Phase transitions
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Our study demonstrates that nanoplasmonic sensing (NPS) can be utilized for the determination of the phase transition temperature (Tm) of phospholipids. During the phase transition, the lipid bilayer undergoes a conformational change. Therefore, it is presumed that the Tm of phospholipids can be determined by detecting conformational changes in liposomes. The studied lipids included 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). Liposomes in gel phase are immobilized onto silicon dioxide sensors and the sensor cell temperature is increased until passing the Tm of the lipid. The results show that, when the system temperature approaches the Tm, a drop of the NPS signal is observed. The breakpoints in the temperatures are 22.5 °C, 41.0 °C, and 55.5 °C for DMPC, DPPC, and DSPC, respectively. These values are very close to the theoretical Tm values, i.e., 24 °C, 41.4 °C, and 55 °C for DMPC, DPPC, and DSPC, respectively. Our studies prove that the NPS methodology is a simple and valuable tool for the determination of the Tm of phospholipids.
OBJECTIVE: To evaluate the dose-response relationship of 10, 20, and 40 mg ponesimod and long-term efficacy and safety of ponesimod 20 mg using an analysis of combined data from the phase 2 Core and Extension studies in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: In the Core study, 464 patients were randomized (1:1:1:1): placebo (n = 121), 10 mg (n = 108), 20 mg (n = 116), or 40 mg ponesimod (n = 119) once daily for 24 weeks. Patients who completed the Core study transitioned into the Extension study, which had treatment period 1 (TP1; up to 96 weeks) and TP2 and TP3 (up to 432 weeks). The 40 mg dose was discontinued due to low tolerability at the end of TP1, and the 10 mg dose was subsequently discontinued due to lower benefit-risk profile vs 20 mg at the end of TP2. All patients received 10 or 20 mg during TP2, followed by 20 mg in TP3. Annualized relapse rate (ARR), 6-month confirmed disability accumulation (CDA), time to first confirmed relapse, MRI outcomes, and safety were evaluated. RESULTS: A total of 435 patients received ≥1 dose of ponesimod (first randomized dose: 10 mg = 139, 20 mg = 145, and 40 mg = 151) at any time during the Core and/or the Extension study. As of March 31, 2019, 214 patients were still on ponesimod treatment. The median (range) of ponesimod exposure was 7.95 (0-9.36) years. Ponesimod 20 mg, from Core up to the end of TP3, was associated with sustained low clinical activity (ARR for confirmed relapses: 0.154; at week 432, Kaplan-Meier estimate for confirmed relapse was 43.9%, and 6-month CDA was 20.4%) and MRI disease activity, and over 64% of patients remained free of a confirmed relapse. Most common adverse events were nasopharyngitis (30%), headache (24%), and upper respiratory tract infection (21%). CONCLUSION: The effects on multiple sclerosis disease control were maintained with ponesimod 20 mg for approximately 8 years with no new safety concerns identified. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in individuals with RRMS, long-term treatment with ponesimod 20 mg was associated with a sustained low annualized confirmed relapse rate (0.154 at week 432), with 64% of patients remaining relapse-free. TRIAL REGISTRATION INFORMATION: EudraCT Number 2008-006786-92 (Core study) and EudraCT Number 2009-011470-15 (Extension study).
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- lidé MeSH
- magnetická rezonanční tomografie MeSH
- recidiva MeSH
- relabující-remitující roztroušená skleróza * diagnostické zobrazování farmakoterapie MeSH
- roztroušená skleróza * farmakoterapie MeSH
- thiazoly MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Ceramides (Cers) with α-hydroxylated acyl chains comprise about a third of all extractable skin Cers and are required for permeability barrier homeostasis. We have probed here the effects of Cer hydroxylation on their behavior in lipid models comprising the major SC lipids, Cer/free fatty acids (C 16-C 24)/cholesterol, and a minor component, cholesteryl sulfate. Namely, Cers with (R)-α-hydroxy lignoceroyl chains attached to sphingosine (Cer AS), dihydrosphingosine (Cer AdS), and phytosphingosine (Cer AP) were compared to their unnatural (S)-diastereomers and to Cers with non-hydroxylated lignoceroyl chains attached to sphingosine (Cer NS), dihydrosphingosine (Cer NdS), and phytosphingosine (Cer NP). By comparing several biophysical parameters (lamellar organization by X-ray diffraction, chain order, lateral packing, phase transitions, and lipid mixing by infrared spectroscopy using deuterated lipids) and the permeabilities of these models (water loss and two permeability markers), we conclude that there is no general or common consequence of Cer α-hydroxylation. Instead, we found a rich mix of effects, highly dependent on the sphingoid base chain, configuration at the α-carbon, and permeability marker used. We found that the model membranes with unnatural Cer (S)-AS have fewer orthorhombically packed lipid chains than those based on the (R)-diastereomer. In addition, physiological (R)-configuration decreases the permeability of membranes, with Cer (R)-AdS to theophylline, and increases the lipid chain order in model systems with natural Cer (R)-AP. Thus, each Cer subclass makes a distinct contribution to the structural organization and function of the skin lipid barrier.
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- acylace MeSH
- ceramidy chemie MeSH
- hydroxylace MeSH
- kůže chemie metabolismus MeSH
- lidé MeSH
- permeabilita MeSH
- sfingosin analogy a deriváty chemie MeSH
- změna skupenství * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The fluorescent molecule diphenylhexatriene (DPH) has been often used in combination with fluorescence anisotropy measurements, yet little is known regarding the non-linear optical properties. In the current work, we focus on them and extend the application to fluorescence, while paying attention to the conformational versatility of DPH when it is embedded in different membrane phases. Extensive hybrid quantum mechanics/molecular mechanics calculations were performed to investigate the influence of the phase- and temperature-dependent lipid environment on the probe. Already, the transition dipole moments and one-photon absorption spectra obtained in the liquid ordered mixture of sphingomyelin (SM)-cholesterol (Chol) (2:1) differ largely from the ones calculated in the liquid disordered DOPC and solid gel DPPC membranes. Throughout the work, the molecular conformation in SM:Chol is found to differ from the other environments. The two-photon absorption spectra and the ones obtained by hyper-Rayleigh scattering depend strongly on the environment. Finally, a stringent comparison of the fluorescence anisotropy decay and the fluorescence lifetime confirm the use of DPH to gain information upon the surrounding lipids and lipid phases. DPH might thus open the possibility to detect and analyze different biological environments based on its absorption and emission properties.
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- cholesterol chemie MeSH
- difenylhexatrien chemie MeSH
- fluorescenční barviva chemie MeSH
- fluorescenční polarizace MeSH
- lipidové dvojvrstvy chemie MeSH
- molekulární konformace MeSH
- sfingomyeliny chemie MeSH
- simulace molekulární dynamiky MeSH
- tranzitní teplota MeSH
- vztahy mezi strukturou a aktivitou MeSH
- změna skupenství MeSH
- Publikační typ
- časopisecké články MeSH
Purpose of this paper is to describe characteristic features of dissolution data by using homogeneous model of dissolution with initial transient phase. To achieve the goal we consider a random lag time before the homogeneous phase of the dissolution begins. The resulting dissolution profiles are characterized by sigmoidal shape commonly observed in empirical dissolution data. Furthermore, probability distribution of repeated measurements at fixed time is deduced from the model and function describing variability of the data in dependency on time is proposed. Three examples with normal, exponential and gamma probability distribution of the lag time are presented. All the models are pairwise compared with the Weibull function with high similarity between them. The result offers an alternative interpretation for the frequently found fit of the Weibull model to experimental data.
Plants and algae have developed various regulatory mechanisms for optimal delivery of excitation energy to the photosystems even during fluctuating light conditions; these include state transitions as well as non-photochemical quenching. The former process maintains the balance by redistributing antennae excitation between the photosystems, meanwhile the latter by dissipating excessive excitation inside the antennae. In the present study, these mechanisms have been analysed in the cryptophyte alga Guillardia theta. Photoprotective non-photochemical quenching was observed in cultures only after they had entered the stationary growth phase. These cells displayed a diminished overall photosynthetic efficiency, measured as CO2 assimilation rate and electron transport rate. However, in the logarithmic growth phase G. theta cells redistributed excitation energy via a mechanism similar to state transitions. These state transitions were triggered by blue light absorbed by the membrane integrated chlorophyll a/c antennae, and green light absorbed by the lumenal biliproteins was ineffective. It is proposed that state transitions in G. theta are induced by small re-arrangements of the intrinsic antennae proteins, resulting in their coupling/uncoupling to the photosystems in state 1 or state 2, respectively. G. theta therefore represents a chromalveolate algae able to perform state transitions.
Some insects rely on the strategy of freeze tolerance for winter survival. During freezing, extracellular body water transitions from the liquid to the solid phase and cells undergo freeze-induced dehydration. Here, we present results of a thermal analysis (from differential scanning calorimetry) of ice fraction dynamics during gradual cooling after inoculative freezing in variously acclimated larvae of two drosophilid flies, Drosophila melanogaster and Chymomyza costata Although the species and variants ranged broadly between 0 and close to 100% survival of freezing, there were relatively small differences in ice fraction dynamics. For instance, the maximum ice fraction (IFmax) ranged between 67.9% and 77.7% total body water (TBW). Chymomyza costata larvae showed statistically significant phenotypic shifts in parameters of ice fraction dynamics (melting point and IFmax) upon entry into diapause, cold acclimation and feeding on a proline-augmented diet. These differences were mostly driven by colligative effects of accumulated proline (ranging between 6 and 487 mmol kg-1 TBW) and other metabolites. Our data suggest that these colligative effects per se do not represent a sufficient mechanistic explanation for high freeze tolerance observed in diapausing, cold-acclimated C. costata larvae. Instead, we hypothesize that accumulated proline exerts its protective role via a combination of mechanisms. Specifically, we found a tight association between proline-induced stimulation of glass transition in partially frozen body liquids (vitrification) and survival of cryopreservation in liquid nitrogen.
- MeSH
- aklimatizace MeSH
- diferenciální skenovací kalorimetrie MeSH
- Drosophila melanogaster růst a vývoj fyziologie MeSH
- Drosophilidae růst a vývoj fyziologie MeSH
- larva fyziologie MeSH
- led * MeSH
- vitrifikace * MeSH
- zmrazování * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Franckeite is a natural superlattice composed of two alternating layers of different composition which has shown potential for optoelectronic applications. In part, the interest in franckeite lies in its layered nature which makes it easy to exfoliate into very thin heterostructures. Not surprisingly, its chemical composition and lattice structure are so complex that franckeite has escaped screening protocols and high-throughput searches of materials with nontrivial topological properties. On the basis of density functional theory calculations, we predict a quantum phase transition originating from stoichiometric changes in one of franckeite composing layers (the quasihexagonal one). While for a large concentration of Sb, franckeite is a sequence of type-II semiconductor heterojunctions, for a large concentration of Sn, these turn into type-III, much alike InAs/GaSb artificial heterojunctions, and franckeite becomes a strong topological insulator. Transmission electron microscopy observations confirm that such a phase transition may actually occur in nature.
The freezing process consists of dissipating heat from the product until the final temperature is lower than the temperature of crystallisation of that product. Freezing can be used for numerous applications, including for disruption of waste-activated sludge (WAS). The aim of this study was to calculate the estimated amount of heat conveyed between the solidified carbon dioxide and the WAS, in the following ratios: 0.25:1; 0.5:1; 0.75:1 and 1:1. In heat of phase transformations, dry ice sublimation, water solidification, the amount of heat transferred by other substances and heat transferred from the sludge (dry sludge) were taken into account during the process of WAS freezing. Heat changes on the surface of WAS were registered using a thermovision camera. The effectiveness of WAS disintegration was confirmed by several biochemical parameters such as soluble chemical oxygen demand (increase over 14 times), degree of disintegration (48%), proteins (increase over 5 times), carbohydrates (increase almost 7 times), RNA (increase by 2.23 mg L-1), ammonia nitrogen (increase over 23 times), phosphates (increase almost 27 times) and turbidity (increased over 7 times). It was found that dry ice pretreatment of WAS can be an intriguing alternative for the conventional methods used.
Vapor phase hydrogen peroxide (VPHP) nowadays finds more and more applications especially as a bio-decontamination agent for enclosed areas. Although this oxidizing agent logically offers a potential for the degradation of hazardous chemical contaminants, the information on the utilization within this area is very limited. The main objective of this study was to examine in detail the influence of basic operational (temperature, concentration of VPHP, relative humidity, condensation) and other conditions (e.g. amount of contaminant, the effect of UV radiation) on the efficiency of the VPHP process for the degradation of the selected model substance, i.e. 4-(dimethylamino)benzaldehyde. For this purpose, a series of different VPHP "wet" decontamination cycles (with a visible condensation) were carried out and compared. The obtained results clearly proved that VPHP could be utilized for the degradation of 4-(dimethylamino)benzaldehyde, however it was necessary to regard this process as a multi-parametric, in which all operational conditions played significant roles, while the molecular distribution of H(2)O and H(2)O(2) at first constituted the key factor for a successful degradation of contaminants on the surface. In order to achieve the highest decomposition efficiency of 4-(dimethylamino)benzaldehyde by the wet VPHP process, it appeared to be necessary to decrease the initial relative humidity in the relevant enclosed area (ideally up to 5%) before the introduction of VPHP and carry out this decontamination procedure ideally at 25°C and maintain the VPHP concentration higher than 500 ppm. Furthermore, it was found that the addition of UV radiation had a positive role on VPHP efficiency (in the best case, the degradation rate increased up to 1.5 times compared to using the sole VPHP). The monitoring of the concentration of VPHP within an enclosed facility is a good tool for the monitoring of the degradation of chemical contaminants by this agent.
- MeSH
- benzaldehydy analýza chemie MeSH
- chemické modely MeSH
- indikátory a reagencie analýza chemie MeSH
- látky znečišťující životní prostředí analýza chemie MeSH
- peroxid vodíku chemie MeSH
- regenerace a remediace životního prostředí metody MeSH
- teplota MeSH
- změna skupenství MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
