Ppd genes, but the role of these alleles in the rates of leaf and spikelet initiation has not been properly analysed. Twelve near isogenic lines (NILs) combining Ppd-1a alleles from different donors introgressed in A, B, and/or D genomes were tested under field conditions during two growing seasons together with the wild type, Paragon. Leaf initiation rate was unaffected by Ppd-1a alleles so the final leaf number (FLN) was reduced in parallel with reductions in the duration of the vegetative phase. Spikelet primordia initiation was accelerated and consequently the effect on spikelets per spike was less than proportional to the effect on the duration of spikelet initiation. The magnitude of these effects on spikelet plastochron depended on the doses of Ppd-1 homoeoalleles and the specific insensitivity alleles carried. Double ridge was consistently later than floral initiation, but the difference between them was not affected by Ppd-1a alleles. These findings have potential for selecting the best combinations from the Ppd-1 homoeoallelic series for manipulating adaptation taking into consideration particular effects on spikelet number.

A Hybrid Parallel Execution Model for Logic Based Requirement Specifications (Invited Paper

Directory of Open Access Journals (Sweden)

Jeffrey J. P. Tsai

1999-05-01

Full Text Available It is well known that undiscovered errors in a requirements specification is extremely expensive to be fixed when discovered in the software maintenance phase. Errors in the requirement phase can be reduced through the validation and verification of the requirements specification. Many logic-based requirements specification languages have been developed to achieve these goals. However, the execution and reasoning of a logic-based requirements specification can be very slow. An effective way to improve their performance is to execute and reason the logic-based requirements specification in parallel. In this paper, we present a hybrid model to facilitate the parallel execution of a logic-based requirements specification language. A logic-based specification is first applied by a data dependency analysis technique which can find all the mode combinations that exist within a specification clause. This mode information is used to support a novel hybrid parallel execution model, which combines both top-down and bottom-up evaluation strategies. This new execution model can find the failure in the deepest node of the search tree at the early stage of the evaluation, thus this new execution model can reduce the total number of nodes searched in the tree, the total processes needed to be generated, and the total communication channels needed in the search process. A simulator has been implemented to analyze the execution behavior of the new model. Experiments show significant improvement based on several criteria.

Development of allele-specific multiplex PCR to determine the length of poly-T in intron 8 of CFTR

Directory of Open Access Journals (Sweden)

Neng Chen

2014-07-01

Full Text Available Cystic fibrosis transmembrane conductance regulator (CFTR gene mutation analysis has been implemented for Cystic Fibrosis (CF carrier screening, and molecular diagnosis of CF and congenital bilateral absence of the vas deferens (CBAVD. Although poly-T allele analysis in intron 8 of CFTR is required when a patient is positive for R117H, it is not recommended for routine carrier screening. Therefore, commercial kits for CFTR mutation analysis were designed either to mask the poly-T allele results, unless a patient is R117H positive, or to have the poly-T analysis as a standalone reflex test using the same commercial platform. There are other standalone assays developed to detect poly-T alleles, such as heteroduplex analysis, High Resolution Melting (HRM curve analysis, allele-specific PCR (AS-PCR and Sanger sequencing. In this report, we developed a simple and easy-to-implement multiplex AS-PCR assay using unlabeled standard length primers, which can be used as a reflex or standalone test for CFTR poly-T track analysis. Out of 115 human gDNA samples tested, results from our new AS-PCR matched to the previous known poly-T results or results from Sanger sequencing.

A Maximum-Likelihood Method to Correct for Allelic Dropout in Microsatellite Data with No Replicate Genotypes

Science.gov (United States)

Wang, Chaolong; Schroeder, Kari B.; Rosenberg, Noah A.

2012-01-01

Allelic dropout is a commonly observed source of missing data in microsatellite genotypes, in which one or both allelic copies at a locus fail to be amplified by the polymerase chain reaction. Especially for samples with poor DNA quality, this problem causes a downward bias in estimates of observed heterozygosity and an upward bias in estimates of inbreeding, owing to mistaken classifications of heterozygotes as homozygotes when one of the two copies drops out. One general approach for avoiding allelic dropout involves repeated genotyping of homozygous loci to minimize the effects of experimental error. Existing computational alternatives often require replicate genotyping as well. These approaches, however, are costly and are suitable only when enough DNA is available for repeated genotyping. In this study, we propose a maximum-likelihood approach together with an expectation-maximization algorithm to jointly estimate allelic dropout rates and allele frequencies when only one set of nonreplicated genotypes is available. Our method considers estimates of allelic dropout caused by both sample-specific factors and locus-specific factors, and it allows for deviation from Hardy–Weinberg equilibrium owing to inbreeding. Using the estimated parameters, we correct the bias in the estimation of observed heterozygosity through the use of multiple imputations of alleles in cases where dropout might have occurred. With simulated data, we show that our method can (1) effectively reproduce patterns of missing data and heterozygosity observed in real data; (2) correctly estimate model parameters, including sample-specific dropout rates, locus-specific dropout rates, and the inbreeding coefficient; and (3) successfully correct the downward bias in estimating the observed heterozygosity. We find that our method is fairly robust to violations of model assumptions caused by population structure and by genotyping errors from sources other than allelic dropout. Because the data sets

[Molecular authentication of Jinyinhua formula granule by using allele-specific PCR].

Science.gov (United States)

Jiang, Chao; Tu, Li-Chan; Yuan, Yuan; Huang, Lu-Qi; Gao, Wei; Jin, Yan

2017-07-01

Traditional authentication method is hard to identify herb's authenticity of traditional Chinese medicine(TCM) formula granules because they have lost all their morphological characteristics. In this study, a new allele-specific PCR method was established for identifying the authentication of Jinyinhua formula granule (made from Lonicerae Japonicae Flos) based on an SNP site in trnL-trnF fragment. Genomic DNA was successfully extracted from Lonicerae Japonicae Flos and its formula granules by using an improved spin column method and then PCR was performed with the designed primer. Approximately 110 bp specific bands was obtained only in the authentic Lonicerae Japonicae Flos and its formula granules, while no bands were found in fake mixed products. In addition, the PCR product sequence was proved from Lonicerae Japonicae Flos trnL-trnF sequence by using BLAST method. Therefore, DNA molecular authentication method could make up the limitations of character identification method and microscopic identification, and quickly identify herb's authenticity of TCM formula granules, with enormous potential for market supervision and quality control. Copyright© by the Chinese Pharmaceutical Association.

[Double mutant alleles in the EXT1 gene not previously reported in a teenager with hereditary multiple exostoses].

Science.gov (United States)

Cammarata-Scalisi, Francisco; Cozar, Mónica; Grinberg, Daniel; Balcells, Susana; Asteggiano, Carla G; Martínez-Domenech, Gustavo; Bracho, Ana; Sánchez, Yanira; Stock, Frances; Delgado-Luengo, Wilmer; Zara-Chirinos, Carmen; Chacín, José Antonio

2015-04-01

Hereditary forms of multiple exostoses, now called EXT1/EXT2-CDG within Congenital Disorders of Glycosylation, are the most common benign bone tumors in humans and clinical description consists of the formation of several cartilage-capped bone tumors, usually benign and localized in the juxta-epiphyseal region of long bones, although wide body dissemination in severe cases is not uncommon. Onset of the disease is variable ranging from 2-3 years up to 13-15 years with an estimated incidence ranging from 1/18,000 to 1/50,000 cases in European countries. We present a double mutant alleles in the EXT1 gene not previously reported in a teenager and her family with hereditary multiple exostoses.

Allele-specific marker generation and linkage mapping on the Xiphophorus sex chromosomes.

Science.gov (United States)

Woolcock, B; Kazianis, S; Lucito, R; Walter, R B; Kallman, K D; Morizot, D C; Vielkind, J R

2006-01-01

There is great interest in the sex chromosomes of Xiphophorus fishes because both WY/YY and XX/XY sex-determining mechanisms function in these species, with at least one taxon possessing all three types of sex chromosomes, and because in certain interspecific hybrids melanoma arises as a consequence of inheritance of the sex-linked macromelanophore determining locus (MDL). Representational difference analysis (RDA) has been used to clone two sequences from the sex-determining region of X. maculatus, including a cholinergic receptor, nicotinic, delta polypeptide (CHRND) orthologue. Allele-specific assays for these sequences, as well as for the sex-linked XMRK1 and XMRK2 genes, were developed to distinguish W, X, and Y chromosomes derived from a X. maculatus (XX/XY) strain and a X. helleri (WY/YY) strain. Linkage mapping localized these markers to linkage group (LG) 24. No recombinants were observed between XMRK2 and MDL, confirming a role for XMRK2 in macromelanophore development. Although the master sex-determining (SD) locus certainly resides on Xiphophorus LG 24, autosomal loci are probably involved in sex determination as well, as indicated by the abnormal sex ratios in the backcross hybrids that contrast theoretical predictions based on LG 24 genotyping. Marker development and allelic discrimination on the Xiphophorus sex chromosomes should prove highly useful for studies that utilize this genus as an animal model.

Allelic barley MLA immune receptors recognize sequence-unrelated avirulence effectors of the powdery mildew pathogen.

Science.gov (United States)

Lu, Xunli; Kracher, Barbara; Saur, Isabel M L; Bauer, Saskia; Ellwood, Simon R; Wise, Roger; Yaeno, Takashi; Maekawa, Takaki; Schulze-Lefert, Paul

2016-10-18

Disease-resistance genes encoding intracellular nucleotide-binding domain and leucine-rich repeat proteins (NLRs) are key components of the plant innate immune system and typically detect the presence of isolate-specific avirulence (AVR) effectors from pathogens. NLR genes define the fastest-evolving gene family of flowering plants and are often arranged in gene clusters containing multiple paralogs, contributing to copy number and allele-specific NLR variation within a host species. Barley mildew resistance locus a (Mla) has been subject to extensive functional diversification, resulting in allelic resistance specificities each recognizing a cognate, but largely unidentified, AVR a gene of the powdery mildew fungus, Blumeria graminis f. sp. hordei (Bgh). We applied a transcriptome-wide association study among 17 Bgh isolates containing different AVR a genes and identified AVR a1 and AVR a13 , encoding candidate-secreted effectors recognized by Mla1 and Mla13 alleles, respectively. Transient expression of the effector genes in barley leaves or protoplasts was sufficient to trigger Mla1 or Mla13 allele-specific cell death, a hallmark of NLR receptor-mediated immunity. AVR a1 and AVR a13 are phylogenetically unrelated, demonstrating that certain allelic MLA receptors evolved to recognize sequence-unrelated effectors. They are ancient effectors because corresponding loci are present in wheat powdery mildew. AVR A1 recognition by barley MLA1 is retained in transgenic Arabidopsis, indicating that AVR A1 directly binds MLA1 or that its recognition involves an evolutionarily conserved host target of AVR A1 Furthermore, analysis of transcriptome-wide sequence variation among the Bgh isolates provides evidence for Bgh population structure that is partially linked to geographic isolation.

Kinetic characterisation of primer mismatches in allele-specific PCR: a quantitative assessment.

Science.gov (United States)

Waterfall, Christy M; Eisenthal, Robert; Cobb, Benjamin D

2002-12-20

A novel method of estimating the kinetic parameters of Taq DNA polymerase during rapid cycle PCR is presented. A model was constructed using a simplified sigmoid function to represent substrate accumulation during PCR in combination with the general equation describing high substrate inhibition for Michaelis-Menten enzymes. The PCR progress curve was viewed as a series of independent reactions where initial rates were accurately measured for each cycle. Kinetic parameters were obtained for allele-specific PCR (AS-PCR) amplification to examine the effect of mismatches on amplification. A high degree of correlation was obtained providing evidence of substrate inhibition as a major cause of the plateau phase that occurs in the later cycles of PCR.

siRNA-mediated Allele-specific Silencing of a COL6A3 Mutation in a Cellular Model of Dominant Ullrich Muscular Dystrophy

Directory of Open Access Journals (Sweden)

Véronique Bolduc

2014-01-01

Full Text Available Congenital muscular dystrophy type Ullrich (UCMD is a severe disorder of early childhood onset for which currently there is no effective treatment. UCMD commonly is caused by dominant-negative mutations in the genes coding for collagen type VI, a major microfibrillar component of the extracellular matrix surrounding the muscle fibers. To explore RNA interference (RNAi as a potential therapy for UCMD, we designed a series of small interfering RNA (siRNA oligos that specifically target the most common mutations resulting in skipping of exon 16 in the COL6A3 gene and tested them in UCMD-derived dermal fibroblasts. Transcript analysis by semiquantitative and quantitative reverse transcriptase PCR showed that two of these siRNAs were the most allele-specific, i.e., they efficiently knocked down the expression from the mutant allele, without affecting the normal allele. In HEK293T cells, these siRNAs selectively suppressed protein expression from a reporter construct carrying the mutation, with no or minimal suppression of the wild-type (WT construct, suggesting that collagen VI protein levels are as also reduced in an allele-specific manner. Furthermore, we found that treating UCMD fibroblasts with these siRNAs considerably improved the quantity and quality of the collagen VI matrix, as assessed by confocal microscopy. Our current study establishes RNAi as a promising molecular approach for treating dominant COL6-related dystrophies.

Linkage disequilibrium between an allele at the dopamine D4 receptor locus and Tourette syndrome, by the transmission-disequilibrium test

Energy Technology Data Exchange (ETDEWEB)

Grice, D.E.; Gelernter, J. [Veterans Administration Connecticut Healthcare System, West Haven, CT (United States); Leckman, J.F.; Pauls, D.L. [Yale Univ. School of Medicine, New Haven, CT (United States)] [and others

1996-09-01

Dopaminergic abnormalities are implicated in the pathogenesis of Tourette syndrome (TS) and chronic multiple tics. We used the transmission-disequilibrium test (TDT) method to test for linkage disequilibrium between a specific allele (the seven-repeat allele (DRD4*7R) of the exon 3 VNTR polymorphic site) at the D4 dopamine receptor locus (DRD4) and expression of chronic multiple tics and TS. This particular allele had been shown in functional studies to have different binding properties compared with the other common alleles in this DRD4 polymorphic system. We studied 64 family trios (consisting of an affected person and two parents, at least one heterozygous for DRD4*7R), including 12 nuclear family trios and 52 trios from four large TS kindreds. The DRD4*7R allele was transmitted significantly more frequently than expected ({chi}{sup 2}{sub TDT} ranging from 8.47 [P < .004] to 10.80 [P = .001], depending on breadth of disease definition and inclusion or exclusion of inferred genotypes). Confirmation of this finding will depend on either replication in other samples or the identification of a transmitted functional mutation within this sample. 56 refs., 2 figs., 3 tabs.

Modelling and simulation of multiple single - phase induction motor in parallel connection

Directory of Open Access Journals (Sweden)

Sujitjorn, S.

2006-11-01

Full Text Available A mathematical model for parallel connected n-multiple single-phase induction motors in generalized state-space form is proposed in this paper. The motor group draws electric power from one inverter. The model is developed by the dq-frame theory and was tested against four loading scenarios in which satisfactory results were obtained.

Design and Analysis of Cooperative Cable Parallel Manipulators for Multiple Mobile Cranes

Directory of Open Access Journals (Sweden)

Bin Zi

2012-11-01

Full Text Available The design, dynamic modelling, and workspace are presented in this paper concerning cooperative cable parallel manipulators for multiple mobile cranes (CPMMCs. The CPMMCs can handle complex tasks that are more difficult or even impossible for a single mobile crane. Kinematics and dynamics of the CPMMCs are studied on the basis of geometric methodology and d'Alembert's principle, and a mathematical model of the CPMMCs is developed and presented with dynamic simulation. The constant orientation workspace analysis of the CPMMCs is carried out additionally. As an example, a cooperative cable parallel manipulator for triple mobile cranes with 6 Degrees of Freedom is investigated on the basis of the above design objectives.

The specification of Stampi, a message passing library for distributed parallel computing

International Nuclear Information System (INIS)

Imamura, Toshiyuki; Takemiya, Hiroshi; Koide, Hiroshi

2000-03-01

At CCSE, Center for Promotion of Computational Science and Engineering, a new message passing library for heterogeneous and distributed parallel computing has been developed, and it is called as Stampi. Stampi enables us to communicate between any combination of parallel computers as well as workstations. Currently, a Stampi system is constructed from Stampi library and Stampi/Java. It provides functions to connect a Stampi application with not only those on COMPACS, COMplex Parallel Computer System, but also applets which work on WWW browsers. This report summarizes the specifications of Stampi and details the development of its system. (author)

Drop-out probabilities of IrisPlex SNP alleles

DEFF Research Database (Denmark)

Andersen, Jeppe Dyrberg; Tvedebrink, Torben; Mogensen, Helle Smidt

2013-01-01

In certain crime cases, information about a perpetrator's phenotype, including eye colour, may be a valuable tool if no DNA profile of any suspect or individual in the DNA database matches the DNA profile found at the crime scene. Often, the available DNA material is sparse and allelic drop-out...... of true alleles is possible. As part of the validation of the IrisPlex assay in our ISO17025 accredited, forensic genetic laboratory, we estimated the probability of drop-out of specific SNP alleles using 29 and 30 PCR cycles and 25, 50 and 100 Single Base Extension (SBE) cycles. We observed no drop-out...... when the amount of DNA was greater than 125 pg for 29 cycles of PCR and greater than 62 pg for 30 cycles of PCR. With the use of a logistic regression model, we estimated the allele specific probability of drop-out in heterozygote systems based on the signal strength of the observed allele...

Infrequent detection of germline allele-specific expression of TGFBR1 in lymphoblasts and tissues of colon cancer patients.

LENUS (Irish Health Repository)

Guda, Kishore

2009-06-15

Recently, germline allele-specific expression (ASE) of the gene encoding for transforming growth factor-beta type I receptor (TGFBR1) has been proposed to be a major risk factor for cancer predisposition in the colon. Germline ASE results in a lowered expression of one of the TGFBR1 alleles (>1.5-fold), and was shown to occur in approximately 20% of informative familial and sporadic colorectal cancer (CRC) cases. In the present study, using the highly quantitative pyrosequencing technique, we estimated the frequency of ASE in TGFBR1 in a cohort of affected individuals from familial clusters of advanced colon neoplasias (cancers and adenomas with high-grade dysplasia), and also from a cohort of individuals with sporadic CRCs. Cases were considered positive for the presence of ASE if demonstrating an allelic expression ratio <0.67 or >1.5. Using RNA derived from lymphoblastoid cell lines, we find that of 46 informative Caucasian advanced colon neoplasia cases with a family history, only 2 individuals display a modest ASE, with allelic ratios of 1.65 and 1.73, respectively. Given that ASE of TGFBR1, if present, would likely be more pronounced in the colon compared with other tissues, we additionally determined the allele ratios of TGFBR1 in the RNA derived from normal-appearing colonic mucosa of sporadic CRC cases. We, however, found no evidence of ASE in any of 44 informative sporadic cases analyzed. Taken together, we find that germline ASE of TGFBR1, as assayed in lymphoblastoid and colon epithelial cells of colon cancer patients, is a relatively rare event.

Specific β-turns precede PPIIL structures binding to allele-specific HLA-DRβ1* PBRs in fully-protective malaria vaccine components

Science.gov (United States)

Bermudez, Adriana; Alba, Martha P.; Vanegas, Magnolia; Patarroyo, Manuel A.; Patarroyo, Manuel E.

2018-04-01

The 3D structural analysis of 62 peptides derived from highly pathogenic Plasmodium falciparum malaria parasite proteins involved in host cell invasion led to finding a striking association between particular β-turn types located in the N-terminal peripheral flanking residue region (preceding the polyproline II left-handed structures fitting into the HLA-DRβ* allele family) and modified immune protection-inducing protein structure induced long-lasting protective immunity. This is the first time association between two different secondary structures associated with a specific immunological function has been described: full, long-lasting protective immunity.

Towards Interactive Visual Exploration of Parallel Programs using a Domain-Specific Language

KAUST Repository

Klein, Tobias; Bruckner, Stefan; Grö ller, M. Eduard; Hadwiger, Markus; Rautek, Peter

2016-01-01

The use of GPUs and the massively parallel computing paradigm have become wide-spread. We describe a framework for the interactive visualization and visual analysis of the run-time behavior of massively parallel programs, especially OpenCL kernels. This facilitates understanding a program's function and structure, finding the causes of possible slowdowns, locating program bugs, and interactively exploring and visually comparing different code variants in order to improve performance and correctness. Our approach enables very specific, user-centered analysis, both in terms of the recording of the run-time behavior and the visualization itself. Instead of having to manually write instrumented code to record data, simple code annotations tell the source-to-source compiler which code instrumentation to generate automatically. The visualization part of our framework then enables the interactive analysis of kernel run-time behavior in a way that can be very specific to a particular problem or optimization goal, such as analyzing the causes of memory bank conflicts or understanding an entire parallel algorithm.

Towards Interactive Visual Exploration of Parallel Programs using a Domain-Specific Language

KAUST Repository

Klein, Tobias

2016-04-19

The use of GPUs and the massively parallel computing paradigm have become wide-spread. We describe a framework for the interactive visualization and visual analysis of the run-time behavior of massively parallel programs, especially OpenCL kernels. This facilitates understanding a program\\'s function and structure, finding the causes of possible slowdowns, locating program bugs, and interactively exploring and visually comparing different code variants in order to improve performance and correctness. Our approach enables very specific, user-centered analysis, both in terms of the recording of the run-time behavior and the visualization itself. Instead of having to manually write instrumented code to record data, simple code annotations tell the source-to-source compiler which code instrumentation to generate automatically. The visualization part of our framework then enables the interactive analysis of kernel run-time behavior in a way that can be very specific to a particular problem or optimization goal, such as analyzing the causes of memory bank conflicts or understanding an entire parallel algorithm.

Identification of quantitative trait loci influencing wood specific gravity in an outbred pedigree of loblolly pine

Science.gov (United States)

A. Groover; M. Devey; T. Fiddler; J. Lee; R. Megraw; T. Mitchel-Olds; B. Sherman; S. Vujcic; C. Williams; D. Neale

1994-01-01

We report the identification of quantitative trait loci (QTL) influencing wood specific gravity (WSG) in an outbred pedigree of loblolly pine (Pinus taeda L.) . QTL mapping in an outcrossing species is complicated by the presence of multiple alleles (>2) at QTL and marker loci. Multiple alleles at QTL allow the examination of interaction among...

Mutation rate heterogeneity and the generation of allele diversity at the human minisatellite MS205 (D16S309).

Science.gov (United States)

May, C A; Jeffreys, A J; Armour, J A

1996-11-01

Many tandemly repeated minisatellite loci display extreme levels of length variation as a consequence of high rates of spontaneous germline mutation altering repeat copy number. Direct screening for new allele lengths by small-pool PCR has shown that instability at the human minisatellite locus MS205 (D16S309) is largely germline specific and usually results in the gain or loss of just a few repeat units. Structural analysis of the order of variant repeats has shown that these events occur preferentially at one end of the tandem array and can result in complex rearrangements including the inter-allelic transfer of repeat units. In contrast, putative mutants recovered from somatic DNA occur at a substantially lower rate and are simple and non-polar in nature. Germline mutation rates vary considerably between alleles, consistent with regulation occurring in cis. Although examination of DNA sequence polymorphisms immediately flanking the minisatellite reveals no definitive associations with germline mutation rate variation, differences in rate may be paralleled by changes in mutation spectrum. These findings help to explain the diversity of MS205 allele structures in modern humans and suggest a common mutation pathway with some other minisatellites.

A and MdMYB1 allele-specific markers controlling apple (Malus x domestica Borkh.) skin color and suitability for marker-assisted selection.

Science.gov (United States)

Zhang, X J; Wang, L X; Chen, X X; Liu, Y L; Meng, R; Wang, Y J; Zhao, Z Y

2014-10-31

Pre-selection for fruit skin color at the seedling stage would be highly advantageous, with marker-assisted selection offering a potential method for apple pre-selection. A and MdMYB1 alleles are allele-specific DNA markers that are potentially associated with apple skin color, and co-segregate with the Rf and Rni loci, respectively. Here, we assessed the potential application of these 2 alleles for marker-assisted breeding across 30 diverse cultivars and 2 apple seedling progenies. The red skin color phenotype was usually associated with the MdMYB1-1 allele and A(1) allele, respectively, while the 2 molecular markers provided approximately 91% predictability in the 'Fuji' x 'Cripps Pink' and 'Fuji' x 'Gala' progenies. The results obtained from the 30 cultivars and 2 progenies were consistent for the 2 molecular markers. Hence, the results supported that Rf and Rni could be located in a gene cluster, or even correspond to alleles of the same gene. Our results are consistent with the hypothesis that red/yellow dimorphism is controlled by a monogenic system, with the presence of the red anthocyanin pigmentation being dominant. In addition, our results supported that the practical utilization of the 2 function markers to efficiently and accurately select red-skinned apple cultivars in apple scion breeding programs.

Hypercube Expert System Shell - Applying Production Parallelism.

Science.gov (United States)

1989-12-01

possible processor organizations, or int( rconntction n thod,, for par- allel architetures . The following are examples of commonlv used interconnection...this timing analysis because match speed-up avaiiah& from production parallelism is proportional to the average number of affected produclions1 ( 11:5

Development of a High Resolution Virulence Allelic Profiling (HReVAP) Approach Based on the Accessory Genome of Escherichia coli to Characterize Shiga-Toxin Producing E. coli (STEC)

Science.gov (United States)

Michelacci, Valeria; Orsini, Massimiliano; Knijn, Arnold; Delannoy, Sabine; Fach, Patrick; Caprioli, Alfredo; Morabito, Stefano

2016-01-01

Shiga-toxin producing Escherichia coli (STEC) strains possess a large accessory genome composed of virulence genes existing in multiple allelic variants, which sometimes segregate with specific STEC subpopulations. We analyzed the allelic variability of 91 virulence genes of STEC by Real Time PCR followed by melting curves analysis in 713 E. coli strains including 358 STEC. The 91 genes investigated were located on the locus of enterocyte effacement (LEE), OI-57, and OI-122 pathogenicity islands and displayed a total of 476 alleles in the study population. The combinations of the 91 alleles of each strain were termed allelic signatures and used to perform cluster analyses. We termed such an approach High Resolution Virulence Allelic Profiling (HReVAP) and used it to investigate the phylogeny of STEC of multiple serogroups. The dendrograms obtained identified groups of STEC segregating approximately with the serogroups and allowed the identification of subpopulations within the single groups. The study of the allelic signatures provided further evidence of the coevolution of the LEE and OI-122, reflecting the occurrence of their acquisition through a single event. The HReVAP analysis represents a sensitive tool for studying the evolution of LEE-positive STEC. PMID:26941726

Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation

DEFF Research Database (Denmark)

Milani, Lili; Lundmark, Anders; Nordlund, Jessica

2008-01-01

To identify genes that are regulated by cis-acting functional elements in acute lymphoblastic leukemia (ALL) we determined the allele-specific expression (ASE) levels of 2, 529 genes by genotyping a genome-wide panel of single nucleotide polymorphisms in RNA and DNA from bone marrow and blood...

Systematic evaluation of the impact of ChIP-seq read designs on genome coverage, peak identification, and allele-specific binding detection.

Science.gov (United States)

Zhang, Qi; Zeng, Xin; Younkin, Sam; Kawli, Trupti; Snyder, Michael P; Keleş, Sündüz

2016-02-24

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) experiments revolutionized genome-wide profiling of transcription factors and histone modifications. Although maturing sequencing technologies allow these experiments to be carried out with short (36-50 bps), long (75-100 bps), single-end, or paired-end reads, the impact of these read parameters on the downstream data analysis are not well understood. In this paper, we evaluate the effects of different read parameters on genome sequence alignment, coverage of different classes of genomic features, peak identification, and allele-specific binding detection. We generated 101 bps paired-end ChIP-seq data for many transcription factors from human GM12878 and MCF7 cell lines. Systematic evaluations using in silico variations of these data as well as fully simulated data, revealed complex interplay between the sequencing parameters and analysis tools, and indicated clear advantages of paired-end designs in several aspects such as alignment accuracy, peak resolution, and most notably, allele-specific binding detection. Our work elucidates the effect of design on the downstream analysis and provides insights to investigators in deciding sequencing parameters in ChIP-seq experiments. We present the first systematic evaluation of the impact of ChIP-seq designs on allele-specific binding detection and highlights the power of pair-end designs in such studies.

Performance Analysis of a Threshold-Based Parallel Multiple Beam Selection Scheme for WDM FSO Systems

KAUST Repository

Nam, Sung Sik; Alouini, Mohamed-Slim; Ko, Young-Chai

2018-01-01

In this paper, we statistically analyze the performance of a threshold-based parallel multiple beam selection scheme for a free-space optical (FSO) based system with wavelength division multiplexing (WDM) in cases where a pointing error has occurred

Associations between gastric dilatation-volvulus in Great Danes and specific alleles of the canine immune-system genes DLA88, DRB1, and TLR5.

Science.gov (United States)

Harkey, Michael A; Villagran, Alexandra M; Venkataraman, Gopalakrishnan M; Leisenring, Wendy M; Hullar, Meredith A J; Torok-Storb, Beverly J

2017-08-01

OBJECTIVE To determine whether specific alleles of candidate genes of the major histocompatibility complex (MHC) and innate immune system were associated with gastric dilatation-volvulus (GDV) in Great Danes. ANIMALS 42 healthy Great Danes (control group) and 39 Great Danes with ≥ 1 GDV episode. PROCEDURES Variable regions of the 2 most polymorphic MHC genes (DLA88 and DRB1) were amplified and sequenced from the dogs in each group. Similarly, regions of 3 genes associated with the innate immune system (TLR5, NOD2, and ATG16L1), which have been linked to inflammatory bowel disease, were amplified and sequenced. Alleles were evaluated for associations with GDV, controlling for age and dog family. RESULTS Specific alleles of genes DLA88, DRB1, and TLR5 were significantly associated with GDV. One allele of each gene had an OR > 2 in the unadjusted univariate analyses and retained a hazard ratio > 2 after controlling for temperament, age, and familial association in the multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE The 3 GDV-associated alleles identified in this study may serve as diagnostic markers for identification of Great Danes at risk for GDV. Additional research is needed to determine whether other dog breeds have the same genetic associations. These findings also provided a new target for research into the etiology of, and potential treatments for, GDV in dogs.

Comparative transcript profiling of fertile and sterile flower buds from multiple-allele-inherited male sterility in Chinese cabbage (Brassica campestris L. ssp. pekinensis).

Science.gov (United States)

Zhou, Xue; Liu, Zhiyong; Ji, Ruiqin; Feng, Hui

2017-10-01

We studied the underlying causes of multiple-allele-inherited male sterility in Chinese cabbage (Brassica campestris L. ssp. pekinensis) by identifying differentially expressed genes (DEGs) related to pollen sterility between fertile and sterile flower buds. In this work, we verified the stages of sterility microscopically and then performed transcriptome analysis of mRNA isolated from fertile and sterile buds using Illumina HiSeq 2000 platform sequencing. Approximately 80% of ~229 million high-quality paired-end reads were uniquely mapped to the reference genome. In sterile buds, 699 genes were significantly up-regulated and 4096 genes were down-regulated. Among the DEGs, 28 pollen cell wall-related genes, 54 transcription factor genes, 45 phytohormone-related genes, 20 anther and pollen-related genes, 212 specifically expressed transcripts, and 417 DEGs located on linkage group A07 were identified. Six transcription factor genes BrAMS, BrMS1, BrbHLH089, BrbHLH091, BrAtMYB103, and BrANAC025 were identified as putative sterility-related genes. The weak auxin signal that is regulated by BrABP1 may be one of the key factors causing pollen sterility observed here. Moreover, several significantly enriched GO terms such as "cell wall organization or biogenesis" (GO:0071554), "intrinsic to membrane" (GO:0031224), "integral to membrane" (GO:0016021), "hydrolase activity, acting on ester bonds" (GO:0016788), and one significantly enriched pathway "starch and sucrose metabolism" (ath00500) were identified in this work. qRT-PCR, PCR, and in situ hybridization experiments validated our RNA-seq transcriptome analysis as accurate and reliable. This study will lay the foundation for elucidating the molecular mechanism(s) that underly sterility and provide valuable information for studying multiple-allele-inherited male sterility in the Chinese cabbage line 'AB01'.

Genetic dissection of the Drosophila melanogaster female head transcriptome reveals widespread allelic heterogeneity.

Science.gov (United States)

King, Elizabeth G; Sanderson, Brian J; McNeil, Casey L; Long, Anthony D; Macdonald, Stuart J

2014-05-01

Modern genetic mapping is plagued by the "missing heritability" problem, which refers to the discordance between the estimated heritabilities of quantitative traits and the variance accounted for by mapped causative variants. One major potential explanation for the missing heritability is allelic heterogeneity, in which there are multiple causative variants at each causative gene with only a fraction having been identified. The majority of genome-wide association studies (GWAS) implicitly assume that a single SNP can explain all the variance for a causative locus. However, if allelic heterogeneity is prevalent, a substantial amount of genetic variance will remain unexplained. In this paper, we take a haplotype-based mapping approach and quantify the number of alleles segregating at each locus using a large set of 7922 eQTL contributing to regulatory variation in the Drosophila melanogaster female head. Not only does this study provide a comprehensive eQTL map for a major community genetic resource, the Drosophila Synthetic Population Resource, but it also provides a direct test of the allelic heterogeneity hypothesis. We find that 95% of cis-eQTLs and 78% of trans-eQTLs are due to multiple alleles, demonstrating that allelic heterogeneity is widespread in Drosophila eQTL. Allelic heterogeneity likely contributes significantly to the missing heritability problem common in GWAS studies.

Prioritizing multiple therapeutic targets in parallel using automated DNA-encoded library screening

Science.gov (United States)

Machutta, Carl A.; Kollmann, Christopher S.; Lind, Kenneth E.; Bai, Xiaopeng; Chan, Pan F.; Huang, Jianzhong; Ballell, Lluis; Belyanskaya, Svetlana; Besra, Gurdyal S.; Barros-Aguirre, David; Bates, Robert H.; Centrella, Paolo A.; Chang, Sandy S.; Chai, Jing; Choudhry, Anthony E.; Coffin, Aaron; Davie, Christopher P.; Deng, Hongfeng; Deng, Jianghe; Ding, Yun; Dodson, Jason W.; Fosbenner, David T.; Gao, Enoch N.; Graham, Taylor L.; Graybill, Todd L.; Ingraham, Karen; Johnson, Walter P.; King, Bryan W.; Kwiatkowski, Christopher R.; Lelièvre, Joël; Li, Yue; Liu, Xiaorong; Lu, Quinn; Lehr, Ruth; Mendoza-Losana, Alfonso; Martin, John; McCloskey, Lynn; McCormick, Patti; O'Keefe, Heather P.; O'Keeffe, Thomas; Pao, Christina; Phelps, Christopher B.; Qi, Hongwei; Rafferty, Keith; Scavello, Genaro S.; Steiginga, Matt S.; Sundersingh, Flora S.; Sweitzer, Sharon M.; Szewczuk, Lawrence M.; Taylor, Amy; Toh, May Fern; Wang, Juan; Wang, Minghui; Wilkins, Devan J.; Xia, Bing; Yao, Gang; Zhang, Jean; Zhou, Jingye; Donahue, Christine P.; Messer, Jeffrey A.; Holmes, David; Arico-Muendel, Christopher C.; Pope, Andrew J.; Gross, Jeffrey W.; Evindar, Ghotas

2017-07-01

The identification and prioritization of chemically tractable therapeutic targets is a significant challenge in the discovery of new medicines. We have developed a novel method that rapidly screens multiple proteins in parallel using DNA-encoded library technology (ELT). Initial efforts were focused on the efficient discovery of antibacterial leads against 119 targets from Acinetobacter baumannii and Staphylococcus aureus. The success of this effort led to the hypothesis that the relative number of ELT binders alone could be used to assess the ligandability of large sets of proteins. This concept was further explored by screening 42 targets from Mycobacterium tuberculosis. Active chemical series for six targets from our initial effort as well as three chemotypes for DHFR from M. tuberculosis are reported. The findings demonstrate that parallel ELT selections can be used to assess ligandability and highlight opportunities for successful lead and tool discovery.

Characterization of the peptide binding specificity of the HLA class I alleles B*38:01 and B*39:06.

Science.gov (United States)

Sidney, John; Schloss, Jennifer; Moore, Carrie; Lindvall, Mikaela; Wriston, Amanda; Hunt, Donald F; Shabanowitz, Jeffrey; DiLorenzo, Teresa P; Sette, Alessandro

2016-03-01

B*38:01 and B*39:06 are present with phenotypic frequencies 39:06 is the B allele most associated with type 1 diabetes susceptibility and 38:01 is most protective. A previous study derived putative main anchor motifs for both alleles based on peptide elution data. The present study has utilized panels of single amino acid substitution peptide libraries to derive detailed quantitative motifs accounting for both primary and secondary influences on peptide binding. From these analyses, both alleles were confirmed to utilize the canonical position 2/C-terminus main anchor spacing. B*38:01 preferentially bound peptides with the positively charged or polar residues H, R, and Q in position 2 and the large hydrophobic residues I, F, L, W, and M at the C-terminus. B*39:06 had a similar preference for R in position 2, but also well-tolerated M, Q, and K. A more dramatic contrast between the two alleles was noted at the C-terminus, where the specificity of B*39:06 was clearly for small residues, with A as most preferred, followed by G, V, S, T, and I. Detailed position-by-position and residue-by-residue coefficient values were generated from the panels to provide detailed quantitative B*38:01 and B*39:06 motifs. It is hoped that these detailed motifs will facilitate the identification of T cell epitopes recognized in the context of two class I alleles associated with dramatically different dispositions towards type 1 diabetes, offering potential avenues for the investigation of the role of CD8 T cells in this disease.

Assigning breed origin to alleles in crossbred animals.

Science.gov (United States)

Vandenplas, Jérémie; Calus, Mario P L; Sevillano, Claudia A; Windig, Jack J; Bastiaansen, John W M

2016-08-22

For some species, animal production systems are based on the use of crossbreeding to take advantage of the increased performance of crossbred compared to purebred animals. Effects of single nucleotide polymorphisms (SNPs) may differ between purebred and crossbred animals for several reasons: (1) differences in linkage disequilibrium between SNP alleles and a quantitative trait locus; (2) differences in genetic backgrounds (e.g., dominance and epistatic interactions); and (3) differences in environmental conditions, which result in genotype-by-environment interactions. Thus, SNP effects may be breed-specific, which has led to the development of genomic evaluations for crossbred performance that take such effects into account. However, to estimate breed-specific effects, it is necessary to know breed origin of alleles in crossbred animals. Therefore, our aim was to develop an approach for assigning breed origin to alleles of crossbred animals (termed BOA) without information on pedigree and to study its accuracy by considering various factors, including distance between breeds. The BOA approach consists of: (1) phasing genotypes of purebred and crossbred animals; (2) assigning breed origin to phased haplotypes; and (3) assigning breed origin to alleles of crossbred animals based on a library of assigned haplotypes, the breed composition of crossbred animals, and their SNP genotypes. The accuracy of allele assignments was determined for simulated datasets that include crosses between closely-related, distantly-related and unrelated breeds. Across these scenarios, the percentage of alleles of a crossbred animal that were correctly assigned to their breed origin was greater than 90 %, and increased with increasing distance between breeds, while the percentage of incorrectly assigned alleles was always less than 2 %. For the remaining alleles, i.e. 0 to 10 % of all alleles of a crossbred animal, breed origin could not be assigned. The BOA approach accurately assigns

Diderot: a Domain-Specific Language for Portable Parallel Scientific Visualization and Image Analysis.

Science.gov (United States)

Kindlmann, Gordon; Chiw, Charisee; Seltzer, Nicholas; Samuels, Lamont; Reppy, John

2016-01-01

Many algorithms for scientific visualization and image analysis are rooted in the world of continuous scalar, vector, and tensor fields, but are programmed in low-level languages and libraries that obscure their mathematical foundations. Diderot is a parallel domain-specific language that is designed to bridge this semantic gap by providing the programmer with a high-level, mathematical programming notation that allows direct expression of mathematical concepts in code. Furthermore, Diderot provides parallel performance that takes advantage of modern multicore processors and GPUs. The high-level notation allows a concise and natural expression of the algorithms and the parallelism allows efficient execution on real-world datasets.

Paradoxical expression of INK4c in proliferative multiple myeloma tumors: bi-allelic deletion vs increased expression

Directory of Open Access Journals (Sweden)

Hanamura Ichiro

2006-10-01

Full Text Available Abstract Background A high proliferative capacity of tumor cells usually is associated with shortened patient survival. Disruption of the RB pathway, which is critically involved in regulating the G1 to S cell cycle transition, is a frequent target of oncogenic events that are thought to contribute to increased proliferation during tumor progression. Previously, we determined that p18INK4c, an essential gene for normal plasma cell differentiation, was bi-allelically deleted in five of sixteen multiple myeloma (MM cell lines. The present study was undertaken to investigate a possible role of p18INK4c in increased proliferation of myeloma tumors as they progress. Results Thirteen of 40 (33% human myeloma cell lines do not express normal p18INK4c, with bi-allelic deletion of p18 in twelve, and expression of a mutated p18 fragment in one. Bi-allelic deletion of p18, which appears to be a late progression event, has a prevalence of about 2% in 261 multiple myeloma (MM tumors, but the prevalence is 6 to10% in the 50 tumors with a high expression-based proliferation index. Paradoxically, 24 of 40 (60% MM cell lines, and 30 of 50 (60% MM tumors with a high proliferation index express an increased level of p18 RNA compared to normal bone marrow plasma cells, whereas this occurs in only five of the 151 (3% MM tumors with a low proliferation index. Tumor progression is often accompanied by increased p18 expression and an increased proliferation index. Retroviral-mediated expression of exogenous p18 results in marked growth inhibition in three MM cell lines that express little or no endogenous p18, but has no effect in another MM cell line that already expresses a high level of p18. Conclusion Paradoxically, although loss of p18 appears to contribute to increased proliferation of nearly 10% of MM tumors, most MM cell lines and proliferative MM tumors have increased expression of p18. Apart from a small fraction of cell lines and tumors that have inactivated

Erasure and reestablishment of random allelic expression imbalance after epigenetic reprogramming.

Science.gov (United States)

Jeffries, Aaron Richard; Uwanogho, Dafe Aghogho; Cocks, Graham; Perfect, Leo William; Dempster, Emma; Mill, Jonathan; Price, Jack

2016-10-01

Clonal level random allelic expression imbalance and random monoallelic expression provides cellular heterogeneity within tissues by modulating allelic dosage. Although such expression patterns have been observed in multiple cell types, little is known about when in development these stochastic allelic choices are made. We examine allelic expression patterns in human neural progenitor cells before and after epigenetic reprogramming to induced pluripotency, observing that loci previously characterized by random allelic expression imbalance (0.63% of expressed genes) are generally reset to a biallelic state in induced pluripotent stem cells (iPSCs). We subsequently neuralized the iPSCs and profiled isolated clonal neural stem cells, observing that significant random allelic expression imbalance is reestablished at 0.65% of expressed genes, including novel loci not found to show allelic expression imbalance in the original parental neural progenitor cells. Allelic expression imbalance was associated with altered DNA methylation across promoter regulatory regions, with clones characterized by skewed allelic expression being hypermethylated compared to their biallelic sister clones. Our results suggest that random allelic expression imbalance is established during lineage commitment and is associated with increased DNA methylation at the gene promoter. © 2016 Jeffries et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Parallel Computing Using Web Servers and "Servlets".

Science.gov (United States)

Lo, Alfred; Bloor, Chris; Choi, Y. K.

2000-01-01

Describes parallel computing and presents inexpensive ways to implement a virtual parallel computer with multiple Web servers. Highlights include performance measurement of parallel systems; models for using Java and intranet technology including single server, multiple clients and multiple servers, single client; and a comparison of CGI (common…

Genetic dissection of the Drosophila melanogaster female head transcriptome reveals widespread allelic heterogeneity.

Directory of Open Access Journals (Sweden)

Elizabeth G King

2014-05-01

Full Text Available Modern genetic mapping is plagued by the "missing heritability" problem, which refers to the discordance between the estimated heritabilities of quantitative traits and the variance accounted for by mapped causative variants. One major potential explanation for the missing heritability is allelic heterogeneity, in which there are multiple causative variants at each causative gene with only a fraction having been identified. The majority of genome-wide association studies (GWAS implicitly assume that a single SNP can explain all the variance for a causative locus. However, if allelic heterogeneity is prevalent, a substantial amount of genetic variance will remain unexplained. In this paper, we take a haplotype-based mapping approach and quantify the number of alleles segregating at each locus using a large set of 7922 eQTL contributing to regulatory variation in the Drosophila melanogaster female head. Not only does this study provide a comprehensive eQTL map for a major community genetic resource, the Drosophila Synthetic Population Resource, but it also provides a direct test of the allelic heterogeneity hypothesis. We find that 95% of cis-eQTLs and 78% of trans-eQTLs are due to multiple alleles, demonstrating that allelic heterogeneity is widespread in Drosophila eQTL. Allelic heterogeneity likely contributes significantly to the missing heritability problem common in GWAS studies.

Specific Silencing of L392V PSEN1 Mutant Allele by RNA Interference

Directory of Open Access Journals (Sweden)

Malgorzata Sierant

2011-01-01

Full Text Available RNA interference (RNAi technology provides a powerful molecular tool to reduce an expression of selected genes in eukaryotic cells. Short interfering RNAs (siRNAs are the effector molecules that trigger RNAi. Here, we describe siRNAs that discriminate between the wild type and mutant (1174 C→G alleles of human Presenilin1 gene (PSEN1. This mutation, resulting in L392V PSEN1 variant, contributes to early onset familial Alzheimer's disease. Using the dual fluorescence assay, flow cytometry and fluorescent microscopy we identified positions 8th–11th, within the central part of the antisense strand, as the most sensitive to mismatches. 2-Thiouridine chemical modification introduced at the 3′-end of the antisense strand improved the allele discrimination, but wobble base pairing adjacent to the mutation site abolished the siRNA activity. Our data indicate that siRNAs can be designed to discriminate between the wild type and mutant alleles of genes that differ by just a single nucleotide.

Allele specific LAMP- gold nanoparticle for characterization of single nucleotide polymorphisms

Directory of Open Access Journals (Sweden)

Fábio Ferreira Carlos

2017-12-01

Full Text Available Due to their relevance as disease biomarkers and for diagnostics, screening of single nucleotide polymorphism (SNPs requires simple and straightforward strategies capable to provide results in medium throughput settings. Suitable approaches relying on isothermal amplification techniques have been evolving to substitute the cumbersome and highly specialized PCR amplification detection schemes. Nonetheless, identification of an individual’s genotype still requires sophisticated equipment and laborious methods.Here, we present a low-cost and reliable approach based on the allele specific loop-mediated isothermal amplification (AS-LAMP coupled to ssDNA functionalized gold nanoparticle (Au-nanoprobe colorimetric sequence discrimination. The Au-nanoprobe integration allows for the colorimetric detection of AS-LAMP amplification product that can be easily interpreted in less than 15 min. We targeted a clinical relevant SNP responsible for lactose intolerance (-13910C/T dbSNP rs#: 4988235 to demonstrate its proof of concept and full potential of this novel approach. Keywords: SNP, Isothermal amplification, Gold nanoparticles, Gold nanoprobes, Lactose intolerance

Efficient computation of the joint probability of multiple inherited risk alleles from pedigree data.

Science.gov (United States)

Madsen, Thomas; Braun, Danielle; Peng, Gang; Parmigiani, Giovanni; Trippa, Lorenzo

2018-06-25

The Elston-Stewart peeling algorithm enables estimation of an individual's probability of harboring germline risk alleles based on pedigree data, and serves as the computational backbone of important genetic counseling tools. However, it remains limited to the analysis of risk alleles at a small number of genetic loci because its computing time grows exponentially with the number of loci considered. We propose a novel, approximate version of this algorithm, dubbed the peeling and paring algorithm, which scales polynomially in the number of loci. This allows extending peeling-based models to include many genetic loci. The algorithm creates a trade-off between accuracy and speed, and allows the user to control this trade-off. We provide exact bounds on the approximation error and evaluate it in realistic simulations. Results show that the loss of accuracy due to the approximation is negligible in important applications. This algorithm will improve genetic counseling tools by increasing the number of pathogenic risk alleles that can be addressed. To illustrate we create an extended five genes version of BRCAPRO, a widely used model for estimating the carrier probabilities of BRCA1 and BRCA2 risk alleles and assess its computational properties. © 2018 WILEY PERIODICALS, INC.

Analysis of a parallel multigrid algorithm

Science.gov (United States)

Chan, Tony F.; Tuminaro, Ray S.

1989-01-01

The parallel multigrid algorithm of Frederickson and McBryan (1987) is considered. This algorithm uses multiple coarse-grid problems (instead of one problem) in the hope of accelerating convergence and is found to have a close relationship to traditional multigrid methods. Specifically, the parallel coarse-grid correction operator is identical to a traditional multigrid coarse-grid correction operator, except that the mixing of high and low frequencies caused by aliasing error is removed. Appropriate relaxation operators can be chosen to take advantage of this property. Comparisons between the standard multigrid and the new method are made.

Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles

DEFF Research Database (Denmark)

Mero, Inger-Lise; Gustavsen, Marte W; Sæther, Hanne S

2013-01-01

The presence of oligoclonal bands (OCB) in cerebrospinal fluid (CSF) is a typical finding in multiple sclerosis (MS). We applied data from Norwegian, Swedish and Danish (i.e. Scandinavian) MS patients from a genome-wide association study (GWAS) to search for genetic differences in MS relating...

