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Distinct actions of intermittent and sustained β-adrenoceptor stimulation on cardiac remodeling

science china(Life sciences) 2011年第6期54卷 493-501页

作者： MA XiaoWei1,3,SONG Yao1,3,CHEN Chao1,3,FU YongNan1,3,SHEN Qiang2,3,LI ZiJian1,3 & ZHANG YouYi1,3 1institute of Vascular Medicine,peking university Third Hospital,beijing 100191,china 2institute of cardiovascular science,peking university,beijing 100191,china 3Key Laboratory of Molecular cardiovascular sciences,Ministry of Education,beijing 100191,china 1. institute of Vascular Medicine Peking University Third Hospital Beijing 100191 China3. Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Beijing 100191 China2. Institute of Cardiovascular Science Peking University Beijing 100191 China

Heart disease is associated with increased sympathetic nerve activity and elevated levels of circulating catecholamines,resulting in chronic stimulation of the β-adrenergic receptors (β-AR) and consequent pathological cardiac ***,chronic administration of the β-AR agonist isoproterenol (ISO) has been most commonly used to model β-AR-induced cardiac ***,it remains unclear whether β-AR-mediated cardiac remodeling and dysfunction differs between sustained versus pulsatile (intermittent) exposure to a β-***,we compare the effects of intermittent versus sustained administration of ISO on cardiac remodeling and function in *** were administered 5 mg (kg d)-1 ISO for 2 weeks either by daily subcutaneous injection,or continuous infusion via an implanted osmotic *** function and remodeling were determined by echocardiography,micromanometry and ***,Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were utilized to define the proteins and genes *** sustained and intermittent administration of ISO resulted in a similar degree of cardiac hypertrophy (16% and 19%,respectively).However,mice receiving ISO by daily injection developed more severe ventricular systolic and diastolic dysfunction and myocardial fibrosis compared with mice receiving ISO via the osmotic *** disparity in results between the delivery methods is suggested to be due,at least in part,to increased expression of fibrogenic factors,including connective tissue growth factor (CTGF) and NADPH oxidase (NOX4),in mice receiving intermittent application of *** summary,compared with sustained exposure to a β-AR agonist,intermittent β-AR stimulation leads to more severe cardiac dysfunction and *** findings not only further our understanding of β-AR function in the setting of cardiac pathophysiology,but also highlight that significant differences can result dependent upon the mod

关键词： β-adrenoceptor reactive oxygen species NADPH oxidase cardiac hypertrophy cardiac fibrosis

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Role of inositol 1,4,5-trisphosphate receptors in α1-adrenergic receptorinduced cardiomyocyte hypertrophy

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Acta Pharmacologica Sinica 2006年第7期27卷 895-900页

作者： Da-li LUO~(2,3,5) Jian GAO~2 Xiao-mei LAN~3 Gang WANG~4 Sheng WEI~4 Rui-ping XIAO~4 Qi-de HAN~32 Department of Pharmacology,School of Chemical Biology & Pharmaceutical sciences,Capital university of Medical sciences,beijing 100069,china 3 institute of cardiovascular science at Health science Center,peking university beijing 100083,china 4 institute of Molecular Medicine and College of Life science,peking university,beijing 100871,china Department of Pharmacology School of Chemical Biology & Pharmaceutical Sciences Capital University of Medical Sciences Beijing 100069 China institute of cardiovascular science at Health science Center Peking University Beijing 100083 China institute of Molecular Medicine and College of Life science Peking University Beijing 100871 China

Aim:Intracellular Ca2+plays pivotal roles in diverse cellular functions,includinggene transcription that underlies cardiac remodeling during stress ***,the role of inositol 1,4,5-trisphosphate receptors（IP3Rs）in the media-tion of cardiac intracellular Ca2+and hypertrophic growth remains *** with neonatal rat ventricular myocytes suggests that activation of IP3Rsmay be linked to α1adrenergic receptor（α1AR）increased stereotyped Ca2+sparkoccurrence and global Ca2+***,we hypothesized that Ca2+releasethrough IP3Rs was necessary for α1AR-stimulated cardiac ***:We used myoinositol 1,4,5-trisphosphate hexakis（butyryloxymethyl）ester（IP3BM）,a membrane-permeant ester of IP3,to activate IP3Rs directly,and Fluo 4/AM tomeasure intracellular Ca2+***:IP3BM(10μmol·L-1)mimicked theeffects of phenylephrine,a selective agonist of α1AR,in increments in local Ca2+spark release（especially in the perinuclear area）and global Ca2+*** importantly,IP3R inhibitors,2-aminoethoxydiphenyl borateand Xestospongin C,abolished the IP3BM-induced Ca2+responses,and signifi-cantly suppressed α1AR-induced cardiomyocyte hypertrophy assayed by cellsize,[3H]leucine incorporation and atrial natriuretic factor gene expression,dur-ing sustained（48 h）phenylephrine ***:These results,therefore,provide cellular mechanisms that link IP3R signaling to α1AR-stimulatedgene expression and cardiomyocyte hypertrophy.

