161 research outputs found

    2nd Generation QUATARA Flight Computer Project

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    Single core flight computer boards have been designed, developed, and tested (DD&T) to be flown in small satellites for the last few years. In this project, a prototype flight computer will be designed as a distributed multi-core system containing four microprocessors running code in parallel. This flight computer will be capable of performing multiple computationally intensive tasks such as processing digital and/or analog data, controlling actuator systems, managing cameras, operating robotic manipulators and transmitting/receiving from/to a ground station. In addition, this flight computer will be designed to be fault tolerant by creating both a robust physical hardware connection and by using a software voting scheme to determine the processor's performance. This voting scheme will leverage on the work done for the Space Launch System (SLS) flight software. The prototype flight computer will be constructed with Commercial Off-The-Shelf (COTS) components which are estimated to survive for two years in a low-Earth orbit

    PCR-based method for targeting 16S-23S rRNA intergenic spacer regions among Vibrio species

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    <p>Abstract</p> <p>Background</p> <p>The genus <it>Vibrio </it>is a diverse group of Gram-negative bacteria comprised of 74 species. Furthermore, the genus has and is expected to continue expanding with the addition of several new species annually. Consequently, it is of paramount importance to have a method which is able to reliably and efficiently differentiate the numerous <it>Vibrio </it>species.</p> <p>Results</p> <p>In this study, a novel and rapid polymerase chain reaction (PCR)-based intergenic spacer (IGS)-typing system for vibrios was developed that is based on the well-known IGS regions located between the 16S and 23S rRNA genes on the bacterial chromosome. The system was optimized to resolve heteroduplex formation as well as to take advantage of capillary gel electrophoresis technology such that reproducible analyses could be achieved in a rapid manner. System validation was achieved through testing of 69 archetypal <it>Vibrio </it>strains, representing 48 <it>Vibrio </it>species, from which an 'IGS-type' profile database was generated. These data, presented here in several cluster analyses, demonstrated successful differentiation of the 69 type strains showing that this PCR-based fingerprinting method easily discriminates bacterial strains at the species level among <it>Vibrio</it>. Furthermore, testing 36 strains each of <it>V. parahaemolyticus </it>and <it>V. vulnificus</it>, important food borne pathogens, isolated from a variety of geographical locations with the IGS-typing method demonstrated distinct IGS-typing patterns indicative of subspecies divergence in both populations making this technique equally useful for intraspecies differentiation, as well.</p> <p>Conclusion</p> <p>This rapid, reliable and efficient IGS-typing system, especially in combination with 16S rRNA gene sequencing, has the capacity to not only discern and identify vibrios at the species level but, in some cases, at the sub-species level, as well. This procedure is particularly well-suited for preliminary species identification and, lends itself nicely to epidemiological investigations providing information more quickly than other time-honoured methods traditionally used in these types of analyses.</p

    High resolution clustering of Salmonella enterica serovar Montevideo strains using a next-generation sequencing approach

