459 research outputs found

    Répartition de diffuseurs pour l'ajustement des caractéristiques d'un canal de propagation simulé dans un contexte V2V

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    National audienceDans ce papier, nous proposons une méthode de type géométrique-stochastique pour modéliser des canaux de propagation d'un système de communication sans-fil de véhicule à véhicule et véhicule à infrastructure (V2X). Cette méthode permet de définir des scénarios dynamiques et sa flexibilité nous offre la possibilité de paramétrer les caractéristiques d'un canal de propagation. Nous montrons pour l'essentiel de quelle manière l'agencement et le nombre de diffuseurs de forme simple peuvent contribuer à influencer les statistiques de l'étalement des retards et la distribution des angles d'arrivée

    MAPfastR: Quantitative Trait Loci Mapping in Outbred Line Crosses

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    MAPfastR is a software package developed to analyze quantitative trait loci data from inbred and outbred line-crosses. The package includes a number of modules for fast and accurate quantitative trait loci analyses. It has been developed in the R language for fast and comprehensive analyses of large datasets. MAPfastR is freely available at: http://www.computationalgenetics.se/?page_id=7.Swedish Foundation for Strategic Research (Future Research Leader program), European Science Foundation (EURYI Award)

    Replication and Explorations of High-Order Epistasis Using a Large Advanced Intercross Line Pedigree

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    Dissection of the genetic architecture of complex traits persists as a major challenge in biology; despite considerable efforts, much remains unclear including the role and importance of genetic interactions. This study provides empirical evidence for a strong and persistent contribution of both second- and third-order epistatic interactions to long-term selection response for body weight in two divergently selected chicken lines. We earlier reported a network of interacting loci with large effects on body weight in an F2 intercross between these high– and low–body weight lines. Here, most pair-wise interactions in the network are replicated in an independent eight-generation advanced intercross line (AIL). The original report showed an important contribution of capacitating epistasis to growth, meaning that the genotype at a hub in the network releases the effects of one or several peripheral loci. After fine-mapping of the loci in the AIL, we show that these interactions were persistent over time. The replication of five of six originally reported epistatic loci, as well as the capacitating epistasis, provides strong empirical evidence that the originally observed epistasis is of biological importance and is a contributor in the genetic architecture of this population. The stability of genetic interaction mechanisms over time indicates a non-transient role of epistasis on phenotypic change. Third-order epistasis was for the first time examined in this study and was shown to make an important contribution to growth, which suggests that the genetic architecture of growth is more complex than can be explained by two-locus interactions only. Our results illustrate the importance of designing studies that facilitate exploration of epistasis in populations for obtaining a comprehensive understanding of the genetics underlying a complex trait

    Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity

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    TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5α but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations

    A genetic algorithm based method for stringent haplotyping of family data

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    <p>Abstract</p> <p>Background</p> <p>The linkage phase, or haplotype, is an extra level of information that in addition to genotype and pedigree can be useful for reconstructing the inheritance pattern of the alleles in a pedigree, and computing for example Identity By Descent probabilities. If a haplotype is provided, the precision of estimated IBD probabilities increases, as long as the haplotype is estimated without errors. It is therefore important to only use haplotypes that are strongly supported by the available data for IBD estimation, to avoid introducing new errors due to erroneous linkage phases.</p> <p>Results</p> <p>We propose a genetic algorithm based method for haplotype estimation in family data that includes a stringency parameter. This allows the user to decide the error tolerance level when inferring parental origin of the alleles. This is a novel feature compared to existing methods for haplotype estimation. We show that using a high stringency produces haplotype data with few errors, whereas a low stringency provides haplotype estimates in most situations, but with an increased number of errors.</p> <p>Conclusion</p> <p>By including a stringency criterion in our haplotyping method, the user is able to maintain the error rate at a suitable level for the particular study; one can select anything from haplotyped data with very small proportion of errors and a higher proportion of non-inferred haplotypes, to data with phase estimates for every marker, when haplotype errors are tolerable. Giving this choice makes the method more flexible and useful in a wide range of applications as it is able to fulfil different requirements regarding the tolerance for haplotype errors, or uncertain marker-phases.</p

