71 research outputs found

    Development strategy of service sector in conditions of federal states entities autonomy increasing

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    © 2016, Econjournals. All rights reserved.The relevance of the study is caused by the necessity to develop the sphere of services as a component of balanced socio-economic development of Federal State’s territories. The purpose of the paper is to define strategies for the development of services in conditions of increasing independence of the Federal State’s entities. A leading approach is the institutional one that considers the strategy of development of service sector in the Federal State as long-term programs of transition to innovative socially oriented type of economic development, reducing interregional differentiation in the level and quality of life of the population, creating equal opportunities for citizens and promoting human development. In the conditions of Federal State entities’ autonomy increasing the strategy of development in the sphere of services consists of citizens’ life conditions and social environment’ quality improving; accelerated development of human potential; competitiveness improving of human and ensuring it economic social sectors’ capital; development of competitive service markets; improving of the efficiency of politico-legal institutions providing social services to the population. Strategies’ defining for the development of services in the conditions of Federal State entities’ autonomy increasing is based on the principles of subsidiarity, sustainability, selectivity, fractals and transvers. Certain strategies of development of services are aimed at reducing territorial socio-economic differentiation to the level, caused by objective differences of the Federation’s entities, as well as ensuring the balance of the revenue base and expenditure commitments

    Two TPX2-Dependent Switches Control the Activity of Aurora A

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    Aurora A is an important oncogenic kinase for mitotic spindle assembly and a potentially attractive target for human cancers. Its activation could be regulated by ATP cycle and its activator TPX2. To understand the activation mechanism of Aurora A, a series of 20 ns molecular dynamics (MD) simulations were performed on both the wild-type kinase and its mutants. Analyzing the three dynamic trajectories (Aurora A-ATP, Aurora A-ADP, and Aurora A-ADP-TPX2) at the residue level, for the first time we find two TPX2-dependent switches, i.e., switch-1 (Lys-143) and switch-2 (Arg-180), which are tightly associated with Aurora A activation. In the absence of TPX2, Lys-143 exhibits a “closed” state, and becomes hydrogen-bonded to ADP. Once TPX2 binding occurs, switch-1 is forced to “open” the binding site, thus pulling ADP away from Aurora A. Without facilitation of TPX2, switch-2 exits in an “open” conformation which accompanies the outward-flipping movement of P·Thr288 (in an inactive conformation), leading to the crucial phosphothreonine exposed and accessible for deactivation. However, with the binding of TPX2, switch-2 is forced to undergo a “closed” movement, thus capturing P·Thr288 into a buried position and locking its active conformation. Analysis of two Aurora A (K143A and R180A) mutants for the two switches further verifies their functionality and reliability in controlling Aurora activity. Our systems therefore suggest two switches determining Aurora A activation, which are important for the development of aurora kinase inhibitors

    Сравнение слабительных препаратов для подготовки к КТ-колонографии при использовании схемы с полным очищением толстой кишки

