Multi-Photon Signals from Composite Models at LHC

We analyze the collider signals of composite scalars that emerge in certain little Higgs models and models of vectorlike confinement. Similar to the decay of the pion into photon pairs, these scalars mainly decay through anomaly-induced interactions into electroweak gauge bosons, leading to a distinct signal with three or more photons in the final state. We study the standard model backgrounds for these signals, and find that the LHC can discover these models over a large range of parameter space with 30 fb$^{-1}$ at 14 TeV. An early discovery at the current 7 TeV run is possible in some regions of parameter space. We also discuss possibilities to measure the spin of the particles in the $\gamma \gamma$ and $Z\gamma$ decay channels.Comment: 18 pages, LaTe

Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

A multi-disciplinary perspective on emergent and future innovations in peer review [version 1; peer review: 2 approved with reservations]

Peer review of research articles is a core part of our scholarly communication system. In spite of its importance, the status and purpose of peer review is often contested. What is its role in our modern digital research and communications infrastructure? Does it perform to the high standards with which it is generally regarded? Studies of peer review have shown that it is prone to bias and abuse in numerous dimensions, frequently unreliable, and can fail to detect even fraudulent research. With the advent of Web technologies, we are now witnessing a phase of innovation and experimentation in our approaches to peer review. These developments prompted us to examine emerging models of peer review from a range of disciplines and venues, and to ask how they might address some of the issues with our current systems of peer review. We examine the functionality of a range of social Web platforms, and compare these with the traits underlying a viable peer review system: quality control, quantified performance metrics as engagement incentives, and certification and reputation. Ideally, any new systems will demonstrate that they out-perform current models while avoiding as many of the biases of existing systems as possible. We conclude that there is considerable scope for new peer review initiatives to be developed, each with their own potential issues and advantages. We also propose a novel hybrid platform model that, at least partially, resolves many of the technical and social issues associated with peer review, and can potentially disrupt the entire scholarly communication system. Success for any such development relies on reaching a critical threshold of research community engagement with both the process and the platform, and therefore cannot be achieved without a significant change of incentives in research environments

Nucleotide and phylogenetic analyses of the Chlamydia trachomatis ompA gene indicates it is a hotspot for mutation

<p>Abstract</p> <p>Background</p> <p>Serovars of the human pathogen <it>Chlamydia trachomatis </it>occupy one of three specific tissue niches. Genomic analyses indicate that the serovars have a phylogeny congruent with their pathobiology and have an average substitution rate of less than one nucleotide per kilobase. In contrast, the gene that determines serovar specificity, <it>ompA</it>, has a phylogenetic association that is not congruent with tissue tropism and has a degree of nucleotide variability much higher than other genomic loci. The <it>ompA </it>gene encodes the major surface-exposed antigenic determinant, and the observed nucleotide diversity at the <it>ompA </it>locus is thought to be due to recombination and host immune selection pressure. The possible contribution of a localized increase in mutation rate, however, has not been investigated.</p> <p>Results</p> <p>Nucleotide diversity and phylogenetic relationships of the five constant and four variable domains of the <it>ompA </it>gene, as well as several loci surrounding <it>ompA</it>, were examined for each serovar. The loci flanking the <it>ompA </it>gene demonstrated that nucleotide diversity increased monotonically as <it>ompA </it>is approached and that their gene trees are not congruent with either <it>ompA </it>or tissue tropism. The variable domains of the <it>ompA </it>gene had a very high level of non-synonymous change, which is expected as these regions encode the surface-exposed epitopes and are under positive selection. However, the synonymous changes are clustered in the variable regions compared to the constant domains; if hitchhiking were to account for the increase in synonymous changes, these substitutions should be more evenly distributed across the gene. Recombination also cannot entirely account for this increase as the phylogenetic relationships of the constant and variable domains are congruent with each other.</p> <p>Conclusions</p> <p>The high number of synonymous substitutions observed within the variable domains of <it>ompA </it>appears to be due to an increased mutation rate within this region of the genome, whereas the increase in nucleotide substitution rate and the lack of phylogenetic congruence in the regions flanking <it>ompA </it>are characteristic motifs of gene conversion. Together, the increased mutation rate in the <it>ompA </it>gene, in conjunction with gene conversion and positive selection, results in a high degree of variability that promotes host immune evasion.</p

An Agent-Based Model to study the epidemiological and evolutionary dynamics of Influenza viruses

