Very high energy particle acceleration powered by the jets of the microquasar SS 433

SS 433 is a binary system containing a supergiant star that is overflowing its Roche lobe with matter accreting onto a compact object (either a black hole or neutron star). Two jets of ionized matter with a bulk velocity of $\sim0.26c$ extend from the binary, perpendicular to the line of sight, and terminate inside W50, a supernova remnant that is being distorted by the jets. SS 433 differs from other microquasars in that the accretion is believed to be super-Eddington, and the luminosity of the system is $\sim10^{40}$ erg s$^{-1}$. The lobes of W50 in which the jets terminate, about 40 pc from the central source, are expected to accelerate charged particles, and indeed radio and X-ray emission consistent with electron synchrotron emission in a magnetic field have been observed. At higher energies (>100 GeV), the particle fluxes of $\gamma$ rays from X-ray hotspots around SS 433 have been reported as flux upper limits. In this energy regime, it has been unclear whether the emission is dominated by electrons that are interacting with photons from the cosmic microwave background through inverse-Compton scattering or by protons interacting with the ambient gas. Here we report TeV $\gamma$-ray observations of the SS 433/W50 system where the lobes are spatially resolved. The TeV emission is localized to structures in the lobes, far from the center of the system where the jets are formed. We have measured photon energies of at least 25 TeV, and these are certainly not Doppler boosted, because of the viewing geometry. We conclude that the emission from radio to TeV energies is consistent with a single population of electrons with energies extending to at least hundreds of TeV in a magnetic field of $\sim16$~micro-Gauss.Comment: Preprint version of Nature paper. Contacts: S. BenZvi, B. Dingus, K. Fang, C.D. Rho , H. Zhang, H. Zho

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

Refining the transit-timing and photometric analysis of TRAPPIST-1: Masses, Radii, densities, dynamics, and ephemerides

We have collected transit times for the TRAPPIST-1 system with the Spitzer Space Telescope over four years. We add to these ground-based, HST and K2 transit time measurements, and revisit an N-body dynamical analysis of the seven-planet system using our complete set of times from which we refine the mass ratios of the planets to the star. We next carry out a photodynamical analysis of the Spitzer light curves to derive the density of the host star and the planet densities. We find that all seven planets' densities may be described with a single rocky mass-radius relation which is depleted in iron relative to Earth, with Fe 21 wt% versus 32 wt% for Earth, and otherwise Earth-like in composition. Alternatively, the planets may have an Earth-like composition, but enhanced in light elements, such as a surface water layer or a core-free structure with oxidized iron in the mantle. We measure planet masses to a precision of 3-5%, equivalent to a radial-velocity (RV) precision of 2.5 cm/sec, or two orders of magnitude more precise than current RV capabilities. We find the eccentricities of the planets are very small; the orbits are extremely coplanar; and the system is stable on 10 Myr timescales. We find evidence of infrequent timing outliers which we cannot explain with an eighth planet; we instead account for the outliers using a robust likelihood function. We forecast JWST timing observations, and speculate on possible implications of the planet densities for the formation, migration and evolution of the planet system

Roles for the Conserved Spc105p/Kre28p Complex in Kinetochore-Microtubule Binding and the Spindle Assembly Checkpoint

Kinetochores attach sister chromatids to microtubules of the mitotic spindle and orchestrate chromosome disjunction at anaphase. Although S. cerevisiae has the simplest known kinetochores, they nonetheless contain approximately 70 subunits that assemble on centromeric DNA in a hierarchical manner. Developing an accurate picture of the DNA-binding, linker and microtubule-binding layers of kinetochores, including the functions of individual proteins in these layers, is a key challenge in the field of yeast chromosome segregation. Moreover, comparison of orthologous proteins in yeast and humans promises to extend insight obtained from the study of simple fungal kinetochores to complex animal cell kinetochores.We show that S. cerevisiae Spc105p forms a heterotrimeric complex with Kre28p, the likely orthologue of the metazoan kinetochore protein Zwint-1. Through systematic analysis of interdependencies among kinetochore complexes, focused on Spc105p/Kre28p, we develop a comprehensive picture of the assembly hierarchy of budding yeast kinetochores. We find Spc105p/Kre28p to comprise the third linker complex that, along with the Ndc80 and MIND linker complexes, is responsible for bridging between centromeric heterochromatin and kinetochore MAPs and motors. Like the Ndc80 complex, Spc105p/Kre28p is also essential for kinetochore binding by components of the spindle assembly checkpoint. Moreover, these functions are conserved in human cells.Spc105p/Kre28p is the last of the core linker complexes to be analyzed in yeast and we show it to be required for kinetochore binding by a discrete subset of kMAPs (Bim1p, Bik1p, Slk19p) and motors (Cin8p, Kar3p), all of which are nonessential. Strikingly, dissociation of these proteins from kinetochores prevents bipolar attachment, even though the Ndc80 and DASH complexes, the two best-studied kMAPs, are still present. The failure of Spc105 deficient kinetochores to bind correctly to spindle microtubules and to recruit checkpoint proteins in yeast and human cells explains the observed severity of missegregation phenotypes

