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Site-directed deuteration of dronedarone preserves cytochrome P4502J2 activity and mitigates its cardiac adverse effects in canine arrhythmic hearts

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Acta Pharmaceutica Sinica B 2022年第10期12卷 3905-3923页

作者： Aneesh V.Karkhanis Gopalakrishnan Venkatesan ryuichi kambayashi Jacqueline Wen Hui Leow Marcus Qingrui Han Hiroko Izumi-Nakaseko Ai Goto Jeremy Kah Sheng Pang Boon Seng Soh Pipin Kojodjojo Atsushi Sugiyama Eric Chun Yong Chan Department of Pharmacy Faculty of ScienceNational University of SingaporeSingapore 117543Singapore Department of Pharmacology Faculty of MedicineToho UniversityTokyo 143-8540Japan Institute of Molecular and Cell Biology Agency for ScienceTechnology and ResearchSingapore 138673Singapore Department of Biological Sciences Faculty of ScienceNational University of SingaporeSingapore 117558Singapore Department of Medicine Yong Loo Lin School of MedicineNational University of SingaporeSingapore 119228Singapore

Cytochrome P4502J2(CYP2J2)metabolizes arachidonic acid(AA)to cardioprotective epoxyeicosatrienoic acids(EETs).Dronedarone,an antiarrhythmic drug prescribed for treatment of atrial fibrillation(AF)induces cardiac adverse effects(AEs)with poorly understood *** previously demonstrated that dronedarone inactivates CYP2J2 potently and irreversibly,disrupts AA-EET pathway leading to cardiac mitochondrial toxicity rescuable via EET *** this study,we investigated if mitigation of CYP2J2 inhibition prevents dronedarone-induced cardiac *** first synthesized a deuterated analogue of dronedarone(termed poyendarone)and demonstrated that it neither inactivates CYP2J2,disrupts AA-EETs metabolism nor causes cardiac mitochondrial toxicity in *** patch-clamp experiments demonstrated that pharmacoelectrophysiology of dronedarone is unaffected by ***,we show that dronedarone treatment or CYP2J2 knockdown in spontaneously beating cardiomyocytes indicative of depleted CYP2J2 activity exacerbates beat-to-beat(BTB)variability reflective of proarrhythmic *** contrast,poyendarone treatment yields significantly lower BTB variability compared to dronedarone in cardiomyocytes indicative of preserved CYP2J2 ***,poyendarone and dronedarone display similar antiarrhythmic properties in the canine model of persistent AF,while poyendarone substantially reduces beat-to-beat variability of repolarization duration suggestive of diminished proarrhythmic *** findings prove that deuteration of dronedarone prevents CYP2J2 inactivation and mitigates dronedarone-induced cardiac AEs.

关键词： Arachidonic acid Atrial fibrillation CYP2J2 Drug-induced proarrhythmia Epoxyeicosatrienoic acids Mechanism-based inactivation Dronedarone

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MicroGrid Designer:user-friendly design,operation and control assist tools for resilient microgrid and autonomous community

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Global Energy Interconnection 2022年第3期5卷 249-258页

作者： ryuichi Yokoyama Yicheng Zhou Energy and Environment and Technology Research Institute and Waseda University 1-22-2 Nishi-Waseda ShinjukuNishi-Waseda East Wing 106Tokyo169-0051Japan

During this decade,many countries have experienced natural and accidental disasters,such as typhoons,floods,earthquakes,and nuclear plant accidents,causing catastrophic damage to *** the end of 2019,all countries of the world are struggling with the COVID-19 and pursuing countermeasures,including inoculation of vaccine,and changes in our lifestyle and social *** these experiences have made the residents in the affected regions keenly aware of the need for new infrastructures that are resilient and autonomous,so that vital lifelines are secured during calamities.A paradigm shift has been taking place toward reorganizing the energy social service management in many countries,including Japan,by effective use of sustainable energy and new supply ***,such new power sources and supply schemes would affect the power grid through intermittency of power output and the deterioration of power quality and ***,new social infrastructures and novel management systems to supply energy and social service will be *** this paper,user-friendly design,operation and control assist tools for resilient microgrids and autonomous communities are proposed and applied to the standard microgrid to verify its effectiveness and performance.

