109 research outputs found

    Membrane Permeabilization by Oligomeric α-Synuclein: In Search of the Mechanism

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    Background: \ud The question of how the aggregation of the neuronal protein α-synuclein contributes to neuronal toxicity in Parkinson's disease has been the subject of intensive research over the past decade. Recently, attention has shifted from the amyloid fibrils to soluble oligomeric intermediates in the α-synuclein aggregation process. These oligomers are hypothesized to be cytotoxic and to permeabilize cellular membranes, possibly by forming pore-like complexes in the bilayer. Although the subject of α-synuclein oligomer-membrane interactions has attracted much attention, there is only limited evidence that supports the pore formation by α-synuclein oligomers. In addition the existing data are contradictory.\ud \ud Methodology/Principal Findings:\ud Here we have studied the mechanism of lipid bilayer disruption by a well-characterized α-synuclein oligomer species in detail using a number of in vitro bilayer systems and assays. Dye efflux from vesicles induced by oligomeric α-synuclein was found to be a fast all-or-none process. Individual vesicles swiftly lose their contents but overall vesicle morphology remains unaltered. A newly developed assay based on a dextran-coupled dye showed that non-equilibrium processes dominate the disruption of the vesicles. The membrane is highly permeable to solute influx directly after oligomer addition, after which membrane integrity is partly restored. The permeabilization of the membrane is possibly related to the intrinsic instability of the bilayer. Vesicles composed of negatively charged lipids, which are generally used for measuring α-synuclein-lipid interactions, were unstable to protein adsorption in general.\ud \ud Conclusions/Significance:\ud The dye efflux from negatively charged vesicles upon addition of α-synuclein has been hypothesized to occur through the formation of oligomeric membrane pores. However, our results show that the dye efflux characteristics are consistent with bilayer defects caused by membrane instability. These data shed new insights into potential mechanisms of toxicity of oligomeric α-synuclein species

    Широкозахватный опрыскиватель с гибким отводом и летательными аппаратами для обработки посевов риса

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    The article presents the brief analysis of existing technical determinations for spraying, the surface injection of liquid solutions, in the course of which about 75 percent of pesticides used in agricultural production are injected in order to preserve the crop from pests, diseases and weeds. (Purpose of the study) To develop the wide-coverage sprinkler with extended operational and technological capabilities for the rice sowings. (Materials and methods) It has been established that the main criterion for the up-to-date creation of the technical equipment used for spraying is the reduction of norms of the working fluid consumption and the level of environmental pollution by pesticides and also that the domesticmachines for this use coming to the market have low technical performance indicators and insufficient reliability. (Results and discussions) The design of a new wide-coverage spraying machine with a flexible tap and vehicles for the spraying of rice and with extended operational and technological capabilities, containing two propulsion units (one with a current generator, the other with a solution tank and a pressure pipeline) has been suggested. They are equipped with the frames with tensioners and are kinematically connected to each other by a flexible carcase on which the vehicles and suspended nodes of the mud channel with spraying machines are placed. The spraying of the rice fields by vehicles confirms theexpediency of their application in the rice industry for the ensuring of significant reduction in the crop losses from plant diseases. The production of new chemicals with low consumption rates and enhanced biological activity served as the basis for the development of the proposed design of wide-coverage sprinkler to meet modern requirements for sprayers of this type and intended for the use in medium and large rice farms. (Conclusions) The use of the presented wide-coverage sprinkler will allow farmers to apply intensive technology of rice cultivation on rice farms, and it will significantly increase the effectiveness of protective measures and reduce the consumption rates of chemicals, as well as reduce haul costs and spraying of working liquid solutions. The adoption of new technologies and technical means of plant protection that meetmodern requirements are worthy of continued work on their improvement and, in particular, the creation of new technicalmeans of weed controlПриведен краткий анализ существующих технических решений для поверхностного внесения жидких растворов – опрыскивания, в процессе которого вносится до 75 процентов применяемых в сельскохозяйственном производстве ядохимикатов с целью сохранения урожая от вредителей, болезней и сорной растительности. (Цель исследований) Разработать широкозахватный опрыскиватель для посевов риса с расширенными эксплуатацион-но-технологическими возможностями. (Материалы и методы) Отметили, что основным критерием, отвечающим современным требованиям по созданию технических средств для опрыскивания, служит снижение норм расхода рабочей жидкости и уровня загрязнения окружающей среды ядохимикатами. Показали, что поступающие на рынок отечественные машины данного назначения имеют низкие технико-эксплуатационные показатели и недостаточную надежность. (Результат и обсуждение) Предложили конструкцию нового широкозахватного опрыскивателя для риса с расширенными эксплуатационно-технологическими возможностями, с гибким отводом и летательными аппаратами. В конструкцию включены два движителя (один с генератором тока, другой – с емкостью дляраствора и напорным трубопроводом). Они оснащены рамами с натяжителями и кинематически связаны между собой гибким остовом, на котором размещены летательные аппараты и подвесные узлы растворопровода с распылителями. Подтвердили целесообразность обработки рисовых полей летательными аппаратами для обеспечениясущественного сокращения потерь урожая от заболеваний растений. Предложили конструкцию широкозахватного опрыскивателя, отвечающего современным требованиям к опрыскивателям данного вида и предназначенного для применения в средних и крупных рисоводческих хозяйствах при использовании новых химических веществ с небольшими нормами расхода и усиленной биологической активностью. (Выводы) Провели теоретические расчеты, позволяющие обосновать конструктивно-технологические параметры разрабатываемого широкозахватного опрыскивателя, учитывающие основные факторы, оказывающие влияние на качество процесса опрыскивания. Показали, что использование представленного широкозахватного опрыскивателя позволит в рисоводческих хозяйствах применить интенсивную технологию возделывания риса, что существенно повысит эффективность защитных мероприятий и сократит нормы расхода химикатов, а также снизит затраты на транспортировку и внесение жидких рабочих растворо

