Taiwan Oscillation Network

The Taiwan Oscillation Network (TON) is a ground-based network to measure solar intensity oscillations to study the internal structure of the Sun. K-line full-disk images of 1000 pixels diameter are taken at a rate of one image per minute. Such data would provide information onp-modes withl as high as 1000. The TON will consist of six identical telescope systems at proper longitudes around the world. Three telescope systems have been installed at Teide Observatory (Tenerife), Huairou Solar Observing Station (near Beijing), and Big Bear Solar Observatory (California). The telescopes at these three sites have been taking data simultaneously since October of 1994. Anl – v diagram derived from 512 images is included to show the quality of the data

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology

An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression

Breast cancer is the most diagnosed malignancy and the second leading cause of cancer mortality in females. Previous association studies have identified variants on 2q35 associated with the risk of breast cancer. To identify functional susceptibility loci for breast cancer, we interrogated the 2q35 gene desert for chromatin architecture and functional variation correlated with gene expression. We report a novel intergenic breast cancer risk locus containing an enhancer copy number variation (enCNV; deletion) located approximately 400Kb upstream to IGFBP5, which overlaps an intergenic ERα-bound enhancer that loops to the IGFBP5 promoter. The enCNV is correlated with modified ERα binding and monoallelic-repression of IGFBP5 following estrogen treatment. We investigated the association of enCNV genotype with breast cancer in 1,182 cases and 1,362 controls, and replicate our findings in an independent set of 62,533 cases and 60,966 controls from 41 case control studies and 11 GWAS. We report a dose-dependent inverse association of 2q35 enCNV genotype (percopy OR=0.68 95%CI 0.55-0.83, P=0.0002; replication OR=0.77 95%CI 0.73-0.82, P=2.1x10(-19)) and identify 13 additional linked variants (r(2)>0.8) in the 20Kb linkage block containing the enCNV (P=3.2x10(-15) - 5.6x10(-17)). These associations were independent of previously reported 2q35 variants, rs13387042/rs4442975 and rs16857609, and were stronger for ER-positive than ER-negative disease. Together, these results suggest that 2q35 breast cancer risk loci may be mediating their effect through IGFBP5

Publisher Correction: Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

This corrects the article DOI: 10.1038/ncomms5999

Static mixers: Mechanisms, applications, and characterization methods - A review

Static mixers and multifunctional heat exchangers/reactors (MHE/R) are qualified as efficient receptacles for processes including physical or chemical transformations accompanied by heat transfer due to their high productivity and reduced energy expenditures. The present work reviews recent conceptual and technological innovations in passive static mixers and continuous in-line reactors. Current industrial applications are discussed from a process intensification perspective, focusing on mixing and mass transfer performance. Typical experimental techniques employed to characterize and quantify the mixing process are explored. The work is complemented by a review of mixing fundamentals, knowledge of which allows the development of theoretical models crucial for the analysis of experimental data, like the chemical probe mixing assessment method. Considering the development of continuous flow equipment in numerous processes, advances in this field will certainly be of increasing interest to the scientific and industrial communities. (C) 2013 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved

An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression

10.1093/hmg/ddw223HUMAN MOLECULAR GENETICS25173863-387

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation (vol 5, 4999, 2014)

10.1038/ncomms16193NATURE COMMUNICATIONS9

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10 -9), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10 -5), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10 -4) identified in the general populations, and rs113824616 (P = 7 × 10 -5) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk. The online version of this article (doi:10.1186/s13058-016-0718-0) contains supplementary material, which is available to authorized users

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10-43) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology