151 research outputs found

    Study of local flow conditions over a hemispherically blunted 25 deg cone for a shallow re-entry trajectory

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    Local flow conditions over hemispherically blunted 25 deg cone for shallow reentry trajector

    Thermal insulating conformal blanket

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    The conformal thermal insulating blanket may have generally rigid batting material covered by an outer insulating layer formed of a high temperature resistant woven ceramic material and an inner insulating layer formed of a woven ceramic fiber material. The batting and insulating layers may be fastened together by sewing or stitching using an outer mold layer thread fabricated of a high temperature resistant material and an inner mold layer thread of a ceramic fiber material. The batting may be formed to a composite structure that may have a firmness factor sufficient to inhibit a pillowing effect after the stitching to not more than 0.03 inch. The outer insulating layer and an upper portion of the batting adjacent the outer insulating layer may be impregnated with a ceramic coating material

    Population genomic analysis reveals a rich speciation and demographic history of orang-utans (Pongo pygmaeus and Pongo abelii)

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    To gain insights into evolutionary forces that have shaped the history of Bornean and Sumatran populations of orang-utans, we compare patterns of variation across more than 11 million single nucleotide polymorphisms found by previous mitochondrial and autosomal genome sequencing of 10 wild-caught orang-utans. Our analysis of the mitochondrial data yields a far more ancient split time between the two populations (~3.4 million years ago) than estimates based on autosomal data (0.4 million years ago), suggesting a complex speciation process with moderate levels of primarily male migration. We find that the distribution of selection coefficients consistent with the observed frequency spectrum of autosomal non-synonymous polymorphisms in orang-utans is similar to the distribution in humans. Our analysis indicates that 35% of genes have evolved under detectable negative selection. Overall, our findings suggest that purifying natural selection, genetic drift, and a complex demographic history are the dominant drivers of genome evolution for the two orang-utan populations.Publisher PDFPeer reviewe

    Transmisión de Klebsiella pneumoniae resistente a carbapenemes en hospitales de EE.UU.

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    Antecedentes. La Klebsiella pneumoniae resistente a los carbapenemes (CRKp) es el Enterobacterales resistente a los carbapenemes más prevalente en los Estados Unidos. Se evaluó la agrupación de CRKp en pacientes de hospitales estadounidenses. Métodos. De abril de 2016 a agosto de 2017, 350 pacientes con grupo clonal 258 CRKp se inscribieron en el Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae, un estudio de cohortes prospectivo y multicéntrico. Se construyó un árbol de máxima verosimilitud utilizando RAxML. Los conglomerados estáticos compartían ≤21 polimorfismos de un solo nucleótido (SNP) y un ancestro común más reciente. Los conglomerados dinámicos incorporaron la distancia SNP, el tiempo de cultivo y las tasas de acumulación y transmisión SNP utilizando el programa R TransCluster. Resultados. La mayoría de los pacientes ingresaron desde su domicilio (n=150, 43%) o desde centros de cuidados de larga duración (n=115, 33%). La orina (n=149, 43%) fue el lugar de aislamiento más común. En total, se identificaron 55 conglomerados estáticos y 47 dinámicos en 210 de 350 (60%) y 194 de 350 (55%) pacientes, respectivamente. Aproximadamente la mitad de los clusters estáticos eran idénticos a los dinámicos. Los conglomerados estáticos consistían en 33 (60%) conglomerados intrasistema y 22 (40%) conglomerados intersistema. Los conglomerados dinámicos estaban formados por 32 (68%) conglomerados intrasistema y 15 (32%) conglomerados intersistema y presentaban menos diferencias de SNP que los conglomerados estáticos (8 frente a 9; P=.045; intervalo de confianza [IC] del 95%: -4 a 0). Los conglomerados dinámicos intersistema contenían más pacientes que los conglomerados dinámicos intrasistema (mediana [intervalo intercuartílico], 4 [2, 7] frente a 2 [2, 2]; P=,007; IC del 95%: -3 a 0). Conclusiones. Se identificó una amplia transmisión intrasistémica e intersistémica de CRKp en pacientes estadounidenses hospitalizados. El uso de diferentes métodos para evaluar la similitud genética sólo dio lugar a diferencias menores en la interpretación.Background. Carbapenem-resistant Klebsiella pneumoniae (CRKp) is the most prevalent carbapenem-resistant Enterobacterales in the United States. We evaluated CRKp clustering in patients in US hospitals. Methods. From April 2016 to August 2017, 350 patients with clonal group 258 CRKp were enrolled in the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae, a prospective, multicenter, cohort study. A maximum likelihood tree was constructed using RAxML. Static clusters shared ≤21 single-nucleotide polymorphisms (SNP) and a most recent common ancestor. Dynamic clusters incorporated SNP distance, culture timing, and rates of SNP accumulation and transmission using the R program TransCluster. Results. Most patients were admitted from home (n=150, 43%) or long-term care facilities (n=115, 33%). Urine (n=149, 43%) was the most common isolation site. Overall, 55 static and 47 dynamics clusters were identified involving 210 of 350 (60%) and 194 of 350 (55%) patients, respectively. Approximately half of static clusters were identical to dynamic clusters. Static clusters consisted of 33 (60%) intrasystem and 22 (40%) intersystem clusters. Dynamic clusters consisted of 32 (68%) intrasystem and 15 (32%) intersystem clusters and had fewer SNP differences than static clusters (8 vs 9; P=.045; 95% confidence interval [CI]: −4 to 0). Dynamic intersystem clusters contained more patients than dynamic intrasystem clusters (median [interquartile range], 4 [2, 7] vs 2 [2, 2]; P=.007; 95% CI: −3 to 0). Conclusions. Widespread intrasystem and intersystem transmission of CRKp was identified in hospitalized US patients. Use of different methods for assessing genetic similarity resulted in only minor differences in interpretation

    Lives saved with vaccination for 10 pathogens across 112 countries in a pre-COVID-19 world.

