| 1. |
- Arking, D. E., et al.
(författare)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 2. |
- Buttery, R. J., et al.
(författare)
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The Impact of 3-D Fields on Tearing Mode Stability of H-modes
- 2011
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Ingår i: Nuclear Fusion. - 1741-4326 .- 0029-5515. ; 51, s. 073016-
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Tidskriftsartikel (refereegranskat)abstract
- New processes have been discovered in the interaction of 3D fields with tearing mode stability at low torque and modest β on DIII-D and NSTX. These are thought to arise from the plasma response at the tearing resonant surface, which theoretically is expected to depend strongly on plasma rotation and underlying intrinsic tearing stability. This leads to sensitivities additional to those previously identified at low density where the plasma rotation is more readily stopped, or at high βN where ideal MHD responses amplify the fields (where βN is the plasma β divided by the ratio of plasma current to minor radius multiplied by toroidal field). It is found that the threshold size for 3D fields to induce modes tends to zero as the natural tearing βN limit is approached. 3D field sensitivity is further enhanced at low rotation, with magnetic probing detecting an increased response to applied fields in such regimes. Modelling with the MARS-F code confirms the interpretation with the usual plasma screening response breaking down in low rotation plasmas and a tearing response developing, opening the door to additional sensitivities to β and the current profile. Typical field thresholds to induce modes in torque-free βN ~ 1.5 H-modes are well below those in ohmic plasmas or plasmas near the ideal βN limit. The strong interaction with the tearing mode βN limit is identified through rotation shear, which is decreased by the 3D field, leading to decreased tearing stability. Thus both locked and rotating mode field thresholds can be considered in terms of a torque balance, with sufficient braking leading to destabilization of a mode. On this basis new measurements of the principal parameter scalings for error field threshold have been obtained in torque-free H-modes leading to new predictions for error field sensitivity in ITER. The scalings have similar exponents to ohmic plasmas, but with seven times lower threshold at the ITER baseline βN value of 1.8, and a linear dependence on proximity to the tearing mode βN limit (~2.2 at zero torque). This reinforces the need to optimize error field correction strategies in ITER, and implement sources to drive plasma rotation.
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