232 research outputs found

    Model B4 : multi-decade creep and shrinkage prediction of traditional and modern concretes

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    To improve the sustainability of concrete infrastructure, engineers face the challenge of incorporating new concrete materials while pushing the expected design life beyond 100 years. The time-dependent creep and shrinkage response of concrete governs the serviceability and durability in this multi-decade time frame. It has been shown that current prediction equations for creep and shrinkage underestimate material deformations observed in structures outside of a laboratory environment. A new prediction model for creep and shrinkage is presented that can overcome some of the shortcomings of the current equations. The model represents an extension and systematic recalibration of model B3, a 1995 RILEM Recommendation, which derives its functional form from the phenomena of diffusion, chemical hydration, moisture sorption, and the evolution of micro-stresses in the cement structure. The model is calibrated through a joint optimization of a new enlarged laboratory test database and a new database of bridge deflection records to overcome the bias towards short-term behavior. A framework for considering effects of aggregates, admixtures, additives, and higher temperatures is also incorporated

    Inheritance, Biochemical Abnormalities, and Clinical Features of Feline Mucolipidosis II: The First Animal Model of Human I-Cell Disease

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    Mucolipidosis II (ML II), also called I-cell disease, is a unique lysosomal storage disease caused by deficient activity of the enzyme N-acetylglucosamine-1-phosphotransferase, which leads to a failure to internalize enzymes into lysosomes. We report on a colony of domestic shorthair cats with ML II that was established from a half-sibling male of an affected cat. Ten male and 9 female kittens out of 89 kittens in 26 litters born to clinically normal parents were affected; this is consistent with an autosomal recessive mode of inheritance. The activities of three lysosomal enzymes from affected kittens, compared to normal adult control cats, were high in serum (11-73 times normal) but low in cultured fibroblasts (9-56% of normal range) that contained inclusion bodies (I-cells), reflecting the unique enzyme defect in ML II. Serum lysosomal enzyme activities of adult obligate carriers were intermediate between normal and affected values. Clinical features in affected kittens were observed from birth and included failure to thrive, behavioral dullness, facial dysmorphia, and ataxia. Radiographic lesions included metaphyseal flaring, radial bowing, joint laxity, and vertebral fusion. In contrast to human ML II, diffuse retinal degeneration leading to blindness by 4 months of age was seen in affected kittens. All clinical signs were progressive and euthanasia or death invariably occurred within the first few days to 7 months of life, often due to upper respiratory disease or cardiac failure. The clinical and radiographic features, lysosomal enzyme activities, and mode of inheritance are homologous with ML II in humans. Feline ML II is currently the only animal model in which to study the pathogenesis of and therapeutic interventions for this unique storage diseas

    Power-Based Droop Control in DC Microgrids Enabling Seamless Disconnection From Upstream Grids

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    This paper proposes a local power-based droop controller for distributed energy resource converters in dc microgrids that are connected to upstream grids by grid-interface converters. During normal operation, the grid-interface converter imposes the microgrid bus voltage, and the proposed controller allows power flow regulation at distributed energy resource converters\u2019 output. On the other hand, during abnormal operation of the grid-interface converter (e.g., due to faults in the upstream grid), the proposed controller allows bus voltage regulation by droop control. Notably, the controller can autonomously convert from power flow control to droop control, without any need of bus voltage variation detection schemes or communication with other microgrid components, which enables seamless transitions between these two modes of operation. Considering distributed energy resource converters employing the power-based droop control, the operation modes of a single converter and of the whole microgrid are defined and investigated herein. The controller design is also introduced. Furthermore, the power sharing performance of this control approach is analyzed and compared with that of classical droop control. The experimental results from a laboratory-scale dc microgrid prototype are reported to show the final performances of the proposed power-based droop control

    Expression and Regulation of the Fkbp5 Gene in the Adult Mouse Brain

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    BACKGROUND: Chronic stress has been found to be a major risk factor for various human pathologies. Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, which is tightly regulated via, among others, the glucocorticoid receptor (GR). The activity of the GR is modulated by a variety of proteins, including the co-chaperone FK506 binding protein 51 (FKBP5). Although FKBP5 has been associated with risk for affective disorders and has been implicated in GR sensitivity, previous studies focused mainly on peripheral blood, while information about basal distribution and induction in the central nervous system are sparse. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we describe the basal expression pattern of Fkbp5 mRNA in the brain of adult male mice and show the induction of Fkbp5 mRNA via dexamethasone treatment or different stress paradigms. We could show that Fkbp5 is often, but not exclusively, expressed in regions also known for GR expression, for example the hippocampus. Furthermore, we were able to induce Fkbp5 expression via dexamethasone in the CA1 and DG subregions of the hippocampus, the paraventricular nucleus (PVN) and the central amygdala (CeA). Increase of Fkbp5 mRNA was also found after restrained stress and 24 hours of food deprivation in the PVN and the CeA, while in the hippocampus only food deprivation caused an increase in Fkbp5 mRNA. CONCLUSIONS/SIGNIFICANCE: Interestingly, regions with a low basal expression showed higher increase in Fkbp5 mRNA following induction than regions with high basal expression, supporting the hypothesis that GR sensitivity is, at least partly, mediated via Fkbp5. In addition, this also supports the use of Fkbp5 gene expression as a marker for GR sensitivity. In summary, we were able to give an overview of the basal expression of fkbp5 mRNA as well as to extend the findings of induction of Fkbp5 and its regulatory influence on GR sensitivity from peripheral blood to the brain

    Instrumentation and Measurement Strategy for the NOAA SENEX Aircraft Campaign as Part of the Southeast Atmosphere Study 2013

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    Natural emissions of ozone-and-aerosol-precursor gases such as isoprene and monoterpenes are high in the southeastern US. In addition, anthropogenic emissions are significant in the southeastern US and summertime photochemistry is rapid. The NOAA-led SENEX (Southeast Nexus) aircraft campaign was one of the major components of the Southeast Atmosphere Study (SAS) and was focused on studying the interactions between biogenic and anthropogenic emissions to form secondary pollutants. During SENEX, the NOAA WP-3D aircraft conducted 20 research flights between 27 May and 10 July 2013 based out of Smyrna, TN. Here we describe the experimental approach, the science goals and early results of the NOAA SENEX campaign. The aircraft, its capabilities and standard measurements are described. The instrument payload is summarized including detection limits, accuracy, precision and time resolutions for all gas-and-aerosol phase instruments. The inter-comparisons of compounds measured with multiple instruments on the NOAA WP-3D are presented and were all within the stated uncertainties, except two of the three NO 2 measurements. The SENEX flights included day- and nighttime flights in the southeastern US as well as flights over areas with intense shale gas extraction (Marcellus, Fayetteville and Haynesville shale). We present one example flight on 16 June 2013, which was a daytime flight over the Atlanta region, where several crosswind transects of plumes from the city and nearby point sources, such as power plants, paper mills and landfills, were flown. The area around Atlanta has large biogenic isoprene emissions, which provided an excellent case for studying the interactions between biogenic and anthropogenic emissions. In this example flight, chemistry in and outside the Atlanta plumes was observed for several hours after emission. The analysis of this flight showcases the strategies implemented to answer some of the main SENEX science questions

    Genome-Wide Progesterone Receptor Binding: Cell Type-Specific and Shared Mechanisms in T47D Breast Cancer Cells and Primary Leiomyoma Cells

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    Progesterone, via its nuclear receptor (PR), exerts an overall tumorigenic effect on both uterine fibroid (leiomyoma) and breast cancer tissues, whereas the antiprogestin RU486 inhibits growth of these tissues through an unknown mechanism. Here, we determined the interaction between common or cell-specific genome-wide binding sites of PR and mRNA expression in RU486-treated uterine leiomyoma and breast cancer cells.ChIP-sequencing revealed 31,457 and 7,034 PR-binding sites in breast cancer and uterine leiomyoma cells, respectively; 1,035 sites overlapped in both cell types. Based on the chromatin-PR interaction in both cell types, we statistically refined the consensus progesterone response element to G•ACA• • •TGT•C. We identified two striking differences between uterine leiomyoma and breast cancer cells. First, the cis-regulatory elements for HSF, TEF-1, and C/EBPα and β were statistically enriched at genomic RU486/PR-targets in uterine leiomyoma, whereas E2F, FOXO1, FOXA1, and FOXF sites were preferentially enriched in breast cancer cells. Second, 51.5% of RU486-regulated genes in breast cancer cells but only 6.6% of RU486-regulated genes in uterine leiomyoma cells contained a PR-binding site within 5 kb from their transcription start sites (TSSs), whereas 75.4% of RU486-regulated genes contained a PR-binding site farther than 50 kb from their TSSs in uterine leiomyoma cells. RU486 regulated only seven mRNAs in both cell types. Among these, adipophilin (PLIN2), a pro-differentiation gene, was induced via RU486 and PR via the same regulatory region in both cell types.Our studies have identified molecular components in a RU486/PR-controlled gene network involved in the regulation of cell growth, cell migration, and extracellular matrix function. Tissue-specific and common patterns of genome-wide PR binding and gene regulation may determine the therapeutic effects of antiprogestins in uterine fibroids and breast cancer

    Background ozone over the United States in summer: Origin, trend, and contribution to pollution episodes

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    Observations indicate that ozone (O3) concentrations in surface air over the United States in summer contain a 20–45 ppbv background contribution, presumably reflecting transport from outside the North American boundary layer. We use a three-dimensional global model of tropospheric chemistry driven by assimilated meteorological observations to investigate the origin of this background and to quantify its contribution to total surface O3 on both average and highly polluted summer days. The model simulation is evaluated with a suite of surface and aircraft observations over the United States from the summer of 1995. The model reproduces the principal features in the observed distributions of O3 and its precursors, including frequency distributions of O3 concentrations and the development of regional high-O3 episodes in the eastern United States. Comparison of simulations with 1995 versus 1980 global fossil fuel emissions indicates that the model captures the previously observed decrease in the high end of the O3 probability distribution in surface air over the United States (reflecting reduction of domestic hydrocarbon emissions) and the increase in the low end (reflecting, at least in the model, rising Asian emissions). In the model, background O3 produced outside of the North American boundary layer contributes an average 25–35 ppbv to afternoon O3 concentrations in surface air in the western United States. and 15–30 ppbv in the eastern United States during the summer of 1995. This background generally decays to below 15 ppbv during the stagnation conditions conducive to exceedances of the 8-hour 0.08 ppmv (80 ppbv) National Ambient Air Quality Standard (NAAQS) for O3. A high background contribution of 25–40 ppbv is found during 9% of these exceedances, reflecting convective mixing of free tropospheric O3 from aloft, followed by rapid production within the U.S. boundary layer. Anthropogenic emissions in Asia and Europe are found to increase afternoon O3 concentrations in surface air over the United States by typically 4–7 ppbv, under both average and highly polluted conditions. This enhancement is particularly large (up to 14 ppbv) for O3 concentrations in the 50–70 ppbv range, and would represent a major concern if the NAAQS were to be tightened
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