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Biological Evaluation of Sulfonate and Sulfate Analogues of Lithocholic Acid: A Bioisosterism-Guided Approach Towards the Discovery of Potential Sialyltransferase Inhibitors for Antimetastatic Study

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SSRN 2023年

作者： Perez, Ser John Lynon P. Chen, Chia-Ling Chang, Tzu-Ting Li, Wen-Shan Institute of Chemistry Academia Sinica Taipei115 Taiwan Department of Applied Chemistry National Yang Ming Chiao Tung University Hsinchu300 Taiwan Sustainable Chemical Science and Technology Taiwan International Graduate Program Academia Sinica Taipei115 Taiwan Biomedical Translation Research Center Academia Sinica Taipei115 Taiwan Department of Medicinal and Applied Chemistry College of Life Science Kaohsiung Medical University Kaohsiung807 Taiwan Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University Taiwan Doctoral Degree Program in Marine Biotechnology National Sun Yat-Sen University Kaohsiung804 Taiwan Department of Chemistry College of Science Tamkang University New Taipei City251 Taiwan

The naturally occurring bile acid lithocholic acid (LCA) has been a crucial core structure for many non-sugar-containing sialyltranferase (ST) inhibitors documented in literature. With the aim of elucidating the impact of the terminal carboxyl acid substituent of LCA on its ST inhibition, in this present study, we report the (bio)isosteric replacement-based design and synthesis of sulfonate and sulfate analogues of LCA. Among these compounds, the sulfate analogue SPP-002 was found to selectively inhibit N-glycan sialylation by at least an order of magnitude, indicating a substantial improvement in both potency and selectivity when compared to the unmodified parent bile acid. Molecular docking analysis supported the stronger binding of the synthetic analogue in the enzyme active site. Treatment with SPP-002 also hampered the migration, adhesion, and invasion of MDA-MB-231 cells in vitro by suppressing the expression of signaling proteins involved in the cancer metastasis-associated FAK/paxillin pathway. In totality, these findings offer not only a novel structural scaffold but also valuable insights for the future development of more potent and selective ST inhibitors with potential therapeutic effects against tumor cancer metastasis. © 2023, The Authors. All rights reserved.

关键词： Sulfur compounds

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A METHODOLOGY FOR EVALUATING ANTIFOULING PAINTS

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Naval Engineers Journal 1967年第1期79.0卷 107-117页

作者： COLOGER, C.P. FREIBERGER, A. Christopher P. Cologer received a B.S. Degree in Wood Utilization at Syracuse University. He joined the staff of the Naval Applied Science Laboratory in 1951 and carried out applied research in the field of wood technology and beginning in 1960 on high temperature elastomeric materials. Since 1962 he has been associated as a Materials Engineer with the Laboratory's program on studies of marine fouling. Arnold Freiberger received his Degree in Chemical Engineering at the City College of New York. Employed as a Materials Engineer at the U. S. Naval Applied Science Laboratory since 1952 he is the Task Leader of the Laboratory's program on naval cold weather problems and has done fundamental and applied research on ice adhesion and ice release coatings. Since 1962 he has been in charge of the Laboratory's marine folding research program and more recently has assumed leadership of the hydrofoil materials research program.

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REARING ACORN BARNACLE CYPRIDS IN THE LABORATORY FOR MARINE FOULING STUDIES

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Naval Engineers Journal 1966年第5期78卷 881-890页

作者： FREIBERGER, A. COLOGER, C.P. Arnold Freiberger received his Degree in Chemical Engineering at the City College of New York. Employed as a Materials Engineer at the U. S. Naval Applied Science Laboratory since 1952 he is the Task Leader of the Laboratory's program on naval cold weather problems and has done fundamental and applied research on ice adhesion and ice release coatings. Since 1962 he has been in charge of the Laboratory's marine fouling research program and more recently has assumed leadership of the hydrofoil materials research program. Christopher P. Cologer received a B.S. Degree in Wood Utilization at Syracuse University. He joined the staff of the Naval Applied Science Laboratory in 1951 and carried out applied research in the field of wood technology and beginning in 1960 on high temperature elastomeric materials. Since 1962 he has been associated as a Materials Engineer with the Laboratory's program on studies of marine fouling.