    Совершенствование технологии и средств механизации для борьбы с сорной растительностью

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    Weed vegetation in orchards and vineyards is one of the main reasons of low productivity. The applied technologies and weed control means provide decrease in contamination of orchards and vineyards insufficiently effectively that leads to a fruits harvest redice. Therefore it is necessary to improve the available methods and means, to develop new ones and on this basis to create scientifically-grounded complex of measures on weed control. This problem drequires further studies with the aim of developing the prospective technologies and technical means of mechanization for the weed control. Results of researches on mechanization of weed control, ways and means for realization of it are presented in the paper. Taking into account biological features of weeds the design of a flame cultivator for weed control in orchards and vineyards is developed and science-based. This cultivator will allow to reduce the prime cost, significantly increase quality and minimize the negative impact of herbicide use on crops, to improve yields, product quality and resource efficiency. Use of the offered flame cultivator will eliminate hand-weeding and help for more effective weed control in the rows of orchards and vineyards.Сорная растительность в садах и виноградниках - одна из главных причин низкой урожайности. Применяемые технологии и средства борьбы недостаточно эффективно обеспечивают снижение засоренности садов и виноградников, что приводит к недобору урожая плодов. Поэтому необходимо усовершенствовать имеющиеся приемы и средства, разработать новые и создать научно-обоснованный комплекс мероприятий по борьбе с сорняками. Данная проблема требует дальнейших исследований с целью разработки перспективных технологий и технических средств механизации борьбы с сорной растительностью. Представлены результаты исследований по механизации борьбы с сорной растительностью, способы и устройства для ее осуществления. С учетом биологических особенностей сорняков разработана и научно обоснована конструкция огневого культиватора для борьбы с сорной растительностью в садах и виноградниках. Он позволит снизить себестоимость обработки и существенно повысить ее качество, а также минимизировать негативное влияние применения гербицидов на культурные растения, повысить урожайность, улучшить качество продукции, обеспечить ресурсосбережение. Применение предлагаемого огневого культиватора исключит ручные прополки и поможет более эффективно бороться с сорняками в междурядьях садов и виноградников

    Sensation of draft at uncovered ankles for women exposed to displacement ventilation and underfloor air distribution systems

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    Draft is defined as unwanted local convective cooling. Existing draft risk models, developed in the 1970s, focus on air movement at the neck. The purpose of the present study is to experimentally evaluate ankle draft risk for women with uncovered ankles because of current widespread use of displacement ventilation and underfloor air distribution systems and changes in dress customs. Thirty female university students participated in nine double-blind randomized tests. The subjects wore sandals with lower legs, ankles and feet uncovered. Exposures occurred in an environmental chamber resembling an office environment. The operative temperature at 1.1 m above the floor was maintained at 24.1 °C. The measured air speeds at the ankle varied between 0.16 and 0.59 m/s and the air temperature at the ankle varied between 18.0 and 21.7 °C. Subjective responses were obtained to assess these parameters: thermal acceptability, comfort, preference and sensation, air movement acceptability and preference, local thermal sensation and comfort, and perceived air quality. Subjects were more sensitive to ankle draft than expected. For all the tested conditions, between 20 and 37% of the subjects found the overall thermal environment not acceptable, while between 23 and 57% of the subjects found air movement at the ankle unacceptable. These dissatisfaction percentages are higher than those of international, American and European standards, indicating the need to develop a draft risk model for displacement ventilation and underfloor air distribution systems

    A Systematic Analysis of the Exclusive B -> K^* l^+ l^- Decay

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    A model-independent analysis for the exclusive, rare B -> K^* l^+ l^- decay is presented. Systematically studied are the experimentally measured quantities, such as, branching ratio, forward-backward asymmetry, longitudinal polarization of the final leptons, and the ratio ΓL/ΓT\Gamma_L/\Gamma_T of the decay widths when KK^\ast meson is longitudinally and transversally polarized. The dependence of the asymmetry parameter α=2ΓL/ΓT1\alpha = 2 \Gamma_L/\Gamma_T -1 on the new Wilson coefficients is also studied in detail. It is found that the afore-mentioned physical observables are quite sensitive to the new Wilson coefficients. Therefore, once we have the experimental data with high statistics and a deviation from the Standard Model, we can interpret the source of such discrepancy.Comment: To be published in PRD (2000

    Thermal comfort, perceived air quality, and cognitive performance when personally controlled air movement is used by tropically acclimatized persons

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    In a warm and humid climate, increasing the temperature setpoint offers considerable energy benefits with low first costs. Elevated air movement generated by a personally controlled fan can compensate for the negative effects caused by an increased temperature setpoint. Fifty-six tropically acclimatized persons in common Singaporean office attire (0.7 clo) were exposed for 90 minutes to each of five conditions: 23, 26, and 29 °C and in the latter two cases with and without occupant controlled air movement. Relative humidity was maintained at 60%. We tested thermal comfort, perceived air quality, sick building syndrome symptoms and cognitive performance. We found that thermal comfort, perceived air quality, and sick building syndrome symptoms are equal or better at 26 °C and 29 °C than at the common setpoint of 23 °C if a personally controlled fan is available for use. The best cognitive performance (as indicated by task speed) was obtained at 26 °C; at 29 °C, the availability of an occupant-controlled fan partially mitigated the negative effect of the elevated temperature. The typical Singaporean indoor air temperature setpoint of 23 °C yielded the lowest cognitive performance. An elevated setpoint in air-conditioned buildings augmented with personally controlled fans might yield benefits for reduced energy use and improved indoor environmental quality in tropical climates

    A systematic review of operating room ventilation

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    Ventilation systems are the primary way of eliminating airborne pathogenic particles in an operating room (OR). However, such systems can be complex due to factors such as different surgical instruments, diverse room sizes, various staff counts, types of clothing used, different surgical types and duration, medications, and patient conditions. OR ventilation should provide a thermally comfortable environment for the surgical staff team members while preventing the patient from suffering from any extreme hypothermia. Many technical, logistical, and ethical implications need to be considered in the early stage of designing a ventilation system for an OR. Years of research and a significant number of publications have highlighted the controversy and disagreement among infection specialists, design engineers, and ventilation experts in this context. This review article aims to provide a good understanding of OR ventilation systems in the context of air quality and infection control from existing research and provide multidimensional insights for appropriate design and operation of the OR. To this end, we have conducted a systematic review of the literature, covering 253 articles in this context. Systematic review and meta-analyses were used to map the evidence and identify research gaps in the existing clinical, practical, and engineering knowledge. The present study is categorized into six research focuses: ventilation system, thermal comfort, staff work practice and obstacles, door operation and passage, air cleaning technology, emission rate, and clothing systems. In the conclusion, we summarize the key limitations of the existing studies and insights for future research direction

    Dengue Virus Ensures Its Fusion in Late Endosomes Using Compartment-Specific Lipids

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    Many enveloped viruses invade cells via endocytosis and use different environmental factors as triggers for virus-endosome fusion that delivers viral genome into cytosol. Intriguingly, dengue virus (DEN), the most prevalent mosquito-borne virus that infects up to 100 million people each year, fuses only in late endosomes, while activation of DEN protein fusogen glycoprotein E is triggered already at pH characteristic for early endosomes. Are there any cofactors that time DEN fusion to virion entry into late endosomes? Here we show that DEN utilizes bis(monoacylglycero)phosphate, a lipid specific to late endosomes, as a co-factor for its endosomal acidification-dependent fusion machinery. Effective virus fusion to plasma- and intracellular- membranes, as well as to protein-free liposomes, requires the target membrane to contain anionic lipids such as bis(monoacylglycero)phosphate and phosphatidylserine. Anionic lipids act downstream of low-pH-dependent fusion stages and promote the advance from the earliest hemifusion intermediates to the fusion pore opening. To reach anionic lipid-enriched late endosomes, DEN travels through acidified early endosomes, but we found that low pH-dependent loss of fusogenic properties of DEN is relatively slow in the presence of anionic lipid-free target membranes. We propose that anionic lipid-dependence of DEN fusion machinery protects it against premature irreversible restructuring and inactivation and ensures viral fusion in late endosomes, where the virus encounters anionic lipids for the first time during entry. Currently there are neither vaccines nor effective therapies for DEN, and the essential role of the newly identified DEN-bis(monoacylglycero)phosphate interactions in viral genome escape from the endosome suggests a novel target for drug design
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