A Luminous Be+White Dwarf Supersoft Source in the Wing of the SMC: MAXI J0158-744

We present a multi-wavelength analysis of the very fast X-ray transient MAXI J0158-744, which was detected by MAXI/GSC on 2011 November 11. The subsequent exponential decline of the X-ray flux was followed with Swift observations, all of which revealed spectra with low temperatures (~100eV) indicating that MAXI J0158-744 is a new Supersoft Source (SSS). The Swift X-ray spectra near maximum show features around 0.8 keV that we interpret as possible absorption from OVIII, and emission from O, Fe, and Ne lines. We obtained SAAO and ESO optical spectra of the counterpart early in the outburst and several weeks later. The early spectrum is dominated by strong Balmer and HeI emission, together with weaker HeII emission. The later spectrum reveals absorption features that indicate a B1/2IIIe spectral type, and all spectral features are at velocities consistent with the Small Magellanic Cloud. At this distance, it is a luminous SSS (>10^37 erg/s) but whose brief peak luminosity of >10^39 erg/s in the 2-4 keV band makes it the brightest SSS yet seen at "hard" X-rays. We propose that MAXI J0158-744 is a Be-WD binary, and the first example to possibly enter ULX territory. The brief hard X-ray flash could possibly be a result of the interaction of the ejected nova shell with the B star wind in which the white dwarf (WD) is embedded. This makes MAXI J0158-744 only the third Be/WD system in the Magellanic Clouds, but it is by far the most luminous. The properties of MAXI J0158-744 give weight to previous suggestions that SSS in nearby galaxies are associated with early-type stellar systems.Comment: 15 pages, 8 figures; ApJ accepte

Observations of Milky Way Dwarf Spheroidal galaxies with the Fermi-LAT detector and constraints on Dark Matter models

We report on the observations of 14 dwarf spheroidal galaxies with the Fermi Gamma-Ray Space Telescope taken during the first 11 months of survey mode operations. The Fermi telescope provides a new opportunity to test particle dark matter models through the expected gamma-ray emission produced by pair annihilation of weakly interacting massive particles (WIMPs). Local Group dwarf spheroidal galaxies, the largest galactic substructures predicted by the cold dark matter scenario, are attractive targets for such indirect searches for dark matter because they are nearby and among the most extreme dark matter dominated environments. No significant gamma-ray emission was detected above 100 MeV from the candidate dwarf galaxies. We determine upper limits to the gamma-ray flux assuming both power-law spectra and representative spectra from WIMP annihilation. The resulting integral flux above 100 MeV is constrained to be at a level below around 10^-9 photons cm^-2 s^-1. Using recent stellar kinematic data, the gamma-ray flux limits are combined with improved determinations of the dark matter density profile in 8 of the 14 candidate dwarfs to place limits on the pair annihilation cross-section of WIMPs in several widely studied extensions of the standard model. With the present data, we are able to rule out large parts of the parameter space where the thermal relic density is below the observed cosmological dark matter density and WIMPs (neutralinos here) are dominantly produced non-thermally, e.g. in models where supersymmetry breaking occurs via anomaly mediation. The gamma-ray limits presented here also constrain some WIMP models proposed to explain the Fermi and PAMELA e^+e^- data, including low-mass wino-like neutralinos and models with TeV masses pair-annihilating into muon-antimuon pairs. (Abridged)Comment: 25 pages, 4 figures, accepted to ApJ, Corresponding authors: J. Cohen-Tanugi, C. Farnier, T.E. Jeltema, E. Nuss, and S. Profum

Targeted p120-Catenin Ablation Disrupts Dental Enamel Development

Dental enamel development occurs in stages. The ameloblast cell layer is adjacent to, and is responsible for, enamel formation. When rodent pre-ameloblasts become tall columnar secretory-stage ameloblasts, they secrete enamel matrix proteins, and the ameloblasts start moving in rows that slide by one another. This movement is necessary to form the characteristic decussating enamel prism pattern. Thus, a dynamic system of intercellular interactions is required for proper enamel development. Cadherins are components of the adherens junction (AJ), and they span the cell membrane to mediate attachment to adjacent cells. p120 stabilizes cadherins by preventing their internalization and degradation. So, we asked if p120-mediated cadherin stability is important for dental enamel formation. Targeted p120 ablation in the mouse enamel organ had a striking effect. Secretory stage ameloblasts detached from surrounding tissues, lost polarity, flattened, and ameloblast E- and N-cadherin expression became undetectable by immunostaining. The enamel itself was poorly mineralized and appeared to be composed of a thin layer of merged spheres that abraded from the tooth. Significantly, p120 mosaic mouse teeth were capable of forming normal enamel demonstrating that the enamel defects were not a secondary effect of p120 ablation. Surprisingly, blood-filled sinusoids developed in random locations around the developing teeth. This has not been observed in other p120-ablated tissues and may be due to altered p120-mediated cell signaling. These data reveal a critical role for p120 in tooth and dental enamel development and are consistent with p120 directing the attachment and detachment of the secretory stage ameloblasts as they move in rows

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Modulation of apoptosis by V protein mumps virus

<p>Abstract</p> <p>Background</p> <p>The Urabe AM9 vaccine strain of mumps virus contains two variants of V protein: VWT (of HN-A1081 viral population) and VGly (of HN-G1081). The V protein is a promoting factor of viral replication by blocking the IFN antiviral pathway.</p> <p>Findings</p> <p>We studied the relationship between V protein variants and IFN-α2b-induced apoptosis. V proteins decrease activation of the extrinsic IFN-α2b-induced apoptotic pathway monitored by the caspase 8 activity, being the effect greater with the VWT protein. Both V proteins decrease the activity of caspase 9 of the intrinsic apoptotic pathway. In a system without IFN, the VWT and VGly proteins expression promotes activation of caspases 3 and 7. However, when the cellular system was stimulated with IFN-α, this activity decreased partially. TUNEL assay shows that for treatment with IFN-α and ibuprofen of cervical adenocarcinoma cells there is nuclear DNA fragmentation but the V protein expression reduces this process.</p> <p>Conclusions</p> <p>The reduction in the levels of caspases and DNA fragmentation, suggesting that V protein, particularly VWT protein of Urabe AM9 vaccine strain, modulates apoptosis. In addition, the VWT protein shows a protective role for cell proliferation in the presence of antiproliferative signals.</p

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

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 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