126 research outputs found

    Профессиональная направленность при обучении английскому языку студентов неязыковых специальностей

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    Предметом статьи является эффективность использования новой технологии при обучении и изучении английского языка с профессиональной направленностью.Предметом статті є ефективність використання нової технології під час навчання та вивчення англійської мови з професійною направленістю.Subject of the article is the effectiveness of using the new technology when teaching and studying English language for specific purposes

    Бизнес-планирование во внешнеэкономической деятельности (ВЭД) предприятия, как инструмент качества корпоративного управления

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    In vitro models, including the widely used PC12 cell line, can increase insight into cellular and molecular mechanisms underlying neurodegenerative processes. An important determinant for the vulnerability of cells for chemical insults may be the endogenous level of oxidative stress. To test this hypothesis, we induced different degrees of cellular stress in PC12 cells by altering their ROS production using dexamethasone, l-dihydroxyphenylalanine (l-DOPA) and iron. These different PC12 models were subsequently used to investigate whether the degree of cellular stress could increase their susceptibility to environmental pollutants. The characteristics of these stressed PC12 cell subtypes and their vulnerability to the reference pesticide rotenone were investigated using a combination of biochemical (oxidative stress, cell viability, and α-synuclein expression) and functional (fluorescent calcium imaging) assays. Our combined data demonstrate that chemically-induced stress in PC12 cells increases the production of reactive oxygen species (ROS) and alters calcium homeostasis and α-synuclein expression. Moreover, l-DOPA and FeSO4 pre-treated PC12 cells show increased vulnerability to rotenone-induced cytotoxicity. These chemically-stressed cell models may therefore prove valuable to investigate how increased cellular stress influences neurotoxic outcome, for example in case of mixture toxicity

    “Національна меншина”: підходи до визначення

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    Основна мета статті полягає в роз’ясненні поняття національної меншини як суспільного явища. Здійснюється аналіз категорій ”національна меншина”, ”національна група”, ”етнічна меншина”. Автор зауважує, що у вітчизняній і світовій політичній літературі не існує універсальної, сталої концепції національних меншин.The main goal of article is to explain national minority phenomenon with a help of etnopolitological conception. National minority, nation, ethnic, ethnic group and ethnic minority conceptions analyze. The author of article says that «Domestic and world political literature don’t have universal concept»

    Интеллигенция как субъект и объект манипуляции

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    Humans are exposed to distinct structural classes of insecticides with different neurotoxic modes of action. Because calcium homeostasis is essential for proper neuronal function and development, we investigated the effects of insecticides from different classes (pyrethroid: (α-)cypermethrin; organophosphate: chlorpyrifos; organochlorine: endosulfan; neonicotinoid: imidacloprid) and mixtures thereof on the intracellular calcium concentration ([Ca(2+)]i). Effects of acute (20 min) exposure to (mixtures of) insecticides on basal and depolarization-evoked [Ca(2+)]i were studied in vitro with Fura-2-loaded PC12 cells and high resolution single-cell fluorescence microscopy. The data demonstrate that cypermethrin, α-cypermethrin, endosulfan, and chlorpyrifos concentration-dependently decreased depolarization-evoked [Ca(2+)]i, with 50% (IC50) at 78nM, 239nM, 250nM, and 899nM, respectively. Additionally, acute exposure to chlorpyrifos or endosulfan (10μM) induced a modest increase in basal [Ca(2+)]i, amounting to 68 ± 8nM and 53 ± 8nM, respectively. Imidacloprid did not disturb basal or depolarization-evoked [Ca(2+)]i at 10μM. Following exposure to binary mixtures, effects on depolarization-evoked [Ca(2+)]i were within the expected effect additivity range, whereas the effect of the tertiary mixture was less than this expected additivity effect range. These results demonstrate that different types of insecticides inhibit depolarization-evoked [Ca(2+)]i in PC12 cells by inhibiting voltage-gated calcium channels (VGCCs) in vitro at concentrations comparable with human occupational exposure levels. Moreover, the effective concentrations in this study are below those for earlier described modes of action. Because inhibition of VGCCs appears to be a common and potentially additive mode of action of several classes of insecticides, this target should be considered in neurotoxicity risk assessment studies

    Філософсько-правові проблеми реалізації права на працю

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    Розкривається зміст категорії «праця». Досліджуються філософсько-правові про­блеми у сфері здійснення права на працю.Раскрывается содержание категории «труд». Исследуются философско-правовые проблемы в сфере осуществления права на труд.In the article the content of the category «labour» is revealed. The philosophical and legal problems in the field of realization of the right to work are being researched

    Обработка оптических измерений траектории летательных объектов

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    Рассмотрены методы уравнивания угловых измерений по способу наименьших квадратов: метод уравнивания измерений отдельно в каждом временном сечении, предполагающий нулевое математическое ожидание случайных ошибок измерений, и метод уравнивания избыточных оптических измерений с подавлением их постоянных систематических ошибок в предположении засоренности измерений как случайными, так и неизвестными по величине и знаку систематическими погрешностями.Розглянуто методи зрівнювання кутових вимірювань за способом найменших квадратів: метод зрівнювання вимірювань окремо в кожному часовому розрізі, що передбачає нульове математичне очікування випадкових похибок вимірювань, і метод зрівнювання надлишкових оптичних вимірювань із заглушенням їх постійних систематичних похибок у припущенні засміченості вимірювань як випадковими, так і невідомими за величиною та знаком систематичними похибками.The methods of equalizing angular measurements according to the method of least squares are examined: the method of equalizing measurements separately in each temporary section, that assumes the zero mathematical expectation of the random errors of measurements, and the method of equalizing excessive optical measurements with suppression of their constant systematic errors under the assumption of the obstruction of measurements by systematic errors both random and unknowns by value and sign