Parallel sorting algorithms

CERN Document Server

Akl, Selim G

1985-01-01

Parallel Sorting Algorithms explains how to use parallel algorithms to sort a sequence of items on a variety of parallel computers. The book reviews the sorting problem, the parallel models of computation, parallel algorithms, and the lower bounds on the parallel sorting problems. The text also presents twenty different algorithms, such as linear arrays, mesh-connected computers, cube-connected computers. Another example where algorithm can be applied is on the shared-memory SIMD (single instruction stream multiple data stream) computers in which the whole sequence to be sorted can fit in the

Parallel multigrid smoothing: polynomial versus Gauss-Seidel

International Nuclear Information System (INIS)

Adams, Mark; Brezina, Marian; Hu, Jonathan; Tuminaro, Ray

2003-01-01

Gauss-Seidel is often the smoother of choice within multigrid applications. In the context of unstructured meshes, however, maintaining good parallel efficiency is difficult with multiplicative iterative methods such as Gauss-Seidel. This leads us to consider alternative smoothers. We discuss the computational advantages of polynomial smoothers within parallel multigrid algorithms for positive definite symmetric systems. Two particular polynomials are considered: Chebyshev and a multilevel specific polynomial. The advantages of polynomial smoothing over traditional smoothers such as Gauss-Seidel are illustrated on several applications: Poisson's equation, thin-body elasticity, and eddy current approximations to Maxwell's equations. While parallelizing the Gauss-Seidel method typically involves a compromise between a scalable convergence rate and maintaining high flop rates, polynomial smoothers achieve parallel scalable multigrid convergence rates without sacrificing flop rates. We show that, although parallel computers are the main motivation, polynomial smoothers are often surprisingly competitive with Gauss-Seidel smoothers on serial machines

Parallel multigrid smoothing: polynomial versus Gauss-Seidel

Science.gov (United States)

Adams, Mark; Brezina, Marian; Hu, Jonathan; Tuminaro, Ray

2003-07-01

Gauss-Seidel is often the smoother of choice within multigrid applications. In the context of unstructured meshes, however, maintaining good parallel efficiency is difficult with multiplicative iterative methods such as Gauss-Seidel. This leads us to consider alternative smoothers. We discuss the computational advantages of polynomial smoothers within parallel multigrid algorithms for positive definite symmetric systems. Two particular polynomials are considered: Chebyshev and a multilevel specific polynomial. The advantages of polynomial smoothing over traditional smoothers such as Gauss-Seidel are illustrated on several applications: Poisson's equation, thin-body elasticity, and eddy current approximations to Maxwell's equations. While parallelizing the Gauss-Seidel method typically involves a compromise between a scalable convergence rate and maintaining high flop rates, polynomial smoothers achieve parallel scalable multigrid convergence rates without sacrificing flop rates. We show that, although parallel computers are the main motivation, polynomial smoothers are often surprisingly competitive with Gauss-Seidel smoothers on serial machines.

Differential ACE expression among tissues in allele-specific Wistar rat lines

NARCIS (Netherlands)

Kamilic, Jelena; Lely, A. Titia; van Goor, Harry; Buikema, Hendrik; Tent, Hilde; Navis, Gerjan J.; Korstanje, Ron

In humans, the insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene accounts for half of the variance in plasma ACE activity. The deletion allele is associated with high plasma ACE activity, cardiovascular disease, and renal disease. In rat, a similar association is found

A dynamic bead-based microarray for parallel DNA detection

International Nuclear Information System (INIS)

Sochol, R D; Lin, L; Casavant, B P; Dueck, M E; Lee, L P

2011-01-01

A microfluidic system has been designed and constructed by means of micromachining processes to integrate both microfluidic mixing of mobile microbeads and hydrodynamic microbead arraying capabilities on a single chip to simultaneously detect multiple bio-molecules. The prototype system has four parallel reaction chambers, which include microchannels of 18 × 50 µm 2 cross-sectional area and a microfluidic mixing section of 22 cm length. Parallel detection of multiple DNA oligonucleotide sequences was achieved via molecular beacon probes immobilized on polystyrene microbeads of 16 µm diameter. Experimental results show quantitative detection of three distinct DNA oligonucleotide sequences from the Hepatitis C viral (HCV) genome with single base-pair mismatch specificity. Our dynamic bead-based microarray offers an effective microfluidic platform to increase parallelization of reactions and improve microbead handling for various biological applications, including bio-molecule detection, medical diagnostics and drug screening

Refining SCJ Mission Specifications into Parallel Handler Designs

Directory of Open Access Journals (Sweden)

Frank Zeyda

2013-05-01

Full Text Available Safety-Critical Java (SCJ is a recent technology that restricts the execution and memory model of Java in such a way that applications can be statically analysed and certified for their real-time properties and safe use of memory. Our interest is in the development of comprehensive and sound techniques for the formal specification, refinement, design, and implementation of SCJ programs, using a correct-by-construction approach. As part of this work, we present here an account of laws and patterns that are of general use for the refinement of SCJ mission specifications into designs of parallel handlers used in the SCJ programming paradigm. Our notation is a combination of languages from the Circus family, supporting state-rich reactive models with the addition of class objects and real-time properties. Our work is a first step to elicit laws of programming for SCJ and fits into a refinement strategy that we have developed previously to derive SCJ programs.

Lipoprotein(a) and HIV: Allele-Specific Apolipoprotein(a) Levels Predict Carotid Intima-Media Thickness in HIV-Infected Young Women in the Women's Interagency HIV Study.

Science.gov (United States)

Enkhmaa, Byambaa; Anuurad, Erdembileg; Zhang, Wei; Li, Chin-Shang; Kaplan, Robert; Lazar, Jason; Merenstein, Dan; Karim, Roksana; Aouizerat, Brad; Cohen, Mardge; Butler, Kenneth; Pahwa, Savita; Ofotokun, Igho; Adimora, Adaora A; Golub, Elizabeth; Berglund, Lars

2017-05-01

In the general population, lipoprotein(a) [Lp(a)] has been established as an independent causal risk factor for cardiovascular disease. Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a) [apo(a)] gene. The roles of Lp(a)/apo(a) in human immunodeficiency virus (HIV)-related elevated cardiovascular disease risk remain unclear. The associations between total plasma Lp(a) level, allele-specific apo(a) level, an Lp(a) level carried by individual apo(a) alleles, and common carotid artery intima-media thickness were assessed in 150 HIV-infected and 100 HIV-uninfected women in the WIHS (Women's Interagency HIV Study). Linear regression analyses with and without adjustments were used. The cohort was young (mean age, ≈31 years), with the majority being Blacks (≈70%). The prevalence of a small size apo(a) (≤22 Kringle repeats) or a high Lp(a) level (≥30 mg/dL) was similar by HIV status. Total plasma Lp(a) level ( P =0.029) and allele-specific apo(a) level carried by the smaller apo(a) sizes ( P =0.022) were significantly associated with carotid artery intima-media thickness in the HIV-infected women only. After accounting for confounders (age, race, smoking, body mass index, blood pressure, hepatitis C virus coinfection, menopause, plasma lipids, treatment status, CD4 + T cell count, and HIV/RNA viral load), the association remained significant for both Lp(a) ( P =0.035) and allele-specific apo(a) level carried by the smaller apo(a) sizes ( P =0.010) in the HIV-infected women. Notably, none of the other lipids/lipoproteins was associated with carotid artery intima-media thickness. Lp(a) and allele-specific apo(a) levels predict carotid artery intima-media thickness in HIV-infected young women. Further research is needed to identify underlying mechanisms of an increased Lp(a) atherogenicity in HIV infection. © 2017 American Heart Association, Inc.

A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci

LENUS (Irish Health Repository)

Prendergast, James G D

2012-05-19

AbstractBackgroundChromatin structure at a given site can differ between chromosome copies in a cell, and such imbalances in chromatin structure have been shown to be important in understanding the molecular mechanisms controlling several disease loci. Human genetic variation, DNA methylation, and disease have been intensely studied, uncovering many sites of allele-specific DNA methylation (ASM). However, little is known about the genome-wide occurrence of sites of allele-specific histone modification (ASHM) and their relationship to human disease. The aim of this study was to investigate the extent and characteristics of sites of ASHM in human embryonic stem cells (hESCs).ResultsUsing a statistically rigorous protocol, we investigated the genomic distribution of ASHM in hESCs, and their relationship to sites of allele-specific expression (ASE) and DNA methylation. We found that, although they were rare, sites of ASHM were substantially enriched at loci displaying ASE. Many were also found at known imprinted regions, hence sites of ASHM are likely to be better markers of imprinted regions than sites of ASM. We also found that sites of ASHM and ASE in hESCs colocalize at risk loci for developmental syndromes mediated by deletions, providing insights into the etiology of these disorders.ConclusionThese results demonstrate the potential importance of ASHM patterns in the interpretation of disease loci, and the protocol described provides a basis for similar studies of ASHM in other cell types to further our understanding of human disease susceptibility.

Identification and removal of low-complexity sites in allele-specific analysis of ChIP-seq data.

Science.gov (United States)

Waszak, Sebastian M; Kilpinen, Helena; Gschwind, Andreas R; Orioli, Andrea; Raghav, Sunil K; Witwicki, Robert M; Migliavacca, Eugenia; Yurovsky, Alisa; Lappalainen, Tuuli; Hernandez, Nouria; Reymond, Alexandre; Dermitzakis, Emmanouil T; Deplancke, Bart

2014-01-15

High-throughput sequencing technologies enable the genome-wide analysis of the impact of genetic variation on molecular phenotypes at unprecedented resolution. However, although powerful, these technologies can also introduce unexpected artifacts. We investigated the impact of library amplification bias on the identification of allele-specific (AS) molecular events from high-throughput sequencing data derived from chromatin immunoprecipitation assays (ChIP-seq). Putative AS DNA binding activity for RNA polymerase II was determined using ChIP-seq data derived from lymphoblastoid cell lines of two parent-daughter trios. We found that, at high-sequencing depth, many significant AS binding sites suffered from an amplification bias, as evidenced by a larger number of clonal reads representing one of the two alleles. To alleviate this bias, we devised an amplification bias detection strategy, which filters out sites with low read complexity and sites featuring a significant excess of clonal reads. This method will be useful for AS analyses involving ChIP-seq and other functional sequencing assays. The R package abs filter for library clonality simulations and detection of amplification-biased sites is available from http://updepla1srv1.epfl.ch/waszaks/absfilter

Advantage of using allele-specific copy numbers when testing for association in regions with common copy number variants.

Directory of Open Access Journals (Sweden)

Gaëlle Marenne

Full Text Available Copy number variants (CNV can be called from SNP-arrays; however, few studies have attempted to combine both CNV and SNP calls to test for association with complex diseases. Even when SNPs are located within CNVs, two separate association analyses are necessary, to compare the distribution of bi-allelic genotypes in cases and controls (referred to as SNP-only strategy and the number of copies of a region (referred to as CNV-only strategy. However, when disease susceptibility is actually associated with allele specific copy-number states, the two strategies may not yield comparable results, raising a series of questions about the optimal analytical approach. We performed simulations of the performance of association testing under different scenarios that varied genotype frequencies and inheritance models. We show that the SNP-only strategy lacks power under most scenarios when the SNP is located within a CNV; frequently it is excluded from analysis as it does not pass quality control metrics either because of an increased rate of missing calls or a departure from fitness for Hardy-Weinberg proportion. The CNV-only strategy also lacks power because the association testing depends on the allele which copy number varies. The combined strategy performs well in most of the scenarios. Hence, we advocate the use of this combined strategy when testing for association with SNPs located within CNVs.

A putative Alzheimer's disease risk allele in PCK1 influences brain atrophy in multiple sclerosis.

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Zongqi Xia

2010-11-01

Full Text Available Brain atrophy and cognitive dysfunction are neurodegenerative features of Multiple Sclerosis (MS. We used a candidate gene approach to address whether genetic variants implicated in susceptibility to late onset Alzheimer's Disease (AD influence brain volume and cognition in MS patients.MS subjects were genotyped for five single nucleotide polymorphisms (snps associated with susceptibility to AD: PICALM, CR1, CLU, PCK1, and ZNF224. We assessed brain volume using Brain Parenchymal Fraction (BPF measurements obtained from Magnetic Resonance Imaging (MRI data and cognitive function using the Symbol Digit Modalities Test (SDMT. Genotypes were correlated with cross-sectional BPF and SDMT scores using linear regression after adjusting for sex, age at symptom onset, and disease duration. 722 MS patients with a mean (±SD age at enrollment of 41 (±10 years were followed for 44 (±28 months. The AD risk-associated allele of a non-synonymous SNP in the PCK1 locus (rs8192708G is associated with a smaller average brain volume (P=0.0047 at the baseline MRI, but it does not impact our baseline estimate of cognition. PCK1 is additionally associated with higher baseline T2-hyperintense lesion volume (P=0.0088. Finally, we provide technical validation of our observation in a subset of 641 subjects that have more than one MRI study, demonstrating the same association between PCK1 and smaller average brain volume (P=0.0089 at the last MRI visit.Our study provides suggestive evidence for greater brain atrophy in MS patients bearing the PCK1 allele associated with AD-susceptibility, yielding new insights into potentially shared neurodegenerative process between MS and late onset AD.

Aperture and counting rate of rectangular telescopes for single and multiple parallel particles. [Spark chamber telescopes

Energy Technology Data Exchange (ETDEWEB)

D' Ettorre Piazzoli, B; Mannocchi, G [Consiglio Nazionale delle Ricerche, Turin (Italy). Lab. di Cosmo-Geofisica; Melone, S [Istituto di Fisica dell' Universita, Ancona, Italy; Picchi, P; Visentin, R [Comitato Nazionale per l' Energia Nucleare, Frascati (Italy). Laboratori Nazionali di Frascati

1976-06-01

Expressions for the counting rate of rectangular telescopes in the case of single as well as multiple particles are given. The aperture for single particles is obtained in the form of a double integral and analytical solutions are given for some cases. The intensity for different multiplicities of parallel particles is related to the geometry of the detectors and to the features of the radiation. This allows an absolute comparison between the data recorded by different devices.

Cubic systems with invariant affine straight lines of total parallel multiplicity seven

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Alexandru Suba

2013-12-01

Full Text Available In this article, we study the planar cubic differential systems with invariant affine straight lines of total parallel multiplicity seven. We classify these system according to their geometric properties encoded in the configurations of invariant straight lines. We show that there are only 17 different topological phase portraits in the Poincar\\'e disc associated to this family of cubic systems up to a reversal of the sense of their orbits, and we provide representatives of every class modulo an affine change of variables and rescaling of the time variable.

The BLAZE language - A parallel language for scientific programming

Science.gov (United States)

Mehrotra, Piyush; Van Rosendale, John

1987-01-01

A Pascal-like scientific programming language, BLAZE, is described. BLAZE contains array arithmetic, forall loops, and APL-style accumulation operators, which allow natural expression of fine grained parallelism. It also employs an applicative or functional procedure invocation mechanism, which makes it easy for compilers to extract coarse grained parallelism using machine specific program restructuring. Thus BLAZE should allow one to achieve highly parallel execution on multiprocessor architectures, while still providing the user with conceptually sequential control flow. A central goal in the design of BLAZE is portability across a broad range of parallel architectures. The multiple levels of parallelism present in BLAZE code, in principle, allow a compiler to extract the types of parallelism appropriate for the given architecture while neglecting the remainder. The features of BLAZE are described and it is shown how this language would be used in typical scientific programming.

The BLAZE language: A parallel language for scientific programming

Science.gov (United States)

Mehrotra, P.; Vanrosendale, J.

1985-01-01

A Pascal-like scientific programming language, Blaze, is described. Blaze contains array arithmetic, forall loops, and APL-style accumulation operators, which allow natural expression of fine grained parallelism. It also employs an applicative or functional procedure invocation mechanism, which makes it easy for compilers to extract coarse grained parallelism using machine specific program restructuring. Thus Blaze should allow one to achieve highly parallel execution on multiprocessor architectures, while still providing the user with onceptually sequential control flow. A central goal in the design of Blaze is portability across a broad range of parallel architectures. The multiple levels of parallelism present in Blaze code, in principle, allow a compiler to extract the types of parallelism appropriate for the given architecture while neglecting the remainder. The features of Blaze are described and shows how this language would be used in typical scientific programming.

Explorations of the implementation of a parallel IDW interpolation algorithm in a Linux cluster-based parallel GIS

Science.gov (United States)

Huang, Fang; Liu, Dingsheng; Tan, Xicheng; Wang, Jian; Chen, Yunping; He, Binbin

2011-04-01

To design and implement an open-source parallel GIS (OP-GIS) based on a Linux cluster, the parallel inverse distance weighting (IDW) interpolation algorithm has been chosen as an example to explore the working model and the principle of algorithm parallel pattern (APP), one of the parallelization patterns for OP-GIS. Based on an analysis of the serial IDW interpolation algorithm of GRASS GIS, this paper has proposed and designed a specific parallel IDW interpolation algorithm, incorporating both single process, multiple data (SPMD) and master/slave (M/S) programming modes. The main steps of the parallel IDW interpolation algorithm are: (1) the master node packages the related information, and then broadcasts it to the slave nodes; (2) each node calculates its assigned data extent along one row using the serial algorithm; (3) the master node gathers the data from all nodes; and (4) iterations continue until all rows have been processed, after which the results are outputted. According to the experiments performed in the course of this work, the parallel IDW interpolation algorithm can attain an efficiency greater than 0.93 compared with similar algorithms, which indicates that the parallel algorithm can greatly reduce processing time and maximize speed and performance.

Infectious mononucleosis-linked HLA class I single nucleotide polymorphism is associated with multiple sclerosis.

Science.gov (United States)

Jafari, Naghmeh; Broer, Linda; Hoppenbrouwers, Ilse A; van Duijn, Cornelia M; Hintzen, Rogier Q

2010-11-01

Multiple sclerosis is a presumed autoimmune disease associated with genetic and environmental risk factors such as infectious mononucleosis. Recent research has shown infectious mononucleosis to be associated with a specific HLA class I polymorphism. Our aim was to test if the infectious mononucleosis-linked HLA class I single nucleotide polymorphism (rs6457110) is also associated with multiple sclerosis. Genotyping of the HLA-A single nucleotide polymorphism rs6457110 using TaqMan was performed in 591 multiple sclerosis cases and 600 controls. The association of multiple sclerosis with the HLA-A single nucleotide polymorphism was tested using logistic regression adjusted for age, sex and HLA-DRB1*1501. HLA-A minor allele (A) is associated with multiple sclerosis (OR = 0.68; p = 4.08 × 10( -5)). After stratification for HLA-DRB1*1501 risk allele (T) carrier we showed a significant OR of 0.70 (p = 0.003) for HLA-A. HLA class I single nucleotide polymorphism rs6457110 is associated with infectious mononucleosis and multiple sclerosis, independent of the major class II allele, supporting the hypothesis that shared genetics may contribute to the association between infectious mononucleosis and multiple sclerosis.

Ploidy mosaicism and allele-specific gene expression differences in the allopolyploid Squalius alburnoides

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Matos Isa

2011-12-01

Full Text Available Abstract Background Squalius alburnoides is an Iberian cyprinid fish resulting from an interspecific hybridisation between Squalius pyrenaicus females (P genome and males of an unknown Anaecypris hispanica-like species (A genome. S. alburnoides is an allopolyploid hybridogenetic complex, which makes it a likely candidate for ploidy mosaicism occurrence, and is also an interesting model to address questions about gene expression regulation and genomic interactions. Indeed, it was previously suggested that in S. alburnoides triploids (PAA composition silencing of one of the three alleles (mainly of the P allele occurs. However, not a whole haplome is inactivated but a more or less random inactivation of alleles varying between individuals and even between organs of the same fish was seen. In this work we intended to correlate expression differences between individuals and/or between organs to the occurrence of mosaicism, evaluating if mosaics could explain previous observations and its impact on the assessment of gene expression patterns. Results To achieve our goal, we developed flow cytometry and cell sorting protocols for this system generating more homogenous cellular and transcriptional samples. With this set-up we detected 10% ploidy mosaicism within the S. alburnoides complex, and determined the allelic expression profiles of ubiquitously expressed genes (rpl8; gapdh and β-actin in cells from liver and kidney of mosaic and non-mosaic individuals coming from different rivers over a wide geographic range. Conclusions Ploidy mosaicism occurs sporadically within the S. alburnoides complex, but in a frequency significantly higher than reported for other organisms. Moreover, we could exclude the influence of this phenomenon on the detection of variable allelic expression profiles of ubiquitously expressed genes (rpl8; gapdh and β-actin in cells from liver and kidney of triploid individuals. Finally, we determined that the expression patterns

Stepped-wedge cluster randomised controlled trials: a generic framework including parallel and multiple-level designs.

Science.gov (United States)

Hemming, Karla; Lilford, Richard; Girling, Alan J

2015-01-30

Stepped-wedge cluster randomised trials (SW-CRTs) are being used with increasing frequency in health service evaluation. Conventionally, these studies are cross-sectional in design with equally spaced steps, with an equal number of clusters randomised at each step and data collected at each and every step. Here we introduce several variations on this design and consider implications for power. One modification we consider is the incomplete cross-sectional SW-CRT, where the number of clusters varies at each step or where at some steps, for example, implementation or transition periods, data are not collected. We show that the parallel CRT with staggered but balanced randomisation can be considered a special case of the incomplete SW-CRT. As too can the parallel CRT with baseline measures. And we extend these designs to allow for multiple layers of clustering, for example, wards within a hospital. Building on results for complete designs, power and detectable difference are derived using a Wald test and obtaining the variance-covariance matrix of the treatment effect assuming a generalised linear mixed model. These variations are illustrated by several real examples. We recommend that whilst the impact of transition periods on power is likely to be small, where they are a feature of the design they should be incorporated. We also show examples in which the power of a SW-CRT increases as the intra-cluster correlation (ICC) increases and demonstrate that the impact of the ICC is likely to be smaller in a SW-CRT compared with a parallel CRT, especially where there are multiple levels of clustering. Finally, through this unified framework, the efficiency of the SW-CRT and the parallel CRT can be compared. © 2014 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Human Platelet Antigen Alleles in 998 Taiwanese Blood Donors Determined by Sequence-Specific Primer Polymerase Chain Reaction

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Shun-Chung Pai

2013-01-01

Full Text Available Polymorphism of human platelet antigens (HPAs leads to alloimmunizations and immune-mediated platelet disorders including fetal-neonatal alloimmune thrombocytopenia (FNAIT, posttransfusion purpura (PTP, and platelet transfusion refractoriness (PTR. HPA typing and knowledge of antigen frequency in a population are important in particular for the provision of HPA-matched blood components for patients with PTR. We have performed allele genotyping for HPA-1 through -6 and -15 among 998 platelet donors from 6 blood centers in Taiwan using sequence-specific primer polymerase chain reaction. The HPA allele frequency was 99.55, and 0.45% for HPA-1a and -1b; 96.49, and 3.51% for HPA-2a and -2b; 55.81, and 44.19% for HPA-3a and -3b; 99.75, and 0.25% for HPA-4a and -4b; 98.50, and 1.50% for HPA-5a and -5b; 97.75 and 2.25% for HPA-6a and -6b; 53.71 and 46.29% for HPA-15a and -15b. HPA-15b and HPA-3a, may be considered the most important, followed by HPA-2, -6, -1, -5, and -4 systems, as a cause of FNAIT, PTP, and PTR based on allele frequency. HPA-4b and HPA-5b role cannot be excluded based on their immunogenicity. A larger-scale study will now be conducted to confirm these hypotheses and to establish an apheresis donor database for the procurement of HPA-matched apheresis platelets for patients with PTR.

Allele-specific primer polymerase chain reaction for a single nucleotide polymorphism (C1205T) of swine Toll-like receptor 5 and comparison of the allelic frequency among several pig breeds in Japan and the Czech Republic

Czech Academy of Sciences Publication Activity Database

Muneta, Y.; Minagawa, Y.; Kusumoto, M.; Shinkai, H.; Uenishi, H.; Šplíchal, Igor

2012-01-01

Roč. 56, č. 6 (2012), s. 385-391 ISSN 0385-5600 R&D Projects: GA ČR GA524/09/0365 Institutional support: RVO:61388971 Keywords : allele-specific PCR * Salmonella enterica serovar Choleraesuis * single nucleotide polymorphism Subject RIV: EC - Immunology Impact factor: 1.545, year: 2012

Column-Parallel Single Slope ADC with Digital Correlated Multiple Sampling for Low Noise CMOS Image Sensors

NARCIS (Netherlands)

Chen, Y.; Theuwissen, A.J.P.; Chae, Y.

2011-01-01

This paper presents a low noise CMOS image sensor (CIS) using 10/12 bit configurable column-parallel single slope ADCs (SS-ADCs) and digital correlated multiple sampling (CMS). The sensor used is a conventional 4T active pixel with a pinned-photodiode as photon detector. The test sensor was

multiPDEVS: A Parallel Multicomponent System Specification Formalism

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Damien Foures

2018-01-01

Full Text Available Based on multiDEVS formalism, we introduce multiPDEVS, a parallel and nonmodular formalism for discrete event system specification. This formalism provides combined advantages of PDEVS and multiDEVS approaches, such as excellent simulation capabilities for simultaneously scheduled events and components able to influence each other using exclusively their state transitions. We next show the soundness of the formalism by giving a construction showing that any multiPDEVS model is equivalent to a PDEVS atomic model. We then present the simulation procedure associated, usually called abstract simulator. As a well-adapted formalism to express cellular automata, we finally propose to compare an implementation of multiPDEVS formalism with a more classical Cell-DEVS implementation through a fire spread application.

SU94. Allele-Specific and Trauma-Related Epigenetic Changes in the FKBP5 Gene: Differences Between Psychotic Patients and Healthy Controls

Science.gov (United States)

Mihaljevic, Marina; Franic, Dusica; Soldatovic, Ivan; Andric, Sanja; Mirjanic, Tijana; Novakovic, Ivana; Adzic, Miroslav; Maric, Nadja

2017-01-01

Abstract Background: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is a proposed etiological mechanism of psychosis. Recent studies highlighted impact of the FKBP5 gene and its functional variant rs1360780, which risk (T) allele affects the activity of HPA axis following stress exposure, on psychotic patients exposed to early trauma (1). Additionally, risk allele and trauma dependent FKBP5 demethylation in intron 7 was observed in traumatized individuals (2). Thus, the purpose of this pilot study was to investigate influence of the risk allele and trauma on FKBP5 DNA methylation levels at intron 7 in psychotic patients and to compare it with healthy individuals. Methods: The sample consisted of 24 psychosis spectrum patients and 24 controls matched by age and gender. All participants were genotyped for rs1360780 and divided into 2 groups depending on the presence of the risk allele (risk and nonrisk group). DNA methylation levels at 3 CpG sites (CpG1, CpG2, and CpG3) in intron 7 were analyzed by Sanger sequencing. Early-life adversities were measured by Childhood Trauma Questionnaire. Pearson correlation and t test were performed as appropriate. Results: Analyses revealed decreased FKBP5 methylation at targeted CpG sites and averaged methylation level (AML) at intron 7 in patients compared to controls (P = .026, P = .017, P = .027, and P = .003, respectively). Decreased AML and methylation at CpG3 were observed comparing risk and nonrisk patients’ groups (P = .018 and P = .016, respectively). Additionally, decreased methylation was found in risk patients’ group compared to risk controls’ group. No differences were found comparing nonrisk groups. Furthermore, strong negative associations between trauma and methylation at CpG3 and AML were observed only in risk controls’ group (r = −0.707, P = .007; r = −0.741, P = .004, respectively). Conclusion: Our preliminary results revealed allele-specific epigenetic changes of the FKBP

Identical parallel machine scheduling with nonlinear deterioration and multiple rate modifying activities

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Ömer Öztürkoğlu

2017-07-01

Full Text Available This study focuses on identical parallel machine scheduling of jobs with deteriorating processing times and rate-modifying activities. We consider non linearly increasing processing times of jobs based on their position assignment. Rate modifying activities are also considered to recover the increase in processing times of jobs due to deterioration. We also propose heuristics algorithms that rely on ant colony optimization and simulated annealing algorithms to solve the problem with multiple RMAs in a reasonable amount of time. Finally, we show that ant colony optimization algorithm generates close optimal solutions and superior results than simulated annealing algorithm.

An Efficient Stepwise Statistical Test to Identify Multiple Linked Human Genetic Variants Associated with Specific Phenotypic Traits.

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Iksoo Huh

Full Text Available Recent advances in genotyping methodologies have allowed genome-wide association studies (GWAS to accurately identify genetic variants that associate with common or pathological complex traits. Although most GWAS have focused on associations with single genetic variants, joint identification of multiple genetic variants, and how they interact, is essential for understanding the genetic architecture of complex phenotypic traits. Here, we propose an efficient stepwise method based on the Cochran-Mantel-Haenszel test (for stratified categorical data to identify causal joint multiple genetic variants in GWAS. This method combines the CMH statistic with a stepwise procedure to detect multiple genetic variants associated with specific categorical traits, using a series of associated I × J contingency tables and a null hypothesis of no phenotype association. Through a new stratification scheme based on the sum of minor allele count criteria, we make the method more feasible for GWAS data having sample sizes of several thousands. We also examine the properties of the proposed stepwise method via simulation studies, and show that the stepwise CMH test performs better than other existing methods (e.g., logistic regression and detection of associations by Markov blanket for identifying multiple genetic variants. Finally, we apply the proposed approach to two genomic sequencing datasets to detect linked genetic variants associated with bipolar disorder and obesity, respectively.

Multiple double cross-section transmission electron microscope sample preparation of specific sub-10 nm diameter Si nanowire devices.

Science.gov (United States)

Gignac, Lynne M; Mittal, Surbhi; Bangsaruntip, Sarunya; Cohen, Guy M; Sleight, Jeffrey W

2011-12-01

The ability to prepare multiple cross-section transmission electron microscope (XTEM) samples from one XTEM sample of specific sub-10 nm features was demonstrated. Sub-10 nm diameter Si nanowire (NW) devices were initially cross-sectioned using a dual-beam focused ion beam system in a direction running parallel to the device channel. From this XTEM sample, both low- and high-resolution transmission electron microscope (TEM) images were obtained from six separate, specific site Si NW devices. The XTEM sample was then re-sectioned in four separate locations in a direction perpendicular to the device channel: 90° from the original XTEM sample direction. Three of the four XTEM samples were successfully sectioned in the gate region of the device. From these three samples, low- and high-resolution TEM images of the Si NW were taken and measurements of the NW diameters were obtained. This technique demonstrated the ability to obtain high-resolution TEM images in directions 90° from one another of multiple, specific sub-10 nm features that were spaced 1.1 μm apart.

Streaming for Functional Data-Parallel Languages

DEFF Research Database (Denmark)

Madsen, Frederik Meisner

In this thesis, we investigate streaming as a general solution to the space inefficiency commonly found in functional data-parallel programming languages. The data-parallel paradigm maps well to parallel SIMD-style hardware. However, the traditional fully materializing execution strategy...... by extending two existing data-parallel languages: NESL and Accelerate. In the extensions we map bulk operations to data-parallel streams that can evaluate fully sequential, fully parallel or anything in between. By a dataflow, piecewise parallel execution strategy, the runtime system can adjust to any target...... flattening necessitates all sub-computations to materialize at the same time. For example, naive n by n matrix multiplication requires n^3 space in NESL because the algorithm contains n^3 independent scalar multiplications. For large values of n, this is completely unacceptable. We address the problem...

Transposable elements generate population-specific insertional patterns and allelic variation in genes of wild emmer wheat (Triticum turgidum ssp. dicoccoides).

Science.gov (United States)

Domb, Katherine; Keidar, Danielle; Yaakov, Beery; Khasdan, Vadim; Kashkush, Khalil

2017-10-27

Natural populations of the tetraploid wild emmer wheat (genome AABB) were previously shown to demonstrate eco-geographically structured genetic and epigenetic diversity. Transposable elements (TEs) might make up a significant part of the genetic and epigenetic variation between individuals and populations because they comprise over 80% of the wild emmer wheat genome. In this study, we performed detailed analyses to assess the dynamics of transposable elements in 50 accessions of wild emmer wheat collected from 5 geographically isolated sites. The analyses included: the copy number variation of TEs among accessions in the five populations, population-unique insertional patterns, and the impact of population-unique/specific TE insertions on structure and expression of genes. We assessed the copy numbers of 12 TE families using real-time quantitative PCR, and found significant copy number variation (CNV) in the 50 wild emmer wheat accessions, in a population-specific manner. In some cases, the CNV difference reached up to 6-fold. However, the CNV was TE-specific, namely some TE families showed higher copy numbers in one or more populations, and other TE families showed lower copy numbers in the same population(s). Furthermore, we assessed the insertional patterns of 6 TE families using transposon display (TD), and observed significant population-specific insertional patterns. The polymorphism levels of TE-insertional patterns reached 92% among all wild emmer wheat accessions, in some cases. In addition, we observed population-specific/unique TE insertions, some of which were located within or close to protein-coding genes, creating allelic variations in a population-specific manner. We also showed that those genes are differentially expressed in wild emmer wheat. For the first time, this study shows that TEs proliferate in wild emmer wheat in a population-specific manner, creating new alleles of genes, which contribute to the divergent evolution of homeologous genes

Parallel arrangements of positive feedback loops limit cell-to-cell variability in differentiation.

Science.gov (United States)

Dey, Anupam; Barik, Debashis

2017-01-01

Cellular differentiations are often regulated by bistable switches resulting from specific arrangements of multiple positive feedback loops (PFL) fused to one another. Although bistability generates digital responses at the cellular level, stochasticity in chemical reactions causes population heterogeneity in terms of its differentiated states. We hypothesized that the specific arrangements of PFLs may have evolved to minimize the cellular heterogeneity in differentiation. In order to test this we investigated variability in cellular differentiation controlled either by parallel or serial arrangements of multiple PFLs having similar average properties under extrinsic and intrinsic noises. We find that motifs with PFLs fused in parallel to one another around a central regulator are less susceptible to noise as compared to the motifs with PFLs arranged serially. Our calculations suggest that the increased resistance to noise in parallel motifs originate from the less sensitivity of bifurcation points to the extrinsic noise. Whereas estimation of mean residence times indicate that stable branches of bifurcations are robust to intrinsic noise in parallel motifs as compared to serial motifs. Model conclusions are consistent both in AND- and OR-gate input signal configurations and also with two different modeling strategies. Our investigations provide some insight into recent findings that differentiation of preadipocyte to mature adipocyte is controlled by network of parallel PFLs.

Distributed parallel messaging for multiprocessor systems

Science.gov (United States)

Chen, Dong; Heidelberger, Philip; Salapura, Valentina; Senger, Robert M; Steinmacher-Burrow, Burhard; Sugawara, Yutaka

2013-06-04

A method and apparatus for distributed parallel messaging in a parallel computing system. The apparatus includes, at each node of a multiprocessor network, multiple injection messaging engine units and reception messaging engine units, each implementing a DMA engine and each supporting both multiple packet injection into and multiple reception from a network, in parallel. The reception side of the messaging unit (MU) includes a switch interface enabling writing of data of a packet received from the network to the memory system. The transmission side of the messaging unit, includes switch interface for reading from the memory system when injecting packets into the network.

A common polymorphism in the promoter region of the TNFSF4 gene is associated with lower allele-specific expression and risk of myocardial infarction.

Directory of Open Access Journals (Sweden)

Massimiliano Ria

Full Text Available BACKGROUND: The TNFSF4/TNFRSF4 system, along with several other receptor-ligand pairs, is involved in the recruitment and activation of T-cells and is therefore tentatively implicated in atherosclerosis and acute coronary syndromes. We have previously shown that genetic variants in TNFSF4 are associated with myocardial infarction (MI in women. This prompted functional studies of TNFSF4 expression. METHODS AND RESULTS: Based on a screening of the TNFSF4 genomic region, a promoter polymorphism (rs45454293 and a haplotype were identified, conceivably involved in gene regulation. The rs45454293T-allele, in agreement with the linked rs3850641G-allele, proved to be associated with increased risk of MI in women. Haplotype-specific chromatin immunoprecipitation of activated polymerase II, as a measure of transcriptional activity in vivo, suggested that the haplotype including the rs45454293 and rs3850641 polymorphisms is functionally important, the rs45454293T- and rs3850641G-alleles being associated with lower transcriptional activity in cells heterozygous for both polymorphisms. The functional role of rs45454293 on transcriptional levels of TNFSF4 was clarified by luciferase reporter assays, where the rs45454293T-allele decreased gene expression when compared with the rs45454293C-allele, while the rs3850641 SNP did not have any effect on TNFSF4 promoter activity. Electromobility shift assay showed that the rs45454293 polymorphism, but not rs3850641, affects the binding of nuclear factors, thus suggesting that the lower transcriptional activity is attributed to binding of one or more transcriptional repressor(s to the T-allele. CONCLUSIONS: Our data indicate that the TNFSF4 rs45454293T-allele is associated with lower TNFSF4 expression and increased risk of MI.

Parallel integer sorting with medium and fine-scale parallelism

Science.gov (United States)

Dagum, Leonardo

1993-01-01

Two new parallel integer sorting algorithms, queue-sort and barrel-sort, are presented and analyzed in detail. These algorithms do not have optimal parallel complexity, yet they show very good performance in practice. Queue-sort designed for fine-scale parallel architectures which allow the queueing of multiple messages to the same destination. Barrel-sort is designed for medium-scale parallel architectures with a high message passing overhead. The performance results from the implementation of queue-sort on a Connection Machine CM-2 and barrel-sort on a 128 processor iPSC/860 are given. The two implementations are found to be comparable in performance but not as good as a fully vectorized bucket sort on the Cray YMP.

Assessment of the myostatin Q204X allele using an allelic discrimination assay

OpenAIRE

Sifuentes-Rincón,Ana M.; Puentes-Montiel,Herlinda E.; Moreno-Medina,Víctor R.; Rosa-Reyna,Xóchitl F. de la

2006-01-01

An allelic discrimination assay was designed and used to determine the genotypic and allelic frequencies of the myostatin (MSTN) gene Q204X allele from two Mexican Full-French herds. The assay is a simple high throughput genotyping method that could be applied to investigate the effect of the Q204X allele on the Charolais breed.

Correlation between carboxylesterase alleles and insecticide resistance in Culex pipiens complex from China

Directory of Open Access Journals (Sweden)

Liu Yangyang

2011-12-01

Full Text Available Abstract Background In China, large amounts of chemical insecticides are applied in fields or indoors every year, directly or indirectly bringing selection pressure on vector mosquitoes. Culex pipiens complex has evolved to be resistant to all types of chemical insecticides, especially organophosphates, through carboxylesterases. Six resistant carboxylesterase alleles (Ester were recorded previously and sometimes co-existed in one field population, representing a complex situation for the evolution of Ester genes. Results In order to explore the evolutionary scenario, we analyzed the data from an historical record in 2003 and a recent investigation on five Culex pipiens pallens populations sampled from north China in 2010. Insecticide bioassays showed that these five populations had high resistance to pyrethroids, medium resistance to organophosphates, and low resistance to carbamates. Six types of Ester alleles, EsterB1, Ester2, Ester8, Ester9, EsterB10, and Ester11 were identified, and the overall pattern of their frequencies in geographic distribution was consistent with the report seven years prior to this study. Statistical correlation analysis indicated that Ester8 and Ester9 positively correlated with resistance to four insecticides, and EsterB10 to one insecticide. The occurrences of these three alleles were positively correlated, while the occurrence of EsterB1 was negatively correlated with Ester8, indicating an allelic competition. Conclusion Our analysis suggests that one insecticide can select multiple Ester alleles and one Ester allele can work on multiple insecticides. The evolutionary scenario of carboxylesterases under insecticide selection is possibly "one to many".

Using the Textpresso Site-Specific Recombinases Web server to identify Cre expressing mouse strains and floxed alleles.

Science.gov (United States)

Condie, Brian G; Urbanski, William M

2014-01-01

Effective tools for searching the biomedical literature are essential for identifying reagents or mouse strains as well as for effective experimental design and informed interpretation of experimental results. We have built the Textpresso Site Specific Recombinases (Textpresso SSR) Web server to enable researchers who use mice to perform in-depth searches of a rapidly growing and complex part of the mouse literature. Our Textpresso Web server provides an interface for searching the full text of most of the peer-reviewed publications that report the characterization or use of mouse strains that express Cre or Flp recombinase. The database also contains most of the publications that describe the characterization or analysis of strains carrying conditional alleles or transgenes that can be inactivated or activated by site-specific recombinases such as Cre or Flp. Textpresso SSR complements the existing online databases that catalog Cre and Flp expression patterns by providing a unique online interface for the in-depth text mining of the site specific recombinase literature.

Introduction to parallel programming

CERN Document Server

Brawer, Steven

1989-01-01

Introduction to Parallel Programming focuses on the techniques, processes, methodologies, and approaches involved in parallel programming. The book first offers information on Fortran, hardware and operating system models, and processes, shared memory, and simple parallel programs. Discussions focus on processes and processors, joining processes, shared memory, time-sharing with multiple processors, hardware, loops, passing arguments in function/subroutine calls, program structure, and arithmetic expressions. The text then elaborates on basic parallel programming techniques, barriers and race

Pyramiding of transgenic Pm3 alleles in wheat results in improved powdery mildew resistance in the field.

Science.gov (United States)

Koller, Teresa; Brunner, Susanne; Herren, Gerhard; Hurni, Severine; Keller, Beat

2018-04-01

The combined effects of enhanced total transgene expression level and allele-specificity combination in transgenic allele-pyramided Pm3 wheat lines result in improved powdery mildew field resistance without negative pleiotropic effects. Allelic Pm3 resistance genes of wheat confer race-specific resistance to powdery mildew (Blumeria graminis f. sp. tritici, Bgt) and encode nucleotide-binding domain, leucine-rich repeat (NLR) receptors. Transgenic wheat lines overexpressing alleles Pm3a, b, c, d, f, and g have previously been generated by transformation of cultivar Bobwhite and tested in field trials, revealing varying degrees of powdery mildew resistance conferred by the transgenes. Here, we tested four transgenic lines each carrying two pyramided Pm3 alleles, which were generated by crossbreeding of lines transformed with single Pm3 alleles. All four allele-pyramided lines showed strongly improved powdery mildew resistance in the field compared to their parental lines. The improved resistance results from the two effects of enhanced total transgene expression levels and allele-specificity combinations. In contrast to leaf segment tests on greenhouse-grown seedlings, no allelic suppression was observed in the field. Plant development and yield scores of the pyramided lines were similar to the mean scores of the corresponding parental lines, and thus, the allele pyramiding did not cause any negative effects. On the contrary, in pyramided line, Pm3b × Pm3f normal plant development was restored compared to the delayed development and reduced seed set of parental line Pm3f. Allele-specific RT qPCR revealed additive transgene expression levels of the two Pm3 alleles in the pyramided lines. A positive correlation between total transgene expression level and powdery mildew field resistance was observed. In summary, allele pyramiding of Pm3 transgenes proved to be successful in enhancing powdery mildew field resistance.

Early Parallel Activation of Semantics and Phonology in Picture Naming: Evidence from a Multiple Linear Regression MEG Study.

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Miozzo, Michele; Pulvermüller, Friedemann; Hauk, Olaf

2015-10-01

The time course of brain activation during word production has become an area of increasingly intense investigation in cognitive neuroscience. The predominant view has been that semantic and phonological processes are activated sequentially, at about 150 and 200-400 ms after picture onset. Although evidence from prior studies has been interpreted as supporting this view, these studies were arguably not ideally suited to detect early brain activation of semantic and phonological processes. We here used a multiple linear regression approach to magnetoencephalography (MEG) analysis of picture naming in order to investigate early effects of variables specifically related to visual, semantic, and phonological processing. This was combined with distributed minimum-norm source estimation and region-of-interest analysis. Brain activation associated with visual image complexity appeared in occipital cortex at about 100 ms after picture presentation onset. At about 150 ms, semantic variables became physiologically manifest in left frontotemporal regions. In the same latency range, we found an effect of phonological variables in the left middle temporal gyrus. Our results demonstrate that multiple linear regression analysis is sensitive to early effects of multiple psycholinguistic variables in picture naming. Crucially, our results suggest that access to phonological information might begin in parallel with semantic processing around 150 ms after picture onset. © The Author 2014. Published by Oxford University Press.

Utilization of a ts-sacB selection system for the generation of a Mycobacterium avium serovar-8 specific glycopeptidolipid allelic exchange mutant

Science.gov (United States)

Irani, Vida R; Lee, Sun-Hwa; Eckstein, Torsten M; Inamine, Julia M; Belisle, John T; Maslow, Joel N

2004-01-01

Background Mycobacterium avium are ubiquitous environmental organisms and a cause of disseminated infection in patients with end-stage AIDS. The glycopeptidolipids (GPL) of M. avium are proposed to participate in the pathogenesis of this organism, however, establishment of a clear role for GPL in disease production has been limited by the inability to genetically manipulate M. avium. Methods To be able to study the role of the GPL in M. avium pathogenesis, a ts-sacB selection system, not previously used in M. avium, was employed as a means to achieve homologous recombination for the rhamnosyltransferase (rtfA) gene of a pathogenic serovar 8 strain of M. avium to prevent addition of serovar-specific sugars to rhamnose of the fatty acyl-peptide backbone of GPL. The genotype of the resultant rtfA mutant was confirmed by polymerase chain reaction and southern hybridization. Disruption in the proximal sugar of the haptenic oligosaccharide resulted in the loss of serovar specific GPL with no change in the pattern of non-serovar specific GPL moieties as shown by thin layer chromatography and gas chromatography/mass spectrometry. Complementation of wild type (wt) rtfA in trans through an integrative plasmid restored serovar-8 specific GPL expression identical to wt serovar 8 parent strain. Results In this study, we affirm our results that rtfA encodes an enzyme responsible for the transfer of Rha to 6d-Tal and provide evidence of a second allelic exchange mutagenesis system suitable for M. avium. Conclusion We report the second allelic exchange system for M. avium utilizing ts-sacB as double-negative and xylE as positive counter-selection markers, respectively. This system of allelic exchange would be especially useful for M. avium strains that demonstrate significant isoniazid (INH) resistance despite transformation with katG. Through the construction of mutants in GPL or other mycobacterial components, their roles in M. avium pathogenesis, biosynthesis, or drug

Utilization of a ts-sacB selection system for the generation of a Mycobacterium avium serovar-8 specific glycopeptidolipid allelic exchange mutant

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Belisle John T

2004-09-01

Full Text Available Abstract Background Mycobacterium avium are ubiquitous environmental organisms and a cause of disseminated infection in patients with end-stage AIDS. The glycopeptidolipids (GPL of M. avium are proposed to participate in the pathogenesis of this organism, however, establishment of a clear role for GPL in disease production has been limited by the inability to genetically manipulate M. avium. Methods To be able to study the role of the GPL in M. avium pathogenesis, a ts-sacB selection system, not previously used in M. avium, was employed as a means to achieve homologous recombination for the rhamnosyltransferase (rtfA gene of a pathogenic serovar 8 strain of M. avium to prevent addition of serovar-specific sugars to rhamnose of the fatty acyl-peptide backbone of GPL. The genotype of the resultant rtfA mutant was confirmed by polymerase chain reaction and southern hybridization. Disruption in the proximal sugar of the haptenic oligosaccharide resulted in the loss of serovar specific GPL with no change in the pattern of non-serovar specific GPL moieties as shown by thin layer chromatography and gas chromatography/mass spectrometry. Complementation of wild type (wt rtfA in trans through an integrative plasmid restored serovar-8 specific GPL expression identical to wt serovar 8 parent strain. Results In this study, we affirm our results that rtfA encodes an enzyme responsible for the transfer of Rha to 6d-Tal and provide evidence of a second allelic exchange mutagenesis system suitable for M. avium. Conclusion We report the second allelic exchange system for M. avium utilizing ts-sacB as double-negative and xylE as positive counter-selection markers, respectively. This system of allelic exchange would be especially useful for M. avium strains that demonstrate significant isoniazid (INH resistance despite transformation with katG. Through the construction of mutants in GPL or other mycobacterial components, their roles in M. avium pathogenesis

HLA Dr beta 1 alleles in Pakistani patients with rheumatoid arthritis

International Nuclear Information System (INIS)

Naqi, N.; Ahmed, T.A.; Bashir, M.M.

2011-01-01

Objective: To determine frequencies of HLA DR beta 1 alleles in rheumatoid arthritis in Pakistani patients. Study Design: Cross sectional / analytical study. Place and Duration of Study: Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi in collaboration with Rheumatology departments of Military Hospital, Rawalpindi and Fauji Foundation Hospital, Rawalpindi, from January 2009 to January 2010. Methodology: HLA DR beta 1 genotyping of one hundred Pakistani patients, diagnosed as having RA as per American College of Rheumatology revised criteria 1987, was done. HLA DR beta 1 genotyping was carried out at allele group level (DR beta 1*01-DR beta 1*16) by sequence specific primers in RA patients. Comparison of HLA DR beta 1 allele frequencies between patients and control groups was made using Pearson's chi-square test to find possible association of HLA DR?1 alleles with RA in Pakistani rheumatoid patients. Results: HLA DR beta 1*04 was expressed with significantly increased frequency in patients with rheumatoid arthritis (p <0.05). HLA DR?1*11 was expressed statistically significantly more in control group as compared to rheumatoid patients indicating a possible protective effect. There was no statistically significant difference observed in frequencies of HLA DR beta 1 allele *01, DR beta 1 allele *03, DR beta 1 allele *07, DR beta 1 allele *08, DR beta 1 allele *09, DR beta 1 allele *10, DR beta 1 allele *12, DR beta 1 allele *13, DR beta 1 allele *14, DR?1 allele *15 and DR beta 1 allele *16 between patients and control groups. Conclusion: The identification of susceptible HLA DR beta 1 alleles in Pakistani RA patients may help physicians to make early decisions regarding initiation of early intensive therapy with disease modifying anti rheumatic medicines and biological agents decreasing disability in RA patients. (author)

The Galley Parallel File System

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Nieuwejaar, Nils; Kotz, David

1996-01-01

Most current multiprocessor file systems are designed to use multiple disks in parallel, using the high aggregate bandwidth to meet the growing I/0 requirements of parallel scientific applications. Many multiprocessor file systems provide applications with a conventional Unix-like interface, allowing the application to access multiple disks transparently. This interface conceals the parallelism within the file system, increasing the ease of programmability, but making it difficult or impossible for sophisticated programmers and libraries to use knowledge about their I/O needs to exploit that parallelism. In addition to providing an insufficient interface, most current multiprocessor file systems are optimized for a different workload than they are being asked to support. We introduce Galley, a new parallel file system that is intended to efficiently support realistic scientific multiprocessor workloads. We discuss Galley's file structure and application interface, as well as the performance advantages offered by that interface.

Parallel point-multiplication architecture using combined group operations for high-speed cryptographic applications.

