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- Walters, R G, et al.
(författare)
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A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 463:7281, s. 671-5
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Tidskriftsartikel (refereegranskat)abstract
- Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.
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- Mariani, A., et al.
(författare)
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First-principle based predictions of the effects of negative triangularity on DTT scenarios
- 2024
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 64:4
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Tidskriftsartikel (refereegranskat)abstract
- Plasmas with negative triangularity (NT) shape have been recently shown to be able to achieve H-mode levels of confinement in L-mode, avoiding detrimental edge localised modes. Therefore, this plasma geometry is now studied as a possible viable option for a future fusion reactor. Within this framework, an NT option is under investigation for the full power scenario of the Divertor Tokamak Test (DTT) facility, under construction in Italy, with δ t o p = − 0.32 / δ b o t t o m ≃ 0.02 top/bottom triangularity values at the separatrix. The transport properties of this scenario are studied in this work. Gyrokinetic GENE simulations and integrated modelling using ASTRA with the quasi-linear trapped gyro-Landau fluid (TGLF) model have been performed. The emerging picture from the ASTRA-TGLF runs with boundary conditions at ρ t o r = 0.94 is that, in the L-mode NT option, the larger peaking of the kinetic profiles in the edge region is not sufficient to recover the loss of the PT H-mode pedestal, and reach similar central temperature values. Two additional shapes are also considered, obtained by flipping the triangularity of the scenarios, to single out the effect of the triangularity sign. A negligible ‘direct’ effect of the triangularity is found for the L-mode, while a small beneficial effect is observed for the H-mode. The ASTRA-TGLF results are validated by GENE and TGLF stand-alone at two selected radii. GENE shows ITG dominant micro-instability and explains the small beneficial effect of the NT for the H-mode as due to a strong reduction of the heat fluxes, when reversing the triangularity, with a relatively high T i stiffness. An improvement of the predicted performances of the NT DTT scenario could come from ρ tor ≳ 0.9 , as indicated by some recent experiments at the tokamak à configuration variable (TCV) and ASDEX Upgrade.
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