195 research outputs found
Supersymmetric Electroweak Baryogenesis Via Resonant Sfermion Sources
We calculate the baryon asymmetry produced at the electroweak phase
transition by quasi-degenerate third generation sfermions in the minimal
supersymmetric extension of the Standard Model. We evaluate constraints from
Higgs searches, from collider searches for supersymmetric particles, and from
null searches for the permanent electric dipole moment (EDM) of the electron,
of the neutron and of atoms. We find that resonant sfermion sources can in
principle provide a large enough baryon asymmetry in various corners of the
sfermion parameter space, and we focus, in particular, on the case of large
, where third-generation down-type (s)fermions become relevant. We
show that in the case of stop and sbottom sources, the viable parameter space
is ruled out by constraints from the non-observation of the Mercury EDM. We
introduce a new class of CP violating sources, quasi-degenerate staus, that
escapes current EDM constraints while providing large enough net chiral
currents to achieve successful "slepton-mediated" electroweak baryogenesis.Comment: 35 pages, 9 figures; v2: several revisions, but conclusions
unchanged. Matches version published in PR
Does evolutionary innovation in pharyngeal jaws lead to rapid lineage diversification in labrid fishes?
<p>Abstract</p> <p>Background</p> <p>Major modifications to the pharyngeal jaw apparatus are widely regarded as a recurring evolutionary key innovation that has enabled adaptive radiation in many species-rich clades of percomorph fishes. However one of the central predictions of this hypothesis, that the acquisition of a modified pharyngeal jaw apparatus will be positively correlated with explosive lineage diversification, has never been tested. We applied comparative methods to a new time-calibrated phylogeny of labrid fishes to test whether diversification rates shifted at two scales where major pharyngeal jaw innovations have evolved: across all of Labridae and within the subclade of parrotfishes.</p> <p>Results</p> <p>Diversification patterns within early labrids did not reflect rapid initial radiation. Much of modern labrid diversity stems from two recent rapid diversification events; one within julidine fishes and the other with the origin of the most species-rich clade of reef-associated parrotfishes. A secondary pharyngeal jaw innovation was correlated with rapid diversification within the parrotfishes. However diversification rate shifts within parrotfishes are more strongly correlated with the evolution of extreme dichromatism than with pharyngeal jaw modifications.</p> <p>Conclusion</p> <p>The temporal lag between pharyngeal jaw modifications and changes in diversification rates casts doubt on the key innovation hypothesis as a simple explanation for much of the richness seen in labrids and scarines. Although the possession of a secondarily modified PJA was correlated with increased diversification rates, this pattern is better explained by the evolution of extreme dichromatism (and other social and behavioral characters relating to sexual selection) within <it>Scarus </it>and <it>Chlorurus</it>. The PJA-innovation hypothesis also fails to explain the most dominant aspect of labrid lineage diversification, the radiation of the julidines. We suggest that pharyngeal jaws might have played a more important role in enabling morphological evolution of the feeding apparatus in labrids and scarines rather than in accelerating lineage diversification.</p
A CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation
BACKGROUND: Increasing the activity of defective cystic fibrosis transmembrane conductance regulator (CFTR) protein is a potential treatment for cystic fibrosis. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to evaluate ivacaftor (VX-770), a CFTR potentiator, in subjects 12 years of age or older with cystic fibrosis and at least one G551D-CFTR mutation. Subjects were randomly assigned to receive 150 mg of ivacaftor every 12 hours (84 subjects, of whom 83 received at least one dose) or placebo (83, of whom 78 received at least one dose) for 48 weeks. The primary end point was the estimated mean change from baseline through week 24 in the percent of predicted forced expiratory volume in 1 second (FEV(1)). RESULTS: The change from baseline through week 24 in the percent of predicted FEV(1) was greater by 10.6 percentage points in the ivacaftor group than in the placebo group (P<0.001). Effects on pulmonary function were noted by 2 weeks, and a significant treatment effect was maintained through week 48. Subjects receiving ivacaftor were 55% less likely to have a pulmonary exacerbation than were patients receiving placebo, through week 48 (P<0.001). In addition, through week 48, subjects in the ivacaftor group scored 8.6 points higher than did subjects in the placebo group on the respiratory-symptoms domain of the Cystic Fibrosis Questionnaire–revised instrument (a 100-point scale, with higher numbers indicating a lower effect of symptoms on the patient’s quality of life) (P<0.001). By 48 weeks, patients treated with ivacaftor had gained, on average, 2.7 kg more weight than had patients receiving placebo (P<0.001). The change from baseline through week 48 in the concentration of sweat chloride, a measure of CFTR activity, with ivacaftor as compared with placebo was −48.1 mmol per liter (P<0.001). The incidence of adverse events was similar with ivacaftor and placebo, with a lower proportion of serious adverse events with ivacaftor than with placebo (24% vs. 42%). CONCLUSIONS: Ivacaftor was associated with improvements in lung function at 2 weeks that were sustained through 48 weeks. Substantial improvements were also observed in the risk of pulmonary exacerbations, patient-reported respiratory symptoms, weight, and concentration of sweat chloride
