Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Effect of compositional variation on the synthesis of magnesite-chrome composite refractory

Magnesite-chrome composites have been prepared by utilizing sintered magnesite and friable chrome ore in presence of titania as additive. Three types of batch compositions containing 5% Cr2O3, 18% Cr2O3 and 30% Cr2O3 have been selected for developing mag-chrome composites. The aggregates were developed by first vibro milling the raw materials and then additives were incorporated in wt.% along with 5% PVA solution as binder to the different batches. It was then properly mixed by fluidized bed mixer and after sieving in 20-mesh BS sieve briquettes were formed uniaxially at a pressure of 100 MPa. The briquettes were first air dried and subsequently oven dried at 110 +/- 5 degreesC for 24 It. Finally, the green briquettes were fired at 1700 and 1750 degreesC in electrically program controlled muffle furnace. The physical properties as well as thermo-mechanical properties and microstructural studies of the sintered aggregates have been evaluated. The common feature observed in the microstructures is the exsolution of spine] phase in magnesia grains. The hot properties of the composites are superior when the Cr2O3 content is increased to 30%. Additives played a significant role in improving the bulk density and strength. (C) 2003 Elsevier Ltd and Techna Group S.r.l. All rights reserved

Effect of alumina reactivity on the densification of reaction sintered nonstoichiometric spinels

Densification of two different nonstoichiometric spinels (Al2O3 content 66 wt.% and 90 wt.%) was studied by using the reaction sintering technique. Sintered sea water magnesia and commercial alumina were used as starting materials. Reactivity of alumina was changed by calcinations between 800 and 1600 degreesC. Sintering for all the batches was carried out in the temperature range of 1600 and 1700 degreesC. Sintered products were characterized by bulk density, phase analysis and microstructure. Alumina calcined at 1200 degreesC was found to be optimum for densification of non-stoichiometric spinels. (C) 2002 Elsevier Science Ltd and Techna S.r.l. All rights reserve