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Md Selim Hossain

Full Text Available In this paper, we propose a novel parallel architecture for fast hardware implementation of elliptic curve point multiplication (ECPM, which is the key operation of an elliptic curve cryptography processor. The point multiplication over binary fields is synthesized on both FPGA and ASIC technology by designing fast elliptic curve group operations in Jacobian projective coordinates. A novel combined point doubling and point addition (PDPA architecture is proposed for group operations to achieve high speed and low hardware requirements for ECPM. It has been implemented over the binary field which is recommended by the National Institute of Standards and Technology (NIST. The proposed ECPM supports two Koblitz and random curves for the key sizes 233 and 163 bits. For group operations, a finite-field arithmetic operation, e.g. multiplication, is designed on a polynomial basis. The delay of a 233-bit point multiplication is only 3.05 and 3.56 μs, in a Xilinx Virtex-7 FPGA, for Koblitz and random curves, respectively, and 0.81 μs in an ASIC 65-nm technology, which are the fastest hardware implementation results reported in the literature to date. In addition, a 163-bit point multiplication is also implemented in FPGA and ASIC for fair comparison which takes around 0.33 and 0.46 μs, respectively. The area-time product of the proposed point multiplication is very low compared to similar designs. The performance ([Formula: see text] and Area × Time × Energy (ATE product of the proposed design are far better than the most significant studies found in the literature.

Performance analysis of a threshold-based parallel multiple beam selection scheme for WDM-based systems for Gamma-Gamma distributions

KAUST Repository

Nam, Sung Sik; Yoon, Chang Seok; Alouini, Mohamed-Slim

2017-01-01

In this paper, we statistically analyze the performance of a threshold-based parallel multiple beam selection scheme (TPMBS) for Free-space optical (FSO) based system with wavelength division multiplexing (WDM) in cases where a pointing error has

An extensive allelic series of Drosophila kae1 mutants reveals diverse and tissue-specific requirements for t6A biogenesis

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Lin, Ching-Jung; Smibert, Peter; Zhao, Xiaoyu; Hu, Jennifer F.; Ramroop, Johnny; Kellner, Stefanie M.; Benton, Matthew A.; Govind, Shubha; Dedon, Peter C.; Sternglanz, Rolf; Lai, Eric C.

2015-01-01

N6-threonylcarbamoyl-adenosine (t6A) is one of the few RNA modifications that is universally present in life. This modification occurs at high frequency at position 37 of most tRNAs that decode ANN codons, and stabilizes cognate anticodon–codon interactions. Nearly all genetic studies of the t6A pathway have focused on single-celled organisms. In this study, we report the isolation of an extensive allelic series in the Drosophila ortholog of the core t6A biosynthesis factor Kae1. kae1 hemizygous larvae exhibit decreases in t6A that correlate with allele strength; however, we still detect substantial t6A-modified tRNAs even during the extended larval phase of null alleles. Nevertheless, complementation of Drosophila Kae1 and other t6A factors in corresponding yeast null mutants demonstrates that these metazoan genes execute t6A synthesis. Turning to the biological consequences of t6A loss, we characterize prominent kae1 melanotic masses and show that they are associated with lymph gland overgrowth and ectopic generation of lamellocytes. On the other hand, kae1 mutants exhibit other phenotypes that reflect insufficient tissue growth. Interestingly, whole-tissue and clonal analyses show that strongly mitotic tissues such as imaginal discs are exquisitely sensitive to loss of kae1, whereas nonproliferating tissues are less affected. Indeed, despite overt requirements of t6A for growth of many tissues, certain strong kae1 alleles achieve and sustain enlarged body size during their extended larval phase. Our studies highlight tissue-specific requirements of the t6A pathway in a metazoan context and provide insights into the diverse biological roles of this fundamental RNA modification during animal development and disease. PMID:26516084

Parallel arrangements of positive feedback loops limit cell-to-cell variability in differentiation.

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Anupam Dey

Full Text Available Cellular differentiations are often regulated by bistable switches resulting from specific arrangements of multiple positive feedback loops (PFL fused to one another. Although bistability generates digital responses at the cellular level, stochasticity in chemical reactions causes population heterogeneity in terms of its differentiated states. We hypothesized that the specific arrangements of PFLs may have evolved to minimize the cellular heterogeneity in differentiation. In order to test this we investigated variability in cellular differentiation controlled either by parallel or serial arrangements of multiple PFLs having similar average properties under extrinsic and intrinsic noises. We find that motifs with PFLs fused in parallel to one another around a central regulator are less susceptible to noise as compared to the motifs with PFLs arranged serially. Our calculations suggest that the increased resistance to noise in parallel motifs originate from the less sensitivity of bifurcation points to the extrinsic noise. Whereas estimation of mean residence times indicate that stable branches of bifurcations are robust to intrinsic noise in parallel motifs as compared to serial motifs. Model conclusions are consistent both in AND- and OR-gate input signal configurations and also with two different modeling strategies. Our investigations provide some insight into recent findings that differentiation of preadipocyte to mature adipocyte is controlled by network of parallel PFLs.

Evolution of the proportions of two sigma viral types in experimental populations of Drosophila melanogaster in the absence of the allele that is restrictive of viral multiplication.

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Fleuriet, A

1999-12-01

A minority of flies in natural populations of Drosophila melanogaster are endemically infected by a rhabdovirus, sigma. The virus is vertically transmitted through male and female gametes. Two alleles of a fly locus, the ref(2)P locus, are present as a polymorphism in all populations: O permissive, and P restrictive for viral multiplication and transmission. Two viral types are known, Type I, which is very sensitive to the P allele, and Type II, which is more resistant. Previous observations have shown that, in presence of the P allele, viral Type II is selected for, in both natural and experimental populations. The aim of the present study was to determine whether, in the absence of P, Type I is selected for, or whether the two types are equivalent. For this purpose, experimental populations deprived of the P allele and differing in the initial proportions of the two viral types were established. After several generations, and despite a possible bias toward Type I, the frequencies of Type I and Type II clones differed in the various populations, depending on their initial values. These findings do not rule out selective advantage of viral Type I in the absence of P, but suggest that, if any, this advantage is in no way comparable to that displayed by viral Type II in the presence of P.

Allele coding in genomic evaluation

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Christensen Ole F

2011-06-01

Full Text Available Abstract Background Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call this centered allele coding. This study considered effects of different allele coding methods on inference. Both marker-based and equivalent models were considered, and restricted maximum likelihood and Bayesian methods were used in inference. Results Theoretical derivations showed that parameter estimates and estimated marker effects in marker-based models are the same irrespective of the allele coding, provided that the model has a fixed general mean. For the equivalent models, the same results hold, even though different allele coding methods lead to different genomic relationship matrices. Calculated genomic breeding values are independent of allele coding when the estimate of the general mean is included into the values. Reliabilities of estimated genomic breeding values calculated using elements of the inverse of the coefficient matrix depend on the allele coding because different allele coding methods imply different models. Finally, allele coding affects the mixing of Markov chain Monte Carlo algorithms, with the centered coding being

Clonal Ordering of 17p and 5q Allelic Losses in Barrett Dysplasia and Adenocarcinoma

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Blount, Patricia L.; Meltzer, Stephen J.; Yin, Jing; Huang, Ying; Krasna, Mark J.; Reid, Brian J.

1993-04-01

Both 17p and 5q allelic losses appear to be involved in the pathogenesis or progression of many human solid tumors. In colon carcinogenesis, there is strong evidence that the targets of the 17p and 5q allelic losses are TP53, the gene encoding p53, and APC, respectively. It is widely accepted that 5q allelic losses precede 17p allelic losses in the progression to colonic carcinoma. The data, however, supporting this proposed order are largely based on the prevalence of 17p and 5q allelic losses in adenomas and unrelated adenocarcinomas from different patients. We investigated the order in which 17p and 5q allelic losses developed during neoplastic progression in Barrett esophagus by evaluating multiple aneuploid cell populations from the same patient. Using DNA content flow cytometric cell sorting and polymerase chain reaction, 38 aneuploid cell populations from 14 patients with Barrett esophagus who had high grade dysplasia, cancer or both were evaluated for 17p and 5q allelic losses. 17p allelic losses preceded 5q allelic losses in 7 patients, both 17p and 5q allelic losses were present in all aneuploid populations of 4 patients, and only 17p (without 5q) allelic losses were present in the aneuploid populations of 3 patients. In no patient did we find that a 5q allelic loss preceded a 17p allelic loss. Our data suggest that 17p allelic losses typically occur before 5q allelic losses during neoplastic progression in Barrett esophagus.

Category-based attentional guidance can operate in parallel for multiple target objects.

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Jenkins, Michael; Grubert, Anna; Eimer, Martin

2018-04-30

The question whether the control of attention during visual search is always feature-based or can also be based on the category of objects remains unresolved. Here, we employed the N2pc component as an on-line marker for target selection processes to compare the efficiency of feature-based and category-based attentional guidance. Two successive displays containing pairs of real-world objects (line drawings of kitchen or clothing items) were separated by a 10 ms SOA. In Experiment 1, target objects were defined by their category. In Experiment 2, one specific visual object served as target (exemplar-based search). On different trials, targets appeared either in one or in both displays, and participants had to report the number of targets (one or two). Target N2pc components were larger and emerged earlier during exemplar-based search than during category-based search, demonstrating the superior efficiency of feature-based attentional guidance. On trials where target objects appeared in both displays, both targets elicited N2pc components that overlapped in time, suggesting that attention was allocated in parallel to these target objects. Critically, this was the case not only in the exemplar-based task, but also when targets were defined by their category. These results demonstrate that attention can be guided by object categories, and that this type of category-based attentional control can operate concurrently for multiple target objects. Copyright © 2018 Elsevier B.V. All rights reserved.

Hybrid male sterility in rice controlled by interaction between divergent alleles of two adjacent genes.

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Long, Yunming; Zhao, Lifeng; Niu, Baixiao; Su, Jing; Wu, Hao; Chen, Yuanling; Zhang, Qunyu; Guo, Jingxin; Zhuang, Chuxiong; Mei, Mantong; Xia, Jixing; Wang, Lan; Wu, Haibin; Liu, Yao-Guang

2008-12-02

Sterility is common in hybrids between divergent populations, such as the indica and japonica subspecies of Asian cultivated rice (Oryza sativa). Although multiple loci for plant hybrid sterility have been identified, it remains unknown how alleles of the loci interact at the molecular level. Here we show that a locus for indica-japonica hybrid male sterility, Sa, comprises two adjacent genes, SaM and SaF, encoding a small ubiquitin-like modifier E3 ligase-like protein and an F-box protein, respectively. Most indica cultivars contain a haplotype SaM(+)SaF(+), whereas all japonica cultivars have SaM(-)SaF(-) that diverged by nucleotide variations in wild rice. Male semi-sterility in this heterozygous complex locus is caused by abortion of pollen carrying SaM(-). This allele-specific gamete elimination results from a selective interaction of SaF(+) with SaM(-), a truncated protein, but not with SaM(+) because of the presence of an inhibitory domain, although SaM(+) is required for this male sterility. Lack of any one of the three alleles in recombinant plants does not produce male sterility. We propose a two-gene/three-component interaction model for this hybrid male sterility system. The findings have implications for overcoming male sterility in inter-subspecific hybrid rice breeding.

[Analysis of allele dropout at TH01 locus in paternity testing].

Science.gov (United States)

Lai, Li; Shen, Xiao-li; Xue, Shi-jie; Hu, Jie

2013-10-01

To analyze allele dropout at TH01 locus in paternity testing in order to determine the accurate genotype. To use a two STR loci genotyping system to verify an abnormal genotype for the TH01 locus with PCR using specific primers, cloning and DNA sequencing. A rare allele at TH01 locus named 5.2, which was undetectable with PowerPlex 21 system, was detected with an Identifiler system. Genetic variations may result in rare alleles and loci loss. To avoid misjudgment, laboratories should have a variety of methods for detecting loci loss.

Parallelizing flow-accumulation calculations on graphics processing units—From iterative DEM preprocessing algorithm to recursive multiple-flow-direction algorithm

Science.gov (United States)

Qin, Cheng-Zhi; Zhan, Lijun

2012-06-01

As one of the important tasks in digital terrain analysis, the calculation of flow accumulations from gridded digital elevation models (DEMs) usually involves two steps in a real application: (1) using an iterative DEM preprocessing algorithm to remove the depressions and flat areas commonly contained in real DEMs, and (2) using a recursive flow-direction algorithm to calculate the flow accumulation for every cell in the DEM. Because both algorithms are computationally intensive, quick calculation of the flow accumulations from a DEM (especially for a large area) presents a practical challenge to personal computer (PC) users. In recent years, rapid increases in hardware capacity of the graphics processing units (GPUs) provided in modern PCs have made it possible to meet this challenge in a PC environment. Parallel computing on GPUs using a compute-unified-device-architecture (CUDA) programming model has been explored to speed up the execution of the single-flow-direction algorithm (SFD). However, the parallel implementation on a GPU of the multiple-flow-direction (MFD) algorithm, which generally performs better than the SFD algorithm, has not been reported. Moreover, GPU-based parallelization of the DEM preprocessing step in the flow-accumulation calculations has not been addressed. This paper proposes a parallel approach to calculate flow accumulations (including both iterative DEM preprocessing and a recursive MFD algorithm) on a CUDA-compatible GPU. For the parallelization of an MFD algorithm (MFD-md), two different parallelization strategies using a GPU are explored. The first parallelization strategy, which has been used in the existing parallel SFD algorithm on GPU, has the problem of computing redundancy. Therefore, we designed a parallelization strategy based on graph theory. The application results show that the proposed parallel approach to calculate flow accumulations on a GPU performs much faster than either sequential algorithms or other parallel GPU

CAPN1, CAST, and DGAT1 genetic effects on preweaning performance, carcass quality traits, and residual variance of tenderness in a beef cattle population selected for haplotype and allele equalization

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Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. A stable composite population (MARC III) was subjected to marker assisted selection for multiple years to equalize specific marker frequencies to 1) estimate effect size an...

Prevalence of Huntington's disease gene CAG trinucleotide repeat alleles in patients with bipolar disorder.

Science.gov (United States)

Ramos, Eliana Marisa; Gillis, Tammy; Mysore, Jayalakshmi S; Lee, Jong-Min; Alonso, Isabel; Gusella, James F; Smoller, Jordan W; Sklar, Pamela; MacDonald, Marcy E; Perlis, Roy H

2015-06-01

Huntington's disease is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms that are caused by huntingtin gene (HTT) CAG trinucleotide repeat alleles of 36 or more units. A greater than expected prevalence of incompletely penetrant HTT CAG repeat alleles observed among individuals diagnosed with major depressive disorder raises the possibility that another mood disorder, bipolar disorder, could likewise be associated with Huntington's disease. We assessed the distribution of HTT CAG repeat alleles in a cohort of individuals with bipolar disorder. HTT CAG allele sizes from 2,229 Caucasian individuals diagnosed with DSM-IV bipolar disorder were compared to allele sizes in 1,828 control individuals from multiple cohorts. We found that HTT CAG repeat alleles > 35 units were observed in only one of 4,458 chromosomes from individuals with bipolar disorder, compared to three of 3,656 chromosomes from control subjects. These findings do not support an association between bipolar disorder and Huntington's disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hydraulic Fracture Induced Seismicity During A Multi-Stage Pad Completion in Western Canada: Evidence of Activation of Multiple, Parallel Faults

Science.gov (United States)

Maxwell, S.; Garrett, D.; Huang, J.; Usher, P.; Mamer, P.

2017-12-01

Following reports of injection induced seismicity in the Western Canadian Sedimentary Basin, regulators have imposed seismic monitoring and traffic light protocols for fracturing operations in specific areas. Here we describe a case study in one of these reservoirs, the Montney Shale in NE British Columbia, where induced seismicity was monitored with a local array during multi-stage hydraulic fracture stimulations on several wells from a single drilling pad. Seismicity primarily occurred during the injection time periods, and correlated with periods of high injection rates and wellhead pressures above fracturing pressures. Sequential hydraulic fracture stages were found to progressively activate several parallel, critically-stressed faults, as illuminated by multiple linear hypocenter patterns in the range between Mw 1 and 3. Moment tensor inversion of larger events indicated a double-couple mechanism consistent with the regional strike-slip stress state and the hypocenter lineations. The critically-stressed faults obliquely cross the well paths which were purposely drilled parallel to the minimum principal stress direction. Seismicity on specific faults started and stopped when fracture initiation points of individual injection stages were proximal to the intersection of the fault and well. The distance ranges when the seismicity occurs is consistent with expected hydraulic fracture dimensions, suggesting that the induced fault slip only occurs when a hydraulic fracture grows directly into the fault and the faults are temporarily exposed to significantly elevated fracture pressures during the injection. Some faults crossed multiple wells and the seismicity was found to restart during injection of proximal stages on adjacent wells, progressively expanding the seismogenic zone of the fault. Progressive fault slip is therefore inferred from the seismicity migrating further along the faults during successive injection stages. An accelerometer was also deployed close

Species specificity in major urinary proteins by parallel evolution.

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Darren W Logan

Full Text Available Species-specific chemosignals, pheromones, regulate social behaviors such as aggression, mating, pup-suckling, territory establishment, and dominance. The identity of these cues remains mostly undetermined and few mammalian pheromones have been identified. Genetically-encoded pheromones are expected to exhibit several different mechanisms for coding 1 diversity, to enable the signaling of multiple behaviors, 2 dynamic regulation, to indicate age and dominance, and 3 species-specificity. Recently, the major urinary proteins (Mups have been shown to function themselves as genetically-encoded pheromones to regulate species-specific behavior. Mups are multiple highly related proteins expressed in combinatorial patterns that differ between individuals, gender, and age; which are sufficient to fulfill the first two criteria. We have now characterized and fully annotated the mouse Mup gene content in detail. This has enabled us to further analyze the extent of Mup coding diversity and determine their potential to encode species-specific cues.Our results show that the mouse Mup gene cluster is composed of two subgroups: an older, more divergent class of genes and pseudogenes, and a second class with high sequence identity formed by recent sequential duplications of a single gene/pseudogene pair. Previous work suggests that truncated Mup pseudogenes may encode a family of functional hexapeptides with the potential for pheromone activity. Sequence comparison, however, reveals that they have limited coding potential. Similar analyses of nine other completed genomes find Mup gene expansions in divergent lineages, including those of rat, horse and grey mouse lemur, occurring independently from a single ancestral Mup present in other placental mammals. Our findings illustrate that increasing genomic complexity of the Mup gene family is not evolutionarily isolated, but is instead a recurring mechanism of generating coding diversity consistent with a species-specific

Endpoint-based parallel data processing in a parallel active messaging interface of a parallel computer

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Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.

2014-08-12

Endpoint-based parallel data processing in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes coupled for data communications through the PAMI, including establishing a data communications geometry, the geometry specifying, for tasks representing processes of execution of the parallel application, a set of endpoints that are used in collective operations of the PAMI including a plurality of endpoints for one of the tasks; receiving in endpoints of the geometry an instruction for a collective operation; and executing the instruction for a collective operation through the endpoints in dependence upon the geometry, including dividing data communications operations among the plurality of endpoints for one of the tasks.

Parallel computing and networking; Heiretsu keisanki to network

Energy Technology Data Exchange (ETDEWEB)

Asakawa, E; Tsuru, T [Japan National Oil Corp., Tokyo (Japan); Matsuoka, T [Japan Petroleum Exploration Co. Ltd., Tokyo (Japan)

1996-05-01

This paper describes the trend of parallel computers used in geophysical exploration. Around 1993 was the early days when the parallel computers began to be used for geophysical exploration. Classification of these computers those days was mainly MIMD (multiple instruction stream, multiple data stream), SIMD (single instruction stream, multiple data stream) and the like. Parallel computers were publicized in the 1994 meeting of the Geophysical Exploration Society as a `high precision imaging technology`. Concerning the library of parallel computers, there was a shift to PVM (parallel virtual machine) in 1993 and to MPI (message passing interface) in 1995. In addition, the compiler of FORTRAN90 was released with support implemented for data parallel and vector computers. In 1993, networks used were Ethernet, FDDI, CDDI and HIPPI. In 1995, the OC-3 products under ATM began to propagate. However, ATM remains to be an interoffice high speed network because the ATM service has not spread yet for the public network. 1 ref.

Vipie: web pipeline for parallel characterization of viral populations from multiple NGS samples.

Science.gov (United States)

Lin, Jake; Kramna, Lenka; Autio, Reija; Hyöty, Heikki; Nykter, Matti; Cinek, Ondrej

2017-05-15

Next generation sequencing (NGS) technology allows laboratories to investigate virome composition in clinical and environmental samples in a culture-independent way. There is a need for bioinformatic tools capable of parallel processing of virome sequencing data by exactly identical methods: this is especially important in studies of multifactorial diseases, or in parallel comparison of laboratory protocols. We have developed a web-based application allowing direct upload of sequences from multiple virome samples using custom parameters. The samples are then processed in parallel using an identical protocol, and can be easily reanalyzed. The pipeline performs de-novo assembly, taxonomic classification of viruses as well as sample analyses based on user-defined grouping categories. Tables of virus abundance are produced from cross-validation by remapping the sequencing reads to a union of all observed reference viruses. In addition, read sets and reports are created after processing unmapped reads against known human and bacterial ribosome references. Secured interactive results are dynamically plotted with population and diversity charts, clustered heatmaps and a sortable and searchable abundance table. The Vipie web application is a unique tool for multi-sample metagenomic analysis of viral data, producing searchable hits tables, interactive population maps, alpha diversity measures and clustered heatmaps that are grouped in applicable custom sample categories. Known references such as human genome and bacterial ribosomal genes are optionally removed from unmapped ('dark matter') reads. Secured results are accessible and shareable on modern browsers. Vipie is a freely available web-based tool whose code is open source.

RHD alleles in the Tunisian population

Science.gov (United States)

Ouchari, Mouna; Jemni-Yaacoub, Saloua; Chakroun, Taher; Abdelkefi, Saida; Houissa, Batoul; Hmida, Slama

2013-01-01

Background: A comprehensive survey of RHD alleles in Tunisia population was lacking. The aim of this study was to use a multiplex RHD typing assay for simultaneous detection of partial D especially with RHD/RHCE deoxyribonucleic acid (DNA) sequence exchange mechanism and some weak D alleles. Materials and Methods: Six RHD specific primer sets were designed to amplify RHD exons 3, 4, 5, 6, 7 and 9. DNA from 2000 blood donors (1777 D+ and 223 D-) from several regions was selected for RHD genotyping using a PCR multiplex assay. Further molecular investigations were done to characterize the RHD variants that were identified by the PCR multiplex assay. Results: In the 1777 D+ samples, only 10 individuals showed the absence of amplification of exons 4 and 5 that were subsequently identified by PCR-SSP as weak D type 4 variants. No hybrid allele was detected. In the 223 D-, RHD amplification of some exons was observed only in 5 samples: 4 individuals expressed only RHD exon 9, and one subject lacking exons 4 and 5. These samples were then screened by PCR-SSPs on d(C) ces and weak D type 4, respectively. Conclusion: The weak D type 4 appears to be the most common D variant allele. We have not found any partial D variant. Findings also indicated that RHD gene deletion is the most prevalent cause of the D- phenotype in the Tunisian population. PMID:24014941

Reliable allele detection using SNP-based PCR primers containing Locked Nucleic Acid: application in genetic mapping

Directory of Open Access Journals (Sweden)

Trognitz Friederike

2007-02-01

Full Text Available Abstract Background The diploid, Solanum caripense, a wild relative of potato and tomato, possesses valuable resistance to potato late blight and we are interested in the genetic base of this resistance. Due to extremely low levels of genetic variation within the S. caripense genome it proved impossible to generate a dense genetic map and to assign individual Solanum chromosomes through the use of conventional chromosome-specific SSR, RFLP, AFLP, as well as gene- or locus-specific markers. The ease of detection of DNA polymorphisms depends on both frequency and form of sequence variation. The narrow genetic background of close relatives and inbreds complicates the detection of persisting, reduced polymorphism and is a challenge to the development of reliable molecular markers. Nonetheless, monomorphic DNA fragments representing not directly usable conventional markers can contain considerable variation at the level of single nucleotide polymorphisms (SNPs. This can be used for the design of allele-specific molecular markers. The reproducible detection of allele-specific markers based on SNPs has been a technical challenge. Results We present a fast and cost-effective protocol for the detection of allele-specific SNPs by applying Sequence Polymorphism-Derived (SPD markers. These markers proved highly efficient for fingerprinting of individuals possessing a homogeneous genetic background. SPD markers are obtained from within non-informative, conventional molecular marker fragments that are screened for SNPs to design allele-specific PCR primers. The method makes use of primers containing a single, 3'-terminal Locked Nucleic Acid (LNA base. We demonstrate the applicability of the technique by successful genetic mapping of allele-specific SNP markers derived from monomorphic Conserved Ortholog Set II (COSII markers mapped to Solanum chromosomes, in S. caripense. By using SPD markers it was possible for the first time to map the S. caripense alleles

Comparison of allele-specific PCR, created restriction-site PCR, and PCR with primer-introduced restriction analysis methods used for screening complex vertebral malformation carriers in Holstein cattle

Science.gov (United States)

Altınel, Ahmet

2017-01-01

Complex vertebral malformation (CVM) is an inherited, autosomal recessive disorder of Holstein cattle. The aim of this study was to compare sensitivity, specificity, positive and negative predictive values, accuracy, and rapidity of allele-specific polymerase chain reaction (AS-PCR), created restriction-site PCR (CRS-PCR), and PCR with primer-introduced restriction analysis (PCR-PIRA), three methods used in identification of CVM carriers in a Holstein cattle population. In order to screen for the G>T mutation in the solute carrier family 35 member A3 (SLC35A3) gene, DNA sequencing as the gold standard method was used. The prevalence of carriers and the mutant allele frequency were 3.2% and 0.016, respectively, among Holstein cattle in the Thrace region of Turkey. Among the three methods, the fastest but least accurate was AS-PCR. Although the rapidity of CRS-PCR and PCR-PIRA were nearly equal, the accuracy of PCR-PIRA was higher than that of CRS-PCR. Therefore, among the three methods, PCR-PIRA appears to be the most efficacious for screening of mutant alleles when identifying CVM carriers in a Holstein cattle population. PMID:28927256

The HLA-B*39 allele increases type 1 diabetes risk conferred by HLA-DRB1*04:04-DQB1*03:02 and HLA-DRB1*08-DQB1*04 class II haplotypes.

Science.gov (United States)

Mikk, M-L; Kiviniemi, M; Laine, A-P; Härkönen, T; Veijola, R; Simell, O; Knip, M; Ilonen, J

2014-01-01

To further characterise the effect of the HLA-B*39 allele on type 1 diabetes risk we assessed its role in different HLA-DR/DQ haplotypes and genotypes using 1764 nuclear families with a diabetic child collected in the framework of the Finnish Paediatric Diabetes Register. HLA assays were based on sequence specific hybridization using lanthanide labelled oligonucleotide probes. Transmissions of major HLA-DR/DQ haplotypes with and without the HLA-B*39 allele to diabetic index cases were analysed by direct haplotype and allele counting. The HLA-B*39 allele significantly increased the disease risk conferred by DRB1*04:04-DQA1*03-DQB1*03:02 and (DR8)-DQB1*04 haplotypes. The same effect was observed on genotype level as disease association for the HLA-B*39 allele was observed in multiple genotypes containing DRB1*04:04-DQA1*03-DQB1*03:02 or (DR8)-DQB1*04 haplotypes. Finally we considered the two common subtypes of the HLA-B*39 allele, B*39:01 and B*39:06 and observed their unequal distribution when stratified for specific DR-DQ haplotypes. The risk for type 1 diabetes conferred by certain DR/DQ haplotypes is modified by the presence of the HLA-B*39 and this confirms the independent disease predisposing effect of the HLA-B*39 allele. The results can be applied in enhancing the sensitivity and specificity of DR/DQ based screening programs for subjects at disease risk. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Preferential Allele Expression Analysis Identifies Shared Germline and Somatic Driver Genes in Advanced Ovarian Cancer

Science.gov (United States)

Halabi, Najeeb M.; Martinez, Alejandra; Al-Farsi, Halema; Mery, Eliane; Puydenus, Laurence; Pujol, Pascal; Khalak, Hanif G.; McLurcan, Cameron; Ferron, Gwenael; Querleu, Denis; Al-Azwani, Iman; Al-Dous, Eman; Mohamoud, Yasmin A.; Malek, Joel A.; Rafii, Arash

2016-01-01

Identifying genes where a variant allele is preferentially expressed in tumors could lead to a better understanding of cancer biology and optimization of targeted therapy. However, tumor sample heterogeneity complicates standard approaches for detecting preferential allele expression. We therefore developed a novel approach combining genome and transcriptome sequencing data from the same sample that corrects for sample heterogeneity and identifies significant preferentially expressed alleles. We applied this analysis to epithelial ovarian cancer samples consisting of matched primary ovary and peritoneum and lymph node metastasis. We find that preferentially expressed variant alleles include germline and somatic variants, are shared at a relatively high frequency between patients, and are in gene networks known to be involved in cancer processes. Analysis at a patient level identifies patient-specific preferentially expressed alleles in genes that are targets for known drugs. Analysis at a site level identifies patterns of site specific preferential allele expression with similar pathways being impacted in the primary and metastasis sites. We conclude that genes with preferentially expressed variant alleles can act as cancer drivers and that targeting those genes could lead to new therapeutic strategies. PMID:26735499

Reduced Height (Rht) Alleles Affect Wheat Grain Quality.

Science.gov (United States)

Casebow, Richard; Hadley, Caroline; Uppal, Rajneet; Addisu, Molla; Loddo, Stefano; Kowalski, Ania; Griffiths, Simon; Gooding, Mike

2016-01-01

The effects of dwarfing alleles (reduced height, Rht) in near isogenic lines on wheat grain quality are characterised in field experiments and related to effects on crop height, grain yield and GA-sensitivity. Alleles included those that conferred GA-insensitivity (Rht-B1b, Rht-B1c, Rht-D1b, Rht-D1c) as well as those that retained GA-sensitivity (rht(tall), Rht8, Rht8 + Ppd-D1a, Rht12). Full characterisation was facilitated by including factors with which the effects of Rht alleles are known to interact for grain yield (i.e. system, [conventional or organic]; tillage intensity [plough-based, minimum or zero]; nitrogen fertilizer level [0-450 kg N/ha]; and genetic backgrounds varying in height [cvs Maris Huntsman, Maris Widgeon, and Mercia]. Allele effects on mean grain weight and grain specific weight were positively associated with final crop height: dwarfing reduced these quality criteria irrespective of crop management or GA-sensitivity. In all but two experiments the effects of dwarfing alleles on grain nitrogen and sulphur concentrations were closely and negatively related to effects on grain yield, e.g. a quadratic relationship between grain yield and crop height manipulated by the GA-insensitive alleles was mirrored by quadratic relationships for nitrogen and sulphur concentrations: the highest yields and most dilute concentrations occurred around 80cm. In one of the two exceptional experiments the GA-insensitive Rht-B1b and Rht-B1c significantly (Pgrain nitrogen concentration in the absence of an effect on yield, and in the remaining experiment the GA-sensitive Rht8 significantly reduced both grain yield and grain nitrogen concentration simultaneously. When Rht alleles diluted grain nitrogen concentration, N:S ratios and SDS-sedimentation volumes were often improved. Hagberg falling number (HFN) was negatively related to crop height but benefits from dwarfing were only seen for GA-insensitive alleles. For HFN, therefore, there was the strongest evidence for

Concordance of the ForenSeq™ system and characterisation of sequence-specific autosomal STR alleles across two major population groups.

Science.gov (United States)

Devesse, Laurence; Ballard, David; Davenport, Lucinda; Riethorst, Immy; Mason-Buck, Gabriella; Syndercombe Court, Denise

2018-05-01

By using sequencing technology to genotype loci of forensic interest it is possible to simultaneously target autosomal, X and Y STRs as well as identity, ancestry and phenotypic informative SNPs, resulting in a breadth of data obtained from a single run that is considerable when compared to that generated with standard technologies. It is important however that this information aligns with the genotype data currently obtained using commercially available kits for CE-based investigations such that results are compatible with existing databases and hence can be of use to the forensic community. In this work, 400 samples were typed using commercially available STR kits and CE, as well as using the Ilumina ForenSeq™ DNA Signature Prep Kit and MiSeq ® FGx to assess concordance of autosomal STRs and population variability. Results show a concordance rate between the two technologies exceeding 99.98% while numerous novel sequence based alleles are described. In order to make use of the sequence variation observed, sequence specific allele frequencies were generated for White British and British Chinese populations. Copyright © 2017 Elsevier B.V. All rights reserved.

Parallel k-means++ for Multiple Shared-Memory Architectures

Energy Technology Data Exchange (ETDEWEB)

Mackey, Patrick S.; Lewis, Robert R.

2016-09-22

In recent years k-means++ has become a popular initialization technique for improved k-means clustering. To date, most of the work done to improve its performance has involved parallelizing algorithms that are only approximations of k-means++. In this paper we present a parallelization of the exact k-means++ algorithm, with a proof of its correctness. We develop implementations for three distinct shared-memory architectures: multicore CPU, high performance GPU, and the massively multithreaded Cray XMT platform. We demonstrate the scalability of the algorithm on each platform. In addition we present a visual approach for showing which platform performed k-means++ the fastest for varying data sizes.

Development Modules for Specification of Requirements for a System of Verification of Parallel Algorithms

Directory of Open Access Journals (Sweden)

Vasiliy Yu. Meltsov

2012-05-01

Full Text Available This paper presents the results of the development of one of the modules of the system verification of parallel algorithms that are used to verify the inference engine. This module is designed to build the specification requirements, the feasibility of which on the algorithm is necessary to prove (test.

Performance of the Galley Parallel File System

Science.gov (United States)

Nieuwejaar, Nils; Kotz, David

1996-01-01

As the input/output (I/O) needs of parallel scientific applications increase, file systems for multiprocessors are being designed to provide applications with parallel access to multiple disks. Many parallel file systems present applications with a conventional Unix-like interface that allows the application to access multiple disks transparently. This interface conceals the parallism within the file system, which increases the ease of programmability, but makes it difficult or impossible for sophisticated programmers and libraries to use knowledge about their I/O needs to exploit that parallelism. Furthermore, most current parallel file systems are optimized for a different workload than they are being asked to support. We introduce Galley, a new parallel file system that is intended to efficiently support realistic parallel workloads. Initial experiments, reported in this paper, indicate that Galley is capable of providing high-performance 1/O to applications the applications that rely on them. In Section 3 we describe that access data in patterns that have been observed to be common.

Parallel multiple instance learning for extremely large histopathology image analysis.

Science.gov (United States)

Xu, Yan; Li, Yeshu; Shen, Zhengyang; Wu, Ziwei; Gao, Teng; Fan, Yubo; Lai, Maode; Chang, Eric I-Chao

2017-08-03

Histopathology images are critical for medical diagnosis, e.g., cancer and its treatment. A standard histopathology slice can be easily scanned at a high resolution of, say, 200,000×200,000 pixels. These high resolution images can make most existing imaging processing tools infeasible or less effective when operated on a single machine with limited memory, disk space and computing power. In this paper, we propose an algorithm tackling this new emerging "big data" problem utilizing parallel computing on High-Performance-Computing (HPC) clusters. Experimental results on a large-scale data set (1318 images at a scale of 10 billion pixels each) demonstrate the efficiency and effectiveness of the proposed algorithm for low-latency real-time applications. The framework proposed an effective and efficient system for extremely large histopathology image analysis. It is based on the multiple instance learning formulation for weakly-supervised learning for image classification, segmentation and clustering. When a max-margin concept is adopted for different clusters, we obtain further improvement in clustering performance.

Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals

International Nuclear Information System (INIS)

Tsuji, Shoji; Martin, B.M.; Stubblefield, B.K.; LaMarca, M.E.; Ginns, E.I.; Barranger, J.A.

1988-01-01

Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is ∼80% informative in all Gaucher patients studied

Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals

Energy Technology Data Exchange (ETDEWEB)

Tsuji, Shoji; Martin, B.M.; Stubblefield, B.K.; LaMarca, M.E.; Ginns, E.I. (National Institute of Mental Health, Bethesda, MD (USA)); Barranger, J.A. (Childrens Hospital of Los Angeles, CA (USA))

1988-04-01

Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is {approx}80% informative in all Gaucher patients studied.

Self-incompatibility of Prunus tenella and evidence that reproductively isolated species of Prunus have different SFB alleles coupled with an identical S-RNase allele.

Science.gov (United States)

Surbanovski, Nada; Tobutt, Kenneth R; Konstantinović, Miroslav; Maksimović, Vesna; Sargent, Daniel J; Stevanović, Vladimir; Bosković, Radovan I

2007-05-01

Many species of Prunus display an S-RNase-based gametophytic self-incompatibility (SI), controlled by a single highly polymorphic multigene complex termed the S-locus. This comprises tightly linked stylar- and pollen-expressed genes that determine the specificity of the SI response. We investigated SI of Prunus tenella, a wild species found in small, isolated populations on the Balkan peninsula, initially by pollination experiments and identifying stylar-expressed RNase alleles. Nine P. tenella S-RNase alleles (S(1)-S(9)) were cloned; their sequence analysis showed a very high ratio of non-synonymous to synonymous nucleotide substitutions (K(a)/K(s)) and revealed that S-RNase alleles of P. tenella, unlike those of Prunus dulcis, show positive selection in all regions except the conserved regions and that between C2 and RHV. Remarkably, S(8)-RNase, was found to be identical to S(1)-RNase from Prunus avium, a species that does not interbreed with P. tenella and, except for just one amino acid, to S(11) of P. dulcis. However, the corresponding introns and S-RNase-SFB intergenic regions showed considerable differences. Moreover, protein sequences of the pollen-expressed SFB alleles were not identical, harbouring 12 amino-acid replacements between those of P. tenella SFB(8) and P. avium SFB(1). Implications of this finding for hypotheses about the evolution of new S-specificities are discussed.

Distribution of coat-color-associated alleles in the domestic horse population and Przewalski's horse.

Science.gov (United States)

Reissmann, Monika; Musa, Lutfi; Zakizadeh, Sonia; Ludwig, Arne

2016-11-01

Considering the hidden mode of inheritance of some coat-color-associated alleles, we investigated the presence/absence of coat-color-associated alleles in 1093 domestic horses of 55 breeds and 20 specimens of Przewalski's horse. For coat-color genotyping, allele specific PCR, pyrosequencing and Li-Cor analyses were conducted on 12 coat-color-associated alleles of five genes. Our data provide deep insight into the distribution of coat-color-associated alleles within breeds. We found that the alleles for the basic colorations (bay, black, and chestnut) are widely distributed and occur in nearly all breeds. Alleles leading to dilutions or patterns are rare in domestic breeds and were not found in Przewalski's horse. Higher frequencies of these alleles are only found in breeds that are selected for their expressed phenotypes (e.g., Kinsky horse, Lewitzer, Tinker). Nevertheless, our study produced strong evidence that molecular testing of the coat color is necessary for well-defined phenotyping to avoid unexpected colorations of offspring that can result in legal action.

Sensitivity and specificity of parallel or serial serological testing for detection of canine Leishmania infection

Directory of Open Access Journals (Sweden)

Mauro Maciel de Arruda

2016-01-01

Full Text Available In Brazil, human and canine visceral leishmaniasis (CVL caused byLeishmania infantum has undergone urbanisation since 1980, constituting a public health problem, and serological tests are tools of choice for identifying infected dogs. Until recently, the Brazilian zoonoses control program recommended enzyme-linked immunosorbent assays (ELISA and indirect immunofluorescence assays (IFA as the screening and confirmatory methods, respectively, for the detection of canine infection. The purpose of this study was to estimate the accuracy of ELISA and IFA in parallel or serial combinations. The reference standard comprised the results of direct visualisation of parasites in histological sections, immunohistochemical test, or isolation of the parasite in culture. Samples from 98 cases and 1,327 noncases were included. Individually, both tests presented sensitivity of 91.8% and 90.8%, and specificity of 83.4 and 53.4%, for the ELISA and IFA, respectively. When tests were used in parallel combination, sensitivity attained 99.2%, while specificity dropped to 44.8%. When used in serial combination (ELISA followed by IFA, decreased sensitivity (83.3% and increased specificity (92.5% were observed. Serial testing approach improved specificity with moderate loss in sensitivity. This strategy could partially fulfill the needs of public health and dog owners for a more accurate diagnosis of CVL.

Genomic analysis of a heterogeneous Mendelian phenotype: multiple novel alleles for inherited hearing loss in the Palestinian population

Directory of Open Access Journals (Sweden)

Walsh Tom

2006-01-01

Full Text Available Abstract Recessively inherited phenotypes are frequent in the Palestinian population, as the result of a historical tradition of marriages within extended kindreds, particularly in isolated villages. In order to characterise the genetics of inherited hearing loss in this population, we worked with West Bank schools for the deaf to identify children with prelingual, bilateral, severe to profound hearing loss not attributable to infection, trauma or other known environmental exposure. Of 156 families enrolled, hearing loss in 17 families (11 per cent was due to mutations in GJB2 (connexin 26, a smaller fraction of GJB2-associated deafness than in other populations. In order to estimate how many different genes might be responsible for hearing loss in this population, we evaluated ten families for linkage to all 36 known human autosomal deafness-related genes, fully sequencing hearing-related genes at any linked sites in informative relatives. Four families harboured four novel alleles of TMPRSS3 (988ΔA = 352stop, otoancorin (1067A >T = D356V and pendrin (716T > A = V239D and 1001G > T = 346stop. In each family, all affected individuals were homozygous for the critical mutation. Each allele was specific to one or a few families in the cohort; none were widespread. Since epidemiological tests of association of mutations with deafness were not feasible for such rare alleles, we used functional and bioinformatics approaches to evaluate their consequences. In six other families, hearing loss was not linked to any known gene, suggesting that these families harbour novel genes responsible for this phenotype. We conclude that inherited hearing loss is highly heterogeneous in this population, with most extended families acting as genetic isolates in this context. We also conclude that the same genes are responsible for hearing loss in this population as elsewhere, so that gene discovery in these families informs the genetics of hearing loss worldwide.

Non-parallel divergence across freshwater and marine three-spined stickleback Gasterosteus aculeatus populations.

Science.gov (United States)

Pujolar, J M; Ferchaud, A L; Bekkevold, D; Hansen, M M

2017-07-01

This work investigated whether multiple freshwater populations of three-spined stickleback Gasterosteus aculeatus in different freshwater catchments in the Jutland Peninsula, Denmark, derived from the same marine populations show repeated adaptive responses. A total of 327 G. aculeatus collected at 13 sampling locations were screened for genetic variation using a combination of 70 genes putatively under selection and 26 neutral genes along with a marker linked to the ectodysplasin gene (eda), which is strongly correlated with plate armour morphs in the species. A highly significant genetic differentiation was found that was higher among different freshwater samples than between marine-freshwater samples. Tests for selection between marine and freshwater populations showed a very low degree of parallelism and no single nucleotide polymorphism was detected as outlier in all freshwater-marine pairwise comparisons, including the eda. This suggests that G. aculeatus is not necessarily the prime example of parallel local adaptation suggested in much of the literature and that important exceptions exist (i.e. the Jutland Peninsula). While marine populations in the results described here showed a high phenotype-genotype correlation at eda, a low association was found for most of the freshwater populations. The most extreme case was found in the freshwater Lake Hald where all low-plated phenotypes were either homozygotes for the allele supposed to be associated with completely plated morphs or heterozygotes, but none were homozygotes for the putative low-plated allele. Re-examination of data from seven G. aculeatus studies agrees in showing a high but partial association between phenotype-genotype at eda in G. aculeatus freshwater populations and that mismatches occur everywhere in the European regions studied (higher in some areas, i.e. Denmark). This is independent of the eda marker used. © 2017 The Fisheries Society of the British Isles.

A parallel robot to assist vitreoretinal surgery

Energy Technology Data Exchange (ETDEWEB)

Nakano, Taiga; Sugita, Naohiko; Mitsuishi, Mamoru [University of Tokyo, School of Engineering, Tokyo (Japan); Ueta, Takashi; Tamaki, Yasuhiro [University of Tokyo, Graduate School of Medicine, Tokyo (Japan)

2009-11-15

This paper describes the development and evaluation of a parallel prototype robot for vitreoretinal surgery where physiological hand tremor limits performance. The manipulator was specifically designed to meet requirements such as size, precision, and sterilization; this has six-degree-of-freedom parallel architecture and provides positioning accuracy with micrometer resolution within the eye. The manipulator is controlled by an operator with a ''master manipulator'' consisting of multiple joints. Results of the in vitro experiments revealed that when compared to the manual procedure, a higher stability and accuracy of tool positioning could be achieved using the prototype robot. This microsurgical system that we have developed has superior operability as compared to traditional manual procedure and has sufficient potential to be used clinically for vitreoretinal surgery. (orig.)

Thread-Level Parallel Indexing of Update Intensive Moving-Object Workloads

DEFF Research Database (Denmark)

Sidlauskas, Darius; Ross, Kenneth A.; Jensen, Christian S.

2011-01-01

as well as contain queries. The non-trivial challenge addressed is that of avoiding contention between long-running queries and frequent updates. Specifically, the paper proposes a grid-based indexing technique. A static grid indexes a near up-to-date snapshot of the data to support queries, while a live......Modern processors consist of multiple cores that each support parallel processing by multiple physical threads, and they offer ample main-memory storage. This paper studies the use of such processors for the processing of update-intensive moving-object workloads that contain very frequent updates...

Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine recepter D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention

NARCIS (Netherlands)

Swanson, J.; Oosterlaan, J.; Murias, M.; Schuck, S.; Flodman, P.; Spence, M.A.; Wasdell, M.; Ding, Y.; Chi, H-C.; Smith, M.; Mann, M.; Carlson, C.; Kennedy, J.L.; Sergeant, J.A.; Leung, P.; Zhang, Y-P.; Sadeh, A.; Chan, C.; Whalen, C.K.; Babb, K.; Moyzis, R.; Posner, M.I.

2000-01-01

An association of the dopamine receptor D4 (DRD4) gene located on chromosome 11p15.5 and attention deficit/hyperactivity disorder (ADHD) has been demonstrated and replicated by multiple investigators. A specific allele [the 7-repeat of a 48-bp variable number of tandem repeats (VNTR) in exon 3] has

Optimization under uncertainty of parallel nonlinear energy sinks

Science.gov (United States)

Boroson, Ethan; Missoum, Samy; Mattei, Pierre-Olivier; Vergez, Christophe

2017-04-01

Nonlinear Energy Sinks (NESs) are a promising technique for passively reducing the amplitude of vibrations. Through nonlinear stiffness properties, a NES is able to passively and irreversibly absorb energy. Unlike the traditional Tuned Mass Damper (TMD), NESs do not require a specific tuning and absorb energy over a wider range of frequencies. Nevertheless, they are still only efficient over a limited range of excitations. In order to mitigate this limitation and maximize the efficiency range, this work investigates the optimization of multiple NESs configured in parallel. It is well known that the efficiency of a NES is extremely sensitive to small perturbations in loading conditions or design parameters. In fact, the efficiency of a NES has been shown to be nearly discontinuous in the neighborhood of its activation threshold. For this reason, uncertainties must be taken into account in the design optimization of NESs. In addition, the discontinuities require a specific treatment during the optimization process. In this work, the objective of the optimization is to maximize the expected value of the efficiency of NESs in parallel. The optimization algorithm is able to tackle design variables with uncertainty (e.g., nonlinear stiffness coefficients) as well as aleatory variables such as the initial velocity of the main system. The optimal design of several parallel NES configurations for maximum mean efficiency is investigated. Specifically, NES nonlinear stiffness properties, considered random design variables, are optimized for cases with 1, 2, 3, 4, 5, and 10 NESs in parallel. The distributions of efficiency for the optimal parallel configurations are compared to distributions of efficiencies of non-optimized NESs. It is observed that the optimization enables a sharp increase in the mean value of efficiency while reducing the corresponding variance, thus leading to more robust NES designs.

Mannose-binding lectin variant alleles and HLA-DR4 alleles are associated with giant cell arteritis

DEFF Research Database (Denmark)

Jacobsen, Soren; Baslund, Bo; Madsen, Hans O.

2002-01-01

/GCA, MBL variant alleles were associated with signs of increased inflammatory activity and clinical signs of arteritic manifestations. This was not found for HLA-DR4 alleles. These findings indicate that HLA-DR4 and MBL are contributing to the pathophysiology of GCA at different levels in the disease...... alleles in controls, patients with PMR only, and patients with GCA was 37, 32, and 53% (p = 0.01), respectively. HLA-DRB1*04 was found in 47% of patients with PMR only and in 54% of patients with GCA, which differed significantly from the 35% found in controls (p = 0.01). HLA-DR4 alleles were...... not associated with any clinical phenotypes of PMR/GCA, whereas MBL variant alleles were associated with cranial arteritis, high erythrocyte sedimentation rate, and low B-hemoglobin. CONCLUSION: We found MBL variant alleles and HLA-DR4 alleles to be weak susceptibility markers for GCA. In patients with PMR...

Mixed-time parallel evolution in multiple quantum NMR experiments: sensitivity and resolution enhancement in heteronuclear NMR

International Nuclear Information System (INIS)

Ying Jinfa; Chill, Jordan H.; Louis, John M.; Bax, Ad

2007-01-01

A new strategy is demonstrated that simultaneously enhances sensitivity and resolution in three- or higher-dimensional heteronuclear multiple quantum NMR experiments. The approach, referred to as mixed-time parallel evolution (MT-PARE), utilizes evolution of chemical shifts of the spins participating in the multiple quantum coherence in parallel, thereby reducing signal losses relative to sequential evolution. The signal in a given PARE dimension, t 1 , is of a non-decaying constant-time nature for a duration that depends on the length of t 2 , and vice versa, prior to the onset of conventional exponential decay. Line shape simulations for the 1 H- 15 N PARE indicate that this strategy significantly enhances both sensitivity and resolution in the indirect 1 H dimension, and that the unusual signal decay profile results in acceptable line shapes. Incorporation of the MT-PARE approach into a 3D HMQC-NOESY experiment for measurement of H N -H N NOEs in KcsA in SDS micelles at 50 o C was found to increase the experimental sensitivity by a factor of 1.7±0.3 with a concomitant resolution increase in the indirectly detected 1 H dimension. The method is also demonstrated for a situation in which homonuclear 13 C- 13 C decoupling is required while measuring weak H3'-2'OH NOEs in an RNA oligomer

Reduced Height (Rht Alleles Affect Wheat Grain Quality.

