667 research outputs found

    Reconstitution of a human ATR-mediated DNA damage checkpoint response

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    The genomes of eukaryotic cells are constantly under assault by exogenous and endogenous forms of DNA damage. In response to DNA damage, cells activate the DNA damage checkpoint response which delays cell cycle progression. Accumulating evidence indicates that genetic checkpoint defects lead to pronounced predisposition to cancer. ATR is a key regulator of the UV-induced DNA damage checkpoint response and activates the downstream Chk1 protein kinase, which in turn affects cell cycle regulatory proteins. Despite recent progress in characterizing the molecular components of the ATR-mediated checkpoint pathway, how the components work coordinately in response to DNA damage remains ill-defined. To understand the molecular mechanism of this checkpoint response, it is necessary to develop an in vitro checkpoint system reconstituted from purified proteins. Therefore, I describe here an in vitro system with purified human checkpoint proteins that recapitulates key elements of the ATR-mediated DNA damage checkpoint. The data from this system show that damaged DNA specifically stimulates TopBP1-dependent activation of ATR kinase activity toward its substrates, Chk1 and p53. Moreover, the in vitro system provides a useful tool for studying the DNA binding and ATR stimulatory activities of TopBP1 and indicates a cooperative activation mechanism for ATR activation. Finally, I demonstrate in vitro evidence indicating the stimulatory effect of RPA-coated ssDNA on TopBP1- dependent ATR activation. I have established a useful in vitro system for studying stimulation of ATR kinase activity by other checkpoint components and provide insight into the molecular mechanism of the ATR-mediated checkpoint response. Moreover, my work will eventually contribute to the reconstitution of the complete in vitro checkpoint response encompassing all identified checkpoint components

    SRZoo: An integrated repository for super-resolution using deep learning

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    Deep learning-based image processing algorithms, including image super-resolution methods, have been proposed with significant improvement in performance in recent years. However, their implementations and evaluations are dispersed in terms of various deep learning frameworks and various evaluation criteria. In this paper, we propose an integrated repository for the super-resolution tasks, named SRZoo, to provide state-of-the-art super-resolution models in a single place. Our repository offers not only converted versions of existing pre-trained models, but also documentation and toolkits for converting other models. In addition, SRZoo provides platform-agnostic image reconstruction tools to obtain super-resolved images and evaluate the performance in place. It also brings the opportunity of extension to advanced image-based researches and other image processing models. The software, documentation, and pre-trained models are publicly available on GitHub.Comment: Accepted in ICASSP 2020, code available at https://github.com/idearibosome/srzo

    Development of Metrology for Modern Biology

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    Status of MgB2 superconducting wires at Sam Dong

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    MgB2 superconducting wires have remarkable potential as cost-effective materials for transformers, generators, power transmission, and superconducting magnetic energy storage to enable highly efficient power-grid networks for sustainable development. Herein, we report multifilamentary MgB2 wires with variously designed architectures that have been developed by Sam Dong Co., Ltd. The customized manufacturing process can also produce long-length pieces up to 3 km in length, indispensable in constructing large-scale devices, including cables. Based on this progress, we will continue to develop high-performance MgB2 wires and related superconducting technologies

    Regulatory gaps between LNG carriers and LNG fuelled ships

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    Given a number of marine vessels treating the liquefied natural gas either as cargo or fuel, this paper examined the regulatory gaps of two different international Codes – the InternationalCodeof the Construction and Equipment of Ships Carrying Liquefied Gases in Bulk and the International Code of Safety for Ships Using Gases or Other Low-flashpoint Fuels – from the regulatory standpoint. Results of the gap analysis have identified and discussed the key areas encountered with regulatory discrepancies or ambiguities that might interrupt the proper design, construction and operation of LNG carrier and LNG fuelled ship. A systematic investigation and harmonisation process across the Codes was proposed to mitigate the potential issues that may arise from the discordant regulations. Also, the International Maritime Organization was suggested to take proactive action to improve such dissonances while a general insight into the importance of filling those gaps was provided for rule-makers and stakeholders
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