Network-based stratification of tumor mutations.

Many forms of cancer have multiple subtypes with different causes and clinical outcomes. Somatic tumor genome sequences provide a rich new source of data for uncovering these subtypes but have proven difficult to compare, as two tumors rarely share the same mutations. Here we introduce network-based stratification (NBS), a method to integrate somatic tumor genomes with gene networks. This approach allows for stratification of cancer into informative subtypes by clustering together patients with mutations in similar network regions. We demonstrate NBS in ovarian, uterine and lung cancer cohorts from The Cancer Genome Atlas. For each tissue, NBS identifies subtypes that are predictive of clinical outcomes such as patient survival, response to therapy or tumor histology. We identify network regions characteristic of each subtype and show how mutation-derived subtypes can be used to train an mRNA expression signature, which provides similar information in the absence of DNA sequence

Benefits of robotic cystectomy with intracorporeal diversion for patients with low cardiorespiratory fitness: a prospective cohort study

Background: Patients undergoing radical cystectomy have associated comorbidities resulting in reduced cardiorespiratory fitness. Preoperative cardiopulmonary exercise testing (CPET) measures including anaerobic threshold (AT) can predict major adverse events (MAE) and hospital length of stay (LOS) for patients undergoing open and robotic cystectomy with extracorporeal diversion. Our objective was to determine the relationship between CPET measures and outcome in patients undergoing robotic radical cystectomy and intracorporeal diversion (intracorporeal robotic assisted radical cystectomy [iRARC]). Methods: A single institution prospective cohort study in patients undergoing iRARC for muscle invasive and high-grade bladder cancer. Inclusion: patients undergoing standardised CPET before iRARC. Exclusions: patients not consenting to data collection. Data on CPET measures (AT, ventilatory equivalent for carbon dioxide [VE/VCO2] at AT, peak oxygen uptake [VO2]), and patient demographics prospectively collected. Outcome measurements included hospital LOS; 30-day MAE and 90-day mortality data, which were prospectively recorded. Descriptive and regression analyses were used to assess whether CPET measures were associated with or predicted outcomes. Results: From June 2011 to March 2015, 128 patients underwent radical cystectomy (open cystectomy, n = 17; iRARC, n = 111). A total of 82 patients who underwent iRARC and CPET and consented to participation were included. Median (interquartile range): age = 65 (58–73); body mass index = 27 (23–30); AT = 10.0 (9–11), Peak VO2 = 15.0 (13–18.5), VE/VCO2 (AT) = 33.0 (30–38). 30-day MAE = 14/111 (12.6%): death = 2, multiorgan failure = 2, abscess = 2, gastrointestinal = 2, renal = 6; 90-day mortality = 3/111 (2.7%). AT, peak VO2, and VE/VCO2 (at AT) were not significant predictors of 30-day MAE or LOS. The results are limited by the absence of control group undergoing open surgery. Conclusions: Poor cardiorespiratory fitness does not predict increased hospital LOS or MAEs in patients undergoing iRARC. Overall, MAE and LOS comparable with other series

Spectral Decomposition of Broad-Line AGNs and Host Galaxies

Using an eigenspectrum decomposition technique, we separate the host galaxy from the broad line active galactic nucleus (AGN) in a set of 4666 spectra from the Sloan Digital Sky Survey (SDSS), from redshifts near zero up to about 0.75. The decomposition technique uses separate sets of galaxy and quasar eigenspectra to efficiently and reliably separate the AGN and host spectroscopic components. The technique accurately reproduces the host galaxy spectrum, its contributing fraction, and its classification. We show how the accuracy of the decomposition depends upon S/N, host galaxy fraction, and the galaxy class. Based on the eigencoefficients, the sample of SDSS broad-line AGN host galaxies spans a wide range of spectral types, but the distribution differs significantly from inactive galaxies. In particular, post-starburst activity appears to be much more common among AGN host galaxies. The luminosities of the hosts are much higher than expected for normal early-type galaxies, and their colors become increasingly bluer than early-type galaxies with increasing host luminosity. Most of the AGNs with detected hosts are emitting at between 1% and 10% of their estimated Eddington luminosities, but the sensitivity of the technique usually does not extend to the Eddington limit. There are mild correlations among the AGN and host galaxy eigencoefficients, possibly indicating a link between recent star formation and the onset of AGN activity. The catalog of spectral reconstruction parameters is available as an electronic table.Comment: 18 pages; accepted for publication in A

Multi-functional anodes boost the transient power and durability of proton exchange membrane fuel cells.