关键词： inositol 1,4,5-trisphosphate receptors Ca2+sparks α1 adrenergic stimulation cardiac hypertrophy

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Taurine antagonized oxidative stress injury induced by homocysteine in rat vascular smooth muscle cells

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Acta Pharmacologica Sinica 2004年第03期25卷 87-92页

作者： Lin CHANG2,3,Jian-xin XU4,Jing ZHAO5,Yong-zheng PANG2,3,Chao-shu TANG2,3,Yong-fen QI5,6 2institute of cardiovascular Diseases,the FirstHospital,peking university,beijing 100034 3institute of cardiovascular Diseases,peking university,beijing 100083 4instituteof Biophysics,Chinese Academy of sciences,beijing 100101 5Department of Physiology,Health science Center,peking university,beijing 100083,china institute of cardiovascular Diseases the First Hospital Peking University institute of cardiovascular Diseases Peking University institute of Biophysics Chinese Academy of Sciences Beijing 100101 Department of Physiology Health Science Center Pe

AIM: To observe protective effects of taurine on reactive oxygen species generation induced by homocysteine in rat vascular smooth muscle cells (VSMC). METHODS: Rat VSMC was incubated with various concentrations of homocysteine and taurine. The lactate dehydrogenase (LDH) activity which released into culture medium was elevated as an indicator for VSMC injury. The reactive oxygen species (ROS) — hydrogen peroxide (H2O2) and superoxide anion (O2ˉ· )were measured with luminol or lucigenin chemiluminescences method, and the mitochondria Mn-superoxide dismutase (Mn-SOD) and catalase (CAT) were also measured in treated VSMC. RESULTS: LDH leakage from cultured VSMC treated with homocystenie, was increased (P2O2generation from VSMC in a con- centration dependent manner (P20 mmol/L) significantly antago- nized 0.5 mmol/L homocysteine-induced H2O2generation in VSMC in a concentration dependent manner (P2O2generation in VSMC (P>0.05 vs control). In this study, the superoxide anion in VSMC was not detectable by chemiluminent method. In addition, treatment of VSMC with taurine increased mitochondria Mn-SOD and CAT activity in a concentration dependent manner (P<0.05), but homocysteine decreased mitochondria Mn-SOD and CAT activity (P<0.01 vs control). In addition, co-administration of taurine markedly ameliorated homocysteine-induced inhibition of Mn-SOD and CAT activity in VSMC (P<0.01 vs homocysteine alone group). CONCLUSION: Taurine antagonized the effects of homocysteine on ROS generation and anti-oxidant enzyme activities in rat VSMC in vitro.

关键词： homocysteine taurine vascular smooth muscle mitochondria reactive oxygen species

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Bursting of Morris-Lecar neuronal model with current-feedback control

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science china(Technological sciences) 2009年第3期52卷 771-781页

作者： DUAN LiXia1, LU QiShao2 & CHENG DaiZhan3 1 College of science, North china university of Technology, beijing 100144, china 2 School of science, beijing university of Aeronautics and Astronautics, beijing 100191, china 3 institute of Systems science, Chinese Academy of sciences, beijing 100190, china College of science North China University of Technology Beijing 100144 China School of science Beijing University of Aeronautics and Astronautics Beijing 100191 China institute of Systems science Chinese Academy of Sciences Beijing 100190 China

The Morris-Lecar (ML) neuronal model with current-feedback control is considered as a typical fast-slow dynamical system to study the combined influences of the reversal potential VCa of Ca2+ and the feedback current I on the generation and transition of different bursting oscillations. Two-parameter bifurcation analysis of the fast subsystem is performed in the parameter (I, VCa)-plane at first. Three important codimension-2 bifurcation points and some codimension-1 bifurcation curves are obtained which enable one to determine the parameter regions for different types of bursting. Next, we further divide the control parameter (V0, VCa)-plane into five different bursting regions, namely, the "fold/fold" bursting region R1, the "fold/Hopf" bursting region R2, the "fold/homoclinic" bursting region R3, the "subHopf/homoclinic" bursting region R4 and the "subHopf/subHopf" bursting region R5, as well as a silence region R6. Codimension-1 and -2 bifurcations are responsible for explanation of transition mechanisms between different types of bursting. The results are instructive for further understanding the dynamical behavior and mechanisms of complex firing activities and information processing in biological nervous systems.

