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Pharmacokinetic-Pharmacodynamic modeling of the analgesic effect of bupredermTM, in mice

Health 2010年第8期2卷 824-831页

作者： min-Hyuk Yun Seung-Wei Jeong chaul-min pai Sun-Ok Kim Samyang Pharmaceutical R&D Center

Purpose: BupredermTM-Buprenorphine transdermal delivery system (BTDS) was developed for the treatment of post-operative and chronic pains. This study examined the relationship between the plasma concentration of buprenorphine and its analgesic effect (tail flick test) in order to assess the usefulness of pharmacokinetic-pharmacodynamic (PK-PD) modeling in describing this relationship. Methods: After patch application, plasma concentrations of bu- prenorphine in mice were measured for 72 hours with a validated LC/MS/MS system, and the analgesic effects were assessed by tail flick test for the period of 24 hours. A modified two- compartment open model was used to explain the PK properties of BTDS, and the PD model was characterized by slow receptor binding. Results: The peak buprenorphine level in plasma was achieved at 1-24 h and the effective therapeutic drug concentration was maintained for 72 hours. BupredermTM induced prolongation of tail-flick latency in a dose and time dependent manner. Maximum analgesic effect was attained at 3-6 h and was maintained for 24 h after patch application. Counter-clockwise hysteresis between the plasma concentration and the analgesic efficacy of BTDS was observed after BupredermTM application, indicating there was a delay between plasma concentrations and the effect observed. From the developed PK-PD model, Kd values (0.69-0.82 nM) that were derived from the pharmacodynamic parameters (Kon and Koff) are similar to the reported values (Kd = 0.76 ± 0.14 nM). Good agreement between the predicted and observed values was noted for the rate of change in analgesic effect data (R2 = 0.822, 0.852 and 0.774 for 0.24, 0.8 and 2.4 mg/patch, respectively). Conclusions: The established PK- PD model successfully described the relationship between plasma concentration of buprenorphine and its analgesic efficacy measured by the tail flick test. Our model might be useful in estimation and prediction of onset, magnitude and time course of concentrati

关键词： Pharmacokinetic-Pharmacodynamic Modeling BupredermTM Buprenorphine Transdermal System Slow Receptor-Binding Model

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Pharmacokinetic-Pharmacodynamic modeling of the analgesic effect of bupredermTM, in mice

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Health（健康） 2010年第8期

作者： min-Hyuk Yun Seung-Wei Jeong chaul-min pai Sun-Ok Kim

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Cryogenic and conventional milling of AZ91 magnesium alloy

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Journal of Magnesium and Alloys 2024年第6期12卷 2503-2519页

作者： Vikas Marakini Srinivasa pai P Gururaj Bolar Bhaskara P Achar Department of Mechanical Engineering Nitte(Deemed to be University)NMAM Institute of Technology(NMAMIT)Nitte 574110India Department of Mechanical and Industrial Engineering Manipal Institute of TechnologyManipal Academy of Higher EducationManipal 576104India

Use of magnesium is the need of the hour due to its low density as well as its high strength-to-weight and stiffness-to-weight ratio *** study focuses on the effectiveness of liquid nitrogen(LN_(2))assisted cryogenic machining on the surface integrity(SI)characteristics of AZ91 magnesium *** milling using uncoated carbide inserts have been performed under liquid nitrogen(LN_(2))assisted cryogenic condition and compared with conventional(dry)*** are performed using machining parameters in terms of cutting speeds of 325,475,625 m/min,feed rates of 0.05,0.1,0.15 mm/teeth and depth of cuts of 0.5,1,1.5 mm *** significant surface integrity characteristics such as surface roughness,microhardness,microstructure,and residual stresses have been *** of SI characteristics with respect to milling parameters have been identified using statistical technique such as ANOVA and signal-to-noise(S/N)ratio ***,the multi criteria decision making(MCDM)techniques such as additive ratio assessment method(ARAS)and complex proportional assessment(COPRAS)have been utilized to identify the optimal conditions for milling AZ91 magnesium alloy under both dry and cryogenic *** of LN_(2)during machining,resulted in reduction in machining temperature by upto 29%with a temperature drop from 251.2℃under dry condition to 178.5℃in cryogenic *** showed the advantage of performing cryogenic milling in improving the surface integrity to a significant *** machining considerably minimized the roughness by upto 28%and maximised the microhardness by upto 23%,when compared to dry *** speed has caused significant impact on surface roughness(95.33%-dry,92.92%-cryogenic)and surface microhardness(80.33%-dry,82.15%-cryogenic).Due to the reduction in machining temperature,cryogenic condition resulted in compressive residual stresses(maximumσ║=-113 MPa)on the alloy *** indicate no

关键词： Magnesium alloy Cryogenic machining Roughness Microhardness Microstructure Residual stress Multi criteria decision making

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Topology Optimization of Metamaterial Microstructures for Negative Poisson’s Ratio under Large Deformation Using a Gradient-Free Method

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Computer Modeling in Engineering & Sciences 2024年第5期139卷 2001-2026页

作者： Weida Wu Yiqiang Wang Zhonghao Gao pai Liu State Key Laboratory of Structural Analysis for Industrial Equipment Dalian University of TechnologyDalian116024China

Negative Poisson’s ratio(NPR)metamaterials are attractive for their unique mechanical behaviors and potential applications in deformation control and energy ***,when subjected to significant stretching,NPR metamaterials designed under small strain assumption may experience a rapid degradation in NPR *** address this issue,this study aims to design metamaterials maintaining a targeted NPR under large deformation by taking advantage of the geometry nonlinearity mechanism.A representative periodic unit cell is modeled considering geometry nonlinearity,and its topology is designed using a gradient-free *** unit cell microstructural topologies are described with the material-field series-expansion(MFSE)*** MFSE method assumes spatial correlation of the material distribution,which greatly reduces the number of required design *** conveniently design metamaterials with desired NPR under large deformation,we propose a two-stage gradient-free metamaterial topology optimization method,which fully takes advantage of the dimension reduction benefits of the MFSE method and the Kriging surrogate model ***,we use homogenization to find a preliminary NPR design under a small deformation *** the second stage,we begin with this preliminary design and minimize deviations in NPR from a targeted value under large *** this strategy and solution technique,we successfully obtain a group of NPR metamaterials that can sustain different desired NPRs in the range of[−0.8,−0.1]under uniaxial stretching up to 20% ***,typical microstructure designs are fabricated and tested through *** experimental results show good consistency with our numerical results,demonstrating the effectiveness of the present gradientfree NPR metamaterial design strategy.

关键词： Topology optimization microstructural design negative Poisson’s ratio large deformation

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Automatic Miscalibration Detection and Correction of LiDAR and Camera Using Motion Cues

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Chinese Journal of Mechanical Engineering 2024年第2期37卷 318-329页

作者： pai Peng Dawei Pi Guodong Yin Yan Wang Liwei Xu Jiwei Feng School of Mechanical Engineering Southeast UniversityNanjing 211102China School of Mechanical Engineering Nanjing University of Science and TechnologyNanjing 210014China School of Mechanical and Aerospace Engineering Nanyang Technological UniversitySingaporeSingapore

This paper aims to develop an automatic miscalibration detection and correction framework to maintain accurate calibration of LiDAR and camera for autonomous vehicle after the sensor ***,a monitoring algorithm that can continuously detect the miscalibration in each frame is designed,leveraging the rotational motion each individual sensor ***,as sensor drift occurs,the projection constraints between visual feature points and LiDAR 3-D points are used to compute the scaled camera motion,which is further utilized to align the drifted LiDAR scan with the camera ***,the proposed method is sufficiently compared with two representative approaches in the online experiments with varying levels of random drift,then the method is further extended to the offline calibration experiment and is demonstrated by a comparison with two existing benchmark methods.

关键词： Autonomous vehicle LiDAR and camera Miscalibration detection and correction Sensor drift

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Enhanced population of excited single state strategy:Irradiation and ultrasound dual-response and host tumor-driven nanosensitizers construction in triple synergistic therapy

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Nano Research 2024年第6期17卷 5501-5511页

作者： Yaning Li Mengyan Tian Tianyue Yang Jiayu Cao Hongli Chen Jun Guo pai Liu Yi Liu State Key Laboratory of Separation Membranes and Membrane Processes School of Materials Science and EngineeringTiangong UniversityTianjin 300387China State Key Laboratory of Separation Membranes and Membrane Processes School of ChemistryTiangong UniversityTianjin 300387China State Key Laboratory of Separation Membranes and Membrane Processes School of Life ScienceTiangong UniversityTianjin 300387China State Key Laboratory of Separation Membrane and Membrane Process&Tianjin Key Laboratory of Green Chemical Technology and Process Engineering School of ChemistryTiangong UniversityTianjin 300387China School of Chemical and Environmental Engineering Wuhan Polytechnic UniversityWuhan 430023China Cangzhou Institute of Tiangong University Cangzhou 061000China

Phototheranostics is an emerging field in synergistic antitumor therapy in which irradiation and sensitizers are combined to produce reactive oxygen species(ROS),bio-images,and high *** of these are arrived from the energy of sensitizers,which located in excited single state(S_(1)).Undeniably,the decentralization of the S_(1)population indirectly decreases the effect of each individual *** this study,a strategy was proposed for enhancing the S_(1)population,and a sensitizer with mitochondrial targeting property,1,4-indolyl iodinated pyrrolo[3,2-b]pyrrole derivative(2I-TPIS),was assembled into adenosine triphosphate(ATP)-responsive nanoparticles(DPA-2I NPs)to achieve dual responses to irradiation and ultrasonication(US)for application to photo-sonodynamic therapy(PSDT).Compared with monotherapies,2I-TPIS generated more ROS in PSDT,inducing mitochondrial autophagy and apoptosis,which in turn triggered immunogenic cell death(ICD).Subsequently,DPA-2I NPs were constructed and self-assembled with the chemotherapeutic agents DPA-Cd and 2I-TPIS to achieve a triple synergistic strategy involving chemotherapy(CT)and ***-2I NPs exhibited absolute sensitization,intra-tumoral overexpression of ATP,and ***,the biosafety and potent antitumor efficiency of the DPA-2I NP-based“PSDT+CT”therapy were revealed using a 4T1 tumor *** study results provide insights into the design of sensitizers possessing a sufficient S_(1)population and a highly efficient tumor ablation capacity derived from molecular structural modulation,further enabling triple synergistic antitumor therapies,and expanding the clinical application of sensitizers.

关键词： triphosphate(ATP)-activated nano-sensitizers photo-sonodynamic therapy aggregation-induced emission enhanced excited state population

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Clinical competency:perceptions of nursing interns and clinical mentors

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Frontiers of Nursing 2024年第1期11卷 105-110页

作者： Jackline Prathibha Radhika R.pai Linu Sara George Fundamentals of Nursing Manipal College of NursingManipal Academy of Higher EducationManipalKarnataka 576104India

Objective:To assess the clinical competency of nursing interns and the perception of clinical nurse mentors toward student nurses'clinical ***:A study was carried out among 104 nursing interns and 26 clinical nurse mentors using the purposive sampling technique.A self-repor ted perception scale was used to collect the ***:In general,most nursing interns perceived themselves as clinically competent during the *** clinical nurse mentors too repor ted that the current internship is helping the nursing interns in becoming ***:Frequent clinical evaluation,buddy system,provision of stipends,good leadership,and coordination between the academic institute and hospital are repor ted as the critical motivating factors for improving the clinical competency of student interns.

关键词： clinical competency clinical nurse mentors competence internship nursing interns perception

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An Integrated Control Framework for Torque Vectoring and Active Suspension System

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Chinese Journal of Mechanical Engineering 2024年第1期37卷 62-73页

作者： Jiwei Feng Jinhao Liang Yanbo Lu Weichao Zhuang Dawei Pi Guodong Yin Liwei Xu pai Peng Chaobin Zhou School of Mechanical Engineering Southeast UniversityNanjing 211189China School of Mechanical Engineering Nanjing University of Science and TechnologyNanjing 210094China School of Mechano-Electronic Engineering Lanzhou University of TechnologyLanzhou 730050China

Four-wheel independently driven electric vehicles(FWID-EV)endow a flexible and scalable control framework to improve vehicle *** paper integrates the torque vectoring and active suspension system(ASS)to enhance the vehicle’s longitudinal and vertical motion control *** the nonlinear characteristic of the tire model leads to a relatively heavier computational *** facilitate the controller design and ease the load,a half-vehicle dynamics system is built and simplified to the linear-time-varying(LTV)*** a model predictive controller is developed by formulating the objective function by comprehensively considering the safety,energy-saving and comfort *** in-wheel motor efficiency and the power loss of tire slip are treated as optimization indices in this work to reduce energy ***,the effectiveness of the proposed controller is verified through the rapid-control-prototype(RCP)*** results demonstrate the enhancement of the energy-saving as well as comfort on the basis of vehicle stability.

