584 research outputs found

    Intense Electromagnetic Outbursts from Collapsing Hypermassive Neutron Stars

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    We study the gravitational collapse of a magnetized neutron star using a novel numerical approach able to capture both the dynamics of the star and the behavior of the surrounding plasma. In this approach, a fully general relativistic magnetohydrodynamics implementation models the collapse of the star and provides appropriate boundary conditions to a force-free model which describes the stellar exterior. We validate this strategy by comparing with known results for the rotating monopole and aligned rotator solutions and then apply it to study both rotating and non-rotating stellar collapse scenarios, and contrast the behavior with what is obtained when employing the electrovacuum approximation outside the star. The non-rotating electrovacuum collapse is shown to agree qualitatively with a Newtonian model of the electromagnetic field outside a collapsing star. We illustrate and discuss a fundamental difference between the force-free and electrovacuum solutions, involving the appearance of large zones of electric-dominated field in the vacuum case. This provides a clear demonstration of how dissipative singularities appear generically in the non-linear time-evolution of force-free fluids. In both the rotating and non-rotating cases, our simulations indicate that the collapse induces a strong electromagnetic transient. In the case of sub-millisecond rotation, the magnetic field experiences strong winding and the transient carries much more energy. This result has important implications for models of gamma-ray bursts.Comment: 28 pages, 20 figures (quality lowered to reduce sizes). Improved initial data and matching condition results in a lower, but still important, energy emission. Added appendix with a discussion on effects of transition laye

    Eight Weeks of a High Dose of Curcumin Supplementation May Attenuate Performance Decrements Following Muscle-Damaging Exercise

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    Background: It is known that unaccustomed exercise—especially when it has an eccentric component—causes muscle damage and subsequent performance decrements. Attenuating muscle damage may improve performance and recovery, allowing for improved training quality and adaptations. Therefore, the current study sought to examine the effect of two doses of curcumin supplementation on performance decrements following downhill running. Methods: Sixty-three physically active men and women (21 ± 2 y; 70.0 ± 13.7 kg; 169.3 ± 15.2 cm; 25.6 ± 14.3 body mass index (BMI), 32 women, 31 men) were randomly assigned to ingest 250 mg of CurcuWIN® (50 mg of curcuminoids), 1000 mg of CurcuWIN® (200 mg of curcuminoids), or a corn starch placebo (PLA) for eight weeks in a double-blind, randomized, placebo-controlled parallel design. At the end of the supplementation period, subjects completed a downhill running protocol intended to induce muscle damage. Muscle function using isokinetic dynamometry and perceived soreness was assessed prior to and at 1 h, 24 h, 48 h, and 72 h post-downhill run. Results: Isokinetic peak extension torque did not change in the 200-mg dose, while significant reductions occurred in the PLA and 50-mg groups through the first 24 h of recovery. Isokinetic peak flexion torque and power both decreased in the 50-mg group, while no change was observed in the PLA or 200-mg groups. All the groups experienced no changes in isokinetic extension power and isometric average peak torque. Soreness was significantly increased in all the groups compared to the baseline. Non-significant improvements in total soreness were observed for the 200-mg group, but these changes failed to reach statistical significance. Conclusion: When compared to changes observed against PLA, a 200-mg dose of curcumin attenuated reductions in some but not all observed changes in performance and soreness after completion of a downhill running bout. Additionally, a 50-mg dose appears to offer no advantage to changes observed in the PLA and 200-mg groups

    High-Throughput Screening Data Interpretation in the Context of In Vivo Transcriptomic Responses to Oral Cr(VI) Exposure

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    The toxicity of hexavalent chromium [Cr(VI)] in drinking water has been studied extensively, and available in vivo and in vitro studies provide a robust dataset for application of advanced toxicological tools to inform the mode of action (MOA). This study aimed to contribute to the understanding of Cr(VI) MOA by evaluating high-throughput screening (HTS) data and other in vitro data relevant to Cr(VI), and comparing these findings to robust in vivo data, including transcriptomic profiles in target tissues. Evaluation of Tox21 HTS data for Cr(VI) identified 11 active assay endpoints relevant to the Ten Key Characteristics of Carcinogens (TKCCs) that have been proposed by other investigators. Four of these endpoints were related to TP53 (tumor protein 53) activation mapping to genotoxicity (KCC#2), and four were related to cell death/proliferation (KCC#10). HTS results were consistent with other in vitro data from the Comparative Toxicogenomics Database. In vitro responses were compared to in vivo transcriptomic responses in the most sensitive target tissue, the duodenum, of mice exposed to ≤ 180 ppm Cr(VI) for 7 and 90 days. Pathways that were altered both in vitro and in vivo included those relevant to cell death/proliferation. In contrast, pathways relevant to p53/DNA damage were identified in vitro but not in vivo. Benchmark dose modeling and phenotypic anchoring of in vivo transcriptomic responses strengthened the finding that Cr(VI) causes cell stress/injury followed by proliferation in the mouse duodenum at high doses. These findings contribute to the body of evidence supporting a non-mutagenic MOA for Cr(VI)-induced intestinal cancer

