Second-generation PLINK: rising to the challenge of larger and richer datasets

PLINK 1 is a widely used open-source C/C++ toolset for genome-wide association studies (GWAS) and research in population genetics. However, the steady accumulation of data from imputation and whole-genome sequencing studies has exposed a strong need for even faster and more scalable implementations of key functions. In addition, GWAS and population-genetic data now frequently contain probabilistic calls, phase information, and/or multiallelic variants, none of which can be represented by PLINK 1's primary data format. To address these issues, we are developing a second-generation codebase for PLINK. The first major release from this codebase, PLINK 1.9, introduces extensive use of bit-level parallelism, O(sqrt(n))-time/constant-space Hardy-Weinberg equilibrium and Fisher's exact tests, and many other algorithmic improvements. In combination, these changes accelerate most operations by 1-4 orders of magnitude, and allow the program to handle datasets too large to fit in RAM. This will be followed by PLINK 2.0, which will introduce (a) a new data format capable of efficiently representing probabilities, phase, and multiallelic variants, and (b) extensions of many functions to account for the new types of information. The second-generation versions of PLINK will offer dramatic improvements in performance and compatibility. For the first time, users without access to high-end computing resources can perform several essential analyses of the feature-rich and very large genetic datasets coming into use.Comment: 2 figures, 1 additional fil

Thin Metal Film Sensors

During the last decade some progress have been made in the field of sensors using thin film techniques. In particular thin metal film strain gauges and thin film temperature sensors based on the temperature dependent resistivity of metal are now commonly used. But changes in other transport parameters with various measurands are also useful for the design of metal film sensors. Difficulty arises in thin film techniques when structural defects are frozen in films

High-order discrete ordinate transport in hexagonal geometry: A new capability in ERANOS

This paper presents the implementation of an arbitrary order discontinuous Galerkin scheme within the framework of a discrete ordinate solver of the neutron transport equation for nuclear reactor calculations. More precisely, it deals with non-conforming spatial meshes for the 2D and 3D modeling of core geometries based on hexagonal assemblies. This work aims at improving the capabilities of the ERANOS code system dedicated to fast reactor analysis and design. Both the angular quadrature and spatial scheme peculiarities for hexagonal geometries are presented. A particular focus is set on the spatial non-conforming mesh and variable order capabilities of this scheme in anticipation to the development of spatial adaptiveness algorithms. These features are illustrated on a 3D numerical benchmark with comparison to a Monte Carlo reference and a 2D benchmark that shows the potential of this scheme for both h- and p-adaptation

Hydrological impacts of climate change on the Tejo and Guadiana Rivers

International audienceA distributed daily rainfall?runoff model is applied to the Tejo and Guadiana river basins in Spain and Portugal to simulate the effects of climate change on runoff production, river flows and water resource availability with results aggregated to the monthly level. The model is calibrated, validated and then used for a series of climate change impact assessments for the period 2070?2100. Future scenarios are derived from the HadRM3H regional climate model (RCM) using two techniques: firstly a bias-corrected RCM output, with monthly mean correction factors calculated from observed rainfall records; and, secondly, a circulation-pattern-based stochastic rainfall model. Major reductions in rainfall and streamflow are projected throughout the year; these results differ from those for previous studies where winter increases are projected. Despite uncertainties in the representation of heavily managed river systems, the projected impacts are serious and pose major threats to the maintenance of bipartite water treaties between Spain and Portugal and the supply of water to urban and rural regions of Portugal

Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models

Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1-6 and determined the infectivity titer of acute-phase plasma pools in additional animals. The courses of first- and second-passage infections were similar, with early appearance of viremia, HCV RNA titers of >10(4.7) IU/mL, and development of acute hepatitis; the chronicity rate was 56%. The challenge pools had titers of 10(3)-10(5) chimpanzee infectious doses/mL. Human liver-chimeric mice developed high-titer infections after inoculation with the challenge viruses of genotypes 1-6. Inoculation studies with different doses of the genotype 1b pool suggested that a relatively high virus dose is required to consistently infect chimeric mice. The challenge pools represent a unique resource for studies of HCV molecular virology and for studies of pathogenesis, protective immunity, and vaccine efficacy in vivo

A new pear scab resistance gene Rvp1 from the European pear cultivar ‘Navara’ maps in a genomic region syntenic to an apple scab resistance gene cluster on linkage group 2

Scab, caused by the ascomycete fungus Venturia pirina, leads to severe damage on European pear varieties resulting in a loss of commercial value and requiring frequent use of fungicides. Identifying scab resistance genes, developing molecular markers linked to these genes and establishing marker-assisted selection would be an effective way to improve European pear breeding for scab resistance. Most of the European pear cultivars (Pyrus communis) are currently reported to be sensitive. The pear cultivar ‘Navara’ was shown to carry a major scab resistance gene whose phenotypic expression in seedling progenies was a typical stellate necrosis symptom. The resistance gene was called Rvp1, for resistance to V. pirina, and was mapped on linkage group 2 of the pear genome close to microsatellite marker CH02b10. This genomic region is known to carry a cluster of scab resistance genes in apple indicating a first functional synteny for scab resistance between apple and pear