Directory of Open Access Journals (Sweden)

Richard Casebow

Full Text Available The effects of dwarfing alleles (reduced height, Rht in near isogenic lines on wheat grain quality are characterised in field experiments and related to effects on crop height, grain yield and GA-sensitivity. Alleles included those that conferred GA-insensitivity (Rht-B1b, Rht-B1c, Rht-D1b, Rht-D1c as well as those that retained GA-sensitivity (rht(tall, Rht8, Rht8 + Ppd-D1a, Rht12. Full characterisation was facilitated by including factors with which the effects of Rht alleles are known to interact for grain yield (i.e. system, [conventional or organic]; tillage intensity [plough-based, minimum or zero]; nitrogen fertilizer level [0-450 kg N/ha]; and genetic backgrounds varying in height [cvs Maris Huntsman, Maris Widgeon, and Mercia]. Allele effects on mean grain weight and grain specific weight were positively associated with final crop height: dwarfing reduced these quality criteria irrespective of crop management or GA-sensitivity. In all but two experiments the effects of dwarfing alleles on grain nitrogen and sulphur concentrations were closely and negatively related to effects on grain yield, e.g. a quadratic relationship between grain yield and crop height manipulated by the GA-insensitive alleles was mirrored by quadratic relationships for nitrogen and sulphur concentrations: the highest yields and most dilute concentrations occurred around 80cm. In one of the two exceptional experiments the GA-insensitive Rht-B1b and Rht-B1c significantly (P<0.05 reduced grain nitrogen concentration in the absence of an effect on yield, and in the remaining experiment the GA-sensitive Rht8 significantly reduced both grain yield and grain nitrogen concentration simultaneously. When Rht alleles diluted grain nitrogen concentration, N:S ratios and SDS-sedimentation volumes were often improved. Hagberg falling number (HFN was negatively related to crop height but benefits from dwarfing were only seen for GA-insensitive alleles. For HFN, therefore, there

Tunable multiple plasmon induced transparencies in parallel graphene sheets and its applications

Science.gov (United States)

khazaee, Sara; Granpayeh, Nosrat

2018-01-01

Tunable plasmon induced transparency is achieved by using only two parallel graphene sheets beyond silicon diffractive grating in mid-infrared region. Excitation of the guided-wave resonance (GWR) in this structure is illustrated on the normal incident transmission spectra and plays the bright resonance mode role. Weak hybridization between two bright modes, creates plasmon induced transparency (PIT) optical response. The resonance frequency of transparency window can be tuned by different geometrical parameters. Also, variation of graphene Fermi energy can be used to achieve tunability of the resonance frequency of transparency window without reconstruction and re-fabrication of the structure. We demonstrate the existence of multiple PIT spectral responses resulting from a series of self-assembled GWRs to be used as the wavelength demultiplexer. This study can be used for design of the optical ultra-compact devices and photonic integrated circuits.

Identification and distribution of three serologically undetected alleles of HLA-DR by oligonucleotide x DNA typing analysis

International Nuclear Information System (INIS)

Tiercy, J.M.; Gorski, J.; Jeannet, M.; Mach, B.

1988-01-01

Recent progress in the molecular biology of human major histocompatibility complex class II genes (HLA-DP, -DQ, -DR) have shown that the genetic complexity and allelic polymorphism are greater than expected. In the case of HLA-DR, three DR β-chain loci have been identified and linked, two of which (DR βI and DR βIII, now assigned names HLA-DR1B and HLA-DR3B) are functional. The authors have shown that the HLA micropolymorphism detected at the DNA sequence level can easily be analyzed by hybridization with allele-specific oligonucleotides (HLA oligotyping). In the case of the HLA DRw52 supertypic specificity, which includes the DR3, DR5, DRw6, and DRw8 haplotypes, three alleles, referred to as DRw52a, DRw52b, and DRw52c, have recently been identified at the HLA-DR3B locus by DNA sequencing. Hybridization with locus- and allele-specific oligonucleotide probes (designated 52a, 52b, and 52c) has been performed on DNA from normal individuals forming a panel of 82 haplotypes to establish the distribution of these three alleles. Individuals of the DR3 haplotype had either the DRw52a or DRw52b allele, and individuals of extended haplotype HLA-A1,B8,DR3 had only the DRw52a allele. DR5 individuals all had the DRw52b allele, while individuals of DRw6 haplotype had the DRw52a, -52b, or -52c allele. None of these three alleles are found in DRw8 individuals. Analysis of this micropolymorphism, undetectable by common typing procedures, is therefore now operational for more accurate HLA matching for transplantation and for improving correlations between HLA and disease susceptibility

Parallel optoelectronic trinary signed-digit division

Science.gov (United States)

Alam, Mohammad S.

1999-03-01

The trinary signed-digit (TSD) number system has been found to be very useful for parallel addition and subtraction of any arbitrary length operands in constant time. Using the TSD addition and multiplication modules as the basic building blocks, we develop an efficient algorithm for performing parallel TSD division in constant time. The proposed division technique uses one TSD subtraction and two TSD multiplication steps. An optoelectronic correlator based architecture is suggested for implementation of the proposed TSD division algorithm, which fully exploits the parallelism and high processing speed of optics. An efficient spatial encoding scheme is used to ensure better utilization of space bandwidth product of the spatial light modulators used in the optoelectronic implementation.

Parallel selection on TRPV6 in human populations

OpenAIRE

Hughes, David A; Tang, Kun; Strotmann, Rainer; Schöneberg, Torsten; Prenen, Jean; Nilius, Bernd; Stoneking, Mark

2008-01-01

We identified and examined a candidate gene for local directional selection in Europeans, TRPV6, and conclude that selection has acted on standing genetic variation at this locus, creating parallel soft sweep events in humans. A novel modification of the extended haplotype homozygosity (EHH) test was utilized, which compares EHH for a single allele across populations, to investigate the signature of selection at TRPV6 and neighboring linked loci in published data sets for Europeans, Asians an...

My-Forensic-Loci-queries (MyFLq) framework for analysis of forensic STR data generated by massive parallel sequencing.

Science.gov (United States)

Van Neste, Christophe; Vandewoestyne, Mado; Van Criekinge, Wim; Deforce, Dieter; Van Nieuwerburgh, Filip

2014-03-01

Forensic scientists are currently investigating how to transition from capillary electrophoresis (CE) to massive parallel sequencing (MPS) for analysis of forensic DNA profiles. MPS offers several advantages over CE such as virtually unlimited multiplexy of loci, combining both short tandem repeat (STR) and single nucleotide polymorphism (SNP) loci, small amplicons without constraints of size separation, more discrimination power, deep mixture resolution and sample multiplexing. We present our bioinformatic framework My-Forensic-Loci-queries (MyFLq) for analysis of MPS forensic data. For allele calling, the framework uses a MySQL reference allele database with automatically determined regions of interest (ROIs) by a generic maximal flanking algorithm which makes it possible to use any STR or SNP forensic locus. Python scripts were designed to automatically make allele calls starting from raw MPS data. We also present a method to assess the usefulness and overall performance of a forensic locus with respect to MPS, as well as methods to estimate whether an unknown allele, which sequence is not present in the MySQL database, is in fact a new allele or a sequencing error. The MyFLq framework was applied to an Illumina MiSeq dataset of a forensic Illumina amplicon library, generated from multilocus STR polymerase chain reaction (PCR) on both single contributor samples and multiple person DNA mixtures. Although the multilocus PCR was not yet optimized for MPS in terms of amplicon length or locus selection, the results show excellent results for most loci. The results show a high signal-to-noise ratio, correct allele calls, and a low limit of detection for minor DNA contributors in mixed DNA samples. Technically, forensic MPS affords great promise for routine implementation in forensic genomics. The method is also applicable to adjacent disciplines such as molecular autopsy in legal medicine and in mitochondrial DNA research. Copyright © 2013 The Authors. Published by

Performance analysis of a threshold-based parallel multiple beam selection scheme for WDM-based systems for Gamma-Gamma distributions

KAUST Repository

Nam, Sung Sik

2017-03-02

In this paper, we statistically analyze the performance of a threshold-based parallel multiple beam selection scheme (TPMBS) for Free-space optical (FSO) based system with wavelength division multiplexing (WDM) in cases where a pointing error has occurred for practical consideration over independent identically distributed (i.i.d.) Gamma-Gamma fading conditions. Specifically, we statistically analyze the characteristics in operation under conventional heterodyne detection (HD) scheme for both adaptive modulation (AM) case in addition to non-AM case (i.e., coherentnon-coherent binary modulation). Then, based on the statistically derived results, we evaluate the outage probability (CDF) of a selected beam, the average spectral efficiency (ASE), the average number of selected beams (ANSB), and the average bit error rate (BER). Some selected results shows that we can obtain the higher spectral efficiency and simultaneously reduce the potential increasing of the complexity of implementation caused by applying the selection based beam selection scheme without a considerable performance loss.

Parallel Breadth-First Search on Distributed Memory Systems

Energy Technology Data Exchange (ETDEWEB)

Computational Research Division; Buluc, Aydin; Madduri, Kamesh

2011-04-15

Data-intensive, graph-based computations are pervasive in several scientific applications, and are known to to be quite challenging to implement on distributed memory systems. In this work, we explore the design space of parallel algorithms for Breadth-First Search (BFS), a key subroutine in several graph algorithms. We present two highly-tuned par- allel approaches for BFS on large parallel systems: a level-synchronous strategy that relies on a simple vertex-based partitioning of the graph, and a two-dimensional sparse matrix- partitioning-based approach that mitigates parallel commu- nication overhead. For both approaches, we also present hybrid versions with intra-node multithreading. Our novel hybrid two-dimensional algorithm reduces communication times by up to a factor of 3.5, relative to a common vertex based approach. Our experimental study identifies execu- tion regimes in which these approaches will be competitive, and we demonstrate extremely high performance on lead- ing distributed-memory parallel systems. For instance, for a 40,000-core parallel execution on Hopper, an AMD Magny- Cours based system, we achieve a BFS performance rate of 17.8 billion edge visits per second on an undirected graph of 4.3 billion vertices and 68.7 billion edges with skewed degree distribution.

Data communications in a parallel active messaging interface of a parallel computer

Science.gov (United States)

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

2013-11-12

Data communications in a parallel active messaging interface (`PAMI`) of a parallel computer composed of compute nodes that execute a parallel application, each compute node including application processors that execute the parallel application and at least one management processor dedicated to gathering information regarding data communications. The PAMI is composed of data communications endpoints, each endpoint composed of a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes and the endpoints coupled for data communications through the PAMI and through data communications resources. Embodiments function by gathering call site statistics describing data communications resulting from execution of data communications instructions and identifying in dependence upon the call cite statistics a data communications algorithm for use in executing a data communications instruction at a call site in the parallel application.

Exploiting Symmetry on Parallel Architectures.

Science.gov (United States)

Stiller, Lewis Benjamin

1995-01-01

This thesis describes techniques for the design of parallel programs that solve well-structured problems with inherent symmetry. Part I demonstrates the reduction of such problems to generalized matrix multiplication by a group-equivariant matrix. Fast techniques for this multiplication are described, including factorization, orbit decomposition, and Fourier transforms over finite groups. Our algorithms entail interaction between two symmetry groups: one arising at the software level from the problem's symmetry and the other arising at the hardware level from the processors' communication network. Part II illustrates the applicability of our symmetry -exploitation techniques by presenting a series of case studies of the design and implementation of parallel programs. First, a parallel program that solves chess endgames by factorization of an associated dihedral group-equivariant matrix is described. This code runs faster than previous serial programs, and discovered it a number of results. Second, parallel algorithms for Fourier transforms for finite groups are developed, and preliminary parallel implementations for group transforms of dihedral and of symmetric groups are described. Applications in learning, vision, pattern recognition, and statistics are proposed. Third, parallel implementations solving several computational science problems are described, including the direct n-body problem, convolutions arising from molecular biology, and some communication primitives such as broadcast and reduce. Some of our implementations ran orders of magnitude faster than previous techniques, and were used in the investigation of various physical phenomena.

Allele coding in genomic evaluation

DEFF Research Database (Denmark)

Standen, Ismo; Christensen, Ole Fredslund

2011-01-01

Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker...... effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous...... genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call...

Genes of the unfolded protein response pathway harbor risk alleles for primary open angle glaucoma.

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Mary Anna Carbone

Full Text Available The statistical power of genome-wide association (GWA studies to detect risk alleles for human diseases is limited by the unfavorable ratio of SNPs to study subjects. This multiple testing problem can be surmounted with very large population sizes when common alleles of large effects give rise to disease status. However, GWA approaches fall short when many rare alleles may give rise to a common disease, or when the number of subjects that can be recruited is limited. Here, we demonstrate that this multiple testing problem can be overcome by a comparative genomics approach in which an initial genome-wide screen in a genetically amenable model organism is used to identify human orthologues that may harbor risk alleles for adult-onset primary open angle glaucoma (POAG. Glaucoma is a major cause of blindness, which affects over 60 million people worldwide. Several genes have been associated with juvenile onset glaucoma, but genetic factors that predispose to adult onset primary open angle glaucoma (POAG remain largely unknown. Previous genome-wide analysis in a Drosophila ocular hypertension model identified transcripts with altered regulation and showed induction of the unfolded protein response (UPR upon overexpression of transgenic human glaucoma-associated myocilin (MYOC. We selected 16 orthologous genes with 62 polymorphic markers and identified in two independent human populations two genes of the UPR that harbor POAG risk alleles, BIRC6 and PDIA5. Thus, effectiveness of the UPR in response to accumulation of misfolded or aggregated proteins may contribute to the pathogenesis of POAG and provide targets for early therapeutic intervention.

Genes of the unfolded protein response pathway harbor risk alleles for primary open angle glaucoma.

Science.gov (United States)

Carbone, Mary Anna; Chen, Yuhong; Hughes, Guy A; Weinreb, Robert N; Zabriskie, Norman A; Zhang, Kang; Anholt, Robert R H

2011-01-01

The statistical power of genome-wide association (GWA) studies to detect risk alleles for human diseases is limited by the unfavorable ratio of SNPs to study subjects. This multiple testing problem can be surmounted with very large population sizes when common alleles of large effects give rise to disease status. However, GWA approaches fall short when many rare alleles may give rise to a common disease, or when the number of subjects that can be recruited is limited. Here, we demonstrate that this multiple testing problem can be overcome by a comparative genomics approach in which an initial genome-wide screen in a genetically amenable model organism is used to identify human orthologues that may harbor risk alleles for adult-onset primary open angle glaucoma (POAG). Glaucoma is a major cause of blindness, which affects over 60 million people worldwide. Several genes have been associated with juvenile onset glaucoma, but genetic factors that predispose to adult onset primary open angle glaucoma (POAG) remain largely unknown. Previous genome-wide analysis in a Drosophila ocular hypertension model identified transcripts with altered regulation and showed induction of the unfolded protein response (UPR) upon overexpression of transgenic human glaucoma-associated myocilin (MYOC). We selected 16 orthologous genes with 62 polymorphic markers and identified in two independent human populations two genes of the UPR that harbor POAG risk alleles, BIRC6 and PDIA5. Thus, effectiveness of the UPR in response to accumulation of misfolded or aggregated proteins may contribute to the pathogenesis of POAG and provide targets for early therapeutic intervention.

Practical enhancement factor model based on GM for multiple parallel reactions: Piperazine (PZ) CO2 capture

DEFF Research Database (Denmark)

Gaspar, Jozsef; Fosbøl, Philip Loldrup

2017-01-01

Reactive absorption is a key process for gas separation and purification and it is the main technology for CO2 capture. Thus, reliable and simple mathematical models for mass transfer rate calculation are essential. Models which apply to parallel interacting and non-interacting reactions, for all......, desorption and pinch conditions.In this work, we apply the GM model to multiple parallel reactions. We deduce the model for piperazine (PZ) CO2 capture and we validate it against wetted-wall column measurements using 2, 5 and 8 molal PZ for temperatures between 40 °C and 100 °C and CO2 loadings between 0.......23 and 0.41 mol CO2/2 mol PZ. We show that overall second order kinetics describes well the reaction between CO2 and PZ accounting for the carbamate and bicarbamate reactions. Here we prove the GM model for piperazine and MEA but we expect that this practical approach is applicable for various amines...

Rapid detection of the CYP2A6*12 hybrid allele by Pyrosequencing® technology

Directory of Open Access Journals (Sweden)

Gallagher Margaret L

2009-08-01

Full Text Available Abstract Background Identification of CYP2A6 alleles associated with reduced enzyme activity is important in the study of inter-individual differences in drug metabolism. CYP2A6*12 is a hybrid allele that results from unequal crossover between CYP2A6 and CYP2A7 genes. The 5' regulatory region and exons 1–2 are derived from CYP2A7, and exons 3–9 are derived from CYP2A6. Conventional methods for detection of CYP2A6*12 consist of two-step PCR protocols that are laborious and unsuitable for high-throughput genotyping. We developed a rapid and accurate method to detect the CYP2A6*12 allele by Pyrosequencing technology. Methods A single set of PCR primers was designed to specifically amplify both the CYP2A6*1 wild-type allele and the CYP2A6*12 hybrid allele. An internal Pyrosequencing primer was used to generate allele-specific sequence information, which detected homozygous wild-type, heterozygous hybrid, and homozygous hybrid alleles. We first validated the assay on 104 DNA samples that were also genotyped by conventional two-step PCR and by cycle sequencing. CYP2A6*12 allele frequencies were then determined using the Pyrosequencing assay on 181 multi-ethnic DNA samples from subjects of African American, European Caucasian, Pacific Rim, and Hispanic descent. Finally, we streamlined the Pyrosequencing assay by integrating liquid handling robotics into the workflow. Results Pyrosequencing results demonstrated 100% concordance with conventional two-step PCR and cycle sequencing methods. Allele frequency data showed slightly higher prevalence of the CYP2A6*12 allele in European Caucasians and Hispanics. Conclusion This Pyrosequencing assay proved to be a simple, rapid, and accurate alternative to conventional methods, which can be easily adapted to the needs of higher-throughput studies.

Estimating the probability of allelic drop-out of STR alleles in forensic genetics

DEFF Research Database (Denmark)

Tvedebrink, Torben; Eriksen, Poul Svante; Mogensen, Helle Smidt

2009-01-01

In crime cases with available DNA evidence, the amount of DNA is often sparse due to the setting of the crime. In such cases, allelic drop-out of one or more true alleles in STR typing is possible. We present a statistical model for estimating the per locus and overall probability of allelic drop......-out using the results of all STR loci in the case sample as reference. The methodology of logistic regression is appropriate for this analysis, and we demonstrate how to incorporate this in a forensic genetic framework....

Development of Allele-Specific Primer PCR for a Swine TLR2 SNP and Comparison of the Frequency among Several Pig Breeds of Japan and the Czech Republic

Czech Academy of Sciences Publication Activity Database

Muneta, Y.; Minagawa, Y.; Kusumoto, M.; Shinkai, H.; Uenishi, H.; Šplíchal, Igor

2012-01-01

Roč. 74, č. 5 (2012), s. 553-559 ISSN 0916-7250 R&D Projects: GA ČR GA524/09/0365 Institutional support: RVO:61388971 Keywords : allele-specific PCR * Mycoplasma hyopneumoniae * single nucleotide polymorphism Subject RIV: EC - Immunology Impact factor: 0.876, year: 2012

Involvement of Multiple Gene-Silencing Pathways in a Paramutation-like Phenomenon in Arabidopsis

Directory of Open Access Journals (Sweden)

Zhimin Zheng

2015-05-01

Full Text Available Paramutation is an epigenetic phenomenon that has been observed in a number of multicellular organisms. The epigenetically silenced state of paramutated alleles is not only meiotically stable but also “infectious” to active homologous alleles. The molecular mechanism of paramutation remains unclear, but components involved in RNA-directed DNA methylation (RdDM are required. Here, we report a multi-copy pRD29A-LUC transgene in Arabidopsis thaliana that behaves like a paramutation locus. The silent state of LUC is induced by mutations in the DNA glycosylase gene ROS1. The silent alleles of LUC are not only meiotically stable but also able to transform active LUC alleles into silent ones, in the absence of ros1 mutations. Maintaining silencing at the LUC gene requires action of multiple pathways besides RdDM. Our study identified specific factors that are involved in the paramutation-like phenomenon and established a model system for the study of paramutation in Arabidopsis.

An efficient parallel simulation of unsteady blood flows in patient-specific pulmonary artery.

Science.gov (United States)

Kong, Fande; Kheyfets, Vitaly; Finol, Ender; Cai, Xiao-Chuan

2018-04-01

Simulation of blood flows in the pulmonary artery provides some insight into certain diseases by examining the relationship between some continuum metrics, eg, the wall shear stress acting on the vascular endothelium, which responds to flow-induced mechanical forces by releasing vasodilators/constrictors. V. Kheyfets, in his previous work, studies numerically a patient-specific pulmonary circulation to show that decreasing wall shear stress is correlated with increasing pulmonary vascular impedance. In this paper, we develop a scalable parallel algorithm based on domain decomposition methods to investigate an unsteady model with patient-specific pulsatile waveforms as the inlet boundary condition. The unsteady model offers tremendously more information about the dynamic behavior of the flow field, but computationally speaking, the simulation is a lot more expensive since a problem which is similar to the steady-state problem has to be solved many times, and therefore, the traditional sequential approach is not suitable anymore. We show computationally that simulations using the proposed parallel approach with up to 10 000 processor cores can be obtained with much reduced compute time. This makes the technology potentially usable for the routine study of the dynamic behavior of blood flows in the pulmonary artery, in particular, the changes of the blood flows and the wall shear stress in the spatial and temporal dimensions. Copyright © 2017 John Wiley & Sons, Ltd.

Immunogenic Targets for Specific Immunotherapy in Multiple Myeloma

Directory of Open Access Journals (Sweden)

Lu Zhang

2012-01-01

Full Text Available Multiple myeloma remains an incurable disease although the prognosis has been improved by novel therapeutics and agents recently. Relapse occurs in the majority of patients and becomes fatal finally. Immunotherapy might be a powerful intervention to maintain a long-lasting control of minimal residual disease or to even eradicate disseminated tumor cells. Several tumor-associated antigens have been identified in patients with multiple myeloma. These antigens are expressed in a tumor-specific or tumor-restricted pattern, are able to elicit immune response, and thus could serve as targets for immunotherapy. This review discusses immunogenic antigens with therapeutic potential for multiple myeloma.

Suspension Array for Multiplex Detection of Eight Fungicide-Resistance Related Alleles in Botrytis cinerea

OpenAIRE

Zhang, Xin; Xie, Fei; Lv, Baobei; Zhao, Pengxiang; Ma, Xuemei

2016-01-01

A simple and high-throughput assay to detect fungicide resistance is required for large-scale monitoring of the emergence of resistant strains of Botrytis cinerea. Using suspension array technology performed on a Bio-Plex 200 System, we developed a single-tube allele-specific primer extension (ASPE) assay that can simultaneously detect eight alleles in one reaction. These eight alleles include E198 and 198A of the β-Tubulin gene (BenA), H272 and 272Y of the Succinate dehydrogenase iron–sulfur...

Data communications in a parallel active messaging interface of a parallel computer

Science.gov (United States)

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

2013-10-29

Data communications in a parallel active messaging interface (`PAMI`) of a parallel computer, the parallel computer including a plurality of compute nodes that execute a parallel application, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes and the endpoints coupled for data communications through the PAMI and through data communications resources, including receiving in an origin endpoint of the PAMI a data communications instruction, the instruction characterized by an instruction type, the instruction specifying a transmission of transfer data from the origin endpoint to a target endpoint and transmitting, in accordance with the instruction type, the transfer data from the origin endpoint to the target endpoint.

Population genetics of Phytophthora infestans in Denmark reveals dominantly clonal populations and specific alleles linked to metalaxyl-M resistance

DEFF Research Database (Denmark)

Montes, M. S.; Nielsen, Bent Jørgen; Schmidt, S. G.

2016-01-01

population of P. infestans was characterized over the course of the 2013 growing season, as was the population genetic structure, using simple sequence repeat (SSR) genotypes and single nucleotide polymorphism (SNP)-based mitochondrial haplotyping of over 80 isolates. Both mating types A1 and A2 were present...... in most fields, but tests for recombination showed that clonal reproduction dominates in Danish populations. Genotype was not linked to haplotype and no differentiation was observed at the haplotype level, but rather between fields. Resistance phenotypes were linked to specific SSR alleles, demonstrating...

Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease.

Science.gov (United States)

Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

2018-01-01

Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score ([Formula: see text]) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing [Formula: see text] >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of [Formula: see text] (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 ([Formula: see text] = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). We confirmed the existence of cis-regulated ASM around

Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease

Science.gov (United States)

Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

2018-01-01

Background Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. Methods CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score (ΔRAS¯) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing ΔRAS¯ >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. Results We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of ΔRAS¯ (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 (ΔRAS¯ = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). Conclusions We confirmed the existence of cis-regulated ASM around IBD

Improvements to a Markerless Allelic Exchange System for Bacillus anthracis.

Directory of Open Access Journals (Sweden)

Roger D Plaut

Full Text Available A system was previously developed for conducting I-SceI-mediated allelic exchange in Bacillus anthracis. In this system, recombinational loss of a chromosomally-integrated allelic exchange vector is stimulated by creation of a double-stranded break within the vector by the homing endonuclease I-SceI. Although this system is reasonably efficient and represents an improvement in the tools available for allelic exchange in B. anthracis, researchers are nonetheless required to "pick and patch" colonies in order to identify candidate "exchangeants." In the present study, a number of improvements have been made to this system: 1 an improved I-SceI-producing plasmid includes oriT so that both plasmids can now be introduced by conjugation, thus avoiding the need for preparing electro-competent cells of each integration intermediate; 2 antibiotic markers have been changed to allow the use of the system in select agent strains; and 3 both plasmids have been marked with fluorescent proteins, allowing the visualization of plasmid segregation on a plate and obviating the need for "picking and patching." These modifications have made the process easier, faster, and more efficient, allowing for parallel construction of larger numbers of mutant strains. Using this improved system, the genes encoding the tripartite anthrax toxin were deleted singly and in combination from plasmid pXO1 of Sterne strain 34F2. In the course of this study, we determined that DNA transfer to B. anthracis could be accomplished by conjugation directly from a methylation-competent E. coli strain.

Parkinson’s disease and low frequency alleles found together throughout LRRK2

Science.gov (United States)

Paisán-Ruiz, Coro; Washecka, Nicole; Nath, Priti; Singleton, Andrew B.; Corder, Elizabeth H.

2016-01-01

Mutations within LRRK2, most notably p.G2019S, cause Parkinson’s disease (PD) in rare monogenic families, and sporadic occurrences in diverse populations. We investigated variation throughout LRRK2 (84 SNPs; genotype or diplotype found for 49 LD blocks) for 275 cases (European ancestry, onset at age 60 or older) and 275 neurologically healthy control subjects (NINDS Neurogenetics Repository). Three grade-of-membership groups, i.e. genetic risk sets, were identified that exactly matched many subjects (cases: 46, 4, 137; controls: 0, 178, 0), and distinguished 94% of the subjects (i.e. > 50% likeness to one set). Set I, affected, carried certain low frequency alleles located in multiple functional domains. Set II was unaffected. Set III, also affected, resembled II except for slightly elevated frequencies of minor alleles not defining set I. We conclude that certain low frequency alleles distributed throughout LRRK2 are a genetic background to a third of cases, defining a distinct subset. PMID:19489756

Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection

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Elissa J. Chesler

2016-12-01

Full Text Available Multi-parent populations (MPPs capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution genetic mapping through the accumulation of recombination events over many generations. Breeding designs that maintain a large effective population size with randomized assignment of breeders at each generation can minimize the impact of selection, inbreeding, and genetic drift on allele frequencies. Small deviations from expected allele frequencies will have little effect on the power and precision of genetic analysis, but a major distortion could result in reduced power and loss of important functional alleles. We detected strong transmission ratio distortion in the Diversity Outbred (DO mouse population on chromosome 2, caused by meiotic drive favoring transmission of the WSB/EiJ allele at the R2d2 locus. The distorted region harbors thousands of polymorphisms derived from the seven non-WSB founder strains and many of these would be lost if the sweep was allowed to continue. To ensure the utility of the DO population to study genetic variation on chromosome 2, we performed an artificial selection against WSB/EiJ alleles at the R2d2 locus. Here, we report that we have purged the WSB/EiJ allele from the drive locus while preserving WSB/EiJ alleles in the flanking regions. We observed minimal disruption to allele frequencies across the rest of the autosomal genome. However, there was a shift in haplotype frequencies of the mitochondrial genome and an increase in the rate of an unusual sex chromosome aneuploidy. The DO population has been restored to genome-wide utility for genetic analysis, but our experience underscores that vigilant monitoring of similar genetic resource populations is needed to ensure their long-term utility.

The link between some alleles on human leukocyte antigen system and autism in children.

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Mostafa, Gehan A; Shehab, Abeer A; Al-Ayadhi, Laila Y

2013-02-15

The reason behind the initiation of autoimmunity to brain in some patients with autism is not well understood. There is an association between some autoimmune disorders and specific alleles of human leukocyte antigen (HLA) system. Thus, we examined the frequency of some HLA-DRB1 alleles in 100 autistic children and 100 healthy matched-children by differential hybridization with sequence-specific oligonucleotide probes. The risk of association between acquisition or absence of these alleles and autism and also a history of autoimmune diseases in autistic relatives was studied. Autistic children had significantly higher frequency of HLA-DRB1*11 allele than controls (P<0.001). In contrast, autistic children had significantly lower frequency of HLA-DRB1*03 allele than controls (P<0.001). Acquisition of HLA-DRB1*011 and absence of HLA-DRB1*3 had significant risk for association with autism (odds ratio: 3.21 and 0.17, respectively; 95% CI: 1.65-6.31 and 0.06-0.45, respectively). HLA-DRB1*11 had a significant risk for association with a family history of autoimmunity in autistic children (odds ratio: 5.67; 95% CI: 2.07-16.3). In conclusions, the link of some HLA alleles to autism and to family history of autoimmunity indicates the possible contributing role of these alleles to autoimmunity in some autistic children. Despite a relatively small sample size, we are the first to report a probable protective association of HLA-DRB1*03 allele with autism. It warrants a replication study of a larger sample to validate the HLA-DRB1 genetic association with autism. This is important to determine whether therapeutic modulations of the immune function are legitimate avenues for novel therapy in selected cases of autism. Copyright © 2012 Elsevier B.V. All rights reserved.

Parallel effects of the inversion In(3R)Payne on body size across the North American and Australian clines in Drosophila melanogaster.

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Kapun, M; Schmidt, C; Durmaz, E; Schmidt, P S; Flatt, T

2016-05-01

Chromosomal inversions are thought to play a major role in climatic adaptation. In D. melanogaster, the cosmopolitan inversion In(3R)Payne exhibits latitudinal clines on multiple continents. As many fitness traits show similar clines, it is tempting to hypothesize that In(3R)P underlies observed clinal patterns for some of these traits. In support of this idea, previous work in Australian populations has demonstrated that In(3R)P affects body size but not development time or cold resistance. However, similar data from other clines of this inversion are largely lacking; finding parallel effects of In(3R)P across multiple clines would considerably strengthen the case for clinal selection. Here, we have analysed the phenotypic effects of In(3R)P in populations originating from the endpoints of the latitudinal cline along the North American east coast. We measured development time, egg-to-adult survival, several size-related traits (femur and tibia length, wing area and shape), chill coma recovery, oxidative stress resistance and triglyceride content in homokaryon lines carrying In(3R)P or the standard arrangement. Our central finding is that the effects of In(3R)P along the North American cline match those observed in Australia: standard arrangement lines were larger than inverted lines, but the inversion did not influence development time or cold resistance. Similarly, In(3R)P did not affect egg-to-adult survival, oxidative stress resistance and lipid content. In(3R)P thus seems to specifically affect size traits in populations from both continents. This parallelism strongly suggests an adaptive pattern, whereby the inversion has captured alleles associated with growth regulation and clinal selection acts on size across both continents. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Pattern-Driven Automatic Parallelization

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Christoph W. Kessler

1996-01-01

Full Text Available This article describes a knowledge-based system for automatic parallelization of a wide class of sequential numerical codes operating on vectors and dense matrices, and for execution on distributed memory message-passing multiprocessors. Its main feature is a fast and powerful pattern recognition tool that locally identifies frequently occurring computations and programming concepts in the source code. This tool also works for dusty deck codes that have been "encrypted" by former machine-specific code transformations. Successful pattern recognition guides sophisticated code transformations including local algorithm replacement such that the parallelized code need not emerge from the sequential program structure by just parallelizing the loops. It allows access to an expert's knowledge on useful parallel algorithms, available machine-specific library routines, and powerful program transformations. The partially restored program semantics also supports local array alignment, distribution, and redistribution, and allows for faster and more exact prediction of the performance of the parallelized target code than is usually possible.

Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations

Science.gov (United States)

Vina, Marcelo A. Fernandez; Hollenbach, Jill A.; Lyke, Kirsten E.; Sztein, Marcelo B.; Maiers, Martin; Klitz, William; Cano, Pedro; Mack, Steven; Single, Richard; Brautbar, Chaim; Israel, Shosahna; Raimondi, Eduardo; Khoriaty, Evelyne; Inati, Adlette; Andreani, Marco; Testi, Manuela; Moraes, Maria Elisa; Thomson, Glenys; Stastny, Peter; Cao, Kai

2012-01-01

The human leucocyte antigen (HLA) system shows extensive variation in the number and function of loci and the number of alleles present at any one locus. Allele distribution has been analysed in many populations through the course of several decades, and the implementation of molecular typing has significantly increased the level of diversity revealing that many serotypes have multiple functional variants. While the degree of diversity in many populations is equivalent and may result from functional polymorphism(s) in peptide presentation, homogeneous and heterogeneous populations present contrasting numbers of alleles and lineages at the loci with high-density expression products. In spite of these differences, the homozygosity levels are comparable in almost all of them. The balanced distribution of HLA alleles is consistent with overdominant selection. The genetic distances between outbred populations correlate with their geographical locations; the formal genetic distance measurements are larger than expected between inbred populations in the same region. The latter present many unique alleles grouped in a few lineages consistent with limited founder polymorphism in which any novel allele may have been positively selected to enlarge the communal peptide-binding repertoire of a given population. On the other hand, it has been observed that some alleles are found in multiple populations with distinctive haplotypic associations suggesting that convergent evolution events may have taken place as well. It appears that the HLA system has been under strong selection, probably owing to its fundamental role in varying immune responses. Therefore, allelic diversity in HLA should be analysed in conjunction with other genetic markers to accurately track the migrations of modern humans. PMID:22312049

MSAProbs-MPI: parallel multiple sequence aligner for distributed-memory systems.

Science.gov (United States)

González-Domínguez, Jorge; Liu, Yongchao; Touriño, Juan; Schmidt, Bertil

2016-12-15

MSAProbs is a state-of-the-art protein multiple sequence alignment tool based on hidden Markov models. It can achieve high alignment accuracy at the expense of relatively long runtimes for large-scale input datasets. In this work we present MSAProbs-MPI, a distributed-memory parallel version of the multithreaded MSAProbs tool that is able to reduce runtimes by exploiting the compute capabilities of common multicore CPU clusters. Our performance evaluation on a cluster with 32 nodes (each containing two Intel Haswell processors) shows reductions in execution time of over one order of magnitude for typical input datasets. Furthermore, MSAProbs-MPI using eight nodes is faster than the GPU-accelerated QuickProbs running on a Tesla K20. Another strong point is that MSAProbs-MPI can deal with large datasets for which MSAProbs and QuickProbs might fail due to time and memory constraints, respectively. Source code in C ++ and MPI running on Linux systems as well as a reference manual are available at http://msaprobs.sourceforge.net CONTACT: jgonzalezd@udc.esSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Parallel grid generation algorithm for distributed memory computers

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Moitra, Stuti; Moitra, Anutosh

1994-01-01

A parallel grid-generation algorithm and its implementation on the Intel iPSC/860 computer are described. The grid-generation scheme is based on an algebraic formulation of homotopic relations. Methods for utilizing the inherent parallelism of the grid-generation scheme are described, and implementation of multiple levELs of parallelism on multiple instruction multiple data machines are indicated. The algorithm is capable of providing near orthogonality and spacing control at solid boundaries while requiring minimal interprocessor communications. Results obtained on the Intel hypercube for a blended wing-body configuration are used to demonstrate the effectiveness of the algorithm. Fortran implementations bAsed on the native programming model of the iPSC/860 computer and the Express system of software tools are reported. Computational gains in execution time speed-up ratios are given.

Ortholog Alleles at Xa3/Xa26 Locus Confer Conserved Race-Specific Resistance against Xanthomonas oryzae in Rice

Institute of Scientific and Technical Information of China (English)

Hong-Jing Li; Xiang-Hua Li; Jing-Hua Xiao; Rod A. Wing; Shi-Ping Wang

2012-01-01

The rice disease resistance (R) gene Xa3/Xa26 (having also been named Xa3 and Xa26) against Xanthomonas oryzae pv.oryzae (Xoo),which causes bacterial blight disease,belongs to a multiple gene family clustered in chromosome 11 and is from an AA genome rice cultivar (Oryza sativa L.).This family encodes leucine-rich repeat (LRR) receptor kinasetype proteins.Here,we show that the orthologs (alleles) of Xa3/Xa26,Xa3/Xa26-2,and Xa3/Xa26-3,from wild Oryza species O.officinalis (CC genome) and O.minuta (BBCC genome),respectively,were also R genes against Xoo.Xa3/Xa26-2 and Xa3/Xa26-3 conferred resistance to 16 of the 18 Xoo strains examined.Comparative sequence analysis of the Xa3/Xa26 families in the two wild Oryza species showed that Xa3/Xa26-3 appeared to have originated from the CC genome of O.minuta.The predicted proteins encoded by Xa3/Xa26,Xa3/Xa26-2,and Xa3/Xa26-3 share 91-99％ sequence identity and 94-99％ sequence similarity.Transgenic plants carrying a single copy of Xa3/Xa26,Xa3/Xa26-2,or Xa3/Xa26-3,in the same genetic background,showed a similar resistance spectrum to a set of Xoo strains,although plants carrying Xa3/Xa26-2 or Xa3/Xa26-3 showed lower resistance levels than the plants carrying Xa3/Xa26.These results suggest that the Xa3/Xa26 locus predates the speciation of A and C genome,which is approximately 7.5 million years ago.Thus,the resistance specificity of this locus has been conserved for a long time.

Genome-wide identification and quantification of cis- and trans-regulated genes responding to Marek’s disease virus infection via analysis of allele-specific expression

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Sean eMaceachern

2012-01-01

Full Text Available Marek’s disease (MD is a commercially important neoplastic disease of chickens caused by Marek’s disease virus (MDV, an oncogenic alphaherpesvirus. Selecting for increased genetic resistance to MD is a control strategy that can augment vaccinal control measures. To identify high-confidence candidate MD resistance genes, we conducted a genome-wide screen for allele-specific expression (ASE amongst F1 progeny of two inbred chicken lines that differ in MD resistance. High throughput sequencing was used to profile transcriptomes from pools of uninfected and infected individuals at 4 days post-infection to identify any genes showing ASE in response to MDV infection. RNA sequencing identified 22,655 single nucleotide polymorphisms (SNPs of which 5,360 in 3,773 genes exhibited significant allelic imbalance. Illumina GoldenGate assays were subsequently used to quantify regulatory variation controlled at the gene (cis and elsewhere in the genome (trans by examining differences in expression between F1 individuals and artificial F1 RNA pools over 6 time periods in 1,536 of the most significant SNPs identified by RNA sequencing. Allelic imbalance as a result of cis-regulatory changes was confirmed in 861 of the 1,233 GoldenGate assays successfully examined. Furthermore we have identified 7 genes that display trans-regulation only in infected animals and approximately 500 SNP that show a complex interaction between cis- and trans-regulatory changes. Our results indicate ASE analyses are a powerful approach to identify regulatory variation responsible for differences in transcript abundance in genes underlying complex traits. And the genes with SNPs exhibiting ASE provide a strong foundation to further investigate the causative polymorphisms and genetic mechanisms for MD resistance. Finally, the methods used here for identifying specific genes and SNPs may have practical implications for applying marker-assisted selection to complex traits that are

Novel polymorphisms within the Dlk1-Dio3 imprinted locus in rat: a putative genetic basis for strain-specific allelic gene expression

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Laura J Sittig

2012-12-01

Full Text Available The imprinted iodothyronine deiodinase-III (Dio3 thyroid hormone metabolizing gene exhibits paternal expression in most fetal tissues, yet exhibits aberrant, maternal expression in the hippocampus in F1 offspring of Sprague Dawley (SD x Brown Norway (BN rats. The maternal hippocampal expression is associated with lower Dio3 mRNA levels specifically in the hippocampus. Here, we tested the hypothesis that genetic polymorphisms between the SD and BN parent strains cause this aberrant allelic Dio3 expression and contribute to behavioral sequelae of higher thyroid hormone levels locally in the hippocampus, including anxiety-related behavior. We mapped and sequenced the Dio3 gene and several previously unmapped regions in the Dlk1-Dio3 locus that could regulate imprinting of the Dio3 gene. In the Dio3 promoter we identified four novel polymorphisms between the BN and SD strains. Next we took advantage of the fact that the Long Evans (LE strain exhibits identical polymorphisms as the SD strain in the region 5’ and including the Dio3 gene. By reciprocally crossing LE and BN strains we tested the relationship among Dio3 promoter region polymorphisms and Dio3 mRNA expression in the hippocampus. Aberrant strain-specific hippocampal Dio3 allelic expression replicated in the LE-BN reciprocal crosses, suggesting that hippocampal-specific imprinting of the Dio3 gene is not the result of a unique genetic or epigenetic characteristic of the SD rat strain, or a unique epistatic interaction between SD and BN. To our knowledge no other studies have reported a genetic x epigenetic interaction of genetic origin in the brain.

Cloud-Coffee: implementation of a parallel consistency-based multiple alignment algorithm in the T-Coffee package and its benchmarking on the Amazon Elastic-Cloud.

Science.gov (United States)

Di Tommaso, Paolo; Orobitg, Miquel; Guirado, Fernando; Cores, Fernado; Espinosa, Toni; Notredame, Cedric

2010-08-01

We present the first parallel implementation of the T-Coffee consistency-based multiple aligner. We benchmark it on the Amazon Elastic Cloud (EC2) and show that the parallelization procedure is reasonably effective. We also conclude that for a web server with moderate usage (10K hits/month) the cloud provides a cost-effective alternative to in-house deployment. T-Coffee is a freeware open source package available from http://www.tcoffee.org/homepage.html

Towards allele mining of bacterial wilt disease resistance gene in tomato

International Nuclear Information System (INIS)

Galvez, H.F.; Narciso, J.O.; Opina, N.L.; Canama, A.O.; Colle, M.G.; Latiza, M.A.; Caspillo, C.L.; Bituin, J.L.; Frankie, R.B.; Hautea, D.M.

2005-01-01

Tomato (Lycopersicon esculentum Mill.) is the most important vegetable commodity of the Philippines. Bacterial wilt caused by Ralstonia solanacearum is one serious constraint in tomato production particularly during off-season planting. A major locus derived from H7996 that confers resistance to bacterial wilt has been mapped in the tomato genome. To validate the biological function of the resistance locus and generate multiple allele -mimics-, targeted mutation was induced in tomato using gamma ray and ethyl methane sulfonate (EMS) mutagens. Suitable mutagen treatment was established by evaluating a wide range of mutagen doses/concentrations for a) percent seed germination, b) reduction in plant height, and c) loss of resistance. Six hundred Gy and 1.0% EMS were identified to generate large M1 families of H7996. From 10,000 initial seeds treated with either gamma ray or EMS, a total of 3,663 M1 plants were generated. M2 seeds were harvested from all surviving M1 plants. Several DNA markers have been resourced and are being developed specific to the bacterial wilt resistant gene. In the large M2 population, of H7996, both the phenotypic manifestation of bacterial wilt susceptibility and nucleotide changes in the resistance locus will be evaluated. Large M3 families for the different allele series of the bacterial wilt resistance gene will be established for future high throughput TILLING (Targeting Induced Local Lesions in Genomes) analysis in the gene region

Structured Parallel Programming Patterns for Efficient Computation

CERN Document Server

McCool, Michael; Robison, Arch

2012-01-01

Programming is now parallel programming. Much as structured programming revolutionized traditional serial programming decades ago, a new kind of structured programming, based on patterns, is relevant to parallel programming today. Parallel computing experts and industry insiders Michael McCool, Arch Robison, and James Reinders describe how to design and implement maintainable and efficient parallel algorithms using a pattern-based approach. They present both theory and practice, and give detailed concrete examples using multiple programming models. Examples are primarily given using two of th

Role of the B Allele of Influenza A Virus Segment 8 in Setting Mammalian Host Range and Pathogenicity.

Science.gov (United States)

Turnbull, Matthew L; Wise, Helen M; Nicol, Marlynne Q; Smith, Nikki; Dunfee, Rebecca L; Beard, Philippa M; Jagger, Brett W; Ligertwood, Yvonne; Hardisty, Gareth R; Xiao, Haixia; Benton, Donald J; Coburn, Alice M; Paulo, Joao A; Gygi, Steven P; McCauley, John W; Taubenberger, Jeffery K; Lycett, Samantha J; Weekes, Michael P; Dutia, Bernadette M; Digard, Paul

2016-10-15

burden on farming and health care sectors. Host adaptation likely involves multiple viral factors. Here, we investigated the role of IAV segment 8. Segment 8 has evolved into two distinct clades: the A and B alleles. The B-allele genes have previously been suggested to be restricted to avian virus species. We introduced a selection of avian virus A- and B-allele segment 8s into human H1N1 and H3N2 virus backgrounds and found that these reassortant viruses were fully competent in mammalian host systems. We also analyzed the currently available public data on the segment 8 gene distribution and found surprisingly little evidence for specific avian host restriction of the B-clade segment. We conclude that B-allele segment 8 genes are, in fact, capable of supporting infection in mammals and that they should be considered during the assessment of the pandemic risk of zoonotic influenza A viruses. Copyright © 2016 Turnbull et al.

Abnormal segregation of alleles in CEPH pedigree DNAs arising from allele loss in lymphoblastoid DNA.

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Royle, N J; Armour, J A; Crosier, M; Jeffreys, A J

1993-01-01

Somatic events that result in the reduction to hemi- or homozygosity at all loci affected by the event have been identified in lymphoblastoid DNA from mothers of two CEPH families. Using suitably informative probes, the allele deficiencies were detected by the abnormal transmission of alleles from grandparents to grandchildren, with the apparent absence of the alleles from the parent. Undetected somatic deficiencies in family DNAs could result in misscoring of recombination events and consequently introduce errors into linkage analysis.

Intrinsic MYH7 expression regulation contributes to tissue level allelic imbalance in hypertrophic cardiomyopathy.

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Montag, Judith; Syring, Mandy; Rose, Julia; Weber, Anna-Lena; Ernstberger, Pia; Mayer, Anne-Kathrin; Becker, Edgar; Keyser, Britta; Dos Remedios, Cristobal; Perrot, Andreas; van der Velden, Jolanda; Francino, Antonio; Navarro-Lopez, Francesco; Ho, Carolyn Yung; Brenner, Bernhard; Kraft, Theresia

2017-08-01

HCM, the most common inherited cardiac disease, is mainly caused by mutations in sarcomeric genes. More than a third of the patients are heterozygous for mutations in the MYH7 gene encoding for the β-myosin heavy chain. In HCM-patients, expression of the mutant and the wildtype allele can be unequal, thus leading to fractions of mutant and wildtype mRNA and protein which deviate from 1:1. This so-called allelic imbalance was detected in whole tissue samples but also in individual cells. There is evidence that the severity of HCM not only depends on the functional effect of the mutation itself, but also on the fraction of mutant protein in the myocardial tissue. Allelic imbalance has been shown to occur in a broad range of genes. Therefore, we aimed to examine whether the MYH7-alleles are intrinsically expressed imbalanced or whether the allelic imbalance is solely associated with the disease. We compared the expression of MYH7-alleles in non-HCM donors and in HCM-patients with different MYH7-missense mutations. In the HCM-patients, we identified imbalanced as well as equal expression of both alleles. Also at the protein level, allelic imbalance was determined. Most interestingly, we also discovered allelic imbalance and balance in non-HCM donors. Our findings therefore strongly indicate that apart from mutation-specific mechanisms, also non-HCM associated allelic-mRNA expression regulation may account for the allelic imbalance of the MYH7 gene in HCM-patients. Since the relative amount of mutant mRNA and protein or the extent of allelic imbalance has been associated with the severity of HCM, individual analysis of the MYH7-allelic expression may provide valuable information for the prognosis of each patient.

Technical aspects of typing for HLA-DP alleles using allele-specific DNA in vitro amplification and sequence-specific oligonucleotide probes. Detection of single base mismatches

DEFF Research Database (Denmark)

Fugger, L; Morling, N; Ryder, L P

1990-01-01

The polymerase chain reaction (PCR) is an effective method for in vitro DNA amplification which combined with probing with synthetic oligonucleotides can be used for, e.g., HLA-typing. We have studied the technical aspects of HLA-DP typing with the technique. DNA from mononuclear nucleated cells...... was extracted with either a simple salting out method or phenol/chloroform. Both DNAs could be readily used for PCR. The MgC2 concentration of the PCR buffer and the annealing temperature of the thermal cycle of the PCR were the two most important variables. The MgCl2 concentration and the temperature must...... be carefully titrated for each primer pair in the PCR. The influence of mismatches between the primer and the DNA template were studied and we found that, by using primers differing only from each other at the 3' end, cross-amplification of closely homologous alleles could be avoided. Thus, single base...

