ReFOLD: a server for the refinement of 3D protein models guided by accurate quality estimates

ReFOLD is a novel hybrid refinement server with integrated high performance global and local Accuracy Self Estimates (ASEs). The server attempts to identify and to fix likely errors in user supplied 3D models of proteins via successive rounds of refinement. The server is unique in providing output for multiple alternative refined models in a way that allows users to quickly visualize the key residue locations, which are likely to have been improved. This is important, as global refinement of a full chain model may not always be possible, whereas local regions, or individual domains, can often be much improved. Thus, users may easily compare the specific regions of the alternative refined models in which they are most interested e.g. key interaction sites or domains. ReFOLD was used to generate hundreds of alternative refined models for the CASP12 experiment, boosting our group's performance in the main tertiary structure prediction category. Our successful refinement of initial server models combined with our built-in ASEs were instrumental to our second place ranking on Template Based Modeling (TBM) and Free Modeling (FM)/TBM targets. The ReFOLD server is freely available at: http://www.reading.ac.uk/bioinf/ReFOLD/

James Parkinson’s chimera:syndrome or disease?

It is two hundred years since James Parkinson published An Essay on the Shaking Palsy. While his monograph continues to be acclaimed for its precedence and clarity of description, what is often overlooked is the originality of Parkinson’s ideas. We show that he appreciated the weakness of the systematic eighteenth century nosologies, which presupposed that medical species, the building blocks of these Linnaean taxonomic schemes, were as distinct as plant and animal species; and that Parkinson made a conceptual leap about combinations of clinical phenomena in recurring patterns, now recognized to be one of the germs of neurological thinking about syndromes. The Essay’s written style underpins another aspect of significance to contemporary neurological practice—an inherent intellectual humility. In this commemorative year we locate the continuing importance of the related notions of syndrome and disease in successive frameworks of knowledge about the Shaking Palsy. Syndrome and disease are interpreted as dual character concepts, one clinically-based and the other restricted to pathophysiological causation. They both remain fundamental to understanding Parkinson’s syndrome-disease toda

The health and education gap 1861: when Europeans died and Aboriginal people thrived

J Willison, CP Kempste

Managerial Work in a Practice-Embodying Institution - The role of calling, the virtue of constancy

What can be learned from a small scale study of managerial work in a highly marginal and under-researched working community? This paper uses the ‘goods-virtues-practices-institutions’ framework to examine the managerial work of owner-directors of traditional circuses. Inspired by MacIntyre’s arguments for the necessity of a narrative understanding of the virtues, interviews explored how British and Irish circus directors accounted for their working lives. A purposive sample was used to select subjects who had owned and managed traditional touring circuses for at least 15 years, a period in which the economic and reputational fortunes of traditional circuses have suffered badly. This sample enabled the research to examine the self-understanding of people who had, at least on the face of it, exhibited the virtue of constancy. The research contributes to our understanding of the role of the virtues in organizations by presenting evidence of an intimate relationship between the virtue of constancy and a ‘calling’ work orientation. This enhances our understanding of the virtues that are required if management is exercised as a domain-related practice

How Close is too Close? The Effect of a Non-Lethal Electric Shark Deterrent on White Shark Behaviour

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Sharks play a vital role in the health of marine ecosystems, but the potential threat that sharks pose to humans is a reminder of our vulnerability when entering the ocean. Personal shark deterrents are being marketed as the solution to mitigate the threat that sharks pose. However, the effectiveness claims of many personal deterrents are based on our knowledge of shark sensory biology rather than robust testing of the devices themselves, as most have not been subjected to independent scientific studies. Therefore, there is a clear need for thorough testing of commercially available shark deterrents to provide the public with recommendations of their effectiveness. Using a modified stereo-camera system, we quantified behavioural interactions between white sharks (Carcharodon carcharias) and a baited target in the presence of a commercially available, personal electric shark deterrent (Shark Shield Freedom7™). The stereo-camera system enabled an accurate assessment of the behavioural responses of C. carcharias when encountering a non-lethal electric field many times stronger than what they would naturally experience. Upon their first observed encounter, all C. carcharias were repelled at a mean (± std. error) proximity of 131 (± 10.3) cm, which corresponded to a mean voltage gradient of 9.7 (± 0.9) V/m. With each subsequent encounter, their proximity decreased by an average of 11.6 cm, which corresponded to an increase in tolerance to the electric field by an average of 2.6 (± 0.5) V/m per encounter. Despite the increase in tolerance, sharks continued to be deterred from interacting for the duration of each trial when in the presence of an active Shark Shield™. Furthermore, the findings provide no support to the theory that electric deterrents attract sharks. The results of this study provide quantitative evidence of the effectiveness of a non-lethal electric shark deterrent, its influence on the behaviour of C. carcharias, and an accurate method for testing other shark deterrent technologies