关键词： Microgrid Autonomous community Grid design and analysis Resilience Unit commitment Economic load dispatch Load frequency control Dynamic power flow Energy management system

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Microgrids and a Community with a Shared Future for Mankind

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Global Energy Interconnection 2022年第3期5卷 I0002-I0005页

作者： Yasuyo Yamazaki ryuichi Yokoyama Waseda University

*** community with a shared future for humankind is the community of the earth’s biosphere The civilization and culture that human beings have created thus far,the economy,society and ideas,the nation,and religion,will vanish if human beings *** developments in astrophysics have been remarkable,and observations have been made from telescopes with incredible accuracy and range at great *** extraterrestrial exploration has reached celestial bodies far away,the existence of“life”is yet to be discovered beyond *** aimed at establishing an earthly“artificial biosphere”on Mars have been unsuccessful.

关键词： earth establishing hough

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A fuzzy control and neural network based rotor speed controller for maximum power point tracking in permanent magnet synchronous wind power generation system

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全球能源互联网:英文版 2023年第5期6卷 554-566页

作者： Min Ding Zili Tao Bo Hu Meng Ye Yingxiong Ou ryuichi Yokoyama School of Automation China University of GeosciencesWuhan 430074P.R.China Hubei Key Laboratory of Advanced Control and Intelligent Automation for Complex Systems Wuhan 430074P.R.China Global Energy Interconnection Group Co. LtdSTATE GRID Corporation of ChinaBeijing 100032P.R.China School of Environment and Energy Engineering Waseda UniversityTokyo169-8050Japan

When the wind speed changes significantly in a permanent magnet synchronous wind power generation system,the maximum power point cannot be easily determined in a timely *** study proposes a maximum power reference signal search method based on fuzzy control,which is an improvement to the climbing search method.A neural network-based parameter regulator is proposed to address external wind speed fluctuations,where the parameters of a proportional-integral controller is adjusted to accurately monitor the maximum power point under different wind speed ***,the effectiveness of this method is verified via Simulink simulation.

关键词： Maximum wind power tracking Fuzzy control Neural network

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A Series of Soluble Planar Oligorylenes up to Hexarylene

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Chinese Journal of Chemistry 2023年第9期41卷 1023-1027页

作者： ryuichi Fujita Shoko Yoshida Haruka Kano Kyohei Matsuo Hironobu Hayashi Hiroko Yamada Naoki Aratani Division of Materials Science Nara Institute of Science and Technology(NAIST)8916-5 Takayama-choIkoma 630-0192Japan

Preparation of large rylenes often needs the use of solubilizing groups along the rylene backbone,which results in the distortion of the skeleton and thus broadening of the absorption *** this work,we successfully synthesized 2,5,8,16,19,22-hexakis[2,6-bis(tri-fluoromethyl)phenyl]hexarylene(H)by using an oxidative fusion reaction of perylene trimer in 5%*** product is soluble in common organic solvents and could be purified with column ***-crystal X-ray diffraction analysis revealed that the hexarylene core is not disturbed by the substituents very much and is almost *** longest absorption of H exhibits a sharp peak at 831 nm and an on-set at 875 nm in toluene with a small full-width-at-half-maximum(FWHM)of 660 cm^(-1).The molar extinction coefficient is as large as 131,000 M^(-1)cm^(-1).The substituents could not perturb the electronic properties of the hexarylene because aryl groups are perpendicular to the hexarylene core and the carbon atoms at 2,5,16,19-positions have negligible coeffi-cients on its HOMO and LUMO,estimated by theoretical *** a result,the hexarylene having less absorption at the visible light region was stable enough in solution under the LED room light for more than 1 *** strategy gives a useful guideline to establish the near-infrared materials that exhibit stability under ambient conditions.

