A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Sodium vanadium fluorophosphates (NVOPF) array cathode designed for high-rate full sodium ion storage device

3D batteries continue to be of widespread interest for flexible energy storage where the 3D nanostructured cathode is the key component to achieve both high energy and power densities. While current work on flexible cathodes tends to emphasize the use of flexible scaffolds such as graphene and/or carbon nanotubes, this approach is often limited by poor electrical contact and structural stability. This communication presents a novel synthetic approach to form 3D array cathode for the first time, the single‐crystalline Na3(VO)2(PO4)2F (NVOPF) by using VO2 array as a seed layer. The NVOPF cathode exhibits both high‐rate capability (charge/discharge in 60 s) and long‐term durability (10,000 cycles at 50 C) for Na ion storage. Utilizing in situ X‐ray diffraction and first principles calculations, the high‐rate properties are correlated with the small volume change, 2D fast ion transport, and the array morphology. A novel all‐array flexible Na+ hybrid energy storage device based on pairing the intercalation‐type NVOPF array cathode with a cogenetic pseudocapacitive VO2 nanosheet array anode is demonstrated.Dongliang Chao, Chun‐Han (Matt) Lai, Pei Liang, Qiulong Wei, Yue‐Sheng Wang, Changrong (Rose) Zhu, Gang Deng ... et al

Sodium Vanadium Fluorophosphates (NVOPF) Array Cathode Designed for High‐Rate Full Sodium Ion Storage Device

3D batteries continue to be of widespread interest for flexible energy storage where the 3D nanostructured cathode is the key component to achieve both high energy and power densities. While current work on flexible cathodes tends to emphasize the use of flexible scaffolds such as graphene and/or carbon nanotubes, this approach is often limited by poor electrical contact and structural stability. This communication presents a novel synthetic approach to form 3D array cathode for the first time, the single‐crystalline Na3(VO)2(PO4)2F (NVOPF) by using VO2 array as a seed layer. The NVOPF cathode exhibits both high‐rate capability (charge/discharge in 60 s) and long‐term durability (10,000 cycles at 50 C) for Na ion storage. Utilizing in situ X‐ray diffraction and first principles calculations, the high‐rate properties are correlated with the small volume change, 2D fast ion transport, and the array morphology. A novel all‐array flexible Na+ hybrid energy storage device based on pairing the intercalation‐type NVOPF array cathode with a cogenetic pseudocapacitive VO2 nanosheet array anode is demonstrated.Dongliang Chao, Chun‐Han (Matt) Lai, Pei Liang, Qiulong Wei, Yue‐Sheng Wang, Changrong (Rose) Zhu, Gang Deng ... et al

The second Sandia Fracture Challenge : predictions of ductile failure under quasi-static and moderate-rate dynamic loading

International audienceDuctile failure of structural metals is relevant to a wide range of engineering scenarios. Computational methods are employed to anticipate the critical conditions of failure, yet they sometimes provide inaccurate and misleading predictions. Challenge scenarios , such as the one presented in the current work, provide an opportunity to assess the blind, quantitative predictive ability of simulation methods against a previously unseen failure problem. Rather than evaluate the predictions of a single simulation approach, the Sandia Fracture Challenge relies on numerous volunteer teams with expertise in computational mechanics to apply a broad range of computational methods, numerical algorithms, and constitutive models to the challenge. This exercise is intended to evaluate the state of health of technologies available for failure prediction. In the first Sandia Fracture Challenge, a wide range of issues were raised in ductile failure modeling, including a lack of consistency in failure models, the importance of shear calibration data, and difficulties in quantifying the uncertainty of prediction [see Boyce et al. (Int J Fract 186:5–68, 2014) for details of these observations]. This second Sandia Fracture Challenge investigated the ductile rupture of a Ti–6Al–4V sheet under both quasi-static and modest-rate dynamic loading (failure in ∼0.1 s). Like the previous challenge, the sheet had an unusual arrangement of notches and holes that added geometric complexity and fostered a competition between tensile-and shear-dominated failure modes. The teams were asked to predict the fracture path and quantitative far-field failure metrics such as the peak force and displacement to cause crack initiation. Fourteen teams contributed blind predictions, and the experimental outcomes were quantified in three independent test labs. Additional shortcomings were revealed in this second challenge such as inconsistency in the application of appropriate boundary conditions, need for a thermomechanical treatment of the heat generation in the dynamic loading condition, and further difficulties in model calibration based on limited real-world engineering data. As with the prior challenge, this work not only documents the 'state-of-the-art' in computational failure prediction of ductile tearing scenarios , but also provides a detailed dataset for non-blind assessment of alternative methods

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. 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; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation; analyses timings and patterns of tumour evolution; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity; and evaluates a range of more-specialized features of cancer genomes