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    BackgroundVaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae, and yellow fever over the years 2000-2030 across 112 countries.MethodsTwenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios.ResultsWe estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000-2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases.ConclusionsThis study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future.FundingVIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill and Melinda Gates Foundation (BMGF) (BMGF grant number: OPP1157270 / INV-009125). Funding from Gavi is channelled via VIMC to the Consortium's modelling groups (VIMC-funded institutions represented in this paper: Imperial College London, London School of Hygiene and Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Métiers, Emory University, National University of Singapore). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: TBH, MJ, XL, SE-L, JT, KW, NMF, KAMG); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). We also acknowledge funding from the UK Medical Research Council and Department for International Development, which supported aspects of VIMC's work (MRC grant number: MR/R015600/1).JHH acknowledges funding from National Science Foundation Graduate Research Fellowship; Richard and Peggy Notebaert Premier Fellowship from the University of Notre Dame. BAL acknowledges funding from NIH/NIGMS (grant number R01 GM124280) and NIH/NIAID (grant number R01 AI112970). The Lives Saved Tool (LiST) receives funding support from the Bill and Melinda Gates Foundation.This paper was compiled by all coauthors, including two coauthors from Gavi. Other funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication

    Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences

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    Mycobacterium tuberculosis drug resistance (DR) challenges effective tuberculosis disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive of DR for 15 anti-tuberculosis drugs was compiled and validated for 11 of them using genomic-phenotypic data from 792 strains. A rapid online ‘TB-Profiler’ tool was developed to report DR and strain-type profiles directly from raw sequences. Using our DR mutation library, in silico diagnostic accuracy was superior to some commercial diagnostics and alternative databases. The library will facilitate sequence-based drug-susceptibility testing

    Transmission of Carbapenem-Resistant Klebsiella pneumoniae in US Hospitals

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    Background: Carbapenem-resistant Klebsiella pneumoniae (CRKp) is the most prevalent carbapenem-resistant Enterobacterales in the United States. We evaluated CRKp clustering in patients in US hospitals. Methods: From April 2016 to August 2017, 350 patients with clonal group 258 CRKp were enrolled in the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae, a prospective, multicenter, cohort study. A maximum likelihood tree was constructed using RAxML. Static clusters shared ≤21 single-nucleotide polymorphisms (SNP) and a most recent common ancestor. Dynamic clusters incorporated SNP distance, culture timing, and rates of SNP accumulation and transmission using the R program TransCluster. Results: Most patients were admitted from home (n = 150, 43%) or long-term care facilities (n = 115, 33%). Urine (n = 149, 43%) was the most common isolation site. Overall, 55 static and 47 dynamics clusters were identified involving 210 of 350 (60%) and 194 of 350 (55%) patients, respectively. Approximately half of static clusters were identical to dynamic clusters. Static clusters consisted of 33 (60%) intrasystem and 22 (40%) intersystem clusters. Dynamic clusters consisted of 32 (68%) intrasystem and 15 (32%) intersystem clusters and had fewer SNP differences than static clusters (8 vs 9; P =. 045; 95% confidence interval [CI]: -4 to 0). Dynamic intersystem clusters contained more patients than dynamic intrasystem clusters (median [interquartile range], 4 [2, 7] vs 2 [2, 2]; P =. 007; 95% CI: -3 to 0). Conclusions: Widespread intrasystem and intersystem transmission of CRKp was identified in hospitalized US patients. Use of different methods for assessing genetic similarity resulted in only minor differences in interpretation

    On plexus representation of dissimilarities

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    Correspondence analysis has found widespread application in analysing vegetation gradients. However, it is not clear how it is robust to situations where structures other than a simple gradient exist. The introduction of instrumental variables in canonical correspondence analysis does not avoid these difficulties. In this paper I propose to examine some simple methods based on the notion of the plexus (sensu McIntosh) where graphs or networks are used to display some of the structure of the data so that an informed choice of models is possible. I showthat two different classes of plexus model are available. These classes are distinguished by the use in one case of a global Euclidean model to obtain well-separated pair decomposition (WSPD) of a set of points which implicitly involves all dissimilarities, while in the other a Riemannian view is taken and emphasis is placed locally, i.e., on small dissimilarities. I showan example of each of these classes applied to vegetation data

    Sequence variation, evolutionary constraint, and selection at the CD163 gene in pigs

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    Abstract Background In this work, we investigated sequence variation, evolutionary constraint, and selection at the CD163 gene in pigs. A functional CD163 protein is required for infection by porcine reproductive and respiratory syndrome virus, which is a serious pathogen with major impacts on pig production. Results We used targeted pooled sequencing of the exons of CD163 to detect sequence variants in 35,000 pigs of diverse genetic backgrounds and to search for potential stop-gain and frameshift indel variants. Then, we used whole-genome sequence data from three pig lines to calculate: a variant intolerance score that measures the tolerance of genes to protein coding variation; an estimate of selection on protein-coding variation over evolutionary time; and haplotype diversity statistics to detect recent selective sweeps during breeding. Conclusions Using a deep survey of sequence variation in the CD163 gene in domestic pigs, we found no potential knockout variants. The CD163 gene was moderately intolerant to variation and showed evidence of positive selection in the pig lineage, but no evidence of recent selective sweeps during breeding
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