Proton exchange membrane fuel cells have been regarded as the most promising candidate for fuel cell vehicles and tools. Their broader adaption, however, has been impeded by cost and lifetime. By integrating a thin layer of tungsten oxide within the anode, which serves as a rapid-response hydrogen reservoir, oxygen scavenger, sensor for power demand, and regulator for hydrogen-disassociation reaction, we herein report proton exchange membrane fuel cells with significantly enhanced power performance for transient operation and low humidified conditions, as well as improved durability against adverse operating conditions. Meanwhile, the enhanced power performance minimizes the use of auxiliary energy-storage systems and reduces costs. Scale fabrication of such devices can be readily achieved based on the current fabrication techniques with negligible extra expense. This work provides proton exchange membrane fuel cells with enhanced power performance, improved durability, prolonged lifetime, and reduced cost for automotive and other applications

Now You See It, Now You Don't: The Disappearing Central Engine of the Quasar J1011+5442

We report the discovery of a new "changing-look" quasar, SDSS J101152.98+544206.4, through repeat spectroscopy from the Time Domain Spectroscopic Survey. This is an addition to a small but growing set of quasars whose blue continua and broad optical emission lines have been observed to decline by a large factor on a time scale of approximately a decade. The 5100 Angstrom monochromatic continuum luminosity of this quasar drops by a factor of > 9.8 in a rest-frame time interval of < 9.7 years, while the broad H-alpha luminosity drops by a factor of 55 in the same amount of time. The width of the broad H-alpha line increases in the dim state such that the black hole mass derived from the appropriate single-epoch scaling relation agrees between the two epochs within a factor of 3. The fluxes of the narrow emission lines do not appear to change between epochs. The light curve obtained by the Catalina Sky Survey suggests that the transition occurs within a rest-frame time interval of approximately 500 days. We examine three possible mechanisms for this transition suggested in the recent literature. An abrupt change in the reddening towards the central engine is disfavored by the substantial difference between the timescale to obscure the central engine and the observed timescale of the transition. A decaying tidal disruption flare is consistent with the decay rate of the light curve but not with the prolonged bright state preceding the decay, nor can this scenario provide the power required by the luminosities of the emission lines. An abrupt drop in the accretion rate onto the supermassive black hole appears to be the most plausible explanation for the rapid dimming.Comment: Submitted to MNRA

Parity transitions in the superconducting ground state of hybrid InSb-Al Coulomb islands

The number of electrons in small metallic or semiconducting islands is quantized. When tunnelling is enabled via opaque barriers this number can change by an integer. In superconductors the addition is in units of two electron charges (2e), reflecting that the Cooper pair condensate must have an even parity. This ground state (GS) is foundational for all superconducting qubit devices. Here, we study a hybrid superconducting-semiconducting island and find three typical GS evolutions in a parallel magnetic field: a robust 2e-periodic even-parity GS, a transition to a 2e-periodic odd-parity GS,and a transition from a 2e- to a 1e-periodic GS. The 2e-periodic odd-parity GS persistent in gate-voltage occurs when a spin-resolved subgap state crosses zero energy. For our 1e-periodic GSs we explicitly show the origin being a single zero-energy state gapped from the continuum, i.e. compatible with an Andreev bound states stabilized at zero energy or the presence of Majorana zero modes

Towards an Understanding of Changing-Look Quasars: An Archival Spectroscopic Search in SDSS

The uncertain origin of the recently-discovered `changing-looking' quasar phenomenon -- in which a luminous quasar dims significantly to a quiescent state in repeat spectroscopy over ~10 year timescales -- may present unexpected challenges to our understanding of quasar accretion. To better understand this phenomenon, we take a first step to building a sample of changing-look quasars with a systematic but simple archival search for these objects in the Sloan Digital Sky Survey Data Release 12. By leveraging the >10 year baselines for objects with repeat spectroscopy, we uncover two new changing-look quasars, and a third discovered previously. Decomposition of the multi-epoch spectra and analysis of the broad emission lines suggest that the quasar accretion disk emission dims due to rapidly decreasing accretion rates (by factors of >2.5), while disfavoring changes in intrinsic dust extinction for the two objects where these analyses are possible. Broad emission line energetics also support intrinsic dimming of quasar emission as the origin for this phenomenon rather than transient tidal disruption events or supernovae. Although our search criteria included quasars at all redshifts and transitions from either quasar-like to galaxy-like states or the reverse, all of the clear cases of changing-look quasars discovered were at relatively low-redshift (z ~ 0.2 - 0.3) and only exhibit quasar-like to galaxy-like transitions.Comment: 15 pages, 8 figures. Updated to accepted versio

The Case of AB Aurigae's Disk in Polarized Light: Is There Truly a Gap?

Using the NICMOS coronagraph, we have obtained high-contrast 2.0 micron imaging polarimetry and 1.1 micron imaging of the circumstellar disk around AB Aurigae on angular scales of 0.3-3 arcsec (40-550 AU). Unlike previous observations, these data resolve the disk in both total and polarized intensity, allowing accurate measurement of the spatial variation of polarization fraction across the disk. Using these observations we investigate the apparent "gap" in the disk reported by Oppenheimer et al. 2008. In polarized intensity, the NICMOS data closely reproduces the morphology seen by Oppenheimer et al., yet in total intensity we find no evidence for a gap in either our 1.1 or 2.0 micron images. We find instead that region has lower polarization fraction, without a significant decrease in total scattered light, consistent with expectations for back-scattered light on the far side of an inclined disk. Radiative transfer models demonstrate this explanation fits the observations. Geometrical scattering effects are entirely sufficient to explain the observed morphology without any need to invoke a gap or protoplanet at that location.Comment: Accepted to ApJ Letter