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/

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

J Willison, CP Kempste

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

A Kinematic Study of Progressive Micrographia in Parkinson's Disease

Progressive micrographia is decrement in character size during writing and is commonly associated with Parkinson's disease (PD). This study has investigated the kinematic features of progressive micrographia during a repetitive writing task. Twenty-four PD patients with duration since diagnosis of <10 years and 24 age-matched controls wrote the letter “e” repeatedly. PD patients were studied in defined off states, with scoring of motor function on the Unified Parkinson's Disease Rating Scale Part III. A digital tablet captured x-y coordinates and ink-pen pressure. Customized software recorded the data and offline analysis derived the kinematic features of pen-tip movement. The average size of the first and the last five letters were compared, with progressive micrographia defined as >10% decrement in letter stroke length. The relationships between dimensional and kinematic features for the control subjects and for PD patients with and without progressive micrographia were studied. Differences between the initial and last letter repetitions within each group were assessed by Wilcoxon signed-rank test, and the Kruskal-Wallis test was applied to compare the three groups. There are five main conclusions from our findings: (i) 66% of PD patients who participated in this study exhibited progressive micrographia; (ii) handwriting kinematic features for all PD patients was significantly lower than controls (p < 0.05); (iii) patients with progressive micrographia lose the normal augmentation of writing speed and acceleration in the x axis with left-to-right writing and show decrement of pen-tip pressure (p = 0.034); (iv) kinematic and pen-tip pressure profiles suggest that progressive micrographia in PD reflects poorly sustained net force; and (v) although progressive micrographia resembles the sequence effect of general bradykinesia, we did not find a significant correlation with overall motor disability, nor with the aggregate UPDRS-III bradykinesia scores for the dominant arm

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

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

Innovation and access to technologies for sustainable development: diagnosing weaknesses and identifying interventions in the Transnational Arena

Sustainable development – improving human well-being across present generations without compromising the ability of future generations to meet their own needs – is a central challenge for the 21st century. Technological innovation can play an important role in moving society toward sustainable development. However, poor, marginalized, and future populations often do not fully benefit from innovation due to their lack of market or political power to influence innovation processes. As a result, current innovation systems fail to contribute as much as they might to meeting sustainable development goals. This paper focuses on how actors and institutions operating in the transnational arena can mitigate such shortfalls. To identify the most important transnational functions required to meet sustainable development needs our analysis undertook three main steps. First, we developed a framework to diagnose blockages in the global innovation system for particular technologies. This framework was built on existing theory and new empirical analysis. On the theory side, we drew from the literatures of systems dynamics; technology and sectoral innovation systems, science and technology studies, the economics of innovation, and global governance. On the empirical front, we conducted eighteen detailed case studies of technology innovation in multiple sectors relevant to sustainable development: water, energy, health, food, and manufactured goods. We use the framework to analyze our case studies in the common language of (1) technology stocks, (2) non-linear flows between stocks substantiated by specific mechanisms, and (3) characteristics of actors and socio-technical conditions (STCs) which mediate the flows between stocks . We identify blockages in the innovation system for each of the cases, diagnosing where in the innovation system flows were hindered and which specific sets of STCs and actor characteristics were associated with these blockages. Figure E.1 displays the components of our framework and how they relate