| 1. |
- Bécoulet, A., et al.
(författare)
-
Science and technology research and development in support to ITER and the Broader Approach at CEA
- 2013
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10
-
Tidskriftsartikel (refereegranskat)abstract
- In parallel to the direct contribution to the procurement phase of ITER and Broader Approach, CEA has initiated research & development programmes, accompanied by experiments together with a significant modelling effort, aimed at ensuring robust operation, plasma performance, as well as mitigating the risks of the procurement phase. This overview reports the latest progress in both fusion science and technology including many areas, namely the mitigation of superconducting magnet quenches, disruption-generated runaway electrons, edge-localized modes (ELMs), the development of imaging surveillance, and heating and current drive systems for steady-state operation. The WEST (W Environment for Steady-state Tokamaks) project, turning Tore Supra into an actively cooled W-divertor platform open to the ITER partners and industries, is presented.
|
|
| 2. |
- Hillairet, J., et al.
(författare)
-
Recent progress on lower hybrid current drive and implications for ITER
- 2013
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:7
-
Tidskriftsartikel (refereegranskat)abstract
- The sustainment of steady-state plasmas in tokamaks requires efficient current drive systems. Lower hybrid current drive is currently the most efficient method to generate a continuous additional off-axis toroidal plasma current and to reduce the poloidal flux consumption during the plasma current ramp-up phase. The operation of the Tore Supra ITER-like lower hybrid (LH) launcher has demonstrated the capability to couple LH power at ITER-like power densities with very low reflected power during long pulses. In addition, the installation of eight 700 kW/CW klystrons at the LH transmitter has allowed increasing the total LH power in long-pulse scenarios. However, in order to achieve pure stationary LH-sustained plasmas, some R&D is needed to increase the reliability of all the systems and codes, from radio-frequency (RF) sources to plasma scenario prediction. The CEA/IRFM is addressing some of these issues by leading a R&D programme towards an ITER LH system and by the validation of an integrated LH modelling suite of codes. In 2011, the RF design of a mode converter was validated at a low power. A 500 kW/5 s RF window is currently under manufacture and will be tested at a high power in 2012 in collaboration with the National Fusion Research Institute. All of this work aims to reduce the operational risks associated with the ITER steady-state operations.
|
|
| 3. |
- Decker, J., et al.
(författare)
-
Modelling of LHCD at various densities in tore supra tokamak
- 2012
-
Ingår i: 39th EPS Conference on Plasma Physics 2012, EPS 2012 and the 16th International Congress on Plasma Physics; Stockholm; Sweden; 2 July 2012 through 6 July 2012; Code 96757. - 9781622769810 ; 2, s. 934-937
-
Konferensbidrag (refereegranskat)
|
|
| 4. |
- Dumont, R.J., et al.
(författare)
-
Advances in multi-megawatt, long pulse operation in Tore Supra
- 2012
-
Ingår i: 39th EPS Conference on Plasma Physics 2012, EPS 2012 and the 16th International Congress on Plasma Physics; Stockholm; Sweden; 2 July 2012 through 6 July 2012; Code 96757. - 9781622769810 ; 2, s. 1118-1121
-
Konferensbidrag (refereegranskat)
|
|
| 5. |
- Dumont, R. J., et al.
(författare)
-
Multi-megawatt, gigajoule plasma operation in Tore Supra
- 2014
-
Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 56:7
-
Tidskriftsartikel (refereegranskat)abstract
- Integrating several important technological elements required for long pulse operation in magnetic fusion devices, the Tore Supra tokamak routinely addresses the physics and technology issues related to this endeavor and, as a result, contributes essential information on critical issues for ITER. During the last experimental campaign, components of the radiofrequency system including an ITER relevant launcher (passive active multijunction (PAM)) and continuous wave/3.7 GHz klystrons, have been extensively qualified, and then used to develop steady state scenarios in which the lower hybrid (LH), ion cyclotron (IC) and electron cyclotron (EC) systems have been combined in fully stationary shots (duration similar to 150 s, injected power up to similar to 8MW, injected/extracted energy up to similar to 1 GJ). Injection of LH power in the 5.0-6.0MW range has extended the domain of accessible plasma parameters to higher densities and non-inductive currents. These discharges exhibit steady electron internal transport barriers (ITBs). We report here on various issues relevant to the steady state operation of future devices, ranging from operational aspects and limitations related to the achievement of long pulses in a fully actively cooled fusion device (e. g. overheating due to fast particle losses), to more fundamental plasma physics topics. The latter include a beneficial influence of IC resonance heating on the magnetohydrodynamic (MHD) stability in these discharges, which has been studied in detail. Another interesting observation is the appearance of oscillations of the central temperature with typical periods of the order of one to several seconds, caused by a nonlinear interplay between LH deposition, MHD activity and bootstrap current in the presence of an ITB.
|
|
| 6. |
|
|
| 7. |
- Nilsson, Emelie, 1985, et al.
(författare)
-
Comparative modelling of lower hybrid current drive with two launcher designs in the Tore Supra tokamak
- 2013
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:8
-
Tidskriftsartikel (refereegranskat)abstract
- Fully non-inductive operation with lower hybrid current drive (LHCD) in the Tore Supra tokamak is achieved using either a fully active multijunction (FAM) launcher or a more recent ITER-relevant passive active multijunction (PAM) launcher, or both launchers simultaneously. While both antennas show comparable experimental efficiencies, the analysis of stability properties in long discharges suggest different current profiles. We present comparative modelling of LHCD with the two different launchers to characterize the effect of the respective antenna spectra on the driven current profile. The interpretative modelling of LHCD is carried out using a chain of codes calculating, respectively, the global discharge evolution (tokamak simulator METIS), the spectrum at the antenna mouth (LH coupling code ALOHA), the LH wave propagation (ray-tracing code C3PO), and the distribution function (3D Fokker-Planck code LUKE). Essential aspects of the fast electron dynamics in time, space and energy are obtained from hard x-ray measurements of fast electron bremsstrahlung emission using a dedicated tomographic system. LHCD simulations are validated by systematic comparisons between these experimental measurements and the reconstructed signal calculated by the code R5X2 from the LUKE electron distribution. An excellent agreement is obtained in the presence of strong Landau damping (found under low density and high-power conditions in Tore Supra) for which the ray-tracing model is valid for modelling the LH wave propagation. Two aspects of the antenna spectra are found to have a significant effect on LHCD. First, the driven current is found to be proportional to the directivity, which depends upon the respective weight of the main positive and main negative lobes and is particularly sensitive to the density in front of the antenna. Second, the position of the main negative lobe in the spectrum is different for the two launchers. As this lobe drives a counter-current, the resulting driven current profile is also different for the FAM and PAM launchers.
|
|
| 8. |
- Nilsson, Emelie J., et al.
(författare)
-
A neutron scattering and modelling study of aqueous solutions of tetramethylammonium and tetrapropylammonium bromide
- 2016
-
Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 18:16, s. 11193-11201
-
Tidskriftsartikel (refereegranskat)abstract
- We have investigated the properties in water of two tetraalkylammonium bromides (tetramethylammonium, TMA+, and tetrapropylammonium, TPA+), at 0.4 M, using neutron scattering coupled with empirical potential structure refinement to arrive at an atomistic description. Having both a polar and an apolar moiety, it is of interest to determine the strength of each moiety as a function of the alkyl chain length. TMA+ and TPA+, having different impact as structure directors in zeolite synthesis, were chosen for this study. Water arranges tetrahedrally around TMA+ and in an almost featureless manner around TPA+. TMA+ and TPA+ show an apolar hydration with TPA+ being slightly more apolar. TPA+ has a tendency to form small clusters of 2-4 molecules and to fold into a compact configuration. Both molecules correlate similarly with the bromide ion but do not dissociate completely at this concentration.
|
|
| 9. |
- Nilsson, Emelie J., et al.
(författare)
-
Stability and behaviour in aqueous solutions of the anionic cubic silsesquioxane substituted with tetramethylammonium
- 2019
-
Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 21:12, s. 6732-6742
-
Tidskriftsartikel (refereegranskat)abstract
- The aqueous behaviour of the anionic octa-tetramethylammonium substituted cubic silsesquioxane, [N(CH 3 ) 4 ] 8 [Si 8 O 20 ], was studied with quantitative 29 Si-NMR. This molecule partially fragments in aqueous solutions, forming several smaller entities. The most abundant silica species are the monomer, dimer, cyclic trimer, cyclic tetramer and double three-ring. Higher concentrations are required in order to prevent complete fragmentation of the cubic structure. Additives such as alcohols and tetraalkylammonium salts have a stabilising effect on the cubic silsesquioxane, unlike sodium salts that destabilise it. A high concentration solution, containing the non-fragmented molecule as well as entities resulting from fragmentations, was investigated with neutron scattering coupled with modelling, using empirical potential structure refinement (EPSR). The modelling reveals that TMA + ions coordinates to all different silica species, with approximately three TMA + per cube. These are located at the faces of the cube.
|
|
| 10. |
|
|
| 11. |
- Dahlin, Sandra, et al.
(författare)
-
Multivariate analysis of the effect of biodiesel-derived contaminants on V2O5-WO3/TiO2 SCR catalysts
- 2016
-
Ingår i: Applied Catalysis B. - : Elsevier. - 0926-3373 .- 1873-3883. ; 183, s. 377-385
-
Tidskriftsartikel (refereegranskat)abstract
- This study investigates the effect of biodiesel-derived contaminants on vanadia-based NH3-SCR catalysts in heavy-duty exhaust aftertreatment. The aim was to study, not only the effect of single contaminants on the catalyst performance, but also of possible interaction effects between poisons.The effect of six potential catalyst poisons (Na, K, Mg, P, S and Zn) was evaluated using an experimental design and multivariate data analysis. Monolithic V2O5-WO3/TiO2 catalysts were subjected to accelerated laboratory-scale aging, where the six contaminants were fed simultaneously using a wet impregnation method. In addition to NOx conversion tests, the catalysts were characterized by means of ICP-OES, SEM-EDX, XPS, N2 physisorption and NH3-TPD. The lab-aged samples were compared to fresh and vehicle-aged catalysts.The accelerated aging method showed good reproducibility and gave rise to surface compounds similar to those found in vehicle-aged catalysts. Despite plausible differences regarding penetration depth of the contaminants into the walls of the catalyst, the aging method appears to be an efficient way to point out significant chemical poisons.The model obtained from the experimental design was found to correlate well with the experimental data and can therefore be used to predict effects of the various poisons and poison interactions. Significant effects on the NO. x conversion were found for P, S, Na, Mg and K as well as for the interactions P. ×. Na, P. ×. K and S. ×. Na. A poisoning effect was found for Mg, Na, K, P. ×. K, and P. ×. Na, where Na and K exhibited the strongest poisoning effect. The deactivating effect of alkali was lowered in the presence of phosphorus and sulfur, which is explained by the formation of phosphates and sulfates, preventing the interaction of the alkali metals with the vanadia active sites.
|
|
| 12. |
- Falk, Magnus, et al.
(författare)
-
Wearable Electronic Tongue for Non-Invasive Assessment of Human Sweat
- 2021
-
Ingår i: Sensors. - : MDPI. - 1424-8220. ; 21:21
-
Tidskriftsartikel (refereegranskat)abstract
- Sweat is a promising biofluid in allowing for non-invasive sampling. Here, we investigate the use of a voltammetric electronic tongue, combining different metal electrodes, for the purpose of non-invasive sample assessment, specifically focusing on sweat. A wearable electronic tongue is presented by incorporating metal electrodes on a flexible circuit board and used to non-invasively monitor sweat on the body. The data obtained from the measurements were treated by multivariate data processing. Using principal component analysis to analyze the data collected by the wearable electronic tongue enabled differentiation of sweat samples of different chemical composition, and when combined with 1H-NMR sample differentiation could be attributed to changing analyte concentrations.
|
|
| 13. |
- Karlsson, Christofer M. G., et al.
