438 research outputs found

    ПСИХОЛОГІЧНІ ТА СОЦІАЛЬНІ АСПЕКТИ ВНЕСЕННЯ ЗМІН ДО ТРАНСПОРТНОЇ СИСТЕМИ МІСТА

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    Definition of the main stratum segments of city transport characteristics depends on social development factors. The street space іn the world countries is changing today. Psychological and sociological conceptual knowledges are necessary to study problems of changing modern city transport problem. The basic directions of research concerning on transport factors are ecological and sociological approaches: health of individuals, quality of life, time of transport corresponding. Best experience of European countries is taken. The most adapted examples for human stay in a street environment are created in Switzerland: sidewalk - green zone - house. Psychological factors transforming transport scheme of the city were analysed. The success of the implementation of changes in the main components of the transport system depends on the perception of these events by the communityof the city.Визначення основних пріоритетів розвитку транспортних характеристик міста залежить від майбутнього соціального розвитку суспільства. Простір вулиці у країнах світу сьогодні змінюється. Необхідні психологічні та соціальні концептуальні знання для вивчення сучасних міських транспортних проблем. Головний напрям вивчення проблем транспорту направлений на екологічні та соціологічні питання: здоров я людей, якість життя, час перевезення. Взято за приклад кращі дослідження європейських країн. Швейцарія в цьому напрямку створила кращі зразки середовища проживання: тротуар – зелена зона – будинок, адаптованого до вимог людини. В статті проаналізовані психологічні фактори, котрі сприятимуть перетворенню транспортної схеми в місті. Успіх впровадження змін основних складових транспортної сітки залежить від сприйняття цих подій громадою міста

    Sequence-specific fluorescence detection of DNA by polyamide-thiazole orange conjugates

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    Fluorescent methods to detect specific double-stranded DNA sequences without the need for denaturation may be useful in the field of genetics. Three hairpin pyrrole-imidazole polyamides 2-4 that target their respective sequences 5'-WGGGWW-3', 5'-WGGCCW-3', and 5'-WGWWCW-3' (W = A or T) were conjugated to thiazole orange dye at the C-termini to examine their fluorescence properties in the presence and absence of match duplex DNA. The conjugates fluoresce weakly in the absence of DNA but showed significant enhancement (>1000-fold) upon the addition of 1 equiv of match DNA and only slight enhancement with the addition of mismatch DNA. The polyamide-dye conjugates bound specific DNA sequences with high affinity (Ka > 10(8) M(-1)) and unwound the DNA duplex through intercalation (unwinding angle, phi, approximately 8 degrees). This new class of polyamides provides a method to specifically detect DNA sequences without denaturation

    Design of a sequence-specific DNA bisintercalator

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    Programmable bisintercalators: Symmetric synthetic DNA bisintercalators (see picture) based on the H-pin polyamide motif afford high affinity and programmable sequence specificity

    Inhibition of vascular endothelial growth factor with a sequence-specific hypoxia response element antagonist

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    Vascular endothelial growth factor (VEGF) and its receptors have been implicated as key factors in tumor angiogenesis that are up-regulated by hypoxia. We evaluated the effects of DNA-binding small molecules on hypoxia-inducible transcription of VEGF. A synthetic pyrrole-imidazole polyamide designed to bind the hypoxia response element (HRE) was found to disrupt hypoxia-inducible factor (HIF) binding to HIRE. In cultured HeLa cells, this resulted in a reduction of VEGF mRNA and secreted protein levels. The observed effects were polyamide-specific and dose-dependent. Analysis of genome-wide effects of the HIRE-specific polyamide revealed that a number of hypoxia-inducible genes were down-regulated. Pathway-based regulation of hypoxia-inducible gene expression with DNA-binding small molecules may represent a new approach for targeting angiogenesis

