Structural snapshots of concerted double E–H bond activation at a transition metal centre

Bond activation at a transition metal centre is a key fundamental step in numerous chemical transformations. The oxidative addition of element–hydrogen bonds, for example, represents a critical step in a range of widely applied catalytic processes. Despite this, experimental studies defining steps along the bond activation pathway are very rare. In this work, we report on fundamental studies defining a new oxidative activation pathway: combined experimental and computational approaches yield structural snapshots of the simultaneous activation of both bonds of a β-diketiminate-stabilized GaH2 unit at a single metal centre. Systematic variation of the supporting phosphine ligands and single crystal X-ray/neutron diffraction are exploited in tandem to allow structural visualization of the activation process, from a η2-H,H σ-complex showing little Ga–H bond activation, through species of intermediate geometry featuring stretched Ga–H and compressed M–H/M–Ga bonds, to a fully activated metal dihydride featuring a neutral (carbene-type) N-heterocyclic GaI ligand

Mapping and simulating systematics due to spatially-varying observing conditions in DES Science Verification data

Spatially-varying depth and characteristics of observing conditions, such as seeing, airmass, or sky background, are major sources of systematic uncertainties in modern galaxy survey analyses, in particular in deep multi-epoch surveys. We present a framework to extract and project these sources of systematics onto the sky, and apply it to the Dark Energy Survey (DES) to map the observing conditions of the Science Verification (SV) data. The resulting distributions and maps of sources of systematics are used in several analyses of DES SV to perform detailed null tests with the data, and also to incorporate systematics in survey simulations. We illustrate the complementarity of these two approaches by comparing the SV data with the BCC-UFig, a synthetic sky catalogue generated by forward-modelling of the DES SV images. We analyse the BCC-UFig simulation to construct galaxy samples mimicking those used in SV galaxy clustering studies. We show that the spatially-varying survey depth imprinted in the observed galaxy densities and the redshift distributions of the SV data are successfully reproduced by the simulation and well-captured by the maps of observing conditions. The combined use of the maps, the SV data and the BCC-UFig simulation allows us to quantify the impact of spatial systematics on $N(z)$, the redshift distributions inferred using photometric redshifts. We conclude that spatial systematics in the SV data are mainly due to seeing fluctuations and are under control in current clustering and weak lensing analyses. The framework presented here is relevant to all multi-epoch surveys, and will be essential for exploiting future surveys such as the Large Synoptic Survey Telescope (LSST), which will require detailed null-tests and realistic end-to-end image simulations to correctly interpret the deep, high-cadence observations of the sky

Dark Energy Survey Year 1 Results: Tomographic cross-correlations between Dark Energy Survey galaxies and CMB lensing from South Pole Telescope+Planck

We measure the cross-correlation between redMaGiC galaxies selected from the Dark Energy Survey (DES) year 1 data and gravitational lensing of the cosmic microwave background (CMB) reconstructed from South Pole Telescope (SPT) and Planck data over 1289 deg2. When combining measurements across multiple galaxy redshift bins spanning the redshift range of 0.1

Dark Energy Survey Year 1 results: galaxy-galaxy lensing

We present galaxy-galaxy lensing measurements from 1321 sq. deg. of the Dark Energy Survey (DES) Year 1 (Y1) data. The lens sample consists of a selection of 660,000 red galaxies with high-precision photometric redshifts, known as redMaGiC, split into five tomographic bins in the redshift range 0.15<z<0.9 . We use two different source samples, obtained from the Metacalibration (26 million galaxies) and Im3shape (18 million galaxies) shear estimation codes, which are split into four photometric redshift bins in the range 0.2<z<1.3 . We perform extensive testing of potential systematic effects that can bias the galaxy-galaxy lensing signal, including those from shear estimation, photometric redshifts, and observational properties. Covariances are obtained from jackknife subsamples of the data and validated with a suite of log-normal simulations. We use the shear-ratio geometric test to obtain independent constraints on the mean of the source redshift distributions, providing validation of those obtained from other photo-z studies with the same data. We find consistency between the galaxy bias estimates obtained from our galaxy-galaxy lensing measurements and from galaxy clustering, therefore showing the galaxy-matter cross-correlation coefficient r to be consistent with one, measured over the scales used for the cosmological analysis. The results in this work present one of the three two-point correlation functions, along with galaxy clustering and cosmic shear, used in the DES cosmological analysis of Y1 data, and hence the methodology and the systematics tests presented here provide a critical input for that study as well as for future cosmological analyses in DES and other photometric galaxy surveys

