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 narrative review on haptic devices: relating the physiology and psychophysical properties of the hand to devices for rehabilitation in central nervous system disorders

Purpose. This paper provides rehabilitation professionals and engineers with a theoretical and pragmatic rationale for the inclusion of haptic feedback in the rehabilitation of central nervous system disorders affecting the hand.Method. A narrative review of haptic devices used in sensorimotor hand rehabilitation was undertaken. Presented papers were selected to outline and clarify the underlying somatosensory mechanisms underpinning these technologies and provide exemplars of the evidence to date.Results. Haptic devices provide kinaesthetic and/or tactile stimulation. Kinaesthetic haptics are beginning to be incorporated in central nervous system rehabilitation, however, there has been limited development of tactile haptics. Clinical research in haptic rehabilitation of the hand is embryonic but initial findings indicate potential clinical benefit. Conclusions. Haptic rehabilitation offers the potential to advance sensorimotor hand rehabilitation but both scientific and pragmatic developments are needed to ensure that its potential is realised.<br/

The compounding effects of high pollen limitation, selfing rates and inbreeding depression leave a New Zealand tree with few viable offspring

Publishe

Characterization of closed-cell aluminium foams subjected to compressive loading

© 2016 by The Minerals, Metals & Materials Society. The mechanical response of closed-cell aluminium metallic foams subjected to low and high strain-rate loading has been investigated. A set of quasi-static and dynamic (shock) compressive tests have been conducted on closed-cell aluminium foams (CYMAT) with densities of 0.50 and 0.30 g/cc. Post-mortem characterization via optical microscopy and electron backscatter diffraction (EBSD) was performed on pristine and deformed specimens to elucidate the dominant deformation mechanisms in these materials. The combination of these techniques allowed for the assessment of critical deformation parameters such as changes in cell geometry and morphology, as well as microstructural evolution and deformation of the aluminium cellular network. These findings aim to aid in the design and development of optimized material structures for impact and blast protection