Comparison of prestellar core elongations and large-scale molecular cloud structures in the Lupus 1 region

Turbulence and magnetic fields are expected to be important for regulating molecular cloud formation and evolution. However, their effects on sub-parsec to 100 parsec scales, leading to the formation of starless cores, are not well understood. We investigate the prestellar core structure morphologies obtained from analysis of the Herschel-SPIRE 350 mum maps of the Lupus I cloud. This distribution is first compared on a statistical basis to the large-scale shape of the main filament. We find the distribution of the elongation position angle of the cores to be consistent with a random distribution, which means no specific orientation of the morphology of the cores is observed with respect to the mean orientation of the large-scale filament in Lupus I, nor relative to a large-scale bent filament model. This distribution is also compared to the mean orientation of the large-scale magnetic fields probed at 350 mum with the Balloon-borne Large Aperture Telescope for Polarimetry during its 2010 campaign. Here again we do not find any correlation between the core morphology distribution and the average orientation of the magnetic fields on parsec scales. Our main conclusion is that the local filament dynamics---including secondary filaments that often run orthogonally to the primary filament---and possibly small-scale variations in the local magnetic field direction, could be the dominant factors for explaining the final orientation of each core

Genome modeling system: A knowledge management platform for genomics

In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms

Empirical modelling of the BLASTPol achromatic half-wave plate for precision submillimetre polarimetry

A cryogenic achromatic half-wave plate (HWP) for submillimetre astronomical polarimetry has been designed, manufactured, tested and deployed in the Balloon-borne Large-Aperture Submillimeter Telescope for Polarimetry (BLASTPol). The design is based on the five-slab Pancharatnam recipe and itworks in thewavelength range 200–600 μm, making it the broadestband HWP built to date at (sub)millimetre wavelengths. The frequency behaviour of the HWP has been fully characterized at room and cryogenic temperatures with incoherent radiation from a polarizing Fourier transform spectrometer. We develop a novel empirical model, complementary to the physical and analytical ones available in the literature, that allows us to recover the HWP Mueller matrix and phase shift as a function of frequency and extrapolated to 4 K. We show that most of the HWP non-idealities can be modelled by quantifying one wavelength-dependent parameter, the position of the HWP equivalent axes, which is then readily implemented in a map-making algorithm. We derive this parameter for a range of spectral signatures of input astronomical sources relevant to BLASTPol, and provide a benchmark example of how our method can yield improved accuracy on measurements of the polarization angle on the sky at submillimetre wavelengths

Pro-oxidant Induced DNA Damage in Human Lymphoblastoid Cells: Homeostatic Mechanisms of Genotoxic Tolerance

Oxidative stress contributes to many disease etiologies including ageing, neurodegeneration, and cancer, partly through DNA damage induction (genotoxicity). Understanding the i nteractions of free radicals with DNA is fundamental to discern mutation risks. In genetic toxicology, regulatory authorities consider that most genotoxins exhibit a linear relationship between dose and mutagenic response. Yet, homeostatic mechanisms, including DNA repair, that allow cells to tolerate low levels of genotoxic exposure exist. Acceptance of thresholds for genotoxicity has widespread consequences in terms of understanding cancer risk and regulating human exposure to chemicals/drugs. Three pro-oxidant chemicals, hydrogen peroxide (H2O2), potassium bromate (KBrO3), and menadione, were examined for low dose-response curves in human lymphoblastoid cells. DNA repair and antioxidant capacity were assessed as possible threshold mechanisms. H2O2 and KBrO3, but not menadione, exhibited thresholded responses, containing a range of nongenotoxic low doses. Levels of the DNA glycosylase 8-oxoguanine glycosylase were unchanged in response to pro- oxidant stress. DNA repair–focused gene expression arrays reported changes in ATM and BRCA1, involved in double-strand break repair, in response to low-dose pro-oxidant exposure; however, these alterations were not substantiated at the protein level. Determination of oxidatively induced DNA damage in H2O2-treated AHH-1 cells reported accumulation of thymine glycol above the genotoxic threshold. Further, the H2O2 dose-response curve was shifted by modulating the antioxidant glutathione. Hence, observed pro- oxidant thresholds were due to protective capacities of base excision repair enzymes and antioxidants against DNA damage, highlighting the importance of homeostatic mechanisms in “genotoxic tolerance.

AMI radio continuum observations of young stellar objects with known outflows

We present 16 GHz (1.9 cm) deep radio continuum observations made with the Arcminute Microkelvin Imager (AMI) of a sample of low-mass young stars driving jets. We combine these new data with archival information from an extensive literature search to examine spectral energy distributions (SEDs) for each source and calculate both the radio and sub-mm spectral indices in two different scenarios: (1) fixing the dust temperature (Td) according to evolutionary class; and (2) allowing Td to vary. We use the results of this analysis to place constraints on the physical mechanisms responsible for the radio emission. From AMI data alone, as well as from model fitting to the full SED in both scenarios, we find that 80 per cent of the objects in this sample have spectral indices consistent with freefree emission. We find an average spectral index in both Td scenarios, consistent with freefree emission. We examine correlations of the radio luminosity with bolometric luminosity, envelope mass and outflow force, and find that these data are consistent with the strong correlation with envelope mass seen in lower luminosity samples. We examine the errors associated with determining the radio luminosity and find that the dominant source of error is the uncertainty on the opacity index, beta. We examine the SEDs for variability in these young objects, and find evidence for possible radio flare events in the histories of L1551 IRS 5 and Serpens SMM 1

Human and mouse essentiality screens as a resource for disease gene discovery.

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery