While mutations in the KRAS oncogene are among the most prevalent in human cancer, there are few successful treatments to target these tumors. It is also likely that heterogeneity in KRAS-mutant ...tumor biology significantly contributes to the response to therapy. We hypothesized that the presence of commonly co-occurring mutations in STK11 and TP53 tumor suppressors may represent a significant source of heterogeneity in KRAS-mutant tumors. To address this, we utilized a large cohort of resected tumors from 442 lung adenocarcinoma patients with data including annotation of prevalent driver mutations (KRAS and EGFR) and tumor suppressor mutations (STK11 and TP53), microarray-based gene expression and clinical covariates, including overall survival (OS). Specifically, we determined impact of STK11 and TP53 mutations on a new KRAS mutation-associated gene expression signature as well as previously defined signatures of tumor cell proliferation and immune surveillance responses. Interestingly, STK11, but not TP53 mutations, were associated with highly elevated expression of KRAS mutation-associated genes. Mutations in TP53 and STK11 also impacted tumor biology regardless of KRAS status, with TP53 strongly associated with enhanced proliferation and STK11 with suppression of immune surveillance. These findings illustrate the remarkably distinct ways through which tumor suppressor mutations may contribute to heterogeneity in KRAS-mutant tumor biology. In addition, these studies point to novel associations between gene mutations and immune surveillance that could impact the response to immunotherapy.
ABSTRACT
We analyse a robust sample of 30 near-infrared-faint (KAB > 25.3, 5σ) submillimetre galaxies (SMGs) selected from a 0.96 deg2 field to investigate their properties and the cause of their ...faintness in optical/near-infrared wavebands. Our analysis exploits precise identifications based on Atacama Large Millimeter Array (ALMA) 870-μm continuum imaging, combined with very deep near-infrared imaging from the UKIDSS Ultra Deep Survey. We estimate that SMGs with KAB > 25.3 mag represent 15 ± 2 per cent of the total population brighter than S870 = 3.6 mJy, with a potential surface density of ∼450 deg−2 above S870 ≥ 1 mJy. As such, they pose a source of contamination in surveys for both high-redshift ‘quiescent’ galaxies and very high redshift Lyman-break galaxies. We show that these K-faint SMGs represent the tail of the broader submillimetre population, with comparable dust and stellar masses to KAB ≤ 25.3 mag SMGs, but lying at significantly higher redshifts (z = 3.44 ± 0.06 versus z = 2.36 ± 0.11) and having higher dust attenuation (AV = 5.2 ± 0.3 versus AV = 2.9 ± 0.1). We investigate the origin of the strong dust attenuation and find indications that these K-faint galaxies have smaller dust continuum sizes than the KAB ≤ 25.3 mag galaxies, as measured by ALMA, which suggests their high attenuation is related to their compact sizes. We identify a correlation of dust attenuation with star formation rate surface density (ΣSFR), with the K-faint SMGs representing the higher ΣSFR and highest AV galaxies. The concentrated, intense star formation activity in these systems is likely to be associated with the formation of spheroids in compact galaxies at high redshifts, but as a result of their high obscuration these galaxies are completely missed in ultraviolet, optical, and even near-infrared surveys.
We report the first results of AS2UDS, an 870 m continuum survey with the Atacama Large Millimeter/Submillimeter Array (ALMA) of a total area of ∼50 arcmin2 comprising a complete sample of 716 ...submillimeter sources drawn from the SCUBA-2 Cosmology Legacy Survey (S2CLS) map of the UKIDSS/UDS field. The S2CLS parent sample covers a 0.96 degree2 field at 850 = 0.90 0.05 mJy beam−1. Our deep, high-resolution ALMA observations with 870 ∼ 0.25 mJy and a 0 15-0 30 FWHM synthesized beam, provide precise locations for 695 submillimeter galaxies (SMGs) responsible for the submillimeter emission corresponding to 606 sources in the low-resolution, single-dish map. We measure the number counts of SMGs brighter than S870 ≥ 4 mJy, free from the effects of blending and show that the normalization of the counts falls by 28% 2% in comparison with the SCUBA-2 published counts, but that the shape remains unchanged. We determine that 44 − 14 + 16 % of the brighter single-dish sources with S850 ≥ 9 mJy consist of a blend of two or more ALMA-detectable SMGs brighter than S870 ∼ 1 mJy (corresponding to a galaxy with a total-infrared luminosity of LIR 1012 L ), in comparison with 28% 2% for the single-dish sources at S850 ≥ 5 mJy. Using the 46 single-dish submillimeter sources that contain two or more ALMA-detected SMGs with photometric redshifts, we show that there is a significant statistical excess of pairs of SMGs with similar redshifts (<1% probability of occurring by chance), suggesting that at least 30% of these blends arise from physically associated pairs of SMGs.
Climate, land use, and other anthropogenic and natural drivers have the potential to influence fire dynamics in many regions. To develop a mechanistic understanding of the changing role of these ...drivers and their impact on atmospheric composition, long-term fire records are needed that fuse information from different satellite and in situ data streams. Here we describe the fourth version of the Global Fire Emissions Database (GFED) and quantify global fire emissions patterns during 1997–2016. The modeling system, based on the Carnegie–Ames–Stanford Approach (CASA) biogeochemical model, has several modifications from the previous version and uses higher quality input datasets. Significant upgrades include (1) new burned area estimates with contributions from small fires, (2) a revised fuel consumption parameterization optimized using field observations, (3) modifications that improve the representation of fuel consumption in frequently burning landscapes, and (4) fire severity estimates that better represent continental differences in burning processes across boreal regions of North America and Eurasia. The new version has a higher spatial resolution (0.25°) and uses a different set of emission factors that separately resolves trace gas and aerosol emissions from temperate and boreal forest ecosystems. Global mean carbon emissions using the burned area dataset with small fires (GFED4s) were 2.2 × 1015 grams of carbon per year (Pg C yr−1) during 1997–2016, with a maximum in 1997 (3.0 Pg C yr−1) and minimum in 2013 (1.8 Pg C yr−1). These estimates were 11 % higher than our previous estimates (GFED3) during 1997–2011, when the two datasets overlapped. This net increase was the result of a substantial increase in burned area (37 %), mostly due to the inclusion of small fires, and a modest decrease in mean fuel consumption (−19 %) to better match estimates from field studies, primarily in savannas and grasslands. For trace gas and aerosol emissions, differences between GFED4s and GFED3 were often larger due to the use of revised emission factors. If small fire burned area was excluded (GFED4 without the s for small fires), average emissions were 1.5 Pg C yr−1. The addition of small fires had the largest impact on emissions in temperate North America, Central America, Europe, and temperate Asia. This small fire layer carries substantial uncertainties; improving these estimates will require use of new burned area products derived from high-resolution satellite imagery. Our revised dataset provides an internally consistent set of burned area and emissions that may contribute to a better understanding of multi-decadal changes in fire dynamics and their impact on the Earth system. GFED data are available from http://www.globalfiredata.org.
The field of dark matter detection is a highly visible and highly competitive one. In this paper, we propose recommendations for presenting dark matter direct detection results particularly suited ...for weak-scale dark matter searches, although we believe the spirit of the recommendations can apply more broadly to searches for other dark matter candidates, such as very light dark matter or axions. To translate experimental data into a final published result, direct detection collaborations must make a series of choices in their analysis, ranging from how to model astrophysical parameters to how to make statistical inferences based on observed data. While many collaborations follow a standard set of recommendations in some areas, for example the expected flux of dark matter particles (to a large degree based on a paper from Lewin and Smith in 1995), in other areas, particularly in statistical inference, they have taken different approaches, often from result to result by the same collaboration. We set out a number of recommendations on how to apply the now commonly used Profile Likelihood Ratio method to direct detection data. In addition, updated recommendations for the Standard Halo Model astrophysical parameters and relevant neutrino fluxes are provided. The authors of this note include members of the DAMIC, DarkSide, DARWIN, DEAP, LZ, NEWS-G, PandaX, PICO, SBC, SENSEI, SuperCDMS, and XENON collaborations, and these collaborations provided input to the recommendations laid out here. Wide-spread adoption of these recommendations will make it easier to compare and combine future dark matter results.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
According to the current understanding of cosmic structure formation, the precursors of the most massive structures in the Universe began to form shortly after the Big Bang, in regions corresponding ...to the largest fluctuations in the cosmic density field. Observing these structures during their period of active growth and assembly-the first few hundred million years of the Universe-is challenging because it requires surveys that are sensitive enough to detect the distant galaxies that act as signposts for these structures and wide enough to capture the rarest objects. As a result, very few such objects have been detected so far. Here we report observations of a far-infrared-luminous object at redshift 6.900 (less than 800 million years after the Big Bang) that was discovered in a wide-field survey. High-resolution imaging shows it to be a pair of extremely massive star-forming galaxies. The larger is forming stars at a rate of 2,900 solar masses per year, contains 270 billion solar masses of gas and 2.5 billion solar masses of dust, and is more massive than any other known object at a redshift of more than 6. Its rapid star formation is probably triggered by its companion galaxy at a projected separation of 8 kiloparsecs. This merging companion hosts 35 billion solar masses of stars and has a star-formation rate of 540 solar masses per year, but has an order of magnitude less gas and dust than its neighbour and physical conditions akin to those observed in lower-metallicity galaxies in the nearby Universe. These objects suggest the presence of a dark-matter halo with a mass of more than 100 billion solar masses, making it among the rarest dark-matter haloes that should exist in the Universe at this epoch.
