Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma

Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5 × 10−8), as did 2 previously reported but unreplicated loci and all 13 established loci. Newly associated SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes in the associated regions, including one involved in telomere biology.

Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3

We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 x 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 x 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.

Commercial mariculture of Oreochromis niloticus using net cages

The culture of tilapia has a long history in Africa. Fossil remains of members of the genus have been found which are about 18 million years old (Fryer and Iles, 1972). Oreochromis niloticus was the subject of detailed observations in Egypt of 5,000 years ago. A bas relief of 2,500B.C. depicts tilapia being reared in ponds in Egypt. However, despite this long history the prolific nature of this fish results in very high populations in pond culture systems. Consequently small size fish are harvested. Several methods have thus been tried to control the excessive reproduction of tilapia in captivity with only partial success. This paper reports how large size tilapia especially O. niloticus averaging at least 150g per piece can be commercially produced using floating net cages in the marine environment

Towards jet flow LES of conceptual nozzles for acoustic predictions

Progress in simulating chevron nozzle jet flows using ILES/RANS-ILES approaches and using the Ffowcs Williams and Hawkings (FW-H) surface integral method to predict the radiated far field sound is presented in this paper. With the focus on the realistic chevron geometries, SMC001 and SMC006, coarse and fine meshes are generated in the range of 3∼13 million mesh cells. Throughout this work, to minimize numerical dissipation introduced by mesh quality issues, the hexahedral cell type is used. Numerical simulations are then carried out with cell-vertex and cell-centered codes. Despite the modest grids, mean velocities and turbulent statistics are found to be in reasonable accord with measurements. Also, far field sound levels predicted by the FW-H post processor are encouraging. Copyright © 2008 by the American Institute of Aeronautics and Astronautics, Inc.

Numerical simulation of single-stream jets from a serrated nozzle

Hybrid large-eddy type simulations for cold jet flows from a serrated nozzle are performed at an acoustic Mach number Ma ac = 0.9 and Re = 1.03×10 6. Since the solver being used tends towards having dissipative qualities, the subgrid scale (SGS) model is omitted, giving a numerical type LES (NLES) or implicit LES (ILES) reminiscent procedure. To overcome near wall streak resolution problems a near wall RANS (Reynolds averaged Navier-Stokes) model is smoothly blended to the LES making a hybrid RANS-ILES. The geometric complexity of the serrated nozzle is fully considered without simplification or emulation. An improved but still modest hexahedral multi-block grid with circa 20 million grid points (with respect to 12.5 million in Xia et al.; Int J Heat Fluid Flow 30:1067-1079, 2009) is used. Despite the modest grid size, encouraging and improved results are obtained. Directly resolved mean and second-order fluctuating quantities along the jet centerline and in the jet shear layer compare favorably with measurements. The radiated far-field sound predicted using the Ffowcs Williams and Hawkings (FW-H) surface integral method shows good agreement with the measurements in directivity and sound spectra. © 2011 Springer Science+Business Media B.V.