Parallel R

CERN Document Server

McCallum, Ethan

2011-01-01

It's tough to argue with R as a high-quality, cross-platform, open source statistical software product-unless you're in the business of crunching Big Data. This concise book introduces you to several strategies for using R to analyze large datasets. You'll learn the basics of Snow, Multicore, Parallel, and some Hadoop-related tools, including how to find them, how to use them, when they work well, and when they don't. With these packages, you can overcome R's single-threaded nature by spreading work across multiple CPUs, or offloading work to multiple machines to address R's memory barrier.

Shared Variable Oriented Parallel Precompiler for SPMD Model

Institute of Scientific and Technical Information of China (English)

无

1995-01-01

For the moment,commercial parallel computer systems with distributed memory architecture are usually provided with parallel FORTRAN or parallel C compliers,which are just traditional sequential FORTRAN or C compilers expanded with communication statements.Programmers suffer from writing parallel programs with communication statements. The Shared Variable Oriented Parallel Precompiler (SVOPP) proposed in this paper can automatically generate appropriate communication statements based on shared variables for SPMD(Single Program Multiple Data) computation model and greatly ease the parallel programming with high communication efficiency.The core function of parallel C precompiler has been successfully verified on a transputer-based parallel computer.Its prominent performance shows that SVOPP is probably a break-through in parallel programming technique.

Mapping robust parallel multigrid algorithms to scalable memory architectures

Science.gov (United States)

Overman, Andrea; Vanrosendale, John

1993-01-01

The convergence rate of standard multigrid algorithms degenerates on problems with stretched grids or anisotropic operators. The usual cure for this is the use of line or plane relaxation. However, multigrid algorithms based on line and plane relaxation have limited and awkward parallelism and are quite difficult to map effectively to highly parallel architectures. Newer multigrid algorithms that overcome anisotropy through the use of multiple coarse grids rather than relaxation are better suited to massively parallel architectures because they require only simple point-relaxation smoothers. In this paper, we look at the parallel implementation of a V-cycle multiple semicoarsened grid (MSG) algorithm on distributed-memory architectures such as the Intel iPSC/860 and Paragon computers. The MSG algorithms provide two levels of parallelism: parallelism within the relaxation or interpolation on each grid and across the grids on each multigrid level. Both levels of parallelism must be exploited to map these algorithms effectively to parallel architectures. This paper describes a mapping of an MSG algorithm to distributed-memory architectures that demonstrates how both levels of parallelism can be exploited. The result is a robust and effective multigrid algorithm for distributed-memory machines.

Induction of Terpene Biosynthesis in Berries of Microvine Transformed with VvDXS1 Alleles

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Lorenza Dalla Costa

2018-01-01

Full Text Available Terpenoids, especially monoterpenes, are major aroma-impact compounds in grape and wine. Previous studies highlighted a key regulatory role for grapevine 1-deoxy-D-xylulose 5-phosphate synthase 1 (VvDXS1, the first enzyme of the methylerythritol phosphate pathway for isoprenoid precursor biosynthesis. Here, the parallel analysis of VvDXS1 genotype and terpene concentration in a germplasm collection demonstrated that VvDXS1 sequence has a very high predictive value for the accumulation of monoterpenes and also has an influence on sesquiterpene levels. A metabolic engineering approach was applied by expressing distinct VvDXS1 alleles in the grapevine model system “microvine” and assessing the effects on downstream pathways at transcriptional and metabolic level in different organs and fruit developmental stages. The underlying goal was to investigate two potential perturbation mechanisms, the former based on a significant over-expression of the wild-type (neutral VvDXS1 allele and the latter on the ex-novo expression of an enzyme with increased catalytic efficiency from the mutated (muscat VvDXS1 allele. The integration of the two VvDXS1 alleles in distinct microvine lines was found to alter the expression of several terpenoid biosynthetic genes, as assayed through an ad hoc developed TaqMan array based on cDNA libraries of four aromatic cultivars. In particular, enhanced transcription of monoterpene, sesquiterpene and carotenoid pathway genes was observed. The accumulation of monoterpenes in ripe berries was higher in the transformed microvines compared to control plants. This effect is predominantly attributed to the improved activity of the VvDXS1 enzyme coded by the muscat allele, whereas the up-regulation of VvDXS1 plays a secondary role in the increase of monoterpenes.

Two alleles of the AtCesA3 gene in Arabidopsis thaliana display intragenic complementation.

Science.gov (United States)

Pysh, Leonard D

2015-09-01

Cellulose is the most abundant biomolecule on the planet, yet the mechanism by which it is synthesized by higher plants remains largely unknown. In Arabidopsis thaliana (L.) Heynh, synthesis of cellulose in the primary cell wall requires three different cellulose synthase genes (AtCesA1, AtCesA3, and AtCesA6-related genes [AtCesA2, AtCesA5, and AtCesA6]). The multiple response expansion1 (mre1) mutant contains a hypomorphic AtCesA3 allele that results in significantly shorter, expanded roots. Crosses between mre1 and another allele of AtCesA3 (constitutive expression of VSP1, cev1) yielded an F1 with roots considerably longer and thinner than either parent, suggesting intragenic complementation. The F2 generation resulting from self-crossing these F1 showed three different root phenotypes: roots like mre1, roots like cev1, and roots like the F1. The segregation patterns of the three root phenotypes in multiple F2 and F3 generations were determined. Multiple characteristics of the roots and shoots were analyzed both qualitatively and quantitatively at different developmental stages, both on plates and on soil. The trans-heterozygous plants differed significantly from the parental mre1 and cev1 lines. The two alleles display intragenic complementation. A classic genetic interpretation of these results would suggest that cellulose synthesis requires homo-multimerization of cellulose synthase monomers. © 2015 Botanical Society of America.

Global phylogeography of the avian malaria pathogen Plasmodium relictum based on MSP1 allelic diversity

Science.gov (United States)

Hellgren, Olof; Atkinson, Carter T.; Bensch, Staffan; Albayrak, Tamer; Dimitrov, Dimitar; Ewen, John G.; Kim, Kyeong Soon; Lima, Marcos R.; Martin, Lynn; Palinauskas, Vaidas; Ricklefs, Robert; Sehgal, Ravinder N. M.; Gediminas, Valkiunas; Tsuda, Yoshio; Marzal, Alfonso

2015-01-01

Knowing the genetic variation that occurs in pathogen populations and how it is distributed across geographical areas is essential to understand parasite epidemiology, local patterns of virulence, and evolution of host-resistance. In addition, it is important to identify populations of pathogens that are evolutionarily independent and thus ‘free’ to adapt to hosts and environments. Here, we investigated genetic variation in the globally distributed, highly invasive avian malaria parasite Plasmodium relictum, which has several distinctive mitochondrial haplotyps (cyt b lineages, SGS1, GRW11 and GRW4). The phylogeography of P. relictum was accessed using the highly variable nuclear gene merozoite surface protein 1 (MSP1), a gene linked to the invasion biology of the parasite. We show that the lineage GRW4 is evolutionarily independent of GRW11 and SGS1 whereas GRW11 and SGS1 share MSP1 alleles and thus suggesting the presence of two distinct species (GRW4 versus SGS1 and GRW11). Further, there were significant differences in the global distribution of MSP1 alleles with differences between GRW4 alleles in the New and the Old World. For SGS1, a lineage formerly believed to have both tropical and temperate transmission, there were clear differences in MSP1 alleles transmitted in tropical Africa compared to the temperate regions of Europe and Asia. Further, we highlight the occurrence of multiple MSP1 alleles in GRW4 isolates from the Hawaiian Islands, where the parasite has contributed to declines and extinctions of endemic forest birds since it was introduced. This study stresses the importance of multiple independent loci for understanding patterns of transmission and evolutionary independence across avian malaria parasites.

A WIDE DISTRIBUTION OF A NEW VRN-B1c ALLELE OF WHEAT TRITICUM AESTIVUM L. IN RUSSIA, UKRAINE AND ADJACENT REGIONS: A LINK WITH THE HEADING TIME AND ADAPTIVE POTENTIAL

Directory of Open Access Journals (Sweden)

Shcherban A.

2012-08-01

Full Text Available The adaptation of common wheat (T. aestivum L. to diverse environmental conditions is greatly under the control of genes involved in determination of vernalization response (Vrn-1 genes. It was found that the variation in common wheat heading time is affected not only by combination of Vrn-1 homoeoalleles but also by multiple alleles at a separate Vrn-1 locus. Previously, we described the Vrn-B1c allele from T.aestivum cv. 'Saratovskaya 29' and found significant differences in the structure of the first (1st intron of this allele when compared to another highly abundant Vrn-B1a allele, specifically, the deletion of 0.8 kb coupled with the duplication of 0.4 kb. We suggested that the changes in the intron 1 of Vrn-B1c allele caused earlier ear emergence in the near-isogenic line and cultivars, carrying this allele. In this study we investigate the distribution of the Vrn-B1c allele in a wide set of spring wheat cultivars from Russia, Ukraine and adjacent regions. The analysis revealed that 40% of Russian and 53% of Ukranian spring wheat cultivars contain the Vrn-B1c allele. The high distribution of the Vrn-B1c allele can be explained by a frequent using of 'Saratovskaya 29' in the breeding process inside the studied area. From the other hand, the predominance of the Vrn-B1c allele among cultivars cultivated in West Siberia and Kazakhstan may be due to the selective advantage of this allele for the region where there is a high risk of early fall frosts.

Synchronization Techniques in Parallel Discrete Event Simulation

OpenAIRE

Lindén, Jonatan

2018-01-01

Discrete event simulation is an important tool for evaluating system models in many fields of science and engineering. To improve the performance of large-scale discrete event simulations, several techniques to parallelize discrete event simulation have been developed. In parallel discrete event simulation, the work of a single discrete event simulation is distributed over multiple processing elements. A key challenge in parallel discrete event simulation is to ensure that causally dependent ...

Development of an allele-specific PCR assay for simultaneous sero-typing of avian pathogenic Escherichia coli predominant O1, O2, O18 and O78 strains.

Science.gov (United States)

Wang, Shaohui; Meng, Qingmei; Dai, Jianjun; Han, Xiangan; Han, Yue; Ding, Chan; Liu, Haiwen; Yu, Shengqing

2014-01-01

Systemic infections by avian pathogenic Escherichia coli (APEC) are economically devastating to poultry industries worldwide. E. coli strains belonging to serotypes O1, O2, O18 and O78 are preferentially associated with avian colibacillosis. The rfb gene cluster controlling O antigen synthesis is usually various among different E. coli serotypes. In present study, the rfb gene clusters of E. coli serotypes O1, O2, O18 and O78 were characterized and compared. Based on the serotype-specific genes in rfb gene cluster, an allele-specific polymerase chain reaction (PCR) assay was developed. This PCR assay was highly specific and reliable for sero-typing of APEC O1, O2, O18 and O78 strains. The sensitivity of the assay was determined as 10 pg DNA or 10 colony forming units (CFUs) bacteria for serotypes O2 and O18 strains, and 500 pg DNA or 1,000 CFUs bacteria for serotypes O1 and O78 strains. Using this PCR system, APEC isolates and the infected tissue samples were categorized successfully. Furthermore, it was able to differentiate the serotypes for the samples with multi-agglutination in the traditional serum agglutination assay. Therefore, the allele-specific PCR is more simple, rapid and accurate assay for APEC diagnosis, epidemiologic study and vaccine development.

Development of an allele-specific PCR assay for simultaneous sero-typing of avian pathogenic Escherichia coli predominant O1, O2, O18 and O78 strains.

Directory of Open Access Journals (Sweden)

Shaohui Wang

Full Text Available Systemic infections by avian pathogenic Escherichia coli (APEC are economically devastating to poultry industries worldwide. E. coli strains belonging to serotypes O1, O2, O18 and O78 are preferentially associated with avian colibacillosis. The rfb gene cluster controlling O antigen synthesis is usually various among different E. coli serotypes. In present study, the rfb gene clusters of E. coli serotypes O1, O2, O18 and O78 were characterized and compared. Based on the serotype-specific genes in rfb gene cluster, an allele-specific polymerase chain reaction (PCR assay was developed. This PCR assay was highly specific and reliable for sero-typing of APEC O1, O2, O18 and O78 strains. The sensitivity of the assay was determined as 10 pg DNA or 10 colony forming units (CFUs bacteria for serotypes O2 and O18 strains, and 500 pg DNA or 1,000 CFUs bacteria for serotypes O1 and O78 strains. Using this PCR system, APEC isolates and the infected tissue samples were categorized successfully. Furthermore, it was able to differentiate the serotypes for the samples with multi-agglutination in the traditional serum agglutination assay. Therefore, the allele-specific PCR is more simple, rapid and accurate assay for APEC diagnosis, epidemiologic study and vaccine development.

CARAT: A novel method for allelic detection of DNA copy number changes using high density oligonucleotide arrays

Directory of Open Access Journals (Sweden)

Ishikawa Shumpei

2006-02-01

Full Text Available Abstract Background DNA copy number alterations are one of the main characteristics of the cancer cell karyotype and can contribute to the complex phenotype of these cells. These alterations can lead to gains in cellular oncogenes as well as losses in tumor suppressor genes and can span small intervals as well as involve entire chromosomes. The ability to accurately detect these changes is central to understanding how they impact the biology of the cell. Results We describe a novel algorithm called CARAT (Copy Number Analysis with Regression And Tree that uses probe intensity information to infer copy number in an allele-specific manner from high density DNA oligonuceotide arrays designed to genotype over 100, 000 SNPs. Total and allele-specific copy number estimations using CARAT are independently evaluated for a subset of SNPs using quantitative PCR and allelic TaqMan reactions with several human breast cancer cell lines. The sensitivity and specificity of the algorithm are characterized using DNA samples containing differing numbers of X chromosomes as well as a test set of normal individuals. Results from the algorithm show a high degree of agreement with results from independent verification methods. Conclusion Overall, CARAT automatically detects regions with copy number variations and assigns a significance score to each alteration as well as generating allele-specific output. When coupled with SNP genotype calls from the same array, CARAT provides additional detail into the structure of genome wide alterations that can contribute to allelic imbalance.

Using multi-locus allelic sequence data to estimate genetic divergence among four Lilium (Liliaceae) cultivars

NARCIS (Netherlands)

Shahin, A.; Smulders, M.J.M.; Tuyl, van J.M.; Arens, P.F.P.; Bakker, F.T.

2014-01-01

Next Generation Sequencing (NGS) may enable estimating relationships among genotypes using allelic variation of multiple nuclear genes simultaneously. We explored the potential and caveats of this strategy in four genetically distant Lilium cultivars to estimate their genetic divergence from

Parallel magnetic resonance imaging

International Nuclear Information System (INIS)

Larkman, David J; Nunes, Rita G

2007-01-01

Parallel imaging has been the single biggest innovation in magnetic resonance imaging in the last decade. The use of multiple receiver coils to augment the time consuming Fourier encoding has reduced acquisition times significantly. This increase in speed comes at a time when other approaches to acquisition time reduction were reaching engineering and human limits. A brief summary of spatial encoding in MRI is followed by an introduction to the problem parallel imaging is designed to solve. There are a large number of parallel reconstruction algorithms; this article reviews a cross-section, SENSE, SMASH, g-SMASH and GRAPPA, selected to demonstrate the different approaches. Theoretical (the g-factor) and practical (coil design) limits to acquisition speed are reviewed. The practical implementation of parallel imaging is also discussed, in particular coil calibration. How to recognize potential failure modes and their associated artefacts are shown. Well-established applications including angiography, cardiac imaging and applications using echo planar imaging are reviewed and we discuss what makes a good application for parallel imaging. Finally, active research areas where parallel imaging is being used to improve data quality by repairing artefacted images are also reviewed. (invited topical review)

Applications of the parallel computing system using network

International Nuclear Information System (INIS)

Ido, Shunji; Hasebe, Hiroki

1994-01-01

Parallel programming is applied to multiple processors connected in Ethernet. Data exchanges between tasks located in each processing element are realized by two ways. One is socket which is standard library on recent UNIX operating systems. Another is a network connecting software, named as Parallel Virtual Machine (PVM) which is a free software developed by ORNL, to use many workstations connected to network as a parallel computer. This paper discusses the availability of parallel computing using network and UNIX workstations and comparison between specialized parallel systems (Transputer and iPSC/860) in a Monte Carlo simulation which generally shows high parallelization ratio. (author)

MEDUSA - An overset grid flow solver for network-based parallel computer systems

Science.gov (United States)

Smith, Merritt H.; Pallis, Jani M.

1993-01-01

Continuing improvement in processing speed has made it feasible to solve the Reynolds-Averaged Navier-Stokes equations for simple three-dimensional flows on advanced workstations. Combining multiple workstations into a network-based heterogeneous parallel computer allows the application of programming principles learned on MIMD (Multiple Instruction Multiple Data) distributed memory parallel computers to the solution of larger problems. An overset-grid flow solution code has been developed which uses a cluster of workstations as a network-based parallel computer. Inter-process communication is provided by the Parallel Virtual Machine (PVM) software. Solution speed equivalent to one-third of a Cray-YMP processor has been achieved from a cluster of nine commonly used engineering workstation processors. Load imbalance and communication overhead are the principal impediments to parallel efficiency in this application.

Scattering by multiple parallel radially stratified infinite cylinders buried in a lossy half space.

Science.gov (United States)

Lee, Siu-Chun

2013-07-01

The theoretical solution for scattering by an arbitrary configuration of closely spaced parallel infinite cylinders buried in a lossy half space is presented in this paper. The refractive index and permeability of the half space and cylinders are complex in general. Each cylinder is radially stratified with a distinct complex refractive index and permeability. The incident radiation is an arbitrarily polarized plane wave propagating in the plane normal to the axes of the cylinders. Analytic solutions are derived for the electric and magnetic fields and the Poynting vector of backscattered radiation emerging from the half space. Numerical examples are presented to illustrate the application of the scattering solution to calculate backscattering from a lossy half space containing multiple homogeneous and radially stratified cylinders at various depths and different angles of incidence.

Genome-wide association study in discordant sibships identifies multiple inherited susceptibility alleles linked to lung cancer.

Science.gov (United States)

Galvan, Antonella; Falvella, Felicia S; Frullanti, Elisa; Spinola, Monica; Incarbone, Matteo; Nosotti, Mario; Santambrogio, Luigi; Conti, Barbara; Pastorino, Ugo; Gonzalez-Neira, Anna; Dragani, Tommaso A

2010-03-01

We analyzed a series of young (median age = 52 years) non-smoker lung cancer patients and their unaffected siblings as controls, using a genome-wide 620 901 single-nucleotide polymorphism (SNP) array analysis and a case-control DNA pooling approach. We identified 82 putatively associated SNPs that were retested by individual genotyping followed by use of the sib transmission disequilibrium test, pointing to 36 SNPs associated with lung cancer risk in the discordant sibs series. Analysis of these 36 SNPs in a polygenic model characterized by additive and interchangeable effects of rare alleles revealed a highly statistically significant dosage-dependent association between risk allele carrier status and proportion of cancer cases. Replication of the same 36 SNPs in a population-based series confirmed the association with lung cancer for three SNPs, suggesting that phenocopies and genetic heterogeneity can play a major role in the complex genetics of lung cancer risk in the general population.

Parallel discrete event simulation

NARCIS (Netherlands)

Overeinder, B.J.; Hertzberger, L.O.; Sloot, P.M.A.; Withagen, W.J.

1991-01-01

In simulating applications for execution on specific computing systems, the simulation performance figures must be known in a short period of time. One basic approach to the problem of reducing the required simulation time is the exploitation of parallelism. However, in parallelizing the simulation

The restriction-modification genes of Escherichia coli K-12 may not be selfish: they do not resist loss and are readily replaced by alleles conferring different specificities.

Science.gov (United States)

O'Neill, M; Chen, A; Murray, N E

1997-12-23

Type II restriction and modification (R-M) genes have been described as selfish because they have been shown to impose selection for the maintenance of the plasmid that encodes them. In our experiments, the type I R-M system EcoKI does not behave in the same way. The genes specifying EcoKI are, however, normally residents of the chromosome and therefore our analyses were extended to monitor the deletion of chromosomal genes rather than loss of plasmid vector. If EcoKI were to behave in the same way as the plasmid-encoded type II R-M systems, the loss of the relevant chromosomal genes by mutation or recombination should lead to cell death because the cell would become deficient in modification enzyme and the bacterial chromosome would be vulnerable to the restriction endonuclease. Our data contradict this prediction; they reveal that functional type I R-M genes in the chromosome are readily replaced by mutant alleles and by alleles encoding a type I R-M system of different specificity. The acquisition of allelic genes conferring a new sequence specificity, but not the loss of the resident genes, is dependent on the product of an unlinked gene, one predicted [Prakash-Cheng, A., Chung, S. S. & Ryu, J. (1993) Mol. Gen. Genet. 241, 491-496] to be relevant to control of expression of the genes that encode EcoKI. Our evidence suggests that not all R-M systems are evolving as "selfish" units; rather, the diversity and distribution of the family of type I enzymes we have investigated require an alternative selective pressure.

Multiple and Periodic Measurement of RBC Aggregation and ESR in Parallel Microfluidic Channels under On-Off Blood Flow Control

Directory of Open Access Journals (Sweden)

Yang Jun Kang

2018-06-01

Full Text Available Red blood cell (RBC aggregation causes to alter hemodynamic behaviors at low flow-rate regions of post-capillary venules. Additionally, it is significantly elevated in inflammatory or pathophysiological conditions. In this study, multiple and periodic measurements of RBC aggregation and erythrocyte sedimentation rate (ESR are suggested by sucking blood from a pipette tip into parallel microfluidic channels, and quantifying image intensity, especially through single experiment. Here, a microfluidic device was prepared from a master mold using the xurography technique rather than micro-electro-mechanical-system fabrication techniques. In order to consider variations of RBC aggregation in microfluidic channels due to continuous ESR in the conical pipette tip, two indices (aggregation index (AI and erythrocyte-sedimentation-rate aggregation index (EAI are evaluated by using temporal variations of microscopic, image-based intensity. The proposed method is employed to evaluate the effect of hematocrit and dextran solution on RBC aggregation under continuous ESR in the conical pipette tip. As a result, EAI displays a significantly linear relationship with modified conventional ESR measurement obtained by quantifying time constants. In addition, EAI varies linearly within a specific concentration of dextran solution. In conclusion, the proposed method is able to measure RBC aggregation under continuous ESR in the conical pipette tip. Furthermore, the method provides multiple data of RBC aggregation and ESR through a single experiment. A future study will involve employing the proposed method to evaluate biophysical properties of blood samples collected from cardiovascular diseases.

An Overview of High-performance Parallel Big Data transfers over multiple network channels with Transport Layer Security (TLS) and TLS plus Perfect Forward Secrecy (PFS)

Energy Technology Data Exchange (ETDEWEB)

Fang, Chin [SLAC National Accelerator Lab., Menlo Park, CA (United States); Corttrell, R. A. [SLAC National Accelerator Lab., Menlo Park, CA (United States)

2015-05-06

This Technical Note provides an overview of high-performance parallel Big Data transfers with and without encryption for data in-transit over multiple network channels. It shows that with the parallel approach, it is feasible to carry out high-performance parallel "encrypted" Big Data transfers without serious impact to throughput. But other impacts, e.g. the energy-consumption part should be investigated. It also explains our rationales of using a statistics-based approach for gaining understanding from test results and for improving the system. The presentation is of high-level nature. Nevertheless, at the end we will pose some questions and identify potentially fruitful directions for future work.

Parallel Application Development Using Architecture View Driven Model Transformations

NARCIS (Netherlands)

Arkin, E.; Tekinerdogan, B.

2015-01-01

o realize the increased need for computing performance the current trend is towards applying parallel computing in which the tasks are run in parallel on multiple nodes. On its turn we can observe the rapid increase of the scale of parallel computing platforms. This situation has led to a complexity

MARBLE: A system for executing expert systems in parallel

Science.gov (United States)

Myers, Leonard; Johnson, Coe; Johnson, Dean

1990-01-01

This paper details the MARBLE 2.0 system which provides a parallel environment for cooperating expert systems. The work has been done in conjunction with the development of an intelligent computer-aided design system, ICADS, by the CAD Research Unit of the Design Institute at California Polytechnic State University. MARBLE (Multiple Accessed Rete Blackboard Linked Experts) is a system of C Language Production Systems (CLIPS) expert system tool. A copied blackboard is used for communication between the shells to establish an architecture which supports cooperating expert systems that execute in parallel. The design of MARBLE is simple, but it provides support for a rich variety of configurations, while making it relatively easy to demonstrate the correctness of its parallel execution features. In its most elementary configuration, individual CLIPS expert systems execute on their own processors and communicate with each other through a modified blackboard. Control of the system as a whole, and specifically of writing to the blackboard is provided by one of the CLIPS expert systems, an expert control system.

Estimated allele substitution effects underlying genomic evaluation models depend on the scaling of allele counts

NARCIS (Netherlands)

Bouwman, Aniek C.; Hayes, Ben J.; Calus, Mario P.L.

2017-01-01

Background: Genomic evaluation is used to predict direct genomic values (DGV) for selection candidates in breeding programs, but also to estimate allele substitution effects (ASE) of single nucleotide polymorphisms (SNPs). Scaling of allele counts influences the estimated ASE, because scaling of

Performance Analysis of a Threshold-Based Parallel Multiple Beam Selection Scheme for WDM FSO Systems

KAUST Repository

Nam, Sung Sik

2018-04-09

In this paper, we statistically analyze the performance of a threshold-based parallel multiple beam selection scheme for a free-space optical (FSO) based system with wavelength division multiplexing (WDM) in cases where a pointing error has occurred under independent identically distributed Gamma-Gamma fading conditions. To simplify the mathematical analysis, we additionally consider Gamma turbulence conditions, which are a good approximation of Gamma-Gamma distribution. Specifically, we statistically analyze the characteristics in operation under conventional detection schemes (i.e., heterodyne detection (HD) and intensity modulation/direct detection (IM/DD) techniques) for both adaptive modulation (AM) case in addition to non-AM case (i.e., coherent/non-coherent binary modulation). Then, based on the statistically derived results, we evaluate the outage probability of a selected beam, the average spectral efficiency (ASE), the average number of selected beams (ANSB) and the average bit error rate (BER). Selected results show that we can obtain higher spectral efficiency and simultaneously reduce the potential for increasing the complexity of implementation caused by applying the selection-based beam selection scheme without considerable performance loss. Especially for the AM case, the ASE can be increased further compared to the non- AM cases. Our derived results based on the Gamma distribution as an approximation of the Gamma-Gamma distribution can be used as approximated performance measure bounds, especially, they may lead to lower bounds on the approximated considered performance measures.

Angiotensin-converting enzyme (ACE) alleles in the Quechua, a high altitude South American native population.

Science.gov (United States)

Rupert, J L; Devine, D V; Monsalve, M V; Hochachka, P W

1999-01-01

Recently it was reported that an allelic variant of the gene encoding angiotensin-converting enzyme (ACE) was significantly over-represented in a cohort of elite British mountaineers. It was proposed that this may be evidence for a specific genetic factor influencing the human capacity for physical performance. The implication that this allele could enhance performance at high altitude prompted us to determine its frequency in Quechua speaking natives living at altitudes greater than 3000m on the Andean Altiplano in South America. We found that the frequency of the putative performance allele in the Quechuas, although significantly higher than in Caucasians, was not different from lowland Native American populations. This observation suggests that, although the higher frequency of the 'performance allele' may have facilitated the migration of the ancestral Quechua to the highlands, the ACE insertion allele has not been subsequently selected for in this high altitude population.

JAK2V617F mutation is associated with special alleles in essential thrombocythemia.

Science.gov (United States)

Hsiao, Hui-Hua; Liu, Yi-Chang; Tsai, Hui-Jen; Lee, Ching-Ping; Hsu, Jui-Feng; Lin, Sheng-Fung

2011-03-01

Janus kinase 2 mutation (JAK2V617F) has been identified in myeloproliferative neoplasms. Furthermore, special single nucleoside polymorphisms (SNPs) have been found to be associated with the JAK2V617F mutation. Therefore, the associations among JAK2V617F and special SNPs and the allelic location between them were investigated in patients with essential thrombocythemia (ET). A total of 61 patients with ET and 106 healthy individuals were enrolled. The PCR-RFLP method was applied to investigate the pattern of three SNPs, rs10974944, rs12343867, and rs12340895. Allele-specific PCR was used to examine the allelic location between rs10974944 and JAK2V617F. Among the patients with ET, 34 (55.7%, 34/61) were JAK2V617F positive (heterozygous) while the other 27 (44.3%, 27/61) were negative, and there were no MPLW515L/K mutations noted. The pattern of special SNPs in JAK2V617F(+) was significantly different from that in normal individuals (p <0.05), while there was no difference between JAK2V617F(-) patients and normal individuals. Allele-specific PCR showed high association of a cis-location between the special G-allele of rs10974944 and JAK2V617F(+). Based on this small numbered study, the results show the association between special SNPs and JAK2V617F mutation and a cis-location between the special G-allelic form of rs10974944 and the JAK2V617F mutation. These data highlight a close relationship between them in patients with ET.

Hierarchical approach to optimization of parallel matrix multiplication on large-scale platforms

KAUST Repository

Hasanov, Khalid; Quintin, Jean-Noë l; Lastovetsky, Alexey

2014-01-01

-scale parallelism in mind. Indeed, while in 1990s a system with few hundred cores was considered a powerful supercomputer, modern top supercomputers have millions of cores. In this paper, we present a hierarchical approach to optimization of message-passing parallel

The acylphosphatase (Acyp) alleles associate with male hybrid sterility in Drosophila.

Science.gov (United States)

Michalak, Pawel; Ma, Daina

2008-06-15

Hybrid defects are believed to result from genetic incompatibilities between genes that have evolved in separate parental lineages. These genetic dysfunctions on the hybrid genomic background, also known as Dobzhansky-Muller incompatibilities, can be an incipient signature of speciation, and as such - a subject of active research. Here we present evidence that Acyp locus (CG16870) that encodes acylphosphatase, a small enzyme that catalyzes the hydrolysis of acylphosphates and participates in ion transport across biological membranes, is involved in genetic incompatibilities leading to male sterility in hybrids between Drosophila simulans and D. mauritiana. There is a strong association between Acyp alleles (genotype) and the sterility/fertility pattern (phenotype), as well as between the phenotype, the genotype and its transcriptional activity. Allele-specific expression in hybrids heterozygous for Acyp suggests a cis-type regulation of this gene, where an allele from one of the parental species (D. simulans) is consistently overexpressed.

The Primordial Soup Algorithm : a systematic approach to the specification of parallel parsers

NARCIS (Netherlands)

Janssen, Wil; Janssen, W.P.M.; Poel, Mannes; Sikkel, Nicolaas; Zwiers, Jakob

1992-01-01

A general framework for parallel parsing is presented, which allows for a unitied, systematic approach to parallel parsing. The Primordial Soup Algorithm creates trees by allowing partial parse trees to combine arbitrarily. By adding constraints to the general algorithm, a large, class of parallel

Fitness differences due to allelic variation at Esterase-4 Locus in ...

Indian Academy of Sciences (India)

Navya

2017-01-04

Jan 4, 2017 ... specific substrate (1-Naphthylacetate AR) and stain (Fast blue RR). On the basis of ... After 24 hr. each pair was transferred to fresh food vials .... derived from the natural populations harbour allelic variation that affects lifespan.

Rubus: A compiler for seamless and extensible parallelism

Science.gov (United States)

Adnan, Muhammad; Aslam, Faisal; Sarwar, Syed Mansoor

2017-01-01

Nowadays, a typical processor may have multiple processing cores on a single chip. Furthermore, a special purpose processing unit called Graphic Processing Unit (GPU), originally designed for 2D/3D games, is now available for general purpose use in computers and mobile devices. However, the traditional programming languages which were designed to work with machines having single core CPUs, cannot utilize the parallelism available on multi-core processors efficiently. Therefore, to exploit the extraordinary processing power of multi-core processors, researchers are working on new tools and techniques to facilitate parallel programming. To this end, languages like CUDA and OpenCL have been introduced, which can be used to write code with parallelism. The main shortcoming of these languages is that programmer needs to specify all the complex details manually in order to parallelize the code across multiple cores. Therefore, the code written in these languages is difficult to understand, debug and maintain. Furthermore, to parallelize legacy code can require rewriting a significant portion of code in CUDA or OpenCL, which can consume significant time and resources. Thus, the amount of parallelism achieved is proportional to the skills of the programmer and the time spent in code optimizations. This paper proposes a new open source compiler, Rubus, to achieve seamless parallelism. The Rubus compiler relieves the programmer from manually specifying the low-level details. It analyses and transforms a sequential program into a parallel program automatically, without any user intervention. This achieves massive speedup and better utilization of the underlying hardware without a programmer’s expertise in parallel programming. For five different benchmarks, on average a speedup of 34.54 times has been achieved by Rubus as compared to Java on a basic GPU having only 96 cores. Whereas, for a matrix multiplication benchmark the average execution speedup of 84 times has been

Rubus: A compiler for seamless and extensible parallelism.

Directory of Open Access Journals (Sweden)

Muhammad Adnan

Full Text Available Nowadays, a typical processor may have multiple processing cores on a single chip. Furthermore, a special purpose processing unit called Graphic Processing Unit (GPU, originally designed for 2D/3D games, is now available for general purpose use in computers and mobile devices. However, the traditional programming languages which were designed to work with machines having single core CPUs, cannot utilize the parallelism available on multi-core processors efficiently. Therefore, to exploit the extraordinary processing power of multi-core processors, researchers are working on new tools and techniques to facilitate parallel programming. To this end, languages like CUDA and OpenCL have been introduced, which can be used to write code with parallelism. The main shortcoming of these languages is that programmer needs to specify all the complex details manually in order to parallelize the code across multiple cores. Therefore, the code written in these languages is difficult to understand, debug and maintain. Furthermore, to parallelize legacy code can require rewriting a significant portion of code in CUDA or OpenCL, which can consume significant time and resources. Thus, the amount of parallelism achieved is proportional to the skills of the programmer and the time spent in code optimizations. This paper proposes a new open source compiler, Rubus, to achieve seamless parallelism. The Rubus compiler relieves the programmer from manually specifying the low-level details. It analyses and transforms a sequential program into a parallel program automatically, without any user intervention. This achieves massive speedup and better utilization of the underlying hardware without a programmer's expertise in parallel programming. For five different benchmarks, on average a speedup of 34.54 times has been achieved by Rubus as compared to Java on a basic GPU having only 96 cores. Whereas, for a matrix multiplication benchmark the average execution speedup of 84

Allelic variation of bile salt hydrolase genes in Lactobacillus salivarius does not determine bile resistance levels.

LENUS (Irish Health Repository)

Fang, Fang

2009-09-01

Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius strains from different sources all harbored a bsh1 allele on their respective megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of two strains that had higher bile resistance levels. Four Bsh1-encoding allele groups were identified, defined by truncations or deletions involving a conserved residue. In vitro analyses showed that this allelic variation was correlated with widely varying bile deconjugation phenotypes. Despite very low activity of the UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile resistance, both in vitro and during intestinal transit in mice. However, the overall bile resistance phenotype of this and other strains was independent of the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure to bile and cholate identified a multiplicity of stress response proteins and putative efflux proteins that appear to broadly compensate for, or mask, the effects of allelic variation of bsh genes. Bsh enzymes with different bile-degrading kinetics, though apparently not the primary determinants of bile resistance in L. salivarius, may have additional biological importance because of varying effects upon bile as a signaling molecule in the host.

Endpoint-based parallel data processing with non-blocking collective instructions in a parallel active messaging interface of a parallel computer

Science.gov (United States)

Archer, Charles J; Blocksome, Michael A; Cernohous, Bob R; Ratterman, Joseph D; Smith, Brian E

2014-11-11

Endpoint-based parallel data processing with non-blocking collective instructions in a PAMI of a parallel computer is disclosed. The PAMI is composed of data communications endpoints, each including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task. The compute nodes are coupled for data communications through the PAMI. The parallel application establishes a data communications geometry specifying a set of endpoints that are used in collective operations of the PAMI by associating with the geometry a list of collective algorithms valid for use with the endpoints of the geometry; registering in each endpoint in the geometry a dispatch callback function for a collective operation; and executing without blocking, through a single one of the endpoints in the geometry, an instruction for the collective operation.

A Laboratory Preparation of Aspartame Analogs Using Simultaneous Multiple Parallel Synthesis Methodology

Science.gov (United States)

Qvit, Nir; Barda, Yaniv; Gilon, Chaim; Shalev, Deborah E.

2007-01-01

This laboratory experiment provides a unique opportunity for students to synthesize three analogues of aspartame, a commonly used artificial sweetener. The students are introduced to the powerful and useful method of parallel synthesis while synthesizing three dipeptides in parallel using solid-phase peptide synthesis (SPPS) and simultaneous…

A matching-allele model explains host resistance to parasites.

Science.gov (United States)

Luijckx, Pepijn; Fienberg, Harris; Duneau, David; Ebert, Dieter

2013-06-17

The maintenance of genetic variation and sex despite its costs has long puzzled biologists. A popular idea, the Red Queen Theory, is that under rapid antagonistic coevolution between hosts and their parasites, the formation of new rare host genotypes through sex can be advantageous as it creates host genotypes to which the prevailing parasite is not adapted. For host-parasite coevolution to lead to an ongoing advantage for rare genotypes, parasites should infect specific host genotypes and hosts should resist specific parasite genotypes. The most prominent genetics capturing such specificity are matching-allele models (MAMs), which have the key feature that resistance for two parasite genotypes can reverse by switching one allele at one host locus. Despite the lack of empirical support, MAMs have played a central role in the theoretical development of antagonistic coevolution, local adaptation, speciation, and sexual selection. Using genetic crosses, we show that resistance of the crustacean Daphnia magna against the parasitic bacterium Pasteuria ramosa follows a MAM. Simulation results show that the observed genetics can explain the maintenance of genetic variation and contribute to the maintenance of sex in the facultatively sexual host as predicted by the Red Queen Theory. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sensory-specific satiety is intact in amnesics who eat multiple meals.

Science.gov (United States)

Higgs, Suzanne; Williamson, Amy C; Rotshtein, Pia; Humphreys, Glyn W

2008-07-01

What is the relationship between memory and appetite? We explored this question by examining preferences for recently consumed food in patients with amnesia. Although the patients were unable to remember having eaten, and were inclined to eat multiple meals, we found that sensory-specific satiety was intact in these patients. The data suggest that sensory-specific satiety can occur in the absence of explicit memory for having eaten and that impaired sensory-specific satiety does not underlie the phenomenon of multiple-meal eating in amnesia. Overeating in amnesia may be due to disruption of learned control by physiological aftereffects of a recent meal or to problems utilizing internal cues relating to nutritional state.

Killer Immunoglobulin-Like Receptor Allele Determination Using Next-Generation Sequencing Technology

Directory of Open Access Journals (Sweden)

Bercelin Maniangou

2017-05-01

Full Text Available The impact of natural killer (NK cell alloreactivity on hematopoietic stem cell transplantation (HSCT outcome is still debated due to the complexity of graft parameters, HLA class I environment, the nature of killer cell immunoglobulin-like receptor (KIR/KIR ligand genetic combinations studied, and KIR+ NK cell repertoire size. KIR genes are known to be polymorphic in terms of gene content, copy number variation, and number of alleles. These allelic polymorphisms may impact both the phenotype and function of KIR+ NK cells. We, therefore, speculate that polymorphisms may alter donor KIR+ NK cell phenotype/function thus modulating post-HSCT KIR+ NK cell alloreactivity. To investigate KIR allele polymorphisms of all KIR genes, we developed a next-generation sequencing (NGS technology on a MiSeq platform. To ensure the reliability and specificity of our method, genomic DNA from well-characterized cell lines were used; high-resolution KIR typing results obtained were then compared to those previously reported. Two different bioinformatic pipelines were used allowing the attribution of sequencing reads to specific KIR genes and the assignment of KIR alleles for each KIR gene. Our results demonstrated successful long-range KIR gene amplifications of all reference samples using intergenic KIR primers. The alignment of reads to the human genome reference (hg19 using BiRD pipeline or visualization of data using Profiler software demonstrated that all KIR genes were completely sequenced with a sufficient read depth (mean 317× for all loci and a high percentage of mapping (mean 93% for all loci. Comparison of high-resolution KIR typing obtained to those published data using exome capture resulted in a reported concordance rate of 95% for centromeric and telomeric KIR genes. Overall, our results suggest that NGS can be used to investigate the broad KIR allelic polymorphism. Hence, these data improve our knowledge, not only on KIR+ NK cell alloreactivity in

A modified parallel constitutive model for elevated temperature flow behavior of Ti-6Al-4V alloy based on multiple regression

Energy Technology Data Exchange (ETDEWEB)

Cai, Jun; Shi, Jiamin; Wang, Kuaishe; Wang, Wen; Wang, Qingjuan; Liu, Yingying [Xi' an Univ. of Architecture and Technology, Xi' an (China). School of Metallurgical Engineering; Li, Fuguo [Northwestern Polytechnical Univ., Xi' an (China). School of Materials Science and Engineering

2017-07-15

Constitutive analysis for hot working of Ti-6Al-4V alloy was carried out by using experimental stress-strain data from isothermal hot compression tests. A new kind of constitutive equation called a modified parallel constitutive model was proposed by considering the independent effects of strain, strain rate and temperature. The predicted flow stress data were compared with the experimental data. Statistical analysis was introduced to verify the validity of the developed constitutive equation. Subsequently, the accuracy of the proposed constitutive equations was evaluated by comparing with other constitutive models. The results showed that the developed modified parallel constitutive model based on multiple regression could predict flow stress of Ti-6Al-4V alloy with good correlation and generalization.

Parallel computing solution of Boltzmann neutron transport equation

International Nuclear Information System (INIS)

Ansah-Narh, T.

2010-01-01

The focus of the research was on developing parallel computing algorithm for solving Eigen-values of the Boltzmam Neutron Transport Equation (BNTE) in a slab geometry using multi-grid approach. In response to the problem of slow execution of serial computing when solving large problems, such as BNTE, the study was focused on the design of parallel computing systems which was an evolution of serial computing that used multiple processing elements simultaneously to solve complex physical and mathematical problems. Finite element method (FEM) was used for the spatial discretization scheme, while angular discretization was accomplished by expanding the angular dependence in terms of Legendre polynomials. The eigenvalues representing the multiplication factors in the BNTE were determined by the power method. MATLAB Compiler Version 4.1 (R2009a) was used to compile the MATLAB codes of BNTE. The implemented parallel algorithms were enabled with matlabpool, a Parallel Computing Toolbox function. The option UseParallel was set to 'always' and the default value of the option was 'never'. When those conditions held, the solvers computed estimated gradients in parallel. The parallel computing system was used to handle all the bottlenecks in the matrix generated from the finite element scheme and each domain of the power method generated. The parallel algorithm was implemented on a Symmetric Multi Processor (SMP) cluster machine, which had Intel 32 bit quad-core x 86 processors. Convergence rates and timings for the algorithm on the SMP cluster machine were obtained. Numerical experiments indicated the designed parallel algorithm could reach perfect speedup and had good stability and scalability. (au)

Identification, genealogical structure and population genetics of S-alleles in Malus sieversii, the wild ancestor of domesticated apple.

Science.gov (United States)

Ma, X; Cai, Z; Liu, W; Ge, S; Tang, L

2017-09-01

The self-incompatibility (SI) gene that is specifically expressed in pistils encodes the SI-associated ribonuclease (S-RNase), functioning as the female-specificity determinant of a gametophytic SI system. Despite extensive surveys in Malus domestica, the S-alleles have not been fully investigated for Malus sieversii, the primary wild ancestor of the domesticated apple. Here we screened the M. sieversii S-alleles via PCR amplification and sequencing, and identified 14 distinct alleles in this species. By contrast, nearly 40 are present in its close wild relative, Malus sylvestris. We further sequenced 8 nuclear genes to provide a neutral reference, and investigated the evolution of S-alleles via genealogical and population genetic analyses. Both shared ancestral polymorphism and an excess of non-synonymous substitution were detected in the S-RNases of the tribe Maleae in Rosaceae, indicating the action of long-term balancing selection. Approximate Bayesian Computations based on the reference neutral loci revealed a severe bottleneck in four of the six studied M. sieversii populations, suggesting that the low number of S-alleles found in this species is mainly the result of diversity loss due to a drastic population contraction. Such a bottleneck may lead to ambiguous footprints of ongoing balancing selection detected at the S-locus. This study not only elucidates the constituents and number of S-alleles in M. sieversii but also illustrates the potential utility of S-allele number shifts in demographic inference for self-incompatible plant species.

Massive parallelization of a 3D finite difference electromagnetic forward solution using domain decomposition methods on multiple CUDA enabled GPUs

Science.gov (United States)

Schultz, A.

2010-12-01

3D forward solvers lie at the core of inverse formulations used to image the variation of electrical conductivity within the Earth's interior. This property is associated with variations in temperature, composition, phase, presence of volatiles, and in specific settings, the presence of groundwater, geothermal resources, oil/gas or minerals. The high cost of 3D solutions has been a stumbling block to wider adoption of 3D methods. Parallel algorithms for modeling frequency domain 3D EM problems have not achieved wide scale adoption, with emphasis on fairly coarse grained parallelism using MPI and similar approaches. The communications bandwidth as well as the latency required to send and receive network communication packets is a limiting factor in implementing fine grained parallel strategies, inhibiting wide adoption of these algorithms. Leading Graphics Processor Unit (GPU) companies now produce GPUs with hundreds of GPU processor cores per die. The footprint, in silicon, of the GPU's restricted instruction set is much smaller than the general purpose instruction set required of a CPU. Consequently, the density of processor cores on a GPU can be much greater than on a CPU. GPUs also have local memory, registers and high speed communication with host CPUs, usually through PCIe type interconnects. The extremely low cost and high computational power of GPUs provides the EM geophysics community with an opportunity to achieve fine grained (i.e. massive) parallelization of codes on low cost hardware. The current generation of GPUs (e.g. NVidia Fermi) provides 3 billion transistors per chip die, with nearly 500 processor cores and up to 6 GB of fast (DDR5) GPU memory. This latest generation of GPU supports fast hardware double precision (64 bit) floating point operations of the type required for frequency domain EM forward solutions. Each Fermi GPU board can sustain nearly 1 TFLOP in double precision, and multiple boards can be installed in the host computer system. We

A Fast Multiple Sampling Method for Low-Noise CMOS Image Sensors With Column-Parallel 12-bit SAR ADCs

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Min-Kyu Kim

2015-12-01

Full Text Available This paper presents a fast multiple sampling method for low-noise CMOS image sensor (CIS applications with column-parallel successive approximation register analog-to-digital converters (SAR ADCs. The 12-bit SAR ADC using the proposed multiple sampling method decreases the A/D conversion time by repeatedly converting a pixel output to 4-bit after the first 12-bit A/D conversion, reducing noise of the CIS by one over the square root of the number of samplings. The area of the 12-bit SAR ADC is reduced by using a 10-bit capacitor digital-to-analog converter (DAC with four scaled reference voltages. In addition, a simple up/down counter-based digital processing logic is proposed to perform complex calculations for multiple sampling and digital correlated double sampling. To verify the proposed multiple sampling method, a 256 × 128 pixel array CIS with 12-bit SAR ADCs was fabricated using 0.18 μm CMOS process. The measurement results shows that the proposed multiple sampling method reduces each A/D conversion time from 1.2 μs to 0.45 μs and random noise from 848.3 μV to 270.4 μV, achieving a dynamic range of 68.1 dB and an SNR of 39.2 dB.

Is Monte Carlo embarrassingly parallel?

Energy Technology Data Exchange (ETDEWEB)

Hoogenboom, J. E. [Delft Univ. of Technology, Mekelweg 15, 2629 JB Delft (Netherlands); Delft Nuclear Consultancy, IJsselzoom 2, 2902 LB Capelle aan den IJssel (Netherlands)

2012-07-01

Monte Carlo is often stated as being embarrassingly parallel. However, running a Monte Carlo calculation, especially a reactor criticality calculation, in parallel using tens of processors shows a serious limitation in speedup and the execution time may even increase beyond a certain number of processors. In this paper the main causes of the loss of efficiency when using many processors are analyzed using a simple Monte Carlo program for criticality. The basic mechanism for parallel execution is MPI. One of the bottlenecks turn out to be the rendez-vous points in the parallel calculation used for synchronization and exchange of data between processors. This happens at least at the end of each cycle for fission source generation in order to collect the full fission source distribution for the next cycle and to estimate the effective multiplication factor, which is not only part of the requested results, but also input to the next cycle for population control. Basic improvements to overcome this limitation are suggested and tested. Also other time losses in the parallel calculation are identified. Moreover, the threading mechanism, which allows the parallel execution of tasks based on shared memory using OpenMP, is analyzed in detail. Recommendations are given to get the maximum efficiency out of a parallel Monte Carlo calculation. (authors)

Is Monte Carlo embarrassingly parallel?

International Nuclear Information System (INIS)

Hoogenboom, J. E.

2012-01-01

Monte Carlo is often stated as being embarrassingly parallel. However, running a Monte Carlo calculation, especially a reactor criticality calculation, in parallel using tens of processors shows a serious limitation in speedup and the execution time may even increase beyond a certain number of processors. In this paper the main causes of the loss of efficiency when using many processors are analyzed using a simple Monte Carlo program for criticality. The basic mechanism for parallel execution is MPI. One of the bottlenecks turn out to be the rendez-vous points in the parallel calculation used for synchronization and exchange of data between processors. This happens at least at the end of each cycle for fission source generation in order to collect the full fission source distribution for the next cycle and to estimate the effective multiplication factor, which is not only part of the requested results, but also input to the next cycle for population control. Basic improvements to overcome this limitation are suggested and tested. Also other time losses in the parallel calculation are identified. Moreover, the threading mechanism, which allows the parallel execution of tasks based on shared memory using OpenMP, is analyzed in detail. Recommendations are given to get the maximum efficiency out of a parallel Monte Carlo calculation. (authors)

System-wide versus component-specific trust using multiple aids.

Science.gov (United States)

Keller, David; Rice, Stephen

2010-01-01

Previous research in operator trust toward automated aids has focused primarily on single aids. The current study focuses on how operator trust is affected by the presence of multiple aids. Two competing theories of multiple-trust are presented. A component-specific trust theory predicts that operators will differentially place their trust in automated aids that vary in reliability. A system-wide trust theory predicts that operators will treat multiple imperfect aids as one "system" and merge their trust across aids despite differences in the aids' reliability. A simulated flight task was used to test these theories, whereby operators performed a pursuit tracking task while concurrently monitoring multiple system gauges that were augmented with perfect or imperfect automated aids. The data revealed that a system-wide trust theory best predicted the data; operators merged their trust across both aids, behaving toward a perfectly reliable aid in the same manner as they did towards unreliable aids.

Sequence analysis of two alleles reveals that intra-and intergenic recombination played a role in the evolution of the radish fertility restorer (Rfo

Directory of Open Access Journals (Sweden)

Budar Françoise

2010-02-01

Full Text Available Abstract Background Land plant genomes contain multiple members of a eukaryote-specific gene family encoding proteins with pentatricopeptide repeat (PPR motifs. Some PPR proteins were shown to participate in post-transcriptional events involved in organellar gene expression, and this type of function is now thought to be their main biological role. Among PPR genes, restorers of fertility (Rf of cytoplasmic male sterility systems constitute a peculiar subgroup that is thought to evolve in response to the presence of mitochondrial sterility-inducing genes. Rf genes encoding PPR proteins are associated with very close relatives on complex loci. Results We sequenced a non-restoring allele (L7rfo of the Rfo radish locus whose restoring allele (D81Rfo was previously described, and compared the two alleles and their PPR genes. We identified a ca 13 kb long fragment, likely originating from another part of the radish genome, inserted into the L7rfo sequence. The L7rfo allele carries two genes (PPR-1 and PPR-2 closely related to the three previously described PPR genes of the restorer D81Rfo allele (PPR-A, PPR-B, and PPR-C. Our results indicate that alleles of the Rfo locus have experienced complex evolutionary events, including recombination and insertion of extra-locus sequences, since they diverged. Our analyses strongly suggest that present coding sequences of Rfo PPR genes result from intragenic recombination. We found that the 10 C-terminal PPR repeats in Rfo PPR gene encoded proteins result from the tandem duplication of a 5 PPR repeat block. Conclusions The Rfo locus appears to experience more complex evolution than its flanking sequences. The Rfo locus and PPR genes therein are likely to evolve as a result of intergenic and intragenic recombination. It is therefore not possible to determine which genes on the two alleles are direct orthologs. Our observations recall some previously reported data on pathogen resistance complex loci.

Quantification of massively parallel sequencing libraries - a comparative study of eight methods

DEFF Research Database (Denmark)

Hussing, Christian; Kampmann, Marie-Louise; Mogensen, Helle Smidt

2018-01-01

Quantification of massively parallel sequencing libraries is important for acquisition of monoclonal beads or clusters prior to clonal amplification and to avoid large variations in library coverage when multiple samples are included in one sequencing analysis. No gold standard for quantification...... estimates followed by Qubit and electrophoresis-based instruments (Bioanalyzer, TapeStation, GX Touch, and Fragment Analyzer), while SYBR Green and TaqMan based qPCR assays gave the lowest estimates. qPCR gave more accurate predictions of sequencing coverage than Qubit and TapeStation did. Costs, time......-consumption, workflow simplicity, and ability to quantify multiple samples are discussed. Technical specifications, advantages, and disadvantages of the various methods are pointed out....

Evidence for parallel consolidation of motion direction and orientation into visual short-term memory.

Science.gov (United States)

Rideaux, Reuben; Apthorp, Deborah; Edwards, Mark

2015-02-12

Recent findings have indicated the capacity to consolidate multiple items into visual short-term memory in parallel varies as a function of the type of information. That is, while color can be consolidated in parallel, evidence suggests that orientation cannot. Here we investigated the capacity to consolidate multiple motion directions in parallel and reexamined this capacity using orientation. This was achieved by determining the shortest exposure duration necessary to consolidate a single item, then examining whether two items, presented simultaneously, could be consolidated in that time. The results show that parallel consolidation of direction and orientation information is possible, and that parallel consolidation of direction appears to be limited to two. Additionally, we demonstrate the importance of adequate separation between feature intervals used to define items when attempting to consolidate in parallel, suggesting that when multiple items are consolidated in parallel, as opposed to serially, the resolution of representations suffer. Finally, we used facilitation of spatial attention to show that the deterioration of item resolution occurs during parallel consolidation, as opposed to storage. © 2015 ARVO.

Collectively loading programs in a multiple program multiple data environment

Science.gov (United States)

Aho, Michael E.; Attinella, John E.; Gooding, Thomas M.; Gooding, Thomas M.; Miller, Samuel J.

2016-11-08

Techniques are disclosed for loading programs efficiently in a parallel computing system. In one embodiment, nodes of the parallel computing system receive a load description file which indicates, for each program of a multiple program multiple data (MPMD) job, nodes which are to load the program. The nodes determine, using collective operations, a total number of programs to load and a number of programs to load in parallel. The nodes further generate a class route for each program to be loaded in parallel, where the class route generated for a particular program includes only those nodes on which the program needs to be loaded. For each class route, a node is selected using a collective operation to be a load leader which accesses a file system to load the program associated with a class route and broadcasts the program via the class route to other nodes which require the program.

Allelic Variation of Bile Salt Hydrolase Genes in Lactobacillus salivarius Does Not Determine Bile Resistance Levels▿ †

Science.gov (United States)

Fang, Fang; Li, Yin; Bumann, Mario; Raftis, Emma J.; Casey, Pat G.; Cooney, Jakki C.; Walsh, Martin A.; O'Toole, Paul W.

2009-01-01

Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius strains from different sources all harbored a bsh1 allele on their respective megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of two strains that had higher bile resistance levels. Four Bsh1-encoding allele groups were identified, defined by truncations or deletions involving a conserved residue. In vitro analyses showed that this allelic variation was correlated with widely varying bile deconjugation phenotypes. Despite very low activity of the UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile resistance, both in vitro and during intestinal transit in mice. However, the overall bile resistance phenotype of this and other strains was independent of the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure to bile and cholate identified a multiplicity of stress response proteins and putative efflux proteins that appear to broadly compensate for, or mask, the effects of allelic variation of bsh genes. Bsh enzymes with different bile-degrading kinetics, though apparently not the primary determinants of bile resistance in L. salivarius, may have additional biological importance because of varying effects upon bile as a signaling molecule in the host. PMID:19592587

Contributions of vitamin D response elements and HLA promoters to multiple sclerosis risk.

Science.gov (United States)

Nolan, David; Castley, Alison; Tschochner, Monika; James, Ian; Qiu, Wei; Sayer, David; Christiansen, Frank T; Witt, Campbell; Mastaglia, Frank; Carroll, William; Kermode, Allan

2012-08-07

The identification of a vitamin D-responsive (VDRE) motif within the HLA-DRB1*15:01 promoter region provides an attractive explanation for the combined effects of HLA-DR inheritance and vitamin D exposure on multiple sclerosis (MS) risk. We therefore sought to incorporate HLA-DRB1 promoter variation, including the VDRE motif, in an assessment of HLA-DRB1-associated MS risk. We utilized 32 homozygous HLA cell lines (covering 17 DRB1 alleles) and 53 heterozygote MS samples (20 DRB1 alleles) for HLA-DRB1 promoter sequencing. The influence of HLA-DRB1 variation on MS risk was then assessed among 466 MS cases and 498 controls. The majority of HLA*DRB1 alleles (including HLA-DRB1*15:01) express the functional VDRE motif, apart from HLA-DRB1*04, *07, and *09 alleles that comprise the HLA-DR53 serologic group. Allele-specific variation within functional X-box and Y-box motifs was also associated with serologically defined HLA-DR haplotypes. Incorporating these results in an analysis of MS risk, we identified a strong protective effect of HLA-DRB1*04, *07, and *09 (DR53) alleles (p = 10(-12)) and elevated risk associated with DRB1*15 and *16 (DR51) and *08 (DR8) alleles (p < 10(-18)). HLA-DRB1 groups corresponding to serologic HLA-DR profiles as well as promoter polymorphism haplotypes effectively stratified MS risk over an 11-fold range, suggesting functional relationships between risk-modifying HLA-DRB1 alleles. An independent contribution of VDRE motif variation to increase MS risk was not discernible, although vitamin D-dependent regulation of HLA-DR expression may still play an important role given that HLA-DRB1*04/*07/*09 (DR53) alleles that express the "nonresponsive" VDRE motif were associated with significantly reduced risk of MS.

Human minisatellite alleles detectable only after PCR amplification.

Science.gov (United States)

Armour, J A; Crosier, M; Jeffreys, A J

1992-01-01

We present evidence that a proportion of alleles at two human minisatellite loci is undetected by standard Southern blot hybridization. In each case the missing allele(s) can be identified after PCR amplification and correspond to tandem arrays too short to detect by hybridization. At one locus, there is only one undetected allele (population frequency 0.3), which contains just three repeat units. At the second locus, there are at least five undetected alleles (total population frequency 0.9) containing 60-120 repeats; they are not detected because these tandem repeats give very poor signals when used as a probe in standard Southern blot hybridization, and also cross-hybridize with other sequences in the genome. Under these circumstances only signals from the longest tandemly repeated alleles are detectable above the nonspecific background. The structures of these loci have been compared in human and primate DNA, and at one locus the short human allele containing three repeat units is shown to be an intermediate state in the expansion of a monomeric precursor allele in primates to high copy number in the longer human arrays. We discuss the implications of such loci for studies of human populations, minisatellite isolation by cloning, and the evolution of highly variable tandem arrays.

[Cloning and sequencing of KIR2DL1 framework gene cDNA and identification of a novel allele].

Science.gov (United States)

Sun, Ge; Wang, Chang; Zhen, Jianxin; Zhang, Guobin; Xu, Yunping; Deng, Zhihui

2016-10-01

To develop an assay for cDNA cloning and haplotype sequencing of KIR2DL1 framework gene and determine the genotype of an ethnic Han from southern China. Total RNA was isolated from peripheral blood sample, and complementary DNA (cDNA) transcript was synthesized by RT-PCR. The entire coding sequence of the KIR2DL1 framework gene was amplified with a pair of KIR2DL1-specific PCR primers. The PCR products with a length of approximately 1.2 kb were then subjected to cloning and haplotype sequencing. A specific target fragment of the KIR2DL1 framework gene was obtained. Following allele separation, a wild-type KIR2DL1*00302 allele and a novel variant allele, KIR2DL1*031, were identified. Sequence alignment with KIR2DL1 alleles from the IPD-KIR Database showed that the novel allele KIR2DL1*031 has differed from the closest allele KIR2DL1*00302 by a non-synonymous mutation at CDS nt 188A>G (codon 42 GAG>GGG) in exon 4, which has caused an amino acid change Glu42Gly. The sequence of the novel allele KIR2DL1*031 was submitted to GenBank under the accession number KP025960 and to the IPD-KIR Database under the submission number IWS40001982. A name KIR2DL1*031 has been officially assigned by the World Health Organization (WHO) Nomenclature Committee. An assay for cDNA cloning and haplotype sequencing of KIR2DL1 has been established, which has a broad applications in KIR studies at allelic level.

Clinical Control of HIV-1 by Cytotoxic T Cells Specific for Multiple Conserved Epitopes.

Science.gov (United States)

Murakoshi, Hayato; Akahoshi, Tomohiro; Koyanagi, Madoka; Chikata, Takayuki; Naruto, Takuya; Maruyama, Rie; Tamura, Yoshiko; Ishizuka, Naoki; Gatanaga, Hiroyuki; Oka, Shinichi; Takiguchi, Masafumi

2015-05-01

Identification and characterization of CD8(+) T cells effectively controlling HIV-1 variants are necessary for the development of AIDS vaccines and for studies of AIDS pathogenesis, although such CD8(+) T cells have been only partially identified. In this study, we sought to identify CD8(+) T cells controlling HIV-1 variants in 401 Japanese individuals chronically infected with HIV-1 subtype B, in which protective alleles HLA-B*57 and HLA-B*27 are very rare, by using comprehensive and exhaustive methods. We identified 13 epitope-specific CD8(+) T cells controlling HIV-1 in Japanese individuals, though 9 of these epitopes were not previously reported. The breadths of the T cell responses to the 13 epitopes were inversely associated with plasma viral load (P = 2.2 × 10(-11)) and positively associated with CD4 count (P = 1.2 × 10(-11)), indicating strong synergistic effects of these T cells on HIV-1 control in vivo. Nine of these epitopes were conserved among HIV-1 subtype B-infected individuals, whereas three out of four nonconserved epitopes were cross-recognized by the specific T cells. These findings indicate that these 12 epitopes are strong candidates for antigens for an AIDS vaccine. The present study highlighted a strategy to identify CD8(+) T cells controlling HIV-1 and demonstrated effective control of HIV-1 by those specific for 12 conserved or cross-reactive epitopes. HLA-B*27-restricted and HLA-B*57-restricted cytotoxic T lymphocytes (CTLs) play a key role in controlling HIV-1 in Caucasians and Africans, whereas it is unclear which CTLs control HIV-1 in Asian countries, where HLA-B*57 and HLA-B*27 are very rare. A recent study showed that HLA-B*67:01 and HLA-B*52:01-C*12:02 haplotypes were protective alleles in Japanese individuals, but it is unknown whether CTLs restricted by these alleles control HIV-1. In this study, we identified 13 CTLs controlling HIV-1 in Japan by using comprehensive and exhaustive methods. They included 5 HLA-B*52:01-restricted

Parallelization in Modern C++

CERN Multimedia

CERN. Geneva

2016-01-01

The traditionally used and well established parallel programming models OpenMP and MPI are both targeting lower level parallelism and are meant to be as language agnostic as possible. For a long time, those models were the only widely available portable options for developing parallel C++ applications beyond using plain threads. This has strongly limited the optimization capabilities of compilers, has inhibited extensibility and genericity, and has restricted the use of those models together with other, modern higher level abstractions introduced by the C++11 and C++14 standards. The recent revival of interest in the industry and wider community for the C++ language has also spurred a remarkable amount of standardization proposals and technical specifications being developed. Those efforts however have so far failed to build a vision on how to seamlessly integrate various types of parallelism, such as iterative parallel execution, task-based parallelism, asynchronous many-task execution flows, continuation s...

Reduced dose uncertainty in MRI-based polymer gel dosimetry using parallel RF transmission with multiple RF sources

International Nuclear Information System (INIS)

Sang-Young Kim; Jung-Hoon Lee; Jin-Young Jung; Do-Wan Lee; Seu-Ran Lee; Bo-Young Choe; Hyeon-Man Baek; Korea University of Science and Technology, Daejeon; Dae-Hyun Kim; Jung-Whan Min; Ji-Yeon Park

2014-01-01

In this work, we present the feasibility of using a parallel RF transmit with multiple RF sources imaging method (MultiTransmit imaging) in polymer gel dosimetry. Image quality and B 1 field homogeneity was statistically better in the MultiTransmit imaging method than in conventional single source RF transmission imaging method. In particular, the standard uncertainty of R 2 was lower on the MultiTransmit images than on the conventional images. Furthermore, the MultiTransmit measurement showed improved dose resolution. Improved image quality and B 1 homogeneity results in reduced dose uncertainty, thereby suggesting the feasibility of MultiTransmit MR imaging in gel dosimetry. (author)

Rin4 causes hybrid necrosis and race-specific resistance in an interspecific lettuce hybrid.

Science.gov (United States)

Jeuken, Marieke J W; Zhang, Ningwen W; McHale, Leah K; Pelgrom, Koen; den Boer, Erik; Lindhout, Pim; Michelmore, Richard W; Visser, Richard G F; Niks, Rients E

2009-10-01

Some inter- and intraspecific crosses may result in reduced viability or sterility in the offspring, often due to genetic incompatibilities resulting from interactions between two or more loci. Hybrid necrosis is a postzygotic genetic incompatibility that is phenotypically manifested as necrotic lesions on the plant. We observed hybrid necrosis in interspecific lettuce (Lactuca sativa and Lactuca saligna) hybrids that correlated with resistance to downy mildew. Segregation analysis revealed a specific allelic combination at two interacting loci to be responsible. The allelic interaction had two consequences: (1) a quantitative temperature-dependent autoimmunity reaction leading to necrotic lesions, lethality, and quantitative resistance to an otherwise virulent race of Bremia lactucae; and (2) a qualitative temperature-independent race-specific resistance to an avirulent race of B. lactucae. We demonstrated by transient expression and silencing experiments that one of the two interacting genes was Rin4. In Arabidopsis thaliana, RIN4 is known to interact with multiple R gene products, and their interactions result in hypersensitive resistance to Pseudomonas syringae. Site-directed mutation studies on the necrosis-eliciting allele of Rin4 in lettuce showed that three residues were critical for hybrid necrosis.

A strategy to discover genes that carry multi-allelic or mono-allelic risk for common diseases: A cohort allelic sums test (CAST)

International Nuclear Information System (INIS)

Morgenthaler, Stephan; Thilly, William G.

2007-01-01

A method is described to discover if a gene carries one or more allelic mutations that confer risk for any specified common disease. The method does not depend upon genetic linkage of risk-conferring mutations to high frequency genetic markers such as single nucleotide polymorphisms. Instead, the sums of allelic mutation frequencies in case and control cohorts are determined and a statistical test is applied to discover if the difference in these sums is greater than would be expected by chance. A statistical model is presented that defines the ability of such tests to detect significant gene-disease relationships as a function of case and control cohort sizes and key confounding variables: zygosity and genicity, environmental risk factors, errors in diagnosis, limits to mutant detection, linkage of neutral and risk-conferring mutations, ethnic diversity in the general population and the expectation that among all exonic mutants in the human genome greater than 90% will be neutral with regard to any effect on disease risk. Means to test the null hypothesis for, and determine the statistical power of, each test are provided. For this 'cohort allelic sums test' or 'CAST', the statistical model and test are provided as an Excel (TM) program, CASTAT (C) at http://epidemiology.mit.edu. Based on genetics, technology and statistics, a strategy of enumerating the mutant alleles carried in the exons and splice sites of the estimated ∼25,000 human genes in case cohort samples of 10,000 persons for each of 100 common diseases is proposed and evaluated: A wide range of possible conditions of multi-allelic or mono-allelic and monogenic, multigenic or polygenic (including epistatic) risk are found to be detectable using the statistical criteria of 1 or 10 ''false positive'' gene associations per 25,000 gene-disease pair-wise trials and a statistical power of >0.8. Using estimates of the distribution of both neutral and gene-inactivating nondeleterious mutations in humans and

Allelic genealogies in sporophytic self-incompatibility systems in plants

DEFF Research Database (Denmark)

Schierup, Mikkel Heide; Vekemans, Xavier; Christiansen, Freddy Bugge

1998-01-01

, alleles act codominantly in both pollen and style, in the SSIdom model, alleles form a dominance hierarchy, and in SSIdomcod, alleles are codominant in the style and show a dominance hierarchy in the pollen. Coalescence times of alleles rarely differ more than threefold from those under gametophytic self...

Association of primary biliary cirrhosis with the allele HLA-DPB1*0301 in a German population.

Science.gov (United States)

Mella, J G; Roschmann, E; Maier, K P; Volk, B A

1995-02-01

The major histocompatibility complex class II alleles at the HLA-DPB1 locus were investigated in 32 German Caucasoid patients with primary biliary cirrhosis (PBC) and compared with those from 47 normal control patients using molecular genotyping techniques. The second exon of the HLA-DPB1 gene was amplified by polymerase chain reaction (PCR) and hybridized with 25 sequence-specific oligonucleotides (SSOs) to assign the HLA-DPB1 alleles on the basis of known sequence variations, according to the protocols of the Eleventh International Histocompatibility Workshop. A strong association of PBC was found with the allele HLA-DPB1*0301. The allele HLA DPB1*0301 was present in 50% (16 of 32) of the patients with PBC compared with 13% (6 of 47) of normal controls (P corrected < .015), whereas the other HLA-DPB1 alleles showed no significant differences in both groups. The relative risk (RR) estimate for the allele HLA-DPB1*0301 was 6.8 (95% confidence limits: 2.27 to 20.57). In summary, this study clearly demonstrates an association of PBC with the HLA-DPB1*0301 allele in German Caucasoids and may add new data to the immunogenetic background of PBC, suggesting a contribution of the HLA-DPB1 gene to the genetic susceptibility of the disease.

Tuning HDF5 subfiling performance on parallel file systems

Energy Technology Data Exchange (ETDEWEB)

Byna, Suren [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Chaarawi, Mohamad [Intel Corp. (United States); Koziol, Quincey [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mainzer, John [The HDF Group (United States); Willmore, Frank [The HDF Group (United States)

2017-05-12

Subfiling is a technique used on parallel file systems to reduce locking and contention issues when multiple compute nodes interact with the same storage target node. Subfiling provides a compromise between the single shared file approach that instigates the lock contention problems on parallel file systems and having one file per process, which results in generating a massive and unmanageable number of files. In this paper, we evaluate and tune the performance of recently implemented subfiling feature in HDF5. In specific, we explain the implementation strategy of subfiling feature in HDF5, provide examples of using the feature, and evaluate and tune parallel I/O performance of this feature with parallel file systems of the Cray XC40 system at NERSC (Cori) that include a burst buffer storage and a Lustre disk-based storage. We also evaluate I/O performance on the Cray XC30 system, Edison, at NERSC. Our results show performance benefits of 1.2X to 6X performance advantage with subfiling compared to writing a single shared HDF5 file. We present our exploration of configurations, such as the number of subfiles and the number of Lustre storage targets to storing files, as optimization parameters to obtain superior I/O performance. Based on this exploration, we discuss recommendations for achieving good I/O performance as well as limitations with using the subfiling feature.

Recombinational micro-evolution of functionally different metallothionein promoter alleles from Orchesella cincta

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van Straalen Nico M

2007-06-01

Full Text Available Abstract Background Metallothionein (mt transcription is elevated in heavy metal tolerant field populations of Orchesella cincta (Collembola. This suggests that natural selection acts on transcriptional regulation of mt in springtails at sites where cadmium (Cd levels in soil reach toxic values This study investigates the nature and the evolutionary origin of polymorphisms in the metallothionein promoter (pmt and their functional significance for mt expression. Results We sequenced approximately 1600 bp upstream the mt coding region by genome walking. Nine pmt alleles were discovered in NW-European populations. They differ in the number of some indels, consensus transcription factor binding sites and core promoter elements. Extensive recombination events between some of the alleles can be inferred from the alignment. A deviation from neutral expectations was detected in a cadmium tolerant population, pointing towards balancing selection on some promoter stretches. Luciferase constructs were made from the most abundant alleles, and responses to Cd, paraquat (oxidative stress inducer and moulting hormone were studied in cell lines. By using paraquat we were able to dissect the effect of oxidative stress from the Cd specific effect, and extensive differences in mt induction levels between these two stressors were observed. Conclusion The pmt alleles evolved by a number of recombination events, and exhibited differential inducibilities by Cd, paraquat and molting hormone. In a tolerant population from a metal contaminated site, promoter allele frequencies differed significantly from a reference site and nucleotide polymorphisms in some promoter stretches deviated from neutral expectations, revealing a signature of balancing selection. Our results suggest that the structural differences in the Orchesella cincta metallothionein promoter alleles contribute to the metallothionein -over-expresser phenotype in cadmium tolerant populations.

Allele frequencies of AVPR1A and MAOA in the Afrikaner population

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J. Christoff Erasmus

2015-07-01

Full Text Available The Afrikaner population was founded mainly by European immigrants that arrived in South Africa from 1652. However, female slaves from Asia and Africa and local KhoeSan women may have contributed as much as 7% to this population’s genes. We quantified variation at two tandem repeats to see if this historical founder effect and/or admixture could be detected. The two loci were chosen because they are in the promoters of genes of neurotransmitters that are known to be correlated with social behaviour. Specifically, arginine vasopressin receptor 1A’s (AVPR1A RS3 locus has been shown to correlate with age of sexual onset and happiness in monogamous relationships while the tandem repeat in the promoter of the monoamine oxidase A (MAOA gene correlates with reactive aggression. The Afrikaner population contained more AVPR1A RS3 alleles than other Caucasoid populations, potentially reflecting a history of admixture. Even though Afrikaners have one of the lowest recorded non-paternity rates in the world, the population did not differ at AVPR1A RS3 locus form other European populations, suggesting a non-genetic explanation, presumably religion, for the low non-paternity rate. By comparing population allele-frequency spectra it was found that different studies have confused AVPR1A RS3 alleles and we make some suggestions to rectify these mistakes in future studies. While MAOA allele frequencies differed between racial groups, the Afrikaner population showed no evidence of admixture. In fact, Afrikaners had more 4-repeat alleles than other populations of European origin, not fewer. The 4-repeat allele may have been selected for during colonisation.

Human leukocyte antigen class II susceptibility conferring alleles among non-insulin dependent diabetes mellitus patients

International Nuclear Information System (INIS)

Tipu, H.N.; Ahmed, T.A.; Bashir, M.M.

2010-01-01

To determine the frequency of Human Leukocyte Antigen (HLA) class II susceptibility conferring alleles among type 2 Diabetes mellitus patients, in comparison with healthy controls. Cross-sectional comparative study. Patients with non-insulin dependent Diabetes mellitus meeting World Health Organization criteria were studied. These were compared with age and gender matched healthy control subjects. For each subject (patients as well as controls), DNA was extracted from ethylene diamine tetra-acetate sample and HLA class II DRB1 typing was carried out at allele group level (DRB1*01-DRB1*16) by sequence specific primers. Human leukocyte antigen DRB1 type was determined by agarose gel electrophoresis and results were recorded. Frequencies were determined as number of an allele divided by total number of alleles per group; p-value was computed using Pearson's chi-square test. Among the 100 patients, there were 63 males and 37 females with 68 controls. A total of 13 different HLA DRB1 alleles were detected, with DRB1*15 being the commonest in both the groups. The allele DRB1*13 had statistically significant higher frequency in patient group as compared to controls (p 0.005). HLA DRB1*13 was found with a significantly increased frequency in non-insulin dependent Diabetes mellitus. (author)

On the interrelation of multiplication and division in secondary school children

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Stefan eHuber

2013-10-01

Full Text Available Multiplication and division are conceptually inversely related: Each division problem can be transformed into as a multiplication problem and vice versa. Recent research has indicated strong developmental parallels between multiplication and division in primary school children. In this study, we were interested in (i whether these developmental parallels persist into secondary school, (ii whether similar developmental parallels can be observed for simple and complex problems, (iii whether skill level modulates this relationship, and (iv whether the correlations are specific and not driven by general cognitive or arithmetic abilities.Therefore, we assessed performance of 5th and 6th graders attending two secondary school types of the German educational system in simple and complex multiplication as well as division while controlling for nonverbal intelligence, short-term memory, and other arithmetic abilities. Accordingly, we collected data from students differing in skills levels due to either age (5th and 6th grade or school type (general and intermediate secondary school.We observed moderate to strong bivariate and partial correlations between multiplication and division with correlations being higher for simple tasks but nevertheless reliable for complex tasks. Moreover, the association between simple multiplication and division depended on students’ skill levels as reflected by school types, but not by age. Partial correlations were higher for intermediate than for general secondary school children.In sum, these findings emphasize the importance of the inverse relationship between multiplication and division which persists into later developmental stages. However, evidence for skill-related differences in the relationship between multiplication and division was restricted to the differences for school types.

Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases.

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Rong Chen

Full Text Available Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may

High Performance Parallel Multigrid Algorithms for Unstructured Grids

Science.gov (United States)

Frederickson, Paul O.

1996-01-01

We describe a high performance parallel multigrid algorithm for a rather general class of unstructured grid problems in two and three dimensions. The algorithm PUMG, for parallel unstructured multigrid, is related in structure to the parallel multigrid algorithm PSMG introduced by McBryan and Frederickson, for they both obtain a higher convergence rate through the use of multiple coarse grids. Another reason for the high convergence rate of PUMG is its smoother, an approximate inverse developed by Baumgardner and Frederickson.

Specificity and multiplicity in the recognition of individuals: implications for the evolution of social behaviour.

Science.gov (United States)

Wiley, R H

2013-02-01

Recognition of conspecifics occurs when individuals classify sets of conspecifics based on sensory input from them and associate these sets with different responses. Classification of conspecifics can vary in specificity (the number of individuals included in a set) and multiplicity (the number of sets differentiated). In other words, the information transmitted varies in complexity. Although recognition of conspecifics has been reported in a wide variety of organisms, few reports have addressed the specificity or multiplicity of this capability. This review discusses examples of these patterns, the mechanisms that can produce them, and the evolution of these mechanisms. Individual recognition is one end of a spectrum of specificity, and binary classification of conspecifics is one end of a spectrum of multiplicity. In some cases, recognition requires no more than simple forms of learning, such as habituation, yet results in individually specific recognition. In other cases, recognition of individuals involves complex associations of multiple cues with multiple previous experiences in particular contexts. Complex mechanisms for recognition are expected to evolve only when simpler mechanisms do not provide sufficient specificity and multiplicity to obtain the available advantages. In particular, the evolution of cooperation and deception is always promoted by specificity and multiplicity in recognition. Nevertheless, there is only one demonstration that recognition of specific individuals contributes to cooperation in animals other than primates. Human capacities for individual recognition probably have a central role in the evolution of complex forms of human cooperation and deception. Although relatively little studied, this capability probably rivals cognitive abilities for language. © 2012 The Author. Biological Reviews © 2012 Cambridge Philosophical Society.

Rin4 Causes Hybrid Necrosis and Race-Specific Resistance in an Interspecific Lettuce Hybrid[W

Science.gov (United States)

Jeuken, Marieke J.W.; Zhang, Ningwen W.; McHale, Leah K.; Pelgrom, Koen; den Boer, Erik; Lindhout, Pim; Michelmore, Richard W.; Visser, Richard G.F.; Niks, Rients E.

2009-01-01

Some inter- and intraspecific crosses may result in reduced viability or sterility in the offspring, often due to genetic incompatibilities resulting from interactions between two or more loci. Hybrid necrosis is a postzygotic genetic incompatibility that is phenotypically manifested as necrotic lesions on the plant. We observed hybrid necrosis in interspecific lettuce (Lactuca sativa and Lactuca saligna) hybrids that correlated with resistance to downy mildew. Segregation analysis revealed a specific allelic combination at two interacting loci to be responsible. The allelic interaction had two consequences: (1) a quantitative temperature-dependent autoimmunity reaction leading to necrotic lesions, lethality, and quantitative resistance to an otherwise virulent race of Bremia lactucae; and (2) a qualitative temperature-independent race-specific resistance to an avirulent race of B. lactucae. We demonstrated by transient expression and silencing experiments that one of the two interacting genes was Rin4. In Arabidopsis thaliana, RIN4 is known to interact with multiple R gene products, and their interactions result in hypersensitive resistance to Pseudomonas syringae. Site-directed mutation studies on the necrosis-eliciting allele of Rin4 in lettuce showed that three residues were critical for hybrid necrosis. PMID:19855048

A solution for automatic parallelization of sequential assembly code

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Kovačević Đorđe

2013-01-01

Full Text Available Since modern multicore processors can execute existing sequential programs only on a single core, there is a strong need for automatic parallelization of program code. Relying on existing algorithms, this paper describes one new software solution tool for parallelization of sequential assembly code. The main goal of this paper is to develop the parallelizator which reads sequential assembler code and at the output provides parallelized code for MIPS processor with multiple cores. The idea is the following: the parser translates assembler input file to program objects suitable for further processing. After that the static single assignment is done. Based on the data flow graph, the parallelization algorithm separates instructions on different cores. Once sequential code is parallelized by the parallelization algorithm, registers are allocated with the algorithm for linear allocation, and the result at the end of the program is distributed assembler code on each of the cores. In the paper we evaluate the speedup of the matrix multiplication example, which was processed by the parallelizator of assembly code. The result is almost linear speedup of code execution, which increases with the number of cores. The speed up on the two cores is 1.99, while on 16 cores the speed up is 13.88.

Parallel Task Processing on a Multicore Platform in a PC-based Control System for Parallel Kinematics

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Harald Michalik

2009-02-01

Full Text Available Multicore platforms are such that have one physical processor chip with multiple cores interconnected via a chip level bus. Because they deliver a greater computing power through concurrency, offer greater system density multicore platforms provide best qualifications to address the performance bottleneck encountered in PC-based control systems for parallel kinematic robots with heavy CPU-load. Heavy load control tasks are generated by new control approaches that include features like singularity prediction, structure control algorithms, vision data integration and similar tasks. In this paper we introduce the parallel task scheduling extension of a communication architecture specially tailored for the development of PC-based control of parallel kinematics. The Sche-duling is specially designed for the processing on a multicore platform. It breaks down the serial task processing of the robot control cycle and extends it with parallel task processing paths in order to enhance the overall control performance.

Experiences in Data-Parallel Programming

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Terry W. Clark

1997-01-01

Full Text Available To efficiently parallelize a scientific application with a data-parallel compiler requires certain structural properties in the source program, and conversely, the absence of others. A recent parallelization effort of ours reinforced this observation and motivated this correspondence. Specifically, we have transformed a Fortran 77 version of GROMOS, a popular dusty-deck program for molecular dynamics, into Fortran D, a data-parallel dialect of Fortran. During this transformation we have encountered a number of difficulties that probably are neither limited to this particular application nor do they seem likely to be addressed by improved compiler technology in the near future. Our experience with GROMOS suggests a number of points to keep in mind when developing software that may at some time in its life cycle be parallelized with a data-parallel compiler. This note presents some guidelines for engineering data-parallel applications that are compatible with Fortran D or High Performance Fortran compilers.

Parallel transposition of sparse data structures

DEFF Research Database (Denmark)

Wang, Hao; Liu, Weifeng; Hou, Kaixi

2016-01-01

Many applications in computational sciences and social sciences exploit sparsity and connectivity of acquired data. Even though many parallel sparse primitives such as sparse matrix-vector (SpMV) multiplication have been extensively studied, some other important building blocks, e.g., parallel tr...... transposition in the latest vendor-supplied library on an Intel multicore CPU platform, and the MergeTrans approach achieves on average of 3.4-fold (up to 11.7-fold) speedup on an Intel Xeon Phi many-core processor....

Parallel universes beguile science

CERN Multimedia

2007-01-01

A staple of mind-bending science fiction, the possibility of multiple universes has long intrigued hard-nosed physicists, mathematicians and cosmologists too. We may not be able -- as least not yet -- to prove they exist, many serious scientists say, but there are plenty of reasons to think that parallel dimensions are more than figments of eggheaded imagination.

Frequency of CCR5Δ32 allele in healthy Bosniak population.

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Grażyna Adler

2014-08-01

Full Text Available Recent evidence has demonstrated the role of CCR5Δ32 in a variety of human diseases: from infectious and inflammatory diseases to cancer. Several studies have confirmed that genetic variants in chemokine receptor CCR5 gene are correlated with susceptibility and resistance to HIV infection. A 32-nucleotide deletion within the CCR5 reading frame is associated with decreased susceptibility to HIV acquisition and a slower progression to AIDS. Mean frequency of CCR5Δ32 allele in Europe is approximately 10%. The highest allele frequency is observed among Nordic populations (about 12% and lower in the regions of Southeast Mediterranean (about 5%. Although the frequency of CCR5Δ32 was determined in numerous European populations, there is a lack of studies on this variant in the Bosnia and Hercegovina population. Therefore, the aim of our study was to assess the frequency of CCR5Δ32 allele in the cohort of Bosniaks and compare the results with European reports. CCR5Δ32 was detected by sequence-specific PCR in a sample of 100 healthy subjects from Bosnia and Herzegovina (DNA collected 2011-2013.  Mean age of the cohort being 58.8 (±10.7 years, with 82% of women. We identified 17 heterozygotes and one mutant homozygote in study group, with mean ∆32 allele frequency of 9.5%. CCR5∆32 allele frequency among Bosniaks is comparable to that found in Caucasian populations and follows the pattern of the north-southern gradient observed for Europe. Further studies on larger cohorts with adequate female-to-male ratio are necessary. 

A note on the nucleation with multiple steps: Parallel and series nucleation

OpenAIRE

Iwamatsu, Masao

2012-01-01

Parallel and series nucleation are the basic elements of the complex nucleation process when two saddle points exist on the free-energy landscape. It is pointed out that the nucleation rates follow formulas similar to those of parallel and series connection of resistors or conductors in an electric circuit. Necessary formulas to calculate individual nucleation rates at the saddle points and the total nucleation rate are summarized and the extension to the more complex nucleation process is su...

Database for the ampC alleles in Acinetobacter baumannii.

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Nabil Karah

Full Text Available Acinetobacter baumannii is a troublesome opportunistic pathogen with a high capacity for clonal dissemination. We announce the establishment of a database for the ampC locus in A. baumannii, in which novel ampC alleles are differentiated based on the occurrence of ≥ 1 nucleotide change, regardless of whether it is silent or missense. The database is openly accessible at the pubmlst platform for A. baumannii (http://pubmlst.org/abaumannii/. Forty-eight distinctive alleles of the ampC locus have so far been identified and deposited in the database. Isolates from clonal complex 1 (CC1, according to the Pasteur multilocus sequence typing scheme, had a variety of the ampC locus alleles, including alleles 1, 3, 4, 5, 6, 7, 8, 13, 14, 17, and 18. On the other hand, isolates from CC2 had the ampC alleles 2, 3, 19, 20, 21, 22, 23, 24, 26, 27, 28, and 46. Allele 3 was characteristic for sequence types ST3 or ST32. The ampC alleles 10, 16, and 25 were characteristic for CC10, ST16, and CC25, respectively. Our study points out that novel gene databases, in which alleles are numbered based on differences in their nucleotide identities, should replace traditional records that use amino acid substitutions to define new alleles.

Allelic Dropout During Polymerase Chain Reaction due to G-Quadruplex Structures and DNA Methylation Is Widespread at Imprinted Human Loci

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Aaron J. Stevens

2017-03-01

Full Text Available Loss of one allele during polymerase chain reaction (PCR amplification of DNA, known as allelic dropout, can be caused by a variety of mechanisms. Allelic dropout during PCR may have profound implications for molecular diagnostic and research procedures that depend on PCR and assume biallelic amplification has occurred. Complete allelic dropout due to the combined effects of cytosine methylation and G-quadruplex formation was previously described for a differentially methylated region of the human imprinted gene, MEST. We now demonstrate that this parent-of-origin specific allelic dropout can potentially occur at several other genomic regions that display genomic imprinting and have propensity for G-quadruplex formation, including AIM1, BLCAP, DNMT1, PLAGL1, KCNQ1, and GRB10. These findings demonstrate that systematic allelic dropout during PCR is a general phenomenon for regions of the genome where differential allelic methylation and G-quadruplex motifs coincide, and suggest that great care must be taken to ensure biallelic amplification is occurring in such situations.

Mendelian randomization shows sex-specific associations between long-chain PUFA-related genotypes and cognitive performance in Danish schoolchildren

DEFF Research Database (Denmark)

Lauritzen, Lotte; Sorensen, Louise B.; Harslof, Laurine B.

2017-01-01

, and performance in the d2 Test of Attention and a reading test were analyzed in multiple regression models including all SNPs, SNP-sex interactions, and covariates related to testing conditions.Results:FADS, rs1535 minor allele carriage associated with lower whole-blood arachidonic acid (P ≤ 0.002), and minor...... alleles of rs174448 tended to associate with lower docosahexaenoic acid (DHA) (P = 0.052). We identified sex interactions in 50% of the SNP performance sets. Sex-dependent associations were observed for rs174448 and rs1535 on the d2 Test of Attention outcomes (P ... reading scores and rs174448 and rs2397142 (P sex-specific analyses showed associations in opposite directions in girls and boys. The minor allele carriage of rs174448 was associated with lower d2 Test of Attention performance (P

Genetic and infectious profiles of Japanese multiple sclerosis patients.

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Satoshi Yoshimura

Full Text Available BACKGROUND: Nationwide surveys conducted in Japan over the past thirty years have revealed a four-fold increase in the estimated number of multiple sclerosis (MS patients, a decrease in the age at onset, and successive increases in patients with conventional MS, which shows an involvement of multiple sites in the central nervous system, including the cerebrum and cerebellum. We aimed to clarify whether genetic and infectious backgrounds correlate to distinct disease phenotypes of MS in Japanese patients. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed HLA-DRB1 and -DPB1 alleles, and IgG antibodies specific for Helicobacter pylori, Chlamydia pneumoniae, varicella zoster virus, and Epstein-Barr virus nuclear antigen (EBNA in 145 MS patients and 367 healthy controls (HCs. Frequencies of DRB1*0405 and DPB1*0301 were significantly higher, and DRB1*0901 and DPB1*0401 significantly lower, in MS patients as compared with HCs. MS patients with DRB1*0405 had a significantly earlier age of onset and lower Progression Index than patients without this allele. The proportion and absolute number of patients with DRB1*0405 successively increased with advancing year of birth. In MS patients without DRB1*0405, the frequency of the DRB1*1501 allele was significantly higher, while the DRB1*0901 allele was significantly lower, compared with HCs. Furthermore, DRB1*0405-negative MS patients were significantly more likely to be positive for EBNA antibodies compared with HCs. CONCLUSIONS: Our study suggests that MS patients harboring DRB1*0405, a genetic risk factor for MS in the Japanese population, have a younger age at onset and a relatively benign disease course, while DRB1*0405-negative MS patients have features similar to Western-type MS in terms of association with Epstein-Barr virus infection and DRB1*1501. The recent increase of MS in young Japanese people may be caused, in part, by an increase in DRB1*0405-positive MS patients.

WASP: a Web-based Allele-Specific PCR assay designing tool for detecting SNPs and mutations

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Assawamakin Anunchai

2007-08-01

Full Text Available Abstract Background Allele-specific (AS Polymerase Chain Reaction is a convenient and inexpensive method for genotyping Single Nucleotide Polymorphisms (SNPs and mutations. It is applied in many recent studies including population genetics, molecular genetics and pharmacogenomics. Using known AS primer design tools to create primers leads to cumbersome process to inexperience users since information about SNP/mutation must be acquired from public databases prior to the design. Furthermore, most of these tools do not offer the mismatch enhancement to designed primers. The available web applications do not provide user-friendly graphical input interface and intuitive visualization of their primer results. Results This work presents a web-based AS primer design application called WASP. This tool can efficiently design AS primers for human SNPs as well as mutations. To assist scientists with collecting necessary information about target polymorphisms, this tool provides a local SNP database containing over 10 million SNPs of various populations from public domain databases, namely NCBI dbSNP, HapMap and JSNP respectively. This database is tightly integrated with the tool so that users can perform the design for existing SNPs without going off the site. To guarantee specificity of AS primers, the proposed system incorporates a primer specificity enhancement technique widely used in experiment protocol. In particular, WASP makes use of different destabilizing effects by introducing one deliberate 'mismatch' at the penultimate (second to last of the 3'-end base of AS primers to improve the resulting AS primers. Furthermore, WASP offers graphical user interface through scalable vector graphic (SVG draw that allow users to select SNPs and graphically visualize designed primers and their conditions. Conclusion WASP offers a tool for designing AS primers for both SNPs and mutations. By integrating the database for known SNPs (using gene ID or rs number

Combination of interleukin-10 gene promoter polymorphisms with HLA-DRB1*15 allele is associated with multiple sclerosis

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Majid Shahbazi

2017-01-01

Interpretation & conclusions: The IL-10 and HLA-DRB1*15 polymorphisms were associated with the susceptibility to MS in Iranian patients. Our results suggest that gene-gene interaction of IL-10 polymorphisms and HLA-DRB1*15 alleles may be important factors in the development of MS.

The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma

International Nuclear Information System (INIS)

Ronchetti, D; Todoerti, K; Tuana, G; Agnelli, L; Mosca, L; Lionetti, M; Fabris, S; Colapietro, P; Miozzo, M; Ferrarini, M; Tassone, P; Neri, A

2012-01-01

Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs involved in the maturation of other RNA molecules and generally located in the introns of host genes. It is now emerging that altered sno/scaRNAs expression may have a pathological role in cancer. This study elucidates the patterns of sno/scaRNAs expression in multiple myeloma (MM) by profiling purified malignant plasma cells from 55 MMs, 8 secondary plasma cell leukemias (sPCLs) and 4 normal controls. Overall, a global sno/scaRNAs downregulation was found in MMs and, even more, in sPCLs compared with normal plasma cells. Whereas SCARNA22 resulted the only sno/scaRNA characterizing the translocation/cyclin D4 (TC4) MM, TC2 group displayed a distinct sno/scaRNA signature overexpressing members of SNORD115 and SNORD116 families located in a region finely regulated by an imprinting center at 15q11, which, however, resulted overall hypomethylated in MMs independently of the SNORD115 and SNORD116 expression levels. Finally, integrative analyses with available gene expression and genome-wide data revealed the occurrence of significant sno/scaRNAs/host genes co-expression and the putative influence of allelic imbalances on specific snoRNAs expression. Our data extend the current view of sno/scaRNAs deregulation in cancer and add novel information to the bio-molecular complexity of plasma cell dyscrasias

Alternative derivation of the parallel ion viscosity

International Nuclear Information System (INIS)

Bravenec, R.V.; Berk, H.L.; Hammer, J.H.

1982-01-01

A set of double-adiabatic fluid equations with additional collisional relaxation between the ion temperatures parallel and perpendicular to a magnetic field are shown to reduce to a set involving a single temperature and a parallel viscosity. This result is applied to a recently published paper [R. V. Bravenec, A. J. Lichtenberg, M. A. Leiberman, and H. L. Berk, Phys. Fluids 24, 1320 (1981)] on viscous flow in a multiple-mirror configuration

Comprehensive Analysis of CD8+-T-Cell Responses against Hepatitis C Virus Reveals Multiple Unpredicted Specificities

OpenAIRE

Lauer, Georg M.; Ouchi, Kei; Chung, Raymond T.; Nguyen, Tam N.; Day, Cheryl L.; Purkis, Deborah R.; Reiser, Markus; Kim, Arthur Y.; Lucas, Michaela; Klenerman, Paul; Walker, Bruce D.

2002-01-01

The hepatitis C virus (HCV)-specific CD8+-T-cell response is thought to play a critical role in HCV infection. Studies of these responses have largely relied on the analysis of a small number of previously described or predicted HCV epitopes, mostly restricted by HLA A2. In order to determine the actual breadth and magnitude of CD8+-T-cell responses in the context of diverse HLA class I alleles, we performed a comprehensive analysis of responses to all expressed HCV proteins. By using a panel...

A note on the nucleation with multiple steps: parallel and series nucleation.

Science.gov (United States)

Iwamatsu, Masao

2012-01-28

Parallel and series nucleation are the basic elements of the complex nucleation process when two saddle points exist on the free-energy landscape. It is pointed out that the nucleation rates follow formulas similar to those of parallel and series connection of resistors or conductors in an electric circuit. Necessary formulas to calculate individual nucleation rates at the saddle points and the total nucleation rate are summarized, and the extension to the more complex nucleation process is suggested. © 2012 American Institute of Physics

Procedures for identifying S-allele genotypes of Brassica.

Science.gov (United States)

Wallace, D H

1979-11-01

Procedures are described for efficient selection of: (1) homozygous and heterozygous S-allele genotypes; (2) homozygous inbreds with the strong self- and sib-incompatibility required for effective seed production of single-cross F1 hybrids; (3) heterozygous genotypes with the high self- and sib-incompatibility required for effective seed production of 3- and 4-way hybrids.From reciprocal crosses between two first generation inbred (I1) plants there are three potential results: both crosses are incompatible; one is incompatible and the other compatible; and both are compatible. Incompatibility of both crosses is useful information only when combined with data from other reciprocal crosses. Each compatible cross, depending on whether its reciprocal is incompatible or compatible, dictates alternative reasoning and additional reciprocal crosses for efficiently and simultaneously identifying: (A) the S-allele genotype of all individual I1 plants, and (B) the expressions of dominance or codominance in pollen and stigma (sexual organs) of an S-allele heterozygous genotype. Reciprocal crosses provide the only efficient means of identifying S-allele genotypes and also the sexual-organ x S-allele-interaction types.Fluorescent microscope assay of pollen tube penetration into the style facilitates quantitation within 24-48 hours of incompatibility and compatibility of the reciprocal crosses. A procedure for quantitating the reciprocal difference is described that maximizes informational content of the data about interactions between S alleles in pollen and stigma of the S-allele-heterozygous genotype.Use of the non-inbred Io generation parent as a 'known' heterozygous S-allele genotype in crosses with its first generation selfed (I1) progeny usually reduces at least 7 fold the effort required for achieving objectives 1, 2, and 3, compared to the method of making reciprocal crosses only among I1 plants.Identifying the heterozygous and both homozygous S-allele genotypes during

Characterization of a Novel MMS-Sensitive Allele of Schizosaccharomyces pombe mcm4+

Science.gov (United States)

Ranatunga, Nimna S.; Forsburg, Susan L.

2016-01-01

The minichromosome maintenance (MCM) complex is the conserved helicase motor of the eukaryotic replication fork. Mutations in the Mcm4 subunit are associated with replication stress and double strand breaks in multiple systems. In this work, we characterize a new temperature-sensitive allele of Schizosaccharomyces pombe mcm4+. Uniquely among known mcm4 alleles, this mutation causes sensitivity to the alkylation damaging agent methyl methanesulfonate (MMS). Even in the absence of treatment or temperature shift, mcm4-c106 cells show increased repair foci of RPA and Rad52, and require the damage checkpoint for viability, indicating genome stress. The mcm4-c106 mutant is synthetically lethal with mutations disrupting fork protection complex (FPC) proteins Swi1 and Swi3. Surprisingly, we found that the deletion of rif1+ suppressed the MMS-sensitive phenotype without affecting temperature sensitivity. Together, these data suggest that mcm4-c106 destabilizes replisome structure. PMID:27473316

Category specific spatial dissociations of parallel processes underlying visual naming.

