387 research outputs found

    Visualisation of trust and quality information for geospatial dataset selection and use:Drawing trust presentation comparisons with B2C e-Commerce

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    The evaluation of geospatial data quality and trustworthiness presents a major challenge to geospatial data users when making a dataset selection decision. Part of the problem arises from the inconsistent and patchy nature of data quality information, which makes intercomparison very difficult. Over recent years, the production and availability of geospatial data has significantly increased, facilitated by the recent explosion of Web-based catalogues, portals, standards and services, and by initiatives such as INSPIRE and GEOSS. Despite this significant growth in availability of geospatial data and the fact that geospatial datasets can, in many respects, be considered commercial products that are available for purchase online, consumer trust has to date received relatively little attention in the GIS domain. In this paper, we discuss how concepts of trust, trust models, and trust indicators (largely derived from B2C e-Commerce) apply to the GIS domain and to geospatial data selection and use. Our research aim is to support data users in more efficient and effective geospatial dataset selection on the basis of quality, trustworthiness and fitness for purpose. To achieve this, we propose a GEO label – a decision support mechanism that visually summarises availability of key geospatial data informational aspects. We also present a Web service that was developed to support generation of dynamic GEO label representations for datasets by combining producer metadata (from standard catalogues or other published locations) with structured user feedback

    Longitudinal plasma measures of trimethylamine N-Oxide and risk of atherosclerotic cardiovascular disease events in community-based older adults

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    Background Trimethylamine N‐oxide (TMAO) is a gut microbiota‐dependent metabolite of dietary choline, L‐carnitine, and phosphatidylcholine‐rich foods. On the basis of experimental studies and patients with prevalent disease, elevated plasma TMAO may increase risk of atherosclerotic cardiovascular disease (ASCVD). TMAO is also renally cleared and may interact with and causally contribute to renal dysfunction. Yet, how serial TMAO levels relate to incident and recurrent ASCVD in community‐based populations and the potential mediating or modifying role of renal function are not established. Methods and Results We investigated associations of serial measures of plasma TMAO, assessed at baseline and 7 years, with incident and recurrent ASCVD in a community‐based cohort of 4131 (incident) and 1449 (recurrent) older US adults. TMAO was measured using stable isotope dilution liquid chromatography–tandem mass spectrometry (laboratory coefficient of variation, <6%). Incident ASCVD (myocardial infarction, fatal coronary heart disease, stroke, sudden cardiac death, or other atherosclerotic death) was centrally adjudicated using medical records. Risk was assessed by multivariable Cox proportional hazards regression, including time‐varying demographics, lifestyle factors, medical history, laboratory measures, and dietary habits. Potential mediating effects and interaction by estimated glomerular filtration rate (eGFR) were assessed. During prospective follow‐up, 1766 incident and 897 recurrent ASCVD events occurred. After multivariable adjustment, higher levels of TMAO were associated with a higher risk of incident ASCVD, with extreme quintile hazard ratio (HR) compared with the lowest quintile=1.21 (95% CI, 1.02–1.42; P‐trend=0.029). This relationship appeared mediated or confounded by eGFR (eGFR‐adjusted HR, 1.07; 95% CI, 0.90–1.27), as well as modified by eGFR (P‐interaction <0.001). High levels of TMAO were associated with higher incidence of ASCVD in the presence of impaired renal function (eGFR <60 mL/min per 1.73 m2: HR, 1.56 [95% CI, 1.13–2.14]; P‐trend=0.007), but not normal or mildly reduced renal function (eGFR ≥60 mL/min per 1.73 m2: HR, 1.03 [95% CI, 0.85–1.25]; P‐trend=0.668). Among individuals with prior ASCVD, TMAO associated with higher risk of recurrent ASCVD (HR, 1.25 [95% CI, 1.01–1.56]; P‐trend=0.009), without significant modification by eGFR. Conclusions In this large community‐based cohort of older US adults, serial measures of TMAO were associated with higher risk of incident ASCVD, with apparent modification by presence of impaired renal function and with higher risk of recurrent ASCVD

    Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection

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    T cell responses precede antibody and may provide early control of infection. We analyzed the clonal basis of this rapid response following SARS-COV-2 infection. We applied T cell receptor (TCR) sequencing to define the trajectories of individual T cell clones immediately. In SARS-COV-2 PCR+ individuals, a wave of TCRs strongly but transiently expand, frequently peaking the same week as the first positive PCR test. These expanding TCR CDR3s were enriched for sequences functionally annotated as SARS-COV-2 specific. Epitopes recognized by the expanding TCRs were highly conserved between SARS-COV-2 strains but not with circulating human coronaviruses. Many expanding CDR3s were present at high frequency in pre-pandemic repertoires. Early response TCRs specific for lymphocytic choriomeningitis virus epitopes were also found at high frequency in the preinfection naive repertoire. High-frequency naive precursors may allow the T cell response to respond rapidly during the crucial early phases of acute viral infection

    Comparing Respondent-Driven Sampling and Targeted Sampling Methods of Recruiting Injection Drug Users in San Francisco

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    The objective of this article is to compare demographic characteristics, risk behaviors, and service utilization among injection drug users (IDUs) recruited from two separate studies in San Francisco in 2005, one which used targeted sampling (TS) and the other which used respondent-driven sampling (RDS). IDUs were recruited using TS (n = 651) and RDS (n = 534) and participated in quantitative interviews that included demographic characteristics, risk behaviors, and service utilization. Prevalence estimates and 95% confidence intervals (CIs) were calculated to assess whether there were differences in these variables by sampling method. There was overlap in 95% CIs for all demographic variables except African American race (TS: 45%, 53%; RDS: 29%, 44%). Maps showed that the proportion of IDUs distributed across zip codes were similar for the TS and RDS sample, with the exception of a single zip code that was more represented in the TS sample. This zip code includes an isolated, predominantly African American neighborhood where only the TS study had a field site. Risk behavior estimates were similar for both TS and RDS samples, although self-reported hepatitis C infection was lower in the RDS sample. In terms of service utilization, more IDUs in the RDS sample reported no recent use of drug treatment and syringe exchange program services. Our study suggests that perhaps a hybrid sampling plan is best suited for recruiting IDUs in San Francisco, whereby the more intensive ethnographic and secondary analysis components of TS would aid in the planning of seed placement and field locations for RDS

    The Pseudomonas Quinolone Signal (PQS) Balances Life and Death in Pseudomonas aeruginosa Populations

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    When environmental conditions deteriorate and become inhospitable, generic survival strategies for populations of bacteria may be to enter a dormant state that slows down metabolism, to develop a general tolerance to hostile parameters that characterize the habitat, and to impose a regime to eliminate damaged members. Here, we provide evidence that the pseudomonas quinolone signal (PQS) mediates induction of all of these phenotypes. For individual cells, PQS, an interbacterial signaling molecule of Pseudomonas aeruginosa, has both deleterious and beneficial activities: on the one hand, it acts as a pro-oxidant and sensitizes the bacteria towards oxidative and other stresses and, on the other, it efficiently induces a protective anti-oxidative stress response. We propose that this dual function fragments populations into less and more stress tolerant members which respond differentially to developing stresses in deteriorating habitats. This suggests that a little poison may be generically beneficial to populations, in promoting survival of the fittest, and in contributing to bacterial multi-cellular behavior. It further identifies PQS as an essential mediator of the shaping of the population structure of Pseudomonas and of its response to and survival in hostile environmental conditions

    The Pattern of R2 Retrotransposon Activity in Natural Populations of Drosophila simulans Reflects the Dynamic Nature of the rDNA Locus