    ARCHITECTURE AND CONSTRUCTION STUDENTS' PERCEPTION OF “TECHNICAL DRAWING” AND “DESCRIPTIVE GEOMETRY" DISCIPLINE CONTENT

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    The present paper highlights the results of pedagogical research conducted at the Architectural Department in the Kamianets-Podilskyi Professional College of Construction, Architecture and Design. The study considers the vocational pre-higher education students’ perceptions of various graphic works in drawing and descriptive geometry in the context of graphic work features, and understanding the significance of drawing works for the formation of a future specialist in the construction industry. Students were suggested to fill in the forms with a list of the curriculum topics and give grades according to three criteria: usefulness for the future profession, the complexity of the graphic work and the engagement in performing the task.Research results provide problem-solving solutions related to teaching methodology of such disciplines as "Technical Drawings", "Drawings and Basics of Descriptive Geometry" and "Descriptive geometry".Based on research findings, the recommendations concerning teaching and increasing interest in educational material can be made. It has been found that certain topics do not arouse much interest in students, so we recommend improving students' motivation in the classroom by employing engaging tasks, taking into account the peculiarities of perception and attention when studying these topics. The topics that are difficult to master according to students' responses require more hours for studying, and the topics that students consider least useful should be reviewed, reformatted, or even excluded from the program.

    УПРАВЛІННЯ ПРОЕКТОМ РОЗВИТКУ ТРАНСПОРТНОЇ МЕРЕЖІ МІСТА ПРИ ТРАНСФОРМАЦІЇ ВИРОБНИЧИХ ЗОН

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    The article deals with urban problems associated with traffic loaded streets. Methods of project oriented management to minimize impact of heavy traffic are suggested. In Urban Transport Planning a scheme of functional separation of settlement with allocation of residential and industrial zones is used and further planning of transport correspondence among particular town districts. According to the observations, some of modern cities are found in the process of changing their sizes and location of functional industrial areas. The reasons were analysed and changes were suggested to be introduced into transport systems. For transport passenger transportation changing of such parameters as direction and time needs reviewing of the characteristics of the traffic routes or revision of transport type replacement for faster, more economical and ecological one.Розглянуто причини виникнення проблем міст, які пов’язані із завантаженням транспортом вулиць. Запропоновано методи проектно-орієнтованого управління щодо мінімізації впливу надлишкової автомобілізації. У транспортному плануванні міст прийнято користуватись схемою функціонального поділу населеного пункту із виділенням сельбищних та виробничих зон та подальшим плануванням транспортних кореспонденцій між окремими районами міста. Згідно із спостереженнями, декотрі сучасні міста знаходяться в процесі зміни величини та місця виробничої функціональної зони. Проаналізовано причини та запропоновано зміни, що повинні бути внесені у транспортні системи. Для транспортних пасажирських перевезень зміна величин таких параметрів, як напрям та час викликає необхідність перегляду характеристик маршрутних перевезень чи перегляд заміни виду транспорту на більш швидкісний, економічний та екологічний

    Parallel synthesis of H-pin polyamides by alkene metathesis on solid phase

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    A small library of H-pin polyamides with variable aliphatic bridge lengths (CH(2))(n)(), where n = 4-8, connecting a central Py/Py pair was prepared via parallel synthesis with Ru-catalyzed alkene metathesis on solid phase as a complexity-generating cross-linking reaction. DNA binding affinities and sequence specificities were analyzed for each member of the library to determine the optimum linker length. An H-pin polyamide with a six-methylene bridge was found to have the highest affinity to its match site with high selectivity over a 1-bp mismatch site. The relationship between the number of methylenes in the linker (CH(2))(n)() and affinity is n = 6 > 4 > 7 > 5 > 8. These results indicate that 6 followed by 4 methylene-bridged polyamides represent the optimum spacer length for the H-pin motif in the DNA minor groove. Importantly, the H-pin is competitive with hairpin polyamides with respect to affinity and specificity. The metathesis-based convergent synthetic route to H-pin polyamides expands the scope of readily available DNA recognition motifs for small molecule-based gene regulation studies

    Parallel synthesis of H-pin polyamides by alkene metathesis on solid phase

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    A small library of H-pin polyamides with variable aliphatic bridge lengths (CH(2))(n)(), where n = 4-8, connecting a central Py/Py pair was prepared via parallel synthesis with Ru-catalyzed alkene metathesis on solid phase as a complexity-generating cross-linking reaction. DNA binding affinities and sequence specificities were analyzed for each member of the library to determine the optimum linker length. An H-pin polyamide with a six-methylene bridge was found to have the highest affinity to its match site with high selectivity over a 1-bp mismatch site. The relationship between the number of methylenes in the linker (CH(2))(n)() and affinity is n = 6 > 4 > 7 > 5 > 8. These results indicate that 6 followed by 4 methylene-bridged polyamides represent the optimum spacer length for the H-pin motif in the DNA minor groove. Importantly, the H-pin is competitive with hairpin polyamides with respect to affinity and specificity. The metathesis-based convergent synthetic route to H-pin polyamides expands the scope of readily available DNA recognition motifs for small molecule-based gene regulation studies

