Rapid and Accurate Assessment of GPCR-Ligand Interactions Using the Fragment Molecular Orbital-Based Density-Functional Tight-Binding Method

The reliable and precise evaluation of receptor–ligand interactions and pair-interaction energy is an essential element of rational drug design. While quantum mechanical (QM) methods have been a promising means by which to achieve this, traditional QM is not applicable for large biological systems due to its high computational cost. Here, the fragment molecular orbital (FMO) method has been used to accelerate QM calculations, and by combining FMO with the density-functional tight-binding (DFTB) method we are able to decrease computational cost 1000 times, achieving results in seconds, instead of hours. We have applied FMO-DFTB to three different GPCR–ligand systems. Our results correlate well with site directed mutagenesis data and findings presented in the published literature, demonstrating that FMO-DFTB is a rapid and accurate means of GPCR–ligand interactions

Anarchy in the UK: Detailed genetic analysis of worker reproduction in a naturally occurring British anarchistic honeybee, Apis mellifera, colony using DNA microsatellites

Anarchistic behaviour is a very rare phenotype of honeybee colonies. In an anarchistic colony, many workers’ sons are reared in the presence of the queen. Anarchy has previously been described in only two Australian colonies. Here we report on a first detailed genetic analysis of a British anarchistic colony. Male pupae were present in great abundance above the queen excluder, which was clearly indicative of extensive worker reproduction and is the hallmark of anarchy. Seventeen microsatellite loci were used to analyse these male pupae, allowing us to address whether all the males were indeed workers’ sons, and how many worker patrilines and individual workers produced them. In the sample, 95 of 96 of the males were definitely workers’ sons. Given that ≈ 1% of workers’ sons were genetically indistinguishable from queen’s sons, this suggests that workers do not move any queen-laid eggs between the part of the colony where the queen is present to the area above the queen excluder which the queen cannot enter. The colony had 16 patrilines, with an effective number of patrilines of 9.85. The 75 males that could be assigned with certainty to a patriline came from 7 patrilines, with an effective number of 4.21. They were the offspring of at least 19 workers. This is in contrast to the two previously studied Australian naturally occurring anarchist colonies, in which most of the workers’ sons were offspring of one patriline. The high number of patrilines producing males leads to a low mean relatedness between laying workers and males of the colony. We discuss the importance of studying such colonies in the understanding of worker policing and its evolution

Demography and disorders of German Shepherd Dogs under primary veterinarycare in the UK

The German Shepherd Dog (GSD) has been widely used for a variety of working roles. However, concerns for the health and welfare of the GSD have been widely aired and there is evidence that breed numbers are now in decline in the UK. Accurate demographic and disorder data could assist with breeding and clinical prioritisation. The VetCompassTM Programme collects clinical data on dogs under primary veterinary care in the UK. This study included all VetCompassTM dogs under veterinary care during 2013. Demographic, mortality and clinical diagnosis data on GSDs were extracted and reported

Entanglement generation outside a Schwarzschild black hole and the Hawking effect

We examine the Hawking effect by studying the asymptotic entanglement of two mutually independent two-level atoms placed at a fixed radial distance outside a Schwarzschild black hole in the framework of open quantum systems. We treat the two-atom system as an open quantum system in a bath of fluctuating quantized massless scalar fields in vacuum and calculate the concurrence, a measurement of entanglement, of the equilibrium state of the system at large times, for the Unruh, Hartle-Hawking and Boulware vacua respectively. We find, for all three vacuum cases, that the atoms turn out to be entangled even if they are initially in a separable state as long as the system is not placed right at the even horizon. Remarkably, only in the Unruh vacuum, will the asymptotic entanglement be affected by the backscattering of the thermal radiation off the space-time curvature. The effect of the back scatterings on the asymptotic entanglement cancels in the Hartle-Hawking vacuum case.Comment: 15 pages, no figures, Revte

Economic impact of hospitalisations among patients in the last year of life: An observational study

Background: Hospital admissions among patients at the end of life have a significant economic impact. Avoiding unnecessary hospitalisations has the potential for significant cost savings and is often in line with patient preference. Objective: To determine the extent of potentially avoidable hospital admissions among patients admitted to hospital in the last year of life and to cost these accordingly. Design: An observational retrospective case note review with economic impact assessment. Setting: Two large acute hospitals in the North of England, serving contrasting socio-demographic populations. Patients: A total of 483 patients who died within 1 year of admission to hospital. Measurements: Data were collected across a range of clinical, demographic, economic and service use variables and were collected from hospital case notes and routinely collected sources. Palliative medicine consultants identified admissions that were potentially avoidable. Results: Of 483 admissions, 35 were classified as potentially avoidable. Avoiding these admissions and caring for the patients in alternative locations would save the two hospitals £5.9 million per year. Reducing length of stay in all 483 patients by 14% has the potential to save the two hospitals £47.5 million per year; however, this cost would have to be offset against increased community care costs. Limitations: A lack of accurate cost data on alternative care provision in the community limits the accuracy of economic estimates. Conclusions: Reducing length of hospital stay in palliative care patients may offer the potential to achieve higher hospital cost savings than preventing avoidable admissions. Further research is required to determine both the feasibility of reducing length of hospital stay for patients with palliative care needs and the economic impact of doing so