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    The pattern and frequency of insertions that enable transposable elements to remain active in a population are poorly understood. The retrotransposable element R2 exclusively inserts into the 28S rRNA genes where it establishes long-term, stable relationships with its animal hosts. Previous studies with laboratory stocks of Drosophila simulans have suggested that control over R2 retrotransposition resides within the rDNA loci. In this report, we sampled 180 rDNA loci of animals collected from two natural populations of D. simulans. The two populations were found to have similar patterns of R2 activity. About half of the rDNA loci supported no or very low levels of R2 transcripts with no evidence of R2 retrotransposition. The remaining half of the rDNA loci had levels of R2 transcripts that varied in a continuous manner over almost a 100-fold range and did support new retrotransposition events. Structural analysis of the rDNA loci in 18 lines that spanned the range of R2 transcript levels in these populations revealed that R2 number and rDNA locus size varied 2-fold; however, R2 activity was not readily correlated with either of these parameters. Instead R2 activity was best correlated with the distribution of elements within the rDNA locus. Loci with no activity had larger contiguous blocks of rDNA units free of R2-insertions. These data suggest a model in which frequent recombination within the rDNA locus continually redistributes R2-inserted units resulting in changing levels of R2 activity within individual loci and persistent R2 activity within the population

    In Vivo Deficiency of Both C/EBPβ and C/EBPε Results in Highly Defective Myeloid Differentiation and Lack of Cytokine Response

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    The CCAAT/enhancer binding proteins (C/EBPs) are transcription factors involved in hematopoietic cell development and induction of several inflammatory mediators. Here, we generated C/EBPβ and C/EBPε double-knockout (bbee) mice and compared their phenotypes to those of single deficient (bbEE and BBee) and wild-type (BBEE) mice. The bbee mice were highly susceptible to fatal infections and died within 2–3 months. Morphologically, their neutrophils were blocked at the myelocytes/metamyelocytes stage, and clonogenic assays of bone marrow cells indicated a significant decrease in the number of myeloid colonies of the bbee mice. In addition, the proportion of hematopoietic progenitor cells [Lin(−)Sca1(+)c-Kit(+)] in the bone marrow of the bbee mice was significantly increased, reflecting the defective differentiation of the myeloid compartment. Furthermore, microarray expression analysis of LPS- and IFNγ-activated bone marrow-derived macrophages from bbee compared to single knockout mice revealed decreased expression of essential immune response-related genes and networks, including some direct C/EBP-targets such as Marco and Clec4e. Overall, the phenotype of the bbee mice is distinct from either the bbEE or BBee mice, demonstrating that both transcription factors are crucial for the maturation of neutrophils and macrophages, as well as the innate immune system, and can at least in part compensate for each other in the single knockout mice

    Zelda Binding in the Early Drosophila melanogaster Embryo Marks Regions Subsequently Activated at the Maternal-to-Zygotic Transition

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    The earliest stages of development in most metazoans are driven by maternally deposited proteins and mRNAs, with widespread transcriptional activation of the zygotic genome occurring hours after fertilization, at a period known as the maternal-to-zygotic transition (MZT). In Drosophila, the MZT is preceded by the transcription of a small number of genes that initiate sex determination, patterning, and other early developmental processes; and the zinc-finger protein Zelda (ZLD) plays a key role in their transcriptional activation. To better understand the mechanisms of ZLD activation and the range of its targets, we used chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq) to map regions bound by ZLD before (mitotic cycle 8), during (mitotic cycle 13), and after (late mitotic cycle 14) the MZT. Although only a handful of genes are transcribed prior to mitotic cycle 10, we identified thousands of regions bound by ZLD in cycle 8 embryos, most of which remain bound through mitotic cycle 14. As expected, early ZLD-bound regions include the promoters and enhancers of genes transcribed at this early stage. However, we also observed ZLD bound at cycle 8 to the promoters of roughly a thousand genes whose first transcription does not occur until the MZT and to virtually all of the thousands of known and presumed enhancers bound at cycle 14 by transcription factors that regulate patterned gene activation during the MZT. The association between early ZLD binding and MZT activity is so strong that ZLD binding alone can be used to identify active promoters and regulatory sequences with high specificity and selectivity. This strong early association of ZLD with regions not active until the MZT suggests that ZLD is not only required for the earliest wave of transcription but also plays a major role in activating the genome at the MZT
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