Suppressed Far-UV stellar activity and low planetary mass-loss in the WASP-18 system

WASP-18 hosts a massive, very close-in Jupiter-like planet. Despite its young age (R′HK activity parameter lies slightly below the basal level; there is no significant time-variability in the log R′HK value; there is no detection of the star in the X-rays. We present results of far-UV observations of WASP-18 obtained with COS on board of HST aimed at explaining this anomaly. From the star’s spectral energy distribution, we infer the extinction (E(B − V) ≈ 0.01mag) and then the ISM column density for a number of ions, concluding that ISM absorption is not the origin of the anomaly. We measure the flux of the four stellar emission features detected in the COS spectrum (C II, C III, C IV, Si IV). Comparing the C II/C IV flux ratio measured for WASP-18 with that derived from spectra of nearby stars with known age, we see that the far-UV spectrum of WASP-18 resembles that of old (>5Gyr), inactive stars, in stark contrast with its young age. We conclude that WASP-18 has an intrinsically low activity level, possibly caused by star-planet tidal interaction, as suggested by previous studies. Re-scaling the solar irradiance reference spectrum to match the flux of the Si IV line, yields an XUV integrated flux at the planet orbit of 10.2 erg s−1 cm−2. We employ the rescaled XUV solar fluxes to model of the planetary upper atmosphere, deriving an extremely low thermal mass-loss rate of 10−20MJ Gyr−1. For such high-mass planets, thermal escape is not energy limited, but driven by Jeans escape

Far-UV spectroscopy of the planet-hosting star WASP-13: High-energy irradiance, distance, age, planetary mass-loss rate, and circumstellar environment

Several transiting hot Jupiters orbit relatively inactive main-sequence stars. For some of those, the {log}{R}{HK}\prime activity parameter lies below the basal level (-5.1). Two explanations have been proposed so far: (i) the planet affects the stellar dynamo, (ii) the {log}{R}{HK}\prime measurements are biased by extrinsic absorption, either by the interstellar medium (ISM) or by material local to the system. We present here Hubble Space Telescope/COS far-UV spectra of WASP-13, which hosts an inflated hot Jupiter and has a measured {log}{R}{HK}\prime value (-5.26), well below the basal level. From the star's spectral energy distribution we obtain an extinction E(B - V) = 0.045 ± 0.025 mag and a distance d = 232 ± 8 pc. We detect at ≳4σ lines belonging to three different ionization states of carbon (C i, C ii, and C iv) and the Si iv doublet at ˜3σ. Using far-UV spectra of nearby early G-type stars of known age, we derive a C iv/C i flux ratio-age relation, from which we estimate WASP-13's age to be 5.1 ± 2.0 Gyr. We rescale the solar irradiance reference spectrum to match the flux of the C iv 1548 doublet. By integrating the rescaled solar spectrum, we obtain an XUV flux at 1 AU of 5.4 erg s-1 cm-2. We use a detailed model of the planet's upper atmosphere, deriving a mass-loss rate of 1.5 × 1011 g s-1. Despite the low {log}{R}{HK}\prime value, the star shows a far-UV spectrum typical of middle-aged solar-type stars, pointing toward the presence of significant extrinsic absorption. The analysis of a high-resolution spectrum of the Ca ii H&K lines indicates that the ISM absorption could be the origin of the low {log}{R}{HK}\prime value. Nevertheless, the large uncertainty in the Ca ii ISM abundance does not allow us to firmly exclude the presence of circumstellar gas. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained from MAST at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These observations are associated with program #13859

Genome-Wide Profiling of H3K56 Acetylation and Transcription Factor Binding Sites in Human Adipocytes

The growing epidemic of obesity and metabolic diseases calls for a better understanding of adipocyte biology. The regulation of transcription in adipocytes is particularly important, as it is a target for several therapeutic approaches. Transcriptional outcomes are influenced by both histone modifications and transcription factor binding. Although the epigenetic states and binding sites of several important transcription factors have been profiled in the mouse 3T3-L1 cell line, such data are lacking in human adipocytes. In this study, we identified H3K56 acetylation sites in human adipocytes derived from mesenchymal stem cells. H3K56 is acetylated by CBP and p300, and deacetylated by SIRT1, all are proteins with important roles in diabetes and insulin signaling. We found that while almost half of the genome shows signs of H3K56 acetylation, the highest level of H3K56 acetylation is associated with transcription factors and proteins in the adipokine signaling and Type II Diabetes pathways. In order to discover the transcription factors that recruit acetyltransferases and deacetylases to sites of H3K56 acetylation, we analyzed DNA sequences near H3K56 acetylated regions and found that the E2F recognition sequence was enriched. Using chromatin immunoprecipitation followed by high-throughput sequencing, we confirmed that genes bound by E2F4, as well as those by HSF-1 and C/EBPα, have higher than expected levels of H3K56 acetylation, and that the transcription factor binding sites and acetylation sites are often adjacent but rarely overlap. We also discovered a significant difference between bound targets of C/EBPα in 3T3-L1 and human adipocytes, highlighting the need to construct species-specific epigenetic and transcription factor binding site maps. This is the first genome-wide profile of H3K56 acetylation, E2F4, C/EBPα and HSF-1 binding in human adipocytes, and will serve as an important resource for better understanding adipocyte transcriptional regulation.Singapore. Agency for Science, Technology and Research (National Science Scholarship )Massachusetts Institute of Technology (Eugene Bell Career Development Chair)National Science Foundation (U.S.) (Award No. DBI-0821391)Pfizer Inc