    Ankle brachial index is equally predictive of exercise-induced limb ischemia in diabetic and non-diabetic patients with walking limitation

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    BACKGROUND: In diabetic patients, arterial stiffness may impair compressibility of vessels and result in higher ankle to brachial index (ABI) than in non-diabetic subjects. METHODS: We studied 1972 non-diabetic and 601 diabetic patients, with suspected peripheral artery disease, Exercise transcutaneous oxygen pressure (Ex-tcpO2), expressed in DROP index (limb tcpO2 change minus chest tcpO2 change), is insensitive to arterial stiffness and can estimate exercise-induced regional blood flow impairment (RBFI). A minimal DROP &lt;-15 mm Hg indicates the presence of RBFI (positive test). ABI was simplified to a category variable (ABIc) by rounding ABI to the closest first decimal. RESULTS: In the ABIc range 0.4 to 1.1 linear regression for mean DROP values were: y = 34 x - 53; (R = 0.211) and y = 33 x - 52; (R = 0.186) in diabetic and Non-diabetic patients, respectively. Both Db and non-D patients showed a high proportion of positive Ex-tcpO2 tests for ABIc in the normal range (ABIc: 1.0 and over) from 27.1 to up to 58%. More than half of patients with borderline ABI (ABIc = 0.9) had RBFI during exercise. it was 65.6% in diabetic and 58.5% non-diabetic patients. CONCLUSIONS: Resting ABI was not a better predictor of exercise-induced RBFI in non-Db than in Diabetic patients. Our results highlights the interest of still measuring resting-ABI in diabetic patients to argue for the vascular origin of exertional limb pain, but also of performing exercise tests in patients with walking impairment

    Fine mapping and replication of QTL in outbred chicken advanced intercross lines

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    Background: Linkage mapping is used to identify genomic regions affecting the expression of complex traits. However, when experimental crosses such as F2 populations or backcrosses are used to map regions containing a Quantitative Trait Locus (QTL), the size of the regions identified remains quite large, i.e. 10 or more Mb. Thus, other experimental strategies are needed to refine the QTL locations. Advanced Intercross Lines (AIL) are produced by repeated intercrossing of F2 animals and successive generations, which decrease linkage disequilibrium in a controlled manner. Although this approach is seen as promising, both to replicate QTL analyses and fine-map QTL, only a few AIL datasets, all originating from inbred founders, have been reported in the literature. Methods: We have produced a nine-generation AIL pedigree (n = 1529) from two outbred chicken lines divergently selected for body weight at eight weeks of age. All animals were weighed at eight weeks of age and genotyped for SNP located in nine genomic regions where significant or suggestive QTL had previously been detected in the F2 population. In parallel, we have developed a novel strategy to analyse the data that uses both genotype and pedigree information of all AIL individuals to replicate the detection of and fine-map QTL affecting juvenile body weight. Results: Five of the nine QTL detected with the original F2 population were confirmed and fine-mapped with the AIL, while for the remaining four, only suggestive evidence of their existence was obtained. All original QTL were confirmed as a single locus, except for one, which split into two linked QTL. Conclusions: Our results indicate that many of the QTL, which are genome-wide significant or suggestive in the analyses of large intercross populations, are true effects that can be replicated and fine-mapped using AIL. Key factors for success are the use of large populations and powerful statistical tools. Moreover, we believe that the statistical methods we have developed to efficiently study outbred AIL populations will increase the number of organisms for which in-depth complex traits can be analyzed

    Measurement of the atmospheric muon charge ratio with the OPERA detector

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    The OPERA detector at the Gran Sasso underground laboratory (LNGS) was used to measure the atmospheric muon charge ratio in the TeV energy region. We analyzed 403069 atmospheric muons corresponding to 113.4 days of livetime during the 2008 CNGS run. We computed separately the muon charge ratio for single and for multiple muon events in order to select different energy regions of the primary cosmic ray spectrum and to test the charge ratio dependence on the primary composition. The measured charge ratio values were corrected taking into account the charge-misidentification errors. Data have also been grouped in five bins of the "vertical surface energy". A fit to a simplified model of muon production in the atmosphere allowed the determination of the pion and kaon charge ratios weighted by the cosmic ray energy spectrum.Comment: 14 pages, 10 figure
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