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On 17 August 2017, gravitational waves (GWs) were detected from a binary neutron star merger, GW170817, along with a coincident short gamma-ray burst, GRB 170817A. An optical transient source, Swope Supernova Survey 17a (SSS17a),was subsequently identified as the counterpart of this event. We present ultraviolet, optical, and infrared light curves of SSS17a extending from 10.9 hours to 18 days postmerger. We constrain the radioactively powered transient resulting from the ejection of neutron-rich material. The fast rise of the light curves, subsequent decay, and rapid color evolution are consistent with multiple ejecta components of differing lanthanide abundance. The late-time light curve indicates that SSS17a produced at least ~0.05 solar masses of heavy elements, demonstrating that neutron star mergers play a role in rapid neutron capture (r-process) nucleosynthesis in the universe.

Many chronic medical conditions are accompanied by cognitive disturbances but these have only to a very limited extent been psychometrically quantified. An exception is liver cirrhosis where hepatic encephalopathy is an inherent risk and mild forms are diagnosed by psychometric tests. The preferred diagnostic test battery in cirrhosis is often the Continuous Reaction Time (CRT) and the Portosystemic Encephalopathy (PSE) tests but the effect on these of other medical conditions is not known. We aimed to examine the effects of common chronic (non-cirrhosis) medical conditions on the CRT and PSE tests. We studied 15 patients with heart failure (HF), 15 with end stage renal failure (ESRF), 15 with dysregulated type II diabetes (DMII), 15 with chronic obstructive pulmonary disease (COPD), and 15 healthy persons. We applied the CRT test, which is a 10-min computerized test measuring sustained attention and reaction time stability and the PSE test, which is a paper-pencil test battery consisting of 5 subtests. We found that a high fraction of the patients with HF (8/15, 0.002) or COPD (7/15, p  = 0.006) had pathological CRT test results; and COPD patients also frequently had an abnormal PSE test result (6/15, p  < 0.0001). Both tests were unaffected by ESRF and DMII. Half of the patients with HF or COPD had psychometrically measurable cognitive deficits, whereas those with ESRF or DMII had not. This adds to the understanding of the clinical consequences of chronic heart- and lung disease, and implies that the psychometric tests should be interpreted with great caution in cirrhosis patients with heart- or lung comorbidity.

We present 18 years of OGLE photometry together with spectra obtained over 12 years, revealing that the early Oe star AzV 493 shows strong photometric (Delta I < 1.2 mag) and spectroscopic variability with a dominant, 14.6-year pattern and ~40-day oscillations. We estimate stellar parameters T_eff = 42000 K, log L/L_sun = 5.83 +/- 0.15, M/M_sun = 50 +/- 9, and vsini = 370 +/- 40 km/s. Direct spectroscopic evidence shows episodes of both gas ejection and infall. There is no X-ray detection, and it is likely a runaway star. AzV 493 may have an unseen companion on a highly eccentric (e > 0.93) orbit. We propose that close interaction at periastron excites ejection of the decretion disk, whose variable emission-line spectrum suggests separate inner and outer components, with an optically thick outer component obscuring both the stellar photosphere and the emission-line spectrum of the inner disk at early phases in the photometric cycle. It is plausible that AzV 493's mass and rotation have been enhanced by binary interaction followed by the core-collapse supernova explosion of the companion, which now could be either a black hole or neutron star. This system in the Small Magellanic Cloud can potentially shed light on OBe decretion disk formation and evolution, massive binary evolution, and compact binary progenitors.

On 2017 August 17, gravitational waves were detected from a binary neutron star merger, GW170817, along with a coincident short gamma-ray burst, GRB170817A. An optical transient source, Swope Supernova Survey 17a (SSS17a), was subsequently identified as the counterpart of this event. We present ultraviolet, optical and infrared light curves of SSS17a extending from 10.9 hours to 18 days post-merger. We constrain the radioactively-powered transient resulting from the ejection of neutron-rich material. The fast rise of the light curves, subsequent decay, and rapid color evolution are consistent with multiple ejecta components of differing lanthanide abundance. The late-time light curve indicates that SSS17a produced at least ~0.05 solar masses of heavy elements, demonstrating that neutron star mergers play a role in r-process nucleosynthesis in the Universe.

