| 1. |
- Bombarda, F., et al.
(författare)
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Runaway electron beam control
- 2019
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Tidskriftsartikel (refereegranskat)
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| 2. |
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| 3. |
- Joffrin, E., et al.
(författare)
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Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Forskningsöversikt (refereegranskat)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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| 4. |
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| 5. |
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- 2018
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1
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Forskningsöversikt (refereegranskat)
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| 15. |
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| 17. |
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| 18. |
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| 19. |
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- 2018
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:9
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Tidskriftsartikel (refereegranskat)
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| 20. |
- Lu, Yingchang, et al.
(författare)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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| 21. |
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| 22. |
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| 23. |
- Lyons, PA, et al.
(författare)
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Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 5120-
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.
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| 24. |
- Elks, Cathy E, et al.
(författare)
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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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Tidskriftsartikel (refereegranskat)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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| 25. |
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| 26. |
- Surakka, Ida, et al.
(författare)
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A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:10, s. e1002333-
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain similar to 25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79 x 10(-9). There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.
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| 27. |
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| 28. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 29. |
- Salewski, M., et al.
(författare)
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MeV-range velocity-space tomography from gamma-ray and neutron emission spectrometry measurements at JET
- 2017
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Ingår i: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 57:5
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the measurement of a 2D MeV-range ion velocity distribution function by velocity-space tomography at JET. Deuterium ions were accelerated into the MeV-range by third harmonic ion cyclotron resonance heating. We made measurements with three neutron emission spectrometers and a high-resolution gamma-ray spectrometer detecting the gamma-rays released in two reactions. The tomographic inversion based on these five spectra is in excellent agreement with numerical simulations with the ASCOT-RFOF and the SPOT-RFOF codes. The length of the measured fast-ion tail corroborates the prediction that very few particles are accelerated above 2 MeV due to the weak wave-particle interaction at higher energies.
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| 30. |
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| 31. |
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| 32. |
- Vimaleswaran, Karani S, et al.
(författare)
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Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study.
- 2014
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Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595 .- 2213-8587. ; 2:9, s. 719-29
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Tidskriftsartikel (refereegranskat)abstract
- Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
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| 33. |
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| 34. |
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| 35. |
- Bourdelle, C., et al.
(författare)
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Fast H isotope and impurity mixing in ion-temperature-gradient turbulence
- 2018
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Ingår i: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 58:7
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Tidskriftsartikel (refereegranskat)abstract
- In ion-temperature-gradient (ITG) driven turbulence, the resonance condition leads to ion particle turbulent transport coefficients significantly larger than electron particle turbulent transport coefficients. This is shown in nonlinear gyrokinetic simulations and explained by an analytical quasilinear model. It is then illustrated by JETTO-QuaLiKiz integrated modelling. Large ion particle transport coefficients implies that the ion density profiles are uncorrelated to the corresponding ion source, allowing peaked isotope density profiles even in the absence of core source. This also implies no strong core accumulation of He ash. Furthermore, the relaxation time of the individual ion profiles in a multi-species plasma can be significantly faster than the total density profile relaxation time which is constrained by the electrons. This leads to fast isotope mixing and fast impurity transport in FM regimes. In trapped-electron- mode (TEM) turbulence, in presence of electron heating about twice the ion heating, the situation is the inverse: ion particle turbulent transport coefficients are smaller than their electron counterpart.
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| 36. |
- Calabro, G., et al.
(författare)
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Divertor currents optimization procedure for JET-ILW high flux expansion experiments
- 2018
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Ingår i: Fusion engineering and design. - : ELSEVIER SCIENCE SA. - 0920-3796 .- 1873-7196. ; 129, s. 115-119
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Tidskriftsartikel (refereegranskat)abstract
- This paper deals with a divertor coil currents optimized procedure to design High Flux Expansion (HFE) configurations in the JET tokamak aimed to study the effects of flux expansion variation on the radiation fraction and radiated power re-distribution. A number of benefits of HFE configuration have been experimentally demonstrated on TCV, EAST, NSTX and DIII-D tokamaks and are under investigation for next generation devices, as DEMO and DTT. The procedure proposed here exploits the linearized relation between the plasma-wall gaps and the Poloidal Field (PF) coil currents. Once the linearized model is provided by means of CREATE-NL code, the divertor coils currents are calculated using a constrained quadratic programming optimization procedure, in order to achieve HFE configuration. Flux expanded configurations have been experimentally realized both in ohmic and heated plasma with and without nitrogen seeding. Preliminary results on the effects of the flux expansion variation on total power radiation increase will be also briefly discussed.
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| 37. |
- Citrin, J., et al.
(författare)
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Tractable flux-driven temperature, density, and rotation profile evolution with the quasilinear gyrokinetic transport model QuaLiKiz
- 2017
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 59:12
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Tidskriftsartikel (refereegranskat)abstract
- Quasilinear turbulent transport models are a successful tool for prediction of core tokamak plasma profiles in many regimes. Their success hinges on the reproduction of local nonlinear gyrokinetic fluxes. We focus on significant progress in the quasilinear gyrokinetic transport model QuaLiKiz (Bourdelle et al 2016 Plasma Phys. Control. Fusion 58 014036), which employs an approximated solution of the mode structures to significantly speed up computation time compared to full linear gyrokinetic solvers. Optimisation of the dispersion relation solution algorithm within integrated modelling applications leads to flux calculations x 10(6-7) faster than local nonlinear simulations. This allows tractable simulation of flux-driven dynamic profile evolution including all transport channels: ion and electron heat, main particles, impurities, and momentum. Furthermore, QuaLiKiz now includes the impact of rotation and temperature anisotropy induced poloidal asymmetry on heavy impurity transport, important for W-transport applications. Application within the JETTO integrated modelling code results in 1 s of JET plasma simulation within 10 h using 10 CPUs. Simultaneous predictions of core density, temperature, and toroidal rotation profiles for both JET hybrid and baseline experiments are
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| 38. |
- Giacomelli, L., et al.
(författare)
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Neutron emission spectroscopy of DT plasmas at enhanced energy resolution with diamond detectors
- 2016
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Ingår i: Review of Scientific Instruments. - : AMER INST PHYSICS. - 0034-6748 .- 1089-7623. ; 87:11
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Tidskriftsartikel (refereegranskat)abstract
- This work presents measurements done at the Peking University Van de Graaff neutron source of the response of single crystal synthetic diamond (SD) detectors to quasi-monoenergetic neutrons of 14-20 MeV. The results show an energy resolution of 1% for incoming 20 MeV neutrons, which, together with 1% detection efficiency, opens up to new prospects for fast ion physics studies in high performance nuclear fusion devices such as SD neutron spectrometry of deuterium-tritium plasmas heated by neutral beam injection.
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| 39. |
- Hamann, Maike, et al.
(författare)
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Inequality and the biosphere
- 2018
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Ingår i: Annual Review of Environment and Resources. - : Annual Reviews. - 1543-5938 .- 1545-2050. ; 43, s. 61-83
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Forskningsöversikt (refereegranskat)abstract
- Rising inequalities and accelerating global environmental change pose two of the most pressing challenges of the twenty-first century. To explore how these phenomena are linked, we apply a social-ecological systems perspective and review the literature to identify six different types of interactions (or "pathways") between inequality and the biosphere. We find that most of the research so far has only considered one-directional effects of inequality on the biosphere, or vice versa. However, given the potential for complex dynamics between socioeconomic and environmental factors within social-ecological systems, we highlight examples from the literature that illustrate the importance of cross-scale interactions and feedback loops between inequality and the biosphere. This review draws on diverse disciplines to advance a systemic understanding of the linkages between inequality and the biosphere, specifically recognizing cross-scale feedbacks and the multidimensional nature of inequality.
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| 40. |
- Jacobsen, A. S., et al.
(författare)
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Velocity-space sensitivities of neutron emission spectrometers at the tokamaks JET and ASDEX Upgrade in deuterium plasmas
- 2017
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Ingår i: Review of Scientific Instruments. - : AMER INST PHYSICS. - 0034-6748 .- 1089-7623. ; 88:7
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Tidskriftsartikel (refereegranskat)abstract
- Future fusion reactors are foreseen to be heated by the energetic alpha particles produced in fusion reactions. For this to happen, it is important that the energetic ions are sufficiently confined. In present day fusion experiments, energetic ions are primarily produced using external heating systems such as neutral beam injection and ion cyclotron resonance heating. In order to diagnose these fast ions, several different fast-ion diagnostics have been developed and implemented in the various experiments around the world. The velocity-space sensitivities of fast-ion diagnostics are given by so-called weight functions. Here instrument-specific weight functions are derived for neutron emission spectrometry detectors at the tokamaks JET and ASDEX Upgrade for the 2.45 MeV neutrons produced in deuterium-deuterium reactions in deuterium plasmas. Using these, it is possible to directly determine which part of velocity space each detector observes.
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| 41. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:8, s. 753-60
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
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| 42. |
- Kiptily, V. G., et al.
(författare)
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Escaping alpha-particle monitor for burning plasmas
- 2018
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Ingår i: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 58:8
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a diagnostic system, gamma-ray alpha-particle monitor (GRAM), for continuous monitoring of deuterium-tritium fusion alpha-particles in the MeV energy range escaped from the plasma to the first wall. The diagnostic is based on the detection of gamma-rays produced in nuclear reactions. The reactions Be-9(alpha,eta,gamma)C-12 and B-10(alpha,p,gamma)C-13 have been selected. For that purpose, Be- or B-10-target is placed on the first wall, where the alphas are expected to be mostly lost. Striking the target, the lost alphas generate specific gamma-rays, if their energy E-alpha > 1.5 MeV. To measure this gamma-ray emission, the target should be in the field of view of a collimated detector, which is protected from neutrons and background gammas. The calibrated detector could deliver absolute values of the lost alpha-particle flux with a temporal resolution depending on intensity of losses. A high-performance gamma-ray spectrometer with a novel architecture, GRITER, is proposed to be used in GRAM. It consists of a stack of the optically isolated high-Z fast scintillators with independent signal readout. GRITER is supposed to be operated at count-rates substantially exceeding the capability of a single crystal detector of the same size. The GRAM diagnostic system consists of two identical spectrometers, which measure both gamma-rays due to alpha-particle loss and gamma-ray background ensuring reliable data in a harsh reactor environment. GRAM could be tested during the non-DT plasma operation monitoring lost DD fusion products, neutral beam heating D-ions (E-D > 0.5 MeV) and ICRF accelerated H- and He-3-ions through the detection of gamma-rays resulting from nuclear reactions. The use of GRAM on JET and ITER, including events with extremely high loss rates, is discussed.
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| 43. |
- Kiptily, V. G., et al.
(författare)
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On a fusion born triton effect in JET deuterium discharges with H-minority ion cyclotron range of frequencies heating
- 2019
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Ingår i: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 59:6
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Tidskriftsartikel (refereegranskat)abstract
- An effect due to fusion born triton production has been observed in JET high-performance deuterium plasma discharges with neutral beam injection (NBI) and H-minority ion cyclotron range of frequencies (ICRF) heating, using DD and deuterium tritium (DT) neutron spectrometry as well as fusion product loss measurements. The observations show that a decrease of the second harmonic omega = 2 omega(cD) enhancement of the DD neutron rate correlates with an increase of the triton burnup rate. An acceleration of tritons due to absorbing ICRH power at the third harmonic omega = 3 omega(cT) has been observed. This effect could indicate a redistribution of ICRH power absorption at omega approximate to omega(cH) = 2 omega(cD) = 3 omega(cT) with increasing triton concentration at the ion cyclotron resonance layer. Also, the reduction of the second harmonic enhancement of the DD neutron rate can be caused by burning of the accelerated deuterium as the tritium concentration grows. This is an extremely non-linear process as both mechanisms intensify with triton concentration. It determines the necessity to consider the ICRH power absorption omega = 3 omega(cT) in modelling of high-performance deuterium discharges with simultaneous NBI and H-minority ICRF heating as well as the assessment of enhanced burnup of ICRF accelerated deuterium for the development of high-performance plasma scenarios and DT fusion rate predictions.
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| 44. |
- Korhonen, Emilia A., et al.
(författare)
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Lymphangiogenesis requires Ang2/Tie/PI3K signaling for VEGFR3 cell-surface expression
- 2022
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Ingår i: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 132:15
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor C (VEGF-C) induces lymphangiogenesis via VEGF receptor 3 (VEGFR3), which is encoded by the most frequently mutated gene in human primary lymphedema. Angiopoietins (Angs) and their Tie receptors regulate lymphatic vessel development, and mutations of the ANGPT2 gene were recently found in human primary lymphedema. However, the mechanistic basis of Ang2 activity in lymphangiogenesis is not fully understood. Here, we used gene deletion, blocking Abs, transgene induction, and gene transfer to study how Ang2, its Tie2 receptor, and Tie1 regulate lymphatic vessels. We discovered that VEGF-C???induced Ang2 secretion from lymphatic endothelial cells (LECs) was involved in full Akt activation downstream of phosphoinositide 3 kinase (PI3K). Neonatal deletion of genes encoding the Tie receptors or Ang2 in LECs, or administration of an Ang2-blocking Ab decreased VEGFR3 presentation on LECs and inhibited lymphangiogenesis. A similar effect was observed in LECs upon deletion of the PI3K catalytic p110?? subunit or with small -molecule inhibition of a constitutively active PI3K located downstream of Ang2. Deletion of Tie receptors or blockade of Ang2 decreased VEGF-C???induced lymphangiogenesis also in adult mice. Our results reveal an important crosstalk between the VEGF-C and Ang signaling pathways and suggest new avenues for therapeutic manipulation of lymphangiogenesis by targeting Ang2/Tie/PI3K signaling.
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| 45. |
- Leta, Tesfaye H., et al.
(författare)
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The use of antibiotic-loaded bone cement and systemic antibiotic prophylactic use in 2,971,357 primary total knee arthroplasties from 2010 to 2020: an international register-based observational study among countries in Africa, Europe, North America, and Oceania
- 2023
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Ingår i: Acta Orthopaedica. - 1745-3674 .- 1745-3682. ; 94, s. 416-425
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose — Antibiotic-loaded bone cement (ALBC) and systemic antibiotic prophylaxis (SAP) have been used to reduce periprosthetic joint infection (PJI) rates. We investigated the use of ALBC and SAP in primary total knee arthroplasty (TKA). Patients and methods — This observational study is based on 2,971,357 primary TKAs reported in 2010–2020 to national/regional joint arthroplasty registries in Australia, Den-mark, Finland, Germany, Italy, the Netherlands, New Zealand, Norway, Romania, South Africa, Sweden, Switzerland, the UK, and the USA. Aggregate-level data on trends and types of bone cement, antibiotic agents, and doses and duration of SAP used was extracted from participating registries. Results — ALBC was used in 77% of the TKAs with variation ranging from 100% in Norway to 31% in the USA. Palacos R+G was the most common (62%) ALBC type used. The primary antibiotic used in ALBC was gentamicin (94%). Use of ALBC in combination with SAP was common practice (77%). Cefazolin was the most common (32%) SAP agent. The doses and duration of SAP used varied from one single preoperative dosage as standard practice in Bolzano, Italy (98%) to 1-day 4 doses in Norway (83% of the 40,709 TKAs reported to the Norwegian arthroplasty register). Conclusion — The proportion of ALBC usage in primary TKA varies internationally, with gentamicin being the most common antibiotic. ALBC in combination with SAP was common practice, with cefazolin the most common SAP agent. The type of ALBC and type, dose, and duration of SAP varied among participating countries.
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| 46. |
- Litaudon, X., et al.
(författare)
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14 MeV calibration of JET neutron detectors-phase 1: Calibration and characterization of the neutron source
- 2018
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:2
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Tidskriftsartikel (refereegranskat)abstract
- In view of the planned DT operations at JET, a calibration of the JET neutron monitors at 14 MeV neutron energy is needed using a 14 MeV neutron generator deployed inside the vacuum vessel by the JET remote handling system. The target accuracy of this calibration is 10% as also required by ITER, where a precise neutron yield measurement is important, e.g. for tritium accountancy. To achieve this accuracy, the 14 MeV neutron generator selected as the calibration source has been fully characterised and calibrated prior to the in-vessel calibration of the JET monitors. This paper describes the measurements performed using different types of neutron detectors, spectrometers, calibrated long counters and activation foils which allowed us to obtain the neutron emission rate and the anisotropy of the neutron generator, i.e.The neutron flux and energy spectrum dependence on emission angle, and to derive the absolute emission rate in 4π sr. The use of high resolution diamond spectrometers made it possible to resolve the complex features of the neutron energy spectra resulting from the mixed D/T beam ions reacting with the D/T nuclei present in the neutron generator target. As the neutron generator is not a stable neutron source, several monitoring detectors were attached to it by means of an ad hoc mechanical structure to continuously monitor the neutron emission rate during the in-vessel calibration. These monitoring detectors, two diamond diodes and activation foils, have been calibrated in terms of neutrons/counts within ± 5% total uncertainty. A neutron source routine has been developed, able to produce the neutron spectra resulting from all possible reactions occurring with the D/T ions in the beam impinging on the Ti D/T target. The neutron energy spectra calculated by combining the source routine with a MCNP model of the neutron generator have been validated by the measurements. These numerical tools will be key in analysing the results from the in-vessel calibration and to derive the response of the JET neutron detectors to DT plasma neutrons starting from the response to the generator neutrons, and taking into account all the calibration circumstances.
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| 47. |
- Maggi, C. F., et al.
(författare)
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Isotope identity experiments in JET-ILW with H and D L-mode plasmas
- 2019
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Ingår i: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 59:7
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Tidskriftsartikel (refereegranskat)abstract
- NBI-heated L-mode plasmas have been obtained in JET with the Be/W ITER-like wall (JET-ILW) in H and D, with matched profiles of the dimensionless plasma parameters, rho*, nu*, beta and q in the plasma core confinement region and same T-i/T-e and Z(eff). The achieved isotope identity indicates that the confinement scale invariance principle is satisfied in the core confinement region of these plasmas, where the dominant instabilities are Ion Temperature Gradient (ITG) modes. The dimensionless thermal energy confinement time, Omega(i) tau(E,th), and the scaled core plasma heat diffusivity, A chi(eff)/B-T, are identical in H and D within error bars, indicating lack of isotope mass dependence of the dimensionless L-mode thermal energy confinement time in JET-ILW. Predictive flux driven simulations with JETTO-TGLF of the H and D identity pair is in very good agreement with experiment for both isotopes: the stiff core heat transport, typical of JET-ILW NBI heated L-modes, overcomes the local gyro-Bohm scaling of gradient-driven TGLF, explaining the lack of isotope mass dependence in the confinement region of these plasmas. The effect of E x B shearing on the predicted heat and particle transport channels is found to be negligible for these low beta and low momentum input plasmas.
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| 48. |
- Matthews, G. F., et al.
(författare)
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Dynamic power balance analysis in JET
- 2017
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Ingår i: Physica Scripta. - : IOP PUBLISHING LTD. - 0031-8949 .- 1402-4896. ; T170
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Tidskriftsartikel (refereegranskat)abstract
- The full scale realisation of nuclear fusion as an energy source requires a detailed understanding of power and energy balance in current experimental devices. In this we explore whether a global power balance model in which some of the calibration factors applied to the source or sink terms are fitted to the data can provide insight into possible causes of any discrepancies in power and energy balance seen in the JET tokamak. We show that the dynamics in the power balance can only be properly reproduced by including the changes in the thermal stored energy which therefore provides an additional opportunity to cross calibrate other terms in the power balance equation. Although the results are inconclusive with respect to the original goal of identifying the source of the discrepancies in the energy balance, we do find that with optimised parameters an extremely good prediction of the total power measured at the outer divertor target can be obtained over a wide range of pulses with time resolution up to similar to 25 ms.
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| 49. |
- Matthews, G. F., et al.
(författare)
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Melt damage to the JET ITER-like Wall and divertor
- 2016
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Ingår i: Physica Scripta. - : IOP PUBLISHING LTD. - 0031-8949 .- 1402-4896. ; T167
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Tidskriftsartikel (refereegranskat)abstract
- In October 2014, JET completed a scoping study involving high power scenario development in preparation for DT along with other experiments critical for ITER. These experiments have involved intentional and unintentional melt damage both to bulk beryllium main chamber tiles and to divertor tiles. This paper provides an overview of the findings of concern for machine protection in JET and ITER, illustrating each case with high resolution images taken by remote handling or after removal from the machine. The bulk beryllium upper dump plate tiles and some other protection tiles have been repeatedly flash melted by what we believe to be mainly fast unmitigated disruptions. The flash melting produced in this way is seen at all toroidal locations and the melt layer is driven by j x B forces radially outward and upwards against gravity. In contrast, the melt pools caused while attempting to use MGI to mitigate deliberately generated runaway electron beams are localized to several limiters and the ejected material appears less influenced by j. x. B forces and shows signs of boiling. In the divertor, transient melting of bulk tungsten by ELMs was studied in support of the ITER divertor material decision using a specially prepared divertor module containing an exposed edge. Removal of the module from the machine in 2015 has provided improved imaging of the melt and this confirms that the melt layers are driven by ELMs. No other melt damage to the other 9215 bulk tungsten lamellas has yet been observed.
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| 50. |
- Meisl, G., et al.
(författare)
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Simulating the nitrogen migration in Be/W tokamaks with WallDYN
- 2016
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Ingår i: Physica Scripta. - : IOP PUBLISHING LTD. - 0031-8949 .- 1402-4896. ; T167
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Tidskriftsartikel (refereegranskat)abstract
- The migration of wall material or seeding impurities plays an important role in the formation of mixed materials, the impurity contamination of the plasma and tritium retention. First, this work presents an improved model for the sputtering from mixed material surfaces in WallDYN. Second, we present dynamic SDTrimSP and WallDYN simulations of the nitrogen implantation in Be and the migration of nitrogen in tokamaks with a Be main wall. The simulations with the binary collision code SDTrimSP predict that N accumulates directly at the surface and that the Be erosion decreases with increasing N surface content. A first application of WallDYN to the nitrogen migration with an ITER-like wall indicates that the Be main wall may cause wall pumping of N by co-deposition with Be.
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