<p>Abstract</p> <p>Background</p> <p>Influenza A viruses exhibit complex epidemiological patterns in a number of mammalian and avian hosts. Understanding transmission of these viruses necessitates taking into account their evolution, which represents a challenge for developing mathematical models. This is because the phrasing of multi-strain systems in terms of traditional compartmental ODE models either requires simplifying assumptions to be made that overlook important evolutionary processes, or leads to complex dynamical systems that are too cumbersome to analyse.</p> <p>Results</p> <p>Here, we develop an Individual-Based Model (IBM) in order to address simultaneously the ecology, epidemiology and evolution of strain-polymorphic pathogens, using Influenza A viruses as an illustrative example.</p> <p>Conclusions</p> <p>We carry out careful validation of our IBM against comparable mathematical models to demonstrate the robustness of our algorithm and the sound basis for this novel framework. We discuss how this new approach can give critical insights in the study of influenza evolution.</p

Healthcare Staff Wellbeing, Burnout, and Patient Safety: A Systematic Review

Objective To determine whether there is an association between healthcare professionals’ wellbeing and burnout, with patient safety. Design Systematic research review. Data Sources PsychInfo (1806 to July 2015), Medline (1946 to July 2015), Embase (1947 to July 2015) and Scopus (1823 to July 2015) were searched, along with reference lists of eligible articles. Eligibility Criteria for Selecting Studies Quantitative, empirical studies that included i) either a measure of wellbeing or burnout, and ii) patient safety, in healthcare staff populations. Results Forty-six studies were identified. Sixteen out of the 27 studies that measured wellbeing found a significant correlation between poor wellbeing and worse patient safety, with six additional studies finding an association with some but not all scales used, and one study finding a significant association but in the opposite direction to the majority of studies. Twenty-one out of the 30 studies that measured burnout found a significant association between burnout and patient safety, whilst a further four studies found an association between one or more (but not all) subscales of the burnout measures employed, and patient safety. Conclusions Poor wellbeing and moderate to high levels of burnout are associated, in the majority of studies reviewed, with poor patient safety outcomes such as medical errors, however the lack of prospective studies reduces the ability to determine causality. Further prospective studies, research in primary care, conducted within the UK, and a clearer definition of healthcare staff wellbeing are needed. Implications This review illustrates the need for healthcare organisations to consider improving employees’ mental health as well as creating safer work environments when planning interventions to improve patient safety

Complete Genome Sequence of Treponema paraluiscuniculi, Strain Cuniculi A: The Loss of Infectivity to Humans Is Associated with Genome Decay

Treponema paraluiscuniculi is the causative agent of rabbit venereal spirochetosis. It is not infectious to humans, although its genome structure is very closely related to other pathogenic Treponema species including Treponema pallidum subspecies pallidum, the etiological agent of syphilis. In this study, the genome sequence of Treponema paraluiscuniculi, strain Cuniculi A, was determined by a combination of several high-throughput sequencing strategies. Whereas the overall size (1,133,390 bp), arrangement, and gene content of the Cuniculi A genome closely resembled those of the T. pallidum genome, the T. paraluiscuniculi genome contained a markedly higher number of pseudogenes and gene fragments (51). In addition to pseudogenes, 33 divergent genes were also found in the T. paraluiscuniculi genome. A set of 32 (out of 84) affected genes encoded proteins of known or predicted function in the Nichols genome. These proteins included virulence factors, gene regulators and components of DNA repair and recombination. The majority (52 or 61.9%) of the Cuniculi A pseudogenes and divergent genes were of unknown function. Our results indicate that T. paraluiscuniculi has evolved from a T. pallidum-like ancestor and adapted to a specialized host-associated niche (rabbits) during loss of infectivity to humans. The genes that are inactivated or altered in T. paraluiscuniculi are candidates for virulence factors important in the infectivity and pathogenesis of T. pallidum subspecies

Neutralization Serotyping of BK Polyomavirus Infection in Kidney Transplant Recipients

