A One-sided, Highly Relativistic Jet from Cygnus X-3

Very Long Baseline Array images of the X-ray binary, Cygnus X-3, were obtained 2, 4 and 7 days after the peak of a 10 Jy flare on 4 February 1997. The first two images show a curved one-sided jet, the third a scatter-broadened disc, presumably at the position of the core. The jet curvature changes from the first to the second epoch, which strongly suggests a precessing jet. The ratio of the flux density in the approaching to that in the (undetected) receding jet is > 330; if this asymmetry is due to Doppler boosting, the implied jet speed is > 0.81c. Precessing jet model fits, together with the assumptions that the jet is intrinsically symmetric and was ejected during or after the major flare, yield the following constraints: the jet inclination to the line of sight must be < 14 degrees; the cone opening angle must be < 12 degrees; and the precession period must be > 60 days.Comment: 12 pages 7 figures, accepted by Ap

Radio Emission and the Timing Properties of the Hard X-ray State of GRS 1915+105

We combine a complete sample of 113 pointed observations taken with the Rossi X-ray Timing Explorer between 1996-1999, monitoring observations taken with the Ryle telescope and the Green Bank Interferometer, and selected observations with the Very Large Array to study the radio and X-ray properties of GRS 1915+105 when its X-ray emission is hard and steady. We establish that radio emission always accompanies the hard-steady state of GRS 1915+105, but that the radio flux density at 15.2 GHz and the X-ray flux between 2-200 keV are not correlated. Therefore we study the X-ray spectral and timing properties of GRS 1915+105 using three approaches: first, by describing in detail the properties of three characteristic observations, then by displaying the time evolution of the timing properties during periods of both faint and bright radio emission, and lastly by plotting the timing properties as a function of the the radio flux density. We find that as the radio emission becomes brighter and more optically thick, 1) the frequency of a ubiquitous 0.5-10 Hz QPO decreases, 2) the Fourier phase lags between hard (11.5-60 keV) and soft (2-4.3 keV) in the frequency range of 0.01-10 Hz change sign from negative to positive, 3) the coherence between hard and soft photons at low frequencies decreases, and 4) the relative amount of low frequency power in hard photons compared to soft photons decreases. We discuss how these results reflect upon basic models from the literature describing the accretion flow around black holes and the possible connection between Comptonizing electrons and compact radio jets.Comment: 22 pages with 8 figures and 2 tables in emulateapj style. Submitted to Ap

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Comprehensive genomic characterization of squamous cell lung cancers

Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers.National Institutes of Health (U.S.) (Grant U24 CA126561)National Institutes of Health (U.S.) (Grant U24 CA126551)National Institutes of Health (U.S.) (Grant U24 CA126554)National Institutes of Health (U.S.) (Grant U24 CA126543)National Institutes of Health (U.S.) (Grant U24 CA126546)National Institutes of Health (U.S.) (Grant U24 CA126563)National Institutes of Health (U.S.) (Grant U24 CA126544)National Institutes of Health (U.S.) (Grant U24 CA143845)National Institutes of Health (U.S.) (Grant U24 CA143858)National Institutes of Health (U.S.) (Grant U24 CA144025)National Institutes of Health (U.S.) (Grant U24 CA143882)National Institutes of Health (U.S.) (Grant U24 CA143866)National Institutes of Health (U.S.) (Grant U24 CA143867)National Institutes of Health (U.S.) (Grant U24 CA143848)National Institutes of Health (U.S.) (Grant U24 CA143840)National Institutes of Health (U.S.) (Grant U24 CA143835)National Institutes of Health (U.S.) (Grant U24 CA143799)National Institutes of Health (U.S.) (Grant U24 CA143883)National Institutes of Health (U.S.) (Grant U24 CA143843)National Institutes of Health (U.S.) (Grant U54 HG003067)National Institutes of Health (U.S.) (Grant U54 HG003079)National Institutes of Health (U.S.) (Grant U54 HG003273

Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

© 2014 Elsevier Inc. Recent genomic analyses of pathologically defined tumor types identify 'within-a-tissue' disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-oforigin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pancancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies