Physical properties of a nickel-base alloy prepared by isostatic pressing and sintering of the powdered metal *

The physical and mechanical properties of samples of a nickel-base alloy fabricated by powder metallurgy were determined. The particle sizes of the powders used to make the samples varied from –80/+ 200 mesh to –325 mesh. The compaction pressure varied from 138 to 414 MN/m 2 and the sintering temperature varied from 1150 to 1250°C. The shrinkage during processing, the porosity, tensile strength, yield strength, elongation, and elastic modulus were used to characterize the samples. The strength of the samples generally increased with decreasing particle size of the powder and increasing compaction pressure and sintering temperatures. The porosity and strength, therefore, could be varied over a wide range by controlling the various parameters. The properties of the samples prepared by powder metallurgy were compared with those of the cast alloy and compact bone. Conditions can be selected that will yield equivalent or better properties by powder metallurgy than by casting.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74945/1/j.1365-2842.1976.tb00939.x.pd

Characterization of porosity of isostatically pressed and sintered nickel-base powdered metal *

Characterization of the pore structure of compacted and sintered parts made from a nickel-base powder was accomplished using the mercury porosimetry method. The theoretical density values for the sintered specimens varied from 56.3 to 96.7% which corresponds to a porosity of 43.7 to 3.3%. A maximum interconnecting median pore diameter of 21 Μm resulted from a −80/+ 200 mesh powder compacted at 138 MN/ m 2 and sintered for 2 h at 1250°C. Photomicrographs of the same sample showed that it had a maximum pore diameter of 200 Μm. The interconnected pore volume decreased with decreasing particle size of the powder, increasing compaction pressure, and increasing sintering temperature. Mechanical properties of tensile strength, yield strength, elastic modulus and percentage elongation were correlated with the pore structure. Proper selection of particle size, compaction pressure, sintering times and sintering temperatures should permit parts with controlled porosity characteristics to be produced that possess adequate mechanical properties for application as implants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74821/1/j.1365-2842.1976.tb00947.x.pd

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits

Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease

BACKGROUND: DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts. METHODS: Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts. RESULTS: Among 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate<0.05). These CpGs map to genes with key roles in calcium regulation (ATP2B2, CASR, GUCA1B, HPCAL1), and genes identified in genome- and epigenome-wide studies of serum calcium (CASR), serum calcium-related risk of CHD (CASR), coronary artery calcified plaque (PTPRN2), and kidney function (CDH23, HPCAL1), among others. Mendelian randomization analyses supported a causal effect of DNA methylation on incident CHD; these CpGs map to active regulatory regions proximal to long non-coding RNA transcripts. CONCLUSION: Methylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe