Features of the pharmacological activity of polypeptide modulators on acid-sensitive ion channels in the experiment

TRPV1 receptors play a significant physiological role. To study pharmacological activity of new agonists and antagonists is important for the development of new drugs. This paper reports on the features of polypeptide antagonists of TRPV1 based on in vivo dat

ффект зарядовой связи в полевом элементе Холла на основе тонкопленочного КНИ МОП транзистора

The influence of the coupling effect on the parameters of field Hall elements based on thin-film MOS transistors has been studied. Analysis of the development of today’s microelectronics shows the necessity of developing the element base for high performance sensors based on silicon technologies. One way to significantly improve the performance of sensing elements including magnetic field sensors is the use of thin-film transistors on the basis of silicon on insulator (SOI) structures. It has been shown that field Hall sensors (FHS) may become the basis of high-performance magnetic field sensors employing the coupling effect occurring in the double gate vertical topology of these sensing elements. Electrophysical studies of FHS have been conducted for different gate bias and power supply modes. The results show that the coupling effect between the gates occurs in FHS if the thickness of the working layer between the gates is 200 nm. This effect leads to an increase in the effective carrier mobility and hence an increase in the magnetic sensitivity of the material. Thus field Hall elements based on thin-film transistors fabricated using silicon technologies provide for a substantial increase in the magnetic sensitivity of the elements and allow their application in highly reliable magnetic field sensors.Работа посвящена изучению влияния эффекта зарядовой связи на характеристики полевого элемента Холла, изготовленного на основе тонкопленочного МОП транзистора. Анализ развития современной микроэлектроники показал необходимость развития элементной базы датчиков внешних воздействий на основе кремниевой технологии с повышенной функциональностью. Одним из способов значительного улучшения характеристик чувствительных элементов различных воздействий, в том числе и магнитного поля, является создание тонкопленочных транзисторов на основе структуры «кремний на изоляторе» (КНИ). Показано, что полевой датчик Холла (ПДХ) может стать основой высокочувствительных датчиков магнитного поля, использующих эффект зарядовой связи, возникающей в двухзатворной вертикальной топологии такого элемента. Проведены электрофизические исследования ПДХ при различных режимах включения затворов и питания. Полученные результаты показывают, что эффект зарядовой связи между затворами наблюдается в ПДХ при толщине рабочего слоя между ними равным 200 нм. Этот эффект приводит к росту эффективной подвижности носителей, и следовательно к росту магнитной чувствительности. Таким образом, полевые элементы Холла на основе тонкопленочных транзисторов, изготовленных по кремниевой технологии, позволяют значительно повысить магнитную чувствительность и использовать их в датчиках магнитного поля повышенной надежности.

Development of a recombinant immunotoxin for the immunotherapy of autoreactive lymphocytes expressing MOG-specific BCRs

© 2016, Springer Science+Business Media Dordrecht.Objective: Myelin oligodendrocyte glycoprotein (MOG) is one of the major autoantigens in multiple sclerosis (MS), therefore selective depletion of autoreactive lymphocytes exposing MOG-specific B cell receptors (BCRs) would be beneficial in terms of MS treatment. Results: Using E. coli we generated an efficient protocol for the purification of the recombinant immunotoxin DT-MOG composed of the extracellular Ig-like domain of MOG fused in frame with the catalytic and translocation subunits of diphtheria toxin (DT, Corynebacterium diphtheriae) under native conditions with a final yield of 1.5 mg per liter of culture medium. Recombinant DT-MOG was recognized in vitro by MOG-reactive antibodies and has catalytic activity comparable with wild-type DT. Conclusion: Enhanced pharmacokinetics (mean residence time in the bloodstream of 61 min) and minimized diminished nonspecific toxicity (LD50 = 1.76 mg/kg) of the DT-MOG makes it a potential candidate for the immunotherapy of MS

Development of a recombinant immunotoxin for the immunotherapy of autoreactive lymphocytes expressing MOG-specific BCRs

© 2016 Springer Science+Business Media DordrechtObjective: Myelin oligodendrocyte glycoprotein (MOG) is one of the major autoantigens in multiple sclerosis (MS), therefore selective depletion of autoreactive lymphocytes exposing MOG-specific B cell receptors (BCRs) would be beneficial in terms of MS treatment. Results: Using E. coli we generated an efficient protocol for the purification of the recombinant immunotoxin DT-MOG composed of the extracellular Ig-like domain of MOG fused in frame with the catalytic and translocation subunits of diphtheria toxin (DT, Corynebacterium diphtheriae) under native conditions with a final yield of 1.5 mg per liter of culture medium. Recombinant DT-MOG was recognized in vitro by MOG-reactive antibodies and has catalytic activity comparable with wild-type DT. Conclusion: Enhanced pharmacokinetics (mean residence time in the bloodstream of 61 min) and minimized diminished nonspecific toxicity (LD50 = 1.76 mg/kg) of the DT-MOG makes it a potential candidate for the immunotherapy of MS

Development of a recombinant immunotoxin for the immunotherapy of autoreactive lymphocytes expressing MOG-specific BCRs

OBJECTIVE: Myelin oligodendrocyte glycoprotein (MOG) is one of the major autoantigens in multiple sclerosis (MS), therefore selective depletion of autoreactive lymphocytes exposing MOG-specific B cell receptors (BCRs) would be beneficial in terms of MS treatment.RESULTS: Using E. coli we generated an efficient protocol for the purification of the recombinant immunotoxin DT-MOG composed of the extracellular Ig-like domain of MOG fused in frame with the catalytic and translocation subunits of diphtheria toxin (DT, Corynebacterium diphtheriae) under native conditions with a final yield of 1.5 mg per liter of culture medium. Recombinant DT-MOG was recognized in vitro by MOG-reactive antibodies and has catalytic activity comparable with wild-type DT.CONCLUSION: Enhanced pharmacokinetics (mean residence time in the bloodstream of 61 min) and minimized diminished nonspecific toxicity (LD50 = 1.76 mg/kg) of the DT-MOG makes it a potential candidate for the immunotherapy of MS

ДЕГРАДАЦИЯ СОЛНЕЧНЫХ ЭЛЕМЕНТОВ НА ОСНОВЕ ГИДРОГЕНИЗИРОВАННОГО АМОРФНОГО КРЕМНИЯ

The operating experience of hydrogenated amorphous silicon (a−Si : H) based solar cells has shown that besides their low efficiency this type of photovoltaics degrade much faster compared to single crystal based solar cells. As far as the processes deter- mining the degradation of amorphous materials based solar cells are not well studied, and the degradation of similar cells without light exposure has also been reported, we conducted an experiment to compare the temporal change characteristics of main solar cell parameters in darkness and under natural light. The demonstration of short circuit current reduction in darkness aged solar cells should be considered as one of the most interesting results of the work. Moreover we have shown that the change of this parameter is on average the same for the illuminated cells, while for some cells short circuit current reduction is substantially higher. This is indicative of the fact that the observed effect is not related to the Staebler—Wronski effect.Опыт эксплуатации солнечных элементов (СЭ) на основе гидрогенизированного аморфного кремния показал, что, помимо низкой эффективности, эти преобразователи значительно быстрее деградируют по сравнению с СЭ на основе монокристаллического кремния. Процессы, которые опреде- ляют деградацию СЭ на аморфных материалах, изучены недостаточно, а также известны сообщения о дегра- дации подобных образцов без света. Проведен эксперимент по сравнению особенностей изменения во времени основных параметров преобразо- вателя в темноте и под действием естественного освещения. Продемонстрировано снижение тока короткого замыкания в образцах, выдержанных в темноте. Показано, что изменение этого параметра у засвеченных образцов в среднем такое же, а для отдельных образцов падение тока короткого замыкания существенно больше. Это свидетельствует о том, что наблюдаемый эффект не связан с эффектом Стеблера—Вронского

A novel expression cassette delivers efficient production of exclusively tetrameric human butyrylcholinesterase with improved pharmacokinetics for protection against organophosphate poisoning

© 2015 Published by Elsevier B.V. Butyrylcholinesterase is a stoichiometric bioscavenger against poisoning by organophosphorus pesticides and nerve agents. The low level of expression and extremely rapid clearance of monomeric recombinant human butyrylcholinesterase (rhBChE) from bloodstream (t1/2;≈2 min) limits its pharmaceutical application. Recently (Ilyushin at al., PNAS, 2013) we described a long-acting polysialylated recombinant butyrylcholinesterase (rhBChE-CAO), stable in the bloodstream, that protects mice against 4.2 LD50 of VR. Here we report a set of modifications of the initial rhBChE expression vector to improve stability of the enzyme in the bloodstream and increase its production in CHO cells by introducing in the expression cassette: (i) the sequence of the natural human PRAD-peptide in frame with rhBChE gene via "self-processing" viral F2A peptide under control of an hEF/HTLV promoter, and (ii) previously predicted in silico MAR 1-68 and MAR X-29 sequences. This provides fully tetrameric rhBChE (4rhBChE) at 70 mg/l, that displays improved pharmacokinetics (t1/2; = 32 ± 1.2 h, MRT = 43 ± 2 h). 3D Fluorescent visualization and distribution of 125I-labeled enzyme reveals similar low level 4rhBChE and rhBChE-CAO accumulation in muscle, fat, and brain. Administered 4rhBChE was mainly catabolized in the liver and breakdown products were excreted in kidney. Injection of 1.2 LD50 and 1.1 LD50 of paraoxon to BALB/c and knockout BChE-/- mice pre-treated with 4rhBChE (50 mg/kg) resulted in 100% and 78% survival, respectively, without perturbation of long-term behavior. In contrast, 100% mortality of non-pre-treated mice was observed. The high expression level of 4rhBChE in CHO cells permits consideration of this new expression system for manufacturing BChE as a biopharmaceutical