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    Purpose. Our study aimed to identify an optimal full-cleanse bowel preparation scheme for patients undergoing CT colonography.Material and methods. The final sample included 118 patients: 81 females (68.6%), with the median age being 75 years (IQR 675-80 years). For bowel preparation 39 (33.1%) patients used PM/Ca, 36 (30.5%) – 2 L PEG + Asc, 19 (16.1%) – 3 L PEG, 24 (20.3%) – 4 L PEG. Otherwise, the preparation did not differ in all four groups. Visual assessment of residual stool, residual fluid, and distension degree was performed using a 4-point Likert scale. The patient’s subjective tolerance assessment was executed according to the survey results using a 5-point Likert scale.Results. There were no statistically significant differences in quality of bowel preparation in all four groups. Mean value of the total residual stool score in groups was 46.2 ± 2.87 for PM/Ca; 46.9 ± 2.34 for 2 L PEG + Asc; 46.5 ± 1.98 for 3 L PEG; 45.9 ± 3.18 for 4 L PEG (p > 0.05). The median of the total residual fluid score in groups was 36 (33–38) for PM/Ca; 36.5 (34–39) for 2 L PEG + Asc; 37 (36–39) for 3 L PEG; 36 (34–40) for 4 L PEG (p > 0.05). Mean value of the total distention degree score in groups was 43 ± 4.34 for PM/Ca; 44.6 ± 3.13 for 2 L PEG + Asc; 44.2 ± 3.98 for 3 L PEG; 43.5 ± 4.9 for 4 L PEG (p > 0.05). There was a statistically significant difference in the patient tolerance total score, depending on the laxative (p = 0.001). The total preparation score was significantly lower for PM/Ca when compared with 2 L PEG + Asc. (p = 0.021), 3 L PEG (p = 0.001), and 4 L PEG (p = 0.043).Conclusion. Use of PM/Ca in CTC preparation lowers the burden of full cleanse exam preparation and can be recommended as a safe laxative choice, including senior age patients. Цель исследования: выявить оптимальную схему подготовки слабительным препаратом с полным очищением кишки для пациентов, проходящих КТ-колонографию (КТК).Материал и методы. В финальную выборку включено 118 пациентов: женщин – 81 (68,6%); медиана возраста составила 75 лет (Q1–Q3: 67,5–80 лет). 39 (33,1%) проходили подготовку слабительным препаратом натрия пикосульфатом, магния оксидом, лимонной кислотой (НП+МО+ЛК), 36 (30,5%) пациентов – 2 л полиэтиленгликоля в сочетании с аскорбиновой кислотой (2 л ПЭГ+АК), 19 (16,1%) – 3 л ПЭГ, 24 (20,3%) – 4 л ПЭГ. В остальном подготовка не отличалась во всех четырех группах. Визуальная оценка остаточного содержимого, остаточной жидкости и степени растяжения проводилась с использованием 4-балльной шкалы Лайкерта. Оценка субъективной переносимости подготовки осуществлялась по 5-балльной шкале Лайкерта.Результаты. Статистически значимой разницы качества подготовки выявлено не было при всех вариантах подготовки. Среднее значение суммарного балла остаточного кишечного содержимого составило 46,2 ± 2,87 для группы НП+МО+ЛК; 46,9 ± 2,34 для группы ПЭГ+АК; 46,5 ± 1,98 для группы 3 л ПЭГ; 45,9 ± 3,18 для группы 4 л ПЭГ (р > 0,05). Медиана суммарного балла остаточной жидкости составила 36 (33–38) для группы НП+МО+ЛК; 36,5 (34–39) для группы ПЭГ+АК; 37 (36–39) для группы 3 л ПЭГ; 36 (34–40) для группы 4 л ПЭГ (р > 0,05). Среднее значение суммарного балла степени растяжения составила 43 ± 4,34 для группы НП+МО+ЛК; 44,6 ± 3,13 для группы ПЭГ+АК; 44,2 ± 3,98 для группы 3 л ПЭГ; 43,5 ± 4,9 для группы 4 л ПЭГ (р > 0,05). Была выявлена статистически значимая разница в суммарном балле переносимости подготовки у исследуемых в зависимости от вида слабительного препарата (p = 0,001). Суммарный балл подготовки был значительно ниже при подготовке НП+МО+ЛК при сравнении с ПЭГ+АК (p = 0,021), 3 л ПЭГ (p = 0,001) и 4 л ПЭГ (p = 0,043).Заключение. Использование НП+МО+ЛК повышает переносимость подготовки к КТК с полным очищением толстой кишки и может быть рекомендовано в качестве безопасного препарата выбора, в том числе у пациентов старшей возрастной группы.

    Two TPX2-Dependent Switches Control the Activity of Aurora A

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    Aurora A is an important oncogenic kinase for mitotic spindle assembly and a potentially attractive target for human cancers. Its activation could be regulated by ATP cycle and its activator TPX2. To understand the activation mechanism of Aurora A, a series of 20 ns molecular dynamics (MD) simulations were performed on both the wild-type kinase and its mutants. Analyzing the three dynamic trajectories (Aurora A-ATP, Aurora A-ADP, and Aurora A-ADP-TPX2) at the residue level, for the first time we find two TPX2-dependent switches, i.e., switch-1 (Lys-143) and switch-2 (Arg-180), which are tightly associated with Aurora A activation. In the absence of TPX2, Lys-143 exhibits a “closed” state, and becomes hydrogen-bonded to ADP. Once TPX2 binding occurs, switch-1 is forced to “open” the binding site, thus pulling ADP away from Aurora A. Without facilitation of TPX2, switch-2 exits in an “open” conformation which accompanies the outward-flipping movement of P·Thr288 (in an inactive conformation), leading to the crucial phosphothreonine exposed and accessible for deactivation. However, with the binding of TPX2, switch-2 is forced to undergo a “closed” movement, thus capturing P·Thr288 into a buried position and locking its active conformation. Analysis of two Aurora A (K143A and R180A) mutants for the two switches further verifies their functionality and reliability in controlling Aurora activity. Our systems therefore suggest two switches determining Aurora A activation, which are important for the development of aurora kinase inhibitors