GATA6 Activates Wnt Signaling in Pancreatic Cancer by Negatively Regulating the Wnt Antagonist Dickkopf-1

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease characterized by late diagnosis and treatment resistance. Recurrent genetic alterations in defined genes in association with perturbations of developmental cell signaling pathways have been associated with PDAC development and progression. Here, we show that GATA6 contributes to pancreatic carcinogenesis during the temporal progression of pancreatic intraepithelial neoplasia by virtue of Wnt pathway activation. GATA6 is recurrently amplified by both quantitative-PCR and fluorescent in-situ hybridization in human pancreatic intraepithelial neoplasia and in PDAC tissues, and GATA6 copy number is significantly correlated with overall patient survival. Forced overexpression of GATA6 in cancer cell lines enhanced cell proliferation and colony formation in soft agar in vitro and growth in vivo, as well as increased Wnt signaling. By contrast siRNA mediated knockdown of GATA6 led to corresponding decreases in these same parameters. The effects of GATA6 were found to be due to its ability to bind DNA, as forced overexpression of a DNA-binding mutant of GATA6 had no effects on cell growth in vitro or in vivo, nor did they affect Wnt signaling levels in these same cells. A microarray analysis revealed the Wnt antagonist Dickopf-1 (DKK1) as a dysregulated gene in association with GATA6 knockdown, and direct binding of GATA6 to the DKK1 promoter was confirmed by chromatin immunoprecipitation and electrophoretic mobility shift assays. Transient transfection of GATA6, but not mutant GATA6, into cancer cell lines led to decreased DKK1 mRNA expression and secretion of DKK1 protein into culture media. Forced overexpression of DKK1 antagonized the effects of GATA6 on Wnt signaling in pancreatic cancer cells. These findings illustrate that one mechanism by which GATA6 promotes pancreatic carcinogenesis is by virtue of its activation of canonical Wnt signaling via regulation of DKK1

The XMM Cluster Survey: Forecasting cosmological and cluster scaling-relation parameter constraints

We forecast the constraints on the values of sigma_8, Omega_m, and cluster scaling relation parameters which we expect to obtain from the XMM Cluster Survey (XCS). We assume a flat Lambda-CDM Universe and perform a Monte Carlo Markov Chain analysis of the evolution of the number density of galaxy clusters that takes into account a detailed simulated selection function. Comparing our current observed number of clusters shows good agreement with predictions. We determine the expected degradation of the constraints as a result of self-calibrating the luminosity-temperature relation (with scatter), including temperature measurement errors, and relying on photometric methods for the estimation of galaxy cluster redshifts. We examine the effects of systematic errors in scaling relation and measurement error assumptions. Using only (T,z) self-calibration, we expect to measure Omega_m to +-0.03 (and Omega_Lambda to the same accuracy assuming flatness), and sigma_8 to +-0.05, also constraining the normalization and slope of the luminosity-temperature relation to +-6 and +-13 per cent (at 1sigma) respectively in the process. Self-calibration fails to jointly constrain the scatter and redshift evolution of the luminosity-temperature relation significantly. Additional archival and/or follow-up data will improve on this. We do not expect measurement errors or imperfect knowledge of their distribution to degrade constraints significantly. Scaling-relation systematics can easily lead to cosmological constraints 2sigma or more away from the fiducial model. Our treatment is the first exact treatment to this level of detail, and introduces a new `smoothed ML' estimate of expected constraints.Comment: 28 pages, 17 figures. Revised version, as accepted for publication in MNRAS. High-resolution figures available at http://xcs-home.org (under "Publications"

A novel μCT analysis reveals different responses of bioerosion and secondary accretion to environmental variability

Corals build reefs through accretion of calcium carbonate (CaCO3) skeletons, but net reef growth also depends on bioerosion by grazers and borers and on secondary calcification by crustose coralline algae and other calcifying invertebrates. However, traditional field methods for quantifying secondary accretion and bioerosion confound both processes, do not measure them on the same time-scale, or are restricted to 2D methods. In a prior study, we compared multiple environmental drivers of net erosion using pre- and post-deployment micro-computed tomography scans (μCT; calculated as the % change in volume of experimental CaCO3 blocks) and found a shift from net accretion to net erosion with increasing ocean acidity. Here, we present a novel μCT method and detail a procedure that aligns and digitally subtracts pre- and post-deployment μCT scans and measures the simultaneous response of secondary accretion and bioerosion on blocks exposed to the same environmental variation over the same time-scale. We tested our method on a dataset from a prior study and show that it can be used to uncover information previously unattainable using traditional methods. We demonstrated that secondary accretion and bioerosion are driven by different environmental parameters, bioerosion is more sensitive to ocean acidity than secondary accretion, and net erosion is driven more by changes in bioerosion than secondary accretion

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Short-Lived Trace Gases in the Surface Ocean and the Atmosphere

The two-way exchange of trace gases between the ocean and the atmosphere is important for both the chemistry and physics of the atmosphere and the biogeochemistry of the oceans, including the global cycling of elements. Here we review these exchanges and their importance for a range of gases whose lifetimes are generally short compared to the main greenhouse gases and which are, in most cases, more reactive than them. Gases considered include sulphur and related compounds, organohalogens, non-methane hydrocarbons, ozone, ammonia and related compounds, hydrogen and carbon monoxide. Finally, we stress the interactivity of the system, the importance of process understanding for modeling, the need for more extensive field measurements and their better seasonal coverage, the importance of inter-calibration exercises and finally the need to show the importance of air-sea exchanges for global cycling and how the field fits into the broader context of Earth System Science