D-brane anomaly inflow revisited

Axial and gravitational anomaly of field theories, when embedded in string theory, must be accompanied by canceling inflow. We give a self-contained overview for various world-volume theories, and clarify the role of smeared magnetic sources in I-brane/D-brane cases. The proper anomaly descent of the source, as demanded by regularity of RR field strengths H's, turns out to be an essential ingredient. We show how this allows correct inflow to be generated for all such theories, including self-dual cases, and also that the mechanism is now insensitive to the choice between the two related but inequivalent forms of D-brane Chern-Simons couplings. In particular, SO(6)_R axial anomaly of d=4 maximal SYM is canceled by the inflow onto D3-branes via the standard minimal coupling to C_4. We also propose how, for the anomaly cancelation, the four types of Orientifold planes should be coupled to the spacetime curvatures, of which conflicting claims existed previously.Comment: 41 pages, references updated; version to appear in JHE

An optimized TOPS+ comparison method for enhanced TOPS models

This article has been made available through the Brunel Open Access Publishing Fund.Background Although methods based on highly abstract descriptions of protein structures, such as VAST and TOPS, can perform very fast protein structure comparison, the results can lack a high degree of biological significance. Previously we have discussed the basic mechanisms of our novel method for structure comparison based on our TOPS+ model (Topological descriptions of Protein Structures Enhanced with Ligand Information). In this paper we show how these results can be significantly improved using parameter optimization, and we call the resulting optimised TOPS+ method as advanced TOPS+ comparison method i.e. advTOPS+. Results We have developed a TOPS+ string model as an improvement to the TOPS [1-3] graph model by considering loops as secondary structure elements (SSEs) in addition to helices and strands, representing ligands as first class objects, and describing interactions between SSEs, and SSEs and ligands, by incoming and outgoing arcs, annotating SSEs with the interaction direction and type. Benchmarking results of an all-against-all pairwise comparison using a large dataset of 2,620 non-redundant structures from the PDB40 dataset [4] demonstrate the biological significance, in terms of SCOP classification at the superfamily level, of our TOPS+ comparison method. Conclusions Our advanced TOPS+ comparison shows better performance on the PDB40 dataset [4] compared to our basic TOPS+ method, giving 90 percent accuracy for SCOP alpha+beta; a 6 percent increase in accuracy compared to the TOPS and basic TOPS+ methods. It also outperforms the TOPS, basic TOPS+ and SSAP comparison methods on the Chew-Kedem dataset [5], achieving 98 percent accuracy. Software Availability: The TOPS+ comparison server is available at http://balabio.dcs.gla.ac.uk/mallika/WebTOPS/.This article is available through the Brunel Open Access Publishing Fun

Exceptional Flux Compactifications

We consider type II (non-)geometric flux backgrounds in the absence of brane sources, and construct their explicit embedding into maximal gauged D=4 supergravity. This enables one to investigate the critical points, mass spectra and gauge groups of such backgrounds. We focus on a class of type IIA geometric vacua and find a novel, non-supersymmetric and stable AdS vacuum in maximal supergravity with a non-semisimple gauge group. Our construction relies on a non-trivial mapping between SL(2) x SO(6,6) fluxes, SU(8) mass spectra and gaugings of E7(7) subgroups.Comment: 51 pages, 2 figures and 4 tables. v3: change of SO(6,6) spinorial conventions, published versio

Persistent problems of access to appropriate, affordable TB services in rural China: experiences of different socio-economic groups

BACKGROUND: Large-scale Tuberculosis (TB) control programmes in China have been hailed a success. Concerns remain, however, about whether the programme is reaching all sections of the population, particularly poorer groups within rural communities, and whether there are hidden costs. This study takes a household perspective to investigate receipt of appropriate care and affordability of services for different socio-economic groups with TB symptoms in rural China. METHODS: Secondary analysis of Chinese National Household Health Survey for 2003: 40,000 rural households containing 143,991 individuals, 2,308 identified as TB suspects. Outcomes: use of services and expenditure of TB suspects, by gender and socio-economic position, indicated by household income, education, material assets, and insurance status. RESULTS: 37% of TB suspects did not seek any professional care, with low-income groups less likely to seek care than more affluent counterparts. Of those seeking care, only 35% received any of the recommended diagnostic tests. Of the 182 patients with a confirmed TB diagnosis, 104 (57%) received treatment at the recommended level, less likely if lacking health insurance or material assets. The burden of payment for services amounted to 45% of annual household income for the low-income group, 16% for the high-income group. CONCLUSION: Access to appropriate, affordable TB services is still problematic in some rural areas of China, and receipt of care and affordability declines with declining socio-economic position. These findings highlight the current shortcomings of the national TB control programme in China and the formidable challenge it faces if it is to reach all sections of the population, including the poor with the highest burden of disease

Adaptive memory: Stereotype activation is not enough

Studies have shown that survival processing leads to superior memorability. The aim of the present study was to examine whether this survival recall advantage might result from stereotype activation. To test this hypothesis, we conducted a pilot study and two experiments in which participants were primed with stereotypes (Experiment 1, professor and elderly person; Experiment 2, survival-stereotype). In Experiment 1, 120 undergraduates were randomly assigned to a survival, professor stereotype, elderly person stereotype, or moving scenario and rated words for their relevance to the imagined scenario. In Experiment 2, 75 undergraduates were given a survival, survival-stereotype (based on our pilot study), or moving scenario. Both experiments showed that survival processing leads to a greater recall advantage over the stereotype groups and control group. These data indicate that the mere activation of stereotypes cannot explain the survival recall advantage

