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

Mathematical modelling of angiogenesis using continuous cell-based models

In this work, we develop a mathematical formalism based on a 3D in vitro model that is used to simulate the early stages of angiogenesis. The model treats cells as individual entities that are migrating as a result of chemotaxis and durotaxis. The phenotypes used here are endothelial cells that can be distinguished into stalk and tip (leading) cells. The model takes into account the dynamic interaction and interchange between both phenotypes. Next to the cells, the model takes into account several proteins such as vascular endothelial growth factor, delta-like ligand 4, urokinase plasminogen activator and matrix metalloproteinase, which are computed through the solution of a system of reaction–diffusion equations. The method used in the present study is classified into the hybrid approaches. The present study, implemented in three spatial dimensions, demonstrates the feasibility of the approach that is qualitatively confirmed by experimental results.Delft Institute of Applied MathematicsElectrical Engineering, Mathematics and Computer Scienc

Surface and environmental effects on ceramic materials /

Creep and recovery phenomena in sintered polycrystalline alumina have been studied. Effects of temperature and impurity content on creep behavior and the results of observation of polished and etched surfaces are discussed. The results are analyzed in terms of a tentative conventional mechanical analog.Includes bibliographical references (page 10).Creep and recovery phenomena in sintered polycrystalline alumina have been studied. Effects of temperature and impurity content on creep behavior and the results of observation of polished and etched surfaces are discussed. The results are analyzed in terms of a tentative conventional mechanical analog.Research supported by the United States Air Force, Air Research and Development Command, and performed by the University of Utah, Solid State Physics Department, under Materials Central Contract No.Mode of access: Internet

Students’ perceptions of school climate as determinants of wellbeing, resilience and identity

© 2015, © The Author(s) 2015. This study examined the relations between school climate variables and students’ feeling of wellbeing, life satisfaction, ethnic identity, moral identity and resilience. Furthermore, the study also examined the interrelationships between these five outcome variables. Six aspects of the school climate were measured: teacher support, peer connectedness, school connectedness, affirming diversity, rule clarity and reporting and seeking help. The participants included 2202 students, the data from whom included 2122 cases that were complete and usable (1058 boys and 1059 girls) from six public high schools in Perth, Western Australia. These data were analysed by means of structural equation modelling (SEM) analysis. All six school climate factors were related to student wellbeing. These relations were primarily indirect (with the exception of teacher support, school connectedness and affirming diversity which had a direct influence), mediated through the students’ sense of ethnic and moral identity, resilience and life satisfaction