Current formulation development strongly relies on trial-and-error experiments in the laboratory by pharmaceutical scientists,which is time-consuming,high cost and waste materials.This research aims to integrate vario...Current formulation development strongly relies on trial-and-error experiments in the laboratory by pharmaceutical scientists,which is time-consuming,high cost and waste materials.This research aims to integrate various computational tools,including machine learning,molecular dynamic simulation and physiologically based absorption modeling(PBAM),to enhance andrographolide(AG)/cyclodextrins(CDs)formulation design.The light GBM prediction model we built before was utilized to predict AG/CDs inclusion's binding free energy.AG/γ-CD inclusion complexes showed the strongest binding affinity,which was experimentally validated by the phase solubility study.The molecular dynamic simulation was used to investigate the inclusion mechanism between AG andγ-CD,which was experimentally characterized by DSC,FTIR and NMR techniques.PBAM was applied to simulate the in vivo behavior of the formulations,which were validated by cell and animal experiments.Cell experiments revealed that the presence of D-α-Tocopherol polyethylene glycol succinate(TPGS)significantly increased the intracellular uptake of AG in MDCKMDR1 cells and the absorptive transport of AG in MDCK-MDR1 monolayers.The relative bioavailability of the AG-CD-TPGS ternary system in rats was increased to 2.6-fold and 1.59-fold compared with crude AG and commercial dropping pills,respectively.In conclusion,this is the first time to integrate various computational tools to develop a new AG-CD-TPGS ternary formulation with significant improvement of aqueous solubility,dissolution rate and bioavailability.The integrated computational tool is a novel and robust methodology to facilitate pharmaceutical formulation design.展开更多
To verify the seismic design response factors of high-rise buildings, five reference structures, varying in height from 20- to 60-stories, were selected and designed according to modern design codes to represent a wid...To verify the seismic design response factors of high-rise buildings, five reference structures, varying in height from 20- to 60-stories, were selected and designed according to modern design codes to represent a wide range of concrete wall structures. Verified fiber-based analytical models for inelastic simulation were developed, considering the geometric nonlinearity and material inelasticity of the structural members. The ground motion uncertainty was accounted for by employing 20 earthquake records representing two seismic scenarios, consistent with the latest understanding of the tectonic setting and seismicity of the selected reference region （UAE）. A large number of Inelastic Pushover Analyses （IPAs） and Incremental Dynamic Collapse Analyses （IDCAs） were deployed for the reference structures to estimate the seismic design response factors. It is concluded that the factors adopted by the design code are adequately conservative. The results of this systematic assessment of seismic design response factors apply to a wide variety of contemporary concrete wall buildings with various characteristics.展开更多
挤压油膜阻尼器(Squeeze Film Dampers,SFDs)是旋转机械中常用的一类支承阻尼结构装置,能够改善转子系统的动力特性.当前工程实际中已经大量使用的两类不同结构形式的挤压油膜阻尼器,仍然存在着减振效果不稳定甚至会导致转子失稳,以及...挤压油膜阻尼器(Squeeze Film Dampers,SFDs)是旋转机械中常用的一类支承阻尼结构装置,能够改善转子系统的动力特性.当前工程实际中已经大量使用的两类不同结构形式的挤压油膜阻尼器,仍然存在着减振效果不稳定甚至会导致转子失稳,以及阻尼器动力学机制不清楚、建模和分析精度差、设计方法欠缺等理论技术难题.本文首先介绍两类典型SFD的结构形式和主要失效模式,然后详细叙述SFD动力学分析与优化设计方法在发展过程中的代表性研究成果,涉及SFD动力学特性、转子-SFD系统动力学特性研究、SFD动力学设计与优化等几个方面的研究,并对SFD的试验测试技术方面的成果进行评述.在此基础上,探讨目前先进航空发动机用大型挤压油膜阻尼器亟须开展的基础研究任务,特别强调了数据驱动与动力学解析模型融合的SFD动力学建模、分析与设计优化的发展方向.展开更多
基金financially supported by the FDCT Project 0029/2018/A1the University of Macao Research Grants(MYRG2019-00041-ICMS)performed in part at the High-Performance Computing Cluster(HPCC)which is supported by Information and Communication Technology Office(ICTO)of the University of Macao。
文摘Current formulation development strongly relies on trial-and-error experiments in the laboratory by pharmaceutical scientists,which is time-consuming,high cost and waste materials.This research aims to integrate various computational tools,including machine learning,molecular dynamic simulation and physiologically based absorption modeling(PBAM),to enhance andrographolide(AG)/cyclodextrins(CDs)formulation design.The light GBM prediction model we built before was utilized to predict AG/CDs inclusion's binding free energy.AG/γ-CD inclusion complexes showed the strongest binding affinity,which was experimentally validated by the phase solubility study.The molecular dynamic simulation was used to investigate the inclusion mechanism between AG andγ-CD,which was experimentally characterized by DSC,FTIR and NMR techniques.PBAM was applied to simulate the in vivo behavior of the formulations,which were validated by cell and animal experiments.Cell experiments revealed that the presence of D-α-Tocopherol polyethylene glycol succinate(TPGS)significantly increased the intracellular uptake of AG in MDCKMDR1 cells and the absorptive transport of AG in MDCK-MDR1 monolayers.The relative bioavailability of the AG-CD-TPGS ternary system in rats was increased to 2.6-fold and 1.59-fold compared with crude AG and commercial dropping pills,respectively.In conclusion,this is the first time to integrate various computational tools to develop a new AG-CD-TPGS ternary formulation with significant improvement of aqueous solubility,dissolution rate and bioavailability.The integrated computational tool is a novel and robust methodology to facilitate pharmaceutical formulation design.
基金UAE University Under Contracts No. 07-34-07-11/07 and 07-01-07-11/09
文摘To verify the seismic design response factors of high-rise buildings, five reference structures, varying in height from 20- to 60-stories, were selected and designed according to modern design codes to represent a wide range of concrete wall structures. Verified fiber-based analytical models for inelastic simulation were developed, considering the geometric nonlinearity and material inelasticity of the structural members. The ground motion uncertainty was accounted for by employing 20 earthquake records representing two seismic scenarios, consistent with the latest understanding of the tectonic setting and seismicity of the selected reference region （UAE）. A large number of Inelastic Pushover Analyses （IPAs） and Incremental Dynamic Collapse Analyses （IDCAs） were deployed for the reference structures to estimate the seismic design response factors. It is concluded that the factors adopted by the design code are adequately conservative. The results of this systematic assessment of seismic design response factors apply to a wide variety of contemporary concrete wall buildings with various characteristics.
文摘挤压油膜阻尼器(Squeeze Film Dampers,SFDs)是旋转机械中常用的一类支承阻尼结构装置,能够改善转子系统的动力特性.当前工程实际中已经大量使用的两类不同结构形式的挤压油膜阻尼器,仍然存在着减振效果不稳定甚至会导致转子失稳,以及阻尼器动力学机制不清楚、建模和分析精度差、设计方法欠缺等理论技术难题.本文首先介绍两类典型SFD的结构形式和主要失效模式,然后详细叙述SFD动力学分析与优化设计方法在发展过程中的代表性研究成果,涉及SFD动力学特性、转子-SFD系统动力学特性研究、SFD动力学设计与优化等几个方面的研究,并对SFD的试验测试技术方面的成果进行评述.在此基础上,探讨目前先进航空发动机用大型挤压油膜阻尼器亟须开展的基础研究任务,特别强调了数据驱动与动力学解析模型融合的SFD动力学建模、分析与设计优化的发展方向.
