985 research outputs found

    Digital analysis of liquid sloshing in rotationally symmetric tanks under weak gravitational fields. Volume 2 - Computational application

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    Digital analysis of liquid sloshing in rotational symmetric tanks under weak gravitational fields - Vol.

    Grazing Behaviour of Beef Steers Grazing Kentucky 31 Endophyte Infected Tall Fescue, Q4508-AR542 Novel Endophyte Tall Fescue, and Lakota Prairie Grass

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    Tall fescue is the most dominant grass used for pasture in the U.S. covering over 14 million ha. As a result, fescue toxicosis is a major concern among producers, especially during the summer months when the symptoms, such as reduced weight gains, are most pronounced. Producers need alternative forages for grazing cattle that do not have the negative effects associated with endophyte infected tall fescue. The objective of this experiment was to determine the grazing behaviour of cattle on Kentucky 31 endophyte infected (E+) tall fescue (Festuca arundinacea Schreb.), Q4508-AR542 (Q) novel endophyte tall fescue, and Lakota (L) prairie grass (Bromus catharticus)

    Ambient dose equivalent versus effective dose for quantifying stray radiation exposures to a patient receiving proton therapy for prostate cancer

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    The purpose of this study was to evaluate the suitability of the quantity ambient dose equivalent H*(10) as a conservative estimate of effective dose E for estimating stray radiation exposures to patients receiving passively scattered proton radiotherapy for cancer of the prostate. H*(10), which is determined from fluence free-in-air, is potentially useful because it is simpler to measure or calculate because it avoids the complexities associated with phantoms or patient anatomy. However, the suitability of H*(10) as a surrogate for E has not been demonstrated for exposures to high-energy neutrons emanating from radiation treatments with proton beams. The suitability was tested by calculating H*(10) and E for a proton treatment using a Monte Carlo model of a double-scattering treatment machine and a computerized anthropomorphic phantom. The calculated E for the simulated treatment was 5.5 mSv/Gy, while the calculated H*(10) at the isocenter was 10 mSv/Gy. A sensitivity analysis revealed that H*(10) conservatively estimated E for the interval of treatment parameters common in proton therapy for prostate cancer. However, sensitivity analysis of a broader interval of parameters suggested that H*(10) may underestimate E for treatments of other sites, particularly those that require large field sizes. Simulations revealed that while E was predominated by neutrons generated in the nozzle, neutrons produced in the patient contributed up to 40% to dose equivalent in near-field organs

    Use of Alkanes to Estimate Dry Matter Intake of Beef Steers Grazing High Quality Pastures

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    Pastures remain the most important source of nutrients for ruminant livestock and nutrition is critical to optimize animal production. The daily quantity of dry matter that is consumed by an animal is a critical measurement to make nutritional inferences about feed and subsequent animal response. Researchers are facing the dilemma that, while estimates of individual animal performance are readily obtained, it is still difficult to estimate the herbage intake of individual animals. The objectives of this experiment were to estimate forage intake in beef steers grazing tall fescue (Festuca arundinacea Schreb.) and alfalfa (Medicago sativa)/tall fescue pastures and to measure the recovery rate of artificial alkanes from a controlled release device under these conditions

    Identification of HLA-DRPheβ47 as the susceptibility marker of hypersensitivity to beryllium in individuals lacking the berylliosis-associated supratypic marker HLA-DPGluβ69

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    BACKGROUND: Susceptibility to beryllium (Be)-hypersensitivity (BH) has been associated with HLA-DP alleles carrying a glutamate at position 69 of the HLA-DP β-chain (HLA-DPGlu69) and with several HLA-DP, -DQ and -DR alleles and polymorphisms. However, no genetic associations have been found between BH affected subjects not carrying the HLA-DPGlu69 susceptibility marker. METHODS: In this report, we re-evaluated an already described patient populations after 7 years of follow-up including new 29 identified BH subjects. An overall population 36 berylliosis patients and 38 Be-sensitization without lung granulomas and 86 Be-exposed controls was analysed to assess the role of the individual HLA-class II polymorphisms associated with BH-susceptibility in HLA-DPGlu69 negative subjects by univariate and multivariate analysis. RESULTS: As previously observed in this population the HLA-DPGlu69 markers was present in higher frequency in berylliosis patients (31 out of 36, 86%) than in Be-sensitized (21 out of 38, 55%, p = 0.008 vs berylliosis) and 41 out of 86 (48%, p < 0.0001 vs berylliosis, p = 0.55 vs Be-sensitized) Be-exposed controls. However, 22 subjects presenting BH did not carry the HLA-DPGlu69 marker. We thus evaluated the contribution of all the HLA-DR, -DP and -DQ polymorphisms in determining BH susceptibility in this subgroup of HLA-Glu69 subjects. In HLA-DPGlu69-negatives a significant association with BH was found for the HLA-DQLeu26, for the HLA-DRB1 locus residues Ser13, Tyr26, His32, Asn37, Phe47 and Arg74 and for the HLA-DRB3 locus clusterized residues Arg11, Tyr26, Asp28, Leu38, Ser60 and Arg74. HLA-DRPhe47 (OR 2.956, p < 0.05) resulting independently associated with BH. Further, Be-stimulated T-cell proliferation in the HLA-DPGlu69-negative subjects (all carrying HLA-DRPhe47) was inhibited by the anti-HLA-DR antibody (range 70–92% inhibition) significantly more than by the anti-HLA-DP antibody (range: 6–29%; p < 0.02 compared to anti-HLA-DR) while it was not affected by the anti-HLA-DQ antibody. CONCLUSION: We conclude that HLA-DPGlu69 is the primary marker of Be-hypersensitivity and HLA-DRPhe47 is associated with BH in Glu69-negative subjects, likely playing a role in Be-presentation and sensitization

