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- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)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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- ELPHINSTONE, RD, et al.
(author)
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OBSERVATIONS IN THE VICINITY OF SUBSTORM ONSET - IMPLICATIONS FOR THE SUBSTORM PROCESS
- 1995
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In: JOURNAL OF GEOPHYSICAL RESEARCH-SPACE PHYSICS. - : AMER GEOPHYSICAL UNION. - 0148-0227. ; 100:A5, s. 7937-7969
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Journal article (other academic/artistic)abstract
- Multi-instrument data sets from the ground and satellites at both low and high altitude have provided new results concerning substorm onset and its source region in the magnetosphere. Twenty-six out of 37 substorm onset events showed evidence of azimuthal
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- Ohtani, S, et al.
(author)
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4 Large-scale field-aligned current systems in the dayside high-latitude region
- 1995
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In: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 100, s. 137-153
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Journal article (peer-reviewed)abstract
- A system of four current sheets of large-scale field-aligned currents (FACs) was discovered in the data set of simultaneous Viking and DMSP-F7 crossings of the dayside high-latitude region. This paper reports four examples of this system that were observed in the prenoon sector. The flow polarities of FACs are upward, downward, upward, and downward, from equatorward to poleward. The lowest-latitude upward current is flowing mostly in the CPS precipitation region, often overlapping with the BPS at its poleward edge, and is interpreted as a region 2 current. The pair of downward and upward FACs in the middle of the structure are collocated with structured electron precipitation. The precipitation of high-energy (>1 keV) electrons is more intense in the lower-latitude downward current sheet. The highest-latitude downward flowing current sheet is located in a weak, low-energy particle precipitation region, suggesting that this current is flowing on open field lines. Simultaneous observations in the postnoon local time sector reveal the standard three-sheet structure of FACs, sometimes described as region 2, region 1, and mantle (referred to the midday region 0) currents. A high correlation was found between the occurrence of the four FAC sheet structure and negative interplanetary magnetic field (IMF) B-Y, We discuss the FAC structure in terms of three types of convection cells: the merging, viscous, and lobe cells. During strongly negative IMF B-Y two convection reversals exist in the prenoon sector; one is inside the viscous cell, and the other is between the viscous cell and the lobe cell. This structure of convection flow is supported by the Viking electric field and auroral UV image data. Based on the convection pattern, the four FAC sheet structure is interpreted as the latitudinal overlap of midday and morning FAC systems. We suggest that the four-current sheet structure is common in a certain prenoon local time sector during strongly negative IMF B-Y.
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