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Extensive permethrin and DDT resistance in Anopheles arabiensis from eastern and central Sudan

<p>Abstract</p> <p>Background</p> <p>The distribution of insecticide treated nets (ITN) has been dramatically scaled up in eastern and central Sudan. Resistance to insecticides has already been reported in this region and there is an urgent need to develop appropriate resistance management strategies, which requires detailed information on the extent and causes of resistance. This study assessed resistance to permethrin and DDT in seven populations of <it>Anopheles arabiensis </it>from Sudan.</p> <p>Results</p> <p>Three out of the seven populations were defined as resistant to permethrin and five of six populations resistant to DDT according to WHO criteria. The 1014F kdr allele was present in all six populations tested and the presence of this allele was significantly correlated with resistance to permethrin (<it>P </it>= 0.0460). While homozygous 1014F individuals were statistically not more likely to survive (53.7%) permethrin than to be killed (38.6%) by the diagnostic dose, there was no difference in the likelihood of permethrin survival in heterozygotes (<it>P </it>= 0.7973). The susceptible genotypes were more likely to be killed by permethrin exposure than to survive (<it>P </it>= 0.0460). The 1014F allele failed to confer a survival advantage to the WHO diagnostic dose of DDT in either the homozygous or heterozygous state. The 1014S allele was not detected in any of the populations tested.</p> <p>Conclusion</p> <p>The kdr allele is certainly contributing to the extensive resistance to permethrin and DDT in Sudan but the high number of DDT (43%) and permethrin (16.7%) survivors that did not contain either kdr alleles suggests that other resistance mechanisms are also present in these populations. The high frequency of permethrin resistance throughout central and eastern Sudan is a cause of great concern for malaria control activities.</p

The non-pathogenic mycobacteria M. smegmatis and M. fortuitum induce rapid host cell apoptosis via a caspase-3 and TNF dependent pathway

<p>Abstract</p> <p>Background</p> <p>The HIV pandemic raised the potential for facultative-pathogenic mycobacterial species like, <it>Mycobacterium kansasii</it>, to cause disseminating disease in humans with immune deficiencies. In contrast, non-pathogenic mycobacterial species, like <it>M. smegmatis</it>, are not known to cause disseminating disease even in immunocompromised individuals. We hypothesized that this difference in phenotype could be explained by the strong induction of an innate immune response by the non-pathogenic mycobacterial species.</p> <p>Results</p> <p>A comparison of two rapid-growing, non-pathogenic species (<it>M. smegmatis </it>and <it>M. fortuitum</it>) with two facultative-pathogenic species (<it>M. kansasii </it>and <it>M. bovis </it>BCG) demonstrated that only the non-pathogenic bacteria induced strong apoptosis in human THP-1 cells and murine bone marrow-derived macrophages (BMDM) and dendritic cells (BMDD). The phospho-<it>myo</it>-inositol modification of lipoarabinomannan (PI-LAM) isolated from non-pathogenic species may be one of the cell wall components responsible for the pro-inflammatory activity of the whole bacteria. Indeed, PI-LAM induces high levels of apoptosis and IL-12 expression compared to the mannosyl modification of LAM isolated from facultative-pathogenic mycobacteria. The apoptosis induced by non-pathogenic <it>M. smegmatis </it>was dependent upon caspase-3 activation and TNF secretion. Consistently, BALB/c BMDM responded by secreting large amounts of TNF upon infection with non-pathogenic but not facultative-pathogenic mycobacteria. Interestingly, C57Bl/6 BMDM do not undergo apoptosis upon infection with non-pathogenic mycobacteria despite the fact that they still induce an increase in TNF secretion. This suggests that the host cell signaling pathways are different between these two mouse genotypes and that TNF is necessary but not sufficient to induce host cell apoptosis.</p> <p>Conclusion</p> <p>These results demonstrate a much stronger induction of the innate immune response by non-pathogenic versus facultative-pathogenic mycobacteria as measured by host cell apoptosis, IL-12 and TNF cytokine induction. These observations lend support to the hypothesis that the strong induction of the innate immune response is a major reason for the lack of pathogenicity in fast-growing mycobacteria.</p