I-TASSER server for protein 3D structure prediction

<p>Abstract</p> <p>Background</p> <p>Prediction of 3-dimensional protein structures from amino acid sequences represents one of the most important problems in computational structural biology. The community-wide Critical Assessment of Structure Prediction (CASP) experiments have been designed to obtain an objective assessment of the state-of-the-art of the field, where I-TASSER was ranked as the best method in the server section of the recent 7th CASP experiment. Our laboratory has since then received numerous requests about the public availability of the I-TASSER algorithm and the usage of the I-TASSER predictions.</p> <p>Results</p> <p>An on-line version of I-TASSER is developed at the KU Center for Bioinformatics which has generated protein structure predictions for thousands of modeling requests from more than 35 countries. A scoring function (C-score) based on the relative clustering structural density and the consensus significance score of multiple threading templates is introduced to estimate the accuracy of the I-TASSER predictions. A large-scale benchmark test demonstrates a strong correlation between the C-score and the TM-score (a structural similarity measurement with values in [0, 1]) of the first models with a correlation coefficient of 0.91. Using a C-score cutoff > -1.5 for the models of correct topology, both false positive and false negative rates are below 0.1. Combining C-score and protein length, the accuracy of the I-TASSER models can be predicted with an average error of 0.08 for TM-score and 2 Å for RMSD.</p> <p>Conclusion</p> <p>The I-TASSER server has been developed to generate automated full-length 3D protein structural predictions where the benchmarked scoring system helps users to obtain quantitative assessments of the I-TASSER models. The output of the I-TASSER server for each query includes up to five full-length models, the confidence score, the estimated TM-score and RMSD, and the standard deviation of the estimations. The I-TASSER server is freely available to the academic community at <url>http://zhang.bioinformatics.ku.edu/I-TASSER</url>.</p

Challenges in Whole Exome Sequencing: An Example from Hereditary Deafness

Whole exome sequencing provides unprecedented opportunities to identify causative DNA variants in rare Mendelian disorders. Finding the responsible mutation via traditional methods in families with hearing loss is difficult due to a high degree of genetic heterogeneity. In this study we combined autozygosity mapping and whole exome sequencing in a family with 3 affected children having nonsyndromic hearing loss born to consanguineous parents. Two novel missense homozygous variants, c.508C>A (p.H170N) in GIPC3 and c.1328C>T (p.T443M) in ZNF57, were identified in the same ∼6 Mb autozygous region on chromosome 19 in affected members of the family. Both variants co-segregated with the phenotype and were absent in 335 ethnicity-matched controls. Biallelic GIPC3 mutations have recently been reported to cause autosomal recessive nonsyndromic sensorineural hearing loss. Thus we conclude that the hearing loss in the family described in this report is caused by a novel missense mutation in GIPC3. Identified variant in GIPC3 had a low read depth, which was initially filtered out during the analysis leaving ZNF57 as the only potential causative gene. This study highlights some of the challenges in the analyses of whole exome data in the bid to establish the true causative variant in Mendelian disease

Different rates of cognitive decline in autosomal dominant and late-onset Alzheimer disease

As prevention trials advance with autosomal dominant Alzheimer disease (ADAD) participants, understanding the similarities and differences between ADAD and "sporadic" late-onset AD (LOAD) is critical to determine generalizability of findings between these cohorts. Cognitive trajectories of ADAD mutation carriers (MCs) and autopsy-confirmed LOAD individuals were compared to address this question. Longitudinal rates of change on cognitive measures were compared in ADAD MCs (n = 310) and autopsy-confirmed LOAD participants (n = 163) before and after symptom onset (estimated/observed). LOAD participants declined more rapidly in the presymptomatic (preclinical) period and performed more poorly at symptom onset than ADAD participants on a cognitive composite. After symptom onset, however, the younger ADAD MCs declined more rapidly. The similar but not identical cognitive trajectories (declining but at different rates) for ADAD and LOAD suggest common AD pathologies but with some differences

Random Amino Acid Mutations and Protein Misfolding Lead to Shannon Limit in Sequence-Structure Communication

The transmission of genomic information from coding sequence to protein structure during protein synthesis is subject to stochastic errors. To analyze transmission limits in the presence of spurious errors, Shannon's noisy channel theorem is applied to a communication channel between amino acid sequences and their structures established from a large-scale statistical analysis of protein atomic coordinates. While Shannon's theorem confirms that in close to native conformations information is transmitted with limited error probability, additional random errors in sequence (amino acid substitutions) and in structure (structural defects) trigger a decrease in communication capacity toward a Shannon limit at 0.010 bits per amino acid symbol at which communication breaks down. In several controls, simulated error rates above a critical threshold and models of unfolded structures always produce capacities below this limiting value. Thus an essential biological system can be realistically modeled as a digital communication channel that is (a) sensitive to random errors and (b) restricted by a Shannon error limit. This forms a novel basis for predictions consistent with observed rates of defective ribosomal products during protein synthesis, and with the estimated excess of mutual information in protein contact potentials