Sofia 2 - An automated, parallel H i source finding pipeline for the WALLABY survey

We present SoFiA 2, the fully automated 3D source finding pipeline for the WALLABY extragalactic HI survey with the Australian SKA Pathfinder (ASKAP). SoFiA 2 is a reimplementation of parts of the original SoFiA pipeline in the C programming language and makes use of OpenMP for multi-threading of the most time-critical algorithms. In addition, we have developed a parallel framework called SoFiA-X that allows the processing of large data cubes to be split across multiple computing nodes. As a result of these efforts, SoFiA 2 is substantially faster and comes with a much reduced memory footprint compared to its predecessor, thus allowing the large WALLABY data volumes of hundreds of gigabytes of imaging data per epoch to be processed in real-time. The source code has been made publicly available to the entire community under an open-source licence. Performance tests using mock galaxies injected into genuine ASKAP data suggest that in the absence of significant imaging artefacts SoFiA 2 is capable of achieving near-100% completeness and reliability above an integrated signal-to-noise ratio of about 5-6. We also demonstrate that SoFiA 2 generally recovers the location, integrated flux and w20 line width of galaxies with high accuracy. Other parameters, including the peak flux density and w50 line width, are more strongly biased due to the influence of the noise on the measurement. In addition, very faint galaxies below an integrated signal-to-noise ratio of about 10 may get broken up into multiple components, thus requiring a strategy to identify fragmented sources and ensure that they do not affect the integrity of any scientific analysis based on the SoFiA 2 output.Comment: 16 pages, 10 figures, 1 table, accepted for publication in MNRA

Cross-validated stepwise regression for identification of novel non-nucleoside reverse transcriptase inhibitor resistance associated mutations

<p>Abstract</p> <p>Background</p> <p>Linear regression models are used to quantitatively predict drug resistance, the phenotype, from the HIV-1 viral genotype. As new antiretroviral drugs become available, new resistance pathways emerge and the number of resistance associated mutations continues to increase. To accurately identify which drug options are left, the main goal of the modeling has been to maximize predictivity and not interpretability. However, we originally selected linear regression as the preferred method for its transparency as opposed to other techniques such as neural networks. Here, we apply a method to lower the complexity of these phenotype prediction models using a 3-fold cross-validated selection of mutations.</p> <p>Results</p> <p>Compared to standard stepwise regression we were able to reduce the number of mutations in the reverse transcriptase (RT) inhibitor models as well as the number of interaction terms accounting for synergistic and antagonistic effects. This reduction in complexity was most significant for the non-nucleoside reverse transcriptase inhibitor (NNRTI) models, while maintaining prediction accuracy and retaining virtually all known resistance associated mutations as first order terms in the models. Furthermore, for etravirine (ETR) a better performance was seen on two years of unseen data. By analyzing the phenotype prediction models we identified a list of forty novel NNRTI mutations, putatively associated with resistance. The resistance association of novel variants at known NNRTI resistance positions: 100, 101, 181, 190, 221 and of mutations at positions not previously linked with NNRTI resistance: 102, 139, 219, 241, 376 and 382 was confirmed by phenotyping site-directed mutants.</p> <p>Conclusions</p> <p>We successfully identified and validated novel NNRTI resistance associated mutations by developing parsimonious resistance prediction models in which repeated cross-validation within the stepwise regression was applied. Our model selection technique is computationally feasible for large data sets and provides an approach to the continued identification of resistance-causing mutations.</p

Infrared and optical spectroscopy of alpha and gamma-phase Ce

We determined the optical properties of alpha- and gamma-phase Ce in the photon energy range from 60 meV to 2.5 eV using ellipsometry and grazing incidence reflectometry. We observe significant changes of the optical conductivity, the dynamical scattering rate, and the effective mass between alpha- and gamma-cerium. The alpha-phase is characterized by Fermi-liquid frequency dependent scattering rate, and an effective mass of about 20 m_e on an energy scale of about 0.2 eV. In gamma-Ce the charge carriers have a large scattering rate in the far infrared, and a carrier mass characteristic of 5d band electrons. In addition we observe a prominent absorption feature in alpha-Ce, which is absent in gamma-Ce, indicating significant differences of the electronic structure between the two phases.Comment: 5 pages, REVTeX, 2 eps-figures, Phys.Rev.Lett., in pres

Comparing the effects of sun exposure and vitamin D supplementation on vitamin D insufficiency, and immune and cardio-metabolic function: The Sun Exposure and Vitamin D Supplementation (SEDS) Study