We present a multi-wavelength analysis of 52 submillimeter galaxies (SMGs), identified using ALMA 870 m continuum imaging in a pilot program to precisely locate bright SCUBA-2-selected submillimeter ...sources in the UKIDSS Ultra Deep Survey (UDS) field. Using the available deep (especially near-infrared) panoramic imaging of the UDS field at optical-to-radio wavelengths we characterize key properties of the SMG population. The median photometric redshift of the bright ALMA/SCUBA-2 UDS (AS2UDS) SMGs that are detected in a sufficient number of wavebands to derive a robust photometric redshift is z = 2.65 0.13. However, similar to previous studies, 27% of the SMGs are too faint at optical-to-near-infrared wavelengths to derive a reliable photometric redshift. Assuming that these SMGs lie at z 3 raises the median redshift of the full sample to z = 2.9 0.2. A subset of 23 unlensed, bright AS2UDS SMGs have sizes measured from resolved imaging of their rest-frame far-infrared emission. We show that the extent and luminosity of the far-infrared emission are consistent with the dust emission arising from regions that are, on average, optically thick at a wavelength of (1 dispersion of 55-90 m). Using the dust masses derived from our optically thick spectral energy distribution models, we determine that these galaxies have a median hydrogen column density of NH = 9.8 × 1023 cm−2, or a corresponding median V-band obscuration of Av = 540 mag, averaged along the line of sight to the source of their rest-frame ∼200 m emission. We discuss the implications of this extreme attenuation by dust for the multi-wavelength study of dusty starbursts and reddening-sensitive tracers of star formation.
ABSTRACT
We present an analysis of the spatial clustering of a large sample of high-resolution, interferometically identified, submillimetre galaxies (SMGs). We measure the projected ...cross-correlation function of ∼350 SMGs in the UKIDSS Ultra Deep-Survey Field across a redshift range of z = 1.5–3 utilizing a method that incorporates the uncertainties in the redshift measurements for both the SMGs and cross-correlated galaxies through sampling their full probability distribution functions. By measuring the absolute linear bias of the SMGs, we derive halo masses of $\log _{10}(M_{\rm halo}{h^{-1}\, \rm M_{\odot }})$ ∼ 12.8 with no evidence of evolution in the halo masses with redshift, contrary to some previous work. From considering models of halo mass growth rates, we predict that the SMGs will reside in haloes of mass $\log _{10}(M_{\rm halo}{h^{-1}\, \rm M_{\odot }})$ ∼ 13.2 at z = 0, consistent with the expectation that the majority of z = 1.5–3 SMGs will evolve into present-day spheroidal galaxies. Finally, comparing to models of stellar-to-halo mass ratios, we show that SMGs may correspond to systems that are maximally efficient at converting their gas reservoirs into stars. We compare them to a simple model for gas cooling in haloes that suggests that the unique properties of the SMG population, including their high levels of star formation and their redshift distribution, are a result of the SMGs being the most massive galaxies that are still able to accrete cool gas from their surrounding intragalactic medium.
We report the experimental generation of highly energetic carbon ions up to 48 MeV per nucleon by shooting double-layer targets composed of well-controlled slightly underdense plasma and ultrathin ...foils with ultraintense femtosecond laser pulses. Particle-in-cell simulations reveal that carbon ions are ejected from the ultrathin foils due to radiation pressure and then accelerated in an enhanced sheath field established by the superponderomotive electron flow. Such a cascaded acceleration is especially suited for heavy ion acceleration with femtosecond laser pulses. The breakthrough of heavy ion energy up to many tens of MeV/u at a high repetition rate would be able to trigger significant advances in nuclear physics, high energy density physics, and medical physics.
Massive galaxy clusters have been found that date to times as early as three billion years after the Big Bang, containing stars that formed at even earlier epochs
. The high-redshift progenitors of ...these galaxy clusters-termed 'protoclusters'-can be identified in cosmological simulations that have the highest overdensities (greater-than-average densities) of dark matter
. Protoclusters are expected to contain extremely massive galaxies that can be observed as luminous starbursts
. However, recent detections of possible protoclusters hosting such starbursts
do not support the kind of rapid cluster-core formation expected from simulations
: the structures observed contain only a handful of starbursting galaxies spread throughout a broad region, with poor evidence for eventual collapse into a protocluster. Here we report observations of carbon monoxide and ionized carbon emission from the source SPT2349-56. We find that this source consists of at least 14 gas-rich galaxies, all lying at redshifts of 4.31. We demonstrate that each of these galaxies is forming stars between 50 and 1,000 times more quickly than our own Milky Way, and that all are located within a projected region that is only around 130 kiloparsecs in diameter. This galaxy surface density is more than ten times the average blank-field value (integrated over all redshifts), and more than 1,000 times the average field volume density. The velocity dispersion (approximately 410 kilometres per second) of these galaxies and the enormous gas and star-formation densities suggest that this system represents the core of a cluster of galaxies that was already at an advanced stage of formation when the Universe was only 1.4 billion years old. A comparison with other known protoclusters at high redshifts shows that SPT2349-56 could be building one of the most massive structures in the Universe today.
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