2,434 research outputs found

    Characterization and performance of an optical-relay switching system for cost-effective multichannel sensing arrays

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    Multisensor technology is now commonly used in many applications to monitor a wide range of complex systems. In many cases, the outputs from the individual sensors are multiplexed through relays or electronic switching systems into the detection and signal conditioning electronics so that only one set of measurement equipment is required. These switching systems are often very expensive and limited to relatively benign laboratory-type environments. Within the work presented here, the performance of commercial off-the-shelf (COTS) optical-relay ICs within a digital switching system is characterized to access their suitability in a cost-effective switching system. A low-cost (sub £(30) optical-relay switch system (ORSS) is developed and characterized that achieves remote switching speeds of over 2800 switches/s. Combining the ORSS with a sourcemeter results in measurement speeds of up to 66 sensors/s with less than 1% error compared with measuring the sensors individually. Finally, in demonstrating the application of the ORSS, multiple temperature sensors were used to monitor the temperature profile of a microcontroller board where a clear temperature profile for the individual components and the printed circuit board (PCB) is measured. Hence demonstrating that this ultrafast and cost-effective ORSS can be used for a wide area of applications including large-scale device characterization, monitoring multichannel sensors for workplace safety, or data acquisition in industry and academia

    The statistical mechanics of a polygenic characterunder stabilizing selection, mutation and drift

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    By exploiting an analogy between population genetics and statistical mechanics, we study the evolution of a polygenic trait under stabilizing selection, mutation, and genetic drift. This requires us to track only four macroscopic variables, instead of the distribution of all the allele frequencies that influence the trait. These macroscopic variables are the expectations of: the trait mean and its square, the genetic variance, and of a measure of heterozygosity, and are derived from a generating function that is in turn derived by maximizing an entropy measure. These four macroscopics are enough to accurately describe the dynamics of the trait mean and of its genetic variance (and in principle of any other quantity). Unlike previous approaches that were based on an infinite series of moments or cumulants, which had to be truncated arbitrarily, our calculations provide a well-defined approximation procedure. We apply the framework to abrupt and gradual changes in the optimum, as well as to changes in the strength of stabilizing selection. Our approximations are surprisingly accurate, even for systems with as few as 5 loci. We find that when the effects of drift are included, the expected genetic variance is hardly altered by directional selection, even though it fluctuates in any particular instance. We also find hysteresis, showing that even after averaging over the microscopic variables, the macroscopic trajectories retain a memory of the underlying genetic states.Comment: 35 pages, 8 figure

    Development of a non-cloggable subsea data logger for harsh turbidity current monitoring

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    Large submarine flows of sediment (sand and mud), known as turbidity currents, transfer and bury significant amounts of organic carbon and pollutants to the deep sea via submarine canyons. They are also significant geohazards, regularly breaking networks of seabed telecommunications cables that carry > 99% of global data that underpin the internet. Despite this, key parameters (notably their sediment concentration) in these flows are yet to be directly measured in real-time due to their inherently harsh environment that is unsuitable for commercial conductivity sensors. To address this issue, a subsea datalogger (SSDL) is developed with a planar conductivity sensor head that can measure the sediment concentration within dense turbidity currents. Unlike conventional sensors, the planar design of the SSDL’s sensor prevents clogging at high sediment concentrations, allowing for continuous measurements within turbidity currents. The conductivity sensor is developed with a temperature sensor which is measured using an external 16-Bit ADC which is controlled with a SAMD21 32-Bit ARM microcontroller. The SSDL measures the temperature and the conductivity of the seawater once every 4 seconds for over a year. In an initial device test, the SSDL can record a turbidity current within the Bute Inlet, Canada. It is found that the seawater’s conductivity increases with salinity concentration and decreases with sediment concentration. The SSDL developed here can thus be used for both conventional subsea datalogging applications and high turbidity current applications

