614 research outputs found

    Using variograms to detect and attribute hydrological change

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    There have been many published studies aiming to identify temporal changes in river flow time series, most of which use monotonic trend tests such as the Mann–Kendall test. Although robust to both the distribution of the data and incomplete records, these tests have important limitations and provide no information as to whether a change in variability mirrors a change in magnitude. This study develops a new method for detecting periods of change in a river flow time series, using temporally shifting variograms (TSVs) based on applying variograms to moving windows in a time series and comparing these to the long-term average variogram, which characterises the temporal dependence structure in the river flow time series. Variogram properties in each moving window can also be related to potential meteorological drivers. The method is applied to 91 UK catchments which were chosen to have minimal anthropogenic influences and good quality data between 1980 and 2012 inclusive. Each of the four variogram parameters (range, sill and two measures of semi-variance) characterise different aspects of the river flow regime, and have a different relationship with the precipitation characteristics. Three variogram parameters (the sill and the two measures of semi-variance) are related to variability (either day-to-day or over the time series) and have the largest correlations with indicators describing the magnitude and variability of precipitation. The fourth (the range) is dependent on the relationship between the river flow on successive days and is most correlated with the length of wet and dry periods. Two prominent periods of change were identified: 1995–2001 and 2004–2012. The first period of change is attributed to an increase in the magnitude of rainfall whilst the second period is attributed to an increase in variability of the rainfall. The study demonstrates that variograms have considerable potential for application in the detection and attribution of temporal variability and change in hydrological systems

    A Comparison of the Genetic Factors Influencing Host Response to Infection with One of Two Isolates of Porcine Reproductive and Respiratory Syndrome Virus

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    Host genetic differences in viral load (VL) and weight gain (WG) during porcine reproductive and respiratory syndrome virus (PRRSV) challenge were assessed for thirteen trials of ~200 commercial crossbred piglets each, from several different commercial suppliers. Piglets were experimentally infected with PRRSV isolates NVSL-97-7895 (NVSL) or KS-2006-72109 (KS06). VL and WG were moderately heritable and were antagonistically related for both virus isolates. The genetic correlation of host response to NVSL with host response to KS06 was high for both VL and WG. Consistent with previous findings, animals that were heterozygous (AB) for the WUR10000125 (WUR) marker on Chromosome 4 (SSC4) had significantly lower VL than their AA counterparts when infected with either virus isolate; however, a significant increase in WG was only observed when piglets were infected with the NVSL isolate. These results suggest that selecting for increased resistance or reduced susceptibility to PRRSV may be effective across virus isolates. Selecting for the AB genotype for WUR is expected to reduce VL across PRRSV isolates but its effect on WG during infection may differ between virus isolates

    Validation of the Effects of a SNP on SSC4 Associated with Viral Load and Weight Gain in Piglets Experimentally Infected with a 2006 PRRS Virus Isolate

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    Host genetic differences in viral load (VL) and weight gain (WG) during challenge were assessed for five trials of ~200 commercial crossbred piglets each, all from different commercial suppliers. Piglets were experimentally infected with porcine reproductive and respiratory syndrome virus (PRRSV) isolate KS-2006-72109 in order to validate the effects of a SNP previously identified on SSC4 (WUR10000125), whereby AB individuals had increased WG and reduced VL when experimentally infected with PRRSV isolate NVSL-97-7895. VL was defined as the area under the curve of logged viremia from 0-21 dpi. WG was defined as the weight gained from 0-42 dpi. The SNP effects on VL and WG were assessed. AB individuals had higher WG and lower VL than AA individuals, suggesting this marker may be useful for genetic selection of pigs for increased resistance or reduced susceptibility to PRRSV isolates that differ genetically and possibly pathogenically

    Factors Associated with N-specific IgG Response in Piglets Experimentally Infected with Porcine Reproductive and Respiratory Syndrome Virus

