1,253 research outputs found

    Signal Recognition Particle (SRP) and SRP Receptor: A New Paradigm for Multistate Regulatory GTPases

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    The GTP-binding proteins or GTPases comprise a superfamily of proteins that provide molecular switches in numerous cellular processes. The β€œGTPase switch” paradigm, in which a GTPase acts as a bimodal switch that is turned β€œon” and β€œoff” by external regulatory factors, has been used to interpret the regulatory mechanism of many GTPases for more than two decades. Nevertheless, recent work has unveiled an emerging class of β€œmultistate” regulatory GTPases that do not adhere to this classical paradigm. Instead of relying on external nucleotide exchange factors or GTPase activating proteins to switch between the on and off states, these GTPases have the intrinsic ability to exchange nucleotides and to sense and respond to upstream and downstream factors. In contrast to the bimodal nature of the GTPase switch, these GTPases undergo multiple conformational rearrangements, allowing multiple regulatory points to be built into a complex biological process to ensure the efficiency and fidelity of the pathway. We suggest that these multistate regulatory GTPases are uniquely suited to provide spatial and temporal control of complex cellular pathways that require multiple molecular events to occur in a highly coordinated fashion

    Ground state sign-changing homoclinic solutions for a discrete nonlinear pp-Laplacian equation with logarithmic nonlinearity

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    By using a direct non-Nehari manifold method from [X.H. Tang, B.T. Cheng. J. Differ. Equations. 261(2016), 2384-2402.], we obtain an existence result of ground state sign-changing homoclinic solution which only changes sign one times and ground state homoclinic solution for a class of discrete nonlinear pp-Laplacian equation with logarithmic nonlinearity. Moreover, we prove that the sign-changing ground state energy is larger than twice of the ground state energy

    A Framework Of Green Insurance To Safeguard Green Certified Commercial Buildings In Malaysia

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    In 2009, Malaysia adopted Green Building Index (GBI) to provide green certification to buildings that fulfil the sustainable requirements. This research is focused on newly built Green Certified Commercial Buildings (GCCB) because the value of the property will appreciate, and it is easier to maintain the certification than residential property because unlike residential property, an individual owned property, GCCB is a shared property handled by a building management team. In addition, the reputation of having a green certification to embrace its market value is essential for a GCCB for business opportunity purpose. Although the number of GCCB is increasing, yet their insurance coverage remains as conventional property insurance, which does not provide the real coverage on the status of the GCCB. Therefore, this study aims to identify the factors that could potentially drive Green Insurance into Malaysia; the strategies to promote Green Insurance effectively in Malaysia and to propose a framework for implementation of Green Insurance. Qualitative research method was used in this research and the research design is exploratory, since the novelty of the research and Malaysia still does not have green insurance for the GCCB. Moreover, the qualitative data is collected from the interview sessions with green building management team and top management from insurance companies. This research provides the insights of the possible factors, suggested strategies to promote Green Insurance effectively and proposed a new framework for implementation of Green Insurance for GCCB in Malaysia. Based on the findings, the factors and strategies have been arranged according to their significant level. The top three most significant factors to drive implementation of Green Insurance are insufficient coverage of standard commercial property insurance, increase value of GCCB and reduce climate change that can reduce catastrophe lost. In addition, based on the findings, it can be concluded that the top three significant strategies to promote Green Insurance effectively are organize community and stakeholder discussions, train the participants in workshops and forming strategic alliances between government, civil society and commercial organizations. Thus, a new framework is proposed based on the significant level of the factors and strategies for implementation of Green Insurance to GCCB. This research has identified that insurance companies and GCCB have the relationship and efforts must be done on both side to raise the awareness of Green Insurance to make it become possible. This research is important because it is time for insurance companies start to consider these GCCB to provide sufficient coverage for them as a new business opportunity. In addition, GCCB also can seek this as an opportunity to have complete risk transfer to insurance companies to safeguard their property value. Currently the insurance companies still not yet ready to provide Green Insurance for GCCB because GCCB still relative new in the market. Therefore, the lack of claim history causes insurance companies still required some time to observe this potential market

    Ground state sign-changing solutions for second order elliptic equation with logarithmic nonlinearity on locally finite graphs

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    We obtain the existence results of ground state sign-changing solutions and ground state solutions for a class of second order elliptic equation with logarithmic nonlinearity on a locally finite graph G=(V,E)G=(V,E), and obtain the sign-changing ground state energy is larger than twice of the ground state energy. The method we used is a direct non-Nehari manifold method in [X.H. Tang, B.T. Cheng. J. Differ. Equations. 261(2016), 2384-2402.

    Fidelity of Cotranslational Protein Targeting by the Signal Recognition Particle

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    Accurate folding, assembly, localization, and maturation of newly synthesized proteins are essential to all cells and require high fidelity in the protein biogenesis machineries that mediate these processes. Here, we review our current understanding of how high fidelity is achieved in one of these processes, the cotranslational targeting of nascent membrane and secretory proteins by the signal recognition particle (SRP). Recent biochemical, biophysical, and structural studies have elucidated how the correct substrates drive a series of elaborate conformational rearrangements in the SRP and SRP receptor GTPases; these rearrangements provide effective fidelity checkpoints to reject incorrect substrates and enhance the fidelity of this essential cellular pathway. The mechanisms used by SRP to ensure fidelity share important conceptual analogies with those used by cellular machineries involved in DNA replication, transcription, and translation, and these mechanisms likely represent general principles for other complex cellular pathways

    On the Importance of Word and Sentence Representation Learning in Implicit Discourse Relation Classification

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    Implicit discourse relation classification is one of the most difficult parts in shallow discourse parsing as the relation prediction without explicit connectives requires the language understanding at both the text span level and the sentence level. Previous studies mainly focus on the interactions between two arguments. We argue that a powerful contextualized representation module, a bilateral multi-perspective matching module, and a global information fusion module are all important to implicit discourse analysis. We propose a novel model to combine these modules together. Extensive experiments show that our proposed model outperforms BERT and other state-of-the-art systems on the PDTB dataset by around 8% and CoNLL 2016 datasets around 16%. We also analyze the effectiveness of different modules in the implicit discourse relation classification task and demonstrate how different levels of representation learning can affect the results.Comment: Accepted by IJCAI 202
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