| 61. |
- Ericsson, H., et al.
(författare)
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Phase 1 Pharmacokinetic Study of AZD5718 in Healthy Volunteers: Effects of Coadministration With Rosuvastatin, Formulation and Food on Oral Bioavailability
- 2020
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Ingår i: Clinical Pharmacology in Drug Development. - : Wiley. - 2160-7648 .- 2160-763X. ; 9:3, s. 411-421
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Tidskriftsartikel (refereegranskat)abstract
- AZD5718 is a first-in-class small-molecule anti-inflammatory drug with the potential to reduce the residual risk of cardiovascular events after myocardial infarction in patients receiving lipid-lowering statin therapy. Leukotrienes are potent proinflammatory and vasoactive mediators synthesized in leukocytes via 5-lipoxygenase and 5-lipoxygenase-activating protein (FLAP). AZD5718 is a FLAP inhibitor that dose-dependently reduced leukotriene biosynthesis in a first-in-human study. We enrolled 12 healthy men in a randomized, open-label, crossover, single-dose phase 1 pharmacokinetic study of AZD5718 to investigate a potential drug-drug interaction with rosuvastatin, and the effects of formulation and food intake (ClinicalTrials.gov identifier: NCT02963116). Rosuvastatin (10 mg) were absorbed more rapidly when coadministered with AZD5718 (200 mg), probably owing to weak inhibition of hepatic statin uptake, but relative bioavailability was unaffected (geometric least-squares mean ratio [GMR], 100%; 90% confidence interval [CI], 86%-116%). AZD5718 pharmacokinetics were unaffected by coadministration of rosuvastatin. AZD5718 (200 mg) was absorbed less rapidly when formulated as tablets than oral suspension, with reduced relative bioavailability (GMR, 72%; 90%CI, 64%-80%). AZD5718 absorption was slower when 200-mg tablets were taken after a high-fat breakfast than after fasting, but relative bioavailability was unaffected (GMR, 96%; 90%CI, 87%-106%). In post hoc pharmacodynamic simulations, plasma leukotriene B-4 levels were inhibited by >90% throughout the day following once-daily AZD5718, regardless of formulation or administration with food. AZD5718 was well tolerated, with no severe or serious adverse events. These data supported the design of a phase 2a efficacy study of AZD5718 in patients with coronary artery disease.
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| 62. |
- Frassinetti, Lorenzo, et al.
(författare)
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Dimensionless scalings of confinement, heat transport and pedestal stability in JET-ILW and comparison with JET-C
- 2017
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 59:1
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Tidskriftsartikel (refereegranskat)abstract
- Three dimensionless scans in the normalized Larmor radius rho*, normalized collisionality nu* and normalized plasma pressure beta have been performed in JET with the ITER-like wall (JET-ILW). The normalized energy confinement and the thermal diffusivity exhibit a scaling with rho* consistent with the earlier results obtained in the carbon wall JET (JET-C) and with a gyro-Bohm scaling. In the pedestal, experimental results show that the stability is not dependent on rho*, qualitatively in agreement with the peeling-ballooning (P-B) model. The nu* dimensionless scaling shows that JET-ILW normalized confinement has a stronger dependence on collisionality than JET-C. This leads to a reduction of the difference in the confinement between JET-ILW and JET-C to approximate to 10% at low nu*. The pedestal stability shows an improvement with decreasing nu*. This is ascribed to the increase of the bootstrap current, to the reduction of the pedestal width and to the reduction of the relative shift between pedestal density and temperature position. The beta dimensionless scan shows that, at low collisionality, JET-ILW normalized confinement has no clear dependence with beta, in agreement with part of the earlier scalings. At high collisionality, a reduction of the normalized confinement with increasing beta is observed. This behaviour is driven mainly by the pedestal where the stability is reduced with increasing beta. The P-B analysis shows that the stability reduction with increasing beta at high nu* is due to the destabilizing effect of the increased relative shift.
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| 63. |
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| 64. |
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| 65. |
- Korsholm, S. B., et al.
(författare)
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Development of novel fuel ion ratio diagnostic techniques
- 2010
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 81:10, s. 10D323-
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Tidskriftsartikel (refereegranskat)abstract
- To overcome the challenge of measuring the fuel ion ratio in the core (rho<0.3) of ITER, a coordinated effort aiming at developing diagnostic techniques has been initiated. The investigated techniques are novel uses or further development of existing methods such as charge exchange recombination spectrometry, neutron spectrometry, and collective Thomson scattering. An overview of the work on the three diagnostic techniques is presented.
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| 66. |
- Krasilnikov, A. V., et al.
(författare)
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Fundamental ion cyclotron resonance heating of JET deuterium plasmas
- 2009
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 51:4, s. 044005-
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Tidskriftsartikel (refereegranskat)abstract
- Radio frequency heating of majority ions is of prime importance for understanding the basic role of auxiliary heating in the activated D-T phase of ITER. Majority deuterium ion cyclotron resonance heating (ICRH) experiments at the fundamental cyclotron frequency were performed in JET. In spite of the poor antenna coupling at 25 MHz, this heating scheme proved promising when adopted in combination with D neutral beam injection (NBI). The effect of fundamental ICRH of a D population was clearly demonstrated in these experiments: by adding similar to 25% of heating power the fusion power was increased up to 30-50%, depending on the type of NBI adopted. At this power level, the ion and electron temperatures increased from T-i similar to 4.0 keV and T-e similar to 4.5 keV (NBI-only phase) to T-i similar to 5.5 keV and T-e similar to 5.2 keV (ICRH + NBI phase), respectively. The increase in the neutron yield was stronger when 80 keV rather than 130 keV deuterons were injected in the plasma. It is shown that the neutron rate, the diamagnetic energy and the electron as well as the ion temperature scale roughly linearly with the applied RF power. A synergistic effect of the combined use of ICRF and NBI heating was observed: (i) the number of neutron counts measured by the neutron camera during the combined ICRF + NBI phases of the discharges exceeded the sum of the individual counts of the NBI-only and ICRF-only phases; (ii) a substantial increase in the number of slowing-down beam ions was detected by the time of flight neutron spectrometer when ICRF power was switched on; (iii) a small D subpopulation with energies slightly above the NBI launch energy was detected by the neutral particle analyzer and gamma-ray spectroscopy.
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| 67. |
- Lanctot, M. J., et al.
(författare)
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Impact of toroidal and poloidal mode spectra on the control of non-axisymmetric fields in tokamaks
- 2017
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Ingår i: Physics of Plasmas. - : American Institute of Physics (AIP). - 1070-664X .- 1089-7674. ; 24:5
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Tidskriftsartikel (refereegranskat)abstract
- In several tokamaks, non-axisymmetric magnetic field studies show that applied magnetic fields with a toroidal harmonic n = 2 can lead to disruptive n = 1 locked modes. In Ohmic plasmas, n = 2 magnetic reconnection thresholds in otherwise stable discharges are readily accessed at edge safety factors q similar to 3, low density, and low rotation. Similar to previous studies with n = 1 fields, the thresholds are correlated with the "overlap" field computed with the IPEC code. The overlap field quantifies the plasma-mediated coupling of the external field to the resonant field. Remarkably, the "critical overlap fields" at which magnetic islands form are similar for applied n = 1 and 2 fields. The critical overlap field increases with plasma density and edge safety factor but is independent of the toroidal field. Poloidal harmonics m> nq dominate the drive for resonant fields while m < nq harmonics have a negligible impact. This contrasts with previous results in H-mode discharges at high plasma pressure in which the toroidal angular momentum is sensitive to low poloidal harmonics. Together, these results highlight unique requirements for n > 1 field control including the need for multiple rows of coils to control selected plasma parameters for specific functions (e.g., rotation control or ELM suppression).
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| 68. |
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| 69. |
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| 70. |
- Oya, Yasuhisa, et al.
(författare)
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Correlation of surface chemical states with hydrogen isotope retention in divertor tiles of JET with ITER-Like Wall
- 2018
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Ingår i: Fusion engineering and design. - : ELSEVIER SCIENCE SA. - 0920-3796 .- 1873-7196. ; 132, s. 24-28
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Tidskriftsartikel (refereegranskat)abstract
- To understand the fuel retention mechanism correlation of surface chemical states and hydrogen isotope retention behavior determined by XPS (X-ray photoelectron spectroscopy) and TDS (Thermal desorption spectroscopy), respectively, for JET ITER-Like Wall samples from operational period 2011-2012 were investigated. It was found that the deposition layer was formed on the upper part of the inner vertical divertor area. At the inner plasma strike point region, the original surface materials, W or Mo, were found, indicating to an erosion-dominated region, but deposition of impurities was also found. Higher heat load would induce the formation of metal carbide. At the outer horizontal divertor tile, mixed material layer was formed with iron as an impurity. TDS showed the H and D desorption behavior and the major D desorption temperature for the upper part of the inner vertical tile was located at 370 degrees C and 530 degrees C. At the strike point region, the D desorption temperature was clearly shifted toward higher release temperatures, indicating the stabilization of D trapping by higher heat load
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