| 1. |
- Labit, B., et al.
(författare)
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Dependence on plasma shape and plasma fueling for small edge-localized mode regimes in TCV and ASDEX Upgrade
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:8
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 Institute of Physics Publishing. All rights reserved. Within the EUROfusion MST1 work package, a series of experiments has been conducted on AUG and TCV devices to disentangle the role of plasma fueling and plasma shape for the onset of small ELM regimes. On both devices, small ELM regimes with high confinement are achieved if and only if two conditions are fulfilled at the same time. Firstly, the plasma density at the separatrix must be large enough (ne,sep/nG ∼ 0.3), leading to a pressure profile flattening at the separatrix, which stabilizes type-I ELMs. Secondly, the magnetic configuration has to be close to a double null (DN), leading to a reduction of the magnetic shear in the extreme vicinity of the separatrix. As a consequence, its stabilizing effect on ballooning modes is weakened.
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| 2. |
- Meyer, H.F., et al.
(författare)
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Overview of physics studies on ASDEX Upgrade
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Forskningsöversikt (refereegranskat)abstract
- The ASDEX Upgrade (AUG) programme, jointly run with the EUROfusion MST1 task force, continues to significantly enhance the physics base of ITER and DEMO. Here, the full tungsten wall is a key asset for extrapolating to future devices. The high overall heating power, flexible heating mix and comprehensive diagnostic set allows studies ranging from mimicking the scrape-off-layer and divertor conditions of ITER and DEMO at high density to fully non-inductive operation (q 95 = 5.5, ) at low density. Higher installed electron cyclotron resonance heating power 6 MW, new diagnostics and improved analysis techniques have further enhanced the capabilities of AUG. Stable high-density H-modes with MW m-1 with fully detached strike-points have been demonstrated. The ballooning instability close to the separatrix has been identified as a potential cause leading to the H-mode density limit and is also found to play an important role for the access to small edge-localized modes (ELMs). Density limit disruptions have been successfully avoided using a path-oriented approach to disruption handling and progress has been made in understanding the dissipation and avoidance of runaway electron beams. ELM suppression with resonant magnetic perturbations is now routinely achieved reaching transiently . This gives new insight into the field penetration physics, in particular with respect to plasma flows. Modelling agrees well with plasma response measurements and a helically localised ballooning structure observed prior to the ELM is evidence for the changed edge stability due to the magnetic perturbations. The impact of 3D perturbations on heat load patterns and fast-ion losses have been further elaborated. Progress has also been made in understanding the ELM cycle itself. Here, new fast measurements of and E r allow for inter ELM transport analysis confirming that E r is dominated by the diamagnetic term even for fast timescales. New analysis techniques allow detailed comparison of the ELM crash and are in good agreement with nonlinear MHD modelling. The observation of accelerated ions during the ELM crash can be seen as evidence for the reconnection during the ELM. As type-I ELMs (even mitigated) are likely not a viable operational regime in DEMO studies of 'natural' no ELM regimes have been extended. Stable I-modes up to have been characterised using -feedback. Core physics has been advanced by more detailed characterisation of the turbulence with new measurements such as the eddy tilt angle - measured for the first time - or the cross-phase angle of and fluctuations. These new data put strong constraints on gyro-kinetic turbulence modelling. In addition, carefully executed studies in different main species (H, D and He) and with different heating mixes highlight the importance of the collisional energy exchange for interpreting energy confinement. A new regime with a hollow profile now gives access to regimes mimicking aspects of burning plasma conditions and lead to nonlinear interactions of energetic particle modes despite the sub-Alfvénic beam energy. This will help to validate the fast-ion codes for predicting ITER and DEMO.
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| 3. |
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| 4. |
- Aurelius, Johan, 1980, et al.
(författare)
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NOX2-dependent immunosuppression in chronic myelomonocytic leukemia
- 2017
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Ingår i: Journal of Leukocyte Biology. - 0741-5400 .- 1938-3673. ; 102:2, s. 459-466
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Tidskriftsartikel (refereegranskat)abstract
- Chronic myelomonocytic leukemia (CMML) is a myeloproliferative and myelodysplastic neoplasm with few treatment options and dismal prognosis. The role of natural killer (NK) cells and other antileukemic lymphocytes in CMML is largely unknown. We aimed to provide insight into the mechanisms of immune evasion in CMML with a focus on immunosuppressive reactive oxygen species (ROS) formed by the myeloid cell NADPH oxidase-2 (NOX2). The dominant population of primary human CMML cells was found to express membrane-bound NOX2 and to release ROS, which, in turn, triggered extensive PARP-1-dependent cell death in cocultured NK cells, CD8(+) T effector memory cells, and CD8(+) T effector cells. Inhibitors of ROS formation and scavengers of extracellular ROS prevented CMML cell-induced lymphocyte death and facilitated NK cell degranulation toward Ab-coated, primary CMML cells. In patients with CMML, elevation of immature cell counts (CD34(+)) in blood was associated with reduced expression of several NK cell-activating receptors. We propose that CMML cells may use extracellular ROS as a targetable mechanism of immune escape.
