Computational protein design with backbone plasticity

The computational algorithms used in the design of artificial proteins have become increasingly sophisticated in recent years, producing a series of remarkable successes. The most dramatic of these is the de novo design of artificial enzymes. The majority of these designs have reused naturally occurring protein structures as “scaffolds” onto which novel functionality can be grafted without having to redesign the backbone structure. The incorporation of backbone flexibility into protein design is a much more computationally challenging problem due to the greatly increase search space but promises to remove the limitations of reusing natural protein scaffolds. In this review, we outline the principles of computational protein design methods and discuss recent efforts to consider backbone plasticity in the design process

Collective emotions online and their influence on community life

E-communities, social groups interacting online, have recently become an object of interdisciplinary research. As with face-to-face meetings, Internet exchanges may not only include factual information but also emotional information - how participants feel about the subject discussed or other group members. Emotions are known to be important in affecting interaction partners in offline communication in many ways. Could emotions in Internet exchanges affect others and systematically influence quantitative and qualitative aspects of the trajectory of e-communities? The development of automatic sentiment analysis has made large scale emotion detection and analysis possible using text messages collected from the web. It is not clear if emotions in e-communities primarily derive from individual group members' personalities or if they result from intra-group interactions, and whether they influence group activities. We show the collective character of affective phenomena on a large scale as observed in 4 million posts downloaded from Blogs, Digg and BBC forums. To test whether the emotions of a community member may influence the emotions of others, posts were grouped into clusters of messages with similar emotional valences. The frequency of long clusters was much higher than it would be if emotions occurred at random. Distributions for cluster lengths can be explained by preferential processes because conditional probabilities for consecutive messages grow as a power law with cluster length. For BBC forum threads, average discussion lengths were higher for larger values of absolute average emotional valence in the first ten comments and the average amount of emotion in messages fell during discussions. Our results prove that collective emotional states can be created and modulated via Internet communication and that emotional expressiveness is the fuel that sustains some e-communities.Comment: 23 pages including Supporting Information, accepted to PLoS ON

The donor heart and organ perfusion technology.

Recent advancement in organ perfusion technology has led to increase clinical transplantation of marginal donor organs and allow for distant procurement of cardiac allograft beyond the time limitation of cold static storage. Ex-situ heart perfusion also provides essential nutrients to maintain cell integrity, thereby reducing the risk of ischaemic injury for functional preservation and provides a platform to assess organ viability and feasibility, with the potential for pharmacotherapy to recover these hearts. Notably, the use of NMP has led to the first distant procurement cardiac transplantation from a donation after circulatory death (DCD) in 2014, which resulted in the adoption of DCD heart transplantation in 4 centres between the United Kingdom and Australia. To date, over 100 DCD heart transplants have been performed utilising cardiac perfusion system with an estimated 10-15% increase in transplant activity in the individual units. This review aims to provide an overview of current experience and outcomes using cardiac perfusion technology, including future technologies and recent advancement within the field

The role of frailty in advanced HF and cardiac transplantation.

Frailty is a complex, multi-system condition often associated with multimorbidity. It has become an important prognostic maker across a range of conditions and is particularly relevant in patients with cardiovascular disease. Frailty encompasses a range of domains including, physical, psychological, and social. There are currently a range of validated tools available to measure frailty. It is an especially important measurement in advanced HF, because frailty occurs in up to 50% of HF patients and is potentially reversible with therapies such as mechanical circulatory support and transplantation. Moreover, frailty is dynamic, and therefore serial measurements are important. This review delves into the measurement of frailty, mechanisms, and its role in different cardiovascular cohorts. Understanding frailty will help determine patients that will benefit from therapies, as well as prognosticate outcomes