Developmental Expression and Glucocorticoid Control of the Leptin Receptor in Fetal Ovine Lung.

The effects of endogenous and synthetic glucocorticoids on fetal lung maturation are well-established, although the role of leptin in lung development before birth is unclear. This study examined mRNA and protein levels of the signalling long-form leptin receptor (Ob-Rb) in fetal ovine lungs towards term, and after experimental manipulation of glucocorticoid levels in utero by fetal cortisol infusion or maternal dexamethasone treatment. In fetal ovine lungs, Ob-Rb protein was localised to bronchiolar epithelium, bronchial cartilage, vascular endothelium, alveolar macrophages and type II pneumocytes. Pulmonary Ob-Rb mRNA abundance increased between 100 (0.69 fractional gestational age) and 144 days (0.99) of gestation, and by 2-4-fold in response to fetal cortisol infusion and maternal dexamethasone treatment. In contrast, pulmonary Ob-Rb protein levels decreased near term and were halved by glucocorticoid treatment, without any significant change in phosphorylated signal transducer and activator of transcription-3 (pSTAT3) at Ser727, total STAT3 or the pulmonary pSTAT3:STAT3 ratio. Leptin mRNA was undetectable in fetal ovine lungs at the gestational ages studied. These findings demonstrate differential control of pulmonary Ob-Rb transcript abundance and protein translation, and/or post-translational processing, by glucocorticoids in utero. Localisation of Ob-Rb in the fetal ovine lungs, including alveolar type II pneumocytes, suggests a role for leptin signalling in the control of lung growth and maturation before birth.This work was supported by the Biotechnology and Biological Sciences Research Council (grant numbers S18103 and BB/H01697X/1).This is the final version of the article. It first appeared from PLoS via http://dx.doi.org/10.1371/journal.pone.013611

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using √s=8 TeV proton-proton collision data

A search for squarks and gluinos in final states containing high-p T jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in s√=8 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb−1. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A 0 = −2m 0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector

Measurement of the top pair production cross section in 8 TeV proton-proton collisions using kinematic information in the lepton plus jets final state with ATLAS

A measurement is presented of the $t\bar{t}$ inclusive production cross-section in $pp$ collisions at a center-of-mass energy of $\sqrt{s}=8$ TeV using data collected by the ATLAS detector at the CERN Large Hadron Collider. The measurement was performed in the lepton+jets final state using a data set corresponding to an integrated luminosity of 20.3 fb$^{-1}$. The cross-section was obtained using a likelihood discriminant fit and $b$-jet identification was used to improve the signal-to-background ratio. The inclusive $t\bar{t}$ production cross-section was measured to be $260\pm 1{\textrm{(stat.)}} ^{+22}_{-23} {\textrm{(syst.)}}\pm 8{\textrm{(lumi.)}}\pm 4{\mathrm{(beam)}}$ pb assuming a top-quark mass of 172.5 GeV, in good agreement with the theoretical prediction of $253^{+13}_{-15}$ pb. The $t\bar{t}\to (e,\mu)+{\mathrm{jets}}$ production cross-section in the fiducial region determined by the detector acceptance is also reported.Comment: Published version, 19 pages plus author list (35 pages total), 3 figures, 2 tables, all figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/TOPQ-2013-06