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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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- Normann, Fredrik, 1982, et al.
(författare)
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Nitrogen and sulphur chemistry in pressurised flue gas systems: A comparison of modelling and experiments
- 2013
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Ingår i: International Journal of Greenhouse Gas Control. - : Elsevier BV. - 1750-5836. ; 12, s. 26-34
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Tidskriftsartikel (refereegranskat)abstract
- The nitrogen and sulphur chemistry is more significant during compression of flue gases than they are under atmospheric conditions. This fact became apparent during the development of oxy-fuel power plant technology to capture carbon dioxide (CO2). In the oxy-fuel power plant, the CO2-rich flue gas stream is compressed to enable efficient transport and storage. During this process, NOx and SOx are removed as acids in the condensed water. However, the chemistry of these steps is not understood well enough to allow for control and design of the process.In the present work, the gas- and liquid-phase chemistry of NOx and SOx at elevated pressures were evaluated by comparing a state-of-the-art reaction mechanism to the results of experimental investigations. The model used confirms previous observations of substantial absorption of NOx and SOx and subsequent formation of acids in pressurised flue gas systems. The results of the modelling show that the oxidation of NO into NO2 governs the absorption of NOx. The complex chemistry of the liquid phase, which includes reactions between HNO2, H2SO3, and possibly H2SO4, is critical for the rate of absorption of NOx and SOx from the gas to the liquid phase. This process is heavily dependent upon the pH level. The modelling suggests that N2O is formed as a stable product through the liquid-phase reactions.
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- Petersson, Klas, 1982-
(författare)
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Population Pharmacodynamic Modeling and Methods for D2-receptor Antagonists
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Early predictions of a potential drug candidate’s time-course of effect and side-effects, based on models describing drug concentrations, drug effects and disease progression, would be valuable to make drug development more efficient. Pharmacodynamic modeling can incorporate and propagate prior knowledge and be used for simulations of different scenarios.In this thesis three population pharmacodynamic models were developed to describe the antipsychotic effects and the side-effects prolactin elevation and Extra Pyramidal Symptoms (EPS) following administration of D2-receptor antagonists, commonly used in the treatment of schizophrenia.Model parameter estimates of prolactin elevating potencies of six compounds correlated with in vitro values of receptor affinities, and parameters related to diurnal prolactin variation and tolerance were similar for the different compounds. The developed prolactin model can thereby be used to predict the time-course of prolactin elevation in patients for a drug candidate using information on in vitro affinity to the D2-receptor. Furthermore, the clinical antipsychotic effect and the prolactin elevation was found to correlate on the individual level for the three antipsychotic compounds investigated and a quantitative relation between D2-receptor occupancy in the brain and prolactin elevation was established. These results support the use of prolactin concentrations as a biomarker in drug development or for individual dose adjustments in clinical care.The developed model for spontaneously reported EPS adverse events, following treatment with one of five antipsychotics drugs, characterized both the duration and severity of EPS. The model successfully described both the proportions and number of transitions between severity grades and was shown to adequately simulate longitudinal categorical EPS data.Complex pharmacodynamic models are often associated with long estimation times and non-normal distributions of individual parameters. A method for shortening computation times by substituting differential equations for difference equations was evaluated and shown to be valuable for some models. In addition, transformation of distributions allowed for non-normal distributions of between-subject variability to be better characterized and thereby simulation properties were improved.In conclusion, population pharmacodynamic models for a range of D2-receptor antagonists were developed and together with the investigated methods the models can facilitate prediction of effects and side-effects in drug development.
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- Petersson, Klas, 1982-, et al.
(författare)
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Predictions of In Vivo Prolactin Levels from In Vitro K (i) Values of D-2 Receptor Antagonists Using an Agonist-Antagonist Interaction Model
- 2013
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Ingår i: AAPS Journal. - : Springer Science and Business Media LLC. - 1550-7416. ; 15:2, s. 533-541
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Tidskriftsartikel (refereegranskat)abstract
- Prolactin elevation is a side effect of all currently available D2 receptor antagonists used in the treatment of schizophrenia. Prolactin elevation is the result of a direct antagonistic D2 effect blocking the tonic inhibition of prolactin release by dopamine. The aims of this work were to assess the correlation between in vitro estimates of D2 receptor affinity and pharmacokinetic–pharmacodynamic model-based estimates obtained from analysis of clinical data using an agonist–antagonist interaction (AAI) model and to assess the value of such a correlation in early prediction of full prolactin time profiles. A population model describing longitudinal prolactin data was fitted to clinical data from 16 clinical phases 1 and 3 trials including five different compounds. Pharmacokinetic data were modeled for each compound and the prolactin model was both fitted in per-compound fits as well as simultaneously to all prolactin data. Estimates of prolactin elevating potency were compared to corresponding in vitro values and their predictability was evaluated through model-based simulations. The model successfully described the prolactin time course for all compounds. Estimates derived from experimental preclinical data and the model fit of the clinical data were strongly correlated (p < 0.001), and simulations adequately predicted the prolactin elevation in five out of six compounds. The AAI model has the potential to be used in drug development to predict prolactin response for a given exposure of D2 antagonists using routinely produced preclinical data.
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