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

A high deposition efficiency method for wire arc additive manufacturing

In this study, single wire arc additive manufacturing (SWAAM) and multi wire arc additive manufacturing (MWAAM) were used to fabricate the TC11 alloy. Microstructure and mechanical properties of TC11 alloy were studied. The results showed that the microstructure of MWAAM TC11 alloy composed of α and β phase, and the proportion of β phase increased slightly than that of SWAAM TC11 sample. Compared with the SWAAM TC11 sample, the microhardness of MWAAM TC11 alloy sample increased from 382 to 407 HV, and average ultimate tensile strength of MWAAM TC11 alloy sample increased from 922.01 to 934.56 MPa. The results indicate that the addition of wires can significantly improve both manufacturing efficiency and mechanical properties of TC11 alloy components

Microstructure and mechanical properties of TC4/NiTi bionic gradient heterogeneous alloy prepared by multi-wire arc additive manufacturing

TC4/NiTi multi-materials structure components have been successfully fabricated via multi-wire arc additive manufacturing (MWAAM). Here we show the interface characteristics and mechanical properties of TC4/NiTi multi-materials structure component under bionic gradient interlayer build strategy. The results indicated that MWAAM TC4/NiTi gradient heterogeneous alloy with ultimate compression strength (1533.33 ± 26 MPa) was obtained. The excellent compression behaviour was mainly contributed to the excellent transition of gradient region indicated by EBSD analysis showing fine grain sizes and smaller difference Schmidt factor values. The phase composition from TC4 region to NiTi region had evolved with the increasing of NiTi content as follows: α-Ti + β-Ti → α-Ti + NiTi2 → NiTi2 → NiTi2 + NiTi → NiTi + Ni3Ti. The microhardness of the gradient heterogeneous alloy ranged from 310 ± 8 HV to 230 ± 11 HV, and the highest hardness value was 669.6 ± 12 HV in region B due to the precipitation of NiTi2 strengthening phase. The ultimate fracture stress and strain of sample were 1533.33 ± 26 MPa and 28.3 ± 6% respectively. The irrecoverable strain of MWAAM TC4/NiTi gradient heterogeneous alloy gradually approached 2.75% during 10 load/unload cycles of compression tes