BK polyomavirus (BKV or BKPyV) associated nephropathy affects up to 10% of kidney transplant recipients (KTRs). BKV isolates are categorized into four genotypes. It is currently unclear whether the four genotypes are also serotypes. To address this issue, we developed high-throughput serological assays based on antibody-mediated neutralization of BKV genotype I and IV reporter vectors (pseudoviruses). Neutralization-based testing of sera from mice immunized with BKV-I or BKV-IV virus-like particles (VLPs) or sera from naturally infected human subjects revealed that BKV-I specific serum antibodies are poorly neutralizing against BKV-IV and vice versa. The fact that BKV-I and BKV-IV are distinct serotypes was less evident in traditional VLP-based ELISAs. BKV-I and BKV-IV neutralization assays were used to examine BKV type-specific neutralizing antibody responses in KTRs at various time points after transplantation. At study entry, sera from 5% and 49% of KTRs showed no detectable neutralizing activity for BKV-I or BKV-IV neutralization, respectively. By one year after transplantation, all KTRs were neutralization seropositive for BKV-I, and 43% of the initially BKV-IV seronegative subjects showed evidence of acute seroconversion for BKV-IV neutralization. The results suggest a model in which BKV-IV-specific seroconversion reflects a de novo BKV-IV infection in KTRs who initially lack protective antibody responses capable of neutralizing genotype IV BKVs. If this model is correct, it suggests that pre-vaccinating prospective KTRs with a multivalent VLP-based vaccine against all BKV serotypes, or administration of BKV-neutralizing antibodies, might offer protection against graft loss or dysfunction due to BKV associated nephropathy

Comparative Genomics of Gardnerella vaginalis Strains Reveals Substantial Differences in Metabolic and Virulence Potential

Gardnerella vaginalis is described as a common vaginal bacterial species whose presence correlates strongly with bacterial vaginosis (BV). Here we report the genome sequencing and comparative analyses of three strains of G. vaginalis. Strains 317 (ATCC 14019) and 594 (ATCC 14018) were isolated from the vaginal tracts of women with symptomatic BV, while Strain 409-05 was isolated from a healthy, asymptomatic individual with a Nugent score of 9.Substantial genomic rearrangement and heterogeneity were observed that appeared to have resulted from both mobile elements and substantial lateral gene transfer. These genomic differences translated to differences in metabolic potential. All strains are equipped with significant virulence potential, including genes encoding the previously described vaginolysin, pili for cytoadhesion, EPS biosynthetic genes for biofilm formation, and antimicrobial resistance systems, We also observed systems promoting multi-drug and lantibiotic extrusion. All G. vaginalis strains possess a large number of genes that may enhance their ability to compete with and exclude other vaginal colonists. These include up to six toxin-antitoxin systems and up to nine additional antitoxins lacking cognate toxins, several of which are clustered within each genome. All strains encode bacteriocidal toxins, including two lysozyme-like toxins produced uniquely by strain 409-05. Interestingly, the BV isolates encode numerous proteins not found in strain 409-05 that likely increase their pathogenic potential. These include enzymes enabling mucin degradation, a trait previously described to strongly correlate with BV, although commonly attributed to non-G. vaginalis species.Collectively, our results indicate that all three strains are able to thrive in vaginal environments, and therein the BV isolates are capable of occupying a niche that is unique from 409-05. Each strain has significant virulence potential, although genomic and metabolic differences, such as the ability to degrade mucin, indicate that the detection of G. vaginalis in the vaginal tract provides only partial information on the physiological potential of the organism

Microarray-Based Transcriptomic Analysis of Differences between Long-Term Gregarious and Solitarious Desert Locusts

Desert locusts (Schistocerca gregaria) show an extreme form of phenotypic plasticity and can transform between a cryptic solitarious phase and a swarming gregarious phase. The two phases differ extensively in behavior, morphology and physiology but very little is known about the molecular basis of these differences. We used our recently generated Expressed Sequence Tag (EST) database derived from S. gregaria central nervous system (CNS) to design oligonucleotide microarrays and compare the expression of thousands of genes in the CNS of long-term gregarious and solitarious adult desert locusts. This identified 214 differentially expressed genes, of which 40% have been annotated to date. These include genes encoding proteins that are associated with CNS development and modeling, sensory perception, stress response and resistance, and fundamental cellular processes. Our microarray analysis has identified genes whose altered expression may enable locusts of either phase to deal with the different challenges they face. Genes for heat shock proteins and proteins which confer protection from infection were upregulated in gregarious locusts, which may allow them to respond to acute physiological challenges. By contrast the longer-lived solitarious locusts appear to be more strongly protected from the slowly accumulating effects of ageing by an upregulation of genes related to anti-oxidant systems, detoxification and anabolic renewal. Gregarious locusts also had a greater abundance of transcripts for proteins involved in sensory processing and in nervous system development and plasticity. Gregarious locusts live in a more complex sensory environment than solitarious locusts and may require a greater turnover of proteins involved in sensory transduction, and possibly greater neuronal plasticity