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- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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- Hobirk, J., et al.
(författare)
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The JET hybrid scenario in Deuterium, Tritium and Deuterium-Tritium
- 2023
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Ingår i: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 63:11
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Tidskriftsartikel (refereegranskat)abstract
- The JET hybrid scenario has been developed from low plasma current carbon wall discharges to the record-breaking Deuterium-Tritium plasmas obtained in 2021 with the ITER-like Be/W wall. The development started in pure Deuterium with refinement of the plasma current, and toroidal magnetic field choices and succeeded in solving the heat load challenges arising from 37 MW of injected power in the ITER like wall environment, keeping the radiation in the edge and core controlled, avoiding MHD instabilities and reaching high neutron rates. The Deuterium hybrid plasmas have been re-run in Tritium and methods have been found to keep the radiation controlled but not at high fusion performance probably due to time constraints. For the first time this scenario has been run in Deuterium-Tritium (50:50). These plasmas were re-optimised to have a radiation-stable H-mode entry phase, good impurity control through edge Ti gradient screening and optimised performance with fusion power exceeding 10 MW for longer than three alpha particle slow down times, 8.3 MW averaged over 5 s and fusion energy of 45.8 MJ.
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- Mantsinen, M. J., et al.
(författare)
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Experiments in high-performance JET plasmas in preparation of second harmonic ICRF heating of tritium in ITER
- 2023
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Ingår i: Nuclear Fusion. - : Institute of Physics (IOP). - 0029-5515 .- 1741-4326. ; 63:11
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Tidskriftsartikel (refereegranskat)abstract
- The reference ion cyclotron resonance frequency (ICRF) heating schemes for ITER deuterium-tritium (D-T) plasmas at the full magnetic field of 5.3 T are second harmonic heating of T and 3He minority heating. The wave-particle resonance location for these schemes coincide and are central at a wave frequency of 53 MHz at 5.3 T. Experiments have been carried out in the second major D-T campaign (DTE2) at JET, and in its prior D campaigns, to integrate these ICRF scenarios in JET high-performance plasmas and to compare their performance with the commonly used hydrogen (H) minority heating. In 50:50 D:T plasmas, up to 35% and 5% larger fusion power and diamagnetic energy content, respectively, were obtained with second harmonic heating of T as compared to H minority heating at comparable total input powers and gas injection rates. The core ion temperature was up to 30% and 20% higher with second harmonic T and 3He minority heating, respectively, with respect to H minority heating. These are favourable results for the use of these scenarios in ITER and future fusion reactors. According to modelling, adding ICRF heating to neutral beam injection using D and T beams resulted in a 10%-20% increase of on-axis bulk ion heating in the D-T plasmas due to its localisation in the plasma core. Central power deposition was confirmed with the break-in-slope and fast Fourier transform analysis of ion and electron temperature in response to ICRF modulation. The tail temperature of fast ICRF-accelerated tritons, their enhancement of the fusion yield and time behaviour as measured by an upgraded magnetic proton recoil spectrometer and neutral particle analyser were found in agreement with theoretical predictions. No losses of ICRF-accelerated ions were observed by fast ion detectors, which was as expected given the high plasma density of n e approximate to 7-8 x 1019 m-3 in the main heating phase that limited the formation of ICRF-accelerated fast ion tails. 3He was introduced in the machine by 3He gas injection, and the 3He concentration was measured by a high-resolution optical penning gauge in the sub-divertor region. The DTE2 experiments with 3He minority heating were carried with a low 3He concentration in the range of 2%-4% given the fact that the highest neutron rates with 3He minority heating in D plasmas were obtained at low 3He concentrations of similar to 2%, which also coincided with the highest plasma diamagnetic energy content. In addition to 3He introduced by 3He gas injection, an intrinsic concentration of 3He of the order of 0.2%-0.4% was measured in D-T plasmas before 3He was introduced in the device, which is attributed to the radioactive decay of tritium to 3He. According to modelling, even such low intrinsic concentrations of 3He lead to significant changes in ICRF power partitioning during second harmonic heating of T due to absorption of up to 30% of the wave power by 3He.
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- Nocente, M., et al.
(författare)
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Fusion product measurements by nuclear diagnostics in the Joint European Torus deuterium-tritium 2 campaign (invited)
- 2022
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Ingår i: Review of Scientific Instruments. - : American Institute of Physics (AIP). - 0034-6748 .- 1089-7623. ; 93:9
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Tidskriftsartikel (refereegranskat)abstract
- A new deuterium-tritium experimental, DTE2, campaign has been conducted at the Joint European Torus (JET) between August 2021 and late December 2021. Motivated by significant enhancements in the past decade at JET, such as the ITER-like wall and enhanced auxiliary heating power, the campaign achieved a new fusion energy world record and performed a broad range of fundamental experiments to inform ITER physics scenarios and operations. New capabilities in the area of fusion product measurements by nuclear diagnostics were available as a result of a decade long enhancement program. These have been tested for the first time in DTE2 and a concise overview is provided here. Confined alpha particle measurements by gamma-ray spectroscopy were successfully demonstrated, albeit with limitations at neutron rates higher than some 10(17) n/s. High resolution neutron spectroscopy measurements with the magnetic proton recoil instrument were complemented by novel data from a set of synthetic diamond detectors, which enabled studies of the supra-thermal contributions to the neutron emission. In the area of escaping fast ion diagnostics, a lost fast ion detector and a set of Faraday cups made it possible to determine information on the velocity space and poloidal distribution of the lost alpha particles for the first time. This extensive set of data provides unique information for fundamental physics studies and validation of the numerical models, which are key to inform the physics and scenarios of ITER. Published under an exclusive license by AIP Publishing.
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- Nocente, M., et al.
(författare)
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Generation and observation of fast deuterium ions and fusion-born alpha particles in JET D-He-3 plasmas with the 3-ion radio-frequency heating scenario
- 2020
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Ingår i: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 60:12
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Tidskriftsartikel (refereegranskat)abstract
- Dedicated experiments to generate energetic D ions and D-(3) He fusion-born alpha particles were performed at the Joint European Torus (JET) with the ITER-like wall (ILW). Using the 3-ion D-(D-NBI)-(3) He radio frequency (RF) heating scenario, deuterium ions from neutral beam injection (NBI) were accelerated in the core of mixed D-(3) He plasmas to higher energies with ion cyclotron resonance frequency (ICRF) waves, in turn leading to a core-localized source of alpha particles. The fast-ion distribution of RF-accelerated D-NBI ions was controlled by varying the ICRF and NBI power (P-ICRF approximate to 4-6 MW, P-NBI approximate to 3-20 MW), resulting in rather high D-D neutron (approximate to 1x10(16) s(-1)) and D-(3) He alpha rates (approximate to 2x10(16) s(-1)) at moderate input heating power. Theory and TRANSP analysis shows that large populations of co-passing MeV-range D ions were generated using the D-(D-NBI)-(3) He 3-ion ICRF scenario. This important result is corroborated by several experimental observations, in particular gamma-ray measurements. The developed experimental scenario at JET provides unique conditions for probing several aspects of future burning plasmas, such as the contribution from MeV range ions to global confinement, but without introducing tritium. Dominant fast-ion core electron heating with T-i approximate to T-e and a rich variety of fast-ion driven Alfven eigenmodes (AEs) were observed in these D-(3) He plasmas. The observed AE activities do not have a detrimental effect on the thermal confinement and, in some cases, may be driven by the fusion born alpha particles. A strong continuous increase in neutron rate was observed during long-period sawteeth (>1 s), accompanied by the observation of reversed shear AEs, which implies that a non monotonic q profile was systematically developed in these plasmas, sustained by the large fast-ion populations generated by the 3-ion ICRF scenario.
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| 10. |
- Kirov, K. K., et al.
(författare)
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Impact of interaction between RF waves and fast NBI ions on the fusion performance in JET DTE2 campaign
- 2024
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Ingår i: Nuclear Fusion. - : IOP Publishing Ltd. - 0029-5515 .- 1741-4326. ; 64:1
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Tidskriftsartikel (refereegranskat)abstract
- This work presents a study of the interaction between radio frequency (RF) waves used for ion cyclotron resonance heating and the fast deuterium (D) and tritium (T) neutral Beam injected (NBI) ions in DT plasma. The focus is on the effects of this interaction, also referred to as synergistic effects, on the fusion performance in the recent JET DTE2 campaign. Experimental data from dedicated pulses at 3.43 T/2.3 MA heated at (i) 51.4 MHz, giving the central minority H and n = 2 D, and at (ii) 32.2 MHz for the central minority 3He and n = 2 T. Resonances are analysed and conclusions are drawn and supported by modelling of the synergistic effects. Modelling with transport code TRANSP runs with and without the RF kick operator predict a moderate increase, of about 10%, in DT rates for the case of the RF wave-fast D NBI ion interactions at the n = 2 harmonic of ion cyclotron resonance, and a negligible impact due to synergistic interaction between fast T NBI ions and RF waves. JETTO modelling gives a 29% enhancement in fusion rates due to the interction between RF waves and fast D NBI ions, and an 18% enhancement in fast T NBI ions. Analysis of experimental neutron rates compared to TRANSP predictions without synergistic effects and magnetic proton recoil neutron spectrometer indicate an enhancement of approximately 25%-28% in fusion rates due to RF interaction with fast D ions, and an enhancement of approximately 5%-8% when RF waves and fast T NBI ions are interacting. The contributions of various heating and fast ion sources are assessed and discussed.
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