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| 5. |
- Krieger, K., et al.
(författare)
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Investigation of transient melting of tungsten by ELMs in ASDEX Upgrade
- 2017
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Ingår i: Physica Scripta. - : IOP PUBLISHING LTD. - 0031-8949 .- 1402-4896. ; T170
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Tidskriftsartikel (refereegranskat)abstract
- Repetitive melting of tungsten by power transients originating from edge localized modes (ELMs) has been studied in the tokamak experiment ASDEX Upgrade. Tungsten samples were exposed to H-mode discharges at the outer divertor target plate using the Divertor Manipulator II system. The exposed sample was designed with an elevated sloped surface inclined against the incident magnetic field to increase the projected parallel power flux to a level were transient melting by ELMs would occur. Sample exposure was controlled by moving the outer strike point to the sample location. As extension to previous melt studies in the new experiment both the current flow from the sample to vessel potential and the local surface temperature were measured with sufficient time resolution to resolve individual ELMs. The experiment provided for the first time a direct link of current flow and surface temperature during transient ELM events. This allows to further constrain the MEMOS melt motion code predictions and to improve the validation of its underlying model assumptions. Post exposure ex situ analysis of the retrieved samples confirms the decreased melt motion observed at shallower magnetic field line to surface angles compared to that at leading edges exposed to the parallel power flux.
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| 6. |
- Mathieu, C., et al.
(författare)
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Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes (the DEPICT-2 Study): 24-Week Results From a Randomized Controlled Trial
- 2018
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 41:9, s. 1938-1946
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEThis 24-week, double-blinded, phase 3 clinical trial (DEPICT-2; ClinicalTrials.gov, NCT02460978) evaluated efficacy and safety of dapagliflozin as adjunct therapy to adjustable insulin in patients with inadequately controlled type 1 diabetes (HbA(1c) 7.5-10.5%).RESEARCH DESIGN AND METHODSPatients were randomized 1:1:1 to dapagliflozin 5 mg (n = 271), dapagliflozin 10 mg (n = 270), or placebo (n = 272) plus insulin. Insulin dose was adjusted by investigators according to self-monitored glucose readings, local guidance, and individual circumstances.RESULTSBaseline characteristics were balanced between treatment groups. At week 24, dapagliflozin significantly decreased HbA(1c) (primary outcome; difference vs. placebo: dapagliflozin 5 mg -0.37% [95% CI -0.49, -0.26], dapagliflozin 10 mg -0.42% [-0.53, -0.30]), total daily insulin dose (-10.78% [-13.73, -7.72] and -11.08% [-14.04, -8.02], respectively), and body weight (-3.21% [-3.96, -2.45] and -3.74% [-4.49, -2.99], respectively) (P < 0.0001 for all). Mean interstitial glucose, amplitude of glucose excursion, and percent of readings within target glycemic range (>70 to 180 mg/dL) versus placebo were significantly improved. More patients receiving dapagliflozin achieved a reduction in HbA(1c) 0.5% without severe hypoglycemia compared with placebo. Adverse events were reported for 72.7%, 67.0%, and 63.2% of patients receiving dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo, respectively. Hypoglycemia, including severe hypoglycemia, was balanced between groups. There were more adjudicated definite diabetic ketoacidosis (DKA) events with dapagliflozin: 2.6%, 2.2%, and 0% for dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo, respectively.CONCLUSIONSDapagliflozin as adjunct therapy to adjustable insulin in patients with type 1 diabetes was well tolerated and improved glycemic control with no increase in hypoglycemia versus placebo but with more DKA events.
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| 7. |
- Mathieu, C., et al.
