646 research outputs found

    Assessment of HY-8 and HEC-RAS Bridge Models for Large-Span Water-Encapsulating Structures

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    Current INDOT policy requires that culvert-like structures with spans greater than 20 ft be treated for purposes of hydraulic analysis as a bridge, and hence mandates the use of software such as HEC-RAS for predicting the headwater, rather than the culvert-specific software, HY-8. In this context, culvert-like structures are assumed to have a standard inlet geometry (e.g., such as those already modeled in HY-8) and a constant barrel geometry. The present study examines the technical basis of this policy, and whether the policy could be revised to allow the application of simpler culvert-hydraulics analysis and HY-8 to culvert-like structures with spans greater than 20 ft. Laboratory experiments were performed with model box culverts of span 1.5 ft and two streamwise lengths, 2.1 ft and 8 ft, and performance curves describing the variation of headwater with discharge were obtained. The effects of bed roughness, the presence or absence of a cover (if present, the rise was 0.5 ft), and a range of tailwater levels, were investigated. The laboratory observa­tions were compared with predictions by HY-8 and HEC-RAS models, and the model performance assessed. In general, HY-8 predictions were found to be as good as, and in some cases superior to, the HEC-RAS predictions, for both long and short culvert-like structures. This was attributed to the empirical information in HY-8 being more tailored to the specific standardized geometry of culvert-like structures, and the automatic inclusion of roughness effects, whereas HEC-RAS, at least when used with default coefficients and settings, relied on generic coefficients and neglected roughness effects. It was therefore recommended that a change in INDOT policy allowing large-span culvert-like structures to be analyzed using conventional culvert hydraulics would be technically justified for problems where the structure could be considered in isolation and accurate input data are available

    A Laboratory Study of Apron-Riprap Design for Small-Culvert Outlets

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    The present study investigated primarily the appropriate stone-sizing of on-grade riprap aprons, and more specifically whether the current INDOT design policy may be overly conservative especially within the context of smaller culverts. In the study, laboratory experiments were performed with two pipe diameters, D = 4.25 in (0.35 ft) and 5.75 in (0.48 ft), and four stone sizes, median diameters estimated to be d50 = 0.61 in, 1.22 in, 1.73 in, and 2.24 in, for a range of discharges and tailwater depths. Video records were made of the laboratory apron to detect stone-mobilization events, and stable and unstable cases were distinguished. Logistic regression was then applied to develop equations delineating the boundary between stable and unstable regions for different riprap size classes in terms of d50/D. These regression equations were then modified to ensure that they formed an ordered system in that each equation was more conservative than the next, to include a safety factor, and to set a minimum size for each size class consistent with the applicability of each equation. Procedures for applying the proposed equations are described. Compared to the current INDOT design policy, the proposed approach typically predicts a smaller standard riprap class required for apron stability. In an application to a sample of actual culverts, the proposed approach, including the recommended safety factors, yielded a smaller required standard INDOT riprap class in 75% of cases, but, in a small number of cases with very low relative tailwater depths, did recommend a more conservative design. Of the other two main approaches to stone sizing for riprap aprons, the HEC-14 model was rather restricted in its range of application, but where applicable it was found to be somewhat more conservative in its stone-size recommendation, though in practice the recommended riprap class largely agreed with the proposed approach. The results of the other main approach, that due to Bohan (1970), were more erratic, with the maximum-tailwater equation being too lax and the minimum-tailwater equation being generally too stringent. Both the HEC-14 and the Bohan models tended to be less conservative than the proposed approach for larger values of d50/D. A secondary aim of the study was an examination of the velocity field downstream of the outlet, and the possible implications for scour downstream of the apron. Point velocity measurements were obtained for four cases, all with the same 4.25-in diameter pipe, three of which involved the largest (d50 = 2.2 in) stone, and one over a smooth bed. In the three cases with a stone apron, the apron extended a distance of ≈9D downstream of the outlet. In all four cases, substantial velocities (maximum velociites greater than 70% of than the average outlet velocity) were observed beyond 4D (which is the minimum specified by INDOT design guidelines) and even beyond 8D (which is the largest apron length specified in HEC-14). A comparison between rough-bed and smooth-bed results indicated a measurable effect on maximum velocity due to the rough apron, but the reduction in maximum velocity is still likely insufficient to prevent scour downstream of the apron in most practical cases even if the apron extends to 9D

    Downregulation of APOBEC3G by xenotropic murine leukemia-virus related virus (XMRV) in prostate cancer cells

