ForestQC: Quality control on genetic variants from next-generation sequencing data using random forest.

Next-generation sequencing technology (NGS) enables the discovery of nearly all genetic variants present in a genome. A subset of these variants, however, may have poor sequencing quality due to limitations in NGS or variant callers. In genetic studies that analyze a large number of sequenced individuals, it is critical to detect and remove those variants with poor quality as they may cause spurious findings. In this paper, we present ForestQC, a statistical tool for performing quality control on variants identified from NGS data by combining a traditional filtering approach and a machine learning approach. Our software uses the information on sequencing quality, such as sequencing depth, genotyping quality, and GC contents, to predict whether a particular variant is likely to be false-positive. To evaluate ForestQC, we applied it to two whole-genome sequencing datasets where one dataset consists of related individuals from families while the other consists of unrelated individuals. Results indicate that ForestQC outperforms widely used methods for performing quality control on variants such as VQSR of GATK by considerably improving the quality of variants to be included in the analysis. ForestQC is also very efficient, and hence can be applied to large sequencing datasets. We conclude that combining a machine learning algorithm trained with sequencing quality information and the filtering approach is a practical approach to perform quality control on genetic variants from sequencing data

Coupling a distributed grid based hydrological model and MM5 meteorological model for flooding alert mapping

International audienceThe increased number of extreme rainfall events seems to be one of the common feature of climate change signal all over the world (Easterlin et al., 2000; Meehl et al., 2000). In the last few years a large number of floods caused by extreme meteorological events has been observed over the river basins of Mediterranean area and they mainly affected small basins (few hundreds until few thousands of square kilometres of drainage area) . A strategic goal of applied meteorology is now to try to predict with high spatial resolution the segments of drainage network where floods may occur. A possible way to reach this aim is the coupling of meteorological mesoscale model with high resolution hydrological model. In this work few case studies of observed floods in the Italian Mediterranean area will be presented. It is shown how a distributed hydrological model, using the precipitation fields predicted by MM5 meteorological model, is able to highlight the area where the major floods may occur

Alkali-activation of aggregate fines from construction and demolition waste: valorisation in view of road pavement subbase applications

This study investigates the potential of fine particles of recycled construction and demolition waste (CDW) aggregate to undergo alkali-activation when mixed with an appropriate alkaline solution. The fine is a natural by-product of the milling process and includes particles from four main material sources (i.e., recycled concrete, recycled asphalt, crushed bricks and tiles, and natural aggregate and excavated soil) and other occasional elements which are too small for identification. The fine was obtained by sifting the material through a 125 μm sieve. Since the reactivity of unselected material depends on its constituents, these were also individually investigated. Firstly, the four constituents of CDW recycled aggregates were separated, then milled to a size smaller than 125 μm, before being tested to measure their reactivity to an alkaline solution. A preliminary chemical and mineralogical characterization of the five powders was carried out to identify the main crystalline phases and ascertain the presence of aluminosilicates needed for the alkali activation process. Particles of each powder were afterwards mixed with three concentrations of the same alkaline solution with a liquid/solid mass ratio of 0.4, cast in prismatic moulds, and cured at room temperature. Mechanical tests after 3, 7, and 28 days of curing demonstrated that powders react positively in a basic environment, showing an increase in strength without any thermal treatment. Hardened pastes of undivided fine aggregate and recycled asphalt exhibited the best results in terms of flexural and compressive strength with the more concentrated solution. A Field Emission Scanning Electron Microscopy analysis was also carried out to observe the microstructure and to support an interpretation of the mechanical strength data. Results demonstrated the feasibility of using a solution to activate unselected CDW fine particles to stabilize CDW aggregates. In full scale applications, CDW aggregates can be stabilized without the addition of any binder

Effect of Degradation on Mechanical Strengths of Alkali-Activated Fines in Stabilized Construction and Demolition Waste Aggregates

Recent works have demonstrated that construction and demolition waste (CDW) aggregates for subbase road pavement applications can be stabilized via the alkali activation of their fine fraction (d<0.125 mm). Despite the promising results with this method, the durability of alkali-activated (AA) CDW fines (which act to stabilize CDW aggregate mixtures) need to be investigated. To this end, the effects on pavement materials of the typical degrading actions of water, deicing salts, and the freeze-thaw process were investigated. Samples of AA fines were subjected to water, deicing salt, and freeze-thaw treatments and assessed based on the variation in 28-day flexural and compressive strength values with respect to not-degraded materials. In addition to the fines normally present in CDW aggregate mixtures (i.e., the undivided fraction), samples with fines of the main CDW constituents (concrete, asphalt, bricks and tiles, aggregates and soil) were also prepared for comparison purposes. One set of specimens was cured at 20°C to replicate field conditions, and another was treated at 80°C to replicate optimal conditions for AA materials. Although 80°C heat-treated specimens achieved higher strength values, those values fell sharply following the degrading action of water and deicing salts. In contrast, the specimens cured at 20°C retained their mechanical property values even after exposure to water and deicing salt degradations

Alkali-activation of marble sludge: Influence of curing conditions and waste glass addition