(författare)
-
Metatranscriptomic analysis uncovers divergent responses of Baltic Sea bacteria to forest and agriculture river loadings
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Climate change is predicted to induce substantial changes in precipitation patterns across the globe. In Northern Europe, precipitation is expected to increase more than the global average (particularly in northern Scandinavia), causing increased river runoff. The Baltic Sea is one of the largest brackish environments on earth with a catchment area that spans 14 countries, encompassing primarily forested areas and agricultural landscapes. Despite the acknowledged role of marine bacteria in nutrient cycling, there is a lack of knowledge in their metabolic responses to inorganic and organic nutrient loading from riverine runoff. We investigated the bacterial growth and gene expression responses in a mesocosm experiment in which river water from boreal forest- (enriched in humic substances) or agriculture- influenced catchment areas were added to Baltic Sea Proper water. The riverine nutrient input triggered extensive phytoplankton blooms and bacterial growth, most notably in the agriculture river treatment. Interestingly, bacterial gene expression analysis (metatranscriptomics) showed similar responses to agriculture and humic river inputs at the start of the experiment (before the phytoplankton bloom), but expression patterns diverged significantly upon bloom senescence.Notably, transcripts associated with phosphate metabolism were significantly enriched , whereas transcripts related to nitrogen metabolism were significantly lower in the agriculture river treatment compared to the boreal forest river treatment. The opposite pattern was observed in the boreal forest river water treatment. Overall, our results showed that interactions between river nutrient loading and phytoplankton organic matter are important in regulating bacterial activities and responses at the molecular level. This suggests that bacterial transformations of organic matter and nutrient cycling in coastal waters and estuarine environments are sensitive to changes in precipitation patterns in a catchment area-dependent manner.
|
|
| 14. |
- Krischer, Jeffrey P, et al.
(författare)
-
Predicting Islet Cell Autoimmunity and Type 1 Diabetes : An 8-Year TEDDY Study Progress Report
- 2019
-
Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 42:6, s. 1051-1060
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Assessment of the predictive power of The Environmental Determinants of Diabetes in the Young (TEDDY)-identified risk factors for islet autoimmunity (IA), the type of autoantibody appearing first, and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: A total of 7,777 children were followed from birth to a median of 9.1 years of age for the development of islet autoantibodies and progression to T1D. Time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated to provide estimates of their individual and collective ability to predict IA and T1D.RESULTS: HLA genotype (DR3/4 vs. others) was the best predictor for IA (Youden's index J = 0.117) and single nucleotide polymorphism rs2476601, in PTPN22, was the best predictor for insulin autoantibodies (IAA) appearing first (IAA-first) (J = 0.123). For GAD autoantibodies (GADA)-first, weight at 1 year was the best predictor (J = 0.114). In a multivariate model, the area under the ROC curve (AUC) was 0.678 (95% CI 0.655, 0.701), 0.707 (95% CI 0.676, 0.739), and 0.686 (95% CI 0.651, 0.722) for IA, IAA-first, and GADA-first, respectively, at 6 years. The AUC of the prediction model for T1D at 3 years after the appearance of multiple autoantibodies reached 0.706 (95% CI 0.649, 0.762).CONCLUSIONS: Prediction modeling statistics are valuable tools, when applied in a time-until-event setting, to evaluate the ability of risk factors to discriminate between those who will and those who will not get disease. Although significantly associated with IA and T1D, the TEDDY risk factors individually contribute little to prediction. However, in combination, these factors increased IA and T1D prediction substantially.
|
|
| 15. |
- Lind, Tania K., et al.
(författare)
-
Effects of ethylene oxide chain length on crystallization of polysorbate 80 and its related compounds
- 2021
-
Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 592, s. 468-484
-
Tidskriftsartikel (refereegranskat)abstract
- As a result of the synthesis protocol polyoxyethylene sorbitan monooleate (polysorbate 80, PS80) is a highly complex mixture of compounds. PS80 was therefore separated into its main constituents, e.g. polyoxyethylene isosorbide esters and polyoxyethylene esters, as well as mono- di- and polyesters using preparative high-performance liquid chromatography. In this comprehensive study the individual components and their ethoxylation level were verified by matrix assisted laser desorption/ionization time-of-flight and their thermotropic behavior was analyzed using differential scanning calorimetry and X-ray diffraction. A distinct correlation was found between the average length of the ethylene oxide (EO) chains in the headgroup and the individual compounds' ability to crystallize. Importantly, a critical number of EO units required for crystallization of the headgroup was determined (6 EO units per chain or 24 per molecule). The investigation also revealed that the hydrocarbon tails only crystallize for polyoxyethylene sorbitan esters if saturated. PS80 is synthesized by reacting with approximately 20 mol of EO per mole of sorbitol, however, the number of EO units in the sorbitan ester in commercial PS80 products is higher than the expected 20 (5 EO units per chain). The complex behavior of all tested compounds revealed that if the amount of several of the linear by-products is reduced, the number of EO units in the chains will stay below the critical number and the product will not be able to crystallize by the EO chains.
|
|
| 16. |
- Morin, Maxim, et al.
(författare)
-
Bicontinuous Cubic Liquid Crystals as Potential Matrices for Non-Invasive Topical Sampling of Low-Molecular-Weight Biomarkers
- 2023
-
Ingår i: Pharmaceutics. - : MDPI. - 1999-4923. ; 15:8
-
Tidskriftsartikel (refereegranskat)abstract
- Many skin disorders, including cancer, have inflammatory components. The non-invasive detection of related biomarkers could therefore be highly valuable for both diagnosis and follow up on the effect of treatment. This study targets the extraction of tryptophan (Trp) and its metabolite kynurenine (Kyn), two compounds associated with several inflammatory skin disorders. We furthermore hypothesize that lipid-based bicontinuous cubic liquid crystals could be efficient extraction matrices. They comprise a large interfacial area separating interconnected polar and apolar domains, allowing them to accommodate solutes with various properties. We concluded, using the extensively studied GMO-water system as test-platform, that the hydrophilic Kyn and Trp favored the cubic phase over water and revealed a preference for locating at the lipid-water interface. The interfacial area per unit volume of the matrix, as well as the incorporation of ionic molecules at the lipid-water interface, can be used to optimize the extraction of solutes with specific physicochemical characteristics. We also observed that the cubic phases formed at rather extreme water activities (>0.9) and that wearing them resulted in efficient hydration and increased permeability of the skin. Evidently, bicontinuous cubic liquid crystals constitute a promising and versatile platform for non-invasive extraction of biomarkers through skin, as well as for transdermal drug delivery.
|
|
| 17. |
- Nilsson, Emelie J., et al.
(författare)
-
Mechanisms of crystallisation in polysorbates and sorbitan esters
- 2020
-
Ingår i: CrystEngComm. - : Royal Society of Chemistry. - 1466-8033. ; 22:22, s. 3840-3853
-
Tidskriftsartikel (refereegranskat)abstract
- Polysorbates (PS), commonly known as Tween (TM), are some of the most extensively used excipients and protein stabilisers in biopharmaceutical products worldwide. It is stipulated in the pharmacopoeia specifications that these ethoxylated surfactants are complex mixtures comprised of a wealth of molecular species. While little is known about the propensity of PSs to crystallise, they are used in applications ranging from food products, cosmetics, different types of drug dosage forms like creams and oral products to parenteral applications. However, in recent years a range of issues and safety concerns have appeared when using them for stabilising biopharmaceutical products including precipitation, particle formation, and adverse biological effects. Therefore, the aim of this study was to thoroughly characterise the thermotropic behaviour and mechanism of crystallisation of polysorbates with different hydrocarbon tails and their non-ethoxylated sorbitan ester equivalents for comparison. A systematic and comprehensive product characterisation was carried out, taking advantage of a combination of complementary techniques such as differential scanning calorimetry, matrix assisted laser desorption ionisation time-of-flight and small- and wide-angle X-ray diffraction. We show that polysorbate 80, having an unsaturated hydrocarbon tail, crystallises by the ethylene oxide chains in the headgroup. Polysorbate 20, 40, and 60, containing saturated hydrocarbon esters tails, crystallise not only by the ethylene oxide chains but also by their hydrocarbon tails. An analogous behaviour was observed for the PS non-ethoxylated equivalents, the sorbitan esters. Sorbitan esters with saturated hydrocarbon tails displayed a crystallisation of the tail upon cooling, whereas the sorbitan ester with unsaturated hydrocarbon tail displayed no crystallisation.
|
|
| 18. |
- Osbeck, Christofer M. G., et al.
(författare)
-
Divergent transcriptional responses of Baltic Sea bacteria to forest and agriculture river loadings
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Climate change is projected to induce substantial changes in precipitation patterns across the globe. In Northern Europe, precipitation is expected to increase more than the global average (particularly in northern Scandinavia), causing increased river runoff. The Baltic Sea is one of the largest brackish environments on earth with a catchment area that spans 14 countries, encompassing primarily forested areas and agricultural landscapes. Despite the acknowledged role of marine bacteria in nutrient cycling, there is a lack of knowledge in their metabolic responses to inorganic and organic nutrient loading from riverine runoff. We investigated the bacterial growth and gene expression responses in a mesocosm experiment in which river water from boreal forest- (enriched in humic substances) or agriculture-influenced catchment areas (enriched in nitrogen) were added to Baltic Proper water. The riverine nutrient input triggered extensive phytoplankton blooms and bacterial growth, most notably in the agriculture river treatment. Interestingly, bacterial gene expression analysis (metatranscriptomics) showed similar responses to agriculture and humic river inputs at the start of the experiment during phytoplankton development, but expression patterns diverged upon bloom senescence. This indicated that interactions between river nutrient loading and phytoplankton organic matter are important in regulating bacterial activities and responses at the molecular level. Notably, transcripts associated with phosphate metabolism were significantly enriched in the agriculture river treatment compared to the boreal forest river treatment, whereas transcripts related to nitrogen metabolism were significantly lower. The opposite pattern was observed in the boreal forest river water treatment. This suggests that bacterial transformations of organic matter and nutrient processing in coastal environments are sensitive to alterations in the precipitation-induced riverine runoff in a catchment area-dependent manner, which has implications for interpreting the ecosystem effects of globally changing precipitation patterns.
|
|
| 19. |
- Psotta, Carolin, et al.
(författare)
-
Bacteria-Infected Artificial Urine Characterization Based on a Combined Approach Using an Electronic Tongue Complemented with 1H-NMR and Flow Cytometry
- 2023
-
Ingår i: Biosensors. - : MDPI. - 2079-6374. ; 13:10, s. 916-916
-
Tidskriftsartikel (refereegranskat)abstract
- The prevailing form of bacterial infection is within the urinary tract, encompassing a wide array of bacteria that harness the urinary metabolome for their growth. Through their metabolic actions, the chemical composition of the growth medium undergoes modifications as the bacteria metabolize urine compounds, leading to the subsequent release of metabolites. These changes can indirectly indicate the existence and proliferation of bacterial organisms. Here, we investigate the use of an electronic tongue, a powerful analytical instrument based on a combination of non-selective chemical sensors with a partial specificity for data gathering combined with principal component analysis, to distinguish between infected and non-infected artificial urine samples. Three prevalent bacteria found in urinary tract infections were investigated, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis. Furthermore, the electronic tongue analysis was supplemented with 1H NMR spectroscopy and flow cytometry. Bacteria-specific changes in compound consumption allowed for a qualitative differentiation between artificial urine medium and bacterial growth.
|
|
| 20. |
- Riaz, Azra, et al.
(författare)
-
Three-Dimensional Oral Mucosal Equivalents as Models for Transmucosal Drug Permeation Studies
- 2023
-
Ingår i: Pharmaceutics. - : MDPI. - 1999-4923. ; 15:5, s. 1513-1513
-
Tidskriftsartikel (refereegranskat)abstract
- Oral transmucosal administration, where drugs are absorbed directly through the non-keratinized, lining mucosa of the mouth, represents a solution to drug delivery with several advantages. Oral mucosal equivalents (OME) developed as 3D in vitro models are of great interest since they express the correct cell differentiation and tissue architecture, simulating the in vivo conditions better than monolayer cultures or animal tissues. The aim of this work was to develop OME to be used as a membrane for drug permeation studies. We developed both full-thickness (i.e., connective plus epithelial tissue) and split-thickness (i.e., only epithelial tissue) OME using non-tumor-derived human keratinocytes OKF6 TERT-2 obtained from the floor of the mouth. All the OME developed here presented similar transepithelial electrical resistance (TEER) values, comparable to the commercial EpiOral™. Using eletriptan hydrobromide as a model drug, we found that the full-thickness OME had similar drug flux to EpiOral™ (28.8 vs. 29.6 µg/cm2/h), suggesting that the model had the same permeation barrier properties. Furthermore, full-thickness OME showed an increase in ceramide content together with a decrease in phospholipids in comparison to the monolayer culture, indicating that lipid differentiation occurred due to the tissue-engineering protocols. The split-thickness mucosal model resulted in 4–5 cell layers with basal cells still undergoing mitosis. The optimum period at the air–liquid interface for this model was twenty-one days; after longer times, signs of apoptosis appeared. Following the 3R principles, we found that the addition of Ca2+, retinoic acid, linoleic acid, epidermal growth factor and bovine pituitary extract was important but not sufficient to fully replace the fetal bovine serum. Finally, the OME models presented here offer a longer shelf-life than the pre-existing models, which paves the way for the further investigation of broader pharmaceutical applications (i.e., long-term drug exposure, effect on the keratinocytes’ differentiation and inflammatory conditions, etc.).
|
|
| 21. |
- Saba, Karim H., et al.
(författare)
-
Disruption of the TP53 locus in osteosarcoma leads to TP53 promoter gene fusions and restoration of parts of the TP53 signalling pathway
- 2023
-
Ingår i: Journal of Pathology. - 0022-3417. ; , s. 147-160
-
Tidskriftsartikel (refereegranskat)abstract
- TP53 is the most frequently mutated gene in human cancer. This gene shows not only loss-of-function mutations but also recurrent missense mutations with gain-of-function activity. We have studied the primary bone malignancy osteosarcoma, which harbours one of the most rearranged genomes of all cancers. This is odd since it primarily affects children and adolescents who have not lived the long life thought necessary to accumulate massive numbers of mutations. In osteosarcoma, TP53 is often disrupted by structural variants. Here, we show through combined whole-genome and transcriptome analyses of 148 osteosarcomas that TP53 structural variants commonly result in loss of coding parts of the gene while simultaneously preserving and relocating the promoter region. The transferred TP53 promoter region is fused to genes previously implicated in cancer development. Paradoxically, these erroneously upregulated genes are significantly associated with the TP53 signalling pathway itself. This suggests that while the classical tumour suppressor activities of TP53 are lost, certain parts of the TP53 signalling pathway that are necessary for cancer cell survival and proliferation are retained. In line with this, our data suggest that transposition of the TP53 promoter is an early event that allows for a new normal state of genome-wide rearrangements in osteosarcoma.
|
|
| 22. |
- Saba, Karim H., et al.
(författare)
-
Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma
- 2020
-
Ingår i: Journal of Pathology: Clinical Research. - : Wiley. - 2056-4538. ; 6:4, s. 231-237
-
Tidskriftsartikel (refereegranskat)abstract
- Osteoblastoma is a locally aggressive tumour of bone. Until recently, its underlying genetic features were largely unknown. During the past two years, reports have demonstrated that acquired structural variations affect the transcription factor FOS in a high proportion of cases. These rearrangements modify the terminal exon of the gene and are believed to stabilise both the FOS transcript and the encoded protein, resulting in high expression levels. Here, we applied in-depth genetic analyses to a series of 29 osteoblastomas, including five classified as epithelioid osteoblastoma. We found recurrent homozygous deletions of the NF2 gene in three of the five epithelioid cases and in one conventional osteoblastoma. These events were mutually exclusive from FOS mutations. Structural variations were determined by deep whole genome sequencing and the number of FOS-rearranged cases was less than previously reported (10/23, 43%). One conventional osteoblastoma displayed a novel mechanism of FOS upregulation; bringing the entire FOS gene under the control of the WNT5A enhancer that is itself activated by FOS. Taken together, we show that NF2 loss characterises a subgroup of osteoblastomas, distinct from FOS-rearranged cases. Both NF2 and FOS are involved in regulating bone homeostasis, thereby providing a mechanistic link to the excessive bone growth of osteoblastoma.
|
|
| 23. |
- Scherman Rydhög, Anna, et al.
(författare)
-
Intravoxel Incoherent Motion (IVIM) Imaging at Different Magnetic Field Strengths: What is Feasible?
- 2014
-
Ingår i: Magnetic Resonance Imaging. - : Elsevier BV. - 1873-5894 .- 0730-725X. ; 32:10, s. 1247-1258
-
Tidskriftsartikel (refereegranskat)abstract
- Due to limited SNR the cerebral applications of the intravoxel incoherent motion (IVIM) concept have been sparse. MRI hardware developments have resulted in improved SNR and this may justify a reassessment of IVIM imaging for non-invasive quantification of the cerebral blood volume (CBV) as a first step towards determining the optimal field strength.
|
|
