175 research outputs found

    Обоснование применения потокоотклоняющих технологий на Западно-Катыльгинском нефтяном месторождении (Томская область)

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    Объектом исследования являются нагнетательные скважины, на которых применяются потокоотклоняющие технологии для выравнивания профиля приёмистости и увеличения нефтеотдачи. Цель работы – обосновать применение потокоотклоняющих технологий на нефтяном месторождении, оценить возможность применения различных составов для выравнивания профиля приёмистости нагнетательных скважин. В процессе исследования были рассмотрены современные потокоотклоняющие технологии и наиболее благоприятные геолого-физические условия их применения.The object of the study is injection wells, which use diverting technologies to align the injectivity profile and increase oil recovery. The purpose of the work is to justify the use of flow diverting technologies in an oil field, to assess the possibility of using various compositions to align the injectivity profile of injection wells. During the study, modern flow diverting technologies and the most favorable geological and physical conditions for their application were considered

    Elucidation of xenobiotic metabolism pathways in human skin and human skin models by proteomic profiling

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    Human skin has the capacity to metabolise foreign chemicals (xenobiotics), but knowledge of the various enzymes involved is incomplete. A broad-based unbiased proteomics approach was used to describe the profile of xenobiotic metabolising enzymes present in human skin and hence indicate principal routes of metabolism of xenobiotic compounds. Several in vitro models of human skin have been developed for the purpose of safety assessment of chemicals. The suitability of these epidermal models for studies involving biotransformation was assessed by comparing their profiles of xenobiotic metabolising enzymes with those of human skin

    Developmental neurotoxicity of MDMA. A systematic literature review summarized in a putative adverse outcome pathway

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    The increasing use of illegal drugs by pregnant women causes a public health concern because it is associated with health risks for mothers and their developing children. One of such drugs is MDMA (3,4-methylenedioxymethamphetamine) or ecstasy due to its high consumption in relevant age and sex groups and its adverse effects on human and rodent developing brains. To Journal Pre-proof 2 thoroughly review the current knowledge on the developmentally neurotoxic potential of MDMA we systematically collected and summarized articles investigating developmental neurotoxicity (DNT) of MDMA in humans and animals in in vivo and in vitro. In addition, we summarized the findings in a putative adverse outcome pathway (AOP). From an initial 299 articles retrieved from the bibliographic databases Web of Science, PubMed and DART, we selected 39 articles according to inclusion/exclusion criteria for data collection after title/abstract and full text screening. Of these 3 where epidemiological studies, 34 where in vivo studies in mice and rats and 2 were in vitro studies. The three epidemiological studies reported from the same longitudinal study and suggested that MDMA exposure during pregnancy impairs neuromotor function in infants. In rat, postnatal exposure towards MDMA also caused locomotor deficits as well as impaired spatial learning that might be associated with decreased serotonin levels in the hippocampus. In vitro MDMA caused cytotoxicity at high concentrations and effects on the serotonergic and neuritogenic alterations at lower concentrations which are in line with some of the in vivo alterations observed. Considering the adverse outcomes of developmental MDMA described in humans and in rodents we summarized the first putative AOP on developmental compound exposure leading to impaired neuromotor function in children. For generation of this AOP, MDMA exposure was taken as a model compound. In addition, we hypothesized a second AOP involving developmental disturbance of the dopaminergic system. However, further in vitro mechanistic studies are needed to understand the molecular initiating event(s) (MIE) triggering the downstream cascades and obtain consistent evidences causally linking the adverse outcome to effects at the cellular, organ and organism level

    Ontogenetic expression of thyroid hormone signaling genes: An in vitro and in vivo species comparison.

