DEAR1 Is a Dominant Regulator of Acinar Morphogenesis and an Independent Predictor of Local Recurrence-Free Survival in Early-Onset Breast Cancer

Ann Killary and colleagues describe a new gene that is genetically altered in breast tumors, and that may provide a new breast cancer prognostic marker

Protection of buried rigid pipes using geogrid-reinforced soil systems subjected to cyclic loading

YesThe performance of buried rigid pipes underneath geogrid-reinforced soil while applying incrementally increased cyclic loading was assessed using a fully instrumented laboratory rig. The influence of varying two parameters of practical importance was investigated; the pipe burial depth and the number of geogrid-layers. Measurements were taken for pipe deformation, footing settlement, strain in pipe and reinforcing layers, and pressure/soil stress on the pipe crown during various stages of cyclic loading. The research outcomes demonstrated a rapid increase in the rate of deformation of the pipe and the footing, and the rate of generated strain in the pipe and the geogrid-layers during the first 300 cycles. While applying further cycles, those rates were significantly decreased. Increasing the pipe burial depth and number of geogrid-layers resulted in reductions in the footing and the pipe deformations, the pressure on pipe crown, and the pipe strains. Redistribution of stresses, due to the inclusion of reinforcing layers, formed a confined zone surrounding the pipe providing it with additional lateral support. The pipe invert experienced a rebound, which was found to be dependent on pressure around the pipe and the degree of densification of the bedding layer. Data for strains measured in the geogrid-layers showed that despite the applied loading value and the pipe burial depth, the tensile strain in the lower geogrid-layer was usually higher than that measured in the upper layer

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