Improved measurement of the K+->pi+nu(nu)over-bar branching ratio

An additional event near the upper kinematic limit for K+-->pi(+)nu(nu) over bar has been observed by experiment E949 at Brookhaven National Laboratory. Combining previously reported and new data, the branching ratio is B(K+-->pi(+)nu(nu) over bar)=(1.47(-0.89)(+1.30))x10(-10) based on three events observed in the pion momentum region 211<P<229 MeV/c. At the measured central value of the branching ratio, the additional event had a signal-to-background ratio of 0.9

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Measurements and computations of flow in an urban street system

We present results from laboratory and computational experiments on the turbulent flow over an array of rectangular blocks modelling a typical, asymmetric urban canopy at various orientations to the approach flow. The work forms part of a larger study on dispersion within such arrays (project DIPLOS) and concentrates on the nature of the mean flow and turbulence fields within the canopy region, recognising that unless the flow field is adequately represented in computationalmodels there is no reason to expect realistic simulations of the nature of the dispersion of pollutants emitted within the canopy. Comparisons between the experimental data and those obtained from both large-eddy simulation (LES) and direct numerical simulation (DNS) are shown and it is concluded that careful use of LES can produce generally excellent agreement with laboratory and DNS results, lending further confidence in the use of LES for such situations. Various crucial issues are discussed and advice offered to both experimentalists and those seeking to compute canopy flows with turbulence resolving models

Fish passage design for sustainable hydropower in the temperate Southern Hemisphere:An evidence review

The development of hydropower and other infrastructure that disrupts river connectivity poses a serious threat to highly endemic and genetically distinct freshwater fish species in temperate parts of the Southern Hemisphere. Such locations have been neglected in previous reviews on fish passage. Fishways have long been constructed to mitigate the impacts of riverine barriers on fish, yet they have often failed for all but the largest, strongest swimming taxa. This is a particular problem in the temperate south, where the majority of species arewhich is home to native species that are non-recreational and generally small-bodied with weak swimming abilities (e.g. Galaxiidae) relative to typical target species for fishway design (e.g. Salmonidae). Using the Eco Evidence method for rapid evidence synthesis, we undertook an assessment of evidence for effective fishway design focusing on species representative of the temperate south, including eel and lamprey. Systematic literature searches resulted in 630 publications. Through a rigorous screening process these were reduced to 46 publications containing 76 evidence items across 19 hypotheses relating to design criteria for upstream and downstream passage. We found an overwhelming lack of evidence for effective fishway design in the temperate south. Particular deficiencies were found with regard to the design of effective facilities for downstream passage. The attraction and entrance of upstream migrating fish into fishways is also relatively under-researched. Given the urgent need for effective fishways in the temperate south, these results justify an approach to fishway design based on a combination of empirical data and expert knowledge. In the meantime, significant resources should be assigned to improve the evidence base through high quality research. The particular deficiencies identified here could guide that research agenda

Relative influence of shredders and fungi on leaf litter decomposition along a river altitudinal gradient

We compared autumn decomposition rates of European alder leaves at four sites along the Lasset–Hers River system, southern France, to test whether changes in litter decomposition rates from upstream (1,300 m elevation) to downstream (690 m) could be attributed to temperature-driven differences in microbial growth, shredder activity, or composition of the shredder community. Alder leaves lost 75–87% of original mass in 57 days, of which 46–67% could be attributed to microbial metabolism and 8–29% to shredder activity, with no trend along the river. Mass loss rates in both fine-mesh (excluding shredders) and coarse-mesh (including shredders) bags were faster at warm, downstream sites (mean daily temperature 7–8°C) than upstream (mean 1–2°C), but the differ- ence disappeared when rates were expressed in heat units to remove the temperature effect. Mycelial biomass did not correlate with mass loss rates. Faster mass loss rates upstream, after temperature correction, evidently arise from more efficient shredding by Nemourid stoneflies than by the Leuctra-dominated assemblage downstream. The influence of water temperature on decomposition rate is therefore expressed both directly, through microbial metabolism, and indirectly, through the structure of shredder commu- nities. These influences are evident even in cold water where temperature variation is small