The effect of high pressure on the NMDA receptor: molecular dynamics simulations

Professional divers exposed to ambient pressures above 11 bar develop the high pressure neurological syndrome (HPNS), manifesting as central nervous system (CNS) hyperexcitability, motor disturbances, sensory impairment, and cognitive deficits. The glutamate-type N-methyl-D-aspartate receptor (NMDAR) has been implicated in the CNS hyperexcitability of HPNS. NMDARs containing different subunits exhibited varying degrees of increased/decreased current at high pressure. The mechanisms underlying this phenomenon remain unclear. We performed 100 ns molecular dynamics (MD) simulations of the NMDAR structure embedded in a dioleoylphosphatidylcholine (DOPC) lipid bilayer solvated in water at 1 bar, hydrostatic 25 bar, and in helium at 25 bar. MD simulations showed that in contrast to hydrostatic pressure, high pressure helium causes substantial distortion of the DOPC membrane due to its accumulation between the two monolayers: reduction of the Sn-1 and Sn-2 DOPC chains and helium-dependent dehydration of the NMDAR pore. Further analysis of important regions of the NMDAR protein such as pore surface (M2 α-helix), Mg2+ binding site, and TMD-M4 α-helix revealed significant effects of helium. In contrast with previous models, these and our earlier results suggest that high pressure helium, not hydrostatic pressure per se, alters the receptor tertiary structure via protein-lipid interactions. Helium in divers’ breathing mixtures may partially contribute to HPNS symptoms. © 2019, The Author(s).The Oak Ridge Leadership Computational Facility (OLCF) at Oak Ridge National Laboratory provided access to the Titan supercomputer. The authors wish to thank Mr. Bogdan Iaparov for calculating the DOPC order parameters, Veronika Bikova and Anastasia Bazhutina for molecular volume and RDF calculations. Y.M. was partly supported by UrFU Competitiveness Enhancement Program (agreement 02.A03.21.0006)

КОМП'ЮТЕРНА ПРЕЗЕНТАЦІЯ ЯК МЕТОД НАВЧАННЯ АНГЛОМОВНОГО ПИСЬМА СТУДЕНТІВ-ПСИХОЛОГІВ

The article is devoted to issues of making presentations as a part of forming student’s communicative skills. Main points of making a presentation in English as aspects of educational activity are showed. The article provides methodology of every stage of teaching and preparing presentation which are followed by the development of not only reading, speaking and listening, but also writing skills.Стаття присвячена питанням навчання створення презентацій як складової частини формування англомовних комунікативних навичок та вмінь у студентів-психологів. Запропоновано методику, за якою кожний етап навчання та підготовки презентації супроводжується розвитком навичок та вмінь не тільки в читанні, говорінні, аудіюванні, а й письмі

Increase in the Reduction Potential of Uranyl upon Interaction with Graphene Oxide Surfaces

Coordination of uranyl (U(VI)) with carboxylate groups on functionalized graphene oxide (GO) surfaces has been shown to alter the reduction potential of the sorbed uranium ion. A quantitative measure of the reduction potential and qualitative estimation of sorption/desorption processes were conducted using cyclic voltammetry, and the proposed coordination environment was determined using the surface sensitive attenuated total reflection mode of infrared spectroscopy (ATR-FTIR). GO is a nanostructured material possessing a large amount of oxygen-containing functional groups both on basal planes and at the edges, which can form strong surface complexes with radionuclides. The presence of these functional groups on the surface of GO allows efficient immobilization of uranium due to sorption of uranyl (UO22+) to carboxylate, hydroxide, or sulfonate functional groups and the potential for enhanced reduction of U(VI) to more strongly sorbing and insoluble U(IV). Herein, binding of U(VI) to carboxylate groups on the GO surface is proposed as the primary sorption mechanism based on the FTIR study. Furthermore, the coordination of uranium with the surface increases the reduction potential of the U(VI)/U(IV) redox couple as compared to the case of the aqueous U(VI)/U(IV) species. This is consistent with the alteration of the electronic structure of the sorbed ion, which can be determined in our case due to the use of a GO-coated working electrode. Thus, GO-coated glassy carbon electrodes and other semi-conducting electrodes with high ion sorption capacities may provide a means of examining the oxidation/reduction potentials of sorbed ions