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    <p>Abstract</p> <p>Background</p> <p>Next-Generation Sequencing (NGS) is increasingly being used as a molecular epidemiologic tool for discerning ancestry and traceback of the most complicated, difficult to resolve bacterial pathogens. Making a linkage between possible food sources and clinical isolates requires distinguishing the suspected pathogen from an environmental background and placing the variation observed into the wider context of variation occurring within a serovar and among other closely related foodborne pathogens. Equally important is the need to validate these high resolution molecular tools for use in molecular epidemiologic traceback. Such efforts include the examination of strain cluster stability as well as the cumulative genetic effects of sub-culturing on these clusters. Numerous isolates of <it>S</it>. Montevideo were shot-gun sequenced including diverse lineage representatives as well as numerous replicate clones to determine how much variability is due to bias, sequencing error, and or the culturing of isolates. All new draft genomes were compared to 34 <it>S</it>. Montevideo isolates previously published during an NGS-based molecular epidemiological case study.</p> <p>Results</p> <p>Intraserovar lineages of <it>S</it>. Montevideo differ by thousands of SNPs, that are only slightly less than the number of SNPs observed between <it>S</it>. Montevideo and other distinct serovars. Much less variability was discovered within an individual <it>S</it>. Montevideo clade implicated in a recent foodborne outbreak as well as among individual NGS replicates. These findings were similar to previous reports documenting homopolymeric and deletion error rates with the Roche 454 GS Titanium technology. In no case, however, did variability associated with sequencing methods or sample preparations create inconsistencies with our current phylogenetic results or the subsequent molecular epidemiological evidence gleaned from these data.</p> <p>Conclusions</p> <p>Implementation of a validated pipeline for NGS data acquisition and analysis provides highly reproducible results that are stable and predictable for molecular epidemiological applications. When draft genomes are collected at 15×-20× coverage and passed through a quality filter as part of a data analysis pipeline, including sub-passaged replicates defined by a few SNPs, they can be accurately placed in a phylogenetic context. This reproducibility applies to all levels within and between serovars of <it>Salmonella </it>suggesting that investigators using these methods can have confidence in their conclusions.</p

    Preliminary evaluation of a novel method for computed tomography quantification of lumbosacral articular process displacement in dogs with and without degenerative lumbosacral stenosis

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    ObjectiveThis study aimed to describe the diagnostic discrimination and reliability of a novel technique for quantifying lumbosacral articular process displacement (LSAPD) on dorsal plane computed tomography (DPCT) imaging in dogs with and without degenerative lumbosacral stenosis (DLSS).Study designDPCT surveys of the lumbosacral vertebral column were performed with dogs positioned in extension and flexion. LSAPD is defined as the distance between the cranial aspects of the L7 and S1 articular processes. The LSAPD ratio is identified by dividing the LSAPD by the length of the L7 articular process. Intraclass correlation coefficients (ICCs) for intra- and inter-observer reliability were calculated, and logistic regressions were used to test for the association of LSAPD and LSAPD ratio with odds of DLSS. Significance was set at 0.05. Receiver operator characteristic (ROC) curves were calculated to determine diagnostic discrimination and optimal cutoff for LSAPD and LSAPD ratio in the diagnosis of DLSS.ResultsIntra- and inter-observer reliabilities were excellent for most measurements. In the current cohort, excluding covariates, the area under the curve (AUC) (95%CI) for LSAPD and LSAPD ratio measured in a flexed position were both 0.89 (0.82–0.96), suggesting potentially excellent discrimination for using this measurement as a marker for diagnosing DLSS, pending further studies. The cutoffs for flexed LSAPD and LSAPD ratio that maximizes Youden’s index were ≥ 1.2 mm and ≥ 9%, respectively. When age and weight were subsequently included as covariates in a multivariable analysis, a significant relationship between LSAPD or LSAPD ratio and odds of diagnosis of DLSS was not demonstrated, suggesting the need for a larger sample size.ConclusionThe results of this study suggest that measurements of LSAPD and LSAPD ratio on DPCT are feasible and reliable, although their diagnostic discrimination in DLSS should be evaluated further in future prospective studies

    Chemical interrogation of nuclear size identifies compounds with cancer cell line specific effects on migration and invasion

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    [Image: see text] Background: Lower survival rates for many cancer types correlate with changes in nuclear size/scaling in a tumor-type/tissue-specific manner. Hypothesizing that such changes might confer an advantage to tumor cells, we aimed at the identification of commercially available compounds to guide further mechanistic studies. We therefore screened for Food and Drug Administration (FDA)/European Medicines Agency (EMA)-approved compounds that reverse the direction of characteristic tumor nuclear size changes in PC3, HCT116, and H1299 cell lines reflecting, respectively, prostate adenocarcinoma, colonic adenocarcinoma, and small-cell squamous lung cancer. Results: We found distinct, largely nonoverlapping sets of compounds that rectify nuclear size changes for each tumor cell line. Several classes of compounds including, e.g., serotonin uptake inhibitors, cyclo-oxygenase inhibitors, β-adrenergic receptor agonists, and Na(+)/K(+) ATPase inhibitors, displayed coherent nuclear size phenotypes focused on a particular cell line or across cell lines and treatment conditions. Several compounds from classes far afield from current chemotherapy regimens were also identified. Seven nuclear size-rectifying compounds selected for further investigation all inhibited cell migration and/or invasion. Conclusions: Our study provides (a) proof of concept that nuclear size might be a valuable target to reduce cell migration/invasion in cancer treatment and (b) the most thorough collection of tool compounds to date reversing nuclear size changes specific to individual cancer-type cell lines. Although these compounds still need to be tested in primary cancer cells, the cell line-specific nuclear size and migration/invasion responses to particular drug classes suggest that cancer type-specific nuclear size rectifiers may help reduce metastatic spread

    Gender Differences in Russian Colour Naming

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    In the present study we explored Russian colour naming in a web-based psycholinguistic experiment (http://www.colournaming.com). Colour singletons representing the Munsell Color Solid (N=600 in total) were presented on a computer monitor and named using an unconstrained colour-naming method. Respondents were Russian speakers (N=713). For gender-split equal-size samples (NF=333, NM=333) we estimated and compared (i) location of centroids of 12 Russian basic colour terms (BCTs); (ii) the number of words in colour descriptors; (iii) occurrences of BCTs most frequent non-BCTs. We found a close correspondence between females’ and males’ BCT centroids. Among individual BCTs, the highest inter-gender agreement was for seryj ‘grey’ and goluboj ‘light blue’, while the lowest was for sinij ‘dark blue’ and krasnyj ‘red’. Females revealed a significantly richer repertory of distinct colour descriptors, with great variety of monolexemic non-BCTs and “fancy” colour names; in comparison, males offered relatively more BCTs or their compounds. Along with these measures, we gauged denotata of most frequent CTs, reflected by linguistic segmentation of colour space, by employing a synthetic observer trained by gender-specific responses. This psycholinguistic representation revealed females’ more refined linguistic segmentation, compared to males, with higher linguistic density predominantly along the redgreen axis of colour space

    Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales

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    We thank Dave Kelly from Albasoft for his support with making primary care data available, and Lynn Morrice, Wendy Inglis Humphrey, and Laura Gonzalez Rienda for their support with project management and administration. This work uses data provided by patients and collected by the NHS as part of their care and support. We would also like to acknowledge all data providers who make anonymised data available for research. We wish to acknowledge the collaborative partnership that enabled acquisition and access to the de-identified data in Wales, which led to this output. The collaboration was led by the Swansea University Health Data Research UK team under the direction of the Welsh Government Technical Advisory Cell and includes the following groups and organisations: the Secure Anonymised Information Linkage Databank, Administrative Data Research Wales, NHS Wales Informatics Service, Public Health Wales, NHS Shared Services Partnership, and the Welsh Ambulance Service Trust. All research conducted has been completed under the permission and approval of the Secure Anonymised Information Linkage Independent Information Governance Review Panel (project number: 0911). We acknowledge the help provided by the staff of the Honest Broker Service (HBS) within the Business Services Organisation Northern Ireland (BSO). The HBS is funded by the BSO and the Department of Health. The authors alone are responsible for the interpretation of the data and any views or opinions presented are solely those of the author and do not necessarily represent those of the BSO. Research in Northern Ireland was conducted under approval by the HBS Governance Board approval number 064. KK is supported by the National Institute for Health Research Applied Research Collaboration East Midlands and Leicester Biomedical Research Centre. This work was supported by the UK Research and Innovation National Core Studies: Data and Connectivity (MC_PC_20029 or MC_PC_20058), with further support from Health Data Research UK (HDR UK), an initiative funded by UK Research and Innovation, Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities. This work was also carried out with the support of the BHF Data Science Centre at HDR UK (SP/19/3/34678). This study makes use of de-identified data held in NHS England's Secure Data Environment service for England and made available via the BHF Data Science Centre's CVD-COVID-UK/COVID-IMPACT consortium. The BHF Data Science Centre (grant No SP/19/3/34678, awarded to HDR UK) funded co-development (with NHS England) of the trusted research environment, provision of linked datasets, data access, user software licences, computational usage, and data management and wrangling support, with additional contributions from the HDR UK Data and Connectivity component of the UK Government Chief Scientific Adviser's National Core Studies programme to coordinate national COVID-19 priority research. Consortium partner organisations funded the time of contributing data analysts, biostatisticians, epidemiologists, and clinicians.Peer reviewe