关键词： neuron bursting bifurcation fast-slow dynamics analysis codimension

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Positioning localities from spatial assertions based on Voronoi neighboring

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science china(Technological sciences) 2010年第S1期53卷 143-149页

作者： GONG YongXi 1,2,3,LI GuiCai 1,LIU Yu 2 & YANG Jian 1 1 Shenzhen Key Lab of Recycling Economy,peking university Shenzhen Graduate School,Shenzhen 518055,china 2institute of Remote Sensing and Geographical Information Systems,peking university,beijing 100871,china 3College of Urban and Environmental science,peking university,beijing 100871,china peking Univ Shenzhen Grad Sch Shenzhen Key Lab Recycling Econ Shenzhen 518055 Peoples R China peking Univ Inst Remote Sensing & Geog Informat Syst Beijing 100871 Peoples R China peking Univ Coll Urban & Environm Sci Beijing 100871 Peoples R China

With the rapid development of Internet,much spatial information contained in non-structured or semi-structured documents is available on the World Wide *** such documents,localities are always textually described using spatial relationships and named places,instead of numerical ***,extracting positional information from locality descriptions is an important *** this paper,we bridge two aspects of locality descriptions,namely generating locality descriptions and positioning localities,and provide a method to compute probability density according to the selection probability of a reference object to describe the position of the target *** operation on uncertainty field is used to deal with locality description involving multiple reference *** metrics are introduced to measure the results of positioning *** choose the mixed selection probability function based on Euclidean distance and Voronoi stolen-area to compute probability density ***,we use three cases to demonstrate the proposed methods.

关键词： geographic information science positioning locality Voronoi neighboring probability density function

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Theory and verification of operator design methodology

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science china(Information sciences) 2012年第2期55卷 480-490页

作者： HU ZiYi1,ZHAO Yong1,WANG XinAn1,HUANG Ru2,WANG Teng1 & ZHANG Xing2 1Key Lab of Integrated Microsystem science and Engineering Applications,peking university Shenzhen Graduate School,Shenzhen 518055,china 2institute of Microelectronics,peking university,beijing 100871,china 1. Key Lab of Integrated Microsystem science and Engineering Applications Peking University Shenzhen Graduate School Shenzhen 518055 China2. Institute of Microelectronics Peking University Beijing 100871 China

Non-recurring-engineering(NRE)and time-to-market play an increasingly important role in the field of IC ***,with the continuous development of IC manufacturing technology,it is necessary to propose a novel design methodology to shorten design cycle and enhance design *** this paper,operator design methodology(ODM)is presented and an H.264 encoder is implemented as a *** to the flow of ODM,the register transfer level(RTL)design of H.264 encoder has been accomplished with 15 man-months,which is lower than the average 19 man-months in the field of traditional application specific integrated circuit(ASIC)***,with the advantage of operator design library,the design has a comparable performance with other ASIC *** obtained design can support a real-time video encoding of 720p at 60 frames per second or 1080p at 30 frames per second,working at 167 MHz with SMIC 0.13 μm CMOS *** results provide good evidence for the practicability and efficiency of ODM.

关键词： operator design methodology H.264 encoder integrated circuit hardware

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Kinetic characteristics of continuous flow polymerase chain reaction chip: A numerical investigation

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science china(Technological sciences) 2010年第7期53卷 1967-1972页

作者： WANG ShiYing1 & WANG Wei2,3 1 School of Physics, peking university, beijing 100871, china 2 institute of Microelectronics, peking university, beijing 100871, china 3 National Key Laboratory of science and Technology on Micro/Nano Fabrication, beijing 100871, china 1. School of Physics Peking University Beijing 100871 China2. Institute of Microelectronics Peking University Beijing 100871 China3. National Key Laboratory of Science and Technology on Micro/Nano Fabrication Beijing 100871 China

Continuous flow PCR (polymerase chain reaction) chip holds impressive advantages compared to micro chamber PCR chip. In order to have better understanding of kinetic characteristics of continuous flow PCR chip, a comprehensive mathematical model is presented in this paper, including melting, annealing and extension phases of a typical PCR process which has the essence of a convection-diffusion-reaction system. Using this model, we can simulate the PCR process in series of reaction cycles. Numerical results show that the average sample velocity plays a significant role in affecting the amplification efficiency. Also, appropriate combination of the PCR mixture is important for high-quality DNA amplification. Giving a large initial DNA concentration range, the continuous flow PCR scheme holds excellent real-time detection ability theoretically. The present numerical model bridges the temperature distribution to the real DNA amplification, and thereby is able to successfully predict continuous flow PCR properties which are important for the chip design.

