Systematic studies of cancer genomes have provided unprecedented insights into the molecular nature of cancer. Using this information to guide the development and application of therapies in the ...clinic is challenging. Here, we report how cancer-driven alterations identified in 11,289 tumors from 29 tissues (integrating somatic mutations, copy number alterations, DNA methylation, and gene expression) can be mapped onto 1,001 molecularly annotated human cancer cell lines and correlated with sensitivity to 265 drugs. We find that cell lines faithfully recapitulate oncogenic alterations identified in tumors, find that many of these associate with drug sensitivity/resistance, and highlight the importance of tissue lineage in mediating drug response. Logic-based modeling uncovers combinations of alterations that sensitize to drugs, while machine learning demonstrates the relative importance of different data types in predicting drug response. Our analysis and datasets are rich resources to link genotypes with cellular phenotypes and to identify therapeutic options for selected cancer sub-populations.
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•We integrate heterogeneous molecular data of 11,289 tumors and 1,001 cell lines•We measure the response of 1,001 cancer cell lines to 265 anti-cancer drugs•We uncover numerous oncogenic aberrations that sensitize to an anti-cancer drug•Our study forms a resource to identify therapeutic options for cancer sub-populations
A look at the pharmacogenomic landscape of 1,001 human cancer cell lines points to new treatment applications for hundreds of known anti-cancer drugs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We present models of the inner region of the circumstellar disk of RY Tau that aim to explain our near-infrared (K-band: 2.1 m) interferometric observations, while remaining consistent with the ...optical to near-infrared portions of the spectral energy distribution. Our submilliarcsecond-resolution CHARA Array observations are supplemented with shorter baseline, archival data from PTI, KI, and VLTI/GRAVITY and modeled using an axisymmetric Monte Carlo radiative transfer code. The K-band visibilities are well fit by models incorporating a central star illuminating a disk with an inner edge shaped by dust sublimation at 0.210 0.005 au, assuming a viewing geometry adopted from millimeter interferometry (65° inclined with a disk major axis position angle of 23°). This sublimation radius is consistent with that expected of silicate grains with a maximum size of 0.36-0.40 m contributing to the opacity, and is an order of magnitude further from the star than the theoretical magnetospheric truncation radius. The visibilities on the longest baselines probed by CHARA indicate that we lack a clear line of sight to the stellar photosphere. Instead, our analysis shows that the central star is occulted by the disk surface layers close to the sublimation rim. While we do not see direct evidence of temporal variability in our multiepoch CHARA observations, we suggest the aperiodic photometric variability of RY Tau is likely related temporal and/or azimuthal variations in the structure of the disk surface layers.
The bright star 55 Cancri is known to host five planets, including a transiting super-Earth. The study presented here yields directly determined values for 55 Cnc's stellar astrophysical parameters ...based on improved interferometry: R = 0.943 ? 0.010 R , T EFF = 5196 ? 24 K. We use isochrone fitting to determine 55 Cnc's age to be 10.2 ? 2.5 Gyr, implying a stellar mass of 0.905 ? 0.015 M . Our analysis of the location and extent of the system's habitable zone (HZ; 0.67-1.32 AU) shows that planet f, with period ~260 days and Msin i = 0.155 M Jupiter, spends the majority of the duration of its elliptical orbit in the circumstellar HZ. Though planet f is too massive to harbor liquid water on any planetary surface, we elaborate on the potential of alternative low-mass objects in planet f's vicinity: a large moon and a low-mass planet on a dynamically stable orbit within the HZ. Finally, our direct value for 55 Cancri's stellar radius allows for a model-independent calculation of the physical diameter of the transiting super-Earth 55 Cnc e (~2.05 ? 0.15 R {circled plus}), which, depending on the planetary mass assumed, implies a bulk density of 0.76 Delta *r{circled plus} or 1.07 Delta *r{circled plus}.
We use near-infrared interferometric data coupled with trigonometric parallax values and spectral energy distribution fitting to directly determine stellar radii, effective temperatures and ...luminosities for the exoplanet host stars 61 Vir, ρ CrB, GJ 176, GJ 614, GJ 649, GJ 876, HD 1461, HD 7924, HD 33564, HD 107383 and HD 210702. Three of these targets are M dwarfs. Statistical uncertainties in the stellar radii and effective temperatures range from 0.5 to 5 per cent and from 0.2 to 2 per cent, respectively. For eight of these targets, this work presents the first directly determined values of radius and temperature; for the other three, we provide updates to their properties. The stellar fundamental parameters are used to estimate stellar mass and calculate the location and extent of each system's circumstellar habitable zone. Two of these systems have planets that spend at least parts of their respective orbits in the system habitable zone: two of GJ 876's four planets and the planet that orbits HD 33564. We find that our value for GJ 876's stellar radius is more than 20 per cent larger than previous estimates and frequently used values in the astronomical literature.
We present direct radii measurements of the well-known transiting exoplanet host stars HD 189733 and HD 209458 using the CHARA Array interferometer. We find the limb-darkened angular diameters to be ...θLD = 0.3848 ± 0.0055 and 0.2254 ± 0.0072 mas for HD 189733 and HD 209458, respectively. HD 189733 and HD 209458 are currently the only two transiting exoplanet systems where detection of the respective planetary companion's orbital motion from high-resolution spectroscopy has revealed absolute masses for both star and planet. We use our new measurements together with the orbital information from radial velocity and photometric time series data, Hipparcos distances, and newly measured bolometric fluxes to determine the stellar effective temperatures (T
eff = 4875 ± 43, 6092 ± 103 K), stellar linear radii (R
* = 0.805 ± 0.016, 1.203 ± 0.061 R⊙), mean stellar densities (ρ* = 1.62 ± 0.11, 0.58 ± 0.14 ρ⊙), planetary radii (R
p = 1.216 ± 0.024, 1.451 ± 0.074 R
Jup), and mean planetary densities (ρp = 0.605 ± 0.029, 0.196 ± 0.033 ρJup) for HD 189733b and HD 209458b, respectively. The stellar parameters for HD 209458, an F9 dwarf, are consistent with indirect estimates derived from spectroscopic and evolutionary modelling. However, we find that models are unable to reproduce the observational results for the K2 dwarf, HD 189733. We show that, for stellar evolutionary models to match the observed stellar properties of HD 189733, adjustments lowering the solar-calibrated mixing-length parameter to αMLT =1.34 need to be employed.
(ProQuest: ... denotes formulae and/or non-USASCII text omitted) The late-type dwarf GJ 436 is known to host a transiting Neptune-mass planet in a 2.6 day orbit. We present results of our ...interferometric measurements to directly determine the stellar diameter (Rlow * = 0.455 + or - 0.018 R sub(middot in circle)) and effective temperature (T sub(EFF) = 3416 + or - 54 K). We combine our stellar parameters with literature time-series data, which allows us to calculate physical and orbital system parameters, including GJ 436's stellar mass (...), stellar density (...), planetary radius (...), and planetary mass (...), implying a mean planetary density of ... These values are generally in good agreement with previous literature estimates based on assumed stellar mass and photometric light curve fitting. Finally, we examine the expected phase curves of the hot Neptune GJ 436b, based on various assumptions concerning the efficiency of energy redistribution in the planetary atmosphere, and find that it could be constrained with Spitzer monitoring observations.
GJ 581 is an M dwarf host of a multiplanet system. We use long-baseline interferometric measurements from the CHARA Array, coupled with trigonometric parallax information, to directly determine its ...physical radius to be 0.299 ? 0.010 R . Literature photometry data are used to perform spectral energy distribution fitting in order to determine GJ 581's effective surface temperature T EFF = 3498 ? 56 K and its luminosity L = 0.01205 ? 0.00024 L . From these measurements, we recompute the location and extent of the system's habitable zone and conclude that two of the planets orbiting GJ 581, planets d and g, spend all or part of their orbit within or just on the edge of the habitable zone.
We present interferometric angular diameter measurements of 21 low-mass, K- and M-dwarfs made with the CHARA Array. This sample is enhanced by adding a collection of radius measurements published in ...the literature to form a total data set of 33 K-M-dwarfs with diameters measured to better than 5%. We use these data in combination with the Hipparcos parallax and new measurements of the star's bolometric flux to compute absolute luminosities, linear radii, and effective temperatures for the stars. Our results show that it is necessary to use metallicity-dependent transformations in order to properly convert colors into stellar temperatures, radii, and luminosities. Alternatively, we find no sensitivity to metallicity on relations we construct to the global properties of a star omitting color information, e.g., temperature-radius and temperature-luminosity. In addition to the empirical relations, we also provide a representative look-up table via stellar spectral classifications using this collection of data.
This article is to alert medical mycologists and infectious disease specialists of recent name changes of medically important species of the filamentous mold
Fusarium
.
Fusarium
species can cause ...localized and life-threating infections in humans. Of the 70
Fusarium
species that have been reported to cause infections, close to one-third are members of the
Fusarium solani
species complex (FSSC), and they collectively account for approximately two-thirds of all reported
Fusarium
infections.
ABSTRACT
This article is to alert medical mycologists and infectious disease specialists of recent name changes of medically important species of the filamentous mold
Fusarium
.
Fusarium
species can cause localized and life-threating infections in humans. Of the 70
Fusarium
species that have been reported to cause infections, close to one-third are members of the
Fusarium solani
species complex (FSSC), and they collectively account for approximately two-thirds of all reported
Fusarium
infections. Many of these species were recently given scientific names for the first time by a research group in the Netherlands, but they were misplaced in the genus
Neocosmospora
. In this paper, we present genetic arguments that strongly support inclusion of the FSSC in
Fusarium
. There are potentially serious consequences associated with using the name
Neocosmospora
for
Fusarium
species because clinicians need to be aware that fusaria are broadly resistant to the spectrum of antifungals that are currently available.
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