3,531 research outputs found

    A recommended numbering scheme for influenza A HA subtypes.

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    Comparisons of residues between sub-types of influenza virus is increasingly used to assess the zoonotic potential of a circulating strain and for comparative studies across subtypes. An analysis of N-terminal cleavage sites for thirteen subtypes of influenza A hemagglutinin (HA) sequences, has previously been described by Nobusawa and colleagues. We have expanded this analysis for the eighteen known subtypes of influenza. Due to differences in the length of HA, we have included strains from multiple clades of H1 and H5, as well as strains of H5 and H7 subtypes with both high and low pathogenicity. Analysis of known structures of influenza A HA enables us to define amino acids which are structurally and functionally equivalent across all HA subtypes using a numbering system based on the mature HA sequence. We provide a list of equivalences for amino acids which are known to affect the phenotype of the virus.Funding provided by (DJS) Bill & Melinda Gates Foundation Global Health (http://www.gatesfoundation.org/) Grant # OPPGH5383, (DJS) European Union FP7 program ANTIGONE (http://cordis.europa.eu/programme/rcn/852_en.html) (278976) and (DJS) National Institute of Allergy and Infectious disease (http://www.niaid.nih.gov) Contract HHSN266200700010C. The funders had no role in the study design, data collection, analysis, decision to publish or preparation of the manuscript.This is the final published version. It originally appeared at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0112302

    Promoting Partnerships for Student Success: Lessons from the SSPIRE Initiative

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    The Student Support Partnership Integrating Resources and Education (SSPIRE) initiative aimed to increase the success of young, low-income, and academically underprepared California community college students by helping colleges strengthen their support services and better integrate these services with academic instruction. This report describes what the nine participating community colleges did to meet the goals of SSPIRE and offers lessons for other institutions drawn from MDRC's research on the initiative

    Emission Characteristics of an Axially Staged Sector Combustor for a Small Core High OPR Subsonic Aircraft Engine

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    This paper presents the nitrogen oxides, carbon monoxide, and particulate matter emissions of a single sector axially staged combustor sector designed and fabricated by United Technologies Research Center (UTRC) in partnership with NASA under a compact low-emissions combustor contract supported by the NASA Advanced Air Transport Technology (AATT) N+3 project. The test was conducted at NASA Glenn Research Center's CE-5 combustion test facility. The facility provided inlet air temperatures up to 922 K and pressures up to 19.0 bar. The combustor design concept, called Axially Controlled Stoichiometry (ACS), was developed by Pratt & Whitney (P&W) under NASA's Environmentally Responsible Aviation (ERA) program for an N+2 combustor for use in twin-aisle subsonic aircraft engines. Under the N+3 project the ACS combustor was scaled-down for application to small-core N+3 engines for use in single-aisle aircraft. The results show that the NOx and CO emissions characteristics are similar in both the N+2 and N+3 applications. The non-volatile particulate matter (nvPM) emissions trends are similar to CO emissions with an exception at high fuel-air ratio, as inlet air temperature and pressure conditions change from taxi to approach. Three NOx correlation equations are generated to describe theNOx emissions of this combustor. The percentage landing and takeoff (LTO) NOx reduction of the N+3 ACS combustor is between 82% and 89% relative to the ICAO CAEP/6 standard, which meets the NASA N+3 goal of exceeding 80% LTO NOx reduction

    The crystal structure of superoxide dismutase from Plasmodium falciparum

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    Background: Superoxide dismutases (SODs) are important enzymes in defence against oxidative stress. In Plasmodium falciparum, they may be expected to have special significance since part of the parasite life cycle is spent in red blood cells where the formation of reactive oxygen species is likely to be promoted by the products of haemoglobin breakdown. Thus, inhibitors of P. falciparum SODs have potential as anti-malarial compounds. As a step towards their development we have determined the crystal structure of the parasite's cytosolic iron superoxide dismutase. Results: The cytosolic iron superoxide dismutase from P. falciparum (PfFeSOD) has been overexpressed in E. coli in a catalytically active form. Its crystal structure has been solved by molecular replacement and refined against data extending to 2.5 angstrom resolution. The structure reveals a two-domain organisation and an iron centre in which the metal is coordinated by three histidines, an aspartate and a solvent molecule. Consistent with ultracentrifugation analysis the enzyme is a dimer in which a hydrogen bonding lattice links the two active centres. Conclusion: The tertiary structure of PfFeSOD is very similar to those of a number of other iron-and manganese-dependent superoxide dismutases, moreover the active site residues are conserved suggesting a common mechanism of action. Comparison of the dimer interfaces of PfFeSOD with the human manganese-dependent superoxide dismutase reveals a number of differences, which may underpin the design of parasite-selective superoxide dismutase inhibitors

    Inferred support for disturbance-recovery hypothesis of North Atlantic phytoplankton blooms

