The accretion and spreading of matter on white dwarfs

For a slowly rotating non-magnetized white dwarf the accretion disk extends all the way to the star. Here the matter impacts and spreads towards the poles as new matter continuously piles up behind it. We have solved the 3d compressible Navier-Stokes equations on an axisymmetric grid to determine the structure of this boundary layer for different viscosities corresponding to different accretion rates. The high viscosity cases show a spreading BL which sets off a gravity wave in the surface matter. The accretion flow moves supersonically over the cusp making it susceptible to the rapid development of gravity wave and/or Kelvin-Helmholtz instabilities. This BL is optically thick and extends more than 30 degrees to either side of the disk plane after 3/4 of a Keplerian rotation period (t=19s). The low viscosity cases also show a spreading BL, but here the accretion flow does not set off gravity waves and it is optically thin.Comment: 6 pages, 5 figures, requires autart.cl

Simulations of the Boundary Layer Between a White Dwarf and its Accretion Disk

Using a 2.5D time-dependent axisymmetric numerical code we recently developed, we solve the full compressible Navier-Stokes equations (including an alpha-viscosity prescription) to determine the structure of the boundary layer between the white dwarf and the accretion disk in non-magnetic cataclysmic varia ble systems. In this preliminary work, our numerical approach does not include radiation. In the energy equation, we either take the dissipation function (Phi) into account or we assumed that the energy is instantly radiated away (Phi). For a slowly rotating non magnetized accreting white dwarf, the accretion disk e xtends all the way to the stellar surface. There, the matter impacts and spread s towards the poles as new matter continuously piles up behind it. We carried out numerical simulations for different values of the alpha viscosity parameter (alpha), corresponding to different mass accretion rates. In the high viscosity cases (alpha=0.1), the spreading boundary layer sets off a gravity wave in the s urface matter. The accretion flow moves supersonically over the cusp making it s usceptible to the rapid development of gravity wave and/or Kelvin-Helmholtz shea ring instabilities. This BL is optically thick and extends more than 30 degrees to either side of the disk plane after only 3/4 of a Keplerian rotation period (19s). In the low viscosity cases (alpha=0.001), the spreading boundary layer does not set off gravity waves and it is optically thin.Comment: final version, ApJ, in pres

Platelets Regulate Pulmonary Inflammation and Tissue Destruction in Tuberculosis.

RATIONALE: Platelets may interact with the immune system in tuberculosis (TB) to regulate human inflammatory responses that lead to morbidity and spread of infection. OBJECTIVES: To identify a functional role of platelets in the innate inflammatory and matrix-degrading response in TB. METHODS: Markers of platelet activation were examined in plasma from 50 patients with TB before treatment and 50 control subjects. Twenty-five patients were followed longitudinally. Platelet-monocyte interactions were studied in a coculture model infected with live, virulent Mycobacterium tuberculosis (M.tb) and dissected using qRT-PCR, Luminex multiplex arrays, matrix degradation assays, and colony counts. Immunohistochemistry detected CD41 (cluster of differentiation 41) expression in a pulmonary TB murine model, and secreted platelet factors were measured in BAL fluid from 15 patients with TB and matched control subjects. MEASUREMENTS AND MAIN RESULTS: Five of six platelet-associated mediators were upregulated in plasma of patients with TB compared with control subjects, with concentrations returning to baseline by Day 60 of treatment. Gene expression of the monocyte collagenase MMP-1 (matrix metalloproteinase-1) was upregulated by platelets in M.tb infection. Platelets also enhanced M.tb-induced MMP-1 and -10 secretion, which drove type I collagen degradation. Platelets increased monocyte IL-1 and IL-10 and decreased IL-12 and MDC (monocyte-derived chemokine; also known as CCL-22) secretion, as consistent with an M2 monocyte phenotype. Monocyte killing of intracellular M.tb was decreased. In the lung, platelets were detected in a TB mouse model, and secreted platelet mediators were upregulated in human BAL fluid and correlated with MMP and IL-1β concentrations. CONCLUSIONS: Platelets drive a proinflammatory, tissue-degrading phenotype in TB

Ab-initio structural, elastic, and vibrational properties of carbon nanotubes

A study based on ab initio calculations is presented on the estructural, elastic, and vibrational properties of single-wall carbon nanotubes with different radii and chiralities. We use SIESTA, an implementation of pseudopotential-density-functional theory which allows calculations on systems with a large number of atoms per cell. Different quantities like bond distances, Young moduli, Poisson ratio and the frequencies of different phonon branches are monitored versus tube radius. The validity of expectations based on graphite is explored down to small radii, where some deviations appear related to the curvature effects. For the phonon spectra, the results are compared with the predictions of the simple zone-folding approximation. Except for the known defficiencies of this approximation in the low-frequency vibrational regions, it offers quite accurate results, even for relatively small radii.Comment: 13 pages, 7 figures, submitted to Phys. Rev. B (11 Nov. 98

Probabilistic Inference for Nucleosome Positioning with MNase-Based or Sonicated Short-Read Data

We describe a model-based method, PING, for predicting nucleosome positions in MNase-Seq and MNase- or sonicated-ChIP-Seq data. PING compares favorably to NPS and TemplateFilter in scalability, accuracy and robustness to low read density. To demonstrate that PING predictions from widely available sonicated data can have sufficient spatial resolution to be to be useful for biological inference, we use Illumina H3K4me1 ChIP-seq data to detect changes in nucleosome positioning around transcription factor binding sites due to tamoxifen stimulation, to discriminate functional and non-functional transcription factor binding sites more effectively than with enrichment profiles, and to confirm that the pioneer transcription factor Foxa2 associates with the accessible major groove of nucleosomal DNA

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

A Non-Targeted Approach Unravels the Volatile Network in Peach Fruit

Volatile compounds represent an important part of the plant metabolome and are of particular agronomic and biological interest due to their contribution to fruit aroma and flavor and therefore to fruit quality. By using a non-targeted approach based on HS-SPME-GC-MS, the volatile-compound complement of peach fruit was described. A total of 110 volatile compounds (including alcohols, ketones, aldehydes, esters, lactones, carboxylic acids, phenolics and terpenoids) were identified and quantified in peach fruit samples from different genetic backgrounds, locations, maturity stages and physiological responses. By using a combination of hierarchical cluster analysis and metabolomic correlation network analysis we found that previously known peach fruit volatiles are clustered according to their chemical nature or known biosynthetic pathways. Moreover, novel volatiles that had not yet been described in peach were identified and assigned to co-regulated groups. In addition, our analyses showed that most of the co-regulated groups showed good intergroup correlations that are therefore consistent with the existence of a higher level of regulation orchestrating volatile production under different conditions and/or developmental stages. In addition, this volatile network of interactions provides the ground information for future biochemical studies as well as a useful route map for breeding or biotechnological purposes

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN