664 research outputs found

    Coherent activation of a synthetic mammalian gene network

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    A quantitative analysis of naturally-occurring regulatory networks, especially those present in mammalian cells, is difficult due to their high complexity. Much simpler gene networks can be engineered in model organisms and analyzed as isolated regulatory modules. Recently, several synthetic networks have been constructed in mammalian systems. However, most of these engineered mammalian networks have been characterized using steady-state population level measurements. Here, we use an integrated experimental-computational approach to analyze the dynamical response of a synthetic positive feedback network in individual mammalian cells. We observe a switch-like activation of the network with variable delay times in individual cells. In agreement with a stochastic model of the network, we find that increasing the strength of the positive feedback results in a decrease in the mean delay time and a more coherent activation of individual cells. Our results are important for gaining insight into biological processes which rely on positive feedback regulation

    Cloud water chemistry in Sequoia National Park

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    Interception of cloudwater by forests in the Sierra Nevada Mountains may contribute significantly to acidic deposition in the region. Cloudwater sampled in Sequoia National Park had pH values ranging from 4.4 to 5.7. The advance of cold fronts into the Park appears to lead to higher aerosol and gas phase concentrations than are seen under normal mountain-valley circulations, producing higher cloud-water concentrations than might otherwise be expected. Estimates of annual deposition rates of NO_3^−, SO_4^(2−), NH_4^+ and H^+ due to cloudwater impaction are comparable to those measured in precipitation

    Дизайн-проект реабилитационного тренажера для разработки суставов кисти руки

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    Объект проектирования: реабилитационный тренажер для разработки суставов кисти руки. Основания для разработки: необходимо разработать конструкцию, которая будет соответствовать эргономическим и эстетическим параметрам. Цель работы: разработать дизайн-проект реабилитационного тренажера для разработки суставов кисти руки для использования в медицинских учреждениях, реабилитационных центрах, а также в домашних условиях. В процессе исследования проводились теоретические исследования и разработка вариантов дизайнерских решений тренажера, формирование основного концепта. В результате исследования был разработан дизайн-проект тренажера, создана трехмерная модель. Результаты проекта по разработке медицинской тренажера могут быть внедрены в процесс оснащения российских реабилитационных центров.Design Object: Rehabilitation simulator for developing the joints of the hand. Reasons for development: It is necessary to develop a design that will correspond to ergonomic and aesthetic parameters. Requirements for ergonomics and technical aesthetics: The facility must have a high level of ergonomics, both for the patient and for medical personnel. Objective: To develop a design project of a rehabilitation simulator for the development of hand joints for use in medical institutions, rehabilitation centers, as well as at home. In the process of research, theoretical studies and development of variants of design solutions for the simulator were carried out, the main concept was formed

    Judicial Review, Irrationality, and the Limits of Intervention by the Courts

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    When exercising judicial review, the courts, on occasions, have intervened in circumstances where administrative decisions were not irrational. However, these low standards of judicial intervention are arguably constitutional, especially since the enactment of the Human Rights Act 1998 (HRA). To this end, this article seeks to establish a zone of executive decision-making, for reasons of democracy, where the courts are clearly excluded. But it is unable to do so. Does this mean, therefore, that judicial intervention on the grounds of irrationality exists without limit? Assuming this to be the case, it is suggested that the courts should show greater respect to the administrative branch of the state where it has genuinely sought to engage with the legal process in arriving at its decisions

    Drug Inhibition Profile Prediction for NFκB Pathway in Multiple Myeloma

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    Nuclear factor κB (NFκB) activation plays a crucial role in anti-apoptotic responses in response to the apoptotic signaling during tumor necrosis factor (TNFα) stimulation in Multiple Myeloma (MM). Although several drugs have been found effective for the treatment of MM by mainly inhibiting NFκB pathway, there are not any quantitative or qualitative results of comparison assessment on inhibition effect between different drugs either used alone or in combinations. Computational modeling is becoming increasingly indispensable for applied biological research mainly because it can provide strong quantitative predicting power. In this study, a novel computational pathway modeling approach is employed to comparably assess the inhibition effects of specific drugs used alone or in combinations on the NFκB pathway in MM and to predict the potential synergistic drug combinations
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