Background: Adults living in the sunny Australian climate are at high risk of skin cancer, but vitamin D deficiency (defined here as a serum 25-hydroxyvitamin D (25(OH)D) concentration of less than 50 nmol/L) is also common. Vitamin D deficiency may be a risk factor for a range of diseases. However, the optimal strategies to achieve and maintain vitamin D adequacy (sun exposure, vitamin D supplementation or both), and whether sun exposure itself has benefits over and above initiating synthesis of vitamin D, remain unclear. The Sun Exposure and Vitamin D Supplementation (SEDS) Study aims to compare the effectiveness of sun exposure and vitamin D supplementation for the management of vitamin D insufficiency, and to test whether these management strategies differentially affect markers of immune and cardio-metabolic function. Methods/Design: The SEDS Study is a multi-centre, randomised controlled trial of two different daily doses of vitamin D supplementation, and placebo, in conjunction with guidance on two different patterns of sun exposure. Participants recruited from across Australia are aged 18-64 years and have a recent vitamin D test result showing a serum 25(OH)D level of 40-60 nmol/L. Discussion: This paper discusses the rationale behind the study design, and considers the challenges but necessity of data collection within a non-institutionalised adult population, in order to address the study aims. We also discuss the challenges of participant recruitment and retention, ongoing engagement of referring medical practitioners and address issues of compliance and participant retention. Trial registration: Australia New Zealand Clinical Trials Registry: ACTRN12613000290796 Registered 14 March 2013

WALLABY Pilot Survey:The Diversity of Ram Pressure Stripping of the Galactic H I Gas in the Hydra Cluster

This study uses HI image data from the WALLABY pilot survey with the ASKAP telescope, covering the Hydra cluster out to 2.5$r_{200}$. We present the projected phase-space distribution of HI-detected galaxies in Hydra, and identify that nearly two thirds of the galaxies within $1.25r_{200}$ may be in the early stages of ram pressure stripping. More than half of these may be only weakly stripped, with the ratio of strippable HI (i.e., where the galactic restoring force is lower than the ram pressure in the disk) mass fraction (over total HI mass) distributed uniformly below 90%. Consequently, the HI mass is expected to decrease by only a few 0.1 dex after the currently strippable portion of HI in these systems has been stripped. A more detailed look at the subset of galaxies that are spatially resolved by WALLABY observations shows that, while it typically takes less than 200 Myr for ram pressure stripping to remove the currently strippable portion of HI, it may take more than 600 Myr to significantly change the total HI mass. Our results provide new clues to understanding the different rates of HI depletion and star formation quenching in cluster galaxies.Comment: 25 pages, 10 figures, 1 table. Accepted for publication at Ap

Extreme genetic fragility of the HIV-1 capsid

Genetic robustness, or fragility, is defined as the ability, or lack thereof, of a biological entity to maintain function in the face of mutations. Viruses that replicate via RNA intermediates exhibit high mutation rates, and robustness should be particularly advantageous to them. The capsid (CA) domain of the HIV-1 Gag protein is under strong pressure to conserve functional roles in viral assembly, maturation, uncoating, and nuclear import. However, CA is also under strong immunological pressure to diversify. Therefore, it would be particularly advantageous for CA to evolve genetic robustness. To measure the genetic robustness of HIV-1 CA, we generated a library of single amino acid substitution mutants, encompassing almost half the residues in CA. Strikingly, we found HIV-1 CA to be the most genetically fragile protein that has been analyzed using such an approach, with 70% of mutations yielding replication-defective viruses. Although CA participates in several steps in HIV-1 replication, analysis of conditionally (temperature sensitive) and constitutively non-viable mutants revealed that the biological basis for its genetic fragility was primarily the need to coordinate the accurate and efficient assembly of mature virions. All mutations that exist in naturally occurring HIV-1 subtype B populations at a frequency &gt;3%, and were also present in the mutant library, had fitness levels that were &gt;40% of WT. However, a substantial fraction of mutations with high fitness did not occur in natural populations, suggesting another form of selection pressure limiting variation in vivo. Additionally, known protective CTL epitopes occurred preferentially in domains of the HIV-1 CA that were even more genetically fragile than HIV-1 CA as a whole. The extreme genetic fragility of HIV-1 CA may be one reason why cell-mediated immune responses to Gag correlate with better prognosis in HIV-1 infection, and suggests that CA is a good target for therapy and vaccination strategies

Probiotics, prebiotics and immunomodulation of gut mucosal defences: homeostasis and immunopathology.

Probiotics are beneficial microbes that confer a realistic health benefit on the host, which in combination with prebiotics, (indigestible dietary fibre/carbohydrate), also confer a health benefit on the host via products resulting from anaerobic fermentation. There is a growing body of evidence documenting the immune-modulatory ability of probiotic bacteria, it is therefore reasonable to suggest that this is potentiated via a combination of prebiotics and probiotics as a symbiotic mix. The need for probiotic formulations has been appreciated for the health benefits in "topping up your good bacteria" or indeed in an attempt to normalise the dysbiotic microbiota associated with immunopathology. This review will focus on the immunomodulatory role of probiotics and prebiotics on the cells, molecules and immune responses in the gut mucosae, from epithelial barrier to priming of adaptive responses by antigen presenting cells: immune fate decision-tolerance or activation? Modulation of normal homeostatic mechanisms, coupled with findings from probiotic and prebiotic delivery in pathological studies, will highlight the role for these xenobiotics in dysbiosis associated with immunopathology in the context of inflammatory bowel disease, colorectal cancer and hypersensitivity

Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin