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- Stork, D., et al.
(författare)
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Overview of transport, fast particle and heating and current drive physics using tritium in JET plasmas
- 2005
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Ingår i: Nuclear Fusion. - 0029-5515 .- 1741-4326. ; 45:10, s. S181-S194
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Tidskriftsartikel (refereegranskat)abstract
- Results are presented from the JET Trace Tritium Experimental (TTE) campaign using minority tritium (T) plasmas (n(T)/n(D) < 3%). Thermal tritium particle transport coefficients (D-T, nu(T)) are found to exceed neo-classical values in all regimes, except in ELMy H-modes at high densities and in the region of internal transport barriers (ITBs) in reversed shear plasmas. In ELMy H-mode dimensionless parameter scans, at q(95) 2.8 and triangularity delta = 0.2, the T particle transport scales in a gyro-Bohm manner in the inner plasma (r/a < 0.4), whilst the outer plasma particle transport scaling is more Bohm-like. Dimensionless parameter scans show contrasting behaviour for the trace particle confinement (increases with collisionality, nu* and beta) and bulk energy confinement (decreases with nu* and is independent of beta). In an extended ELMy H-mode data set, with rho*, nu*, and q varied but with neo-classical tearing modes (NTMs) either absent or limited to weak, benign core modes (4/3 or above), the multiparameter fit to the normalized diffusion coefficient in the outer plasma (0.65 < r/a < 0.8) gives D-T/B-phi similar to rho*(2.46) nu*(-0.23) beta(-1.01) q(2.03). In hybrid scenarios (q(min) similar to 1, low positive shear, no sawteeth), the T particle confinement is found to scale with increasing triangularity and plasma current. Comparing regimes (ELMy H-mode, ITB plasma and hybrid scenarios) in the outer plasma region, a correlation of high values of D-T with high values Of nu(T) is seen. The normalized diffusion coefficients for the hybrid and ITB scenarios do not fit the scaling derived for ELMy H-modes. The normalized tritium diffusion scales with normalized poloidal Larmor radius (rho(theta)* = q rho*) in a manner close to gyro-Bohm (similar to rho(sigma)*(3)), with an added inverse P dependence. The effects of ELMs, sawteeth and NTMs on the T particle transport are described. Fast-ion confinement in current-hole (CH) plasmas was tested in TTE by tritium neutral beam injection into JET CH plasmas. gamma-rays from the reactions of fusion alpha and beryllium impurities (Be-9(alpha, n gamma)C-12) characterized the fast fusion-alpha population evolution. The gamma-decay times are consistent with classical alpha plus parent fast triton slowing down times (tau(Ts) + tau(alpha s)) for high plasma currents (I-p > 2 MA) and monotonic q-profiles. In CH discharges the gamma-ray emission decay times are much lower than classical (tau(Ts) + tau(alpha s)), indicating alpha confinement degradation, due to the orbit losses and particle orbit drift predicted by a 3-D Fokker-Planck numerical code and modelled using TRANSP.
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| 9. |
- Grosche, S, et al.
(författare)
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Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 6618-
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels. We identify rare exonic variants in DUSP1, NOTCH4, and SLC9A4 to be associated with eczema. In DUSP1 and NOTCH4 missense variants are predicted to impact conserved functional domains. In addition, five novel common variants at SATB1-AS1/KCNH8, TRIB1/LINC00861, ZBTB1, TBX21/OSBPL7, and CSF2RB are discovered. While genes prioritized based on rare variants are significantly up-regulated in the skin, common variants point to immune cell function. Over 20% of the single nucleotide variant-based heritability is attributable to rare and low-frequency variants. The identified rare/low-frequency variants located in functional protein domains point to promising targets for novel therapeutic approaches to eczema.
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| 11. |
- Loarer, T., et al.
(författare)
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Fuel retention in L and H mode experiments in JET
- 2007
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Ingår i: 34th EPS Conference on Plasma Physics 2007, EPS 2007 - Europhysics Conference Abstracts. - 9781622763344 ; , s. 13-16
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Konferensbidrag (refereegranskat)abstract
- The fuel retention has been studied out in JET in L mode, Type III and Type I ELMy H-modes using gas balance in series of repetitive pulses with an overall accuracy of about 1.2%. The short term (dynamic) retention is important for both L mode and Type III ELMy H-mode over the heating phases (respectively 13 and 17 sec) but decreases already significantly during the pulse. It becomes small already after 6 sec for the Type I ELMy H-mode conditions. In all the cases, the recovery after the pulse contributes for a weak part in the gas balance and in the overall fuel retention. The absolute long term fuel retention (on the time basis of typically 5 hours) for the different plasma conditions is between 1.3 and 2.8 1021Ds-1 (averaged over the plasma heating time) and in reasonable agreement with the value deduced from post mortem tile analysis of about 5 1020Ds-1 considering the additional long term outgassing, conditioning and disruptions included in the post mortem analysis. The increase of the long term retention observed from L mode to Type I ELMy H-mode is associated to the increase of the recycling flux and the ELM energy. This larger long term retention is attributed to an enhanced carbon erosion and transport in the SOL leading to stronger carbon deposition and fuel codeposition. The results confirm the strong concerns about fuel retention in a carbon clad tokamak and a possible full carbon wall ITER which could reach the T-inventory limit in only a small number of high performance shots. A reasonable ITER operation time depends thus on a significant reduced T codeposition under the different ITER material conditions (which has to be confirmed in a relevant tokamak experiment such as the JET ILW project) and an effective routine T removal technique.
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- Mansouri, Kamel, et al.
(författare)
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CERAPP : Collaborative Estrogen Receptor Activity Prediction Project
- 2016
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 124:7, s. 1023-1033
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Humans are exposed to thousands of man-made chemicals in the environment. Some chemicals mimic natural endocrine hormones and, thus, have the potential to be endocrine disruptors. Most of these chemicals have never been tested for their ability to interact with the estrogen receptor (ER). Risk assessors need tools to prioritize chemicals for evaluation in costly in vivo tests, for instance, within the U.S. EPA Endocrine Disruptor Screening Program. OBJECTIVES: We describe a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project) and demonstrate the efficacy of using predictive computational models trained on high-throughput screening data to evaluate thousands of chemicals for ER-related activity and prioritize them for further testing. METHODS: CERAPP combined multiple models developed in collaboration with 17 groups in the United States and Europe to predict ER activity of a common set of 32,464 chemical structures. Quantitative structure-activity relationship models and docking approaches were employed, mostly using a common training set of 1,677 chemical structures provided by the U.S. EPA, to build a total of 40 categorical and 8 continuous models for binding, agonist, and antagonist ER activity. All predictions were evaluated on a set of 7,522 chemicals curated from the literature. To overcome the limitations of single models, a consensus was built by weighting models on scores based on their evaluated accuracies. RESULTS: Individual model scores ranged from 0.69 to 0.85, showing high prediction reliabilities. Out of the 32,464 chemicals, the consensus model predicted 4,001 chemicals (12.3%) as high priority actives and 6,742 potential actives (20.8%) to be considered for further testing.CONCLUSION: This project demonstrated the possibility to screen large libraries of chemicals using a consensus of different in silico approaches. This concept will be applied in future projects related to other end points.
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- Schuette, Moritz, et al.
(författare)
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Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling 44,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab.
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