    Comparison of the Effects of Hexavalent Chromium in the Alimentary Canal of F344 Rats and B6C3F1 Mice Following Exposure in Drinking Water: Implications for Carcinogenic Modes of Action

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    Exposure to high concentrations of hexavalent chromium (Cr[VI]) in drinking water is reported to induce oral mucosa tumors in F344 rats and intestinal tumors in B6C3F1 mice. To investigate the modes of action underlying these tumors, 90-day drinking water studies (with interim necropsy at day 8) were conducted with concentrations of 0.1–182 mg/l Cr(VI), administered as 0.3–520 mg/l sodium dichromate dihydrate. Blood and tissue samples were analyzed for chromium content, oxidative stress, iron levels, and gross and microscopic lesions. Results for the F344 rats are described herein and compared with results from B6C3F1 mice published previously. After 90 days of exposure, total chromium concentrations in the rat and mouse oral mucosae were comparable, yet significant dose-dependent decreases in the reduced-to-oxidized glutathione ratio (GSH/GSSG) were observed only in rats. In the duodenum, changes in GSH/GSSG were only observed in mice. Levels of 8-hydroxydeoxyguanosine were not increased in the oral or duodenal mucosae of either species. Glutathione levels were increased in the duodenum but decreased in the jejunum of both species, indicating potential differential responses in the intestinal segments. Histiocytic infiltration was observed in the duodenum of both species, yet duodenal cytokines were repressed in mice but increased in rats. Serum and bone marrow iron levels were more decreased in rats than mice. Collectively, these data suggest that Cr(VI)-induced carcinogenesis in the rodent alimentary canal involves oxidative stress; however, differences in histopathology, cytokines, and iron status suggest potential contributions from other factors as well

    A Targeted Conservation Approach for Improving Environmental Quality: Multiple Benefits and Expanded Opportunities

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    Find out how targeted conservation practices can have the most impact on environmental quality while causing only a small change in overall agricultural production. Environmental benefits are discussed related to clean air and water, productive soils, diverse wildlife and plant habitat, and biological controls for crop protection.https://lib.dr.iastate.edu/extension_ag_pubs/1084/thumbnail.jp

    Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

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    A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

    A scalable, fully automated process for construction of sequence-ready human exome targeted capture libraries

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    Genome targeting methods enable cost-effective capture of specific subsets of the genome for sequencing. We present here an automated, highly scalable method for carrying out the Solution Hybrid Selection capture approach that provides a dramatic increase in scale and throughput of sequence-ready libraries produced. Significant process improvements and a series of in-process quality control checkpoints are also added. These process improvements can also be used in a manual version of the protocol

    Comprehensive comparative analysis of strand-specific RNA sequencing methods

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    Strand-specific, massively parallel cDNA sequencing (RNA-seq) is a powerful tool for transcript discovery, genome annotation and expression profiling. There are multiple published methods for strand-specific RNA-seq, but no consensus exists as to how to choose between them. Here we developed a comprehensive computational pipeline to compare library quality metrics from any RNA-seq method. Using the well-annotated Saccharomyces cerevisiae transcriptome as a benchmark, we compared seven library-construction protocols, including both published and our own methods. We found marked differences in strand specificity, library complexity, evenness and continuity of coverage, agreement with known annotations and accuracy for expression profiling. Weighing each method's performance and ease, we identified the dUTP second-strand marking and the Illumina RNA ligation methods as the leading protocols, with the former benefitting from the current availability of paired-end sequencing. Our analysis provides a comprehensive benchmark, and our computational pipeline is applicable for assessment of future protocols in other organisms.Howard Hughes Medical InstituteUnited States-Israel Binational Science Foundatio
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