Benchmarking consensus model quality assessment for protein fold recognition

Background: Selecting the highest quality 3D model of a protein structure from a number of alternatives remains an important challenge in the field of structural bioinformatics. Many Model Quality Assessment Programs (MQAPs) have been developed which adopt various strategies in order to tackle this problem, ranging from the so called "true" MQAPs capable of producing a single energy score based on a single model, to methods which rely on structural comparisons of multiple models or additional information from meta-servers. However, it is clear that no current method can separate the highest accuracy models from the lowest consistently. In this paper, a number of the top performing MQAP methods are benchmarked in the context of the potential value that they add to protein fold recognition. Two novel methods are also described: ModSSEA, which based on the alignment of predicted secondary structure elements and ModFOLD which combines several true MQAP methods using an artificial neural network. Results: The ModSSEA method is found to be an effective model quality assessment program for ranking multiple models from many servers, however further accuracy can be gained by using the consensus approach of ModFOLD. The ModFOLD method is shown to significantly outperform the true MQAPs tested and is competitive with methods which make use of clustering or additional information from multiple servers. Several of the true MQAPs are also shown to add value to most individual fold recognition servers by improving model selection, when applied as a post filter in order to re-rank models. Conclusion: MQAPs should be benchmarked appropriately for the practical context in which they are intended to be used. Clustering based methods are the top performing MQAPs where many models are available from many servers; however, they often do not add value to individual fold recognition servers when limited models are available. Conversely, the true MQAP methods tested can often be used as effective post filters for re-ranking few models from individual fold recognition servers and further improvements can be achieved using a consensus of these methods.

A chimeric N-terminal Escherichia coli C-terminal Rhodobacter sphaeroides FliG rotor protein supports bidirectional E coli flagellar rotation and chemotaxis

Flagellate bacteria such as Escherichia coli and Salmonella enterica serovar Typhimurium typically express 5 to 12 flagellar filaments over their cell surface that rotate in clockwise (CW) and counterclockwise directions. These bacteria modulate their swimming direction towards favorable environments by biasing the direction of flagellar rotation in response to various stimuli. In contrast, Rhodobacter sphaeroides expresses a single subpolar flagellum that rotates only CW and responds tactically by a series of biased stops and starts. Rotor protein FliG transiently links the MotAB stators to the rotor, to power rotation and also has an essential function in flagellar export. In this study, we sought to determine whether the FliG protein confers directionality on flagellar motors by testing the functional properties of R. sphaeroides FliG and a chimeric FliG protein, EcRsFliG (N-terminal and central domains of E. coli FliG fused to an R. sphaeroides FliG C terminus), in an E. coli FliG null background. The EcRsFliG chimera supported flagellar synthesis and bidirectional rotation; bacteria swam and tumbled in a manner qualitatively similar to that of the wild type and showed chemotaxis to amino acids. Thus, the FliG C terminus alone does not confer the unidirectional stop-start character of the R. sphaeroides flagellar motor, and its conformation continues to support tactic, switch-protein interactions in a bidirectional motor, despite its evolutionary history in a bacterium with a unidirectional motor.

Mental rotation in Williams syndrome: an impaired ability

Typically developing young children and individuals with intellectual disabilities often perform poorly on mental rotation tasks when the stimulus they are rotating lacks a salient component. However. performance can he improved when salience is increased. The present study investigated the effect of salience oil mental rotation performance by individuals with Williams syndrome. Individuals with Williams syndrome and matched controls were presented with two versions of a mental rotation task: a no salient component condition and a salient component condition. The results showed that component salience did not benefit individuals with Williams syndrome in the same manner as it did controls.