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    Thyroid hormone (TH) is essential for brain development. While disruption of TH signaling by environmental chemicals has been discussed as a mechanism of developmental neurotoxicity (DNT) for more than a decade, there remains a paucity of information linking specific TH disrupting chemicals to adverse neurodevelopmental outcomes. This data gap reflects, in part, the fact that the molecular machinery of TH signaling is complex and varies according to cell type and developmental time. Thus, establishing a baseline of the ontogenetic profile of expression of TH signaling molecules in relevant cell types is critical for developing in vitro and alternative systems-based models for screening TH disrupting chemicals for DNT. Here, we characterize the transcriptomic profile of molecules critical to TH signaling across three species-human, rat, and zebrafish-in vitro and in vivo across different stages of neurodevelopment. Our data indicate that while cultured human and rat neural progenitor cells, primary cultures of rat cortical cells, and larval zebrafish all express a fairly comprehensive transcriptome of TH signaling molecules, the spatiotemporal expression profiles as well as the responses to TH vary across species and developmental stages. The data presented here provides a roadmap for identifying appropriate in vitro and in simpler systems-based models for mechanistic studies and screening of chemicals that alter neurodevelopment via interference with TH action

    Differential cellular metabolite alterations in HaCaT cells caused by exposure to the aryl hydrocarbon receptor-binding polycyclic aromatic hydrocarbons chrysene, benzo[a]pyrene and dibenzo[a,l]pyrene

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    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the human environment. Since they are present in crude oilfractions used for the production of rubber and plastics, consumers may come into direct dermal contacts with these compounds (e.g., via tool handles) on a daily basis. Some individual PAHs are identified as genotoxic mutagens thereby prompting particular toxicological and environmental concern. Among this group, benzo[a]pyrene (BAP) constitutes a model carcinogen which is also used as reference compound for risk assessment purposes. It acts as a strong agonist of the aryl hydrocarbon receptor (AHR) and becomes metabolically activated toward mutagenic and carcinogenic intermediates by cytochrome P450-dependent monooxygenases (CYPs). While BAP has been exhaustively characterized with regard to its toxicological properties, there is much less information available for other PAHs. We treated an AHR-proficient immortal human keratinocyte cell line (i.e., HaCaT) with three selected PAHs: BAP, chrysene (CRY) and dibenzo[a,l]pyrene (DALP). Compound-mediated alterations of endogenous metabolites were investigated by an LC–MS/MS-based targeted approach. To examine AHR-dependent changes of the measured metabolites, AHR-deficient HaCaT knockdown cells (AHR-KD) were used for comparison. Our results reveal that 24 metabolites are sufficient to separate the PAH-exposed cells from untreated controls by application of a multivariate model. Alterations in the metabolomics profiles caused by each PAH show influences on the energy and lipid metabolism of the cells indicating reduced tricarboxylic acid (TCA) cycle activity and β-oxidation. Up-regulation of sphingomyelin levels after exposure to BAP and DALP point to pro-apoptotic processes caused by these two potent PAHs. Our results suggest that in vitro metabolomics can serve as tool to develop bioassays for application in hazard assessment. Keywords: Polycyclic aromatic hydrocarbons, Metabolomics, Aryl hydrocarbon receptor, Keratinocyte

    Sex-Specific Associations of Testosterone With Metabolic Traits

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    Background: Testosterone levels are differentially linked with diabetes risk in men and women: lower testosterone levels in men and higher testosterone levels in women are associated with type 2 diabetes, though, the mechanisms are not fully clear. We addressed sex-specific links between testosterone and major pathogenetic mechanisms of diabetes.Methods: We analyzed data of 623 subjects (202 male, 345 female without, and 76 female with oral contraceptive therapy [OCT]) for whom insulin sensitivity and insulin secretion were assessed by oral glucose tolerance test. Body fat percentage was assessed by bioelectrical impedance. Testosterone was measured by enzyme-linked immunoassay; free testosterone and Framingham risk score were calculated.Results: There were significant interactions between testosterone and sex for all tested metabolic traits. Increasing testosterone was associated with less body fat, elevated insulin sensitivity, and reduced glycemia, independent of adiposity in men. In women without OCT, testosterone correlated with more body fat, insulin resistance, and higher glucose concentrations. Testosterone was not associated with insulin secretion in either sex, but with lower Framingham risk score in men and higher Framingham risk score in women.Conclusions: Similar to diabetes risk, insulin resistance has different association directions with testosterone levels in males and females. Insulin resistance could therefore constitute the best biological candidate linking testosterone levels and diabetes prevalence. The question of antiandrogen therapy being able to improve metabolism, glucose tolerance and cardiovascular risk in women was not clarified in our study but should be reviewed with higher numbers in a carefully matched study to reduce the influence of confounding variables

    Разработка технологии сборки и сварки стыкового соединения труба-лист из низколегированной стали

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    Соединение вида труба-лист является одним из распространенных типов сварных соединений. К примеру, оно часто применяется при изготовлении металлических колонн и несущих опор каркасов зданий. Применение низколегированных сталей взамен углеродистых при изготовлении данных металлоконструкций обеспечивает существенное снижение металлоемкости, а также позволяет повысить различные прочностные характеристики соединения. Цель работы – разработка технологии сборки и сварки стыкового соединения труба-лист из стали 09Г2С. В процессе работы был выбран способ сварки, сварочное оборудование и сварочные материалы. Произведены расчеты параметров режима сварки, рассчитаны оптимальные геометрические характеристики шва, а также его ожидаемый химический состав.Pipe-to-sheet joint is one of common welded joints. For example it is used to make of metal columns and load-bearing supports of building frames. The use of low alloy steels instead of carbon steels in the manufacture of metal structures reduces metal consumption and allows to increase the strength characteristics of joint. Purpose of the work is development of fitting up and welding technology of a butt pipe-to-sheet joint steel 09G2S. In the progress, a welding method, welding equipment and welding materials were selected. The parameters of the welding mode, geometric characteristics and chemical composition are calculated

    Экскурсионная деятельность как актуальный способ развития туризма в г. Новосибирске

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    Последнее десятилетие в Российской Федерации возрос интерес правительства в комплексном развитии туризма: как во всем государстве, так и в отдельных регионах. Для качественного развития массового въездного и внутреннего туризма в регионах России, в частности в городе Новосибирске, необходимо уделить отдельное внимание экскурсионному обслуживанию. Именно обзорные экскурсии создают первое впечатление о городе у его гостей. От экскурсионной деятельности во многом зависит как воспримут туристы посещаемые места, захотят ли побывать в них еще раз. Поэтому целью моей работы является разработка пакета экскурсионных маршрутов по принципу Hop-on Hop-off для туристов по городу Новосибирску.The last decade in the Russian Federation has increased the interest of the government in the integrated development of tourism: both in the whole state and in certain regions. For the qualitative development of mass inbound and domestic tourism in the regions of Russia, in particular in the city of Novosibirsk, it is necessary to pay special attention to excursion services. It is the sightseeing tours that create the first impression of the city at its guests. From the excursion activity in many respects depends on how the tourists will perceive the places visited, whether they will want to visit them again. Therefore the purpose of my work is elaboration of a package of sightseeing routes on the principle of Hop-on Hop-off for tourists around the city of Novosibirsk

    Human Neurospheres as Three-Dimensional Cellular Systems for Developmental Neurotoxicity Testing

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    Bac k g r o u n d: Developmental neurotoxicity (DNT) of environmental chemicals is a serious threat to human health. Current DNT testing guidelines propose investigations in rodents, which require large numbers of animals. With regard to the “3 Rs ” (reduction, replacement, and refinement) of animal testing and the European regulation of chemicals [Registration, Evaluation, and Authorisation of Chemicals (REACH)], alternative testing strategies are needed in order to refine and reduce animal experiments and allow faster and less expensive screening. Objectives: The goal of this study was to establish a three-dimensional test system for DNT screening based on human fetal brain cells. Met h o d s: We established assays suitable for detecting disturbances in basic processes of brain development by employing human neural progenitor cells (hNPCs), which grow as neurospheres. Furthermore, we assessed effects of mercury and oxidative stress on these cells. Re s u l t s: We found that human neurospheres imitate proliferation, differentiation, and migration in vitro. Exposure to the proapoptotic agent staurosporine further suggests that human neurospheres possess functioning apoptosis machinery. The developmental neurotoxicants methylmercury chloride and mercury chloride decreased migration distance and number of neuronal-like cells in differentiated hNPCs. Furthermore, hNPCs undergo caspase-independent apoptosis when exposed toward high amounts of oxidative stress. Co n c l u s i o n s: Human neurospheres are likely to imitate basic processes of brain development, and these processes can be modulated by developmental neurotoxicants. Thus, this three-dimensional cell system is a promising approach for DNT testing. Key w o r d s: apoptosis, differentiation, DNT, human neurospheres, mercury, migration, proliferation. Environ Health Perspect 117:1131–1138 (2009). doi:10.1289/ehp.0800207 available vi
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