Electroweak baryogenesis
Electroweak baryogenesis (EWBG) remains a theoretically attractive and
experimentally testable scenario for explaining the cosmic baryon asymmetry. We
review recent progress in computations of the baryon asymmetry within this
framework and discuss their phenomenological consequences. We pay particular
attention to methods for analyzing the electroweak phase transition and
calculating CP-violating asymmetries, the development of Standard Model
extensions that may provide the necessary ingredients for EWBG, and searches
for corresponding signatures at the high energy, intensity, and cosmological
frontiers.Comment: 42 pages, 13 figures, invited review for the New Journal of Physics
focus issue on 'Origin of Matter
An interdisciplinary team communication framework and its application to healthcare 'e-teams' systems design
<p>Abstract</p> <p>Background</p> <p>There are few studies that examine the processes that interdisciplinary teams engage in and how we can design health information systems (HIS) to support those team processes. This was an exploratory study with two purposes: (1) To develop a framework for interdisciplinary team communication based on structures, processes and outcomes that were identified as having occurred during weekly team meetings. (2) To use the framework to guide 'e-teams' HIS design to support interdisciplinary team meeting communication.</p> <p>Methods</p> <p>An ethnographic approach was used to collect data on two interdisciplinary teams. Qualitative content analysis was used to analyze the data according to structures, processes and outcomes.</p> <p>Results</p> <p>We present details for team meta-concepts of structures, processes and outcomes and the concepts and sub concepts within each meta-concept. We also provide an exploratory framework for interdisciplinary team communication and describe how the framework can guide HIS design to support 'e-teams'.</p> <p>Conclusion</p> <p>The structures, processes and outcomes that describe interdisciplinary teams are complex and often occur in a non-linear fashion. Electronic data support, process facilitation and team video conferencing are three HIS tools that can enhance team function.</p
Photodynamic and Antibiotic Therapy Impair the Pathogenesis of Enterococcus faecium in a Whole Animal Insect Model
Enterococcus faecium has emerged as one of the most important pathogens in healthcare-associated infections worldwide due to its intrinsic and acquired resistance to many antibiotics, including vancomycin. Antimicrobial photodynamic therapy (aPDT) is an alternative therapeutic platform that is currently under investigation for the control and treatment of infections. PDT is based on the use of photoactive dye molecules, widely known as photosensitizer (PS). PS, upon irradiation with visible light, produces reactive oxygen species that can destroy lipids and proteins causing cell death. We employed Galleria mellonella (the greater wax moth) caterpillar fatally infected with E. faecium to develop an invertebrate host model system that can be used to study the antimicrobial PDT (alone or combined with antibiotics). In the establishment of infection by E. faecium in G. mellonella, we found that the G. mellonella death rate was dependent on the number of bacterial cells injected into the insect hemocoel and all E. faecium strains tested were capable of infecting and killing G. mellonella. Antibiotic treatment with ampicillin, gentamicin or the combination of ampicillin and gentamicin prolonged caterpillar survival infected by E. faecium (P = 0.0003, P = 0.0001 and P = 0.0001, respectively). In the study of antimicrobial PDT, we verified that methylene blue (MB) injected into the insect followed by whole body illumination prolonged the caterpillar survival (P = 0.0192). Interestingly, combination therapy of larvae infected with vancomycin-resistant E. faecium, with antimicrobial PDT followed by vancomycin, significantly prolonged the survival of the caterpillars when compared to either antimicrobial PDT (P = 0.0095) or vancomycin treatment alone (P = 0.0025), suggesting that the aPDT made the vancomycin resistant E. faecium strain more susceptible to vancomycin action. In summary, G. mellonella provides an invertebrate model host to study the antimicrobial PDT and to explore combinatorial aPDT-based treatments
PDBe: improved accessibility of macromolecular structure data from PDB and EMDB
© 2015 The Authors. Published by OUP. This is an open access article available under a Creative Commons licence.