    Securitization and lending standards: Evidence from the European wholesale loan market

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    We assess the relative effect of securitization activity on banks’ lending rates employing a uniquely detailed dataset from the euro-denominated syndicated loan market. We find that in the run-up to the 2007–2009 crisis banks more active at originating asset-backed securities did not price their loans more aggressively (i.e. with narrower lending spreads) than non-active banks. We show that also within the set of loans that were previously securitized, the relative level of securitization activity by the originating bank is not related to narrower lending spreads. Our findings, which are limited to the cross-sectional impact of securitization, suggest that the effect of securitization on the cost of corporate funding appears to be quite limited

    Undervaccination and severe COVID-19 outcomes : meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales

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    Background: Undervaccination (receiving fewer than the recommended number of SARS-CoV-2 vaccine doses) could be associated with increased risk of severe COVID-19 outcomes—ie, COVID-19 hospitalisation or death—compared with full vaccination (receiving the recommended number of SARS-CoV-2 vaccine doses). We sought to determine the factors associated with undervaccination, and to investigate the risk of severe COVID-19 outcomes in people who were undervaccinated in each UK nation and across the UK. Methods: We used anonymised, harmonised electronic health record data with whole population coverage to carry out cohort studies in England, Northern Ireland, Scotland, and Wales. Participants were required to be at least 5 years of age to be included in the cohorts. We estimated adjusted odds ratios for undervaccination as of June 1, 2022. We also estimated adjusted hazard ratios (aHRs) for severe COVID-19 outcomes during the period June 1 to Sept 30, 2022, with undervaccination as a time-dependent exposure. We combined results from nation-specific analyses in a UK-wide fixed-effect meta-analysis. We estimated the reduction in severe COVID-19 outcomes associated with a counterfactual scenario in which everyone in the UK was fully vaccinated on June 1, 2022. Findings: The numbers of people undervaccinated on June 1, 2022 were 26 985 570 (45·8%) of 58 967 360 in England, 938 420 (49·8%) of 1 885 670 in Northern Ireland, 1 709 786 (34·2%) of 4 992 498 in Scotland, and 773 850 (32·8%) of 2 358 740 in Wales. People who were younger, from more deprived backgrounds, of non-White ethnicity, or had a lower number of comorbidities were less likely to be fully vaccinated. There was a total of 40 393 severe COVID-19 outcomes in the cohorts, with 14 156 of these in undervaccinated participants. We estimated the reduction in severe COVID-19 outcomes in the UK over 4 months of follow-up associated with a counterfactual scenario in which everyone was fully vaccinated on June 1, 2022 as 210 (95% CI 94–326) in the 5–15 years age group, 1544 (1399–1689) in those aged 16–74 years, and 5426 (5340–5512) in those aged 75 years or older. aHRs for severe COVID-19 outcomes in the meta-analysis for the age group of 75 years or older were 2·70 (2·61–2·78) for one dose fewer than recommended, 3·13 (2·93–3·34) for two fewer, 3·61 (3·13–4·17) for three fewer, and 3·08 (2·89–3·29) for four fewer. Interpretation: Rates of undervaccination against COVID-19 ranged from 32·8% to 49·8% across the four UK nations in summer, 2022. Undervaccination was associated with an elevated risk of severe COVID-19 outcomes. Funding: UK Research and Innovation National Core Studies: Data and Connectivity
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