| 1. |
- Winkler, TW, et al.
(författare)
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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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| 2. |
- Teumer, A, et al.
(författare)
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Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4130-
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Tidskriftsartikel (refereegranskat)abstract
- Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
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| 3. |
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| 4. |
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| 5. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 6. |
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| 7. |
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| 8. |
- Brkovic, IB, et al.
(författare)
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Simultaneous Mass Spectrometry-Based Apolipoprotein Profiling and Apolipoprotein E Phenotyping in Patients with ASCVD and Mild Cognitive Impairment
- 2022
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:12
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein E (apoE) occurs on the majority of plasma lipoproteins and plays a major role in the lipid metabolism in the periphery and in the central nervous system. ApoE is a polymorphic protein with three common isoforms, apoE2, apoE3 and apoE4, derived from respective alleles ε2, ε3 and ε4. The aim of this study was to develop a sample pretreatment protocol combined with rapid mass spectrometry (MS)-based assay for simultaneous apolipoprotein profiling and apoE phenotype identification. This assay was validated in 481 samples from patients with stable atherosclerotic cardiovascular disease (ASCVD) and applied to study association with mild cognitive impairment (MCI) in the LIFE Adult study, including overall 690 study subjects. Simultaneous quantification of 8–12 major apolipoproteins including apoA-I, apoB-100 and apoE could be performed within 6.5 min. Phenotyping determined with the developed MS assay had good agreement with the genotyping by real-time fluorescence PCR (97.5%). ApoE2 isoform was associated with the highest total apoE concentration compared to apoE3 and apoE4 (p < 0.001). In the subgroup of diabetic atherosclerotic cardiovascular disease (ASCVD) patients, apoE2 isoform was related to higher apoC-I levels (apoE2 vs. apoE3, p < 0.05), while in the subgroup of ASCVD patients under statin therapy apoE2 was related to lower apoB-100 levels (apoE2 vs. apoE3/apoE4, p < 0.05). A significant difference in apoE concentration observed between mild cognitive impairment (MCI) subjects and controls was confirmed for each apoE phenotype. In conclusion, this study provides evidence for the successful implementation of an MS-based apoE phenotyping assay, which can be used to assess phenotype effects on plasma lipid and apolipoprotein levels.
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| 9. |
- Buermans, J., et al.
(författare)
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Characterization of ECRH plasmas in TOMAS
- 2024
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Ingår i: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 31:5
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Tidskriftsartikel (refereegranskat)abstract
- To improve the plasma performance and control the density and plasma quality during the flat top phase, wall conditioning techniques are used in large fusion devices like W7-X and in JT60-SA. To study the performance of electron cyclotron wall conditioning, numerous experiments were performed on the TOroidally MAgnetized System, which is operated by LPP-ERM/KMS at the FZ-Jülich. It is a facility designed to study plasma production, wall conditioning, and plasma-surface interactions. The produced electron cyclotron resonance heating plasmas are characterized in various conditions by density and temperature measurements using a movable triple Langmuir probe in the horizontal and the vertical direction, complemented by video and spectroscopic data, to obtain a 2D extrapolation of the plasma parameters in the machine. A way to calibrate the triple Langmuir probe measurements is also investigated. These data can be used to determine the direction of the plasma drift in the vessel and identify the power absorption mechanisms. This will give more insight in the plasma behavior and improve the efficiency of wall conditioning and sample exposure experiments.
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| 10. |
- Buermans, J., et al.
(författare)
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Study of the Electron cyclotron power deposition in TOMAS
- 2024
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Ingår i: Physica Scripta. - : IOP Publishing. - 0031-8949 .- 1402-4896. ; 99:8
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Tidskriftsartikel (refereegranskat)abstract
- Efficient Electron Cyclotron Resonance Heating (ECRH) breakdown and pre-ionization can be achieved with fundamental X-mode, while higher harmonics can introduce excessive stray radiation. Fundamental heating however is characterized by a low cut-off density, introducing additional power absorption mechanisms in the plasma. A good knowledge of these mechanisms is necessary to use fundamental X-mode as an efficient pre-ionization method. Numerous experiments were performed on the TOroidally MAgnetized System (TOMAS) to study the power deposition for ECRH in helium. It is a facility designed to study plasma production, wall conditioning and plasma-surface interactions and is operated by LPP-ERM/KMS at the FZ-J & uuml;lich. The influence of the injected power P EC and the magnetic field B 0 on the absorption mechanisms is examined, in order to reduce stray radiation and improve the absorption efficiency. This will allow to determine the best scenarios for plasma start-up and pre-ionization.
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| 11. |
- Buermans, J., et al.
(författare)
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Triple Langmuir probe calibration in TOMAS ECRH plasma
- 2023
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Ingår i: AIP Advances. - : AIP Publishing. - 2158-3226. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- In the TOMAS device, a triple Langmuir probe is used to measure the electron temperature and density. The accuracy of this measurement depends on correct determination of the effective collecting area of the probe, which depends on complex plasma transport processes. The probe can be calibrated by electron cyclotron resonance heating experiments using the cut-off density of the ordinary wave (O-wave). This threshold only depends on the frequency of the injected wave, and the occurrence of this phenomenon is clearly visible in the temperature evolution. The value of density is consequently known at this point and can be used to calibrate the density measurements of the triple Langmuir probe.
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| 12. |
- Buermans, Johan, et al.
(författare)
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X-mode electron cyclotron heating scenarios beyond the cut-off density
- 2023
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Ingår i: 24th Topical Conference on Radio-Frequency Power in Plasmas. - : AIP Publishing.
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Konferensbidrag (refereegranskat)abstract
- Electron Cyclotron Heating (ECH) at the fundamental resonance in X-mode is limited by a low cut-off density. Electromagnetic waves cannot propagate in the region between this cut-off and the Upper Hybrid Resonance (UHR) and cannot reach the Electron Cyclotron Resonance (ECR) position. Higher harmonic heating is hence preferred in nowadays ECH plasma heating scenarios to overcome this problem. However, if this evanescent region is small compared to the wavelength of the waves, additional power deposition mechanisms can occur to increase the plasma density. This includes collisional losses in the evanescent region, tunneling of the X-wave with resonant coupling at the ECR, and conversion to the Electron Bernstein Wave (EBW) with resonant coupling. Several ECH plasma production experiments were performed on the TOMAS device with simple toroidal magnetic field to identify these additional heating regimes and to study the influence of the heating power on the ECH plasma parameters and the power deposition. Density and temperature profiles were measured with Langmuir Probes. Measurements of the forwarded and reflected power allow to estimate the coupling efficiency. The results help to understand ECH plasma production for tokamak plasma breakdown assistance and Electron Cyclotron Wall Conditioning (ECWC).
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| 13. |
- Crombé, K., et al.
(författare)
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Radio frequency plasma production on the TOMAS device
- 2023
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Ingår i: 24th Topical Conference on Radio-Frequency Power in Plasmas. - : AIP Publishing.
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Konferensbidrag (refereegranskat)abstract
- The study of discharge initiation by an Ion Cyclotron Range of Frequency (ICRF) antenna is of importance for operational scenarios at low magnetic field in e.g., ITER and Wendelstein 7-X. At low magnetic fields ohmic breakdown is difficult because of relatively short connection lengths and the electron cyclotron (EC) systems cannot assist because of a low-density cut-off. In that case ion cyclotron (IC) start-up, with waves in the Radio Frequency (RF) wavelength range, can be a good alternative solution. To explore in more detail the processes at play during the initial breakdown phase and to test measurement requirements, the diagnostic's capabilities of the TOMAS experimental device are being enlarged to allow for IC breakdown studies. A first set of IC breakdown experiments has been performed and data was taken by a newly installed spectrometer and a horizontal triple Langmuir probe. Limitations were found in pressure, ICRF power, and hydrogen concentration. Further diagnostic's upgrades and extensions of the experimental sessions will allow for a more complete study in support of modelling and experiments on other machines.
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| 14. |
- Dittrich, Christian, et al.
(författare)
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ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016
- 2016
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 1:5
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Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ ASCO Global Curriculum (GC) thanks to contribution of 64 ESMOappointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.
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| 15. |
- Dittrich, K., et al.
(författare)
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Gravoturbulent Planetesimal Formation: The Positive Effect of long-lived Zonal Flows
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X. ; 763:2
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Tidskriftsartikel (refereegranskat)abstract
- Recent numerical simulations have shown long-lived axisymmetric sub- and super-Keplerian flows in protoplanetary disks. These zonal flows are found in local as well as global simulations of disks unstable to the magnetorotational instability. This paper covers our study of the strength and lifetime of zonal flows and the resulting long-lived gas over- and underdensities as functions of the azimuthal and radial size of the local shearing box. We further investigate dust particle concentrations without feedback on the gas and without self-gravity. The strength and lifetime of zonal flows increase with the radial extent of the simulation box, but decrease with the azimuthal box size. Our simulations support earlier results that zonal flows have a natural radial length scale of 5-7 gas pressure scale heights. This is the first study that combines three-dimensional MHD simulations of zonal flows and dust particles feeling the gas pressure. The pressure bumps trap particles with St = 1 very efficiently. We show that St = 0.1 particles (of some centimeters in size if at 5 AU in a minimum mass solar nebula) reach a hundred-fold higher density than initially. This opens the path for particles of St = 0.1 and dust-to-gas ratio of 0.01 or for particles of St >= 0.5 and dust-to-gas ratio 10(-4) to still reach densities that potentially trigger the streaming instability and thus gravoturbulent formation of planetesimals.
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| 16. |
- Dittrich, Laura, et al.
(författare)
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Impact of ion irradiation and film deposition on optical and fuel retention properties of Mo polycrystalline and single crystal mirrors
- 2023
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Ingår i: Nuclear Materials and Energy. - : Elsevier BV. - 2352-1791. ; 37
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Tidskriftsartikel (refereegranskat)abstract
- Polycrystalline (PC) and single crystal (SC) molybdenum mirrors were irradiated with 98Mo+, 1H+, 4He+, 11B+ and 184W+. Energies were chosen to impact the optically active region (up to 30 nm deep) of Mo mirrors. Some surfaces were coated by magnetron sputtering either with B or W films 4–65 nm thick. The overall objective was to simulate the neutron-induced damage and transmutation (H, He), and the impact of H, He, B, W on the optical performance of test mirrors, and on fuel retention. In parallel, a set of PC Mo mirrors irradiated with 1.6 MeV 98Mo3+ to a damage of 2 dpa and 20 dpa was installed in the JET tokamak for exposure during deuterium-tritium campaigns. Data from spectrophotometric, ion beam and microscopy techniques reveal: (i) the irradiation decreased specular reflectivity, whereby the differences between PC and SC in reflectivity are very small, (ii) He is retained in bubbles within 25–30 nm of the subsurface layer in all irradiated materials, (iii) W, either deposited or implanted, decreases reflectivity, but the strongest reflectivity degradation is caused by B deposition. Laboratory studies show the correlation of damage and H retention. Several cycles of W deposition and its removal from SC-Mo mirrors by plasma-assisted methods were also performed.
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| 17. |
- Goriaev, A., et al.
(författare)
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First studies of local ion fluxes in radio frequency plasmas for ion cyclotron wall conditioning applications in the TOMAS device
- 2023
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Ingår i: AIP Conference Proceedings. - : American Institute of Physics Inc..
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Konferensbidrag (refereegranskat)abstract
- To measure the local ion energy distribution functions for support of Ion Cyclotron Wall Conditioning (ICWC) application studies in the TOMAS device, a Semion Retarding Field Energy Analyzer (RFEA) by Impedans Ltd. has been installed in the sample load-lock system. The RFEA system has been commissioned in hydrogen Radio-Frequency (RF) plasmas. The first studies have been performed on the influence of the neutral hydrogen pressure, the input power, the magnetic field and the location on the average ion energy and ion flux density.
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| 18. |
- Kovtun, Yu, et al.
(författare)
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Measurement of hydrogen plasma parameters of the combined ECR+RF discharge in the TOMAS facility
- 2023
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Ingår i: 24TH TOPICAL CONFERENCE ON RADIO-FREQUENCY POWER IN PLASMAS. - : AIP Publishing.
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Konferensbidrag (refereegranskat)abstract
- The plasma electron density and temperature were measured in hydrogen electron-cyclotron resonance (ECR) plasma and combined ECR + radio-frequency (RF) discharges in the TOMAS facility. The results of ECR and combined ECR+RF discharges studies are compared. With an addition of RF, it is possible to vary the plasma parameters around the values provided by the ECR discharge. The propagation of slow (SW) and fast (FW) waves in hydrogen plasma is analyzed. Depending on the plasma density and the parallel component of the wave vector three cases are possible: SW propagation only, SW and FW simultaneous propagation, and FW propagation only.
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| 19. |
- Kovtun, Yu., et al.
(författare)
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Overview of TOMAS plasma diagnostics
- 2023
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Ingår i: Journal of Instrumentation. - : IOP Publishing. - 1748-0221. ; 18:2
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents an overview of the TOMAS plasma diagnostics. The Langmuir probe method is employed to measure electron temperature, density and floating potential distributions. Two triple probes (horizontal and vertical distributions) and a single probe (horizontal distribution) are used. The measured plasma parameters by the triple and single probes are compared. The ion and neutral atom flux and energy distribution is respectively characterized with a Residual Field Energy Analyzer and a Time-of-Flight Neutral Particle Ana-lyzer. To determine the elemental/charge content of the plasma, the passive method of time-resolved optical emission spectroscopy is used. The time dependence of the integral flow of plasma emission from the discharge is registered by a photodetector. Using a filter allows the photodetector to measure spectral line intensities. To record a wide variety of plasma events several video diagnostics are used. It includes slow video cameras and one high-speed camera in the visible range including Hα.
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| 20. |
- López-Rodríguez, D., et al.
(författare)
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Characterisation of radio frequency plasmas in the upgraded TOMAS device
- 2023
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Konferensbidrag (refereegranskat)abstract
- To complement wall conditioning research in TOMAS, a characterisation of radio-frequency hydrogen plasmas has been performed using a radially movable triple Langmuir probe. Experimental measurements of electron temperature and density radial profiles at different magnetic field on axis strengths and neutral pressures have been performed. First results of simulations of the radial profiles with the code TOMATOR-1D can qualitatively reproduce the measurements of the diagnostic and may be used to understand the behaviour of the waves inside the plasma.
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| 21. |
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