关键词： Oligorylenes Undistorted skeleton Near infrared absorption Crystal structure Effective conjugation length

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Liquid–liquid equilibrium extraction of ethanol with mixed solvent for bioethanol concentration

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Chinese Journal of Chemical Engineering 2016年第2期24卷 253-258页

作者： Hiroaki Habaki Haihao Hu ryuichi Egashira Department of International Development Engineering Graduate School of Science and EngineeringTokyo Institute of Technology

The extraction of ethanol with the solvents of aldehydes mixed with m-xylene was studied for the bioethanol concentration *** and benzaldehyde were selected as extraction solvents,with which the solubility of water is small,expecting large distribution coefficient of *** liquid–liquid two-phase region was the largest with m-xylene solvent,followed by benzaldehyde and *** region of two liquid–liquid phase became larger with the mixed solvent of m-xylene and furfural than that with furfural *** NRTL model was applied to the ethanol–water–furfural–m-xylene system,and the model could well express the liquid–liquid equilibrium of the *** any solvent used in this study,the separation selectivity of ethanol relative to water decreased as the distribution coefficient of ethanol *** separation selectivity with m-xylene was the largest among the employed solvents,but the distribution coefficient was the *** solvent mixture of furfural and m-xylene showed relatively high distribution coefficient of ethanol and separation selectivity,even in the higher mass fraction of m-xylene in the solvent *** ethanol extraction with a countercurrent multistage extractor by a continuous operation was simulated to evaluate the extraction *** ethanol content could be concentrated in the extract phase with relatively small number of extraction stages but low yield of ethanol was obtained.

关键词：混合溶剂乙醇浓度萃取平衡分离选择性乙醇提取混合二甲苯间二甲苯分布系数

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A Simple Method for Synthesizing Ultra-high-molecular-weight Polystyrene through Emulsion Polymerization Using Alkyl-9-BBN as an Initiator

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Chinese Journal of Polymer Science 2018年第5期36卷 592-597页

作者： Chao Zhao ryuichi Sugimoto Yusuke Naruoka School of Environmental Science and Engineering Kochi University of Technology

Styrene emulsion polymerization using an alkyl-9-BBN, synthesized by reacting 9-BBN（9-borabicyclo-[3.3.1]-nonane） and styrene, in an aqueous sodium dodecyl sulfate（SDS） solution was studied. Ultra-high-molecular-weight（〉 1.0 × 10~7） polystyrene was synthesized using a radical initiator formed through the aerobic oxidation of this alkyl-9-BBN in a high yield（〉 80%）. The kinetics of this emulsion polymerization of styrene with the alkyl-9-BBN was investigated. We confirmed that in the initial stage of the polymerization, the initial reaction rate followed first-order kinetics. The activation energy for this emulsion polymerization of styrene was approximately 56.2 kJ/mol.

关键词： Emulsion polymerization 9-BBN Ultra-high molecular weight polystyrene

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The Dauki Fault at the Shillong Plateau-Bengal Basin Boundary in Northeastern India:2D Finite Element Modeling

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Journal of Earth Science 2012年第6期23卷 854-863页

作者： Md Shofiqul Islam ryuichi Shinjo Faculty of Science University of the RyukyusOkinawa 903-0213Japan Department of Petroleum and Mining Engineering Shahjalal University of Science and TechnologySylhet 3114Bangladesh

The Dauki fault is a major fault along the southern boundary of the Shillong plateau that may be a source of destructive seismic hazards for the adjoining areas, including northeastern Bangladesh. In this study, we simulated the present stress distribution and the ongoing convergence deformation within the study area using numerical simulation. This simulation attempts to deter- mine the proper dip angle of the Dauki fault from a variety of differently established models but with the same realistic boundary conditions. The simulated stress field helped to predict the type of tec- tonic environment and the faulting patterns of the study area. The best-fit model can account for the compressive stress regime in the study area, except in the uppermost part of the Shillong plateau, the Bengal basin, and Assam areas where extensional stress regimes exists. In the model, the elements for which Mohr-Coulomb＇s failure occurs correspond with the observed earthquake data that refer to the Dauki fault as a north-dipping thrust fault.

关键词： Dauki fault Bengal basin tectonic stress earthquake.

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Tectonics in the Northwestern West Philippine Basin

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Journal of China University of Geosciences 2008年第3期19卷 191-199页

作者：倪祥龙吴时国 Shinjo ryuichi Key Laboratory of Marine Geology and Environment Institute of Oceanology Chinese Academy of SciencesQingdao 266071 Research Institute of Petroleum Exploration ＆ Development-Northwest （NWGI） PetroChina Lanzhou 730020 China Graduate University of Chinese Academy of Sciences Beijing 100049 China Key Laboratory of Marine Geology and Environment Institute of Oceanology Chinese Academy of Sciences Qingdao 266071 China China University of Petroleum （Huadong） Qingdao 266555 China Department of Physics and Earth Sciences University of the Ryukyus Senbaru-1 Nishihara Okinawa 903-0213 Japan

The West Philippine basin （WPB） is a currently inactive marginal basin belonging to Philippine Sea plate, which has a complex formation history and various crust structures. Based on gravity, magnetic and seismic data, the tectonics in West Philippine basin is characterized by amagma spreading stage and strike slip fractures. NNE trending Okinawa-Luzon fracture zone is a large fracture zone with apparent geomorphology and shows a right-handed movement. The results of joint gravity-magnetic-seismic inversion suggest that the Okinawa-Luzon fracture zone has intensive deformation and is a transform fault. Western existence of the NW trending fractures under Ryukyu Islands Arc is the main cause of the differences between south and north Okinawa Trough. The Urdaneta plateau is not a remained arc, but remnant of mantle plume although its lava chemistry is similar to oceanic island basalt （OIB）.

关键词： tectonics amagma spreading gravity anomaly magnetic anomaly West Philippine basin.

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GIS-based Frequency Ratio and Logistic Regression Modelling for Landslide Susceptibility Mapping of Debre Sina Area in Central Ethiopia

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Journal of Mountain Science 2015年第6期12卷 1355-1372页

作者： Matebie METEN Netra Prakash BHANDARY ryuichi YATABE Geo-Disaster Research Laboratory Graduate School of Science and Engineering Ehime University

Ethiopia has a mountainous landscape which can be divided into the Northwestern and Southeastern plateaus by the Main Ethiopian Rift and Afar Depression. Debre Sina area is located in Central Ethiopia along the escarpment where landslide problem is frequent due to steep slope, complex geology, rift tectonics, heavy rainfall and seismicity. In order to tackle this problem, preparing a landslide susceptibility map is very important. For this, GISbased frequency ratio(FR) and logistic regression(LR) models have been applied using landslide inventory and the nine landslide factors(i.e. lithology, land use, distance from river & fault, slope, aspect, elevation, curvature and annual rainfall). Database construction, weighting each factor classes or factors, preparing susceptibility map and validation were the major steps to be undertaken. Both models require a rasterized landslide inventory and landslide factor maps. The former was classified into training and validation landslides. Using FR model, weights for each factor classes were calculated and assigned so that all the weighted factor maps can be added to produce a landslide susceptibility map. In the case of LR model, the entire study area is firstly divided into landslide and non-landslide areas using the training landslides. Then, these areas are changed into landslide and non-landslide points so as to extract the FR maps of the nine landslide factors. Then a linear relationship is established between training landslides and landslide factors in SPSS. Based on this relationship, the final landslide susceptibility map is prepared using LR equation. The success-rate and prediction-rate of FR model were 74.8% and 73.5%, while in case of LR model these were 75.7% and 74.5% respectively. A close similarity in the prediction and validation rates showed that the model is acceptable. Accuracy of LR model is slightly better in predicting the landslide susceptibility of the area compared to FR model.

关键词： Logistic回归模型埃塞俄比亚山体滑坡敏感性频率比 GIS 新浪模型预测

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