Flexible rules cum constrained discretion: a new consensus in monetary policy

This paper demonstrates that recent influential contributions to monetary policy imply an emerging consensus whereby neither rigid rules nor complete discretion are found optimal. Instead, middle-ground monetary regimes based on rules (operative under 'normal' circumstances) to anchor inflation expectations over the long run, but designed with enough flexibility to mitigate the short-run effect of shocks (with communicated discretion in 'exceptional' circumstances temporarily overriding these rules), are gaining support in theoretical models and policy formulation and implementation. The opposition of 'rules versus discretion' has, thus, reappeared as the synthesis of 'rules cum discretion', in essence as inflation-forecast targeting. But such synthesis is not without major theoretical problems, as we argue in this contribution. Furthermore, the very recent real-world events have made it obvious that the inflation targeting strategy of monetary policy, which rests upon the new consensus paradigm in modern macroeconomics is at best a 'fair weather' model. In the turbulent economic climate of highly unstable inflation, deep financial crisis and world-wide, abrupt economic slowdown nowadays this approach needs serious rethinking to say the least, if not abandoning it altogether

Givens rotation based fast backward elimination algorithm for RBF neural network pruning

A fast backward elimination algorithm is introduced based on a QR decomposition and Givens transformations to prune radial-basis-function networks. Nodes are sequentially removed using an increment of error variance criterion. The procedure is terminated by using a prediction risk criterion so as to obtain a model structure with good generalisation properties. The algorithm can be used to postprocess radial basis centres selected using a k-means routine and, in this mode, it provides a hybrid supervised centre selection approach.

Centennial changes in the heliospheric magnetic field and open solar flux: the consensus view from geomagnetic data and cosmogenic isotopes and its implications

Svalgaard and Cliver (2010) recently reported a consensus between the various reconstructions of the heliospheric field over recent centuries. This is a significant development because, individually, each has uncertainties introduced by instrument calibration drifts, limited numbers of observatories, and the strength of the correlations employed. However, taken collectively, a consistent picture is emerging. We here show that this consensus extends to more data sets and methods than reported by Svalgaard and Cliver, including that used by Lockwood et al. (1999), when their algorithm is used to predict the heliospheric field rather than the open solar flux. One area where there is still some debate relates to the existence and meaning of a floor value to the heliospheric field. From cosmogenic isotope abundances, Steinhilber et al. (2010) have recently deduced that the near-Earth IMF at the end of the Maunder minimum was 1.80 ± 0.59 nT which is considerably lower than the revised floor of 4nT proposed by Svalgaard and Cliver. We here combine cosmogenic and geomagnetic reconstructions and modern observations (with allowance for the effect of solar wind speed and structure on the near-Earth data) to derive an estimate for the open solar flux of (0.48 ± 0.29) × 1014 Wb at the end of the Maunder minimum. By way of comparison, the largest and smallest annual means recorded by instruments in space between 1965 and 2010 are 5.75 × 1014 Wb and 1.37 × 1014 Wb, respectively, set in 1982 and 2009, and the maximum of the 11 year running means was 4.38 × 1014 Wb in 1986. Hence the average open solar flux during the Maunder minimum is found to have been 11% of its peak value during the recent grand solar maximum.

Current level of consensus on probiotic science: report of an expert meeting, London, 23 November 2009

The present paper summarizes  the consensus views of a group of 9 European clinicians and scientists on the current state of scientific knowledge on probiotics, covering those areas where there is substantial evidence for beneficial effects and those  where the evidence base is poor or inconsistent. There was general agreement that probiotic effects were species and often strain specific. The experts agreed  that some probiotics were effective in reducing the incidence and duration of rotavirus diarrhoea in infants, antibiotic-associated diarrhoea in adults and, for certain probiotics, Clostridium difficile infections. Some probiotics are associated with symptomatic improvements in irritable bowel syndrome and alleviation of digestive discomfort. Probiotics can reduce the frequency and severity of necrotizing enterocolitis in premature infants and have been shown to regulate intestinal immunity.  Several other clinical effects of probiotics, including their role in inflammatory bowel disease, atopic dermatitis, respiratory or genito-urinary infections or H.pylori adjuvant treatment were thought promising but inconsistent.