Cortisol, cognition and the ageing prefrontal cortex

The structural and functional decline of the ageing human brain varies by brain region, cognitive function and individual. The underlying biological mechanisms are poorly understood. One potentially important mechanism is exposure to glucocorticoids (GCs; cortisol in humans); GC production is increasingly varied with age in humans, and chronic exposure to high levels is hypothesised to result in cognitive decline via cerebral remodelling. However, studies of GC exposure in humans are scarce and methodological differences confound cross-study comparison. Furthermore, there has been little focus on the effects of GCs on the frontal lobes and key white matter tracts in the ageing brain. This thesis therefore examines relationships among cortisol levels, structural brain measures and cognitive performance in 90 healthy, elderly community-dwelling males from the Lothian Birth Cohort 1936. Salivary cortisol samples characterised diurnal (morning and evening) and reactive profiles (before and after a cognitive test battery). Structural variables comprised Diffusion Tensor Imaging measures of major brain tracts and a novel manual parcellation method for the frontal lobes. The latter was based on a systematic review of current manual methods in the context of putative function and cytoarchitecture. Manual frontal lobe brain parcellation conferred greater spatial and volumetric accuracy when compared to both single- and multi-atlas parcellation at the lobar level. Cognitive ability was assessed via tests of general cognitive ability, and neuropsychological tests thought to show differential sensitivity to the integrity of frontal lobe sub-regions. The majority of, but not all frontal lobe test scores shared considerable overlap with general cognitive ability, and cognitive scores correlated most consistently with the volumes of the anterior cingulate. This is discussed in light of the diverse connective profile of the cingulate and a need to integrate information over more diffuse cognitive networks according to proposed de-differentiation or compensation in ageing. Individuals with higher morning, evening or pre-test cortisol levels showed consistently negative relationships with specific regional volumes and tract integrity. Participants whose cortisol levels increased between the start and end of cognitive testing showed selectively larger regional volumes and lower tract diffusivity (correlation magnitudes <.44). The significant relationships between cortisol levels and cognition indicated that flatter diurnal slopes or higher pre-test levels related to poorer test performance. In contrast, higher levels in the morning generally correlated with better scores (correlation magnitudes <.25). Interpretation of all findings was moderated by sensitivity to type I error, given the large number of comparisons conducted. Though there were limited candidates for mediation analysis, cortisol-function relationships were partially mediated by tract integrity (but not sub-regional frontal volumes) for memory and post-error slowing. This thesis offers a novel perspective on the complex interplay among glucocorticoids, cognition and the structure of the ageing brain. The findings suggest some role for cortisol exposure in determining age-related decline in complex cognition, mediated via brain structure

Measurement of Λb0 , Λc+ , and Λ decay parameters using Λb0→Λc+h− decays

A comprehensive study of the angular distributions in the bottom-baryon decays Λ0 b → Λ c+h−(h = π, K), followed by Λþ c → Λhþ with Λ → pπ− or Λþ c → pK0 S decays, is performed using a data sample of proton-proton collisions corresponding to an integrated luminosity of 9 fb−1 collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. The decay parameters and the associated charge-parity (CP) asymmetries are measured, with no significant CP violation observed. For the first time, the Λ0 b → Λþ c h− decay parameters are measured. The most precise measurements of the decay parameters α, β, and γ are obtained for Λþ c decays and an independent measurement of the decay parameters for the strange-baryon Λ decay is provided. The results deepen our understanding of weak decay dynamics in baryon decays