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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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- Josefson, Lennart, 1954, et al.
(författare)
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BENCHMARK STUDY OF WELDING DEFORMATIONS IN STIFFENED PLATE
- 2022
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Ingår i: Proceedings of the International Conference on Offshore Mechanics and Arctic Engineering - OMAE. ; 3
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Konferensbidrag (refereegranskat)abstract
- The fabrication of ship hulls involves welding operations, one typical operation is fillet welding of stiffeners to plates (panels) a so-called T-joint. The residual stresses from the welding process will influence the fatigue life of the structure, and residual deformations will increase the risk for buckling of the panel and give poor fabrication tolerances which may complicate the assembly of a built-up structure. Though this weld geometry has been frequently studied in the literature both experimentally and numerically, the focus has been on the residual stress field and if residual deformations are studied, the angular distortion and the typical V-shape seen in the welded plate (panel) are reported. This benchmark focusses on the residual shape after two-pass fillet welding of a stiffener to a plate (T-joint and the influence of the constraints used during welding. The information of the full welding residual deformations may be useful for the fabrication of larger complex welded structures. The benchmark study clearly shows that careful consideration is needed when defining a reference plane for comparison of resulting deformations from FE-simulations and from experiments as well as good documentation of the actual boundary conditions and steps carried after the completion of the welding and before measuring residual deformations. The FE-simulations have shown that it is difficult to obtain the full antisymmetric, twisted shape of the plate as measured in the experiments, although a trend similar to the experiments can be seen as the plate tends to move upwards at the end of each weld pass, i.e a slight influence of the weld pass direction.
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- Markmann, James F., et al.
(författare)
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Executive Summary of IPITA-TTS Opinion Leaders Report on the Future of beta-Cell Replacement
- 2016
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 100:7, s. E25-E31
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Forskningsöversikt (refereegranskat)abstract
- The International Pancreas and Islet Transplant Association (IPITA), in conjunction with the Transplantation Society (TTS), convened a workshop to consider the future of pancreas and islet transplantation in the context of potential competing technologies that are under development, including the artificial pancreas, transplantation tolerance, xenotransplantation, encapsulation, stem cell derived beta cells, beta cell proliferation, and endogenous regeneration. Separate workgroups for each topic and then the collective group reviewed the state of the art, hurdles to application, and proposed research agenda for each therapy that would allow widespread application. Herein we present the executive summary of this workshop that focuses on obstacles to application and the research agenda to overcome them; the full length article with detailed background for each topic is published as an online supplement to Transplantation.
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