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- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. 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 promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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2. |
- Laue, Jan, et al.
(författare)
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Piles and shallow foundations under cyclic loadings
- 1997
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Ingår i: Proceedings of the International Offshore and Polar Engineering Conference. - Golden, CO : International Society of Offshore & Polar Engineers. ; , s. 803-810
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Konferensbidrag (refereegranskat)abstract
- To describe the soil structure-interaction of cyclic loaded structures, centrifuge model tests are carried out on laterally loaded piles and vertically loaded shallow foundations. The principle of deformation behaviour of sand will be with briefly. In addition to the presentation of the test results, possibilities of research on cyclic problems in the Bochum geotechnical centrifuge are presented. The obtained data from centrifuge model tests under dry conditions is related to foundations of coastal and offshore structures. It is shown, that the observed mechanisms have to be regarded even in saturated conditions too. The evaluated data is compared with the results and equations obtained from cyclic and dynamic triaxial tests. Thus, the differences between element tests and the real soil-structure interaction behaviour are established.
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