Viral evasion of innate immune defense: The case of resistance of pandemic H1N1 influenza A virus to human mannose-binding proteins

Mannose-binding lectins effectively inhibit most seasonal strains of influenza A virus and contribute to the innate host defense vs. these viruses. In contrast, pandemic IAV strains are largely resistant to these lectins, likely contributing to increased spread and worse outcomes. In this paper, we evaluated the inhibition of IAV by mannose-binding lectins of human, bacterial, and fungal origin to understand and possibly increase activity vs. the pandemic IAV. A modified version of the human surfactant protein D (SP-D) neck and carbohydrate recognition domain (NCRD) with combinatorial substitutions at the 325 and 343 positions, previously shown to inhibit pandemic H3N2 IA

Second and Third Quarter Hanford Seismic Report for Fiscal Year 2001

This report describes the seismic activity on the Hanford Site during the 2nd and 3rd quarters of FY0

Topological Reduction of 4D SYM to 2D σ\sigma--Models

By considering a (partial) topological twisting of supersymmetric Yang-Mills compactified on a 2d space with `t Hooft magnetic flux turned on we obtain a supersymmetric $\sigma$-model in 2 dimensions. For N=2 SYM this maps Donaldson observables on products of two Riemann surfaces to quantum cohomology ring of moduli space of flat connections on a Riemann surface. For N=4 SYM it maps $S$-duality to $T$-duality for $\sigma$-models on moduli space of solutions to Hitchin equations.Comment: 30 pages, harvma

Mental and substance use disorders from early adolescence to young adulthood among indigenous young people: final diagnostic results from an 8-year panel study

Objective—Our objective was to investigate change in prevalence rates for mental and substance abuse disorders between early adolescence and young adulthood in a cohort of indigenous adolescents who participated in an 8-year panel study. Method—The data are from a lagged, sequential study of 671 indigenous adolescents (Wave 1) from a single culture in the Northern Midwest USA and Canada. At Wave 1 (mean age 11.3 years, Wave 4 (mean age 14.3 years), Wave 6 (mean age 16.2 years), and at Wave 8 (mean age 18.3 years) the tribally enrolled adolescents completed a computer-assisted personal interview that included DISC-R assessment for 11 diagnoses. Our yearly retention rates by diagnostic wave were: Wave 2, 94.7 %; Wave 4, 87.7 %; Wave 6, 88.0 %; Wave 8, 78.5 %. Results—The findings show a dramatic increase in lifetime prevalence rates for substance use disorders. By young adulthood, over half had met criteria of substance abuse or dependence disorder. Also at young adulthood, 58.2 % had met lifetime criteria of a single substance use or mental disorder and 37.2 % for two or more substance use or mental disorders. The results are compared to other indigenous diagnostic studies and to the general population. Conclusions—A mental health crisis exists within the indigenous populations that participated in this study. Innovations within current mental health service systems are needed to address the unmet demand of adolescents and families

Mental and substance use disorders from early adolescence to young adulthood among indigenous young people: final diagnostic results from an 8-year panel study

Objective—Our objective was to investigate change in prevalence rates for mental and substance abuse disorders between early adolescence and young adulthood in a cohort of indigenous adolescents who participated in an 8-year panel study. Method—The data are from a lagged, sequential study of 671 indigenous adolescents (Wave 1) from a single culture in the Northern Midwest USA and Canada. At Wave 1 (mean age 11.3 years, Wave 4 (mean age 14.3 years), Wave 6 (mean age 16.2 years), and at Wave 8 (mean age 18.3 years) the tribally enrolled adolescents completed a computer-assisted personal interview that included DISC-R assessment for 11 diagnoses. Our yearly retention rates by diagnostic wave were: Wave 2, 94.7 %; Wave 4, 87.7 %; Wave 6, 88.0 %; Wave 8, 78.5 %. Results—The findings show a dramatic increase in lifetime prevalence rates for substance use disorders. By young adulthood, over half had met criteria of substance abuse or dependence disorder. Also at young adulthood, 58.2 % had met lifetime criteria of a single substance use or mental disorder and 37.2 % for two or more substance use or mental disorders. The results are compared to other indigenous diagnostic studies and to the general population. Conclusions—A mental health crisis exists within the indigenous populations that participated in this study. Innovations within current mental health service systems are needed to address the unmet demand of adolescents and families

Collaboration between Science and Religious Education teachers in Scottish Secondary schools