    ОБ’ЄКТНО-ОРІЄНТОВАНЕ УПРАВЛІННЯ ПРОЕКТАМИ МАРШРУТНИХ ПЕРЕВЕЗЕНЬ ЗАСОБАМИ GPS - МОНІТОРИНГУ

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    The structure of object-oriented control passenger traffic of megapolis cities using newer hardware, in particular, GPS-monitoring as a control system for vehicle location and condition is suggested. Models of traffic management of vehicles and special transport, mainly of passenger destination taking into account specificity of mobile passenger traffic in the city are developed. The unified model of passengers flow management with the appointment of primary and secondary highways in the city concerning loading of passenger transport means is defined. The necessity of centralized management of passenger traffic, providing minimization of congestions and accidents is demostrated. A geometric model of passenger transport highways loading into active life periods of the megapolis day concerning points identification of compromise geometric optimization streets loading with passenger transport vehicles and even distribution of passengers traffic taking into account principles and methods of the theory of object-oriented centralized project managementoptimization of passengers and targeted traffic for loss conditions of classic characteristics of the urban area population is elaborated. The model provides the possibilities of special-purpose vehicles safe passage in the city.Запропонована структура об’єктно-орієнтованого управління пасажиропотоками міст-мегаполісів з використанням більш нових технічних засобів, зокрема, GPS-моніторингу як системи контролю транспорту за місцеположенням і станом. Розроблено моделі управління рухом транспортних засобів та спеціального транспорту, головно, пасажирського призначення з урахуванням специфіки мобільних пасажирських перевезень в межах міста. Запропонована єдина модель управління пасажиропотоками з призначенням головних і другорядних транспортних магістралей в місті стосовно завантаження пасажирськими транспортними засобами. Показано необхідність централізованого управління пасажиропотоками, що забезпечує мінімізацію заторів та аварійних ситуацій. Розроблена геометрична модель завантаження транспортних пасажирських магістралей в активні періоди дня життєдіяльності мегаполісу щодо визначення точок компромісної геометричної оптимізації завантаження вулиць пасажирськими транспортними засобами і рівномірного розподілу пасажиропотоків з урахуванням принципів та методів теорії об’єктно - орієнтованого централізованого управління проектами оптимізації пасажиропотоків та цільових перевезень для умов втрати класичної характеристики міської території заселення. Модель передбачає можливості безперешкодного пересування містом автомобілів спеціального призначення

    Improved nuclear localization of DNA-binding polyamides

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    Regulation of endogenous genes by DNA-binding polyamides requires effective nuclear localization. Previous work employing confocal microscopy to study uptake of fluorophore-labeled polyamides has demonstrated the difficulty of predicting a priori the nuclear uptake of a given polyamide. The data suggest that dye identity influences uptake sufficiently such that a dye-conjugate cannot be used as a proxy for unlabeled analogs. Polyamides capable of nuclear localization unaided by fluorescent dyes are desirable due to size and other limitations of fluorophores. Recently, a polyamide-fluorescein conjugate targeted to the hypoxia response element (HRE) was found to inhibit vascular endothelial growth factor (VEGF) expression in cultured HeLa cells. The current study uses inhibition of VEGF expression as a biological read-out for effective nuclear localization of HRE-targeted polyamides. We synthesized a focused library of non-fluorescent, HRE-targeted polyamides in which the C-terminus ‘tail’ has been systematically varied. Members of this library bind the HRE with affinities comparable or superior to that of the fluorescein-labeled analog. Although most library members demonstrate modest or no biological activity, two non-fluorescent polyamides are reported with activity rivaling that of the previously reported fluorescein-labeled polyamide. We also show evidence that promoter occupancy by HIF-1, the transcription factor that binds the HRE, is inhibited by HRE-targeted polyamides
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