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    Analyses of satellite-derived chlorophyll data indicate that the phase of rapid phytoplankton population growth in the North Atlantic (the ‘spring bloom') is actually initiated in the winter rather than the spring, contradicting Sverdrup's Critical Depth Hypothesis. An alternative disturbance-recovery hypothesis (DRH) has been proposed to explain this discrepancy, in which the rapid deepening of the mixed layer reduces zooplankton grazing rates sufficiently to initiate the bloom. We use Bayesian parameter inference on a simple Nutrient-Phytoplankton-Zooplankton (NPZ) to investigate the DRH and also investigate how well the model can capture the multiyear and spatial dynamics of phytoplankton concentrations and population growth rates. Every parameter in our NPZ model was inferred as a probability distribution given empirical constraints, this provides a more objective method to identify a model parameterisation given available empirical evidence, rather than fixing or tuning individual parameter values. Our model explains around 75% of variation in the seasonal dynamics of phytoplankton concentrations, 30% of variation in their population rates of change, and correctly predicts the phases of population growth and decline. Our parameter-inferred model supports DRH, revealing the sustained reduction of grazing due to mixed layer deepening as the driving mechanism behind bloom initiation, with the relaxation of nutrient limitation being another contributory mechanism. Our results also show that the continuation of the bloom is caused in part by the maintenance of phytoplankton concentrations below a level that can support positive zooplankton population growth. Our approach could be employed to formally assess alternative hypotheses for bloom formatio

    HTLV-I-Infected T Cells Evade the Antiproliferative Action of IFN-β

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    AbstractHuman T-cell lymphotropic virus type I (HTLV-I)-infected T-cell clones enter the S-phase of the cell cycle in the absence of exogenous IL-2. The pathway by which HTLV-I activates the host T cell may circumvent normal immunoregulatory mechanisms and thus be important for the pathogenesis of HTLV-I-induced diseases. The early control of viral infections is in part mediated by interferons (IFNs), which possess both antiviral and antiproliferative functions. In order to investigate the antiproliferative effect of IFN-β on HTLV-I-induced T-cell activation, we generated T-cell clones from patients with HTLV-I-associated myelopathy/tropical spastic paraparesis by single-cell cloning under limiting dilution conditions. Here we demonstrate that HTLV-I-induced T-cell proliferation is resistant to the antiproliferative action of IFN-β. Moreover, HTLV-I-infected T-cell clones continue to constitutively secrete IFN-γ in the presence of high doses of IFN-β. HTLV-I-infected T cells express normal levels of IFNAR1 and are able to respond to IFN-β by phosphorylation of STAT1 on Tyr701, although they display a relative increase in phosphorylation of the transcriptionally inactive STAT1β when compared with STAT1α. Thus, HTLV-I promotes cell cycle progression in G1by a mechanism that overcomes inhibitory signals, thereby circumventing an innate immune defense mechanism

    A scoping review to catalogue tinnitus problems in children

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    © 2019 The Authors Background: The reported prevalence of tinnitus in children is similar to that in adults. However, unlike adults, there is relatively little understanding of the tinnitus-related problems children experience. Knowledge of the problems experienced by adults has led to the development of numerous clinical questionnaires used by health professionals in assessment and treatment practices; to date no child-specific questionnaire measure of tinnitus has been developed. To support development of a questionnaire measure of tinnitus in children, the aim of this scoping review was to catalogue the peer-reviewed and grey scientific literature according to 1) the methods used to identify problems experienced by children with tinnitus, 2) tinnitus-related problems observed in or reported by children, and 3) research recommendations suggested by investigators with regards to tinnitus in children. Methods: A scoping review was conducted following an established methodological framework. Records were included where a tinnitus-related problem was reported in a child 18 years or younger, and tinnitus was reported as the primary complaint. Tinnitus problems were extracted and categorised into problem themes. Results: Thirty-five records met the inclusion criteria for this review. Methods used to identify tinnitus-related problems in children, and the number and range of problems reported, varied across the records. Symptom impact was summarised according to six problem themes; Physical health, Cognitive health, Hearing and listening, Emotional health, Quality of life, and Feeling different/isolated. Identified research recommendations highlighted a demand for more standardised approaches. Conclusions: The findings evidence the detrimental impact tinnitus can have on a child's quality of life and emotional wellbeing. The current British Society of Audiology Tinnitus in Children Practice Guidance recommends management practices to address the most broadly reported problems identified in this review; sleep difficulties, emotional difficulties, and concentration and hearing problems at school. Given the finding of this review, we suggest problems relating to the impact of tinnitus on quality of life and feelings of isolation are also important problem domains to consider when managing a child who has tinnitus. Current variability in the approach to identifying children's tinnitus problems underlines the importance of developing a standardised and dedicated measure of tinnitus in children
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