    Sequence analysis and characterization of active human alu subfamilies based on the 1000 genomes pilot project

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    © The Author(s) 2015. The goal of the 1000 Genomes Consortium is to characterize human genome structural variation (SV), including forms of copy number variations such as deletions, duplications, and insertions. Mobile element insertions, particularly Alu elements, are major contributors to genomic SV among humans. During the pilot phase of the project we experimentally validated 645 (611 intergenic and 34 exon targeted) polymorphic young Alu insertion events, absent fromthe human reference genome. Here, we report high resolution sequencing of 343 (322 unique) recent Alu insertion events, along with their respective target site duplications, precise genomic breakpoint coordinates, subfamily assignment, percent divergence, and estimated A-rich tail lengths.All the sequenced Alu lociwerederived from the Alu Y lineagewith no evidence of retrotransposition activity involving older Alu families (e.g., AluJandAluS). AluYa5 is currently themost active Alu subfamily in the human lineage, followed by AluYb8, andmany others including three newly identified subfamilieswe have termed AluYb7a3, AluYb8b1, and AluYa4a1. This report provides the structural details of 322 unique Alu variants from individual human genomes collectively adding about 100 kb of genomic variation. Many Alu subfamilies are currently active in human populations, including a surprising level of AluY retrotransposition. Human Alu subfamilies exhibit continuous evolution with potential drivers sprouting new Alu lineages

    Identification of beryllium-dependent peptides recognized by CD4+ T cells in chronic beryllium disease

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    Chronic beryllium disease (CBD) is a granulomatous disorder characterized by an influx of beryllium (Be)-specific CD4(+) T cells into the lung. The vast majority of these T cells recognize Be in an HLA-DP–restricted manner, and peptide is required for T cell recognition. However, the peptides that stimulate Be-specific T cells are unknown. Using positional scanning libraries and fibroblasts expressing HLA-DP2, the most prevalent HLA-DP molecule linked to disease, we identified mimotopes and endogenous self-peptides that bind to MHCII and Be, forming a complex recognized by pathogenic CD4(+) T cells in CBD. These peptides possess aspartic and glutamic acid residues at p4 and p7, respectively, that surround the putative Be-binding site and cooperate with HLA-DP2 in Be coordination. Endogenous plexin A peptides and proteins, which share the core motif and are expressed in lung, also stimulate these TCRs. Be-loaded HLA-DP2–mimotope and HLA-DP2–plexin A4 tetramers detected high frequencies of CD4(+) T cells specific for these ligands in all HLA-DP2(+) CBD patients tested. Thus, our findings identify the first ligand for a CD4(+) T cell involved in metal-induced hypersensitivity and suggest a unique role of these peptides in metal ion coordination and the generation of a common antigen specificity in CBD

    Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance.

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    BACKGROUND: Colorectal cancer (CRC) progression is associated with suppression of host cell-mediated immunity and local immune escape mechanisms. Our aim was to assess the immune function in terms of expression of TNF, IFNG and FOXP3 in CRC. METHODS: Sixty patients with CRC and 15 matched controls were recruited. TaqMan quantitative PCR and methylation-specific PCR was performed for expression and DNA methylation analysis of TNF, IFNG and FOXP3. Survival analysis was performed over a median follow-up of 48 months. RESULTS: TNF was suppressed in tumour and IFNG was suppressed in peripheral blood mononuclear cells (PBMCs) of patients with CRC. Tumours showed enhanced expression of FOXP3 and was significantly higher when tumour size was >38 mm (median tumour size; P=0.006, Mann-Whitney U-test). Peripheral blood mononuclear cell IFNG was suppressed in recurrent CRC (P=0.01). Methylated TNFpromoter (P=0.003) and TNFexon1 (P=0.001) were associated with significant suppression of TNF in tumours. Methylated FOXP3cpg was associated with significant suppression of FOXP3 in both PBMC (P=0.018) and tumours (P=0.010). Reduced PBMC FOXP3 expression was associated with significantly worse overall survival (HR=8.319, P=0.019). CONCLUSIONS: We have detected changes in the expression of immunomodulatory genes that could act as biomarkers for prognosis and future immunotherapeutic strategies
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