Elevated atmospheric CO2 changes phosphorus fractions in soils under a short rotation poplar plantation (EuroFACE)

Future high levels of atmospheric carbon dioxide (CO2) may increase biomass production of terrestrial plants and hence plant requirements for soil mineral nutrients to sustain a greater biomass production. Phosphorus (P), an element essential for plant growth, is found in soils both in inorganic and in organic forms. In this work, three genotypes of Populus were grown under ambient and elevated atmospheric CO2 concentrations (FACE) for 5 years. An N fertilisation treatment was added in years 4 and 5 after planting. Using a fractionation scheme, total P was sequentially extracted using H2O, NaOH, HCl and HNO3, and P determined as both molybdate (Mo) reactive and total P. Molybdate-reactive P is defined as mainly inorganic but also some labile organic P which is determined by Vanado-molybdophosphoric acid colorimetric methods. Organic P was also measured to assess all plant available and weatherable P pools. We tested the hypotheses that higher P demand due to increased growth is met by a depletion of easily weatherable soil P pools, and that increased biomass inputs increases the amount of organic P in the soil. The concentration of organic P increased under FACE, but was associated with a decrease in total soil organic matter. The greatest increase in the soil P due to elevated CO2 was found in the HCl-extractable P fraction in the non-fertilised treatment. In the NaOH-extractable fraction the Mo-reactive P increased under FACE, but total P did not differ between ambient and FACE. The increase in both the NaOH- and HCl-extractable fractions was smaller after N addition. The results showed that elevated atmospheric CO2 has a positive effect on soil P availability rather than leading to depletion.We suggest that the increase in the NaOH- and HCl-extractable fractions is biologically driven by organic matter mineralization, weathering and mycorrhizal hyphal turnover.

Social consensus, moral intensity and willingness to pay to address a farm animal welfare issue

An experimental contingent valuation (CV) survey of university students was undertaken to explore the impact of social consensus information on people's stated willingness to pay (wtp) to address a farm animal welfare issue. The survey found that additional information presented to respondents on social consensus concerning the moral dimensions of the issue led to a greater perception of social consensus by respondents. This greater perception of social consensus appeared to result in a higher level of moral intensity associated with the issue and a higher stated wtp by respondents for policy to address the issue. However, as for many CV studies of public goods, a question remains as to whether the estimated wtp is a true measure of people's preferences and relative values or merely a measure of attitudes on an arbitrary monetary scale.

Effect of patient age on management decisions in breast cancer: consensus from a national consultation

This qualitative study investigated the attitudes, perceptions, and practices of breast cancer specialists with reference to the effect of patient age on management decisions in breast cancer, and attempted to identify national consensus on this issue. One hundred thirty-three relevant specialists, including 75 surgeons and 43 oncologists, participated in a virtual consultation using e-mailed questionnaires and open-ended discussion documents, culminating in the development of proposed consensus statements sent to participants for validation. A strong consensus was seen in favor of incorporating minimum standards of diagnostic services, treatment, and care for older patients with breast cancer into relevant national guidance, endorsed by professional bodies. Similarly, an overwhelming majority of participants agreed that simple, evidence-based protocols or guidelines on standardizing assessment of biological and chronological age should be produced by the National Institute for Health and Clinical Excellence and the Scottish Medicines Consortium, developed in collaboration with specialist oncogeriatricians, and endorsed by professional bodies. A further recommendation that all breast cancer patient treatment and diagnostic procedures be undertaken in light of up-to-date, relevant scientific data met with majority support. This study was successful in gauging national specialist opinion regarding the effect of patient age on management decisions in breast cancer in the U.K.

Shot by both sides: Punk, politics and the end of “Consensus”

This article examines the ways in which political organisations of the far left and far right responded to punk-informed youth culture in Britain during the late 1970s. It examines how both tried to understand punk within their own ideological framework, particularly in relation to the perceived socio-economic and political crises of the late 1970s, before then endeavouring to appropriate—or use—punk for their own ends. Ultimately, however, the article suggests that while punk may indeed be seen as a cultural response to the breakdown of what some have described as the post-war ‘consensus’ in the 1970s, the far left and far right's focus on cultural expression cut across the basic foundations on which they had been built. Consequently, neither left nor right proved able to provide an effective political conduit through which the disaffections expressed by punk could be channelled.