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- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 5. |
- Stroth, U., et al.
(författare)
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Progress from ASDEX Upgrade experiments in preparing the physics basis of ITER operation and DEMO scenario development
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- An overview of recent results obtained at the tokamak ASDEX Upgrade (AUG) is given. A work flow for predictive profile modelling of AUG discharges was established which is able to reproduce experimental H-mode plasma profiles based on engineering parameters only. In the plasma center, theoretical predictions on plasma current redistribution by a dynamo effect were confirmed experimentally. For core transport, the stabilizing effect of fast ion distributions on turbulent transport is shown to be important to explain the core isotope effect and improves the description of hollow low-Z impurity profiles. The L-H power threshold of hydrogen plasmas is not affected by small helium admixtures and it increases continuously from the deuterium to the hydrogen level when the hydrogen concentration is raised from 0 to 100%. One focus of recent campaigns was the search for a fusion relevant integrated plasma scenario without large edge localised modes (ELMs). Results from six different ELM-free confinement regimes are compared with respect to reactor relevance: ELM suppression by magnetic perturbation coils could be attributed to toroidally asymmetric turbulent fluctuations in the vicinity of the separatrix. Stable improved confinement mode plasma phases with a detached inner divertor were obtained using a feedback control of the plasma β. The enhanced D α H-mode regime was extended to higher heating power by feedback controlled radiative cooling with argon. The quasi-coherent exhaust regime was developed into an integrated scenario at high heating power and energy confinement, with a detached divertor and without large ELMs. Small ELMs close to the separatrix lead to peeling-ballooning stability and quasi continuous power exhaust. Helium beam density fluctuation measurements confirm that transport close to the separatrix is important to achieve the different ELM-free regimes. Based on separatrix plasma parameters and interchange-drift-Alfvén turbulence, an analytic model was derived that reproduces the experimentally found important operational boundaries of the density limit and between L- and H-mode confinement. Feedback control for the X-point radiator (XPR) position was established as an important element for divertor detachment control. Stable and detached ELM-free phases with H-mode confinement quality were obtained when the XPR was moved 10 cm above the X-point. Investigations of the plasma in the future flexible snow-flake divertor of AUG by means of first SOLPS-ITER simulations with drifts activated predict beneficial detachment properties and the activation of an additional strike point by the drifts.
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| 7. |
- Andersson, Maria L.E. 1968-, et al.
(författare)
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Associations Between Chronic Widespread Pain, Pressure Pain Thresholds and Leptin in Individuals with Knee Pain
- 2022
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Previous studies have reported associations between obesity, chronic pain and increased pain sensitivity. The adipokine leptin has been suggested to be involved in the osteoarthritis process as well as in pain sensitisation.ObjectivesThe aim was to study associations between chronic widespread pain, pain sensitivity and leptin in individuals with knee pain.MethodsIn all, 306 individuals with knee pain were included in the Halland osteoarthritis cohort, ClinicalTrials.gov NCT04928170. Of those, 265 were included in this cross-sectional baseline study. The mean age (sd) was 51.6 (8.8) years, and 71% was women. The participants marked their painful areas on a pain figure with 18 predefined areas. They were categorised in three different pain groups according to the modified WP2019 definition (1), with knees excluded (due to highest goodness of fit): Chronic widespread pain (CWP), chronic regional pain (ChRP) if CWP was not met, and no chronic pain (NCP). The group with CWP were compared with those reporting no CWP (ChRP and NCP). The pressure pain thresholds (PPT) were measured using a computerised pressure algometry (AlgoMed, Medoc) on eight predefined tender points (trapezius (bilateral), right second rib, right lateral epicondyle, knees, gluteal (bilateral)) (2). Increased pain sensitivity was defined as having PPT in the lowest third in all tender points. Obesity was measured via waistline measurement and a bioimpedance (InBody 770) measuring BMI and visceral fat area (VFA). Serum-Leptin were analysed with an ELISA method (Alpco). Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to describe the groups.ResultsIn this baseline study, 16% reported CWP, and 15% had low pain pressure thresholds at baseline in the study. Those fulfilling CWP were more often women, had higher BMI, VFA, and increased leptin levels and worse KOOS in four of five subscores, see Table 1A. The age and gender-adjusted leptin levels were 21.6 ng/ml (95% CI 18.2-25.0) in the group with no CWP vs. 35.5 ng/ml (95% CI 27.6-43.4) in the CWP group, p=0.002. In a logistic regression adjusting for age and gender, leptin was associated with reporting CWP OR 1.015 (95% CI 1.004-1.027, p= 0.008).Table 1.A Comparisons between those without CWP and those fulfilling CWP and table 1B comparisons between those not having low PPT and those with low PPT.ABNo CWPMean (sd)CWPMean (sd)p-valueNot Low PPTMean (sd)Low PPTMean (sd)p-valuen2104022639Age51.8 (8.7)52.8 (7.6)0.46552.1 (8.5)48.8 (9.9)0.030Gender, female n(%)67900.00472670.524BMI (kg/m2)26.2 (4.6)28.0 (5.0)0.02226.4 (4.9)27.5 (4.3)0.213VFA (cm2)107 (50)137 (56)0.001110 (54)127 (49)0.088Leptin (ng/ml)21.0 (23.9)39.0 (36.6)<0.00123.0 (26.0)31.8 (31.6)0.061CRP (mg/L)1.9 (2.7)2.2 (2.3)0.6022.0 (2.7)1.9 (1.8)0.825KOOSPain (0-100, worst to best)74 (15)61 (17)<0.00173 (15)65 (18)0.002Symptom (0-100, worst to best)72 (17)64 (18)0.01671 (17)67 (19)0.188ADL (0-100, worst to best)84 (13)69 (19)<0.00184 (14)72 (21)<0.001Sport/rec (0-100, worst to best)49 (26)34 (27)0.00149 (26)36 (25)0.009QoL (0-100, worst to best)53 (18)46 (20)0.05053 (18)45 (21)0.017BMI, body mass index; VFA, visceral fat area; CRP, C-reactive protein; KOOS, knee injury and osteoarthritis outcome score; ADL; function in daily living; sport/Rec, Function in sport and recreation; QOL, knee-related Quality of lifeThe participants with low PPT were younger and had a mean (sd) leptin 31.8 ng/ml (31.6) vs 23.0 (26.0), p=0.061 in the group not having low PPT, Table 1B. In a logistic regression adjusting for age and gender, leptin was associated with low PPT OR 1.016 (95% CI 1.004-1.029, p= 0.012).ConclusionThe pathophysiological mechanism causing widespread pain is probably multifactorial, involving both biological and physical factors. The adipokine leptin could be involved in some of these mechanisms, but longitudinal studies are needed to be able to study causal relationships.References[1]Wolfe F, et al. Scand J Pain. 2019;20:77-86.[2]Wolfe F, et al. Arthritis and rheumatism. 1990;33:160-72.Disclosure of InterestsNone declared
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| 8. |
- Andersson, Maria L.E. 1968-, et al.
(författare)
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Associations between chronic widespread pain, pressure pain thresholds and leptin in individuals with knee pain
- 2022
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Previous studies have reported associations between obesity, chronic pain and increased pain sensitivity. The adipokine leptin has been suggested to be involved in the osteoarthritis process as well as in pain sensitisation.Objective: The aim was to study associations between chronic widespread pain, pain sensitivity and leptin in individuals with knee pain.Method: In all, 306 individuals with knee pain were included in the Halland osteoarthritis cohort, ClinicalTrials.gov NCT04928170. Of those, 265 were included in this cross-sectional baseline study. The mean age (sd) was 51.6 (8.8) years, and 71% was women. The participants marked their painful areas on a pain figure with 18 predefined areas. According to their answer, they were categorised in three different pain groups according to the modified WP2019 definition (1), with knees excluded (due to highest goodness of fit): Chronic widespread pain (CWP), chronic regional pain (ChRP) if CWP was not met, and no chronic pain (NCP). The groupwith CWP were compared with those reporting no CWP (ChRP and NCP). The pressure pain thresholds (PPT) were measured using a computerised pressure algometry (AlgoMed, Medoc) on eight predefined tender points (trapezius (bilateral), right second rib, right lateral epicondyle, knees, gluteal (bilateral)) out of the total 18 points that are part of the definition of fibromyalgia (2). Increased pain sensitivity was defined as having PPT in the lowest third in all tender points. Obesity was measured via waistline measurement and a bioimpedance (InBody 770) measuring BMI, visceral fat area (VFA), and body fat percentage. Serum-Leptin were analysed with an ELISA method (Alpco). C-reactive protein (CRP) >1.0 mg/L were measured according to the current laboratory standards in Sweden. CRP below 1.0 mg/L, were further analysed with a sensitive CRP enzyme-linked immunosorbent assay (ELISA) method (Abnova). Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to describe the groups.Result: In this baseline study, 16% reported CWP, and 15% had low pain pressure thresholds at baseline in the study. Those fulfilling CWP were more often women, had higher BMI, VFA, and increased leptin levels and worse KOOS in four of five subscores, see table 1A. The age and gender-adjusted leptin levels were 21.6 ng/ml (95% CI 18.2-25.0) in the group with no CWP vs. 35.5 ng/ml (95% CI 27.6-43.4) in the CWP group, p=0.002. In a logistic regression adjusting for age and gender, leptin was associated with reporting CWP OR 1.015 (95% CI 1.004-1.027, p= 0.008).The participants with low PPT were younger and had a mean (sd) leptin 31.8 ng/ml (31.6) vs 23.0 (26.0), p=0.061 in the group not having low PPT, table 1B. In a logistic regression adjusting for age and gender, leptin was associated with low PPT OR 1.016 (95% CI 1.004-1.029, p= 0.012).There were no increased CRP levels in any of the pain groups (CWP and low PPT), table 1A and B.Conclusion: The pathophysiological mechanism causing widespread pain is probably multifactorial, involving both biological and physical factors. The adipokin leptin could be involved in some of these mechanisms, but longitudinal studies are needed to be able to study causal relationships.
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| 9. |
- Andersson, Maria L.E. 1968-, et al.
(författare)
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Associations between chronic widespread pain, pressure pain thresholds, leptin, and metabolic factors in individuals with knee pain
- 2023
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Ingår i: BMC Musculoskeletal Disorders. - London : BioMed Central (BMC). - 1471-2474. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim was to study associations between chronic widespread pain, widespread pain sensitivity, leptin, and metabolic factors in individuals with knee pain. A secondary aim was to study these associations in a subgroup of individuals with normal BMI.METHOD: This cross-sectional study included 265 individuals. The participants were categorised into three different pain groups: Chronic widespread pain (CWP), chronic regional pain (ChRP), or no chronic pain (NCP). The pressure pain thresholds (PPTs) were assessed using computerised pressure algometry. Low PPTs were defined as having PPTs in the lowest third of all tender points. Leptin and metabolic factors such as BMI, visceral fat area (VFA), lipids, and glucose were also assessed.RESULT: Sixteen per cent reported CWP, 15% had low PPTs, and 4% fulfilled both criteria. Those who fulfilled the criteria for CWP were more often women, more obese, and had increased leptin levels. In logistic regression, adjusted for age and gender, leptin was associated with fulfilling criteria for CWP, OR 1.015 (95% CI 1.004-1.027, p = 0.008). In logistic regression, adjusted for age and gender, leptin was associated with low PPTs, OR 1.016 (95% CI 1.004-1.029, p = 0.012). Leptin was also associated with fulfilling both criteria, adjusted for age, sex, and visceral fat area (VFA), OR 1.030 (95% CI 1.001-1.060), p = 0.040.CONCLUSION: Leptin was associated with fulfilling the combined criteria for chronic widespread pain and low PPTs, even after adjusting for the visceral fat area (VFA). Longitudinal studies are needed to study the causal relationships between leptin and the development of widespread pain.
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| 10. |
- Chuang, Tzu-Po, et al.
(författare)
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ALK fusion NSCLC oncogenes promote survival and inhibit NK cell responses via SERPINB4 expression
- 2023
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Ingår i: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 120:8
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Tidskriftsartikel (refereegranskat)abstract
- Anaplastic lymphoma kinase (ALK) fusion variants in Non-Small Cell Lung Cancer (NSCLC) consist of numerous dimerizing fusion partners. Retrospective investigations suggest that treatment benefit in response to ALK tyrosine kinase inhibitors (TKIs) differs dependent on the fusion variant present in the patient tumor. Therefore, under -standing the oncogenic signaling networks driven by different ALK fusion variants is important. To do this, we developed controlled inducible cell models expressing either Echinoderm Microtubule Associated Protein Like 4 (EML4)-ALK-V1, EML4-ALK-V3, Kinesin Family Member 5B (KIF5B)-ALK, or TRK-fused gene (TFG)-ALK and investi-gated their transcriptomic and proteomic responses to ALK activity modulation together with patient-derived ALK-positive NSCLC cell lines. This allowed identification of both common and isoform-specific responses downstream of these four ALK fusions. An inflammatory signature that included upregulation of the Serpin B4 serine protease inhibitor was observed in both ALK fusion inducible and patient-derived cells. We show that Signal transducer and activator of transcription 3 (STAT3), Nuclear Factor Kappa B (NF-kappa B) and Activator protein 1 (AP1) are major transcriptional regulators of SERPINB4 downstream of ALK fusions. Upregulation of SERPINB4promotes survival and inhibits natural killer cell-mediated cytotoxicity, which has potential for therapeutic impact targeting the immune response together with ALK TKIs in NSCLC.
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