66 research outputs found
Interpretative and predictive modelling of Joint European Torus collisionality scans
Transport modelling of Joint European Torus (JET) dimensionless collisionality scaling experiments in various operational scenarios is presented. Interpretative simulations at a fixed radial position are combined with predictive JETTO simulations of temperatures and densities, using the TGLF transport model. The model includes electromagnetic effects and collisions as well as âĄ(ââŹE ) X âĄ(ââŹB ) shear in Miller geometry. Focus is on particle transport and the role of the neutral beam injection (NBI) particle source for the density peaking. The experimental 3-point collisionality scans include L-mode, and H-mode (D and H and higher beta D plasma) plasmas in a total of 12 discharges. Experimental results presented in (Tala et al 2017 44th EPS Conf.) indicate that for the H-mode scans, the NBI particle source plays an important role for the density peaking, whereas for the L-mode scan, the influence of the particle source is small. In general, both the interpretative and predictive transport simulations support the experimental conclusions on the role of the NBI particle source for the 12 JET discharges
EUROfusion Integrated Modelling (EU-IM) capabilities and selected physics applications
International audienceRecent developments and achievements of the EUROfusion Code Development for Integrated Modelling project (WPCD), which aim is to provide a validated integrated modelling suite for the simulation and prediction of complete plasma discharges in any tokamak, are presented. WPCD develops generic complex integrated simulations, workflows, for physics applications, using the standardized European Integrated Modelling (EU-IM) framework. Selected physics applications of EU-IM workflows are illustrated in this paper
Cellular permeability assessment of drugs through biomimetic droplet interface bilayers
L'amĂ©lioration de la biodisponibilitĂ© orale des mĂ©dicaments est un dĂ©fi majeur tant dâun point de vue Ă©conomique que de santĂ© publique. Aujourdâhui, ce problĂšme se pose de plus en plus avec lâessor des biotechnologies. La faible permĂ©abilitĂ© cellulaire des nouvelles formulations mĂ©dicamenteuses a Ă©tĂ© identifiĂ©e comme Ă©tant le principal paramĂštre limitant pour une administration orale. Une capacitĂ© rĂ©duite Ă franchir les barriĂšres cellulaires est en effet Ă lâorigine dâĂ©checs lors du dĂ©veloppement de mĂ©dicaments, et ce, souvent Ă un stade avancĂ© des essais cliniques. Les solutions offertes pour lâĂ©valuation de la permĂ©abilitĂ© cellulaire de mĂ©dicaments souffrent dâun pouvoir prĂ©dictif assez alĂ©atoire. Dans le cas des puits PAMPA, les limitations sont certainement liĂ©es Ă la structure de la membrane qui manque de ressemblance avec celle des vĂ©ritables membranes cellulaires. La conception de nouveaux outils prĂ©dictifs permettant une bonne Ă©valuation de la permĂ©abilitĂ© cellulaire semble essentielle. Pour cela, nous avons dĂ©veloppĂ© un nouveau systĂšme in vitro de membranes artificielles biomimĂ©tiques. Ce systĂšme sâappuie sur les propriĂ©tĂ©s singuliĂšres des Ă©mulsions adhĂ©sives pour reconstruire une bicouche de phospholipides dont la structure tend vers une membrane cellulaire rĂ©elle. Au cours de cette thĂšse, nous avons caractĂ©risĂ© notre systĂšme en Ă©valuant sa permĂ©abilitĂ© membranaire en fonction de la composition en huile et en phospholipides. Il a Ă©tĂ© notamment montrĂ© que les bicouches formĂ©es dans une phase continue composĂ©e de triglycĂ©rides aboutissent Ă des membranes plus fines, de tension trĂšs faible et permettent Ă la contribution des phospholipides de prĂ©dominer sur celle de lâhuile Ă propos de la permĂ©abilitĂ©. Avec ce systĂšme, nous avons Ă©galement validĂ© lâimpact de la compaction des phospholipides sur la permĂ©abilitĂ© membranaire. Par la suite, nous avons comparĂ© les capacitĂ©s prĂ©dictives du systĂšme dâĂ©mulsions adhĂ©sives biomimĂ©tiques Ă celles des systĂšmes PAMPA et Caco-2 sur une gamme de petits peptides hydrophobes. En travaillant entre autres sur la cyclisation et la mĂ©thylation, nous avons montrĂ© que les Ă©mulsions adhĂ©sives Ă©taient capables dâĂ©valuer lâimpact de modifications structurelles minimes sur le caractĂšre pĂ©nĂ©trant des peptides. Cette Ă©tude a aussi permis de placer le systĂšme de bicouche dâĂ©mulsions adhĂ©sives comme une alternative prometteuse au systĂšme PAMPA. Finalement, une preuve de concept de la possibilitĂ© de former des Ă©mulsions adhĂ©sives et de quantifier leur permĂ©abilitĂ© de maniĂšre automatisĂ©e a Ă©tĂ© fournie, ouvrant la voie Ă lâanalyse Ă haute frĂ©quence de gammes plus larges de formulations mĂ©dicamenteuses. En prenant lâexemple de lâĂ©valuation de la permĂ©abilitĂ© membranaire, facteur limitant au dĂ©veloppement de nouveaux mĂ©dicaments, ce travail de thĂšse illustre comment les systĂšmes issus de la matiĂšre molle pourraient constituer lâoutillage de lâindustrie chimique du