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Developing a prototype concurrent design tool for composite topside structures

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NAVAL ENGINEERS JOURNAL 1997年第3期109卷 279-290页

作者： Dirlik, S Hambric, S Azarm, S Marquardt, M Hellman, A Bartlett, S Castelli, V Steve Dirlik:began his career at the Naval Surface Warfare Center Carderock Division in 1981 as an aerospace engineer co-op student. He completed his bachelor of science degree in aeropace and ocean engineering from Virginia Polytechnic Institute and State University in 1985 and his master of science degree in aerospace engineering from the University of Maryland in 1990. Mr. Dirlik recently completed a master of science program in applied physics at The Johns Hopins University and currently works in the Radar Cross Section and Target Physics Branch of the Signatures Directorate at the Naval Surface Warfare Center Corderoke Division. He has worked on Navy low observable programs since 1990. Stephen Hambric:is a research associate at the Applied Research Laboratory at The Pennsylvania State University. He received his B. S. and M.S. degree in mechanical engineering from Virginia Polytechnic Institute and State University and his D. Sc. in mechnical engineering from the George Washington University. He has worked on several computer aided multidiscikplinary design and optimization projects over the years including an automated propeller design system and a structural acoustic optimization capability. Dr. Shpour Azarm:is currently working as an associate professor with the Design and Manufacturing Group of the Department of Mechanical Engineering at the University of maryland at College Park. Dr Azarm's expertise is in the areas of optimization-based designed and concurrent design and optimization of multidisciplinary systems. He was a consultant at Black & Decker Corporation (summer 1996) and worked as a Navy senior summer faculty fellow (summer 1995) and a NASA summer faculty fellow (summer 1994). He was a visiting scientist at NASA Langley Research Center for Multidisciplinary Analysis and Applied Structural Optimzatiom at the University of Siegen in Germany (spring 1992) and the Design Institute of the Technical University of Denmark (summer 1990). Dr Azarm was an associate technical editor of the ASME Jour

A prototype concurrent engineering tool has been developed for the preliminary design of composite topside structures for modern navy warships. This tool, named GELS for the Concurrent Engineering of Layered Structures, provides designers with an immediate assessment of the impacts of their decisions on several disciplines which are important to the performance of a modern naval topside structure, including electromagnetic interference effects (EMI), radar cross section (RCS), structural integrity, cost, and weight. Preliminary analysis modules in each of these disciplines are integrated to operate from a common set of design variables and a common materials database. Performance in each discipline and an overall fitness function for the concept are then evaluated. A graphical user interface (GUI) is used to define requirements and to display the results from the technical analysis modules. Optimization techniques, including feasible sequential quadratic programming (FSQP) and exhaustive search are used to modify the design variables to satisfy all requirements simultaneously. The development of this tool, the technical modules, and their integration are discussed noting the decisions and compromises required to develop and integrate the modules into a prototype conceptual design tool.

关键词： Warships

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Drone-borne calibration pulser for radio observatories detecting ultra-high-energy cosmic rays and neutrinos 38

Drone-borne calibration pulser for radio observatories detec...

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38th International Cosmic Ray Conference, ICRC 2023

作者： Nam, J. Kuo, C.-Y. Shin, B.K. Chen, P. Chen, Y. Hsu, S.-Y. Huang, J.-J. Huang, M.-H.A. Leung, C.H. Liu, T.-C. Wang, S.-H. Wang, M.-Z. Wang, Y.-H. Besson, D. Novikov, A. Hornhuber, C. Young, R. Department of Physics National Taiwan University Taipei Taiwan Leung Center for Cosmology and Particle Astrophysics National Taiwan University Taipei Taiwan Ulsan National Institute of Science and Technology Ulsan Korea Republic of Department of Energy and Resources National United University Miaoli Taiwan Department of Electrophysics National Yang Ming Chiao Tung University Hsinchu300 Taiwan Department of applied physics National PingTung university PingTung900 Taiwan Chung Cheng Institute of Technology National Defense University TaoYuan335 Taiwan Undergraduate Degree Program of Systems Engineering and Technology National Yang Ming Chiao Tung University Hsinchu300 Taiwan Department of Physics and Astronomy University of Kansas Lawrence United States Instrumentation Design Lab University of Kansas Lawrence United States Moscow Russia Institute of Astronomy and Astrophysics Academia Sinica Astronomy-Mathematics Building No. 1 Sec. 4 Roosevelt Rd. Taipei Taiwan