The article reports on quantitative research that examines: (1) the current practice in collaboration; and (2) potential for collaboration between Science and Religious Education teachers in a large sample of Scottish secondary schools. The authors adopt and adapt three models (conflict; concordat and consonance) to interrogate the relationship between science and religion (and the perceived relation between these two subjects in schools) (Astley and Francis 2010). The findings indicate that there is evidence of limited collaboration and, in a few cases, a dismissive attitude towards collaboration (conflict and concordat and very weak consonance). There is, however, evidence of a genuine aspiration for greater collaboration among many teachers (moving towards a more robust consonance model). The article concludes by discussing a number of key factors that must be realised for this greater collaboration to be enacted

MarkUs: a server to navigate sequence–structure–function space

We describe MarkUs, a web server for analysis and comparison of the structural and functional properties of proteins. In contrast to a ‘structure in/function out’ approach to protein function annotation, the server is designed to be highly interactive and to allow flexibility in the examination of possible functions, suggested either automatically by various similarity measures or specified by a user directly. This is combined with tools that allow a user to assess independently whether or not a suggested function is consistent with the bioinformatic and biophysical properties of a given query structure, further allowing the user to generate testable hypotheses. The server is available at http://wiki.c2b2.columbia.edu/honiglab_public/index.php/Software:Mark-Us

PredUs: a web server for predicting protein interfaces using structural neighbors

We describe PredUs, an interactive web server for the prediction of protein–protein interfaces. Potential interfacial residues for a query protein are identified by ‘mapping’ contacts from known interfaces of the query protein’s structural neighbors to surface residues of the query. We calculate a score for each residue to be interfacial with a support vector machine. Results can be visualized in a molecular viewer and a number of interactive features allow users to tailor a prediction to a particular hypothesis. The PredUs server is available at: http://wiki.c2b2.columbia.edu/honiglab_public/index.php/Software:PredUs

Affine modifications and affine hypersurfaces with a very transitive automorphism group

We study a kind of modification of an affine domain which produces another affine domain. First appeared in passing in the basic paper of O. Zariski (1942), it was further considered by E.D. Davis (1967). The first named author applied its geometric counterpart to construct contractible smooth affine varieties non-isomorphic to Euclidean spaces. Here we provide certain conditions which guarantee preservation of the topology under a modification. As an application, we show that the group of biregular automorphisms of the affine hypersurface $X \subset C^{k+2}$ given by the equation $uv=p(x_1,...,x_k)$ where $p \in C[x_1,...,x_k],$ acts $m-$transitively on the smooth part reg$X$ of $X$ for any $m \in N.$ We present examples of such hypersurfaces diffeomorphic to Euclidean spaces.Comment: 39 Pages, LaTeX; a revised version with minor changes and correction

Variation in treatment of acute childhood wheeze in emergency departments of the United Kingdom and Ireland: An international survey of clinician practice

© 2015, BMJ Publishing Group. All rights reserved. Objective: National clinical guidelines for childhood wheeze exist, yet despite being one of the most common reasons for childhood emergency department (ED) attendance, signi ficant variation in practice occurs in other settings. We, therefore, evaluated practice variations of ED clinicians in the UK and Ireland. Design: Two-stage survey undertaken in March 2013. Stage one examined department practice and stage two assessed ED consultant practice in acute childhood wheeze. Questions interrogated pharmacological and other management strategies, including inhaled and intravenous therapies. Setting and participants: Member departments of Paediatric Emergency Research in the United Kingdom and Ireland and ED consultants treating children with acute wheeze. Results: 30 EDs and 183 (81%) clinicians responded. 29 (97%) EDs had wheeze guidelines and 12 (40%) had care pathways. Variation existed between clinicians in dose, timing and frequency of inhaled bronchodilators across severities. When escalating to intravenous bronchodilators, 99 (54%) preferred salbutamol first line, 52 (28%) magnesium sulfate (MgSO4) and 27 (15%) aminophylline. 87 (48%) administered intravenous bronchodilators sequentially and 30 (16%) concurrently, with others basing approach on case severity. 146 (80%) continued inhaled therapy after commencing intravenous bronchodilators. Of 170 who used intravenous salbutamol, 146 (86%) gave rapid boluses, 21 (12%) a longer loading dose and 164 (97%) an ongoing infusion, each with a range of doses and durations. Of 173 who used intravenous MgSO4, all used a bolus only. 41 (24%) used non-invasive ventilation. Conclusions: Signi ficant variation in ED consultant management of childhood wheeze exists despite the presence of national guidance. This reflects the lack of evidence in key areas of childhood wheeze and emphasises the need for further robust multicentre research studies