关键词： Four-wheel independently driven electric vehicles Tire nonlinearity Linear-time-varying(LTV)model Model predictive control Rapid control prototype

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A new insight into LPSO phase transformation and mechanical properties uniformity of large-scale Mg-Gd-Y-Zn-Zr alloy prepared by multi-pass friction stir processing

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Journal of Magnesium and Alloys 2024年第5期12卷 2041-2056页

作者： Xiaohu Guan Wen Wang Ting Zhang pai Peng Qiang Liu Peng Han Ke Qiao Jun Cai Liqiang Wang Kuaishe Wang School of Metallurgical Engineering National and Local Joint Engineering Research Center for Functional Materials ProcessingXi’an University of Architecture and TechnologyNo.13 Yanta RoadXi’anShaanxi 710055China Xi’an Rare Metal Materials Institute Co.Ltd Xi’an 710016China State Key Laboratory of Metal Matrix Composites School of Material Science and EngineeringShanghai Jiao Tong UniversityNo.800 Dongchuan RoadShanghai 200240China

A large-scale fine-grained Mg-Gd-Y-Zn-Zr alloy plate with high strength and ductility was successfully prepared by multi-pass friction stir processing(MFSP)technology in this *** structure of grains and long period stacking ordered(LPSO)phase were characterized,and the mechanical properties uniformity was ***,a quantitative relationship between the microstructure and tensile yield strength was *** results showed that the grains in the processed zone(PZ)and interfacial zone(IZ)were refined from 50μm to 3μm and 4μm,respectively,and numerous original LPSO phases were *** IZ,some block-shaped 18R LPSO phases were transformed into needle-like 14H LPSO phases due to stacking faults and the short-range diffusion of solute *** severe shear deformation in the form of kinetic energy caused profuse stacking fault to be generated and move rapidly,greatly increasing the transformation rate of LPSO *** MFSP,the ultimate tensile strength,yield strength and elongation to failure of the large-scale plate were 367 MPa,305 MPa and 18.0% *** refinement and LPSO phase strengthening were the major strengthening mechanisms for the MFSP *** particularly,the strength of IZ was comparable to that of PZ because the strength contribution of the 14H LPSO phase offsets the lack of grain refinement strengthening in *** result opposes the widely accepted notion that IZ is a weak region in MFSP-prepared large-scale fine-grained plate.

关键词： Friction stir processing Multi-pass Mg-Gd-Y-Zn-Zr alloy LPSO phase transformation Mechanical properties

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Cooperative enhancement of mechanical and tribological properties through tailoring TiN transition interface in boron nitride nanosheets reinforced copper composites

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Rare Metals 2024年第10期43卷 5202-5215页

作者： Zhong-Hua Li Liang Liu Xin You Jian-Hong Yi Rui Bao ming-Yi Zhu Song Lu Jun-Jun pai Faculty of Materials Science and Engineering Kunming University of Science and Technology Key Laboratory of Advanced Materials of Yunnan Province Kunming University of Science and Technology

Strengthening interface bonding between boron nitride nanosheets(BNNS) and copper matrix is an essential prerequisite for exploiting a new generation of copper matrix composites(CMCs) with high strength and wear resistance. Herein, BNNS/Cu composites were fabricated by the powder metallurgy route, matrix-alloying(adding 1.0 wt% Ti) strategy was adopted to improve the interfacial wettability and strengthen interface adhesion. A typical "sandwich"-like multiply interface structure involving TiN transition layers, BNNS and Cu matrix had been well constructed through the rational heat treatment(900℃for 120 min). Additionally, nano-sized TiB whisker was in situ formed in the vicinity of the interface, it had linked the BNNS-Cu-TiN multiply interface, which played a role of "threading the needle" and significantly strengthened the multi-interfaces bonding. This specific interface structure was finely characterized, and the formation mechanism of solid-state interfacial reaction feature was proposed. The results demonstrated that the ultimate tensile strength(UTS) of BNNS/Cu-(Ti)-900℃ increased from 248 to 530 MPa(increased by 114%), and the coefficient of friction(COF) decreased from 0.51 to 0.28 than pure Cu. This work highlights the importance of interface configuration design, which contributes to the development of CMCs with prominent comprehensive properties.

关键词： Boron nitride nanosheets Copper matrix composites Interface structure Mechanical and frictional properties

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