Science.gov (United States)

Conner, Christopher R; Chen, Gang; Pieters, Thomas A; Tandon, Nitin

2014-10-01

The constituent elements and dynamics of the networks responsible for word production are a central issue to understanding human language. Of particular interest is their dependency on lexical category, particularly the possible segregation of nouns and verbs into separate processing streams. We applied a novel mixed-effects, multilevel analysis to electrocorticographic data collected from 19 patients (1942 electrodes) to examine the activity of broadly disseminated cortical networks during the retrieval of distinct lexical categories. This approach was designed to overcome the issues of sparse sampling and individual variability inherent to invasive electrophysiology. Both noun and verb generation evoked overlapping, yet distinct nonhierarchical processes favoring ventral and dorsal visual streams, respectively. Notable differences in activity patterns were noted in Broca's area and superior lateral temporo-occipital regions (verb > noun) and in parahippocampal and fusiform cortices (noun > verb). Comparisons with functional magnetic resonance imaging (fMRI) results yielded a strong correlation of blood oxygen level-dependent signal and gamma power and an independent estimate of group size needed for fMRI studies of cognition. Our findings imply parallel, lexical category-specific processes and reconcile discrepancies between lesional and functional imaging studies. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hyper-systolic matrix multiplication

NARCIS (Netherlands)

Lippert, Th.; Petkov, N.; Palazzari, P.; Schilling, K.

A novel parallel algorithm for matrix multiplication is presented. It is based on a 1-D hyper-systolic processor abstraction. The procedure can be implemented on all types of parallel systems. (C) 2001 Elsevier Science B,V. All rights reserved.

Short term scheduling of multiple grid-parallel PEM fuel cells for microgrid applications

Energy Technology Data Exchange (ETDEWEB)

El-Sharkh, M.Y.; Rahman, A.; Alam, M.S. [Dept. of Electrical and Computer Engineering, University of South Alabama, Mobile, AL 36688 (United States)

2010-10-15

This paper presents a short term scheduling scheme for multiple grid-parallel PEM fuel cell power plants (FCPPs) connected to supply electrical and thermal energy to a microgrid community. As in the case of regular power plants, short term scheduling of FCPP is also a cost-based optimization problem that includes the cost of operation, thermal power recovery, and the power trade with the local utility grid. Due to the ability of the microgrid community to trade power with the local grid, the power balance constraint is not applicable, other constraints like the real power operating limits of the FCPP, and minimum up and down time are therefore used. To solve the short term scheduling problem of the FCPPs, a hybrid technique based on evolutionary programming (EP) and hill climbing technique (HC) is used. The EP is used to estimate the optimal schedule and the output power from each FCPP. The HC technique is used to monitor the feasibility of the solution during the search process. The short term scheduling problem is used to estimate the schedule and the electrical and thermal power output of five FCPPs supplying a maximum power of 300 kW. (author)

Construction of a digital elevation model: methods and parallelization

International Nuclear Information System (INIS)

Mazzoni, Christophe

1995-01-01

The aim of this work is to reduce the computation time needed to produce the Digital Elevation Models (DEM) by using a parallel machine. It is made in collaboration between the French 'Institut Geographique National' (IGN) and the Laboratoire d'Electronique de Technologie et d'Instrumentation (LETI) of the French Atomic Energy Commission (CEA). The IGN has developed a system which provides DEM that is used to produce topographic maps. The kernel of this system is the correlator, a software which automatically matches pairs of homologous points of a stereo-pair of photographs. Nevertheless the correlator is expensive In computing time. In order to reduce computation time and to produce the DEM with same accuracy that the actual system, we have parallelized the IGN's correlator on the OPENVISION system. This hardware solution uses a SIMD (Single Instruction Multiple Data) parallel machine SYMPATI-2, developed by the LETI that is involved in parallel architecture and image processing. Our analysis of the implementation has demonstrated the difficulty of efficient coupling between scalar and parallel structure. So we propose solutions to reinforce this coupling. In order to accelerate more the processing we evaluate SYMPHONIE, a SIMD calculator, successor of SYMPATI-2. On an other hand, we developed a multi-agent approach for what a MIMD (Multiple Instruction, Multiple Data) architecture is available. At last, we describe a Multi-SIMD architecture that conciliates our two approaches. This architecture offers a capacity to apprehend efficiently multi-level treatment image. It is flexible by its modularity, and its communication network supplies reliability that interest sensible systems. (author) [fr

Mobility and Sector-specific Effects of Changes in Multiple Sources ...

African Journals Online (AJOL)

Using the second and third Cameroon household consumption surveys, this study examined mobility and sector-specific effects of changes in multiple sources of deprivation in Cameroon. Results indicated that between 2001 and 2007, deprivations associated with human capital and labour capital reduced, while ...

Allele-dependent differences in quorum-sensing dynamics result in variant expression of virulence genes in Staphylococcus aureus.

Science.gov (United States)

Geisinger, Edward; Chen, John; Novick, Richard P

2012-06-01

Agr is an autoinducing, quorum-sensing system that functions in many Gram-positive species and is best characterized in the pathogen Staphylococcus aureus, in which it is a global regulator of virulence gene expression. Allelic variations in the agr genes have resulted in the emergence of four quorum-sensing specificity groups in S. aureus, which correlate with different strain pathotypes. The basis for these predilections is unclear but is hypothesized to involve the phenomenon of quorum-sensing interference between strains of different agr groups, which may drive S. aureus strain isolation and divergence. Whether properties intrinsic to each agr allele directly influence virulence phenotypes within S. aureus is unknown. In this study, we examined group-specific differences in agr autoinduction and virulence gene regulation by utilizing congenic strains, each harboring a unique S. aureus agr allele, enabling a dissection of agr locus-dependent versus genotype-dependent effects on quorum-sensing dynamics and virulence factor production. Employing a reporter fusion to the principal agr promoter, P3, we observed allele-dependent differences in the timing and magnitude of agr activation. These differences were mediated by polymorphisms within the agrBDCA genes and translated to significant variations in the expression of a key transcriptional regulator, Rot, and of several important exoproteins and surface factors involved in pathogenesis. This work uncovers the contribution of divergent quorum-sensing alleles to variant expression of virulence determinants within a bacterial species.

Convergent Evolution of Hemoglobin Function in High-Altitude Andean Waterfowl Involves Limited Parallelism at the Molecular Sequence Level.

Directory of Open Access Journals (Sweden)

Chandrasekhar Natarajan

2015-12-01

Full Text Available A fundamental question in evolutionary genetics concerns the extent to which adaptive phenotypic convergence is attributable to convergent or parallel changes at the molecular sequence level. Here we report a comparative analysis of hemoglobin (Hb function in eight phylogenetically replicated pairs of high- and low-altitude waterfowl taxa to test for convergence in the oxygenation properties of Hb, and to assess the extent to which convergence in biochemical phenotype is attributable to repeated amino acid replacements. Functional experiments on native Hb variants and protein engineering experiments based on site-directed mutagenesis revealed the phenotypic effects of specific amino acid replacements that were responsible for convergent increases in Hb-O2 affinity in multiple high-altitude taxa. In six of the eight taxon pairs, high-altitude taxa evolved derived increases in Hb-O2 affinity that were caused by a combination of unique replacements, parallel replacements (involving identical-by-state variants with independent mutational origins in different lineages, and collateral replacements (involving shared, identical-by-descent variants derived via introgressive hybridization. In genome scans of nucleotide differentiation involving high- and low-altitude populations of three separate species, function-altering amino acid polymorphisms in the globin genes emerged as highly significant outliers, providing independent evidence for adaptive divergence in Hb function. The experimental results demonstrate that convergent changes in protein function can occur through multiple historical paths, and can involve multiple possible mutations. Most cases of convergence in Hb function did not involve parallel substitutions and most parallel substitutions did not affect Hb-O2 affinity, indicating that the repeatability of phenotypic evolution does not require parallelism at the molecular level.

Neoclassical parallel flow calculation in the presence of external parallel momentum sources in Heliotron J

Energy Technology Data Exchange (ETDEWEB)

Nishioka, K.; Nakamura, Y. [Graduate School of Energy Science, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Nishimura, S. [National Institute for Fusion Science, 322-6 Oroshi-cho, Toki, Gifu 509-5292 (Japan); Lee, H. Y. [Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Kobayashi, S.; Mizuuchi, T.; Nagasaki, K.; Okada, H.; Minami, T.; Kado, S.; Yamamoto, S.; Ohshima, S.; Konoshima, S.; Sano, F. [Institute of Advanced Energy, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan)

2016-03-15

A moment approach to calculate neoclassical transport in non-axisymmetric torus plasmas composed of multiple ion species is extended to include the external parallel momentum sources due to unbalanced tangential neutral beam injections (NBIs). The momentum sources that are included in the parallel momentum balance are calculated from the collision operators of background particles with fast ions. This method is applied for the clarification of the physical mechanism of the neoclassical parallel ion flows and the multi-ion species effect on them in Heliotron J NBI plasmas. It is found that parallel ion flow can be determined by the balance between the parallel viscosity and the external momentum source in the region where the external source is much larger than the thermodynamic force driven source in the collisional plasmas. This is because the friction between C{sup 6+} and D{sup +} prevents a large difference between C{sup 6+} and D{sup +} flow velocities in such plasmas. The C{sup 6+} flow velocities, which are measured by the charge exchange recombination spectroscopy system, are numerically evaluated with this method. It is shown that the experimentally measured C{sup 6+} impurity flow velocities do not contradict clearly with the neoclassical estimations, and the dependence of parallel flow velocities on the magnetic field ripples is consistent in both results.

Fractional populations in multiple gene inheritance.

Science.gov (United States)

Chung, Myung-Hoon; Kim, Chul Koo; Nahm, Kyun

2003-01-22

With complete knowledge of the human genome sequence, one of the most interesting tasks remaining is to understand the functions of individual genes and how they communicate. Using the information about genes (locus, allele, mutation rate, fitness, etc.), we attempt to explain population demographic data. This population evolution study could complement and enhance biologists' understanding about genes. We present a general approach to study population genetics in complex situations. In the present approach, multiple allele inheritance, multiple loci inheritance, natural selection and mutations are allowed simultaneously in order to consider a more realistic situation. A simulation program is presented so that readers can readily carry out studies with their own parameters. It is shown that the multiplicity of the loci greatly affects the demographic results of fractional population ratios. Furthermore, the study indicates that some high infant mortality rates due to congenital anomalies can be attributed to multiple loci inheritance. The simulation program can be downloaded from http://won.hongik.ac.kr/~mhchung/index_files/yapop.htm. In order to run this program, one needs Visual Studio.NET platform, which can be downloaded from http://msdn.microsoft.com/netframework/downloads/default.asp.

Use of allele-specific FAIRE to determine functional regulatory polymorphism using large-scale genotyping arrays

DEFF Research Database (Denmark)

Smith, Frank Andrew; Howard, Philip; Shah, Sonia

2012-01-01

Following the widespread use of genome-wide association studies (GWAS), focus is turning towards identification of causal variants rather than simply genetic markers of diseases and traits. As a step towards a high-throughput method to identify genome-wide, non-coding, functional regulatory...... discrimination. Examination of this SNP in two prospective Caucasian cohorts comprising 15,000 individuals confirmed the association with HDL-C levels (combined beta = 0.016; p = 0.0006), and analysis of gene expression identified an allelic association with LXR-α expression in heart tissue. Using increasingly...

Forensic genetic informativeness of an SNP panel consisting of 19 multi-allelic SNPs.

Science.gov (United States)

Gao, Zehua; Chen, Xiaogang; Zhao, Yuancun; Zhao, Xiaohong; Zhang, Shu; Yang, Yiwen; Wang, Yufang; Zhang, Ji

2018-05-01

Current research focusing on forensic personal identification, phenotype inference and ancestry information on single-nucleotide polymorphisms (SNPs) has been widely reported. In the present study, we focused on tetra-allelic SNPs in the Chinese Han population. A total of 48 tetra-allelic SNPs were screened out from the Chinese Han population of the 1000 Genomes Database, including Chinese Han in Beijing (CHB) and Chinese Han South (CHS). Considering the forensic genetic requirement for the polymorphisms, only 11 tetra-allelic SNPs with a heterozygosity >0.06 were selected for further multiplex panel construction. In order to meet the demands of personal identification and parentage identification, an additional 8 tri-allelic SNPs were combined into the final multiplex panel. To ensure application in the degraded DNA analysis, all the PCR products were designed to be 87-188 bp. Employing multiple PCR reactions and SNaPshot minisequencing, 511 unrelated Chinese Han individuals from Sichuan were genotyped. The combined match probability (CMP), combined discrimination power (CDP), and cumulative probability of exclusion (CPE) of the panel were 6.07 × 10 -11 , 0.9999999999393 and 0.996764, respectively. Based on the population data retrieved from the 1000 Genomes Project, Fst values between Chinese Han in Sichuan (SCH) and all the populations included in the 1000 Genomes Project were calculated. The results indicated that two SNPs in this panel may contain ancestry information and may be used as markers of forensic biogeographical ancestry inference. Copyright © 2018 Elsevier B.V. All rights reserved.

Use of parallel counters for triggering

International Nuclear Information System (INIS)

Nikityuk, N.M.

1991-01-01

Results of investigation of using parallel counters, majority coincidence schemes, parallel compressors for triggering in multichannel high energy spectrometers are described. Concrete examples of methods of constructing fast and economic new devices used to determine multiplicity hits t>900 registered in a hodoscopic plane and a pixel detector are given. For this purpose the author uses the syndrome coding method and cellular arrays. In addition, an effective coding matrix has been created which can be used for light signal coding. For example, such signals are supplied from scintillators to photomultipliers. 23 refs.; 21 figs

Portable parallel programming in a Fortran environment

International Nuclear Information System (INIS)

May, E.N.

1989-01-01

Experience using the Argonne-developed PARMACs macro package to implement a portable parallel programming environment is described. Fortran programs with intrinsic parallelism of coarse and medium granularity are easily converted to parallel programs which are portable among a number of commercially available parallel processors in the class of shared-memory bus-based and local-memory network based MIMD processors. The parallelism is implemented using standard UNIX (tm) tools and a small number of easily understood synchronization concepts (monitors and message-passing techniques) to construct and coordinate multiple cooperating processes on one or many processors. Benchmark results are presented for parallel computers such as the Alliant FX/8, the Encore MultiMax, the Sequent Balance, the Intel iPSC/2 Hypercube and a network of Sun 3 workstations. These parallel machines are typical MIMD types with from 8 to 30 processors, each rated at from 1 to 10 MIPS processing power. The demonstration code used for this work is a Monte Carlo simulation of the response to photons of a ''nearly realistic'' lead, iron and plastic electromagnetic and hadronic calorimeter, using the EGS4 code system. 6 refs., 2 figs., 2 tabs

Common breast cancer risk alleles and risk assessment

DEFF Research Database (Denmark)

Näslund-Koch, C; Nordestgaard, B G; Bojesen, S E

2017-01-01

general population were followed in Danish health registries for up to 21 years after blood sampling. After genotyping 72 breast cancer risk loci, each with 0-2 alleles, the sum for each individual was calculated. We used the simple allele sum instead of the conventional polygenic risk score......, as it is likely more sensitive in detecting associations with risks of other endpoints than breast cancer. RESULTS: Breast cancer incidence in the 19,010 women was increased across allele sum quintiles (log-rank trend test; p=1*10(-12)), but not incidence of other cancers (p=0.41). Age- and study-adjusted hazard...... ratio for the 5(th) vs. 1(st) allele sum quintile was 1.82(95% confidence interval;1.53-2.18). Corresponding hazard ratios per allele were 1.04(1.03-1.05) and 1.05(1.02-1.08) for breast cancer incidence and mortality, similar across risk factors. In 50-year old women, the starting age for screening...

Swine Leukocyte Antigen (SLA) class I allele typing of Danish swine herds and identification of commonly occurring haplotypes using sequence specific low and high resolution primers

DEFF Research Database (Denmark)

Pedersen, Lasse Eggers; Jungersen, Gregers; Sørensen, Maria Rathmann

2014-01-01

of such peptide-MHC complexes (pMHC) naïve T cells can become activated and respond to a given pathogen leading to its elimination and the generation of memory cells. Hence SLA plays a crucial role in maintaining overall adaptive immunologic resistance to pathogens. Knowing which SLA alleles that are commonly...... occurring can be of great importance in regard to future vaccine development and the establishment of immune protection in swine through broad coverage, highly specific, subunit based vaccination against viruses such as swine influenza, porcine reproductive and respiratory syndrome virus, vesicular...

Genetic structure, diversity, and allelic richness in composite collection and reference set in chickpea (Cicer arietinum L.

Directory of Open Access Journals (Sweden)

Gowda Cholenahalli LL

2008-10-01

Full Text Available Abstract Background Plant genetic resources (PGR are the basic raw materials for future genetic progress and an insurance against unforeseen threats to agricultural production. An extensive characterization of PGR provides an opportunity to dissect structure, mine allelic variations, and identify diverse accessions for crop improvement. The Generation Challenge Program http://www.generationcp.org conceptualized the development of "composite collections" and extraction of "reference sets" from these for more efficient tapping of global crop-related genetic resources. In this study, we report the genetic structure, diversity and allelic richness in a composite collection of chickpea using SSR markers, and formation of a reference set of 300 accessions. Results The 48 SSR markers detected 1683 alleles in 2915 accessions, of which, 935 were considered rare, 720 common and 28 most frequent. The alleles per locus ranged from 14 to 67, averaged 35, and the polymorphic information content was from 0.467 to 0.974, averaged 0.854. Marker polymorphism varied between groups of accessions in the composite collection and reference set. A number of group-specific alleles were detected: 104 in Kabuli, 297 in desi, and 69 in wild Cicer; 114 each in Mediterranean and West Asia (WA, 117 in South and South East Asia (SSEA, and 10 in African region accessions. Desi and kabuli shared 436 alleles, while wild Cicer shared 17 and 16 alleles with desi and kabuli, respectively. The accessions from SSEA and WA shared 74 alleles, while those from Mediterranean 38 and 33 alleles with WA and SSEA, respectively. Desi chickpea contained a higher proportion of rare alleles (53% than kabuli (46%, while wild Cicer accessions were devoid of rare alleles. A genotype-based reference set captured 1315 (78% of the 1683 composite collection alleles of which 463 were rare, 826 common, and 26 the most frequent alleles. The neighbour-joining tree diagram of this reference set represents

Structure of HLA-A*0301 in complex with a peptide of proteolipid protein: insights into the role of HLA-A alleles in susceptibility to multiple sclerosis

International Nuclear Information System (INIS)

McMahon, Róisín M.; Friis, Lone; Siebold, Christian; Friese, Manuel A.; Fugger, Lars; Jones, E. Yvonne

2011-01-01

The structure of the human major histocompatability (MHC) class I molecule HLA-A*0301 (HLA-A3) in complex with a nonameric peptide (KLIETYFSK) has been determined by X-ray crystallography to 2.7 Å resolution. The structure of the human major histocompatability (MHC) class I molecule HLA-A*0301 (HLA-A3) in complex with a nonameric peptide (KLIETYFSK) has been determined by X-ray crystallography to 2.7 Å resolution. HLA-A3 is a predisposing allele for multiple sclerosis (MS), an autoimmune disease of the central nervous system. The KLIETYFSK peptide is a naturally processed epitope of proteolipid protein, a myelin protein and candidate target for immune-mediated myelin destruction in MS. Comparison of the structure of HLA-A3 with that of HLA-A2, an MHC class I molecule which is protective against MS, indicates that both MHC class I molecules present very similar faces for T-cell receptor recognition whilst differing in the specificity of their peptide-binding grooves. These characteristics may underlie the opposing (predisposing versus protective) associations that they exhibit both in humans and in mouse models of MS-like disease. Furthermore, subtle alterations within the peptide-binding groove of HLA-A3 and other A3-like MHC class I molecules, members of the so-called A3 superfamily, may be sufficient to alter their presentation of autoantigen peptides such as KLIETYFSK. This in turn may modulate their contribution to the associated risk of autoimmune disease

Allelic Dropout During Polymerase Chain Reaction due to G-Quadruplex Structures and DNA Methylation Is Widespread at Imprinted Human Loci.

Science.gov (United States)

Stevens, Aaron J; Taylor, Millie G; Pearce, Frederick Grant; Kennedy, Martin A

2017-03-10

Loss of one allele during polymerase chain reaction (PCR) amplification of DNA, known as allelic dropout, can be caused by a variety of mechanisms. Allelic dropout during PCR may have profound implications for molecular diagnostic and research procedures that depend on PCR and assume biallelic amplification has occurred. Complete allelic dropout due to the combined effects of cytosine methylation and G-quadruplex formation was previously described for a differentially methylated region of the human imprinted gene, MEST We now demonstrate that this parent-of-origin specific allelic dropout can potentially occur at several other genomic regions that display genomic imprinting and have propensity for G-quadruplex formation, including AIM1 , BLCAP , DNMT1 , PLAGL1 , KCNQ1 , and GRB10 These findings demonstrate that systematic allelic dropout during PCR is a general phenomenon for regions of the genome where differential allelic methylation and G-quadruplex motifs coincide, and suggest that great care must be taken to ensure biallelic amplification is occurring in such situations. Copyright © 2017 Stevens et al.

Productive Parallel Programming: The PCN Approach

Directory of Open Access Journals (Sweden)

Ian Foster

1992-01-01

Full Text Available We describe the PCN programming system, focusing on those features designed to improve the productivity of scientists and engineers using parallel supercomputers. These features include a simple notation for the concise specification of concurrent algorithms, the ability to incorporate existing Fortran and C code into parallel applications, facilities for reusing parallel program components, a portable toolkit that allows applications to be developed on a workstation or small parallel computer and run unchanged on supercomputers, and integrated debugging and performance analysis tools. We survey representative scientific applications and identify problem classes for which PCN has proved particularly useful.

Modelling and parallel calculation of a kinetic boundary layer

International Nuclear Information System (INIS)

Perlat, Jean Philippe

1998-01-01

This research thesis aims at addressing reliability and cost issues in the calculation by numeric simulation of flows in transition regime. The first step has been to reduce calculation cost and memory space for the Monte Carlo method which is known to provide performance and reliability for rarefied regimes. Vector and parallel computers allow this objective to be reached. Here, a MIMD (multiple instructions, multiple data) machine has been used which implements parallel calculation at different levels of parallelization. Parallelization procedures have been adapted, and results showed that parallelization by calculation domain decomposition was far more efficient. Due to reliability issue related to the statistic feature of Monte Carlo methods, a new deterministic model was necessary to simulate gas molecules in transition regime. New models and hyperbolic systems have therefore been studied. One is chosen which allows thermodynamic values (density, average velocity, temperature, deformation tensor, heat flow) present in Navier-Stokes equations to be determined, and the equations of evolution of thermodynamic values are described for the mono-atomic case. Numerical resolution of is reported. A kinetic scheme is developed which complies with the structure of all systems, and which naturally expresses boundary conditions. The validation of the obtained 14 moment-based model is performed on shock problems and on Couette flows [fr

Parallelizing AT with MatlabMPI

International Nuclear Information System (INIS)

2011-01-01

The Accelerator Toolbox (AT) is a high-level collection of tools and scripts specifically oriented toward solving problems dealing with computational accelerator physics. It is integrated into the MATLAB environment, which provides an accessible, intuitive interface for accelerator physicists, allowing researchers to focus the majority of their efforts on simulations and calculations, rather than programming and debugging difficulties. Efforts toward parallelization of AT have been put in place to upgrade its performance to modern standards of computing. We utilized the packages MatlabMPI and pMatlab, which were developed by MIT Lincoln Laboratory, to set up a message-passing environment that could be called within MATLAB, which set up the necessary pre-requisites for multithread processing capabilities. On local quad-core CPUs, we were able to demonstrate processor efficiencies of roughly 95% and speed increases of nearly 380%. By exploiting the efficacy of modern-day parallel computing, we were able to demonstrate incredibly efficient speed increments per processor in AT's beam-tracking functions. Extrapolating from prediction, we can expect to reduce week-long computation runtimes to less than 15 minutes. This is a huge performance improvement and has enormous implications for the future computing power of the accelerator physics group at SSRL. However, one of the downfalls of parringpass is its current lack of transparency; the pMatlab and MatlabMPI packages must first be well-understood by the user before the system can be configured to run the scripts. In addition, the instantiation of argument parameters requires internal modification of the source code. Thus, parringpass, cannot be directly run from the MATLAB command line, which detracts from its flexibility and user-friendliness. Future work in AT's parallelization will focus on development of external functions and scripts that can be called from within MATLAB and configured on multiple nodes, while

Algorithms for parallel computers

International Nuclear Information System (INIS)

Churchhouse, R.F.

1985-01-01

Until relatively recently almost all the algorithms for use on computers had been designed on the (usually unstated) assumption that they were to be run on single processor, serial machines. With the introduction of vector processors, array processors and interconnected systems of mainframes, minis and micros, however, various forms of parallelism have become available. The advantage of parallelism is that it offers increased overall processing speed but it also raises some fundamental questions, including: (i) which, if any, of the existing 'serial' algorithms can be adapted for use in the parallel mode. (ii) How close to optimal can such adapted algorithms be and, where relevant, what are the convergence criteria. (iii) How can we design new algorithms specifically for parallel systems. (iv) For multi-processor systems how can we handle the software aspects of the interprocessor communications. Aspects of these questions illustrated by examples are considered in these lectures. (orig.)

HAlign-II: efficient ultra-large multiple sequence alignment and phylogenetic tree reconstruction with distributed and parallel computing.

Science.gov (United States)

Wan, Shixiang; Zou, Quan

2017-01-01

Multiple sequence alignment (MSA) plays a key role in biological sequence analyses, especially in phylogenetic tree construction. Extreme increase in next-generation sequencing results in shortage of efficient ultra-large biological sequence alignment approaches for coping with different sequence types. Distributed and parallel computing represents a crucial technique for accelerating ultra-large (e.g. files more than 1 GB) sequence analyses. Based on HAlign and Spark distributed computing system, we implement a highly cost-efficient and time-efficient HAlign-II tool to address ultra-large multiple biological sequence alignment and phylogenetic tree construction. The experiments in the DNA and protein large scale data sets, which are more than 1GB files, showed that HAlign II could save time and space. It outperformed the current software tools. HAlign-II can efficiently carry out MSA and construct phylogenetic trees with ultra-large numbers of biological sequences. HAlign-II shows extremely high memory efficiency and scales well with increases in computing resource. THAlign-II provides a user-friendly web server based on our distributed computing infrastructure. HAlign-II with open-source codes and datasets was established at http://lab.malab.cn/soft/halign.

Multi-lane detection based on multiple vanishing points detection

Science.gov (United States)

Li, Chuanxiang; Nie, Yiming; Dai, Bin; Wu, Tao

2015-03-01

Lane detection plays a significant role in Advanced Driver Assistance Systems (ADAS) for intelligent vehicles. In this paper we present a multi-lane detection method based on multiple vanishing points detection. A new multi-lane model assumes that a single lane, which has two approximately parallel boundaries, may not parallel to others on road plane. Non-parallel lanes associate with different vanishing points. A biological plausibility model is used to detect multiple vanishing points and fit lane model. Experimental results show that the proposed method can detect both parallel lanes and non-parallel lanes.

MPI_XSTAR: MPI-based Parallelization of the XSTAR Photoionization Program

Science.gov (United States)

Danehkar, Ashkbiz; Nowak, Michael A.; Lee, Julia C.; Smith, Randall K.

2018-02-01

We describe a program for the parallel implementation of multiple runs of XSTAR, a photoionization code that is used to predict the physical properties of an ionized gas from its emission and/or absorption lines. The parallelization program, called MPI_XSTAR, has been developed and implemented in the C++ language by using the Message Passing Interface (MPI) protocol, a conventional standard of parallel computing. We have benchmarked parallel multiprocessing executions of XSTAR, using MPI_XSTAR, against a serial execution of XSTAR, in terms of the parallelization speedup and the computing resource efficiency. Our experience indicates that the parallel execution runs significantly faster than the serial execution, however, the efficiency in terms of the computing resource usage decreases with increasing the number of processors used in the parallel computing.

The variability of sesquiterpenes emitted from two Zea mays cultivars is controlled by allelic variation of two terpene synthase genes encoding stereoselective multiple product enzymes.

Science.gov (United States)

Köllner, Tobias G; Schnee, Christiane; Gershenzon, Jonathan; Degenhardt, Jörg

2004-05-01

The mature leaves and husks of Zea mays release a complex blend of terpene volatiles after anthesis consisting predominantly of bisabolane-, sesquithujane-, and bergamotane-type sesquiterpenes. The varieties B73 and Delprim release the same volatile constituents but in significantly different proportions. To study the molecular genetic and biochemical mechanisms controlling terpene diversity and distribution in these varieties, we isolated the closely related terpene synthase genes terpene synthase4 (tps4) and tps5 from both varieties. The encoded enzymes, TPS4 and TPS5, each formed the same complex mixture of sesquiterpenes from the precursor farnesyl diphosphate but with different proportions of products. These mixtures correspond to the sesquiterpene blends observed in the varieties B73 and Delprim, respectively. The differences in the stereoselectivity of TPS4 and TPS5 are determined by four amino acid substitutions with the most important being a Gly instead of an Ala residue at position 409 at the catalytic site of the enzyme. Although both varieties contain tps4 and tps5 alleles, their differences in terpene composition result from the fact that B73 has only a single functional allele of tps4 and no functional alleles of tps5, whereas Delprim has only a functional allele of tps5 and no functional alleles of tps4. Lack of functionality was shown to be attributable to frame-shift mutations or amino acid substitutions that greatly reduce the activity of their encoded proteins. Therefore, the diversity of sesquiterpenes in these two maize cultivars is strongly influenced by single nucleotide changes in the alleles of two terpene synthase genes.

Always look on both sides: phylogenetic information conveyed by simple sequence repeat allele sequences.

Directory of Open Access Journals (Sweden)

Stéphanie Barthe

Full Text Available Simple sequence repeat (SSR markers are widely used tools for inferences about genetic diversity, phylogeography and spatial genetic structure. Their applications assume that variation among alleles is essentially caused by an expansion or contraction of the number of repeats and that, accessorily, mutations in the target sequences follow the stepwise mutation model (SMM. Generally speaking, PCR amplicon sizes are used as direct indicators of the number of SSR repeats composing an allele with the data analysis either ignoring the extent of allele size differences or assuming that there is a direct correlation between differences in amplicon size and evolutionary distance. However, without precisely knowing the kind and distribution of polymorphism within an allele (SSR and the associated flanking region (FR sequences, it is hard to say what kind of evolutionary message is conveyed by such a synthetic descriptor of polymorphism as DNA amplicon size. In this study, we sequenced several SSR alleles in multiple populations of three divergent tree genera and disentangled the types of polymorphisms contained in each portion of the DNA amplicon containing an SSR. The patterns of diversity provided by amplicon size variation, SSR variation itself, insertions/deletions (indels, and single nucleotide polymorphisms (SNPs observed in the FRs were compared. Amplicon size variation largely reflected SSR repeat number. The amount of variation was as large in FRs as in the SSR itself. The former contributed significantly to the phylogenetic information and sometimes was the main source of differentiation among individuals and populations contained by FR and SSR regions of SSR markers. The presence of mutations occurring at different rates within a marker's sequence offers the opportunity to analyse evolutionary events occurring on various timescales, but at the same time calls for caution in the interpretation of SSR marker data when the distribution of within

Detection of EGFR mutations in plasma and biopsies from non-small cell lung cancer patients by allele-specific PCR assays

DEFF Research Database (Denmark)

Weber, Britta; Meldgaard, Peter; Hager, Henrik

2014-01-01

samples with allele-specific PCR assays. METHODS: Pairs of the diagnostic biopsy and plasma obtained just prior to start of erlotinib treatment were collected from 199 patients with adenocarcinoma of non-small-cell lung cancer. DNA from both sample types was isolated and examined for the presence...... of mutations in exons 18-21 of the EGFR gene, employing the cobas(®) EGFR Tissue Test and cobas(®) EGFR Blood Test (in development, Roche Molecular Systems, Inc., CA, USA). RESULTS: Test results were obtained in all 199 (100%) plasma samples and 196/199 (98%) of the biopsies. EGFR-activating mutations were...... identified in 24/199 (12%) plasma samples and 28/196 (14%) biopsy samples, and 17/196 (9%) matched pairs contained the same mutation. Six EGFR mutations were present only in plasma samples but not in the biopsy samples. The overall concordance of the EGFR gene mutations detected in plasma and biopsy tissue...

Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots.

Science.gov (United States)

Baker, Christopher L; Petkova, Pavlina; Walker, Michael; Flachs, Petr; Mihola, Ondrej; Trachtulec, Zdenek; Petkov, Petko M; Paigen, Kenneth

2015-09-01

Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity, questions remain about the influences different alleles have in heterozygous individuals where the two variant forms of PRDM9 typically do not activate equivalent populations of hotspots. We now find that, in addition to activating its own hotspots, the presence of one Prdm9 allele can modify the activity of hotspots activated by the other allele. PRDM9 function is also dosage sensitive; Prdm9+/- heterozygous null mice have reduced numbers and less active hotspots and increased numbers of aberrant germ cells. In mice carrying two Prdm9 alleles, there is allelic competition; the stronger Prdm9 allele can partially or entirely suppress chromatin modification and recombination at hotspots of the weaker allele. In cell cultures, PRDM9 protein variants form functional heteromeric complexes which can bind hotspots sequences. When a heteromeric complex binds at a hotspot of one PRDM9 variant, the other PRDM9 variant, which would otherwise not bind, can still methylate hotspot nucleosomes. We propose that in heterozygous individuals the underlying molecular mechanism of allelic suppression results from formation of PRDM9 heteromers, where the DNA binding activity of one protein variant dominantly directs recombination initiation towards its own hotspots, effectively titrating down recombination by the other protein variant. In natural populations with many heterozygous individuals, allelic competition will influence the recombination landscape.

Xyce parallel electronic simulator : users' guide.

Energy Technology Data Exchange (ETDEWEB)

Mei, Ting; Rankin, Eric Lamont; Thornquist, Heidi K.; Santarelli, Keith R.; Fixel, Deborah A.; Coffey, Todd Stirling; Russo, Thomas V.; Schiek, Richard Louis; Warrender, Christina E.; Keiter, Eric Richard; Pawlowski, Roger Patrick

2011-05-01

This manual describes the use of the Xyce Parallel Electronic Simulator. Xyce has been designed as a SPICE-compatible, high-performance analog circuit simulator, and has been written to support the simulation needs of the Sandia National Laboratories electrical designers. This development has focused on improving capability over the current state-of-the-art in the following areas: (1) Capability to solve extremely large circuit problems by supporting large-scale parallel computing platforms (up to thousands of processors). Note that this includes support for most popular parallel and serial computers; (2) Improved performance for all numerical kernels (e.g., time integrator, nonlinear and linear solvers) through state-of-the-art algorithms and novel techniques. (3) Device models which are specifically tailored to meet Sandia's needs, including some radiation-aware devices (for Sandia users only); and (4) Object-oriented code design and implementation using modern coding practices that ensure that the Xyce Parallel Electronic Simulator will be maintainable and extensible far into the future. Xyce is a parallel code in the most general sense of the phrase - a message passing parallel implementation - which allows it to run efficiently on the widest possible number of computing platforms. These include serial, shared-memory and distributed-memory parallel as well as heterogeneous platforms. Careful attention has been paid to the specific nature of circuit-simulation problems to ensure that optimal parallel efficiency is achieved as the number of processors grows. The development of Xyce provides a platform for computational research and development aimed specifically at the needs of the Laboratory. With Xyce, Sandia has an 'in-house' capability with which both new electrical (e.g., device model development) and algorithmic (e.g., faster time-integration methods, parallel solver algorithms) research and development can be performed. As a result, Xyce is

Parallelization of Subchannel Analysis Code MATRA

International Nuclear Information System (INIS)

Kim, Seongjin; Hwang, Daehyun; Kwon, Hyouk

2014-01-01

A stand-alone calculation of MATRA code used up pertinent computing time for the thermal margin calculations while a relatively considerable time is needed to solve the whole core pin-by-pin problems. In addition, it is strongly required to improve the computation speed of the MATRA code to satisfy the overall performance of the multi-physics coupling calculations. Therefore, a parallel approach to improve and optimize the computability of the MATRA code is proposed and verified in this study. The parallel algorithm is embodied in the MATRA code using the MPI communication method and the modification of the previous code structure was minimized. An improvement is confirmed by comparing the results between the single and multiple processor algorithms. The speedup and efficiency are also evaluated when increasing the number of processors. The parallel algorithm was implemented to the subchannel code MATRA using the MPI. The performance of the parallel algorithm was verified by comparing the results with those from the MATRA with the single processor. It is also noticed that the performance of the MATRA code was greatly improved by implementing the parallel algorithm for the 1/8 core and whole core problems

Allele-Selective Transcriptome Recruitment to Polysomes Primed for Translation: Protein-Coding and Noncoding RNAs, and RNA Isoforms.

Directory of Open Access Journals (Sweden)

Roshan Mascarenhas

Full Text Available mRNA translation into proteins is highly regulated, but the role of mRNA isoforms, noncoding RNAs (ncRNAs, and genetic variants remains poorly understood. mRNA levels on polysomes have been shown to correlate well with expressed protein levels, pointing to polysomal loading as a critical factor. To study regulation and genetic factors of protein translation we measured levels and allelic ratios of mRNAs and ncRNAs (including microRNAs in lymphoblast cell lines (LCL and in polysomal fractions. We first used targeted assays to measure polysomal loading of mRNA alleles, confirming reported genetic effects on translation of OPRM1 and NAT1, and detecting no effect of rs1045642 (3435C>T in ABCB1 (MDR1 on polysomal loading while supporting previous results showing increased mRNA turnover of the 3435T allele. Use of high-throughput sequencing of complete transcript profiles (RNA-Seq in three LCLs revealed significant differences in polysomal loading of individual RNA classes and isoforms. Correlated polysomal distribution between protein-coding and non-coding RNAs suggests interactions between them. Allele-selective polysome recruitment revealed strong genetic influence for multiple RNAs, attributable either to differential expression of RNA isoforms or to differential loading onto polysomes, the latter defining a direct genetic effect on translation. Genes identified by different allelic RNA ratios between cytosol and polysomes were enriched with published expression quantitative trait loci (eQTLs affecting RNA functions, and associations with clinical phenotypes. Polysomal RNA-Seq combined with allelic ratio analysis provides a powerful approach to study polysomal RNA recruitment and regulatory variants affecting protein translation.

Parallel algorithms for continuum dynamics

International Nuclear Information System (INIS)

Hicks, D.L.; Liebrock, L.M.

1987-01-01

Simply porting existing parallel programs to a new parallel processor may not achieve the full speedup possible; to achieve the maximum efficiency may require redesigning the parallel algorithms for the specific architecture. The authors discuss here parallel algorithms that were developed first for the HEP processor and then ported to the CRAY X-MP/4, the ELXSI/10, and the Intel iPSC/32. Focus is mainly on the most recent parallel processing results produced, i.e., those on the Intel Hypercube. The applications are simulations of continuum dynamics in which the momentum and stress gradients are important. Examples of these are inertial confinement fusion experiments, severe breaks in the coolant system of a reactor, weapons physics, shock-wave physics. Speedup efficiencies on the Intel iPSC Hypercube are very sensitive to the ratio of communication to computation. Great care must be taken in designing algorithms for this machine to avoid global communication. This is much more critical on the iPSC than it was on the three previous parallel processors

SSR allelic variation in almond (Prunus dulcis Mill.).

Science.gov (United States)

Xie, Hua; Sui, Yi; Chang, Feng-Qi; Xu, Yong; Ma, Rong-Cai

2006-01-01

Sixteen SSR markers including eight EST-SSR and eight genomic SSRs were used for genetic diversity analysis of 23 Chinese and 15 international almond cultivars. EST- and genomic SSR markers previously reported in species of Prunus, mainly peach, proved to be useful for almond genetic analysis. DNA sequences of 117 alleles of six of the 16 SSR loci were analysed to reveal sequence variation among the 38 almond accessions. For the four SSR loci with AG/CT repeats, no insertions or deletions were observed in the flanking regions of the 98 alleles sequenced. Allelic size variation of these loci resulted exclusively from differences in the structures of repeat motifs, which involved interruptions or occurrences of new motif repeats in addition to varying number of AG/CT repeats. Some alleles had a high number of uninterrupted repeat motifs, indicating that SSR mutational patterns differ among alleles at a given SSR locus within the almond species. Allelic homoplasy was observed in the SSR loci because of base substitutions, interruptions or compound repeat motifs. Substitutions in the repeat regions were found at two SSR loci, suggesting that point mutations operate on SSRs and hinder the further SSR expansion by introducing repeat interruptions to stabilize SSR loci. Furthermore, it was shown that some potential point mutations in the flanking regions are linked with new SSR repeat motif variation in almond and peach.

Parallelism measurement for base plate of standard artifact with multiple tactile approaches

Science.gov (United States)

Ye, Xiuling; Zhao, Yan; Wang, Yiwen; Wang, Zhong; Fu, Luhua; Liu, Changjie

2018-01-01

Nowadays, as workpieces become more precise and more specialized which results in more sophisticated structures and higher accuracy for the artifacts, higher requirements have been put forward for measuring accuracy and measuring methods. As an important method to obtain the size of workpieces, coordinate measuring machine (CMM) has been widely used in many industries. In order to achieve the calibration of a self-developed CMM, it is found that the parallelism of the base plate used for fixing the standard artifact is an important factor which affects the measurement accuracy in the process of studying self-made high-precision standard artifact. And aimed to measure the parallelism of the base plate, by using the existing high-precision CMM, gauge blocks, dial gauge and marble platform with the tactile approach, three methods for parallelism measurement of workpieces are employed, and comparisons are made within the measurement results. The results of experiments show that the final accuracy of all the three methods is able to reach micron level and meets the measurement requirements. Simultaneously, these three approaches are suitable for different measurement conditions which provide a basis for rapid and high-precision measurement under different equipment conditions.

A new electrophoresis technique to separate microsatellite alleles ...

African Journals Online (AJOL)

A new electrophoresis technique to separate microsatellite alleles* ... African Journal of Biotechnology ... with the CEQTM 8000 Genetic Analysis System and ABI 3130xl DNA Sequencer easily separated products and determined allelic size, ...

Characterization of ROP18 alleles in human toxoplasmosis.

Science.gov (United States)

Sánchez, Víctor; de-la-Torre, Alejandra; Gómez-Marín, Jorge Enrique

2014-04-01

The role of the virulent gene ROP18 polymorphisms is not known in human toxoplasmosis. A total of 320 clinical samples were analyzed. In samples positive for ROP18 gene, we determined by an allele specific PCR, if patients got the upstream insertion positive ROP18 sequence Toxoplasma strain (mouse avirulent strain) or the upstream insertion negative ROP18 sequence Toxoplasma strain (mouse virulent strain). We designed an ELISA assay for antibodies against ROP18 derived peptides from the three major clonal lineages of Toxoplasma. 20 clinical samples were of quality for ROP18 allele analysis. In patients with ocular toxoplasmosis, a higher inflammatory reaction on eye was associated to a PCR negative result for the upstream region of ROP18. 23.3%, 33% and 16.6% of serums from individuals with ocular toxoplasmosis were positive for type I, type II and type III ROP18 derived peptides, respectively but this assay was affected by cross reaction. The absence of Toxoplasma ROP18 promoter insertion sequence in ocular toxoplasmosis was correlated with severe ocular inflammatory response. Determination of antibodies against ROP18 protein was not useful for serotyping in human toxoplasmosis. © 2013.

Directional Positive Selection on an Allele of Arbitrary Dominance

OpenAIRE

Teshima, Kosuke M.; Przeworski, Molly

2006-01-01

Most models of positive directional selection assume codominance of the beneficial allele. We examine the importance of this assumption by implementing a coalescent model of positive directional selection with arbitrary dominance. We find that, for a given mean fixation time, a beneficial allele has a much weaker effect on diversity at linked neutral sites when the allele is recessive.

Characterization of new allele influencing flowering time in bread wheat introgressed from Triticum militinae.

Science.gov (United States)

Ivaničová, Zuzana; Jakobson, Irena; Reis, Diana; Šafář, Jan; Milec, Zbyněk; Abrouk, Michael; Doležel, Jaroslav; Järve, Kadri; Valárik, Miroslav

2016-09-25

Flowering time variation was identified within a mapping population of doubled haploid lines developed from a cross between the introgressive line 8.1 and spring bread wheat cv. Tähti. The line 8.1 carried introgressions from tetraploid Triticum militinae in the cv. Tähti genetic background on chromosomes 1A, 2A, 4A, 5A, 7A, 1B and 5B. The most significant QTL for the flowering time variation was identified within the introgressed region on chromosome 5A and its largest effect was associated with the VRN-A1 locus, accounting for up to 70% of phenotypic variance. The allele of T. militinae origin was designated as VRN-A1f-like. The effect of the VRN-A1f-like allele was verified in two other mapping populations. QTL analysis identified that in cv. Tähti and cv. Mooni genetic background, VRN-A1f-like allele incurred a delay of 1.9-18.6 days in flowering time, depending on growing conditions. Sequence comparison of the VRN-A1f-like and VRN-A1a alleles from the parental lines of the mapping populations revealed major mutations in the promoter region as well as in the first intron, including insertion of a MITE element and a large deletion. The sequence variation allowed construction of specific diagnostic PCR markers for VRN-A1f-like allele determination. Identification and quantification of the effect of the VRN-A1f-like allele offers a useful tool for wheat breeding and for studying fine-scale regulation of flowering pathways in wheat. Copyright © 2016 Elsevier B.V. All rights reserved.

An SSP-PCR method for the rapid detection of disease-associated alleles HLA-A*29 and HLA-B*51.

Science.gov (United States)

Amstutz, U; Schaerer, D; Andrey, G; Wirthmueller, U; Largiadèr, C R

2018-05-15

HLA-A*29 and HLA-B*51 are associated with birdshot uveitis and Behçet's disease, respectively, and are used as a diagnostic criterion in patients with suspected disease, requiring their detection in diagnostic laboratories. While commercial tests for individual HLA alleles are available for other disease-associated HLA variants, no similar allele-specific assays are available for HLA-A*29 and -B*51. Here, we report SSP-PCR methods for the detection of HLA-A*29 and -B*51 using a single PCR reaction per allele. The assays were tested in 30 and 32 previously HLA-typed samples, respectively, representing >97% of HLA-A alleles and >93% of HLA-B alleles in a European population. A concordance of 100% was observed with previous typing results, validating these methods for use in a diagnostic or research context. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

HLA alleles and haplotypes in Burmese (Myanmarese) and Karen in Thailand.

Science.gov (United States)

Kongmaroeng, C; Romphruk, A; Puapairoj, C; Leelayuwat, C; Kulski, J K; Inoko, H; Dunn, D S; Romphruk, A V

2015-09-01

This is the first report on human leukocyte antigen (HLA) allele and haplotype frequencies at three class I loci and two class II loci in unrelated healthy individuals from two ethnic groups, 170 Burmese and 200 Karen, originally from Burma (Myanmar), but sampled while residing in Thailand. Overall, the HLA allele and haplotype frequencies detected by polymerase chain reaction sequence-specific primer (PCR-SSP) at five loci (A, B, C, DRB1 and DRQB1) at low resolution showed distinct differences between the Burmese and Karen. In Burmese, five HLA-B*15 haplotypes with different HLA-A and HLA-DR/DQ combinations were detected with three of these not previously reported in other Asian populations. The data are important in the fields of anthropology, transplantation and disease-association studies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Allelic imbalance modulates surface expression of the tolerance-inducing HLA-G molecule on primary trophoblast cells.

Science.gov (United States)

Djurisic, S; Teiblum, S; Tolstrup, C K; Christiansen, O B; Hviid, T V F

2015-03-01

The HLA-G molecule is expressed on trophoblast cells at the feto-maternal interface, where it interacts with local immune cells, and upholds tolerance against the semi-allogeneic fetus. Aberrant HLA-G expression in the placenta and reduced soluble HLA-G levels are observed in pregnancy complications, partly explained by HLA-G polymorphisms which are associated with differences in the alternative splicing pattern and of the stability of HLA-G mRNA. Of special importance is a 14 bp insertion/deletion polymorphism located in the 3'-untranslated region of the HLA-G gene. In the current study, we present novel evidence for allelic imbalance of the 14 bp insertion/deletion polymorphism, using a very accurate and sensitive Digital droplet PCR technique. Allelic imbalance in heterozygous samples was observed as differential expression levels of 14 bp insertion/deletion allele-specific mRNA transcripts, which was further associated with low levels of HLA-G surface expression on primary trophoblast cells. Full gene sequencing of HLA-G allowed us to study correlations between HLA-G extended haplotypes and single-nucleotide polymorphisms and HLA-G surface expression. We found that a 1:1 expression (allelic balance) of the 14 bp insertion/deletion mRNA alleles was associated with high surface expression of HLA-G and with a specific HLA-G extended haplotype. The 14 bp del/del genotype was associated with a significantly lower abundance of the G1 mRNA isoform, and a higher abundance of the G3 mRNA isoform. Overall, the present study provides original evidence for allelic imbalance of the 14 bp insertion/deletion polymorphism, which influences HLA-G surface expression on primary trophoblast cells, considered to be important in the pathogenesis of pre-eclampsia and other pregnancy complications. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Parallel object-oriented term rewriting : the booleans

NARCIS (Netherlands)

Rodenburg, P.H.; Vrancken, J.L.M.

As a first case study in parallel object-oriented term rewriting, we give two implementations of term rewriting algorithms for boolean terms, using the parallel object-oriented features of the language Pool-T. The term rewriting systems are specified in the specification formalism

Genetic analysis of gamma-ray mutagenesis in yeast. II. Allele-specific control of mutagenesis

International Nuclear Information System (INIS)

McKee, R.H.; Lawrence, C.W.

1979-01-01

We find that partially different sets of gene functions are required for the production of different kinds of mutations induced by 60 Co γ rays in Saccharomyces cerevisiae. This observation is very similar to others made previously with respect to uv mutagenesis and confirms the conclusion that such distinctive patterns of genetic control reflect properties of the test alleles and their genetic locations, rather than the kinds of lesions required to revert them. The data also support the model of mutagenic repair outlined in the first paper of this series in which partially different sets of gene functions are required for the production of different kinds of mutations, the formation of mutations at different genetic sites and the induction of mutations by different mutagens

One weird trick for parallelizing convolutional neural networks

OpenAIRE

Krizhevsky, Alex

2014-01-01

I present a new way to parallelize the training of convolutional neural networks across multiple GPUs. The method scales significantly better than all alternatives when applied to modern convolutional neural networks.

Association between diabetes type 1 and DQB1 alleles in a case-control study conducted in Montevideo, Uruguay.