The use of marble sludge as precursor for new alkali activated materials was assessed studying three different curing conditions (air, humid and water immersion, respectively), after an initial curing at 60 °C for 24 h, and two glass powder fractions additions (2.5 and 5.0 vol%). Microstructural, physical (drying shrinkage, Fourier transform-infrared (FT-IR) spectroscopy, X-ray spectroscopy (XPS)), thermal (differential thermal analysis – thermogravimetric analysis, DTA-TGA) and mechanical (flexural and compressive strength) properties were investigated. Air curing was the most favourable atmosphere for mechanical properties development because it promotes Si-O-Si polymerization and gel densification, as demonstrated by FT-IR and FE-SEM observations, respectively. Satisfactory mechanical properties were achieved (18 MPa and 45 MPa, for flexural and compressive strength, respectively) in particular for glass containing mixtures. Moreover, glass powder addition significantly reduced drying shrinkage of air-cured samples because it operated as a rigid aggregate in the matrix and strengthened the formed gel

Immunosuppressive effect and global dysregulation of blood transcriptome in response to psychosocial stress in vervet monkeys (Chlorocebus sabaeus).

Psychosocial stressors - life events that challenge social support and relationships - represent powerful risk factors for human disease; included amongst these events are relocation, isolation and displacement. To evaluate the impact of a controlled psychosocial stressor on physiology and underlying molecular pathways, we longitudinally studied the influence of a 28-day period of quarantine on biomarkers of immune signalling, microbial translocation, glycaemic health and blood transcriptome in the wild-born vervet monkey. This event caused a coordinated, mostly transient, reduction of circulating levels of nine immune signalling molecules. These were paralleled by a massive dysregulation of blood transcriptome, including genes implicated in chronic pathologies and immune functions. Immune and inflammatory functions were enriched among the genes downregulated in response to stress. An upregulation of genes involved in blood coagulation, platelet activation was characteristic of the rapid response to stress induction. Stress also decreased neutrophils and increased CD4 + T cell proportions in blood. This model of psychosocial stress, characterised by an immune dysregulation at the transcriptomic, molecular and cellular levels, creates opportunities to uncover the underlying mechanisms of stress-related diseases with an immune component, including cardiovascular diseases and susceptibility to infections

Numerical comparison of CBS and SGS as stabilization techniques for the incompressible Navier–Stokes equations

In this work, we present numerical comparisons of some stabilization methods for the incompressible Navier&ndash;Stokes. The first is the characteristic‐based split (CBS). It combines the characteristic Galerkin method to deal with convection‐dominated flows with a classical splitting technique, which in some cases allows us to use equal velocity&ndash;pressure interpolations. The other two approaches are particular cases of the subgrid scale (SGS) method. The first, obtained after an algebraic approximation of the subgrid scales, is very similar to the popular Galerkin/least‐squares (GLS) method, whereas in the second, the subscales are assumed to be orthogonal to the finite element space. It is shown that all these formulations display similar stabilization mechanisms, provided the stabilization parameter of the SGS methods is identified with the time step of the CBS approach. This paper provides the numerical experiments for the comparison of formulations made by Codina and Zienkiewicz in a previous article

Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy.

Retinal nerve fibre layer (RNFL) thickness is related to the axonal anterior visual pathway and is considered a marker of overall white matter 'integrity'. We hypothesised that RNFL changes would occur in people with epilepsy, independently of vigabatrin exposure, and be related to clinical characteristics of epilepsy

The Cepheids of NGC1866: A Precise Benchmark for the Extragalactic Distance Scale and Stellar Evolution from Modern UBVI Photometry

We present the analysis of multiband time-series data for a sample of 24 Cepheids in the field of the Large Magellanic Cloud cluster NGC1866. Very accurate BVI VLT photometry is combined with archival UBVI data, covering a large temporal window, to obtain precise mean magnitudes and periods with typical errors of 1-2% and of 1 ppm, respectively. These results represent the first accurate and homogeneous dataset for a substantial sample of Cepheid variables belonging to a cluster and hence sharing common distance, age and original chemical composition. Comparisons of the resulting multiband Period-Luminosity and Wesenheit relations to both empirical and theoretical results for the Large Magellanic Cloud are presented and discussed to derive the distance of the cluster and to constrain the mass-luminosity relation of the Cepheids. The adopted theoretical scenario is also tested by comparison with independent calibrations of the Cepheid Wesenheit zero point based on trigonometric parallaxes and Baade-Wesselink techniques. Our analysis suggests that a mild overshooting and/or a moderate mass loss can affect intermediate-mass stellar evolution in this cluster and gives a distance modulus of 18.50 +- 0.01 mag. The obtained V,I color-magnitude diagram is also analysed and compared with both synthetic models and theoretical isochrones for a range of ages and metallicities and for different efficiencies of core overshooting. As a result, we find that the age of NGC1866 is about 140 Myr, assuming Z = 0.008 and the mild efficiency of overshooting suggested by the comparison with the pulsation models.Comment: 13 pages, 10 figures, accepted in MNRAS (2016 January 14