122 research outputs found

    Basic Robotecnical Platform for Implementation of Accurate Farming Technologies

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    Improvement of modern technical systems and technologies. Increasing the productivity of modern agricultural machines with increasing their weight, which leads, in the course of their work, to a significant compaction of the soil. The heterogeneity of the soil, as a bearing surface, causes not adjustable fluctuations in the workplace, which makes automation of the application of robotics more difficult. Modern solutions to the problems of reducing the negative impact on the soil, increasing the permeability of aggregates due to the reconstruction of the propulsors do not give the proper effect. More cardinally solve these problems, as well as the ability to implement automation and robotics bridge systems such as ABAC, moving along rail tracks, AASP on vertical piles and point gravel-halide supports with concrete platforms. The most promising of these is the AAS platform, which is a 30x10 m bridge structure that moves by step-by-step extension, the beams onto 3 subsequent pads located 10 m away. After entering the new position of the bridge platform, along the long 30-meter span beams Moves the work-technological module with a set of working elements, performing the programmed operations. Thus, in the AASP bridge system under consideration, the soil area subjected to compaction at reference points is just over 1% of the 70% protraction of modern machines. Compared to the ABAC system, moving along railways, the equipment of point supports is much less expensive and requires insignificant operating costs. At the same time, the rigidity of AASP design ensures stable operation of technological mechanisms in a programmed robotic mode with a minimum of unproductive energy costs associated with movement

    The mechanism of SARS-CoV-2 nucleocapsid protein recognition by the human 14-3-3 proteins

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    The coronavirus nucleocapsid protein (N) controls viral genome packaging and contains numerous phosphorylation sites located within unstructured regions. Binding of phosphorylated SARS-CoV N to the host 14-3-3 protein in the cytoplasm was reported to regulate nucleocytoplasmic N shuttling. All seven isoforms of the human 14-3-3 are abundantly present in tissues vulnerable to SARS-CoV-2, where N can constitute up to ∼1% of expressed proteins during infection. Although the association between 14-3-3 and SARS-CoV-2 N proteins can represent one of the key host-pathogen interactions, its molecular mechanism and the specific critical phosphosites are unknown. Here, we show that phosphorylated SARS-CoV-2 N protein (pN) dimers, reconstituted via bacterial co-expression with protein kinase A, directly associate, in a phosphorylation-dependent manner, with the dimeric 14-3-3 protein, but not with its monomeric mutant. We demonstrate that pN is recognized by all seven human 14-3-3 isoforms with various efficiencies and deduce the apparent KD to selected isoforms, showing that these are in a low micromolar range. Serial truncations pinpointed a critical phosphorylation site to Ser197, which is conserved among related zoonotic coronaviruses and located within the functionally important, SR-rich region of N. The relatively tight 14-3-3/pN association could regulate nucleocytoplasmic shuttling and other functions of N via occlusion of the SR-rich region, and could also hijack cellular pathways by 14-3-3 sequestration. As such, the assembly may represent a valuable target for therapeutic intervention

    Animal models of major depressive disorder and the implications for drug discovery and development

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    Introduction: Depression is a highly debilitating psychiatric disorder that affects the global population and causes severe disabilities and suicide. Depression pathogenesis remains poorly understood, and the disorder is often treatment-resistant and recurrent, necessitating the development of novel therapies, models and concepts in this field. Areas covered: Animal models are indispensable for translational biological psychiatry, and markedly advance the study of depression. Novel approaches continuously emerge that may help untangle the disorder heterogeneity and unclear categories of disease classification systems. Some of these approaches include widening the spectrum of model species used for translational research, using a broader range of test paradigms, exploring new pathogenic pathways and biomarkers, and focusing more closely on processes beyond neural cells (e.g. glial, inflammatory and metabolic deficits). Expert opinion: Dividing the core symptoms into easily translatable, evolutionarily conserved phenotypes is an effective way to reevaluate current depression modeling. Conceptually novel approaches based on the endophenotype paradigm, cross-species trait genetics and ‘domain interplay concept’, as well as using a wider spectrum of model organisms and target systems will enhance experimental modeling of depression and antidepressant drug discovery. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group