    Коннотации этнонима. Лингвокультурологический аспект (на материале английского языка)

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    Статья посвящена исследованию коннотаций этнонимической лексики в рамках лингвокультурологического подхода. Предпринимается попытка создания языкового портрета ирландца на номинативном материале английского языка и выявления этнокультурных стереотипов в отношении представителей этого этноса.Стаття присвячується дослідженню коннотацій етнонимічної лексики у межах лінгвокультурологичного підходу. Автор робить спробу створити лінгвистичний портрет ирландця спираючись на номінативний матеріал англійської мови і виявити етнокультурні стереотипи у відношенні представників цього етносу.The article deals with the analysis of ethnonym connotation in the aspect of linguistic culturology. The author makes an attempt to create the linguistic portrait of an Irishman on the basis of English language and reveal the ethnocultural stereotypes in relation to the Irish

    Enterovirus D-68 Infection of Primary Rat Cortical Neurons: Entry, Replication, and Functional Consequences

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    Enterovirus D68 (EV-D68) is an emerging pathogen associated with mild to severe respiratory disease. Since 2014, EV-D68 is also linked to acute flaccid myelitis (AFM), causing paralysis and muscle weakness in children. However, it remains unclear whether this is due to an increased pathogenicity of contemporary EV-D68 clades or increased awareness and detection of this virus. Here, we describe an infection model of primary rat cortical neurons to study the entry, replication, and functional consequences of different EV-D68 strains, including historical and contemporary strains. We demonstrate that sialic acids are important (co)receptors for infection of both neurons and respiratory epithelial cells. Using a collection of glycoengineered isogenic HEK293 cell lines, we show that sialic acids on either N-glycans or glycosphingolipids can be used for infection. Additionally, we show that both excitatory glutamatergic and inhibitory GABA-ergic neurons are susceptible and permissive to historical and contemporary EV-D68 strains. EV-D68 infection of neurons leads to the reorganization of the Golgi-endomembranes forming replication organelles, first in the soma and later in the processes. Finally, we demonstrate that the spontaneous neuronal activity of EV-D68-infected neuronal network cultured on microelectrode arrays (MEA) is decreased, independent of the virus strain. Collectively, our findings provide novel insights into neurotropism and -pathology of different EV-D68 strains, and argue that it is unlikely that increased neurotropism is a recently acquired phenotype of a specific genetic lineage. IMPORTANCE Acute flaccid myelitis (AFM) is a serious neurological illness characterized by muscle weakness and paralysis in children. Since 2014, outbreaks of AFM have emerged worldwide, and they appear to be caused by nonpolio enteroviruses, particularly enterovirus-D68 (EV-D68), an unusual enterovirus that is known to mainly cause respiratory disease. It is unknown whether these outbreaks reflect a change of EV-D68 pathogenicity or are due to increased detection and awareness of this virus in recent years. To gain more insight herein, it is crucial to define how historical and circulating EV-D68 strains infect and replicate in neurons and how they affect their physiology. This study compares the entry and replication in neurons and the functional consequences on the neural network upon infection with an old "historical" strain and contemporary "circulating" strains of EV-D68

    Rational design of highly potent broad-spectrum enterovirus inhibitors targeting the nonstructural protein 2C

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    There is a great need for antiviral drugs to treat enterovirus (EV) and rhinovirus (RV) infections, which can be severe and occasionally life-threatening. The conserved nonstructural protein 2C, which is an AAA+ ATPase, is a promising target for drug development. Here, we present a structure-activity relationship study of a previously identified compound that targets the 2C protein of EV-A71 and several EV-B species members, but not poliovirus (PV) (EV-C species). This compound is structurally related to the Food and Drug Administration (FDA)-approved drug fluoxetine—which also targets 2C—but has favorable chemical properties. We identified several compounds with increased antiviral potency and broadened activity. Four compounds showed broad-spectrum EV and RV activity and inhibited contemporary strains of emerging EVs of public health concern, including EV-A71, coxsackievirus (CV)-A24v, and EV-D68. Importantly, unlike (S)-fluoxetine, these compounds are no longer neuroactive. By raising resistant EV-A71, CV-B3, and EV-D68 variants against one of these inhibitors, we identified novel 2C resistance mutations. Reverse engineering of these mutations revealed a conserved mechanism of resistance development. Resistant viruses first acquired a mutation in, or adjacent to, the α2 helix of 2C. This mutation disrupted compound binding and provided drug resistance, but this was at the cost of viral fitness. Additional mutations at distantly localized 2C residues were then acquired to increase resistance and/or to compensate for the loss of fitness. Using computational methods to identify solvent accessible tunnels near the α2 helix in the EV-A71 and PV 2C crystal structures, a conserved binding pocket of the inhibitors is proposed
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