futur, miniature et sans dĂ©chet.Enhancing the oral bioavailability of drugs is a major challenge in the field of biomedical research. Today, the low cellular permeability of new drug formulations has been identified as the main limiting parameter for oral administration. A reduced capacity to cross cell barriers is indeed a reason for failures in drug development, often at a late stage of clinical trials. The existing solutions for the evaluation of the cellular permeability of drugs suffer from a rather random predictivity. In the case of PAMPA wells, the limitations are certainly related to their structure which lacks resemblance to that of genuine cell membranes. The design of new predictive tools allowing a good assessment of cell permeability is thus essential. For this purpose, we have developed a new in vitro system of biomimetic artificial membranes. This system relies on the singular properties of droplet interface bilayers which can reconstruct a phospholipid barrier whose structure is close to a real cell membrane. During this thesis, we have characterized our system by evaluating its permeability as a function of oil and phospholipid composition. It has been shown that bilayers formed in a continuous phase made of triglycerides result in thinner membranes, with very low tension and allow the contribution of phospholipids to predominate over that of oil in terms of permeability. With this system, we also validated the impact of phospholipid compaction on membrane permeability. Subsequently, we compared the predictive capabilities of the biomimetic adhesive emulsion system to those of the PAMPA and Caco-2 systems on a range of small hydrophobic peptides. By working on cyclization and methylation, we showed that the adhesive emulsions were able to assess the impact of the modification of tiny structural features on the penetration ability of the peptides. This study also positioned the adhesive emulsion bilayer system as a promising alternative to the PAMPA system. Finally, a proof of concept of the ability to form adhesive emulsions and quantify their permeability in an automated way was provided, paving the way for high-frequency analysis of a wider range of drug formulations. This thesis illustrates how soft matter systems can be a solution to the major drug development challenge that is membrane permeability assessment, and how they could be the miniature and zero waste tool of our future chemical industry
Ăvaluation de la permĂ©abilitĂ© cellulaire de formulations mĂ©dicamenteuses au travers de membranes dâĂ©mulsions adhĂ©sives biomimĂ©tiques
Enhancing the oral bioavailability of drugs is a major challenge in the field of biomedical research. Today, the low cellular permeability of new drug formulations has been identified as the main limiting parameter for oral administration. A reduced capacity to cross cell barriers is indeed a reason for failures in drug development, often at a late stage of clinical trials. The existing solutions for the evaluation of the cellular permeability of drugs suffer from a rather random predictivity. In the case of PAMPA wells, the limitations are certainly related to their structure which lacks resemblance to that of genuine cell membranes. The design of new predictive tools allowing a good assessment of cell permeability is thus essential. For this purpose, we have developed a new in vitro system of biomimetic artificial membranes. This system relies on the singular properties of droplet interface bilayers which can reconstruct a phospholipid barrier whose structure is close to a real cell membrane. During this thesis, we have characterized our system by evaluating its permeability as a function of oil and phospholipid composition. It has been shown that bilayers formed in a continuous phase made of triglycerides result in thinner membranes, with very low tension and allow the contribution of phospholipids to predominate over that of oil in terms of permeability. With this system, we also validated the impact of phospholipid compaction on membrane permeability. Subsequently, we compared the predictive capabilities of the biomimetic adhesive emulsion system to those of the PAMPA and Caco-2 systems on a range of small hydrophobic peptides. By working on cyclization and methylation, we showed that the adhesive emulsions were able to assess the impact of the modification of tiny structural features on the penetration ability of the peptides. This study also positioned the adhesive emulsion bilayer system as a promising alternative to the PAMPA system. Finally, a proof of concept of the ability to form adhesive emulsions and quantify their permeability in an automated way was provided, paving the way for high-frequency analysis of a wider range of drug formulations. This thesis illustrates how soft matter systems can be a solution to the major drug development challenge that is membrane permeability assessment, and how they could be the miniature and zero waste tool of our future chemical industry.L'amĂ©lioration de la biodisponibilitĂ© orale des mĂ©dicaments est un dĂ©fi majeur tant dâun point de vue Ă©conomique que de santĂ© publique. Aujourdâhui, ce problĂšme se pose de plus en plus avec lâessor des biotechnologies. La faible permĂ©abilitĂ© cellulaire des nouvelles formulations mĂ©dicamenteuses a Ă©tĂ© identifiĂ©e comme Ă©tant le principal paramĂštre limitant pour une administration orale. Une capacitĂ© rĂ©duite Ă franchir les barriĂšres cellulaires est en effet Ă lâorigine dâĂ©checs lors du dĂ©veloppement de mĂ©dicaments, et ce, souvent Ă un stade avancĂ© des essais cliniques. Les solutions offertes pour lâĂ©valuation de la permĂ©abilitĂ© cellulaire de mĂ©dicaments souffrent dâun pouvoir prĂ©dictif assez alĂ©atoire. Dans le cas des puits PAMPA, les limitations sont certainement liĂ©es Ă la structure de la membrane qui manque de ressemblance avec celle des vĂ©ritables membranes cellulaires. La conception de nouveaux outils prĂ©dictifs permettant une bonne Ă©valuation de la permĂ©abilitĂ© cellulaire semble essentielle. Pour cela, nous avons dĂ©veloppĂ© un nouveau systĂšme in vitro de membranes artificielles biomimĂ©tiques. Ce systĂšme sâappuie sur les propriĂ©tĂ©s singuliĂšres des Ă©mulsions adhĂ©sives pour reconstruire une bicouche de phospholipides dont la structure tend vers une membrane cellulaire rĂ©elle. Au cours de cette thĂšse, nous avons caractĂ©risĂ© notre systĂšme en Ă©valuant sa permĂ©abilitĂ© membranaire en fonction de la composition en huile et en phospholipides. Il a Ă©tĂ© notamment montrĂ© que les bicouches formĂ©es dans une phase continue composĂ©e de triglycĂ©rides aboutissent Ă des membranes plus fines, de tension trĂšs faible et permettent Ă la contribution des phospholipides de prĂ©dominer sur celle de lâhuile Ă propos de la permĂ©abilitĂ©. Avec ce systĂšme, nous avons Ă©galement validĂ© lâimpact de la compaction des phospholipides sur la permĂ©abilitĂ© membranaire. Par la suite, nous avons comparĂ© les capacitĂ©s prĂ©dictives du systĂšme dâĂ©mulsions adhĂ©sives biomimĂ©tiques Ă celles des systĂšmes PAMPA et Caco-2 sur une gamme de petits peptides hydrophobes. En travaillant entre autres sur la cyclisation et la mĂ©thylation, nous avons montrĂ© que les Ă©mulsions adhĂ©sives Ă©taient capables dâĂ©valuer lâimpact de modifications structurelles minimes sur le caractĂšre pĂ©nĂ©trant des peptides. Cette Ă©tude a aussi permis de placer le systĂšme de bicouche dâĂ©mulsions adhĂ©sives comme une alternative prometteuse au systĂšme PAMPA. Finalement, une preuve de concept de la possibilitĂ© de former des Ă©mulsions adhĂ©sives et de quantifier leur permĂ©abilitĂ© de maniĂšre automatisĂ©e a Ă©tĂ© fournie, ouvrant la voie Ă lâanalyse Ă haute frĂ©quence de gammes plus larges de formulations mĂ©dicamenteuses. En prenant lâexemple de lâĂ©valuation de la permĂ©abilitĂ© membranaire, facteur limitant au dĂ©veloppement de nouveaux mĂ©dicaments, ce travail de thĂšse illustre comment les systĂšmes issus de la matiĂšre molle pourraient constituer lâoutillage de lâindustrie chimique du futur, miniature et sans dĂ©chet
Mode-locking of a pulsed Nd :YAG laser based on polarization switching in type I SHG crystal by means of cascading effects
International audienc
Membrane determinants for the passive translocation of analytes through droplet interface bilayers
International audienc
Nonlinear polarization evolution in type I and type II second-harmonic-generation crystals applied to the mode locking of a pulsed Nd:YAG laser
International audienc
Cascading dans un cristal doubleur de type I appliqué au blocage de modes par commutation de polarisation
vol.10, n°8
Design of a new oligotriazole peptide nucleic acid analogue (oT-PNA)
International audienceWe describe in this Letter the synthesis of an original thymine azido-heterotrimer generated by Click Chemistry. This trimer has been obtained from an azido-thymidine and a new chloroethyl-propargylated PNA monomer analogue, after two azidation/click-reaction cycles. Conformational preferences of a rotameric intermediate have also been studied
Time-course evolution of two water-soluble vitamins (Ascorbic acid, Nicotinic acid) and two amino-acids (L-Cysteine and L-Methionine) following thermal processing in water at 100 °C
Reactions of thermally processed vitamins andamino acids, in particular, ascorbic acid, nicotinicacid, L-cysteine and L-methionine wereinvestigated in water at 100 °C. For such analysis,in situ quantitative nuclear magnetic resonancespectroscopy (is q 1H NMR) was used whichmeans that the samples were directly analyzed inwater. This method has the advantage to be fastand non-invasive, without any extraction process.Under these experimental conditions, there were18 % of ascorbic acid and 37 % of cysteineremaining after 96 h of reaction. Nicotinic acid andL-methionine were both found to be stable, evenafter 96 h of thermal processing
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