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    This study examined serum porcine reproductive and respiratory syndrome virus (PRRSV) N protein-specific IgG levels from sera collected from 464 Large White-Landrace commercial crossbred piglets from three separate experimental infection trials with PRRSV isolate NVSL-97- 7895. IgG levels at 42 days post infection (dpi) were measured by fluorescent microsphere immunoassay, herein referred to as total antibody (tAb) response. tAb levels were assessed for an association with different disease-related traits, the presence of a heritable genetic component, and for genomic regions associated with tAb response. tAb response was negatively associated with viral load (VL) and weight gain from 28-42 dpi (WG) and positively associated with virus rebound (REB) and neutralizing antibody (nAb) levels. Furthermore, tAb response had a heritable genetic component, with a major QTL located on chromosome 7 in the major histocompatibility complex (MHC), whereby heterozygous individuals had a lower tAb response and increased weight gain from 28-42 dpi. These results suggest that genetic selection for tAb response may be useful for selecting for pigs that have increased resistance or reduced susceptibility to PRRSV

    Horizontal gene transfer contributed to the evolution of extracellular surface structures

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    The single-cell layered ectoderm of the fresh water polyp Hydra fulfills the function of an epidermis by protecting the animals from the surrounding medium. Its outer surface is covered by a fibrous structure termed the cuticle layer, with similarity to the extracellular surface coats of mammalian epithelia. In this paper we have identified molecular components of the cuticle. We show that its outermost layer contains glycoproteins and glycosaminoglycans and we have identified chondroitin and chondroitin-6-sulfate chains. In a search for proteins that could be involved in organising this structure we found PPOD proteins and several members of a protein family containing only SWT (sweet tooth) domains. Structural analyses indicate that PPODs consist of two tandem β-trefoil domains with similarity to carbohydrate-binding sites found in lectins. Experimental evidence confirmed that PPODs can bind sulfated glycans and are secreted into the cuticle layer from granules localized under the apical surface of the ectodermal epithelial cells. PPODs are taxon-specific proteins which appear to have entered the Hydra genome by horizontal gene transfer from bacteria. Their acquisition at the time Hydra evolved from a marine ancestor may have been critical for the transition to the freshwater environment

    Uranium and Radon in Private Bedrock Well Water in Maine: Geospatial Analysis at Two Scales

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    In greater Augusta of central Maine, 53 out of 1093 (4.8%) private bedrock well water samples from 1534 km² contained [U] > 30 μg/L, the U.S. Environmental Protection Agency’s (EPA) Maximum Contaminant Level (MCL) for drinking water; and 226 out of 786 (29%) samples from 1135 km² showed [Rn] > 4,000 pCi/L (148 Bq/L), the U.S. EPA’s Alternative MCL. Groundwater pH, calcite dissolution and redox condition are factors controlling the distribution of groundwater U but not Rn due to their divergent chemical and hydrological properties. Groundwater U is associated with incompatible elements (S, As, Mo, F, and Cs) in water samples within granitic intrusions. Elevated [U] and [Rn] are located within 5–10 km distance of granitic intrusions but do not show correlations with metamorphism at intermediate scales (10⁰−10¹ km). This spatial association is confirmed by a high-density sampling (n = 331, 5–40 samples per km²) at local scales (≤10–1 km) and the statewide sampling (n = 5857, 1 sample per 16 km²) at regional scales (10²–103 km). Wells located within 5 km of granitic intrusions are at risk of containing high levels of [U] and [Rn]. Approximately 48 800–63 900 and 324 000 people in Maine are estimated at risk of exposure to U (> 30 μg/L) and Rn (> 4000 pCi/L) in well water, respectively

    Lifelongα-tocopherol supplementation increases the median life span of C57BL/6 mice in the cold but has only minor effects on oxidative damage

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    The effects of dietary antioxidant supplementation on oxidative stress and life span are confused. We maintained C57BL/6 mice at 7 ± 2°C and supplemented their diet with α-tocopherol from 4 months of age. Supplementation significantly increased (p = 0.042) median life span by 15% (785 days, n = 44) relative to unsupplemented controls (682 days, n = 43) and also increased maximum life span (oldest 10%, p = 0.028). No sex or sex by treatment interaction effects were observed on life span, with treatment having no effect on resting or daily metabolic rate. Lymphocyte and hepatocyte oxidative DNA damage and hepatic lipid peroxidation were unaffected by supplementation, but hepatic oxidative DNA damage increased with age. Using a cDNA macroarray, genes associated with xenobiotic metabolism were significantly upregulated in the livers of female mice at 6 months of age (2 months supplementation). At 22 months of age (18 months supplementation) this response had largely abated, but various genes linked to the p21 signaling pathway were upregulated at this time. We suggest that α-tocopherol may initially be metabolized as a xenobiotic, potentially explaining why previous studies observe a life span extension generally when lifelong supplementation is initiated early in life. The absence of any significant effect on oxidative damage suggests that the life span extension observed was not mediated via any antioxidant properties of α-tocopherol. We propose that the life span extension observed following α-tocopherol supplementation may be mediated via upregulation of cytochrome p450 genes after 2 months of supplementation and/or upregulation of p21 signaling genes after 18 months of supplementation. However, these signaling pathways now require further investigation to establish their exact role in life span extension following α-tocopherol supplementation