Background Perioperative hemorrhage may depend on coagulation competence and this study evaluated the influence of coagulation competence on blood loss during cystectomy due to bladder cancer. Methods Forty patients undergoing radical cystectomy were included in a randomized controlled trial to receive either lactated Ringer’s solution or Dextran 70 (Macrodex ®) that affects coagulation competence. Results By thrombelastography evaluated coagulation competence, Dextran 70 reduced “maximal amplitude” (MA) by 25 % versus a 1 % reduction with the administration of lactated Ringer’s solution ( P <0.001). Blinded evaluation of the blood loss was similar in the two groups of patients - 2339 ml with the use of Dextran 70 and 1822 ml in the lactated Ringer’s group ( P  = 0.27). Yet, the blood loss was related to the reduction in MA ( r  = −0.427, P  = 0.008) and by multiple regression analysis independently associated with MA ( P  = 0.01). Thus, 11 patients in the dextran group (58 %) developed a clinical significant blood loss (>1500 ml) compared to only four patients (22 %) in the lactated Ringer’s group ( P  = 0.04). Conclusions With the use of Dextran 70 vs. lactated Ringer’s solution during cystectomy, a relation between hemorrhage and coagulation competence is demonstrated. Significant bleeding develops based on an about 25 % reduction in thrombelastography determined maximal amplitude. A multivariable model including maximal amplitude discriminates patients with severe perioperative bleeding during cystectomy. Trial registration The study was accepted on January 7 th , 2013 at www.clinicaltrialsregister.eu EudraCT 2012-005040-20 .

In serum, the major part of vascular endothelial growth factor derives from in vitro degranulation of granulocytes and platelets. Therefore, plasma may be preferred for vascular endothelial growth factor measurements. However, which specimen is the best predictor of survival is still debated. The present study analyzed the prognostic value of matched preoperative serum and plasma vascular endothelial growth factor concentrations in patients with colorectal cancer. To establish the reference range among healthy people, vascular endothelial growth factor was analyzed in 50 matched EDTA-plasma and serum samples from healthy blood donors. Preoperatively, in 524 patients with colorectal cancer, matched plasma and serum vascular endothelial growth factor concentrations were analyzed. In the colorectal cancer patients, the median plasma vascular endothelial growth factor concentration (44 pg ml −1 ) was significantly ( P =0.01) higher than the median plasma vascular endothelial growth factor concentration (30 pg ml −1 ) in the healthy blood donors. In serum, no significant ( P =0.30) difference in the median vascular endothelial growth factor concentration was found between colorectal cancer patients (268 pg ml −1 ) and healthy blood donors (220 pg ml −1 ). The preoperative vascular endothelial growth factor concentrations were dichotomized by the 95th percentile of the healthy blood donors (plasma=112 pg ml −1 , serum=533 pg ml −1 ). In univariate survival analyses, both high plasma vascular endothelial growth factor (>112 pg ml −1 ) and high serum vascular endothelial growth factor (>533 pg ml −1 ) predicted a reduced survival. In multivariate survival analyses, high serum vascular endothelial growth factor (>533 pg ml −1 ) independently predicted a reduced survival (HR=1.65, P =0.015), while high plasma vascular endothelial growth factor (>112 pg ml −1 ) did not (HR=1.27, P =0.23). This study indicates that preoperative serum vascular endothelial growth factor apparently is a better predictor of overall survival than the preoperative plasma vascular endothelial growth factor.

Novel high-resolution convection-permitting regional climate simulations over the US employing the pseudo-global warming approach are used to investigate changes in the convective population and thermodynamic environments in a future climate. Two continuous 13-year simulations were conducted using (1) ERA-Interim reanalysis and (2) ERA-Interim reanalysis plus a climate perturbation for the RCP8.5 scenario. The simulations adequately reproduce the observed precipitation diurnal cycle, indicating that they capture organized and propagating convection that most climate models cannot adequately represent. This study shows that weak to moderate convection will decrease and strong convection will increase in frequency in a future climate. Analysis of the thermodynamic environments supporting convection shows that both convective available potential energy (CAPE) and convective inhibition (CIN) increase downstream of the Rockies in a future climate. Previous studies suggest that CAPE will increase in a warming climate, however a corresponding increase in CIN acts as a balancing force to shift the convective population by suppressing weak to moderate convection and provides an environment where CAPE can build to extreme levels that may result in more frequent severe convection. An idealized investigation of fundamental changes in the thermodynamic environment was conducted by shifting a standard atmospheric profile by ± 5 °C. When temperature is increased, both CAPE and CIN increase in magnitude, while the opposite is true for decreased temperatures. Thus, even in the absence of synoptic and mesoscale variations, a warmer climate will provide more CAPE and CIN that will shift the convective population, likely impacting water and energy budgets on Earth.

