Comparison of K-doped and pure cold-rolled tungsten sheets: As-rolled condition and recrystallization behaviour after isochronal annealing at different temperatures

Severely deformed cold-rolled tungsten is a promising structural material for future fusion reactor applications due to high melting temperature and excellent mechanical properties. However, the fine-grained microstructure after deformation is not stable at temperatures above 800 °C, leading to brittle material behaviour. In this study, we utilize potassium-doping to inhibit recrystallization of tungsten sheets, a mechanism well known from incandescent lamp wires. We produced K-doped tungsten sheets by warm-rolling and subsequent cold-rolling with five different logarithmic strains up to 4.6, and equivalently rolled pure tungsten sheets. Both sets of materials are compared using EBSD and microhardness testing. In both materials, the hardness increases and the grain size along normal direction decreases with strain; the densities of low and high angle boundaries increase in particular during cold-rolling. The K-doped W sheet reaches the highest hardness with 772 ± 8 HV0.1, compared to the pure W sheet with 711 ± 14 HV0.1. All boundaries taken into account, a Hall-Petch relation describes the hardness evolution nicely, except a deviation of the K-doped tungsten sheet rolled to highest strain with its much higher hardness. The similar structural and mechanical properties of both materials in the as-rolled condition allow further studies of recrystallization behaviour of the new K-doped material with a benchmark against the equivalent pure tungsten sheets. Isochronal annealing for 1 h was performed at different temperatures between 700 °C and 2200 °C. A sharp decrease in hardness to intermediate values is observed at around 900 °C for both materials, presumably reflecting extended recovery. A second decrease is observed at 1400 °C for pure tungsten, approaching the hardness of a single crystal and indicating recrystallization and severe growth of grains. For K-doped tungsten, however, the occurrence of the second decrease is shifted to higher temperatures from 1400 °C to 1800 °C with increasing strain and an intermediate hardness is maintained up to 1800 °C. We refer this dependence of the recrystallization resistance on strain in the K-doped material to the dispersion of K-bubbles, resulting in increased Zener pinning forces retarding boundary motion

CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome.

Multiple genome-wide studies have identified associations between outcome of human immunodeficiency virus (HIV) infection and polymorphisms in and around the gene encoding the HIV co-receptor CCR5, but the functional basis for the strongest of these associations, rs1015164A/G, is unknown. We found that rs1015164 marks variation in an activating transcription factor 1 binding site that controls expression of the antisense long noncoding RNA (lncRNA) CCR5AS. Knockdown or enhancement of CCR5AS expression resulted in a corresponding change in CCR5 expression on CD4+ T cells. CCR5AS interfered with interactions between the RNA-binding protein Raly and the CCR5 3' untranslated region, protecting CCR5 messenger RNA from Raly-mediated degradation. Reduction in CCR5 expression through inhibition of CCR5AS diminished infection of CD4+ T cells with CCR5-tropic HIV in vitro. These data represent a rare determination of the functional importance of a genome-wide disease association where expression of a lncRNA affects HIV infection and disease progression

High-fat diet impact on intestinal cholesterol conversion by the microbiota and serum cholesterol levels

Cholesterol-to-coprostanol conversion by the intestinal microbiota has been suggested to reduce intestinal and serum cholesterol availability, but the relationship between intestinal cholesterol conversion and the gut microbiota, dietary habits, and serum lipids has not been characterized in detail. We measured conserved proportions of cholesterol high and low-converter types in individuals with and without obesity from two distinct, independent low-carbohydrate high-fat (LCHF) dietary intervention studies. Across both cohorts, cholesterol conversion increased in previous low-converters after LCHF diet and was positively correlated with the fecal relative abundance of Eubacterium coprostanoligenes. Lean cholesterol high-converters had increased serum triacylglycerides and decreased HDL-C levels before LCHF diet and responded to the intervention with increased LDL-C, independently of fat, cholesterol, and saturated fatty acid intake. Our findings identify the cholesterol high-converter type as a microbiome marker, which in metabolically healthy lean individuals is associated with increased LDL-C in response to LCHF.publishedVersio

Depletion of B2 but Not B1a B Cells in BAFF Receptor-Deficient ApoE−/− Mice Attenuates Atherosclerosis by Potently Ameliorating Arterial Inflammation

We have recently identified conventional B2 cells as atherogenic and B1a cells as atheroprotective in hypercholesterolemic ApoE−/− mice. Here, we examined the development of atherosclerosis in BAFF-R deficient ApoE−/− mice because B2 cells but not B1a cells are selectively depleted in BAFF-R deficient mice. We fed BAFF-R−/− ApoE−/− (BaffR.ApoE DKO) and BAFF-R+/+ApoE−/− (ApoE KO) mice a high fat diet (HFD) for 8-weeks. B2 cells were significantly reduced by 82%, 81%, 94%, 72% in blood, peritoneal fluid, spleen and peripheral lymph nodes respectively; while B1a cells and non-B lymphocytes were unaffected. Aortic atherosclerotic lesions assessed by oil red-O stained-lipid accumulation and CD68+ macrophage accumulation were decreased by 44% and 50% respectively. B cells were absent in atherosclerotic lesions of BaffR.ApoE DKO mice as were IgG1 and IgG2a immunoglobulins produced by B2 cells, despite low but measurable numbers of B2 cells and IgG1 and IgG2a immunoglobulin concentrations in plasma. Plasma IgM and IgM deposits in atherosclerotic lesions were also reduced. BAFF-R deficiency in ApoE−/− mice was also associated with a reduced expression of VCAM-1 and fewer macrophages, dendritic cells, CD4+ and CD8+ T cell infiltrates and PCNA+ cells in lesions. The expression of proinflammatory cytokines, TNF-α, IL1-β and proinflammatory chemokine MCP-1 was also reduced. Body weight and plasma cholesterols were unaffected in BaffR.ApoE DKO mice. Our data indicate that B2 cells are important contributors to the development of atherosclerosis and that targeting the BAFF-R to specifically reduce atherogenic B2 cell numbers while preserving atheroprotective B1a cell numbers may be a potential therapeutic strategy to reduce atherosclerosis by potently reducing arterial inflammation