We report on the development of a drone-borne calibration pulser (cal-pulser) for radio observatories detecting ultra-high energy (UHE) cosmic rays and neutrinos. This system allows us to calibrate the radio detector in its field of view regardless of the accessibility of the site. The system is compact and sufficiently lightweight to be attached to a commercial drone. It consists of a solid-state high-power pulse generator, a programmable attenuator, a transmitting antenna, and a differential GPS (D-GPS) module. The drone, with the ∼1.3 kg payload, has a typical flight time of around 25 minutes, corresponding to a maximum flight distance of around 10 km. After developing the first version of the system in 2019, it successfully demonstrated its calibration performance with the TAROGE stations in Taiwan and the TAROGE-M station in Mt. Melbourne, Antarctica. In 2022, the system was upgraded with a dual-band D-GPS for more reliable operation and more accurate determination of the coordinates of the cal-pulser. In addition to the cal-pulser, we investigated aerial photogrammetry using the built-in camera and the D-GPS, which is an efficient method to determine the coordinates of the detector. For objects within 10 m of the drone, an accuracy of a few millimeter was achieved. These drone-borne cal-pulser and the photogrammetry have become essential calibration procedures in the TAROGE-M experiment. We suggest these approaches may find application in many other radio experiments that detect UHE cosmic rays and neutrinos, such as ARIANNA, BEACON, GRAND, as well as IceCube-Gen2. © Copyright owned by the author(s) under the terms of the Creative Commons.

关键词： Cosmic rays

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Human systems integration and advanced technology in engineering department workload and manpower reduction

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NAVAL ENGINEERS JOURNAL 2003年第1期115卷 57-65页

作者： Lively, KA Seman, AJ Kirkpatrick, M KENNETH A. LIVELY graduated from the University of Colorado with a BS in applied mathematics and an MS in mathematics in 1976 and from the Massachusetts Institute of Technology with an MS in electrical engineering and the degree ocean engineer in naval architecture and marine engineering in 1984. He retired from the U.S. Navy in 1989 after 23 years of service. Assignments included electrical officer on the USS Constellation (CV 64) project engineer for the DDG 51 machinery control system (NAVSEA) and DDG 51 Technical Director (NAVSEA). He was vice president of the PDI Division of Bird-Johnson Company from July 1989 to November 1998 where he managed various gas turbine and machinery controls related development projects. He joined Anteon Corporation's Systems Engineering Group as senior controls engineer in December 1998 where he provided technical support to the integrated power systems program (NAVSEA PMS 510) and managed the Office of Naval Research Afloat Laboratory. DR. MARK KIRKPATRICK is currently an independent consultant in human factors and work-load/manning analysis and modeling. He holds a Ph.D. degree in experimental psychology from The Ohio State University and has 34 years of experience in applied human factors. From 1982 through 2000 Dr. Kirkpatrick served as the senior vice president of Carlow International. Prior to joining Carlow in 1982 Dr. Kirkpatrick served as a member of the technical staff at North American Rockwell's Missiles Division and as a project director and vice president for Essex Corporation. His areas of expertise include workload simulation task analysis operator-in-the-loop simulation human performance experimentation statistical analysis and human factors T&E. He has directed and/or participated in human factors projects for the U.S. Navy U.S. Army NASA Department of Transportation the U.S. Nuclear Regulatory Commission and private industry. ANTHONY J. SEMAN III is the technical manager for the reduced ship's crew by virtual presence (RSVP) advanced technology d

Aboard current ships, such as the DDG 51, engineering control and damage control activities are manpower intensive. It is anticipated that, for future combatants, the workload demand arising from operation of systems under conditions of normal steaming and during casualty response will need to be markedly reduced via automated monitoring, autonomous control, and other technology initiatives. Current DDG 51 class ships can be considered as a manpower baseline and under Condition III typical engineering control involves seven to eight watchstanders at manned stations in the Central Control Station, the engine rooms and other machinery spaces. In contrast to this manning level, initiatives such as DD 21 and the integrated engineering plant (IEP) envision a partnership between the operator and the automation system, with more and more of the operator's functions being shifted to the automation system as manning levels decrease. This paper describes some human systems integration studies of workload demand reduction and, consequently, manning reduction that can be achieved due to application of several advanced technology concepts. Advanced system concept studies in relation to workload demand are described and reviewed including. Piecemeal applications of diverse automation and remote control technology concepts to selected high driver tasks in current DDG 51 activities. Development of the reduced ship's crew by virtual presence system that will provide automated monitoring and display to operators of machinery health, compartment conditions, and personnel health. The IEP envisions the machinery control system as a provider of resources that are used by various consumers around the ship. Resource needs and consumer priorities are at all times dependent upon the ship's current mission and the availability of equipment pawnbrokers.

关键词： Naval warfare

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A Comparative Study of Gaussian Process Machine Learning and Time Series Analysis Techniques for Predicting Unemployment Rate

A Comparative Study of Gaussian Process Machine Learning and...

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International Conference on Computer and Automation Engineering, ICCAE

作者： Muhammad Naeim Mohd Aris Shalini Nagaratnam Nurul Nnadiah Zakaria Muhammad Fadhirul Anuar Mohd Azami Muhammad Afiq Ikram Samsudin Ernee Sazlinayati Othman Department of American Degree Transfer Program School of American Education Sunway University Bandar Sunway Malaysia Department of Econometrics and Business Statistics School of Business Monash University Malaysia Bandar Sunway Malaysia Department of Fundamental and Applied Sciences Faculty of Science and Information Technology Universiti Teknologi PETRONAS Seri Iskandar Malaysia Department of American Degree Transfer Programme School of American Education Sunway University Bandar Sunway Malaysia College of Computing Informatics and Mathematics Universiti Teknologi MARA Seremban 3 Malaysia Centre of Foundation Studies Universiti Teknologi MARA Cawangan Selangor Kampus Dengkil Dengkil Malaysia

ISBN: (数字)9798350370058

ISBN: (纸本)9798350370164

This study explores and compares the capability of Gaussian process machine learning (GPML) with time series analysis techniques, which are autoregressive integrated moving average (ARIMA), seasonal ARIMA (SARIMA) and cubic spline interpolation, in modeling unemployment rate in Malaysia over the period of 1991 to 2022. Six predictive models are developed based on the observations. The predictive performance of each model is quantified using mean absolute error (MAE) and mean squared error (MSE). GPML demonstrated the best predictive model, exhibiting minimal MAE and MSE compared to the time series analysis techniques. The statistical analysis also concluded no significant mean difference between the GPML model and the actual observations, implying a robust predictive model in predicting the unemployment rate in Malaysia.

关键词： Analytical models Interpolation Statistical analysis Time series analysis Gaussian processes Machine learning Predictive models

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Estimation of solar radiation using Angstrom-Prescott model and interpolation of empirical coefficients in Thailand

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Journal of Physics: Conference Series 2018年第1期1144卷

作者： K Keawsang-in S Ratjiranukool P Ratjiranukool PhD's Degree Program in Applied Physics Faculty of Science Chiang Mai University Department of Physics and Materials Faculty of Science Chiang Mai University Department of Physics Faculty of Science and Technology Chiang Mai Rajabhat University

Angstrom-Prescott model, defined by , was applied to estimate solar L so J radiation for 11 meteorological stations in Thailand. In this research, the empirical coefficients ('a' and 'b') were calculated by using the least square model. Statistical values, i.e., root mean square error (RMSE) and correlation, were analyzed the model ability in estimating solar radiation by compared with the measurement. The empirical coefficients overall Thailand were interpolated by using geographic information system (GIS). This technique can be calculated for estimation of solar radiation in every region in Thailand. In the results, the statistical tests show the ability of Angstrom-Prescott model to estimate solar radiation in Thailand and the least square method is suitable for computing empirical coefficients.

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Transcriptomic analysis of World Trade Center particulate Matter-induced pulmonary inflammation and drug treatments

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Environment International 2023年 177卷 108027页

作者： Chen, Yun-Ti Li, Jinhui Chang, Jen-Ning Luo, Yong-Chun Yu, Wuyue Chen, Lung-Chi Yang, Jinn-Moon Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu30010 Taiwan Department of Chemistry and Chemical Biology Harvard University CambridgeMA02138 United States Department of Urology Stanford University Medical Center StanfordCA94304 United States Department of Environmental Medicine New York University School of Medicine New YorkNY10010 United States Degree Program of Applied Science and Technology National Yang Ming Chiao Tung University Hsinchu30010 Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu30010 Taiwan Center for Intelligent Drug Systems and Smart Bio-devices National Yang Ming Chiao Tung University Hsinchu30010 Taiwan

Over 400,000 people are estimated to have been exposed to World Trade Center particulate matter (WTCPM) since the attack on the Twin Towers in Lower Manhattan on September 11, 2001. Epidemiological studies have found that exposure to dust may cause respiratory ailments and cardiovascular diseases. However, limited studies have performed a systematic analysis of transcriptomic data to elucidate the biological responses to WTCPM exposure and the therapeutic options. Here, we developed an in vivo mouse exposure model of WTCPM and administered two drugs (i.e., rosoxacin and dexamethasone) to generate transcriptomic data from lung samples. WTCPM exposure increased the inflammation index, and this index was significantly reduced by both drugs. We analyzed the transcriptomics derived omics data using a hierarchical systems biology model (HiSBiM) with four levels, including system, subsystem, pathway, and gene analyses. Based on the selected differentially expressed genes (DEGs) from each group, WTCPM and the two drugs commonly affected the inflammatory responses, consistent with the inflammation index. Among these DEGs, the expression of 31 genes was affected by WTCPM exposure and consistently reversed by the two drugs, and these genes included Psme2, Cldn18, and Prkcd, which are involved in immune- and endocrine-related subsystems and pathways such as thyroid hormone synthesis, antigen processing and presentation, and leukocyte transendothelial migration. Furthermore, the two drugs reduced the inflammatory effects of WTCPM through distinct pathways, e.g., vascular-associated signaling by rosoxacin, whereas mTOR-dependent inflammatory signaling was found to be regulated by dexamethasone. To the best of our knowledge, this study constitutes the first investigation of transcriptomics data of WTCPM and an exploration of potential therapies. We believe that these findings provide strategies for the development of promising optional interventions and therapies for airborne part

关键词： Dust

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Low-to-Moderate Arsenic Exposure and Urothelial Tract Cancers with a Long Latent Period of Follow-Up in an Arseniasis Area

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Journal of Epidemiology and Global Health 2023年第4期13卷 807-815页

作者： Liao, Pei-Ju Lee, Chih-Hung Wang, Shu-Li Chiou, Hung-Yi Chen, Chien-Jen Seak, Chen-June Wu, I-Wen Hsu, Kuang-Hung International Program of Health Informatics and Management Chang Gung University Taoyuan Taiwan Master Degree Program in Health and Long-Term Care Industry Chang Gung University Taoyuan Taiwan Division of Nephrology Chang Gung Memorial Hospital Keelung Taiwan Department of Dermatology Kaohsiung Chang Gung Memorial Hospital Kaohsiung Taiwan National Institute of Environmental Health Sciences National Health Research Institutes Miaoli Taiwan Institute of Population Health Sciences National Health Research Institutes Zhunan Miaoli County Taiwan Master Program in Applied Epidemiology College of Public Health Taipei Medical University Taipei Taiwan Genomics Research Center Academia Sinica Taipei Taiwan Department of Emergency Medicine New Taipei Municipal Tucheng Hospital New Taipei City Taiwan Department of Emergency Medicine Lin-Kou Medical Center Chang Gung Memorial Hospital Taoyuan Taiwan College of Medicine Chang Gung University Taoyuan Taiwan Laboratory for Epidemiology Department of Health Care Management and Healthy Aging Research Center Chang Gung University No. 259 Wen-Hwa 1St Road Kwei-Shan Taoyuan 333 Taiwan Research Center for Food and Cosmetic Safety College of Human Ecology Chang Gung University of Science and Technology Taoyuan Taiwan Department of Safety Health and Environmental Engineering Ming Chi University of Technology New Taipei City Taiwan

Background: Arsenic exposure can cause adverse health effects. The effects of long-term low-to-moderate exposure and methylations remain unclear. Objective: This study aims to examine the association between low-to-moderate arsenic exposure and urothelial tract cancers while considering the effects of methylation capacity. Methods: In this study, 5,811 participants were recruited from an arseniasis area in Taiwan for inorganic arsenic metabolite analysis. This follow-up study was conducted between August 1995 and December 2017. We identified 85 urothelial tract cancers in these participants, including 49 bladder and 36 upper urothelial tract cancer cases. A Cox proportional hazards model was employed. Results: The analyses revealed a significant association between concentrations of inorganic arsenic in water > 100 ug/L and bladder cancer occurrence, with a hazard ratio (HR) of 4.88 (95% CI 1.35–17.61). A monotonic trend was observed between concentrations of inorganic arsenic in water (from 0 to > 100 ug/L) and the incidence of urothelial tract cancer, including bladder cancer (p < 0.05) and upper urothelial tract cancers (p < 0.05). Participants with a lower primary methylation index or higher secondary methylation index had a prominent effect. Conclusions: Rigorous regulations and active interventions should be considered for populations with susceptible characteristics. © 2023, The Author(s).

关键词： Bladder cancer Dose–response relationship Long latency arsenic exposure Methylation capacity Upper urothelial tract cancers

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