    Widespread Expression of BORIS/CTCFL in Normal and Cancer Cells

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    BORIS (CTCFL) is the paralog of CTCF (CCCTC-binding factor; NM_006565), a ubiquitously expressed DNA-binding protein with diverse roles in gene expression and chromatin organisation. BORIS and CTCF have virtually identical zinc finger domains, yet display major differences in their respective C- and N-terminal regions. Unlike CTCF, BORIS expression has been reported only in the testis and certain malignancies, leading to its classification as a “cancer-testis” antigen. However, the expression pattern of BORIS is both a significant and unresolved question in the field of DNA binding proteins. Here, we identify BORIS in the cytoplasm and nucleus of a wide range of normal and cancer cells. We compare the localization of CTCF and BORIS in the nucleus and demonstrate enrichment of BORIS within the nucleolus, inside the nucleolin core structure and adjacent to fibrillarin in the dense fibrillar component. In contrast, CTCF is not enriched in the nucleolus. Live imaging of cells transiently transfected with GFP tagged BORIS confirmed the nucleolar accumulation of BORIS. While BORIS transcript levels are low compared to CTCF, its protein levels are readily detectable. These findings show that BORIS expression is more widespread than previously believed, and suggest a role for BORIS in nucleolar function

    EuPRAXIA - A compact, cost-efficient particle and radiation source

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    Plasma accelerators present one of the most suitable candidates for the development of more compact particle acceleration technologies, yet they still lag behind radiofrequency (RF)-based devices when it comes to beam quality, control, stability and power efficiency. The Horizon 2020-funded project EuPRAXIA ("European Plasma Research Accelerator with eXcellence In Applications") aims to overcome the first three of these hurdles by developing a conceptual design for a first international user facility based on plasma acceleration. In this paper we report on the main features, simulation studies and potential applications of this future research infrastructure

    Horizon 2020 EuPRAXIA design study

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    Horizon 2020 EuPRAXIA design study

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    The Horizon 2020 Project EuPRAXIA ("European Plasma Research Accelerator with eXcellence In Applications") is preparing a conceptual design report of a highly compact and cost-effective European facility with multi-GeV electron beams using plasma as the acceleration medium. The accelerator facility will be based on a laser and/or a beam driven plasma acceleration approach and will be used for photon science, high-energy physics (HEP) detector tests, and other applications such as compact X-ray sources for medical imaging or material processing. EuPRAXIA started in November 2015 and will deliver the design report in October 2019. EuPRAXIA aims to be included on the ESFRI roadmap in 2020

    Status of the Horizon 2020 EuPRAXIA conceptual design study

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    The Horizon 2020 project EuPRAXIA (European Plasma Research Accelerator with eXcellence In Applications) is producing a conceptual design report for a highly compact and cost-effective European facility with multi-GeV electron beams accelerated using plasmas. EuPRAXIA will be set up as a distributed Open Innovation platform with two construction sites, one with a focus on beam-driven plasma acceleration (PWFA) and another site with a focus on laser-driven plasma acceleration (LWFA). User areas at both sites will provide access to free-electron laser pilot experiments, positron generation and acceleration, compact radiation sources, and test beams for high-energy physics detector development. Support centres in four different countries will complement the pan-European implementation of this infrastructure

    Опыт применения противовирусной терапии врожденной генерализованной цитомегаловирусной инфекции

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    The article presents the results of observation and treatment with ganciclovir and oral valganciclovir form of a premature infant with congenital generalized symptomatic cytomegalovirus infection (CMVI) involving pathology of CNS, cholangitis, spontaneous pathologic fracture of femoral bone. When using ganciclovir and valganciclovir demonstrated gradual normalization of clinical and hematological parameters. In the course of treatment with ganciclovir and valganciclovir was not revealed any adverse reactions. While maintaining the CMV DNA in the blood, the duration of specific therapy, according to international recommendations, should be not less than 6 months. The decision to use a specific therapy should be made on the basis of the medical consultation, the conclusions of the medical commission and informed consent of the parents.В статье представлены результаты наблюдения и лечения ганцикловиром и пероральной формой валганцикловира недоношенного ребенка с врожденной манифестной генерализованной цитомегаловирусной инфекцией (ВЦМВИ), протекающей с поражением ЦНС, холангитом, спонтанным патологическим переломом бедренной кости. При использовании ганцикловира и валганцикловира продемонстрирована постепенная нормализация клинических и гематологических показателей. В процессе лечения ганцикловиром и валганцикловиром не было выявлено каких-либо побочных реакций. Основным методом мониторинга специфического лечения должно быть определение вирусной нагрузки (количество ДНК ЦМВ в лейкоцитах крови). При сохранении ДНК ЦМВ в крови, длительность специфической терапии, согласно международным рекомендациям, должна быть не меньше 6 месяцев. Решение об использовании специфической терапии должно приниматься на основании врачебного консилиума, заключения медицинской комиссии и получения информированного согласия родителей
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