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Previously, we have described a successful molecular switch (8-(benzo[d]thiazol-2-yl)quinolin-7-ol), working on the basis of long-range proton transfer. Bearing in mind that its switching efficiency in low-polarity aprotic solvents is not sufficient, in the current communication, we investigate in detail the effect of the substitution in the benzothiazole ring. By using the DFT approach, the ground-state stability of the tautomeric forms, involved in the switching process, is modeled with the aim of finding conditions where clean switching could be possible in variety of aprotic solvents. The results indicate that the substitution with electron-acceptor substituents could increase the switching efficiency, but the overall improvement depends on the positions and electronic effect of the particular substituent.

Although, the basic concept of a fuel cell is quite simple, creating new designs and optimizing their performance takes serious work and a mastery of several technical areas. PEM Fuel Cell Modeling and Simulation Using Matlab, provides design engineers and researchers with a valuable tool for understanding and overcoming barriers to designing and building the next generation of PEM Fuel Cells. With this book, engineers can test components and verify designs in the development phase, saving both time and money. Easy to read and understand, this book provides design and modelling tips for fuel cell components such as: modelling proton exchange structure, catalyst layers, gas diffusion, fuel distribution structures, fuel cell stacks and fuel cell plant. This book includes design advice and MATLAB and FEMLAB codes for Fuel Cell types such as: polymer electrolyte, direct methanol and solid oxide fuel cells. This book also includes types for one, two and three dimensional modeling and two-phase flow phenomena and microfluidics.

Levothyroxine sodium (LT4) absorption is known to be affected by proton pump inhibitors (PPIs). Normal gastric acid secretion is important for the subsequent intestinal absorption of LT4. A reduced gastric acidity may diminish the dissolution of the LT4 tablet in the stomach and the release of LT4 to the gut. The dissolution profile of LT4 soft capsules has been reported to be less affected by pH than that of tablets. Previous studies in healthy subjects administered with LT4 and PPIs, as well as in hypothyroid patients with atrophic gastritis confirmed little or no impact of increased gastric pH on LT4 absorption when administered in soft capsule formulation. The present study was aimed at evaluating whether LT4 soft capsules may provide better control of thyroid stimulating hormone (TSH) in thyroidectomized patients undergoing chronic replacement therapy with LT4, who were also on chronic use of PPIs.Forty-seven (47) patients were enrolled in this multicenter study. Upon switching to Tirosint capsules at the same previous dose of LT4 tablets and while maintaining the same dose of PPI, TSH (when measured on week 12 of treatment) was significantly reduced from a mean±SD of 1.34±1.51 mIU/L to 0.75±1.08 mIU/L (p<0.0001) in the Intention-To-Treat population analysis on original data. No significant changes were detected in the level of free and total thyroxine (T4), while slight but significant (p<0.05) increases were measured in free and total triiodothyronine (T3). The measured extent of TSH decrease is consonant with the extent of TSH increase previously reported by other authors upon start of PPI therapy in hypothyroid patients treated with LT4 tablets.In conclusion, these data confirm previous reports that LT4 soft capsules absorption is not affected by increased gastric pH due to PPIs. This may be relevant to improve TSH stabilization in patients who take PPIs intermittently or those with gastric pH altered by concomitant pathologies. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m.

The membrane-bound proton-pumping pyrophosphatase (V-PPase), together with the V-type H+-ATPase, generates the proton motive force that drives vacuolar membrane solute transport. Transgenic plants constitutively overexpressing V-PPases were shown to have improved salinity tolerance, but the relative impact of increasing PPi hydrolysis and proton-pumping functions has yet to be dissected. For a better understanding of the molecular processes underlying V-PPase-dependent salt tolerance, we transiently overexpressed the pyrophosphate-driven proton pump (NbVHP) in Nicotiana benthamiana leaves and studied its functional properties in relation to salt treatment by primarily using patch-clamp, impalement electrodes and pH imaging. NbVHP overexpression led to higher vacuolar proton currents and vacuolar acidification. After 3 d in salt-untreated conditions, V-PPase-overexpressing leaves showed a drop in photosynthetic capacity, plasma membrane depolarization and eventual leaf necrosis. Salt, however, rescued NbVHP-hyperactive cells from cell death. Furthermore, a salt-induced rise in V-PPase but not of V-ATPase pump currents was detected in nontransformed plants. The results indicate that under normal growth conditions, plants need to regulate the V-PPase pump activity to avoid hyperactivity and its negative feedback on cell viability. Nonetheless, V-PPase proton pump function becomes increasingly important under salt stress for generating the pH gradient necessary for vacuolar proton-coupled Na+ sequestration.

ObjectiveTo establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO).DesignIn this phase III, double-blind, multicentre study, patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs).ResultsIn the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI –3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI –1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI –4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI –5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI –8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI –9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively.ConclusionOur findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms.Trial registration number NCT02388724.

Due to a high antiproton beam resolution the p¯ANDA experiment at FAIR will offer a unique possibility to perform precise resonance energy scans. Thereby a precise line shape and width measurement of very narrow resonances like the charmonium-like X (3872), which is discussed to be exotic, becomes feasible. Monte Carlo studies have been performed, to address the achievable sensitivities of such measurements, assuming different signal cross-sections, line shapes and luminosity combinations.

Hyperon production in p¯p→Y¯Y reactions is one of the main parts of the P¯ANDA physics program. By colliding antiprotons and protons with HESR at FAIR, antihyperon hyperon pairs can be produced via the annihilation of light antiquark quark pairs and the production of s¯s pairs. Feasibility studies have been performed for a set of p¯p→Y¯Y reactions. Reconstruction rates for these reactions at P¯ANDA have been estimated. In particular, the feasibility of measuring spin observables in the p¯p→Ξ¯+Ξ− reaction at pbeam = 7.0 GeV/c is presented.

ObjectiveWe aim to compare the effects of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) on the gut microbiota through longitudinal analysis.DesignHealthy volunteers were randomly assigned to receive either PPI (n=23) or H2RA (n=26) daily for seven consecutive days. We collected oral (saliva) and faecal samples before and after the intervention for metagenomic next-generation sequencing. We analysed intervention-induced alterations in the oral and gut microbiome including microbial abundance and growth rates, oral-to-gut transmissions, and compared differences between the PPI and H2RA groups.ResultsBoth interventions disrupted the gut microbiota, with PPIs demonstrating more pronounced effects. PPI usage led to a significantly higher extent of oral-to-gut transmission and promoted the growth of specific oral microbes in the gut. This led to a significant increase in both the number and total abundance of oral species present in the gut, including the identification of known disease-associated species like Fusobacterium nucleatum and Streptococcus anginosus. Overall, gut microbiome-based machine learning classifiers could accurately distinguish PPI from non-PPI users, achieving an area under the receiver operating characteristic curve (AUROC) of 0.924, in contrast to an AUROC of 0.509 for H2RA versus non-H2RA users.ConclusionOur study provides evidence that PPIs have a greater impact on the gut microbiome and oral-to-gut transmission than H2RAs, shedding light on the mechanism underlying the higher risk of certain diseases associated with prolonged PPI use.Trial registration numberChiCTR2300072310.