Oncogene-evoked replication stress (RS) fuels genomic instability in diverse cancer types. Here we report that BRCA1, traditionally regarded a tumour suppressor, plays an unexpected tumour-promoting role in glioblastoma (GBM), safeguarding a protective response to supraphysiological RS levels. Higher BRCA1 positivity is associated with shorter survival of glioma patients and the abrogation of BRCA1 function in GBM enhances RS, DNA damage (DD) accumulation and impairs tumour growth. Mechanistically, we identify a novel role of BRCA1 as a transcriptional co-activator of RRM2 (catalytic subunit of ribonucleotide reductase), whereby BRCA1-mediated RRM2 expression protects GBM cells from endogenous RS, DD and apoptosis. Notably, we show that treatment with a RRM2 inhibitor triapine reproduces the BRCA1-depletion GBM-repressive phenotypes and sensitizes GBM cells to PARP inhibition. We propose that GBM cells are addicted to the RS-protective role of the BRCA1-RRM2 axis, targeting of which may represent a novel paradigm for therapeutic intervention in GBM. BRCA1 loss can result in collapse of replication forks into DNA double strand breaks that can contribute to malignant transformation. Here, the authors find that BRCA1 promotes the expression of RRM2 protecting glioblastoma cells from replication stress, DNA damage and apoptosis.

Conformation-specific antibodies capable of monitoring the activation state of a G-protein-coupled seven-transmembrane receptor, the β 2 -adrenoceptor, reveals receptor and G-protein activation not only in the plasma membrane, but also in the endosome. Adrenoceptor signalling linked to endosomes It is widely assumed that G-protein-linked signalling occurs only at the plasma membrane. In this study, Mark von Zastrow and colleagues use conformation-specific single-chain antibodies to directly probe the activation of the β2-adrenoceptor, which is a prototypical G-protein-coupled receptor, and its cognate G protein, G s , in living cells. They show that classical or canonical G-protein-linked signalling occurs from endosomes as well as from the plasma membrane. A long-held tenet of molecular pharmacology is that canonical signal transduction mediated by G-protein-coupled receptor (GPCR) coupling to heterotrimeric G proteins is confined to the plasma membrane. Evidence supporting this traditional view is based on analytical methods that provide limited or no subcellular resolution 1 . It has been subsequently proposed that signalling by internalized GPCRs is restricted to G-protein-independent mechanisms such as scaffolding by arrestins 2 , 3 , or GPCR activation elicits a discrete form of persistent G protein signalling 4 , 5 , 6 , 7 , 8 , 9 , or that internalized GPCRs can indeed contribute to the acute G-protein-mediated response 10 . Evidence supporting these various latter hypotheses is indirect or subject to alternative interpretation, and it remains unknown if endosome-localized GPCRs are even present in an active form. Here we describe the application of conformation-specific single-domain antibodies (nanobodies) to directly probe activation of the β 2 -adrenoceptor, a prototypical GPCR 11 , and its cognate G protein, G s (ref. 12 ), in living mammalian cells. We show that the adrenergic agonist isoprenaline promotes receptor and G protein activation in the plasma membrane as expected, but also in the early endosome membrane, and that internalized receptors contribute to the overall cellular cyclic AMP response within several minutes after agonist application. These findings provide direct support for the hypothesis that canonical GPCR signalling occurs from endosomes as well as the plasma membrane, and suggest a versatile strategy for probing dynamic conformational change in vivo .

A unique, high-resolution, hydroclimate reanalysis, 40-plus-year (October 1979–September 2021), 4 km (named as CONUS404), has been created using the Weather Research and Forecasting Model by dynamically downscaling of the fifth-generation European Centre for Medium-Range Weather Forecasts (ECMWF) atmospheric reanalysis of the global climate dataset (ERA5) over the conterminous United States. The paper describes the approach for generating the dataset, provides an initial evaluation, including biases, and indicates how interested users can access the data. The motivation for creating this National Center for Atmospheric Research (NCAR)–U.S. Geological Survey (USGS) collaborative dataset is to provide research and end-user communities with a high-resolution, self-consistent, long-term, continental-scale hydroclimate dataset appropriate for forcing hydrological models and conducting hydroclimate scientific analyses over the conterminous United States. The data are archived and accessible on the USGS Black Pearl tape system and on the NCAR supercomputer Campaign storage system.