(författare)
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Glucose Variables in Type 1 Diabetes Studies With Dapagliflozin: Pooled Analysis of Continuous Glucose Monitoring Data From DEPICT-1 and-2
- 2019
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 42:6, s. 1081-1087
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEThis pooled analysis assessed continuous glucose monitoring (CGM) in patients with inadequately controlled type 1 diabetes (HbA(1c) >= 7.7 to <= 11.0% [>= 61 to <= 97 mmol/mol]) who received dapagliflozin as an adjunct to adjustable insulin.RESEARCH DESIGN AND METHODSCGM data were pooled from two 24-week, double-blind, randomized, phase 3 studies: Dapagliflozin Evaluation in Patients with Inadequately Controlled Type 1 Diabetes (DEPICT-1 and DEPICT-2). These studies comprised 1,591 patients receiving dapagliflozin 5 mg (n = 530), dapagliflozin 10 mg (n = 529), or placebo (n = 532).RESULTSBaseline characteristics were balanced between treatment groups. Patients receiving dapagliflozin 5 mg or 10 mg both spent more time with blood glucose in the range >3.9 to <= 10.0 mmol/L (>70 to <= 180 mg/dL) over 24 h than those receiving the placebo. The adjusted mean (SE) change from baseline at week 24 was 6.48% (0.60) with dapagliflozin 5 mg, 8.08% (0.60) with dapagliflozin 10 mg, and -2.59% (0.61) with placebo. At week 24, the mean amplitude of glucose excursion over 24 h, mean 24-h glucose values, and postprandial glucose values were also improved in patients receiving dapagliflozin over those receiving placebo. No marked differences were found at week 24 between dapagliflozin 5 or 10 mg and placebo in the percentage of glucose values <= 3.9 mmol/L (<= 70 mg/dL) or <= 3.0 mmol/L (<= 54 mg/dL) over 24 h, or in nocturnal (0000-0559 h) glucose values <= 3.9 mmol/L (<= 70 mg/dL).CONCLUSIONSIn patients with type 1 diabetes, treatment with dapagliflozin over 24 weeks improved time in range, mean glucose, and glycemic variability without increasing the time spent in the range indicating hypoglycemia.
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| 8. |
- Pesce, S., et al.
(författare)
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The Innate Immune Cross Talk between NK Cells and Eosinophils Is Regulated by the Interaction of Natural Cytotoxicity Receptors with Eosinophil Surface Ligands
- 2017
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies suggested that the cross talk between NK cells and other cell types is crucial for the regulation of both innate and adaptive immune responses. In the present study, we analyzed the phenotypic and functional outcome of the interaction between resting or cytokine-activated NK cells and eosinophils derived from non-atopic donors. Our results provide the first evidence that a natural cytotoxicity receptor (NCR)/NCR ligand-dependent cross talk between NK cells and eosinophils may be important to upregulate the activation state and the effector function of cytokine-primed NK cells. This interaction also promotes the NK-mediated editing process of dendritic cells that influence the process of Th1 polarization. In turn, this cross talk also resulted in eosinophil activation and acquisition of the characteristic features of antigen-presenting cells. At higher NK/eosinophil ratios, cytokine-primed NK cells were found to kill eosinophils via NKp46 and NKp30, thus suggesting a potential immunoregulatory role for NK cells in dampening inflammatory responses involving eosinophils.
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| 9. |
- Ratynskaia, S., et al.
(författare)
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Interaction of metal dust adhered on castellated substrates with the ELMy H-mode plasmas of ASDEX-Upgrade
- 2018
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Ingår i: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 58:10
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Tidskriftsartikel (refereegranskat)abstract
- Castellated substrates with adhered micron dust have been exposed in the outer ASDEX-Upgrade divertor to ELMy H-mode discharges. Beryllium proxy (chromium, copper) and refractory metal (tungsten, molybdenum) dust has been deposited on the plasma-facing and plasma-shadowed sides of the monoblocks as well as the bottom of the gaps. Interaction with time-averaged transient heat loads up to 5 MWm(-2) led to dust remobilization, clustering, melting and wetting-induced coagulation. The amount of dust released in the vessel has been quantified and remobilized dust trajectories inferred. Gaps can efficiently trap locally adhered dust, but dust detaching from adjacent monoblocks does not preferentially move inside the gaps implying that they do not constitute a dust accumulation site. Heat transfer simulations of melting events are also reported taking into account heat constriction due to the finite contact area and the presence of surface roughness.
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| 10. |
- Ratynskaia, Svetlana V., et al.
(författare)
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Tungsten dust remobilization under steady-state and transient plasma conditions
- 2017
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Ingår i: NUCLEAR MATERIALS AND ENERGY. - : Elsevier. - 2352-1791. ; 12, s. 569-574
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Tidskriftsartikel (refereegranskat)abstract
- Remobilization is one of the most prominent unresolved fusion dust-relevant issues, strongly related to the lifetime of dust in plasma-wetted regions, the survivability of dust on hot plasma-facing surfaces and the formation of dust accumulation sites. A systematic cross-machine study has been initiated to investigate the remobilization of tungsten micron-size dust from tungsten surfaces implementing a newly developed technique based on controlled pre-adhesion by gas dynamics methods. It has been utilized in a number of devices and has provided new insights on remobilization under steady-state and transient conditions. The experiments are interpreted with contact mechanics theory and heat conduction models.
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