    Laminin α4 contributes to airway remodeling and inflammation in asthma

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    Airway inflammation and remodeling are characteristic features of asthma, both contributing to airway hyperresponsiveness (AHR) and lung function limitation. Airway smooth muscle (ASM) accumulation and extracellular matrix deposition are characteristic features of airway remodeling, which may contribute to persistent AHR. Laminins containing the α2 chain contribute to characteristics of ASM remodeling in vitro and AHR in animal models of asthma. The role of other laminin chains, including the laminin α4 and α5 chains, which contribute to leukocyte migration in other diseases, is currently unknown. The aim of the current study was to investigate the role of these laminin chains in ASM function and in AHR, remodeling and inflammation in asthma. Expression of both laminin α4 and α5 was observed in the human and mouse ASM bundle. In vitro, laminin α4 was found to promote a pro-proliferative, pro-contractile and pro-fibrotic ASM cell phenotype. In line, treatment with laminin α4 and α5 function-blocking antibodies reduced allergen-induced increases in ASM mass in a mouse model of allergen-induced asthma. Moreover, eosinophilic inflammation was reduced by the laminin α4 function-blocking antibody as well. Using airway biopsies from healthy subjects and asthmatic patients, we found inverse correlations between ASM α4 chain expression and lung function and AHR, whereas eosinophil numbers correlated positively with expression of laminin α4 in the ASM bundle. This study for the first time indicates a prominent role for laminin α4 in ASM function and in inflammation, AHR and remodeling in asthma, whereas the role of laminin α5 is more subtle

    Processing of Chlamydia abortus polymorphic membrane protein 18D during the chlamydial developmental cycle

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    BACKGROUND: Chlamydia possess a unique family of autotransporter proteins known as the Polymorphic membrane proteins (Pmps). While the total number of pmp genes varies between Chlamydia species, all encode a single pmpD gene. In both Chlamydia trachomatis (C. trachomatis) and C. pneumoniae, the PmpD protein is proteolytically cleaved on the cell surface. The current study was carried out to determine the cleavage patterns of the PmpD protein in the animal pathogen C. abortus (termed Pmp18D). METHODOLOGY/PRINCIPAL FINDINGS: Using antibodies directed against different regions of Pmp18D, proteomic techniques revealed that the mature protein was cleaved on the cell surface, resulting in a100 kDa N-terminal product and a 60 kDa carboxy-terminal protein. The N-terminal protein was further processed into 84, 76 and 73 kDa products. Clustering analysis resolved PmpD proteins into three distinct clades with C. abortus Pmp18D, being most similar to those originating from C. psittaci, C. felis and C. caviae. CONCLUSIONS/SIGNIFICANCE: This study indicates that C. abortus Pmp18D is proteolytically processed at the cell surface similar to the proteins of C. trachomatis and C. pneumoniae. However, patterns of cleavage are species-specific, with low sequence conservation of PmpD across the genus. The absence of conserved domains indicates that the function of the PmpD molecule in chlamydia remains to be elucidated

    ‘Seeing the bigger picture’: a post-graduate online learning community facilitates political competence for occupational therapists

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    © 2019, © 2019 UCU. Occupational therapists are increasingly required to work beyond traditional health-care settings in new and emerging community roles. This study explored the learning experiences of a cohort of international students studying an online post-graduate module aimed at facilitating political competence. The evaluation used an ethnographic approach and methods included online data from online communication tools: semi-structured interviews, and tutors’ reflective diaries. Data were subjected to thematic analysis. Results showed shifts in students’ knowledge, skills and attitudes in seeing the bigger picture; developing collaborative partnerships and navigating the politics of practice at the margins of personal, political and professional positions. Themes from learning which promoted changes were interacting with online resources, valuing and sharing experiences, a safe and supportive environment, integrated learning and assessment, critical self and peer review. Importantly the democratic approach of online learning was shown to align with the principles of political and critical occupational therapy practice. Online learning within an international community can extend opportunities for developing professional knowledge and behaviours in the politics of community-based practice

    Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

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    Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases

    Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission.

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    Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.This work was supported by the Wellcome Trust Senior Research Fellowships 108070/Z/15/Z to MPW, 215515/Z/19/Z to SGB and 207498/Z/17/Z to IGG; Collaborative award 206298/B/17/Z to IGG; Principal Research Fellowship 210688/Z/18/Z to PJL; Investigator Award 200871/Z/16/Z to KGCS; Addenbrooke’s Charitable Trust (to MPW, SGB, IGG and PJL); the Medical Research Council (CSF MR/P008801/1 to NJM); NHS Blood and Transfusion (WPA15-02 to NJM); National Institute for Health Research (Cambridge Biomedical Research Centre at CUHNFT), to JRB, MET, AC and GD, Academy of Medical Sciences and the Health Foundation (Clinician Scientist Fellowship to MET), Engineering and Physical Sciences Research Council (EP/P031447/1 and EP/N031938/1 to RS),Cancer Research UK (PRECISION Grand Challenge C38317/A24043 award to JY). Components of this work were supported by the COVID-19 Genomics UK Consortium, (COG-UK), which is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institut
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