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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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- Hatch, D. R., et al.
(författare)
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Microtearing modes as the source of magnetic fluctuations in the JET pedestal
- 2021
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 61:3
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Tidskriftsartikel (refereegranskat)abstract
- We report on a detailed study of magnetic fluctuations in the JET pedestal, employing basic theoretical considerations, gyrokinetic simulations, and experimental fluctuation data to establish the physical basis for their origin, role, and distinctive characteristics. We demonstrate quantitative agreement between gyrokinetic simulations of microtearing modes (MTMs) and two magnetic frequency bands with corresponding toroidal mode numbers n = 4 and 8. Such disparate fluctuation scales, with substantial gaps between toroidal mode numbers, are commonly observed in pedestal fluctuations. Here we provide a clear explanation, namely the alignment of the relevant rational surfaces (and not others) with the peak in the omega(*) profile, which is localized in the steep gradient region of the pedestal. We demonstrate that a global treatment is required to capture this effect. Nonlinear simulations suggest that the MTM fluctuations produce experimentally-relevant transport levels and saturate by relaxing the background electron temperature gradient, slightly downshifting the fluctuation frequencies from the linear predictions. Scans in collisionality are compared with a simple MTM dispersion relation. At the experimental points considered, MTM growth rates can either increase or decrease with collision frequency depending on the parameters thus defying any simple characterization of collisionality dependence.
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- Frassinetti, Lorenzo, et al.
(författare)
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Role of the separatrix density in the pedestal performance in deuterium low triangularity JET-ILW plasmas and comparison with JET-C
- 2021
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Ingår i: Nuclear Fusion. - : IOP Publishing Ltd. - 0029-5515 .- 1741-4326. ; 61:12
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Tidskriftsartikel (refereegranskat)abstract
- A reduction of the pedestal pressure with increasing separatrix density over pedestal density (n (e) (sep)/n (e) (ped)) has been observed in JET. The physics behind this correlation is investigated. The correlation is due to two distinct mechanisms. The increase of n (e) (sep)/n (e) (ped) till approximate to 0.4 shifts the pedestal pressure radially outwards, decreasing the peeling-balloning stability and reducing the pressure height. The effect of the position saturates above n (e) (sep)/n (e) (ped) approximate to 0.4. For higher values, the reduction of the pedestal pressure is ascribed to increased turbulent transport and, likely, to resistive MHD effects. The increase of n (e) (sep)/n (e) (ped) above approximate to 0.4 reduces backward difference n (e) /n (e), increasing eta (e) and the pedestal turbulent transport. This reduces the pressure gradient and the pedestal temperature, producing an increase in the pedestal resistivity. The work suggests that the increase in resistivity might destabilize resistive balloning modes, further reducing the pedestal stability.
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- Field, A. R., et al.
(författare)
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The dependence of exhaust power components on edge gradients in JET-C and JET-ILW H-mode plasmas
- 2020
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP PUBLISHING LTD. - 0741-3335 .- 1361-6587. ; 62:5
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Tidskriftsartikel (refereegranskat)abstract
- Exhaust power components due to ELMs, radiation and heat transport across the edge transport barrier (ETB) between ELMs are quantifed for H-mode plasmas in JET-C and JET-ILW for comparison with simulations of pedestal heat transport. In low-current, JET-ILW pulses with a low rate of gas fuelling, the pedestal heat transport is found not to be stiff, i.e. the effective, mean heat diffusivity ac n eff does not increase with the electron temperature gradient adTe dRnped across the pedestal and the parameter he = Lne LTe increases with the conducted loss power across the pedestal, with the latter saturating at mean values.h.. 2 e ped. This increase in pedestal temperature gradient is partly due to a relative reduction of the ion neo-classical heat transport (which is more significant at low plasma current) with decreasing collisionality at higher power. In JET-ILW pulses, significantly more power is required at a high gas puffing rate to achieve a similar pedestal pressure and normalised confinement to that in otherwise similar JET-C pulses without gas-puffing. The increased heat transport across the JET-ILW pedestals is caused by changes to the pedestal structure induced by the gas puffing, which is required to mitigate contamination by W impurities sputtered from the target plates. In high-power JET-ILW pulses, the radiated power is dominated by that from W, which exhibits a highly asymmetric poloidal distribution due to toroidal rotation. During the ELMy H-mode phase, the W is concentrated in the outer `mantle' region (0.7. r. 0.96 N) inside the pedestal top by a favourable alignment of profile gradients, where it can be effectively flushed by ELMs. Transport analysis reveals that the strong mantle radiation cools the outer region of the plasma, causing more of the heat to be lost through the electron channel. However, direct cooling by W radiation from the ETB region is shown to be insignificant compared to the power conducted through the pedestal.
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- Chapman-Oplopoiou, B., et al.
(författare)
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The role of ETG modes in JET-ILW pedestals with varying levels of power and fuelling
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:8
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of GENE gyrokinetic calculations based on a series of JET-ITER-like-wall (ILW) type I ELMy H-mode discharges operating with similar experimental inputs but at different levels of power and gas fuelling. We show that turbulence due to electron-temperature-gradient (ETGs) modes produces a significant amount of heat flux in four JET-ILW discharges, and, when combined with neoclassical simulations, is able to reproduce the experimental heat flux for the two low gas pulses. The simulations plausibly reproduce the high-gas heat fluxes as well, although power balance analysis is complicated by short ELM cycles. By independently varying the normalised temperature gradients (omega(T)(e)) and normalised density gradients (omega(ne )) around their experimental values, we demonstrate that it is the ratio of these two quantities eta(e) = omega(Te)/omega(ne) that determines the location of the peak in the ETG growth rate and heat flux spectra. The heat flux increases rapidly as eta(e) increases above the experimental point, suggesting that ETGs limit the temperature gradient in these pulses. When quantities are normalised using the minor radius, only increases in omega(Te) produce appreciable increases in the ETG growth rates, as well as the largest increases in turbulent heat flux which follow scalings similar to that of critical balance theory. However, when the heat flux is normalised to the electron gyro-Bohm heat flux using the temperature gradient scale length L-Te, it follows a linear trend in correspondence with previous work by different authors.
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