    Factors Associated with Neutralizing Antibody Response in Piglets Experimentally Infected with Porcine Reproductive and Respiratory Virus

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    Host genetic differences and other factors associated with neutralizing antibody (NAb) response were examined in 464 Large White-Landrace piglets that were experimentally challenged with porcine reproductive and respiratory virus (PRRSv) isolate NVSL-97-7895. Serum samples and viremia data were collected on piglets periodically for 42 days post infection (dpi). NAb response was defined as the inverse of the highest 1:2 serial dilution of serum without cytopathic effects. Heritability and other factors associated with NAb response were estimated using an animal model in ASReml. These analyses identified two aspects of viremia that were associated with NAb response: viral load (area under the curve from 0-21 dpi) and virus rebound (a two Log increase in viremia after the virus had started to clear). These results also suggested that NAb response may be lowly heritable and provided the groundwork for further characterization of NAb response

    Insulin-like growth factor binding protein-3 has dual effects on gastrointestinal stromal tumor cell viability and sensitivity to the anti-tumor effects of imatinib mesylate in vitro

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    <p>Abstract</p> <p>Background</p> <p>Imatinib mesylate has significantly improved survival and quality of life of patients with gastrointestinal stromal tumors (GISTs). However, the molecular mechanism through which imatinib exerts its anti-tumor effects is not clear. Previously, we found up-regulation of insulin-like growth factor binding protein-3 (IGFBP3) expression in imatinib-responsive GIST cells and tumor samples. Because IGFBP3 regulates cell proliferation and survival and mediates the anti-tumor effects of a number of anti-cancer agents through both IGF-dependent and IGF-independent mechanisms, we hypothesized that IGFBP3 mediates GIST cell response to imatinib. To test this hypothesis, we manipulated IGFBP3 levels in two imatinib-responsive GIST cell lines and observed cell viability after drug treatment.</p> <p>Results</p> <p>In the GIST882 cell line, imatinib treatment induced endogenous IGFBP3 expression, and IGFBP3 down-modulation by neutralization or RNA interference resulted in partial resistance to imatinib. In contrast, IGFBP3 overexpression in GIST-T1, which had no detectable endogenous IGFBP3 expression after imatinib, had no effect on imatinib-induced loss of viability. Furthermore, both the loss of IGFBP3 in GIST882 cells and the overexpression of IGFBP3 in GIST-T1 cells was cytotoxic, demonstrating that IGFBP3 has opposing effects on GIST cell viability.</p> <p>Conclusion</p> <p>This data demonstrates that IGFBP3 has dual, opposing roles in modulating GIST cell viability and response to imatinib <it>in vitro</it>. These preliminary findings suggest that there may be some clinical benefits to IGFBP3 therapy in GIST patients, but further studies are needed to better characterize the functions of IGFBP3 in GIST.</p

    Applying Phenomenography to Develop a Comprehensive Understanding of Ethics in Engineering Practice

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    This Work-in-Progress Research paper describes (1) the contemporary research space on ethics education in engineering; (2) our long-term research plan; (3) the theoretical underpinnings of Phase 1 of our research plan (phenomenography); and (4) the design and developmental process of a phenomenographic interview protocol to explore engineers' experiences with ethics. Ethical behavior is a complex phenomenon that is complicated by the institutional and cultural contexts in which it occurs. Engineers also have varied roles and often work in a myriad of capacities that influence their experiences with and understanding of ethics in practice. We are using phenomenography, a qualitative research approach, to explore and categorize the ways engineers experience and understand ethical engineering practice. Specifically, phenomenography will allow us to systematically investigate the range and complexity of ways that engineers experience ethics in professional practice in the health products industry. Phenomenographic data will be obtained through a specialized type of semi-structured interview. Here we introduce the design of our interview protocol and its four sections: Background, Experience, Conceptual, and Summative. We also describe our iterative process for framing questions throughout each section
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