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

Finger pad friction and tactile perception of laser treated, stamped and cold rolled micro-structured stainless steel sheet surfaces

Tactile perception is a complex system, which depends on frictional interactions between skin and counter-body. The contact mechanics of tactile friction is governed by many factors such as the state and properties of skin and counter-body. In order to discover the connection between perception and tactile friction on textured stainless steel sheets, both perception experiments (subjective) and tactile friction measurements (objective) were performed in this research. The perception experiments were carried out by using a panel test method to identify the perceived roughness, perceived stickiness and comfort level from the participants. For the friction experiments, tactile friction was measured by a multi-axis force/torque transducer in vivo. The perceived stickiness was illustrated as an effective subjective stimulus, which has a negative correlation to the comfort perception. No significant evidence was revealed to the connection between the perceived roughness and comfort perception, and this relationship may be influenced by the participants’ individual experience, gender and moisture level of skin. Furthermore, the kinetic tactile friction was concluded as an objective stimulus to the comfort perception with a negative correlation.Railway Engineerin

Selection of micro-fabrication techniques on stainless steel sheet for skin friction

This review gives a concise introduction to the state-of-art techniques used for surface texturing, e.g., wet etching, plasma etching, laser surface texturing (LST), 3D printing, etc. In order to fabricate deterministic textures with the desired geometric structures and scales, the innovative texturing technologies are developed and extended. Such texturing technology is an emerging frontier with revolutionary impact in industrial and scientific fields. With the help of the latest fabrication technologies, surface textures are scaling down and more complex deterministic patterns may be fabricated with desired functions, e.g., lotus effect (hydrophobic), gecko feet (adhesive), haptic tactile, etc. The objective of this review is to explore the surface texturing technology and its contributions to the applications.Railway Engineerin

Measurement of the diffractive cross-section in deep inelastic scattering

Diffractive scattering of $\gamma^* p \to X + N$, where $N$ is either a proton or a nucleonic system with $M_N~<~4$~GeV has been measured in deep inelastic scattering (DIS) at HERA. The cross section was determined by a novel method as a function of the $\gamma^* p$ c.m. energy $W$ between 60 and 245~GeV and of the mass $M_X$ of the system $X$ up to 15~GeV at average $Q^2$ values of 14 and 31~GeV$^2$. The diffractive cross section $d\sigma^{diff} /dM_X$ is, within errors, found to rise linearly with $W$. Parameterizing the $W$ dependence by the form d\sigma^{diff}/dM_X \propto (W^2)^{(2\overline{\mbox{\alpha_{_{I\hspace{-0.2em}P}}}} -2)} the DIS data yield for the pomeron trajectory \overline{\mbox{\alpha_{_{I\hspace{-0.2em}P}}}} = 1.23 \pm 0.02(stat) \pm 0.04 (syst) averaged over $t$ in the measured kinematic range assuming the longitudinal photon contribution to be zero. This value for the pomeron trajectory is substantially larger than \overline{\mbox{\alpha_{_{I\hspace{-0.2em}P}}}} extracted from soft interactions. The value of \overline{\mbox{\alpha_{_{I\hspace{-0.2em}P}}}} measured in this analysis suggests that a substantial part of the diffractive DIS cross section originates from processes which can be described by perturbative QCD. From the measured diffractive cross sections the diffractive structure function of the proton F^{D(3)}_2(\beta,Q^2, \mbox{x_{_{I\hspace{-0.2em}P}}}) has been determined, where $\beta$ is the momentum fraction of the struck quark in the pomeron. The form F^{D(3)}_2 = constant \cdot (1/ \mbox{x_{_{I\hspace{-0.2em}P}}})^a gives a good fit to the data in all $\beta$ and $Q^2$ intervals with $a = 1.46 \pm 0.04 (stat) \pmComment: 45 pages, including 16 figure

COSMIC (Cohort Studies of Memory in an International Consortium): An international consortium to identify risk and protective factors and biomarkers of cognitive ageing and dementia in diverse ethnic and sociocultural groups.

International audienceBACKGROUND: A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders.Methods/design: Longitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress. DISCUSSION: The challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing