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Ser38-His93-Asn91 triad confers resistance of JFH1 HCV NS5A-Y93H variant to NS5A inhibitors

FEBS Journal 2024年第6期291卷 1264-1274页

作者： Lee, Wei-Ping Tsai, Keng-Chang Liao, Shi-Xian Huang, Yi-Hsiang Hou, Ming-Chih Lan, Keng-Hsin Department of Medical Research Taipei Veterans General Hospital Taiwan Institute of Biochemistry and Molecular Biology School of Life Sciences National Yang Ming Chiao Tung University Taipei Taiwan National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei Taiwan The Ph.D. Program for Medical Biotechnology College of Medical Science and Technology Taipei Medical University Taiwan Division of Gastroenterology and Hepatology Department of Medicine Taipei Veterans General Hospital Taiwan School of Medicine College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Institute of Clinical Medicine School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Institute of Pharmacology College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan

HCV NS5A is a dimeric phosphoprotein involved in HCV replication. NS5A inhibitors are among direct-acting antivirals (dAA) for HCV therapy. The Y93H mutant of NS5A is resistant to NS5A inhibitors, but the precise mechanism remains unclear. In this report, we proposed a Ser38-His93-Asn91 triad to dissect the mechanism. Using pymol 1.3 software, the homology structure of JFH1 NS5A was determined based on the dimer structure of genotype 1b extracted from the database Protein dataBank (***/pdbsum) with codes 1ZH1 and 3FQM/3FQQ. FLAG-NS5A-WT failed to form dimer in the absence of nonstructural proteins from subgenomic replicon (NS3-5A);however, FLAG-NS5A-Y93H was able to form dimer without the aid of NS3-5A. The Ser38-His93-Asn91 triad in the dimer of the Y93H variant predicts a structural crash of the cleft receiving the NS5A inhibitor daclatasvir. The dimerization assay revealed that the existence of JFH1-NS5A-1ZH1 and -3FQM homology dimers depended on each other for existence and that both NS5A-WT 1ZH1 and 3FQM dimers cooperated to facilitate RNA replication. However, NS5A-Y93H 1ZH1 alone could form dimer and conduct RNA replication in the absence of the 3FQM structure. In conclusion, this study provides novel insight into the functional significance of the Ser38-His93-Asn91 triad in resistance of the Y93H variant to NS5A inhibitors. © 2023 Federation of European Biochemical Societies.

关键词： dimerization drug resistance Hepatitis C virus inhibitor NS5A Y93H mutant

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Autonomous Vehicles for All?

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ACM Journal on Autonomous Transportation Systems 2024年第1期1卷 1-8页

作者： Sakib Mahmud Khan M Sabbir Salek Vareva Harris Gurcan Comert Eric A. Morris Mashrur Chowdhury Intelligent Transportation Systems Lead MITRE Corporation McLean VA Ph.D. Candidate Glenn Department of Civil Engineering Clemson University Clemson SC Vice President for Corporate Engagement O Analytics Incorporated Fairmont WV Associate Professor Computer Science Physics and Engineering Department Benedict College Columbia SC USA Professor Nieri Department of Construction Development and Planning Clemson University Clemson SC USA Professor Glenn Department of Civil Engineering Clemson University Clemson SC USA

The traditional build-and-expand approach is not a viable solution to keep roadway traffic rolling safely, so technological solutions, such as autonomous vehicles (AVs), are favored. AVs have considerable potential to increase the carrying capacity of roads, ameliorate the chore of driving, improve safety, provide mobility for those who cannot drive, and help the environment. However, they also raise concerns over whether they are socially responsible, taking into account issues such as fairness, equity, and transparency. Regulatory bodies have focused on AV safety, cybersecurity, privacy, and legal liability issues, but have failed to adequately address social responsibility. Thus, existing AV developers do not have to embed social responsibility factors in their proprietary technology. Adverse bias may therefore occur in the development and deployment of AV technology. For instance, an artificial intelligence-based pedestrian detection application used in an AV may, in limited lighting conditions, be biased to detect pedestrians who belong to a particular racial demographic more efficiently compared to pedestrians from other racial demographics. Also, AV technologies tend to be costly, with a unique hardware and software setup which may be beyond the reach of lower-income people. In addition, data generated by AVs about their users may be misused by third parties such as corporations, criminals, or even foreign governments. AVs promise to dramatically impact labor markets, as many jobs that involve driving will be made redundant. We argue that the academic institutions, industry firms, and government agencies overseeing AV development and deployment must act proactively to ensure that AVs serve all and do not increase the digital divide in our society.

关键词： Autonomous vehicles Social responsibility Fairness Equity Transparency

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Fabrication of tantalum silicate films with low TCR and low resistivity by magnetron sputtering

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Vacuum 2024年 226卷

作者： Chen, Cheng-Lung Huang, Cheng Chen, Sheng-Chi Liu, Yen-Chen Chuang, Min-Chen Wen, Chao-Kuang Huang, Wei-Sheng Yang, Wen-Sheng Chen, Yang-Yuan Graduate School of Materials Science National Yunlin University of Science and Technology Yunlin64002 Taiwan Department of Materials Engineering and Center for Plasma and Thin Film Technologies Ming Chi University of Technology 243 New Taipei City Taiwan College of Engineering and Center for Green Technology Chang Gung University 333 Taoyuan Taiwan International Ph.D. Program in Plasma and Thin Film Technology Ming Chi University of Technology 243 New Taipei City Taiwan TPH Research & Develop Dept. Chien Hwa Coating Technology Inc. Hsinchu300 Taiwan National Engineering Research Center for Rare Earth Materials Grirem Advanced Materials Co. Ltd. General Research Institute for Nonferrous Metals Beijing100088 China Institute of Physics Academia Sinica 115 Taipei Taiwan

Tantalum silicate (Ta–Si–O) thin film materials have gained significant interest in hybrid renewable energy systems and thin-film resistors due to their exceptional thermal stability and adjustable electrical properties. In this study, we investigated the effects of target compositions and sputtering power densities on the material structures, chemical compositions, microstructures, and electrical properties of Ta–Si–O films. Two target compositions, Ta65(SiO2)35 and Ta80(SiO2)20, were utilized in the deposition process. Notably, we observed substantial variations in the temperature coefficient of resistance (TCR) value and resistivity of Ta–Si–O thin films with different Ta concentrations. Most importantly, when the Ta content of the film is controlled at 62 ± 0.6 % by using this target, the resistivity of the Ta0.62Si0.20O0.18 film can be as small as 2.31 ± 0.05 × 10−4 Ω-cm and has an extremely small TCR of 22 ± 0.4 ppm/°C, which shows an excellent opportunity for the development of precision thin film resistors. A TCR value close to zero can be finely tuned by controlling the Ta concentration in the Ta–Si–O film. These intriguing electrical behaviors were found to be highly correlated with the predominant formation of metallic Ta5Si3 as the main structural phase in the films. This work presents a simple and effective approach to produce Ta–Si–O thin films with near-zero TCR, making them highly suitable for applications under high-temperature conditions. Our findings contribute to the development of tailored thin film materials with desirable electrical properties for advanced electronic and energy devices. © 2024 Elsevier Ltd

关键词： Thin films

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Multi-wavelength edge detection based on nonlocal multilayer GaAs–AlAs thin films

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Optics Letters 2025年第12期50卷 3856-3859页

作者： Sina Mohammadi Matthew Markowitz Francesco Monticone Mohammad Ali Miri Maria Tamargo Ph.D. Program in Physics The Graduate Center of the City University of New York New York New York 10016 USA Department of Physics Queens College of the City University of New York Queens New York 11367 USA School of Electrical and Computer Engineering Cornell University Ithaca New York 14853 USA Department of Chemistry The City College of New York New York New York 10031 USA

We demonstrate a compact multilayer GaAs–AlAs structure for passive optical edge detection at multiple wavelengths. Through the inverse design of the layer thicknesses, this structure manipulates spatial frequency components of an incoming wavefront, selectively reflecting high-frequency features while suppressing low-frequency intensity variations. Simulations reveal a reflectance transition from minimal to near-total as a function of numerical aperture, a property leveraged for enhancing edge contrast in optical imaging. For the first time, to our knowledge, we utilize molecular beam epitaxy (MBE) to fabricate edge detection devices, ensuring structural fidelity. Material characterization confirms high-quality interfaces, precise thickness control, and excellent uniformity, validating the suitability of MBE for this application. Experimental angle-resolved reflectance measurements closely align with theoretical predictions, demonstrating the feasibility of this approach for real-time, hardware-based optical image processing. The proposed design automatically works for at least two wavelengths and can be readily extended to operate at multiple wavelengths simultaneously. This work opens new possibilities for employing multilayer interference structures in high-performance optical imaging and real-time signal processing.

关键词： digital image processing Edge detection Inverse design Optical imaging Signal processing Thin films

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Removal of nitrogen and phosphorus pollutants from swine wastewater

Removal of nitrogen and phosphorus pollutants from swine was...

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2021 International Symposium on Intelligent Signal Processing and Communication Systems, ISPACS 2021

作者： Nguyen, Minh-Ky Lin, Chitsan Nhut, Huynh Tan Trung Hiep, Nguyen Hung, Nguyen T.Q. Huu Tuan, Tran National Kaohsiung University of Science and Technology College of Maritime Ph.D. Program In Maritime Science and Technology Kaohsiung Taiwan National Kaohsiung University of Science and Technology Department of Marine Environmental Engineering Kaohsiung Taiwan Nong Lam University of Ho Chi Minh City Faculty of Environment and Natural Resources Ho Chi Minh Viet Nam National Kaohsiung University of Science and Technology College of Maritime Kaohsiung Taiwan

ISBN: (纸本)9781665419512

This study investigated the simultaneous removal of nitrogen and phosphorus from swine wastewater by a magnesium ammonium phosphate crystallization. The precipitation of struvite was determined from swine wastewater, obtaining the optimal ph, Mg/N/P molar ratio, and reaction time were 9.0, 1.6/1/1.5 and 30 min, respectively. Ammonium and phosphate removal efficiencies were 98.1 ± 0.5% and 98.9 ± 0.4% under optimal conditions, and the highest crystallization mass obtained was 14.6 ± 0.6 g/L. Results illustrated that struvite precipitation is an efficient method for removing ammonium and phosphate in swine wastewater. © 2021 IEEE.

关键词： phosphorus

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design of Optical System of Augmented Reality Near Eye device

Design of Optical System of Augmented Reality Near Eye Devic...

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Educational Innovation (ECEI), IEEE Eurasian Conference on

作者： Chao-Kai Chang Feng-Ming Yeh Jiann-Hwa Lue Hsuan-Fu Wang Ya-Hui Hsieh Chun-Yu Chiang der-Chin Chen Chuen-Lin Tien Department of Optometry Yuanpei University of Medical Technology Hsinchu Taiwan Department of Optometry Taiwan University of Science and Technology Taichung Taiwan Department of Aeronautical Engineering National Formosa University Yunlin Taiwan Department of Healthcare Information and Management Ming Chuan University Taoyuan Taiwan Ph.D. Program of Electrical and Communications Engineering Feng Chia University Taichung Taiwan Department of Electrical Engineering Feng Chia University Taichung Taiwan

Augmented reality (AR) is a technology that instantly merges digital pictures with the real scene. The perspective near-eye display is a key module of AR, through which computer-generated pictures or videos can be displayed in the existing environment. The purpose of this research is to establish the system structure of an augmented reality near-eye display device and to design the off-axis two-piece reflective aspherical mirror. Because AR glasses are wearable and are worn close to the eyes, not only the optical performance of the display but also the clear vision of the user needs to be considered. In this study, an off-axis two-piece reflective aspherical mirror is used as the optical system of the AR for displaying the digital image. The micro-display is placed at the focal point of the optical system to form a digital image, and the horizontal movement of the micro-display along the optical axis is controlled by a precise displacement mechanism so that the patient with uncorrected myopia or hyperopia can see the digital picture and real scene. Because the right and left micro-displays move horizontally independently, the user can see the images on the AR device, which becomes the biggest feature of this study.

关键词： Performance evaluation Technological innovation Optical design digital images Optical imaging Optical reflection Augmented reality

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Extraction of c- F os Protein Regions from Mouse Brain Slice Images using Multi-channelization, 1 x 1 Convolution and U -Net

Extraction of c- F os Protein Regions from Mouse Brain Slice...

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International Symposium on Soft Computing and Intelligent Systems (SCIS)

作者： Ziyue Wang Hibiki Okamura Shijie Luo Yu Hayashi Hotaka Takizawa Master's Program in Computer Science University of Tsukuba Tsukuba Japan Ph.D. Program in Humanics International Institute for Integrative Sleep Medicine University of Tsukuba Tsukuba Japan International Institute for Integrative Sleep Medicine University of Tsukuba Tsukuba Japan Institute of Systems and Information Engineering Academic Computing & Communications Center University of Tsukuba Tsukuba Japan

ISBN: (数字)9798350373332

ISBN: (纸本)9798350373349

This study proposed a novel extraction method of c-Fos protein regions in dAB(3,3‘-diaminobenzidine)-stained mouse brain slice images using the U-Net model combined with the multi-channelization and $1\times 1$ convolution techniques. Our U-Net m odel, called $1\times 1$ conv U-Net, was applied to three dAB- strainedmouse slice images whose resolutions were $1000\mathrm{x}1000$ pixels. The experimental results demonstrated that the $1\times 1$ conv U-Net outperformed the conventional U-Net.

关键词： Proteins Visualization Image resolution Image analysis Convolution Feature extraction Brain modeling Biology Biomedical imaging

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ROBUST PARAMETER ESTIMATION FOR RATIONAL ORdINARY dIFFERENTIAL EQUATIONS

arXiv

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arXiv 2023年

作者： Bassik, Oren Berman, Yosef Go, Soo Hong, Hoon Ilmer, Ilia Ovchinnikov, Alexey Rackauckas, Chris Soto, Pedro Yap, Chee Ph.D. Program in Mathematics CUNY Graduate Center New YorkNY United States Ph.D. Program in Computer Science CUNY Graduate Center New YorkNY United States Department of Mathematics North Carolina State University RaleighNC United States Department of Mathematics CUNY Queens College United States Ph.D. Programs in Mathematics and Computer Science CUNY Graduate Center New YorkNY United States Department of Mathematics Massachusetts Institute of Technology CambridgeMA United States Mathematical Institute University of Oxford Oxford United Kingdom Department of Computer Science Courant Institute of Mathematical Science New York University New YorkNY United States

We present a new approach for estimating parameters in rational OdE models from given (measured) time series data. In typical existing approaches, an initial guess for the parameter values is made from a given search interval. Then, in a loop, the corresponding outputs are computed by solving the OdE numerically, followed by computing the error from the given time series data. If the error is small, the loop terminates and the parameter values are returned. Otherwise, heuristics/theories are used to possibly improve the guess and continue the loop. These approaches tend to be non-robust in the sense that their accuracy depend on the search interval and the true parameter values;furthermore, they cannot handle the case where the parameters are locally identifiable. In this paper, we propose a new approach, which does not suffer from the above non-robustness. In particular, it does not require making good initial guesses for the parameter values or specifying search intervals. Instead, it uses differential algebra, interpolation of the data using rational functions, and multivariate polynomial system solving. We also compare the performance of the resulting software with several other estimation software packages. © 2023, CC BY-NC-SA.

关键词： Parameter estimation

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Future of Cybersecurity

Future of Cybersecurity

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Recent Trends in Information technology (CSCTIT), college of science International Conference of

作者： Yasamin Alagrash Senior lecturer in the computer science department college of science Mustansiriyah University Baghdad Iraq Department of computer science Ph.D. in computer science and informatics college of engineering Oakland university MI USA Computer science department MSC in data security university of technology Baghdad Iraq

Cybersecurity is critical to the digital world's ongoing progress. Whether you are a company owner or a customer, you must be prepared to adapt to new technology, policies, and methods that will aid in the creation of a safer and more secure online environment. As a result, the frequency of exposed network surfaces compels us to invest in more advanced protection measures.

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Jing-Si Herbal Tea Suppresses H2O2-Instigated Inflammation and Apoptosis by Inhibiting Bax and Mitochondrial Cytochrome C Release in HIG-82 Synoviocytes

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Environmental Toxicology 2024年第12期39卷 5347-5356页

作者： Kao, Shih-Wen Chang, Yu-Chun Lin, Feng-Huei Huang, Tai-Lung Chen, Tung-Sheng Lin, Shinn-Zong Lin, Kuan-Ho Kuo, Wei-Wen Ho, Tsung-Jung Huang, Chih-Yang Graduate Institute of Aging Medicine China Medical University Taichung Taiwan Department of Orthopedic Surgery Chung-Shan Medical University Hospital Taichung Taiwan Department of Biological Science and Technology College of Life Sciences China Medical University Taichung Taiwan Cardiovascular and Mitochondrial Related Disease Research Center Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Institute of Biomedical Engineering College of Medicine and College of Engineering National Taiwan University Taipei Taiwan Division of Biomedical Engineering and Nanomedicine Research National Health Research Institute Miaoli Taiwan Department of Orthopedics Chung-Kang Branch Cheng Ching General Hospital Taichung Taiwan School of Life Science National Taiwan Normal University Taipei Taiwan Department of Neurosurgery Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Bioinnovation Center Buddhist Tzu Chi Medical Foundation Hualien Taiwan Department of Emergency Medicine China Medical University Hospital Taichung Taiwan College of Medicine China Medical University Taichung Taiwan Ph.D. Program for Biotechnology Industry China Medical University Taichung Taiwan School of Pharmacy China Medical University Taichung Taiwan School of Post-Baccalaureate Chinese Medicine College of Medicine Tzu chi University Hualien Taiwan Department of Chinese Medicine Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Tzu Chi University Hualien Taiwan Integration Center of Traditional Chinese and Modern Medicine Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan

Inflammation is an intrinsic protective mechanism against various forms of cellular injuries in humans;however, its undesired activation results in tissue damage and cell death. The onset of chronic inflammation and oxidative stress are the key characteristics of autoimmune inflammatory diseases such as rheumatoid arthritis (RA), for which an effective treatment is yet to be developed. Therefore, in this study, we investigated the protective effects and molecular mechanisms of a novel herbal preparation, Jing-Si herbal tea (JS), against H2O2-induced inflammation and cellular damage in HIG-82 synoviocytes. We found that JS did not show any significant alterations in cell viability at 2O2-induced pathological oxidative stress (ROS) in HIG-82 cells. Interestingly, JS treatment not only reduced the ROS levels but also significantly repressed the protein expressions of collagen degrading proteases in a dose-dependent manner. Treatment with JS showed enhanced cell viability against H2O2-induced toxic ROS levels. The expressions of cell protective aggrecan, Collagen II, and Bcl-2 were increased, whereas MMP-13, AdAMTS-2, Cytochrome C, and cleaved Caspase 3 were decreased by JS under inflammatory agents H2O2, MIA, LPS, and TNF-α treatment, respectively, in HIG-82 cells. Interestingly, the cytoprotective effect of JS treatment was attributed to a decreased mitochondrial localization of Bax and a reduction of Cytochrome C release into the cytoplasm of H2O2-treated HIG-82 cells. Collectively, our results suggest a novel protective mechanism of JS for RA treatment, which could be potentially applied as a complementary treatment or as an alternative therapeutic approach to mitigate inflammatory diseases. © 2024 Wiley Periodicals LLC.

关键词： Cell death

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