Black Holes in Gravity with Conformal Anomaly and Logarithmic Term in Black Hole Entropy

We present a class of exact analytic and static, spherically symmetric black hole solutions in the semi-classical Einstein equations with Weyl anomaly. The solutions have two branches, one is asymptotically flat and the other asymptotically de Sitter. We study thermodynamic properties of the black hole solutions and find that there exists a logarithmic correction to the well-known Bekenstein-Hawking area entropy. The logarithmic term might come from non-local terms in the effective action of gravity theories. The appearance of the logarithmic term in the gravity side is quite important in the sense that with this term one is able to compare black hole entropy up to the subleading order, in the gravity side and in the microscopic statistical interpretation side.Comment: Revtex, 10 pages. v2: minor changes and to appear in JHE

Effect of treatment of gestational diabetes mellitus on pregnancy outcomes

Copyright © 2005 Massachusetts Medical Society.Background: We conducted a randomized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications. Methods: We randomly assigned women between 24 and 34 weeks’ gestation who had gestational diabetes to receive dietary advice, blood glucose monitoring, and insulin therapy as needed (the intervention group) or routine care. Primary outcomes included serious perinatal complications (defined as death, shoulder dystocia, bone fracture, and nerve palsy), admission to the neonatal nursery, jaundice requiring phototherapy, induction of labor, cesarean birth, and maternal anxiety, depression, and health status. Results: The rate of serious perinatal complications was significantly lower among the infants of the 490 women in the intervention group than among the infants of the 510 women in the routine-care group (1 percent vs. 4 percent; relative risk adjusted for maternal age, race or ethnic group, and parity, 0.33; 95 percent confidence interval, 0.14 to 0.75; P=0.01). However, more infants of women in the intervention group were admitted to the neonatal nursery (71 percent vs. 61 percent; adjusted relative risk, 1.13; 95 percent confidence interval, 1.03 to 1.23; P=0.01). Women in the intervention group had a higher rate of induction of labor than the women in the routine-care group (39 percent vs. 29 percent; adjusted relative risk, 1.36; 95 percent confidence interval, 1.15 to 1.62; P<0.001), although the rates of cesarean delivery were similar (31 percent and 32 percent, respectively; adjusted relative risk, 0.97; 95 percent confidence interval, 0.81 to 1.16; P=0.73). At three months post partum, data on the women’s mood and quality of life, available for 573 women, revealed lower rates of depression and higher scores, consistent with improved health status, in the intervention group. Conclusions: Treatment of gestational diabetes reduces serious perinatal morbidity and may also improve the woman’s health-related quality of life.Caroline A. Crowther, Janet E. Hiller, John R. Moss, Andrew J. McPhee, William S. Jeffries and Jeffrey S. Robinso

Modelling and simulating change in reforesting mountain landscapes using a social-ecological framework

Natural reforestation of European mountain landscapes raises major environmental and societal issues. With local stakeholders in the Pyrenees National Park area (France), we studied agricultural landscape colonisation by ash (Fraxinus excelsior) to enlighten its impacts on biodiversity and other landscape functions of importance for the valley socio-economics. The study comprised an integrated assessment of land-use and land-cover change (LUCC) since the 1950s, and a scenario analysis of alternative future policy. We combined knowledge and methods from landscape ecology, land change and agricultural sciences, and a set of coordinated field studies to capture interactions and feedback in the local landscape/land-use system. Our results elicited the hierarchically-nested relationships between social and ecological processes. Agricultural change played a preeminent role in the spatial and temporal patterns of LUCC. Landscape colonisation by ash at the parcel level of organisation was merely controlled by grassland management, and in fact depended on the farmer's land management at the whole-farm level. LUCC patterns at the landscape level depended to a great extent on interactions between farm household behaviours and the spatial arrangement of landholdings within the landscape mosaic. Our results stressed the need to represent the local SES function at a fine scale to adequately capture scenarios of change in landscape functions. These findings orientated our modelling choices in the building an agent-based model for LUCC simulation (SMASH - Spatialized Multi-Agent System of landscape colonization by ASH). We discuss our method and results with reference to topical issues in interdisciplinary research into the sustainability of multifunctional landscapes

Black Holes in Quasi-topological Gravity

We construct a new gravitational action which includes cubic curvature interactions and which provides a useful toy model for the holographic study of a three parameter family of four- and higher-dimensional CFT's. We also investigate the black hole solutions of this new gravity theory. Further we examine the equations of motion of quasi-topological gravity. While the full equations in a general background are fourth-order in derivatives, we show that the linearized equations describing gravitons propagating in the AdS vacua match precisely the second-order equations of Einstein gravity.Comment: 33 pages, 4 figures; two references adde