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

Durability of sulphate resisting slag blended cements and mortars in sea water

35-40<span style="font-size:11.0pt;line-height:115%; font-family:" calibri","sans-serif";mso-fareast-font-family:"times="" new="" roman";="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">The hydration characteristics as well as the sea water attack of sulphate-resisting slag content up to one year have been studied. The results show that with the increase in slag content the rate of hydration of cement pastes in water decreases. The compressive strength of the cement mortars immersed in sea water increases up to 6 months then decreases. The free lime content decreases with time due to the reaction of chloride ions with Ca(OH)2 The CI- and SO3 contents increase with time of immersion in sea water.</span

Experimental Models of Glioma

The development and refinement of animal models of gliomagenesis has been fundamental to test hypotheses concerning the aetiology of gliomas and their molecular and cellular pathogenesis. During the last few decades, modeling has gained in complexity and is nowadays mostly relying on the cell type-specific modulation of the expression of candidate oncogenes and oncosup-pressors. Despite such technological advances, the recent appreciation of the molecular heterogeneity underlying human high-grade glioma variability re-vealed the need for a deeper characterization of the available models. It is now clear that most of the existing animal systems mimic one of the human molecular classes, known as "proneural", leaving the other groups un-derrepresented. While there is thus the need for an expansion of the range of available models, existing ones have already proven useful as translational research platforms, allowing preliminary assessment of the efficacy of classi-cal and innovative therapeutic approaches. In this contribution, we provide a general view of the field and synthesize our understanding of the biology of the most thoroughly studied model family, that of PDGF-induced gliomas