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    <p>Abstract</p> <p>Background</p> <p>Xenotropic murine leukemia virus (MLV)-related virus (XMRV) is a gammaretrovirus that was discovered in prostate cancer tissues. Recently, it has been proposed that XMRV is a laboratory contaminant and may have originated via a rare recombination event. Host restriction factor APOBEC3G (A3G) has been reported to severely restrict XMRV replication in human peripheral blood mononuclear cells. Interestingly, XMRV infects and replicates efficiently in prostate cancer cells of epithelial origin. It has been proposed that due to lack off or very low levels of A3G protein XMRV is able to productively replicate in these cells.</p> <p>Findings</p> <p>This report builds on and challenges the published data on the absence of A3G protein in prostate epithelial cells lines. We demonstrate the presence of A3G in prostate epithelial cell lines (LNCaP and DU145) by western blot and mass spectrometry. We believe the discrepancy in A3G detection is may be due to selection and sensitivity of A3G antibodies employed in the prior studies. Our results also indicate that XMRV produced from A3G expressing LNCaP cells can infect and replicate in target cells. Most importantly our data reveal downregulation of A3G in XMRV infected LNCaP and DU145 cells.</p> <p>Conclusions</p> <p>We propose that XMRV replicates efficiently in prostate epithelial cells by downregulating A3G expression. Given that XMRV lacks accessory proteins such as HIV-1 Vif that are known to counteract A3G function in human cells, our data suggest a novel mechanism by which retroviruses can counteract the antiviral effects of A3G proteins.</p

    Strand-specific single-cell methylomics reveals distinct modes of DNA demethylation dynamics during early mammalian development

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    DNA methylation (5mC) is central to cellular identity. The global erasure of 5mC from the parental genomes during preimplantation mammalian development is critical to reset the methylome of gametes to the cells in the blastocyst. While active and passive modes of demethylation have both been suggested to play a role in this process, the relative contribution of these two mechanisms to 5mC erasure remains unclear. Here, we report a single-cell method (scMspJI-seq) that enables strand-specific quantification of 5mC, allowing us to systematically probe the dynamics of global demethylation. When applied to mouse embryonic stem cells, we identified substantial cell-to-cell strand-specific 5mC heterogeneity, with a small group of cells displaying asymmetric levels of 5mCpG between the two DNA strands of a chromosome suggesting loss of maintenance methylation. Next, in preimplantation mouse embryos, we discovered that methylation maintenance is active till the 16-cell stage followed by passive demethylation in a fraction of cells within the early blastocyst at the 32-cell stage of development. Finally, human preimplantation embryos qualitatively show temporally delayed yet similar demethylation dynamics as mouse embryos. Collectively, these results demonstrate that scMspJI-seq is a sensitive and cost-effective method to map the strand-specific genome-wide patterns of 5mC in single cells. Erasure of DNA methylation from the parental genomes is critical to reset the methylome of differentiated gametes to pluripotent cells in the blastocyst. Here, the authors present a high-throughput single-cell method that enables strand-specific quantification of DNA methylation and identify distinct modes of DNA demethylation dynamics during early mammalian development

    Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells

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    Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large lamina-associated domains (LADs). We report a method to map NL contacts genome-wide in single human cells. Analysis of nearly 400 maps reveals a core architecture consisting of gene-poor LADs that contact the NL with high cell-to-cell consistency, interspersed by LADs with more variable NL interactions. The variable contacts tend to be cell-type specific and are more sensitive to changes in genome ploidy than the consistent contacts. Single-cell maps indicate that NL contacts involve multivalent interactions over hundreds of kilobases. Moreover, we observe extensive intra-chromosomal coordination of NL contacts, even over tens of megabases. Such coordinated loci exhibit preferential interactions as detected by Hi-C. Finally, the consistency of NL contacts is inversely linked to gene activity in single cells and correlates positively with the heterochromatic histone modification H3K9me3. These results highlight fundamental principles of single-cell chromatin organization.National Institutes of Health (U.S.) (Grant R01 GM114190)National Human Genome Research Institute (U.S.) (Grant R01 HG003143

    Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016

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    Background A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0–100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0–100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings In 2016, HAQ Index performance spanned from a high of 97·1 (95% UI 95·8–98·1) in Iceland, followed by 96·6 (94·9–97·9) in Norway and 96·1 (94·5–97·3) in the Netherlands, to values as low as 18·6 (13·1–24·4) in the Central African Republic, 19·0 (14·3–23·7) in Somalia, and 23·4 (20·2–26·8) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91·5 (89·1–93·6) in Beijing to 48·0 (43·4–53·2) in Tibet (a 43·5-point difference), while India saw a 30·8-point disparity, from 64·8 (59·6–68·8) in Goa to 34·0 (30·3–38·1) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4·8-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20·9-point to 17·0-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17·2-point to 20·4-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle- SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view—and subsequent provision—of quality health care for all populations.info:eu-repo/semantics/publishedVersio

    Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

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    Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis
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