    Geospatial data analysis in Russia’s geoweb

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    The chapter examines the role of geospatial data in Russia’s online ecosystem. Facilitated by the rise of geographic information systems and user-generated content, the distribution of geospatial data has blurred the line between physical spaces and their virtual representations. The chapter discusses different sources of these data available for Digital Russian Studies (e.g., social data and crowdsourced databases) together with the novel techniques for extracting geolocation from various data formats (e.g., textual documents and images). It also scrutinizes different ways of using these data, varying from mapping the spatial distribution of social and political phenomena to investigating the use of geotag data for cultural practices’ digitization to exploring the use of geoweb for narrating individual and collective identities online

    СИНТЕЗ И ХАРАКТЕРИЗАЦИЯ ТРИМЕТИЛ(ФЕНИЛ)СИЛАНА — ПРЕДШЕСТВЕННИКА ДЛЯ ГАЗОФАЗНЫХ ПРОЦЕССОВ ОСАЖДЕНИЯ ПЛЕНОК SiCx : H

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    The technique of synthesis and purification of trimethyl(phenyl)silane PhSiMe3, allowing to obtain the product with high yield. Individuality of the product was confirmed by elemental analysis for C, H, Si. IR, UV and 1H NMR–spectroscopic studies, defined its spectral characteristics. Complex thermal analysis and thermogravimetric defined thermoanalytical behavior effects of PhSiMe3 in an inert atmosphere. Tensimetric studies have shown that the compound has sufficient volatility and thermal stability for use as a precursor in the process of chemical vapor deposition (CVD). The composition and temperature limits of the possible crystalline phase complexes in equilibrium with the gas phase of different composition has been determed by method of thermodynamic modeling. Calculated CVD diagrams allow us to select the optimum conditions of film deposition. The possibility of using trimethyl(phenyl)silane in CVD processes for producing dielectric films of hydrogenated silicon carbide has been demonstrated. Разработана методика синтеза и очистки триметил(фенил)силана PhSiMe3, позволяющая получать целевой продукт с высоким выходом. Индивидуальность соединения подтверждена элементным анализом на C, H, Si. ИК−, УФ− и ЯМР−спектроскопическими исследованиями (1Н, 13C, 29Si) определены его спектральные характеристики. С помощью комплексного термического анализа определены термоаналитические и термогравиметрические эффекты поведения PhSiMe3 в инертной атмосфере. На основе данных тензометрических исследований показано, что это соединение обладает достаточной летучестью и термической устойчивостью для использования в качестве прекурсора в процессах химического осаждения из газовой фазы (CVD). Методом термодинамического моделирования определен состав и температурные границы возможных кристаллических фазовых комплексов в равновесии с газовой фазой различного состава. Рассчитанные CVD− диаграммы позволяют выбрать оптимальные условия процессов осаждения из газовой фазы пленок. Показана возможность использования PhSiMe3 в процессах CVD для получения диэлектрических пленок гидрогенизированного карбида кремния.

    Prospects in Analytical Atomic Spectrometry

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    Tendencies in five main branches of atomic spectrometry (absorption, emission, mass, fluorescence and ionization spectrometry) are considered. The first three techniques are the most widespread and universal, with the best sensitivity attributed to atomic mass spectrometry. In the direct elemental analysis of solid samples, the leading roles are now conquered by laser-induced breakdown and laser ablation mass spectrometry, and the related techniques with transfer of the laser ablation products into inductively-coupled plasma. Advances in design of diode lasers and optical parametric oscillators promote developments in fluorescence and ionization spectrometry and also in absorption techniques where uses of optical cavities for increased effective absorption pathlength are expected to expand. Prospects for analytical instrumentation are seen in higher productivity, portability, miniaturization, incorporation of advanced software, automated sample preparation and transition to the multifunctional modular architecture. Steady progress and growth in applications of plasma- and laser-based methods are observed. An interest towards the absolute (standardless) analysis has revived, particularly in the emission spectrometry.Comment: Proofread copy with an added full reference list of 279 citations. A pdf version of the final published review may be requested from Alexander Bol'shakov <[email protected]

    Оптимизация алгоритма стадирования впервые выявленного рака предстательной железы путем применения ПЭТ/КТ с 68Ga-ПСМА: ретроспективное исследование

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    INTRODUCTION: Prostate cancer (PC) is the most common malignancy in men worldwide and ranks third in mortality. Improvement of the results of staging of newly detected prostate cancer is rightfully associated with the active use in clinical practice of positron emission tomography combined with computed tomography (PET/CT) with radiotracers based on prostate-specific membrane antigen (PSMA) ligands.OBJECTIVE: The aim of the study was to determine the capabilities of PET/CT with 68Ga-PSMA in evaluating the prevalence of newly diagnosed breast cancer in comparison with traditional imaging techniques (computed tomography, magnetic resonance imaging and bone scan) and to determine the role of this technology in the choice of treatment algorithm.MATERIALS AND METHODS: 120 patients aged 46 to 74 years (median age 62.5 years) with histologically verified prostate cancer underwent PET/CT with 68Ga-PSMA in our center to assess disease prevalence. The selection criteria for the study were: prostate-specific antigen (PSA) level of 5 ng/ml and above, presence of newly detected, histologically verified prostate cancer, no treatment, suspected metastatic lesion of pelvic and skeletal lymph nodes according to CT, MRI and OSG. All patients were divided into groups according to PSA level and Gleason score. Statistics: Statistical processing of the results was performed by methods of variance statistics using Statistica 10.0, GraphPad Prism 9.3.1. Wilcoxon-Mann-Whitney and Friedman tests for ANOVA were used to determine the significance of differences between comparison groups. The chi-square test with Yates correction was used to determine the reliability of intergroup differences for nominal measures (such as the presence of previous recurrences). The level of correlation was assessed using Spearman criterion.RESULTS: PET/CT imaging analysis in addition to MRI, CT, and OSG data showed TNM staging changes in 63 of 120 patients (52.3%) due to the detection of additional foci of metastatic lesions. Change of data about local spread of tumor with increasing of TNM stage due to detection of pathological RFP accumulation in seminal vesicles in 10 of 120 patients (8.3%), without structural changes using conventional imaging methods. In 20 of 64 patients (31.3%), PET/CT revealed lesions of regional lymph nodes (N) that were not visualized by conventional imaging methods due to their small size. Metastatic lesions of distant lymph nodes (M1a) and bones (M1b) undetected by CT, MRI, and OSG were found in 27 (22.5%) and 32 (26.7%) of 120 patients, respectively. At the same time, foci of pathological accumulation of 68Ga-PSMA in the bones without structural changes on CT were detected in 7 and 32 patients (21.8%).DISCUSSION: One of the objectives of this study was to compare the diagnostic capabilities of standard diagnostic imaging techniques, in particular MRI, CT and Bone scan, with the hybrid technology of PET/CT with 68Ga-PSMA to improve the accuracy of PCa staging in order to determine treatment tactics. The results demonstrate minimal superiority of PET/CT with 68Ga-PSMA over MRI in terms of sensitivity (96% and 94%, respectively) in assessing local disease prevalence. Tumor invasion of the seminal vesicles, in most cases, was detected in patients with a Gleason score greater than 8. At the same time there was a tendency for an increase in the level of radiotracer accumulation in the tumor tissue of the seminal vesicles depending on the differentiation group of PCa. Analysis of the histological material obtained after the prostatectomy demonstrated tumorous invasion of the seminal vesicles in 26 (37.1%) out of 70 operated patients. Coincidence of histological examination results with PET/CT data was found in 22 patients, with MRI data — in 20 patients. The sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT were 85%, 92%, 85%, and 92%, while the corresponding values from MRI were as follows: 77%, 88%, 77%, and 88%. Analyzing the levels of 68Ga-PSMA uptake in the tumor tissue, we found that with increasing prostate differentiation group, there was a persistent increase in radiotracer accumulation in the prostate tumor tissue. We also evaluated the interrelation of RFP accumulation with PSA level. The patients with PCa with PSA level ≥10.0 ng/ml demonstrated high accumulation of radiotracer accumulation compared to those with PSA &lt;10.0 ng/ml (p&lt;0.001).CONCLUSIONS: The use of 68Ga-PSMA PET/CT in the staging of newly diagnosed and untreated cancers provides comprehensive information on the local, regional, and distant extent of the disease, and in some cases contributes to a change in TNM stage of the disease in a single study. The use of this method before planned surgical treatment of PCa can significantly reduce the risk of early postoperative relapse, especially in patients with a Gleason score of more than 7 and a PSA level greater than 20 ng/ml.ВВЕДЕНИЕ: Рак предстательной железы (РПЖ) является наиболее распространенным злокачественным новообразованием у мужчин во всем мире и занимает третье место по смертности. Улучшение результатов стадирования впервые выявленного РПЖ по праву связано с активным использованием в клинической практике позитронно-эмиссионной томографии, совмещенной с компьютерной томографией (ПЭТ/КТ) с радиотрейсерами на основе лигандов простатспецифического мембранного антигена (ПСМА).ЦЕЛЬ: Определить возможности ПЭТ/КТ с 68Ga-ПСМА в оценке распространенности впервые выявленного РПЖ по сравнению с традиционными методами лучевой визуализации (компьютерной томографией, магнитно-резонансной томографией и остеосцинтиграфией) и установить роль этой технологии в выборе алгоритма лечения.МАТЕРИАЛЫ И МЕТОДЫ: 120 больным в возрасте от 46 до 74 лет (медиана 62,5 года) с гистологически верифицированным РПЖ в нашем центре была выполнена ПЭТ/КТ с 68Ga-ПСМА с целью оценки распространенности заболевания. Критериями отбора для выполнения исследования являлись: уровень простатспецифического антигена (ПСА) от 5 нг/мл, наличие впервые выявленного, гистологически верифицированного РПЖ, отсутствие лечения, подозрение на метастатическое поражение лимфатических узлов таза и скелета по данным КТ, МРТ и ОСГ. Все больные подразделялись на группы по уровню ПСА и сумме баллов Глисона. Статистика: Статистическую обработку результатов проводили методами вариационной статистики с использованием набора статистических программ Statistica 10.0, GraphPad Prism 9.3.1. Для определения достоверности различий между группами сравнения использовали критерий Вилкоксона–Манна–Уитни и Фридмана для ANOVA. Для выявления достоверности межгрупповых различий для номинальных показателей (таких как наличие предшествующих рецидивов) использовали тест хи-квадрат с поправкой Йейтса. Уровень корреляции оценивали с помощью критерия Спирмена.РЕЗУЛЬТАТЫ: При анализе ПЭТ/КТ-изображений дополнительно к данным МРТ, КТ и ОСГ у 63 из 120 пациентов (52,3%) была изменена стадия TNM вследствие выявления дополнительных очагов метастатического поражения. Изменение данных о местном распространении опухоли с повышением стадии по критерию Т за счет выявления патологического накопления РФП в семенных пузырьках у 10 из 120 пациентов (8,3%), без структурных изменений при традиционных методах лучевой визуализации. У 20 из 64 пациентов (31,3%) по данным ПЭТ/КТ было выявлено поражение регионарных лимфоузлов (N), не визуализируемое с помощью традиционных методов лучевой диагностики вследствие их малых размеров. Метастатическое поражение отдаленных лимфоузлов (M1а) и костей (М1b), не обнаруженное при КТ, МРТ и ОСГ, определялось у 27 (22,5%), и 32 (26,7%) из 120 пациентов соответственно. При этом очаги патологического накопления 68Ga-ПСМА в костях без структурных изменений по данным КТ были обнаружены у 7 и 32 пациентов (21,8%).ОБСУЖДЕНИЕ: Одной из задач настоящего исследования являлось сравнение диагностических возможностей стандартных методов лучевой диагностики, в частности МРТ, КТ и ОСГ, с гибридной технологией ПЭТ/КТ с 68Ga-ПСМА, для повышения точности стадирования РПЖ с целью определения тактики лечения. Полученные результаты исследования демонстрируют минимальное превосходство ПЭТ/КТ с 68Ga-ПСМА над МРТ по показателю чувствительности (96% и 94% соответственно) в оценке местной распространенности заболевания. Опухолевая инвазия семенных пузырьков в большинстве случаев была обнаружена у больных с суммой Глисона более 8 баллов. При этом была определена тенденция к увеличению уровня накопления РФП в опухолевой ткани семенных пузырьков в зависимости от группы дифференцировки РПЖ. Анализ гистологического материала, полученного после РПЭ, показал опухолевую инвазию семенных пузырьков у 26 из 70 прооперированных больных (37,1%). Совпадение результатов гистологического исследования (ГИ) с данными ПЭТ/КТ было обнаружено у 22 больных, с данными МРТ — у 20 больных. Чувствительность, специфичность, положительная прогностическая ценность и отрицательная прогностическая ценность ПЭТ/КТ составили 85%, 92%, 85% и 92%, при этом по результатам МРТ были получены следующие соответствующие показатели: 77%, 88%, 77% и 88%. Анализируя уровни захвата 68Ga-ПСМА в опухолевой ткани, мы обнаружили, что с увеличением группы дифференцировки РПЖ наблюдается стойкое повышение накопления РФП в опухолевой ткани предстательной железы. При этом также оценивалась взаимосвязь накопления РФП от уровня ПСА. Больные РПЖ при уровне ПСА ≥10,0 нг/мл демонстрировали высокое накопление РФП по сравнению с пациентами, обладающими ПСА &lt;10,0 нг/мл (p&lt;0,001).ЗАКЛЮЧЕНИЕ: Использование ПЭТ/КТ 68Ga-ПСМА при стадировании впервые выявленного и не подвергавшегося лечению РПЖ за одно исследование позволяет получить исчерпывающую информацию о местной, регионарной и отдаленной распространенности заболевания, а в некоторых случаях способствует изменению стадии TNM болезни. Применение данного метода перед планируемым хирургическим лечением РПЖ позволяет выявить значимые риски раннего послеоперационного рецидива, особенно у больных с индексом Глисона более 7 баллов

    The Lsm1-7/Pat1 complex binds to stress-activated mRNAs and modulates the response to hyperosmotic shock

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    RNA-binding proteins (RBPs) establish the cellular fate of a transcript, but an understanding of these processes has been limited by a lack of identified specific interactions between RNA and protein molecules. Using MS2 RNA tagging, we have purified proteins associated with individual mRNA species induced by osmotic stress, STL1 and GPD1. We found members of the Lsm1-7/Pat1 RBP complex to preferentially bind these mRNAs, relative to the non-stress induced mRNAs, HYP2 and ASH1. To assess the functional importance, we mutated components of the Lsm1-7/Pat1 RBP complex and analyzed the impact on expression of osmostress gene products. We observed a defect in global translation inhibition under osmotic stress in pat1 and lsm1 mutants, which correlated with an abnormally high association of both non-stress and stress-induced mRNAs to translationally active polysomes. Additionally, for stress-induced proteins normally triggered only by moderate or high osmostress, in the mutants the protein levels rose high already at weak hyperosmosis. Analysis of ribosome passage on mRNAs through co-translational decay from the 5' end (5P-Seq) showed increased ribosome accumulation in lsm1 and pat1 mutants upstream of the start codon. This effect was particularly strong for mRNAs induced under osmostress. Thus, our results indicate that, in addition to its role in degradation, the Lsm1-7/Pat1 complex acts as a selective translational repressor, having stronger effect over the translation initiation of heavily expressed mRNAs. Binding of the Lsm1-7/Pat1p complex to osmostress-induced mRNAs mitigates their translation, suppressing it in conditions of weak or no stress, and avoiding a hyperresponse when triggered
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