The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1093/nar/gkv1047The Protein Data Bank in Europe (http://pdbe.org) accepts and annotates depositions of macromolecular structure data in the PDB and EMDB archives and enriches, integrates and disseminates structural information in a variety of ways. The PDBe website has been redesigned based on an analysis of user requirements, and now offers intuitive access to improved and value-added macromolecular structure information. Unique value-added information includes lists of reviews and research articles that cite or mention PDB entries as well as access to figures and legends from full-text open-access publications that describe PDB entries. A powerful new query system not only shows all the PDB entries that match a given query, but also shows the 'best structures' for a given macromolecule, ligand complex or sequence family using data-quality information from the wwPDB validation reports. A PDBe RESTful API has been developed to provide unified access to macromolecular structure data available in the PDB and EMDB archives as well as value-added annotations, e.g. regarding structure quality and up-to-date cross-reference information from the SIFTS resource. Taken together, these new developments facilitate unified access to macromolecular structure data in an intuitive way for non-expert users and support expert users in analysing macromolecular structure data.The Wellcome Trust [88944, 104948]; UK Biotechnology and Biological Sciences Research Council [BB/J007471/1, BB/K016970/1, BB/M013146/1, BB/M011674/1]; National Institutes of Health [GM079429]; UK Medical Research Council [MR/L007835/1]; European Union [284209]; CCP4; European Molecular Biology Laboratory (EMBL). Funding for open access charge: The Wellcome Trust.Published versio
Effect of Virulence Factors on the Photodynamic Inactivation of Cryptococcus neoformans
Opportunistic fungal pathogens may cause an array of superficial infections or serious invasive infections, especially in immunocompromised patients. Cryptococcus neoformans is a pathogen causing cryptococcosis in HIV/AIDS patients, but treatment is limited due to the relative lack of potent antifungal agents. Photodynamic inactivation (PDI) uses the combination of non-toxic dyes called photosensitizers and harmless visible light, which produces singlet oxygen and other reactive oxygen species that produce cell inactivation and death. We report the use of five structurally unrelated photosensitizers (methylene blue, Rose Bengal, selenium derivative of a Nile blue dye, a cationic fullerene and a conjugate between poly-L-lysine and chlorin(e6)) combined with appropriate wavelengths of light to inactivate C. neoformans. Mutants lacking capsule and laccase, and culture conditions that favoured melanin production were used to probe the mechanisms of PDI and the effect of virulence factors. The presence of cell wall, laccase and melanin tended to protect against PDI, but the choice of the appropriate photosensitizers and dosimetry was able to overcome this resistance.Fundação de Amparo à Pesquisa do Estado de São Paulo (2010/13313–9
Distinguishing Molecular Features and Clinical Characteristics of a Putative New Rhinovirus Species, Human Rhinovirus C (HRV C)
Background: Human rhinoviruses (HRVs) are the most frequently detected pathogens in acute respiratory tract infections (ARTIs) and yet little is known about the prevalence, recurrence, structure and clinical impact of individual members. During 2007, the complete coding sequences of six previously unknown and highly divergent HRV strains were reported. To catalogue the molecular and clinical features distinguishing the divergent HRV strains, we undertook, for the first time, in silico analyses of all available polyprotein sequences and performed retrospective reviews of the medical records of cases in which variants of the prototype strain, HRV-QPM, had been detected
Network Formation with Local Complements and Global Substitutes: The Case of R&D Networks
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