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

Effects of polypropylene, polyester and glass fibres on various strengths of ordinary and standard concretes

This research is attributed to ordinary and standard concretes reinforced with four varieties of fibres. Results of experimental investigations on mechanical properties of M20 and M40 control and fibre reinforced concretes are presented. Comparative performance of 12 mm and 20 mm length monofilament polypropylene fibres, graded fibrillated polypropylene fibres, 12 mm polyester fibres & 12 mm AR glass fibres is evaluated. Fibre content is varied as 0, 0.8 kg & 1.6 kg per m(3) of concrete respectively. Compressive, Split Tensile and flexure Strengths are evaluated at the age of 7, 14 and 28 days. Cubes of 150 x 150 x 150 mm are cast to measure compressive & split tensile strengths and beams of 100 x 100 x 500 mm are prepared to evaluate flexural strength. Broken pieces of flexural specimens are tested in compression and tension, to compare results obtained using 'equivalent cube test' and 'splitting prism test' approach. Workability of concrete is measured which reduces with increase in dosage for all fibres. Failure shapes and unit weight have been recorded. A detailed discussion is carried out by comparing results of three strengths. A significant improvement is obtained in various strengths for different fibre varieties tried. Comparative analysis is carried out on performance of concretes for both grades. An attempt is made to correlate results of compressive and tensile strengths evaluated by above two approaches. Suggestions are included for further improvement in terms of strengths & for proper correlation of tensile and compressive strengths between exact and equivalent tests

Interaction between heating-cooling cycles, sodium sulfate solution and external loading of concrete with and without polypropylene fiber reinforcement

Polypropylene fibers added to concrete are expected to contribute to its post peak ductility. They should be durable when exposed to environment to sustain composite action. Though protected inside concrete, are always susceptible due to cracking of concrete sections. They are popular and used in structural & non-structural applications in India today. Looking to these issues, a study is planned to evaluate effects of environments on concrete incorporating monofilament polypropylene fibres. This paper presents results of experimental investigations to evaluate mechanical properties of 6 dinear 12 & 20 mm length polypropylene fibre reinforced concretes with fibre contents as 0, 0.5 & 3 kg/m(3) of concrete respectively. Specimens are given heating-cooling cycles, wetting-drying cycles to induce sulfate attack and combined cycles of temperature and sulphate attack. At 28-days, half of total specimens are given 40% external equivalent load before initiating above exposures, whereas remaining are given exposures without giving any loads. All mixes are exposed to 100 & 200 temperature and chemical attack cycles and 50 & 100 combined cycles respectively. Compressive, Split Tensile and Flexure strengths are evaluated. Slump, Compaction Factor, Change in weight, Ultra Pulse Velocity, Failure shapes, unit weights etc. is measured. Behaviour of mixes considering effects of temperature & sulfate attack individually and combined is discussed. Performance of fibres at same and different dosages & effect of loading is also evaluated. In general it is observed that all fibre mixes have exhibited superior performance compared to control mix at all stages of the experimentation