Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Mechanical Properties of High and Very-High Strength Steel at Elevated Temperatures and After Cooling Down

High-strength steels (HSS) are produced using special chemical composition or/and manufacturing processes. Both aspects affect their mechanical properties at elevated temperatures and after cooling down, and particularly the residual strength and the ductility of the structural members. As HSS equates the design of lighter structural elements, higher temperatures are developed internally compared to the elements designed with conventional carbon steel. Therefore, the low thickness members, along with the severe effect of high temperature on the mechanical properties of the HSS, constitute to the increased vulnerability of such structures in fire. Moreover, the re-use and reinstatement of these structures are more challenging due to the lower residual mechanical properties of HSS after the cooling down period. This paper presents a review of the available experimental studies of the mechanical properties of HSS at elevated temperatures and after cooling down. The experimental results are collected and compared with the proposed material model (reduction factors) of EN1993–1-2. Based on these comparisons, modified equations describing the effect of elevated temperatures on the mechanical properties of HSS are proposed. Also, the post-fire mechanical properties of HSS are examined. A comprehensive discussion on the effect of influencing parameters, such as manufacturing process, microstructure, loading conditions, maximum temperature, and others is further explored

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

A review of class 4 slender section properties calculation for thin-walled steel sections according to EC3

A review is given to the procedure suggested by the Eurocode 3 for the section properties calculations of thin-walled Class 4 slender steel sections consists of plate elements. Focus will be given to the effective width approach described in the Eurocode 3. The essential steps for the effective width calculation for single plate element subjected to different direct stress distribution are first given. It is then followed by a study that compares the two different procedures, namely the full iteration procedure and the simplified procedure adopted by Eurocode 3 for Class 4 slender section properties calculation. Calculation examples are then given to demonstrate the calculation steps for both the full and the simplified approaches. Results of the calculation examples indicate that while the simplified procedure eliminates the tedious iteration steps and is much more convenient for manual calculation, the full iteration method in general will lead to less conservative effective area and section modulus and thus could result in more economical design in practice

Post weld heat treatment for high strength steel welded connections

In this study, experiments were conducted to investigate the effect of post-weld heat treatment (PWHT) on the reheated, quenched and tempered (RQT) grade S690 high strength steel welded connections. Firstly, the effect of PWHT on the mechanical properties after welding is investigated. It is found that the loss of both strength and ductility after welding could be serious but PWHT could be able to improve the ductility of the affected specimens at the expense of strength. Secondly, four Y-shape plate-to-plate (Y-PtP) and nine T-stub RQT-S690 joints are fabricated to study the effect of PWHT on the residual stress level near the weld toe and the tensile behavior of the joints, respectively. The hole drilling tests employed to study the residual stress reveal that PWHT is able to decrease the residual stress level near the weld toe significantly. The tensile test results show that proper PWHT could improve both the ductility and the maximum resistance while the reduction of plastic resistance can be kept in a negligible level. However, it is found that if the specimens are overheated, although the ductility could still be increased, the reduction of load carrying capacity was severe

Residual stress distribution of roller bending of steel rectangular structural hollow sections

Curved steel rectangular structural hollow sections, which have a wide range of applications in construction industry, are commonly produced by cold roller bending using pyramid-type 3-roller machine on hot finished steel hollow sections. The roller bending process induces local deformations and residual stress in the hot finished section walls. While the residual stress magnitude and distribution could have sufficient influence on the member's stability and buckling resistance, few studies have paid attention to the residual stress distribution caused by roller bending. In this paper, a proper numerical modelling procedure is employed to simulate the rolling process and reproduce the residual stress. In addition, a small scale parametric study is conducted to investigate the effects of some key roller bending parameters, including the rolling boundary conditions, the bending ratio, the steel yield stress, the thickness ratio and the shape factor, on the resulted residual stress distribution of the bended sections. Based on the results obtained from the parametric studies, a simple residual stresses model which could predict the residual stress distribution of the curved member is proposed

Recent Progress in Steel and Composite Structures - Proceedings of the 13th International Conference on Metal Structures, ICMS 2016

High strength steel box column are usually fabricated from steel slab by applying welding. The welding process can introduce residual stresses and geometric imperfections into the columns and influence the column strength. In this study, a numerical investigation on the behavior of high strength steel thin-walled box column under the compression force was carried out. The welding processes were firstly simulated with commercial package ABAQUS in this study to find out the residual stress distributions in high strength steel box column. After that, the column behaviors under the compression were modelled with predefined field from the previous step. The effect of the welding process (including FCAW and SAW), heating treatment (including preheating and post-weld heat treatment) and geometrical imperfection on the residual stress field and box column strength was investigated and discussed