The functional state of placenta in the women with a long intergenetic interval

The examination of 70 pregnant women have been conducted, among them there have been 30 women with a long (over 10 years) intergenetic interval between giving the first and the second births (the first group), 20 aged primigravidas have been included in the second group and 20 pregnant women who have had a birth with a break of 3-5 years have been included in the third group (control group). The average age of the women of group I was 33.3 years old, of group II – 36.5 years old, of group III – 28.4 years old. All the studied hormones of the women with big intergenetic intervals have been significantly reduced with respect to the comparison group (III). In the women of the Ist group they decreased by 2.8 times, and in the women of the IInd they group – by 2.4 times with respect to the comparison group. The concentration of cortisol in the blood serum of the women of the Ist and IInd groups has significantly increased. The indicator of the first group has been significantly higher than that of the second group. Large birth spacing in pregnant women is accompanied by a significant decrease in the concentration of the hormones of placenta, which characterizes the state of placental insufficiency in the majority of the women at the 26-28th week of gestation period. The increase of serotonin concentration and the decrease of progesterone concentration can be attributed to the women with a long intergenetic interval, who are at risk of the development of a preterm birth. A significant increase of cortisol and serotonin in the blood of the women with a long intergenetic interval indicates a disorder of the adaptation mechanisms in this group of pregnant women. One-pointedness of the hormonal changes in the women with a long intergenetic interval and the age factor of the primiparous women confirm the role of age in the development of hormonal disorders in the pregnant women of the examined contingent

Drug-induced pulmonary artery hypertension

Pulmonary arterial hypertension is a condition characterized by an increase in mean pressure in the pulmonary artery. This pathology is associated with high mortality, and specific therapy for pulmonary arterial hypertension does not affect the cause of the disease and is extremely expensive. In this regard, it is especially important to study the modifiable etiological factors of pulmonary arterial hypertension. One such factor is drugs. One of the leading groups of drugs-inductors is anorexigenic drugs. It was the representatives of this group, such as aminorex, who were the first inducers of pulmonary hypertension. Moreover, this adverse reaction was so significant that it led to the withdrawal of these drugs. Currently, the leading role in the context of drug-induced pulmonary hypertension is played by such drugs as anticancer, antiviral drugs, and interferons. These drugs lead to pulmonary hypertension through various pathophysiological mechanisms. The leading measures to prevent this pathology are to limit the use of culprit medications, reduce the spread of HIV infection, since several groups of drugs can be used to treat HIV-infected patients, leading to the development of pulmonary hypertension

Optimization of the Cascade Code Parameters by the Criterion of the Boundary Value of the Interference Band and the Selection of the Decoding Algorithm

Рассмотрен когерентный канал передачи данных с псевдослучайной перестройкой рабочей частоты (ППРЧ), каскадным кодом на основе ансамбля ортогональных сигналов и кода Рида-Соломона, с различными алгоритмами приема-декодирования в условиях одновременного действия на канал двух помех – заградительной и сосредоточенной в части полосы ППРЧ. Получены оценки граничного значения части полосы ППРЧ, накрытой помехой, характеристики оптимального каскадного кода, а также выбран алгоритм приема-декодирования, при котором граничное значение части полосы, накрытой помехой, принимает максимальное значение в заданной помеховой обстановкеA coherent data transmission channel with pseudo-random tuning of the operating frequency (FH) is considered, a concatenated code based on an ensemble of orthogonal signals and a Reed-Solomon code, with various reception-decoding algorithms under conditions of simultaneous action on the channel of two interference – a barrage and a FH concentrated in a part of the band. The estimates of the boundary value of the part of the FH band covered by the interference, the characteristics of the optimal concatenated code, are obtained, and also the receive-decoding algorithm is selected, in which the boundary value of the part of the band covered by the interference takes the maximum value in a given interference environmen

A Generalized Technique for Studying the Information Properties of Channels and Recognition Systems

В работе предложена обобщённая методика исследования информационных свойств каналов и систем распознавания, применимая для анализа комплексных систем распознавания. Применение методики показало, что при объединении разнородных каналов для распознавания эффективно использование не только прямой, но и косвенной информации о принадлежности объекта к классам в алфавите окончательных (общих) решений. Объединение каналов с основной и косвенной информацией увеличило количество получаемой информации на 10–40 %The paper proposes a generalized methodology for studying the information properties of channels and recognition systems, applicable to the analysis of complex recognition systems. The application of the technique showed that when combining heterogeneous channels for recognition, it is effective to use not only direct, but also indirect information about the object’s belonging to classes in the alphabet of final (general) solutions. Combining channels with basic and indirect information increased the amount of information received by 10–40 percen

PREDICTING THE LIFETIME OF HIGH-POWER LASER DIODES FROM THE CURRENT DEPENDENCE OF THEIR SPECTRAL CHARACTERISTICS

The high power laser diodes lifetime prediction method which is based on current de-pendence line form analysis skirting laser radiation spectrum after 200 hours of service is offered

Причины отказа от назначения антикоагулянтов в стационаре больным с фибрилляцией предсердий и высоким риском инсульта: какой должна быть оптимальная тактика ведения этих пациентов?

The objective of our study was to determine the reasons for not prescribing anticoagulant therapy (ACT) in the therapeutic department of university clinic for patients with atrial fibrillation (AF) and a high risk of stroke and to discuss the optimal management of these patients.Methods and materials. A retrospective analysis of 1307 case histories of AF patients admitted to a university therapeutic clinic from 2014 to 2018 presented. The reasons for not prescribing ACT to patients with AF and high risk of stroke and optimal ACT discussed.Results. ACT was not prescribed to 109 (9.7 %) hospitalized patients out of 1128 patients with AF without prosthetic valves and mitral stenosis who had a high risk of stroke ((4.5±1.1) points on the CHA2DS2VASc scale). The risk of bleeding – (1.6±0.1) (HAS-BLED). The age of patients was (73.8±10.4) years. From 2014 to 2018, the frequency of unjustified non-prescribing ACT decreased by 3.7 times – from 47/205 (22.9 %) in 2014 to 11/178 (6.2 %) in 2018 (p=0.001). In general, over 5 years of observations, subjective reasons for not prescribing ACT were: lack of stroke risk assessment (78.0 %), senile age of patients and the presence of dementia (42.2 %), the first paroxysm of AF (22.9 %) during myocardial infarction and heart surgery, planned surgical treatment, effective radiofrequency ablation and patient refusal. Objective (usually transient) reasons for not prescribing ACT were: severe and moderate anemia (24.8 %), recent bleeding (11.9 %), gastrointestinal diseases predisposing to bleedings (9.2 %), oncology (12.8 %), end-stage chronic kidney disease (2.8 %), thrombocytopenia (2.8 %). Often various reasons for not prescribing ACT were combined.Conclusion. In patients with AF and a high risk of stroke, the incidence of not prescribing ACT decreased by 3.7 times from 2014 to 2018. In 2014, the most common reasons for not prescribing ACT were the lack of stroke risk assessment and the senile age of patients, and in 2017–2018 senile age, the first paroxysm of AF, effective radiofrequency ablation, anemia, recent bleeding, and gastrointestinal diseases predisposing to bleedings.Цель – определить причины отказов от назначения антикоагулянтной терапии (АКТ) в терапевтическом стационаре больным с фибрилляцией предсердий (ФП) и высоким риском инсульта и обсудить оптимальную тактику антитромботической терапии.Методы и материалы. Ретроспективный анализ 1307 историй болезней пациентов с ФП, госпитализированных в университетскую терапевтическую клинику в 2014–2018 гг. Изучены причины отказов от назначения АКТ у больных с высоким риском инсульта и приведена оптимальная антитромботическая терапия.Результаты. Антикоагулянты не были назначены 109 (9,7 %) госпитализированным пациентам из 1128 больных с ФП без механических протезов клапанов и митрального стеноза с высоким риском инсульта ((4,5±1,1) балла пошкале CHA2DS2VASc). Риск кровотечений – (1,6±0,1) балла (шкала HAS-BLED), возраст пациентов – (73,8±10,4) года. С 2014 по 2018 г. частота отказов от назначения АКТ при наличии показаний снизилась в 3,7 раза – с 47/205 (22,9 %) в 2014 г. до 11/178 (6,2 %) в 2018 г. (р=0,001). В целом за пять лет наблюдений субъективными причинами отказаот назначения АКТ служили отсутствие оценки риска инсульта (78,0 %), старческий возраст и наличие деменции (42,2 %), первый пароксизм ФП (22,9 %), в том числе на фоне инфаркта миокарда и операции на сердце, планируемое хирургическое лечение, эффективная радиочастотная абляция и отказ больного. Объективные (чаще временные) причины отказов от АКТ: тяжелая и средней тяжести анемия в сочетании с другими причинами (24,8 %), недавнее кровотечение (11,9 %), заболевания желудочно-кишечного тракта (ЖКТ), предрасполагающие к кровотечениям (9,2 %), онкопатология (12,8 %), терминальная стадия хронической болезни почек (2,8 %) и значимая тромбоцитопения (2,8 %). Нередко различные причины отказов от АКТ сочетались.Заключение. У пациентов с ФП и высоким риском инсульта частота отказов от назначения АКТ снизилась с 2014 по 2018 г. в 3,7 раза. В 2014 г. самые частые причины отказов от АКТ – отсутствие оценки риска инсульта и старческий возраст, а в 2017–2018 гг. – старческий возраст, первый пароксизм ФП, эффективная радиочастотная абляция, анемия, недавнее кровотечение и наличие патологии ЖКТ, предрасполагающей к кровотечению