Science.gov (United States)

Mimbacas, Adriana; Pérez-Bravo, Francisco; Hidalgo, Pedro C; Javiel, Gerardo; Pisciottano, Carmen; Grignola, Rosario; Jorge, Ana María; Gallino, Juan Pablo; Gasagoite, Jackeline; Cardoso, Horacio

2003-03-31

We studied HLA DQB1 allele frequencies and the relative risk (RR) of various genotypes in 72 type 1 diabetic patients and 40 control individuals in Uruguay. This is a tri-racial (Caucasian, Black and Indo-American) mixed population. The products of the polymerase chain reaction amplifications were hybridized with oligonucleotides by allele-specific oligonucleotide reverse or dot blot methods. Significant differences between these two groups were observed only for allele DQB1*0302 (35%, RR = 7.34, P<0.001). The frequency of the alleles carrying a non-aspartic acid residue at position 57 was significantly higher in the diabetic patients (85 vs 53%, P<0.001). In contrast, the frequency of Asp alleles was negatively associated with type 1 diabetes (RR = 0.20, P<0.001). The genotype DQB1*0302/DQB1*0201 (33%, RR = 5.41, P<0.05) was positively associated with this disease. The genotype frequencies associated with type 1 diabetes in our population were significantly different from what is known for Caucasian and Black populations as well as compared with another admixed population, from Chile.

Dynamic ligand modulation of EPO receptor pools, and dysregulation by polycythemia-associated EPOR alleles.

Directory of Open Access Journals (Sweden)

Seema Singh

Full Text Available Erythropoietin (EPO and its cell surface receptor (EPOR are essential for erythropoiesis; can modulate non-erythroid target tissues; and have been reported to affect the progression of certain cancers. Basic studies of EPOR expression and trafficking, however, have been hindered by low-level EPOR occurrence, and the limited specificity of anti-EPOR antibodies. Consequently, these aspects of EPOR biology are not well defined, nor are actions of polycythemia- associated mutated EPOR alleles. Using novel rabbit monoclonal antibodies to intracellular, PY- activated and extracellular EPOR domains, the following properties of the endogenous hEPOR in erythroid progenitors first are unambiguously defined. 1 High- Mr EPOR forms become obviously expressed only when EPO is limited. 2 EPOR-68K plus -70K species sequentially accumulate, and EPOR-70K comprises an apparent cell surface EPOR population. 3 Brefeldin A, N-glycanase and associated analyses point to EPOR-68K as a core-glycosylated intracellular EPOR pool (of modest size. 4 In contrast to recent reports, EPOR inward trafficking is shown (in UT7epo cells, and primary proerythroblasts to be sharply ligand-dependent. Beyond this, when C-terminal truncated hEPOR-T mutant alleles as harbored by polycythemia patients are co-expressed with the wild-type EPOR in EPO-dependent erythroid progenitors, several specific events become altered. First, EPOR-T alleles are persistently activated upon EPO- challenge, yet are also subject to apparent turn-over (to low-Mr EPOR products. Furthermore, during exponential cell growth EPOR-T species become both over-represented, and hyper-activated. Interestingly, EPOR-T expression also results in an EPO dose-dependent loss of endogenous wild-type EPOR's (and, therefore, a squelching of EPOR C-terminal- mediated negative feedback effects. New knowledge concerning regulated EPOR expression and trafficking therefore is provided, together with new insight into mechanisms via

Dynamic Ligand Modulation of EPO Receptor Pools, and Dysregulation by Polycythemia-Associated EPOR Alleles

Science.gov (United States)

Singh, Seema; Verma, Rakesh; Pradeep, Anamika; Leu, Karen; Mortensen, R. Bruce; Young, Peter R.; Oyasu, Miho; Schatz, Peter J.; Green, Jennifer M.; Wojchowski, Don M.

2012-01-01

Erythropoietin (EPO) and its cell surface receptor (EPOR) are essential for erythropoiesis; can modulate non-erythroid target tissues; and have been reported to affect the progression of certain cancers. Basic studies of EPOR expression and trafficking, however, have been hindered by low-level EPOR occurrence, and the limited specificity of anti-EPOR antibodies. Consequently, these aspects of EPOR biology are not well defined, nor are actions of polycythemia- associated mutated EPOR alleles. Using novel rabbit monoclonal antibodies to intracellular, PY- activated and extracellular EPOR domains, the following properties of the endogenous hEPOR in erythroid progenitors first are unambiguously defined. 1) High- Mr EPOR forms become obviously expressed only when EPO is limited. 2) EPOR-68K plus -70K species sequentially accumulate, and EPOR-70K comprises an apparent cell surface EPOR population. 3) Brefeldin A, N-glycanase and associated analyses point to EPOR-68K as a core-glycosylated intracellular EPOR pool (of modest size). 4) In contrast to recent reports, EPOR inward trafficking is shown (in UT7epo cells, and primary proerythroblasts) to be sharply ligand-dependent. Beyond this, when C-terminal truncated hEPOR-T mutant alleles as harbored by polycythemia patients are co-expressed with the wild-type EPOR in EPO-dependent erythroid progenitors, several specific events become altered. First, EPOR-T alleles are persistently activated upon EPO- challenge, yet are also subject to apparent turn-over (to low-Mr EPOR products). Furthermore, during exponential cell growth EPOR-T species become both over-represented, and hyper-activated. Interestingly, EPOR-T expression also results in an EPO dose-dependent loss of endogenous wild-type EPOR's (and, therefore, a squelching of EPOR C-terminal- mediated negative feedback effects). New knowledge concerning regulated EPOR expression and trafficking therefore is provided, together with new insight into mechanisms via which

A silent allele in the locus D5S818 contained within the PowerPlex®21 PCR Amplification Kit.

Science.gov (United States)

Chen, Ling; Tai, Yunchun; Qiu, Pingming; Du, Weian; Liu, Chao

2015-11-01

Three paternity tests cases were found with a single locus mismatch at the locus D5S818 with PowerPlex®21 PCR Amplification Kit (Promega). Forward and reverse primers were redesigned to type the samples again and to evaluate if there were alleles dropped out. The results showed the existence of a silent allele 12 in all the three families, due to a point mutation that changed cytosine to adenine at 90 nucleotides upstream from the 5' end of the AGAT repeat sequences in all the six individuals. A single locus mismatch due to a silent allele may occur in any locus using any kit. Therefore, we recommend using multiple kits to confirm the results in paternity testing cases with mismatches, especially when there is a single locus mismatch with homozygote involved. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study

International Nuclear Information System (INIS)

Castillejo, Adela; Guillén-Ponce, Carmen; Carrato, Alfredo; Soto, José-Luís; Mata-Balaguer, Trinidad; Montenegro, Paola; Ochoa, Enrique; Lázaro, Rafael; Martínez-Cantó, Ana; Castillejo, María-Isabel; Guarinos, Carla; Barberá, Víctor-Manuel

2009-01-01

TGF-β receptor type I is a mediator of growth inhibitory signals. TGFBR1*6A (rs11466445) is a common polymorphic variant of the TGF-β receptor I gene and has been associated with tumour susceptibility. Nevertheless, the role of this polymorphism as a risk factor for colorectal cancer is controversial. The aim of this study was to assess the association between TGFBR1*6A and colorectal cancer, age, sex, tumour location and tumour stage in a Spanish population. The case-control study involved 800 Spanish subjects: 400 sporadic colorectal cancer patients and 400 age-, sex-, and ethnic-matched controls. The odds ratio (OR) and 95% confidence interval (95% CI) for the TGFBR1*6A polymorphism were calculated using unconditional logistic regression adjusted for age and sex. Analysis of somatic mutations at the GCG repeat of TGFBR1 exon 1 and germline allele-specific expression were also conducted to obtain further information on the contribution of the TGFBR1*6A allele to CRC susceptibility. There was no statistically significant association between the TGFBR1*6A allele and CRC (p > 0.05). The OR was 1.147 (95% CI: 0.799–1.647) for carriers of the TGFBR1*6A allele and 0.878 (95% CI: 0.306–2.520) for homozygous TGFBR1*6A individuals compared with the reference. The frequency of the polymorphism was not affected by age, sex or tumour stage. The TGFBR1*6A allele was more prevalent among colon tumour patients than among rectal tumour patients. Tumour somatic mutations were found in only two of 69 cases (2.9%). Both cases involved a GCG deletion that changed genotype 9A/9A in normal DNA to genotype 9A/8A. Interestingly, these two tumours were positive for microsatellite instability, suggesting that these mutations originated because of a deficient DNA mismatch repair system. Allele-specific expression of the 9A allele was detected in seven of the 14 heterozygous 9A/6A tumour cases. This could have been caused by linkage disequilibrium of the TGFBR1*6A allele with

Association of gliadin antibodies, HLA alleles, and schizophrenia in Cuban population patients

Directory of Open Access Journals (Sweden)

José A. Galván

2016-05-01

Full Text Available Introduction: Several lines of evidence have suggested an interesting link between gluten ingestion and schizophrenia. For example, increased levels of gliadin and transglutaminase antibodies have been observed in patients with schizophrenia. Methods: To verify these observations we compared the prevalence of gliadin and transglutaminse antibodies, as well as the presence of the HLA alleles, HLA DQA1*0501-DQB1*02 (DQ2 and HLA-DQA1*0301-DQB1*0302 (DQ8, among patients with schizophrenia and healthy controls. A total of 108 patients with schizophrenia and 60 healthy controls were evaluated. Gliadin antibodies were determined by a visual semiquantitative assay and tissue transglutaminase antibodies were determined both by one-step immunochromatografic assay and ELISA. HLA typing was performed by PCR amplification using sequence-specific primers for each allele. Results: We found a strong association between the presence of gliadin antibodies and schizophrenia (OR 3.488; 95% CI, 1.43-8.44. However, tissue transglutaminase antibodies were not detected in either group neither by immunochromatograpic or ELISA. No significant association was found for the DQ2 or DQ8 heterodimer and the disease, but a significant positive association between schizophrenia and HLA alleles DQA1*0301 and DQB1*02 was present (OR = 2.80; 95% CI, 1.27-6.17, and OR = 2.37, 95% CI, 1.24-4.53, respectively. Conclusions: The present study showed that the presence of gliadin antibodies was not correlated with the presence of HLA DQA1*0301 or DQB1*02 alleles within the group of patients with schizophrenia. Our study replicates the findings that anti-gliadin antibodies are associated with schizophrenia but also suggests that the presence of these antibodies and the HLA alleles DQB1*02 and DQA1*0301 are independently associated with susceptibility to schizophrenia.

VNTR alleles associated with the {alpha}-globin locus are haplotype and population related

Energy Technology Data Exchange (ETDEWEB)

Martinson, J.J.; Clegg, J.B.; Boyce, A.J. [Univ. of Oxford (United Kingdom)

1994-09-01

The human {alpha}-globin complex contains several polymorphic restriction-enzyme sites (i.e., RFLPs) linked to form haplotypes and is flanked by two hypervariable VNTR loci, the 5{prime} hypervariable region (HVR) and the more highly polymorphic 3{prime}HVR. Using a combination of RFLP analysis and PCR, the authors have characterized the 5{prime}HVR and 3{prime}HVR alleles associated with the {alpha}-globin haplotypes of 133 chromosomes, and they here show that specific {alpha}-globin haplotypes are each associated with discrete subsets of the alleles observed at these two VNTR loci. This statistically highly significant association is observed over a region spanning {approximately} 100 kb. With the exception of closely related haplotypes, different haplotypes do not share identically sized 3{prime}HVR alleles. Earlier studies have shown that {alpha}-globin haplotype distributions differ between populations; the current findings also reveal extensive population substructure in the repertoire of {alpha}-globin VNTRs. If similar features are characteristic of other VNTR loci, this will have important implications for forensic and anthropological studies. 42 refs., 5 figs., 5 tabs.

Increased risk for CRC in diabetic patients with the nonrisk allele of SNPs at 8q24.

Science.gov (United States)

Ishimaru, Shinya; Mimori, Koshi; Yamamoto, Ken; Inoue, Hiroshi; Imoto, Seiya; Kawano, Shuichi; Yamaguchi, Rui; Sato, Tetsuya; Toh, Hiroyuki; Iinuma, Hisae; Maeda, Toyoki; Ishii, Hideshi; Suzuki, Sadao; Tokudome, Shinkan; Watanabe, Masahiko; Tanaka, Jun-ichi; Kudo, Shin-ei; Sugihara, Ken-ichi; Hase, Kazuo; Mochizuki, Hidetaka; Kusunoki, Masato; Yamada, Kazutaka; Shimada, Yasuhiro; Moriya, Yoshihiro; Barnard, Graham F; Miyano, Satoru; Mori, Masaki

2012-09-01

Colorectal cancer (CRC) oncogenesis was considered to be determined by interactions between genetic and environmental factors. Specific interacting factors that influence CRC morbidity have yet to be fully investigated. A multi-institutional collaborative study with 1511 CRC patients and 2098 control subjects was used to compare the odds ratios for the occurrence of polymorphisms at 11 known single nucleotide polymorphisms (SNPs). TaqMan PCR and questionnaires were used to evaluate the effects of environmental exposures. Variants of rs6983267 on 8q24 were the most significant markers of risk for CRC (odds ratio 1.16, 95% confidence interval 1.06-1.27, P = 0.0015). Non-insulin-dependent diabetes mellitus (DM), a higher body mass index at age 20, and meat consumption were environmental risk factors, whereas a tuna-rich diet and vitamin intake were protective factors. The cohort of rs6983267 SNP major (T) allele at 8q24 and DM had a 1.66-fold higher risk ratio than the cohort of major allele patients without DM. We confirmed that interactions between the genetic background and environmental factors are associated with increased risk for CRC. There is a robust risk of the minor G allele at the 8q24 rs6983267 SNP; however, a major T allele SNP could more clearly reveal a correlation with CRC specifically when DM is present.

HLA-class II alleles in patients with drug-resistant pulmonary tuberculosis in Kazakhstan.

Science.gov (United States)

Kuranov, A B; Kozhamkulov, U A; Vavilov, M N; Belova, E S; Bismilda, V L; Alenova, A H; Ismailov, S S; Momynaliev, K T

2014-02-01

The human leukocyte antigen (HLA) system has a major role in the regulation of the immune response as it is involved in the defense against pathogens. Some studies have reported that HLA class II genes play a strong role in severe cases of pulmonary tuberculosis (PTB) in several populations. Thus the aim of the study was to compare the HLA-class II alleles of patients with drug resistant tuberculosis with those of healthy controls from the same ethnic group in Kazakhstan. The aim of the present study was to evaluate the correlation of HLA-class II alleles by patients with drug resistant tuberculosis and the healthy controls of the same ethnic group in Kazakhstan. The HLA-class II alleles of 76 patients with tuberculosis (TB) and 157 healthy volunteers were investigated using sequence-based typing (SBT)-method. HLA-DQA1*03:02 HLA-DRB1*08:01 and DRB1*08:03 occurred more frequently (P = 0.05) in patients with drug resistant tuberculosis than in controls. We observed a possible association between certain HLA alleles and TB that are specific for the Kazakh population. Further studies are needed to confirm our findings using a larger number of patients with drug resistant tuberculosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Protein Maker: an automated system for high-throughput parallel purification

International Nuclear Information System (INIS)

Smith, Eric R.; Begley, Darren W.; Anderson, Vanessa; Raymond, Amy C.; Haffner, Taryn E.; Robinson, John I.; Edwards, Thomas E.; Duncan, Natalie; Gerdts, Cory J.; Mixon, Mark B.; Nollert, Peter; Staker, Bart L.; Stewart, Lance J.

2011-01-01

The Protein Maker instrument addresses a critical bottleneck in structural genomics by allowing automated purification and buffer testing of multiple protein targets in parallel with a single instrument. Here, the use of this instrument to (i) purify multiple influenza-virus proteins in parallel for crystallization trials and (ii) identify optimal lysis-buffer conditions prior to large-scale protein purification is described. The Protein Maker is an automated purification system developed by Emerald BioSystems for high-throughput parallel purification of proteins and antibodies. This instrument allows multiple load, wash and elution buffers to be used in parallel along independent lines for up to 24 individual samples. To demonstrate its utility, its use in the purification of five recombinant PB2 C-terminal domains from various subtypes of the influenza A virus is described. Three of these constructs crystallized and one diffracted X-rays to sufficient resolution for structure determination and deposition in the Protein Data Bank. Methods for screening lysis buffers for a cytochrome P450 from a pathogenic fungus prior to upscaling expression and purification are also described. The Protein Maker has become a valuable asset within the Seattle Structural Genomics Center for Infectious Disease (SSGCID) and hence is a potentially valuable tool for a variety of high-throughput protein-purification applications

Xyce Parallel Electronic Simulator - Users' Guide Version 2.1.

Energy Technology Data Exchange (ETDEWEB)

Hutchinson, Scott A; Hoekstra, Robert J.; Russo, Thomas V.; Rankin, Eric; Pawlowski, Roger P.; Fixel, Deborah A; Schiek, Richard; Bogdan, Carolyn W.; Shirley, David N.; Campbell, Phillip M.; Keiter, Eric R.

2005-06-01

This manual describes the use of theXyceParallel Electronic Simulator.Xycehasbeen designed as a SPICE-compatible, high-performance analog circuit simulator, andhas been written to support the simulation needs of the Sandia National Laboratorieselectrical designers. This development has focused on improving capability over thecurrent state-of-the-art in the following areas:%04Capability to solve extremely large circuit problems by supporting large-scale par-allel computing platforms (up to thousands of processors). Note that this includessupport for most popular parallel and serial computers.%04Improved performance for all numerical kernels (e.g., time integrator, nonlinearand linear solvers) through state-of-the-art algorithms and novel techniques.%04Device models which are specifically tailored to meet Sandia's needs, includingmany radiation-aware devices.3 XyceTMUsers' Guide%04Object-oriented code design and implementation using modern coding practicesthat ensure that theXyceParallel Electronic Simulator will be maintainable andextensible far into the future.Xyceis a parallel code in the most general sense of the phrase - a message passingparallel implementation - which allows it to run efficiently on the widest possible numberof computing platforms. These include serial, shared-memory and distributed-memoryparallel as well as heterogeneous platforms. Careful attention has been paid to thespecific nature of circuit-simulation problems to ensure that optimal parallel efficiencyis achieved as the number of processors grows.The development ofXyceprovides a platform for computational research and de-velopment aimed specifically at the needs of the Laboratory. WithXyce, Sandia hasan %22in-house%22 capability with which both new electrical (e.g., device model develop-ment) and algorithmic (e.g., faster time-integration methods, parallel solver algorithms)research and development can be performed. As a result,Xyceis a unique electricalsimulation capability

HLA-DR alleles among Pakistani patients of coeliac disease

International Nuclear Information System (INIS)

Saleem, N.; Ahmed, T.A.; Bashir, M.; Ali, S.; Iqbal, M.

2013-01-01

Objectives: To investigate whether certain DR alleles might also contribute to the genetic susceptibility among Coeliac disease patients in Pakistan. Methods: The case-control study was conducted at the Military Hospital, Rawalpindi, from October 2011 to January 2012, and analysed 25 children diagnosed to have coeliac disease as per the criteria set by the European Society of Paediatric Gastroenterology and Nutrition, which included histopathological alterations in duodenal biopsies, clinical response to gluten withdrawal, and presence of anti-endomyseal antibodies. Patients were compared with a group of 150 healthy subjects. Dioxyribonucleic acid was extracted from peripheral blood collected in ethylenediaminetetraacetic acid.K3. Human leukocyte antigen DRB1 typing was carried out on allele level (DRB1*01 - DRB1*16) using sequence specific primers. Human leukocyte antigen type was determined by agarose gel electrophoresis and results were recorded. Phenotype frequency of various alleles among the patient group and the control group was calculated by direct counting, and significance of their association was determined by Fisher Exact Test. Results: A total of 11 (44%) female paediatric coeliac patients in age range 1-9 (mean 7.2+-4.8 years) and 14 (56%) male paediatric patients in the age range 6-14 (mean 8.6+-5.1 years) were genotyped for HLA-DRB1 loci. A statistically significant positive association of the disease with HLA-DRB1*03 (n=23; 92% versus n=31; 21% in controls, p <0.01) was observed. Conclusion: HLA-DRB1*03 is associated with increased risk of developing coeliac disease. (author)

Site-specific antibodies distinguish single amino acid substitutions in position 57 in HLA-DQ beta-chain alleles associated with insulin-dependent diabetes

DEFF Research Database (Denmark)

Atar, D; Dyrberg, T; Michelsen, Birgitte

1989-01-01

The HLA-DQ beta-chain gene shows a close association with susceptibility or resistance to autoimmune insulin-dependent diabetes mellitus (IDDM) and it has been suggested that the amino acid in position 57 may be of pathogenetic importance. To study the expression of the IDDM associated HLA-DQ beta......-chain alleles, we immunized rabbits with 12 to 13 amino acid long peptides representing HLA-DQw7 and -DQw8 allelic sequences, differing only by one amino acid in position 57 being aspartic acid (Asp) and alanine (Ala), respectively. Immunoblot analysis of lymphoblastoid cells showed that several antisera...

Co-simulation of dynamic systems in parallel and serial model configurations

International Nuclear Information System (INIS)

Sweafford, Trevor; Yoon, Hwan Sik

2013-01-01

Recent advancement in simulation software and computation hardware make it realizable to simulate complex dynamic systems comprised of multiple submodels developed in different modeling languages. The so-called co-simulation enables one to study various aspects of a complex dynamic system with heterogeneous submodels in a cost-effective manner. Among several different model configurations for co-simulation, synchronized parallel configuration is regarded to expedite the simulation process by simulation multiple sub models concurrently on a multi core processor. In this paper, computational accuracies as well as computation time are studied for three different co-simulation frameworks : integrated, serial, and parallel. for this purpose, analytical evaluations of the three different methods are made using the explicit Euler method and then they are applied to two-DOF mass-spring systems. The result show that while the parallel simulation configuration produces the same accurate results as the integrated configuration, results of the serial configuration, results of the serial configuration show a slight deviation. it is also shown that the computation time can be reduced by running simulation in the parallel configuration. Therefore, it can be concluded that the synchronized parallel simulation methodology is the best for both simulation accuracy and time efficiency.

Stranger that fiction parallel universes beguile science

CERN Document Server

2007-01-01

Is the universe -- correction: 'our' universe -- no more than a speck of cosmic dust amid an infinite number of parallel worlds? A staple of mind-bending science fiction, the possibility of multiple universes has long intrigued hard-nosed physicists, mathematicians and cosmologists too.

Stranger than fiction: parallel universes beguile science

CERN Document Server

Hautefeuille, Annie

2007-01-01

Is the universe-correction: 'our' universe-no more than a speck of cosmic dust amid an infinite number of parallel worlds? A staple of mind-bending science fiction, the possibility of multiple universes has long intrigued hard-nosed physicists, mathematicians and cosmologists too.

Characterization of a New Pm2 Allele Conferring Powdery Mildew Resistance in the Wheat Germplasm Line FG-1

Science.gov (United States)

Ma, Pengtao; Xu, Hongxng; Li, Lihui; Zhang, Hongxia; Han, Guohao; Xu, Yunfeng; Fu, Xiaoyi; Zhang, Xiaotian; An, Diaoguo

2016-01-01

Powdery mildew has a negative impact on wheat production. Novel host resistance increases the diversity of resistance genes and helps to control the disease. In this study, wheat line FG-1 imported from France showed a high level of powdery mildew resistance at both the seedling and adult stages. An F2 population and F2:3 families from the cross FG-1 × Mingxian 169 both fit Mendelian ratios for a single dominant resistance gene when tested against multiple avirulent Blumeria tritici f. sp. tritici (Bgt) races. This gene was temporarily designated PmFG. PmFG was mapped on the multi-allelic Pm2 locus of chromosome 5DS using seven SSR, 10 single nucleotide polymorphism (SNP)-derived and two SCAR markers with the flanking markers Xbwm21/Xcfd81/Xscar112 (distal) and Xbwm25 (proximal) at 0.3 and 0.5 cM being the closest. Marker SCAR203 co-segregated with PmFG. Allelism tests between PmFG and documented Pm2 alleles confirmed that PmFG was allelic with Pm2. Line FG-1 produced a significantly different reaction pattern compared to other lines with genes at or near Pm2 when tested against 49 Bgt isolates. The PmFG-linked marker alleles detected by the SNP-derived markers revealed significant variation between FG-1 and other lines with genes at or near Pm2. It was concluded that PmFG is a new allele at the Pm2 locus. Data from seven closely linked markers tested on 31 wheat cultivars indicated opportunities for marker-assisted pyramiding of this gene with other genes for powdery mildew resistance and additional traits. PMID:27200022

Origin of allelic diversity in antirrhinum S locus RNases.

Science.gov (United States)

Xue, Y; Carpenter, R; Dickinson, H G; Coen, E S

1996-01-01

In many plant species, self-incompatibility (SI) is genetically controlled by a single multiallelic S locus. Previous analysis of S alleles in the Solanaceae, in which S locus ribonucleases (S RNases) are responsible for stylar expression of SI, has demonstrated that allelic diversity predated speciation within this family. To understand how allelic diversity has evolved, we investigated the molecular basis of gametophytic SI in Antirrhinum, a member of the Scrophulariaceae, which is closely related to the Solanaceae. We have characterized three Antirrhinum cDNAs encoding polypeptides homologous to S RNases and shown that they are encoded by genes at the S locus. RNA in situ hybridization revealed that the Antirrhinum S RNase are primarily expressed in the stylar transmitting tissue. This expression is consistent with their proposed role in arresting the growth of self-pollen tubes. S alleles from the Scrophulariaceae form a separate group from those of the Solanaceae, indicating that new S alleles have been generated since these families separated (approximately 40 million years). We propose that the recruitment of an ancestral RNase gene into SI occurred during an early stage of angiosperm evolution and that, since that time, new alleles subsequently have arisen at a low rate. PMID:8672882

Evaluation of efficiency of nested multiplex allele-specific PCR assay for detection of multidrug resistant tuberculosis directly from sputum samples.

Science.gov (United States)

Mistri, S K; Sultana, M; Kamal, S M M; Alam, M M; Irin, F; Nessa, J; Ahsan, C R; Yasmin, M

2016-05-01

For an effective control of tuberculosis, rapid detection of multidrug resistant tuberculosis (MDR-TB) is necessary. Therefore, we developed a modified nested multiplex allele-specific polymerase chain reaction (MAS-PCR) method that enables rapid MDR-TB detection directly from sputum samples. The efficacy of this method was evaluated using 79 sputum samples collected from suspected tuberculosis patients. The performance of nested MAS-PCR method was compared with other MDR-TB detection methods like drug susceptibility testing (DST) and DNA sequencing. As rifampicin (RIF) resistance conforms to MDR-TB in greater than 90% cases, only the presence of RIF-associated mutations in rpoB gene was determined by DNA sequencing and nested MAS-PCR to detect MDR-TB. The concordance between nested MAS-PCR and DNA sequencing results was found to be 96·3%. When compared with DST, the sensitivity and specificity of nested MAS-PCR for RIF-resistance detection were determined to be 92·9 and 100% respectively. For developing- and high-TB burden countries, molecular-based tests have been recommended by the World Health Organization for rapid detection of MDR-TB. The results of this study indicate that, nested MAS-PCR assay might be a practical and relatively cost effective molecular method for rapid detection of MDR-TB from suspected sputum samples in developing countries with resource poor settings. © 2016 The Society for Applied Microbiology.

Performance of Molecular Inversion Probes (MIP) in Allele CopyNumber Determination

Energy Technology Data Exchange (ETDEWEB)

Wang, Yuker; Moorhead, Martin; Karlin-Neumann, George; Wang,Nicolas J.; Ireland, James; Lin, Steven; Chen, Chunnuan; Heiser, LauraM.; Chin, Koei; Esserman, Laura; Gray, Joe W.; Spellman, Paul T.; Faham,Malek

2007-05-14

We have developed a new protocol for using MolecularInversion Probes (MIP) to accurately and specifically measure allele copynumber (ACN). The new protocol provides for significant improvementsincluding the reduction of input DNA (from 2?g) by more than 25 fold (to75ng total genomic DNA), higher overall precision resulting in one orderof magnitude lower false positive rate, and greater dynamic range withaccurate absolute copy number up to 60 copies.

GACT: a Genome build and Allele definition Conversion Tool for SNP imputation and meta-analysis in genetic association studies.

Science.gov (United States)

Sulovari, Arvis; Li, Dawei

2014-07-19

Genome-wide association studies (GWAS) have successfully identified genes associated with complex human diseases. Although much of the heritability remains unexplained, combining single nucleotide polymorphism (SNP) genotypes from multiple studies for meta-analysis will increase the statistical power to identify new disease-associated variants. Meta-analysis requires same allele definition (nomenclature) and genome build among individual studies. Similarly, imputation, commonly-used prior to meta-analysis, requires the same consistency. However, the genotypes from various GWAS are generated using different genotyping platforms, arrays or SNP-calling approaches, resulting in use of different genome builds and allele definitions. Incorrect assumptions of identical allele definition among combined GWAS lead to a large portion of discarded genotypes or incorrect association findings. There is no published tool that predicts and converts among all major allele definitions. In this study, we have developed a tool, GACT, which stands for Genome build and Allele definition Conversion Tool, that predicts and inter-converts between any of the common SNP allele definitions and between the major genome builds. In addition, we assessed several factors that may affect imputation quality, and our results indicated that inclusion of singletons in the reference had detrimental effects while ambiguous SNPs had no measurable effect. Unexpectedly, exclusion of genotypes with missing rate > 0.001 (40% of study SNPs) showed no significant decrease of imputation quality (even significantly higher when compared to the imputation with singletons in the reference), especially for rare SNPs. GACT is a new, powerful, and user-friendly tool with both command-line and interactive online versions that can accurately predict, and convert between any of the common allele definitions and between genome builds for genome-wide meta-analysis and imputation of genotypes from SNP-arrays or deep

Parallel and Multivalued Logic by the Two-Dimensional Photon-Echo Response of a Rhodamine–DNA Complex

Science.gov (United States)

2015-01-01

Implementing parallel and multivalued logic operations at the molecular scale has the potential to improve the miniaturization and efficiency of a new generation of nanoscale computing devices. Two-dimensional photon-echo spectroscopy is capable of resolving dynamical pathways on electronic and vibrational molecular states. We experimentally demonstrate the implementation of molecular decision trees, logic operations where all possible values of inputs are processed in parallel and the outputs are read simultaneously, by probing the laser-induced dynamics of populations and coherences in a rhodamine dye mounted on a short DNA duplex. The inputs are provided by the bilinear interactions between the molecule and the laser pulses, and the output values are read from the two-dimensional molecular response at specific frequencies. Our results highlights how ultrafast dynamics between multiple molecular states induced by light–matter interactions can be used as an advantage for performing complex logic operations in parallel, operations that are faster than electrical switching. PMID:25984269

Ultra-high resolution HLA genotyping and allele discovery by highly multiplexed cDNA amplicon pyrosequencing

Directory of Open Access Journals (Sweden)

Lank Simon M

2012-08-01

Full Text Available Abstract Background High-resolution HLA genotyping is a critical diagnostic and research assay. Current methods rarely achieve unambiguous high-resolution typing without making population-specific frequency inferences due to a lack of locus coverage and difficulty in exon-phase matching. Achieving high-resolution typing is also becoming more challenging with traditional methods as the database of known HLA alleles increases. Results We designed a cDNA amplicon-based pyrosequencing method to capture 94% of the HLA class I open-reading-frame with only two amplicons per sample, and an analogous method for class II HLA genes, with a primary focus on sequencing the DRB loci. We present a novel Galaxy server-based analysis workflow for determining genotype. During assay validation, we performed two GS Junior sequencing runs to determine the accuracy of the HLA class I amplicons and DRB amplicon at different levels of multiplexing. When 116 amplicons were multiplexed, we unambiguously resolved 99%of class I alleles to four- or six-digit resolution, as well as 100% unambiguous DRB calls. The second experiment, with 271 multiplexed amplicons, missed some alleles, but generated high-resolution, concordant typing for 93% of class I alleles, and 96% for DRB1 alleles. In a third, preliminary experiment we attempted to sequence novel amplicons for other class II loci with mixed success. Conclusions The presented assay is higher-throughput and higher-resolution than existing HLA genotyping methods, and suitable for allele discovery or large cohort sampling. The validated class I and DRB primers successfully generated unambiguously high-resolution genotypes, while further work is needed to validate additional class II genotyping amplicons.

An improved assay for the determination of Huntington`s disease allele size

Energy Technology Data Exchange (ETDEWEB)

Reeves, C.; Klinger, K.; Miller, G. [Intergrated Genetics, Framingham, MA (United States)

1994-09-01

The hallmark of Huntington`s disease (HD) is the expansion of a polymorphic (CAG)n repeat. Several methods have been published describing PCR amplification of this region. Most of these assays require a complex PCR reaction mixture to amplify this GC-rich region. A consistent problem with trinucleotide repeat PCR amplification is the presence of a number of {open_quotes}stutter bands{close_quotes} which may be caused by primer or amplicon slippage during amplification or insufficient polymerase processivity. Most assays for HD arbitrarily select a particular band for diagnostic purposes. Without a clear choice for band selection such an arbitrary selection may result in inconsistent intra- or inter-laboratory findings. We present an improved protocol for the amplification of the HD trinucleotide repeat region. This method simplifies the PCR reaction buffer and results in a set of easily identifiable bands from which to determine allele size. HD alleles were identified by selecting bands of clearly greater signal intensity. Stutter banding was much reduced thus permitting easy identification of the most relevant PCR product. A second set of primers internal to the CCG polymorphism was used in selected samples to confirm allele size. The mechanism of action of N,N,N trimethylglycine in the PCR reaction is not clear. It may be possible that the minimal isostabilizing effect of N,N,N trimethylglycine at 2.5 M is significant enough to affect primer specificity. The use of N,N,N trimethylglycine in the PCR reaction facilitated identification of HD alleles and may be appropriate for use in other assays of this type.

Allelic imbalance and cytogenetic deletion of 1p in colorectal adenomas: a target region identified between DIS199 and DIS234

DEFF Research Database (Denmark)

Bomme, L; Heim, S; Bardi, G

1998-01-01

short-term cultured and karyotyped colorectal adenomas for allelic imbalance at eight microsatellite loci in 1p. Allelic imbalances were detected in seven of the 12 adenomas that had cytogenetically visible abnormalities of chromosome 1, as well as in four adenomas that either had a normal karyotype...... region. This genomic area contains the human homologue of the tumor modifier gene Mom1 (1p35-36.1), which, in mice, modifies the number of intestinal tumors in multiple intestinal neoplasia (Min)-mutated animals. To evaluate whether the imbalances corresponded to interstitial deletions of 1p material, we...

Improving parallel imaging by jointly reconstructing multi-contrast data.

Science.gov (United States)

Bilgic, Berkin; Kim, Tae Hyung; Liao, Congyu; Manhard, Mary Kate; Wald, Lawrence L; Haldar, Justin P; Setsompop, Kawin

2018-08-01

To develop parallel imaging techniques that simultaneously exploit coil sensitivity encoding, image phase prior information, similarities across multiple images, and complementary k-space sampling for highly accelerated data acquisition. We introduce joint virtual coil (JVC)-generalized autocalibrating partially parallel acquisitions (GRAPPA) to jointly reconstruct data acquired with different contrast preparations, and show its application in 2D, 3D, and simultaneous multi-slice (SMS) acquisitions. We extend the joint parallel imaging concept to exploit limited support and smooth phase constraints through Joint (J-) LORAKS formulation. J-LORAKS allows joint parallel imaging from limited autocalibration signal region, as well as permitting partial Fourier sampling and calibrationless reconstruction. We demonstrate highly accelerated 2D balanced steady-state free precession with phase cycling, SMS multi-echo spin echo, 3D multi-echo magnetization-prepared rapid gradient echo, and multi-echo gradient recalled echo acquisitions in vivo. Compared to conventional GRAPPA, proposed joint acquisition/reconstruction techniques provide more than 2-fold reduction in reconstruction error. JVC-GRAPPA takes advantage of additional spatial encoding from phase information and image similarity, and employs different sampling patterns across acquisitions. J-LORAKS achieves a more parsimonious low-rank representation of local k-space by considering multiple images as additional coils. Both approaches provide dramatic improvement in artifact and noise mitigation over conventional single-contrast parallel imaging reconstruction. Magn Reson Med 80:619-632, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.

Comparative genomics in the Asteraceae reveals little evidence for parallel evolutionary change in invasive taxa.

Science.gov (United States)

Hodgins, Kathryn A; Bock, Dan G; Hahn, Min A; Heredia, Sylvia M; Turner, Kathryn G; Rieseberg, Loren H

2015-05-01

Asteraceae, the largest family of flowering plants, has given rise to many notorious invasive species. Using publicly available transcriptome assemblies from 35 Asteraceae, including six major invasive species, we examined evidence for micro- and macro-evolutionary genomic changes associated with invasion. To detect episodes of positive selection repeated across multiple introductions, we conducted comparisons between native and introduced genotypes from six focal species and identified genes with elevated rates of amino acid change (dN/dS). We then looked for evidence of positive selection at a broader phylogenetic scale across all taxa. As invasive species may experience founder events during colonization and spread, we also looked for evidence of increased genetic load in introduced genotypes. We rarely found evidence for parallel changes in orthologous genes in the intraspecific comparisons, but in some cases we identified changes in members of the same gene family. Using among-species comparisons, we detected positive selection in 0.003-0.69% and 2.4-7.8% of the genes using site and stochastic branch-site models, respectively. These genes had diverse putative functions, including defence response, stress response and herbicide resistance, although there was no clear pattern in the GO terms. There was no indication that introduced genotypes have a higher proportion of deleterious alleles than native genotypes in the six focal species, suggesting multiple introductions and admixture mitigated the impact of drift. Our findings provide little evidence for common genomic responses in invasive taxa of the Asteraceae and hence suggest that multiple evolutionary pathways may lead to adaptation during introduction and spread in these species. © 2014 John Wiley & Sons Ltd.

The − 5 A/G single-nucleotide polymorphism in the core promoter region of MT2A and its effect on allele-specific gene expression and Cd, Zn and Cu levels in laryngeal cancer

Energy Technology Data Exchange (ETDEWEB)

Starska, Katarzyna, E-mail: katarzyna.starska@umed.lodz.pl [I Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Kopcinskiego 22, 90-153 Łódź (Poland); Krześlak, Anna; Forma, Ewa [Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236 Łódź (Poland); Olszewski, Jurek [II Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Żeromskiego 113, 90-549 Łódź (Poland); Morawiec-Sztandera, Alina [Department of Head and Neck Surgery, Medical University of Łódź, Paderewskiego 4, 93-509 Łódź (Poland); Aleksandrowicz, Paweł [Department of Otolaryngology and Laryngological Oncology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin (Poland); Lewy-Trenda, Iwona [Department of Pathology, Medical University of Łódź, Pomorska 251, 92-213 Łódź (Poland); and others

2014-10-15

Metallothioneins (MTs) are low molecular weight, cysteine-rich heavy metal-binding proteins which participate in the mechanisms of Zn homeostasis, and protect against toxic metals. MTs contain metal-thiolate cluster groups and suppress metal toxicity by binding to them. The aim of this study was to determine the − 5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene and to investigate its effect on allele-specific gene expression and Cd, Zn and Cu content in squamous cell laryngeal cancer (SCC) and non-cancerous laryngeal mucosa (NCM) as a control. The MT2A promoter region − 5 A/G SNP was determined by restriction fragment length polymorphism using 323 SCC and 116 NCM. MT2A gene analysis was performed by quantitative real-time PCR. The frequency of A allele carriage was 94.2% and 91.8% in SCC and NCM, respectively, while G allele carriage was detected in 5.8% and 8.2% of SCC and NCM samples, respectively. As a result, a significant association was identified between the − 5 A/G SNP in the MT2A gene with mRNA expression in both groups. Metal levels were analyzed by flame atomic absorption spectrometry. The significant differences were identified between A/A and both the A/G and G/G genotypes, with regard to the concentration of the contaminating metal. The Spearman rank correlation results showed that the MT2A expression and Cd, Zn, Cu levels were negatively correlated. Results obtained in this study suggest that − 5 A/G SNP in MT2A gene may have an effect on allele-specific gene expression and accumulation of metal levels in laryngeal cancer. - Highlights: • MT2A gene expression and metal content in laryngeal cancer tissues • Association between SNP (rs28366003) and expression of MT2A • Significant associations between the SNP and Cd, Zn and Cu levels • Negative correlation between MT2A gene expression and Cd, Zn and Cu levels.

The − 5 A/G single-nucleotide polymorphism in the core promoter region of MT2A and its effect on allele-specific gene expression and Cd, Zn and Cu levels in laryngeal cancer

International Nuclear Information System (INIS)

Starska, Katarzyna; Krześlak, Anna; Forma, Ewa; Olszewski, Jurek; Morawiec-Sztandera, Alina; Aleksandrowicz, Paweł; Lewy-Trenda, Iwona

2014-01-01

Metallothioneins (MTs) are low molecular weight, cysteine-rich heavy metal-binding proteins which participate in the mechanisms of Zn homeostasis, and protect against toxic metals. MTs contain metal-thiolate cluster groups and suppress metal toxicity by binding to them. The aim of this study was to determine the − 5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene and to investigate its effect on allele-specific gene expression and Cd, Zn and Cu content in squamous cell laryngeal cancer (SCC) and non-cancerous laryngeal mucosa (NCM) as a control. The MT2A promoter region − 5 A/G SNP was determined by restriction fragment length polymorphism using 323 SCC and 116 NCM. MT2A gene analysis was performed by quantitative real-time PCR. The frequency of A allele carriage was 94.2% and 91.8% in SCC and NCM, respectively, while G allele carriage was detected in 5.8% and 8.2% of SCC and NCM samples, respectively. As a result, a significant association was identified between the − 5 A/G SNP in the MT2A gene with mRNA expression in both groups. Metal levels were analyzed by flame atomic absorption spectrometry. The significant differences were identified between A/A and both the A/G and G/G genotypes, with regard to the concentration of the contaminating metal. The Spearman rank correlation results showed that the MT2A expression and Cd, Zn, Cu levels were negatively correlated. Results obtained in this study suggest that − 5 A/G SNP in MT2A gene may have an effect on allele-specific gene expression and accumulation of metal levels in laryngeal cancer. - Highlights: • MT2A gene expression and metal content in laryngeal cancer tissues • Association between SNP (rs28366003) and expression of MT2A • Significant associations between the SNP and Cd, Zn and Cu levels • Negative correlation between MT2A gene expression and Cd, Zn and Cu levels

Allele and genotype frequencies of -β lactoglobulin gene in Iranian ...

African Journals Online (AJOL)

STORAGESEVER

2009-08-04

Aug 4, 2009 ... Blood samples were supplied from 80 Najdi cattle and 80 buffalo from different cities of Khouzestan province. ... The allele B of β-Lactoglobulin occurred at a higher frequency than the allele A in both. Najdi cattle and buffalo. .... that of the B allele in both groups of animals studied. Expected heterozygosity ...

Parallel implementation of many-body mean-field equations

International Nuclear Information System (INIS)

Chinn, C.R.; Umar, A.S.; Vallieres, M.; Strayer, M.R.

1994-01-01

We describe the numerical methods used to solve the system of stiff, nonlinear partial differential equations resulting from the Hartree-Fock description of many-particle quantum systems, as applied to the structure of the nucleus. The solutions are performed on a three-dimensional Cartesian lattice. Discretization is achieved through the lattice basis-spline collocation method, in which quantum-state vectors and coordinate-space operators are expressed in terms of basis-spline functions on a spatial lattice. All numerical procedures reduce to a series of matrix-vector multiplications and other elementary operations, which we perform on a number of different computing architectures, including the Intel Paragon and the Intel iPSC/860 hypercube. Parallelization is achieved through a combination of mechanisms employing the Gram-Schmidt procedure, broadcasts, global operations, and domain decomposition of state vectors. We discuss the approach to the problems of limited node memory and node-to-node communication overhead inherent in using distributed-memory, multiple-instruction, multiple-data stream parallel computers. An algorithm was developed to reduce the communication overhead by pipelining some of the message passing procedures

Humoral immune responses to a single allele PfAMA1 vaccine in healthy malaria-naïve adults.

Directory of Open Access Journals (Sweden)

Edmond J Remarque

Full Text Available Plasmodium falciparum: apical membrane antigen 1 (AMA1 is a candidate malaria vaccine antigen expressed on merozoites and sporozoites. The polymorphic nature of AMA1 may compromise vaccine induced protection. The humoral response induced by two dosages (10 and 50 µg of a single allele AMA1 antigen (FVO formulated with Alhydrogel, Montanide ISA 720 or AS02 was investigated in 47 malaria-naïve adult volunteers. Volunteers were vaccinated 3 times at 4 weekly intervals and serum samples obtained four weeks after the third immunization were analysed for (i Antibody responses to various allelic variants, (ii Domain specificity, (iii Avidity, (iv IgG subclass levels, by ELISA and (v functionality of antibody responses by Growth Inhibition Assay (GIA. About half of the antibodies induced by vaccination cross reacted with heterologous AMA1 alleles. The choice of adjuvant determined the magnitude of the antibody response, but had only a marginal influence on specificity, avidity, domain recognition or subclass responses. The highest antibody responses were observed for AMA1 formulated with AS02. The Growth Inhibition Assay activity of the antibodies was proportional to the amount of antigen specific IgG and the functional capacity of the antibodies was similar for heterologous AMA1-expressing laboratory strains.ClinicalTrials.gov NCT00730782.

The Study of Morphological Traits and Identification of Self-incompatibility Alleles in Almond Cultivars and Genotypes

Directory of Open Access Journals (Sweden)

Mousa Rasouli

2017-12-01

Full Text Available The evaluation of an almond collection using morphological variables and identification of self-incompatibility genotype  is useful for selecting pollinizers and for the design of crossing in almond breeding programs. In this study, important morphological traits and self-incompatibilities in 71 almond cultivars and genotypes were studied. Simple and multiplex specific PCR analyses were used in order to identify self-incompatibility alleles. Based on the results, cultivars and genotypes including ‘Dir Ras–e-Savojbolagh’, ‘D-124’, ‘D-99’, ‘Shahrood 12’, ‘Tuono’, ‘Nonpareil’, ‘Price’, ‘Mirpanj-e-Tehran’, ‘Pakotahe-e- Taleghan’, ‘V-13-34’, ‘V-16-8, ‘V-11-10’, ‘Zarghan 10’, ‘Uromiyeh 68’, ‘Barg dorosht-e-Hamedan’ and ‘Yazd 60’ were late flowering and had the highest quality of nut and kernel characters. The result of the PCR method using combined primers AS1II and AmyC5R showed amplification of ten self-incompatibility alleles (S1, S2, S3, S5, S6, S7, S8, S10, S12,and S unknown allele and three Sfalleles. Moreover, S1 had the highest frequencies in comparison with other known S-alleles. Also, unknown alleles with different sizes were detected and 58 new bands were found in some cultivars.

Stress-related methylation of the catechol-O-methyltransferase Val 158 allele predicts human prefrontal cognition and activity.

Science.gov (United States)

Ursini, Gianluca; Bollati, Valentina; Fazio, Leonardo; Porcelli, Annamaria; Iacovelli, Luisa; Catalani, Assia; Sinibaldi, Lorenzo; Gelao, Barbara; Romano, Raffaella; Rampino, Antonio; Taurisano, Paolo; Mancini, Marina; Di Giorgio, Annabella; Popolizio, Teresa; Baccarelli, Andrea; De Blasi, Antonio; Blasi, Giuseppe; Bertolino, Alessandro

2011-05-04

DNA methylation at CpG dinucleotides is associated with gene silencing, stress, and memory. The catechol-O-methyltransferase (COMT) Val(158) allele in rs4680 is associated with differential enzyme activity, stress responsivity, and prefrontal activity during working memory (WM), and it creates a CpG dinucleotide. We report that methylation of the Val(158) allele measured from peripheral blood mononuclear cells (PBMCs) of Val/Val humans is associated negatively with lifetime stress and positively with WM performance; it interacts with stress to modulate prefrontal activity during WM, such that greater stress and lower methylation are related to reduced cortical efficiency; and it is inversely related to mRNA expression and protein levels, potentially explaining the in vivo effects. Finally, methylation of COMT in prefrontal cortex and that in PBMCs of rats are correlated. The relationship of methylation of the COMT Val(158) allele with stress, gene expression, WM performance, and related brain activity suggests that stress-related methylation is associated with silencing of the gene, which partially compensates the physiological role of the high-activity Val allele in prefrontal cognition and activity. Moreover, these results demonstrate how stress-related DNA methylation of specific functional alleles impacts directly on human brain physiology beyond sequence variation.

TypeLoader: A fast and efficient automated workflow for the annotation and submission of novel full-length HLA alleles.

Science.gov (United States)

Surendranath, V; Albrecht, V; Hayhurst, J D; Schöne, B; Robinson, J; Marsh, S G E; Schmidt, A H; Lange, V

2017-07-01

Recent years have seen a rapid increase in the discovery of novel allelic variants of the human leukocyte antigen (HLA) genes. Commonly, only the exons encoding the peptide binding domains of novel HLA alleles are submitted. As a result, the IPD-IMGT/HLA Database lacks sequence information outside those regions for the majority of known alleles. This has implications for the application of the new sequencing technologies, which deliver sequence data often covering the complete gene. As these technologies simplify the characterization of the complete gene regions, it is desirable for novel alleles to be submitted as full-length sequences to the database. However, the manual annotation of full-length alleles and the generation of specific formats required by the sequence repositories is prone to error and time consuming. We have developed TypeLoader to address both these facets. With only the full-length sequence as a starting point, Typeloader performs automatic sequence annotation and subsequently handles all steps involved in preparing the specific formats for submission with very little manual intervention. TypeLoader is routinely used at the DKMS Life Science Lab and has aided in the successful submission of more than 900 novel HLA alleles as full-length sequences to the European Nucleotide Archive repository and the IPD-IMGT/HLA Database with a 95% reduction in the time spent on annotation and submission when compared with handling these processes manually. TypeLoader is implemented as a web application and can be easily installed and used on a standalone Linux desktop system or within a Linux client/server architecture. TypeLoader is downloadable from http://www.github.com/DKMS-LSL/typeloader. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.