关键词： continuous flow PCR chip numerical simulation convection-diffusion-reaction system

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Key Parameters and Conceptual Configuration of Unmanned Combat Aerial Vehicle Concept

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Chinese Journal of Aeronautics 2009年第4期22卷 393-400页

作者： Wang Ganglin Faculty 513,School of Aeronautic science and Engineering,beijing university of Aeronautics and Astronautics,beijing 100191,china [a]Faculty 513 School of Aeronautic Science and Engineering Beijing University of Aeronautics and Astronautics Beijing 100191 China

The nature and characteristics of attack unmanned combat aerial vehicle （UCAV） are analyzed. The principles of selecting takeoff thrust-weight ratio and takeoff weight of attack UCAV are presented by analyzing the statistical data of weights for various main combat aircraft. The UCAV airborne weapons are analyzed, followed by the preliminary estimation of the payload weight. Various typical engines are analyzed and one of them is selected. Then the takeoff weight of the UCAV is determined. Based on some basic parameters and assumptions, the qualitative decomposition calculation for takeoff weight is completed. The key factors for obtaining longer endurance of aircraft with small aspect ratio configuration are found to be high lift-drag ratio and internal space. On the basis of the conclusions mentioned above, a highly blended flying-wing plus lifting body concept is proposed. According to this concept, the UCAV configuration is designed and optimized. Finally, the UCAV configuration with small aspect ratio, high lift-drag ratio, and high stealth characteristic is obtained.

关键词： aircraft design unmanned aerial vehicles unmanned combat aerial vehicles conceptual design aerodynamicsstealth

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Nonlinear Aeroelastic Response of High-aspect-ratio Flexible Wings

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Chinese Journal of Aeronautics 2009年第4期22卷 355-363页

作者： Zhang Jian,Xiang Jinwu School of Aeronautic science and Engineering,beijing university of Aeronautics and Astronautics,beijing 100191,china [a]School of Aeronautic science and Engineering Beijing University of Aeronautics and Astronautics Beijing 100191 China

The aeroelastic analysis of high-altitude, long-endurance （HALE） aircraft that features high-aspect-ratio flexible wings needs take into account structural geometrical nonlinearities and dynamic stall. For a generic nonlinear aeroelastic system, besides the stability boundary, the characteristics of the limit-cycle oscillation （LCO） should also be accurately predicted. In order to conduct nonlinear aeroelastic analysis of high-aspect-ratio flexible wings, a first-order, state-space model is developed by combining a geometrically exact, nonlinear anisotropic beam model with nonlinear ONERA （Edlin） dynamic stall model. The present investigations focus on the initiation and sustaining mechanism of the LCO and the effects of flight speed and drag on aeroelastic behaviors. Numerical results indicate that structural geometrical nonlinearities could lead to the LCO without stall occurring. As flight speed increases, dynamic stall becomes dominant and the LCO increasingly complicated. Drag could be negligible for LCO type, but should be considered to exactly predict the onset speed of flutter or LCO of high-aspect-ratio flexible wings.

关键词： nonlinear aeroelasticity limit-cycle oscillation Galerkin methods geometrical nonlinearities dynamic stall HALEaircraft

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The numerical method for three-dimensional impact with friction of multi-rigid-body system

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science china(Physics,Mechanics & Astronomy) 2006年第1期49卷 102-118页

作者： ZHAO Zhen1,2, LIU Caishan2 & CHEN Bin2 1. beijing institute of Graphic Communication, beijing 102600, china 2. Department of Mechanics & Engineering science, peking university, beijing 100871, china beijing institute of Graphic Communication Beijing 102600 China Department of Mechanics & Engineering science Peking University Beijing 100871 China

The differential equations for planar impacts reduce to an algebraic form, and can be easily solved. For three dimensional impacts with friction, there is no closed-form solution, and numerical integration is required due to the swerve behavior of tangential impulse during collisions. The dynamic governing equations in the impact process are built up in impulse space based on the Lagrangian equation in this paper. The coefficient of restitution defined by Poisson is used as the condition of impact termination. A valid nu- merical method for solving three-dimensional frictional impact of multi-rigid body system is established. The singular cases of tangential movement in sticking point are especially noticed and analyzed. Several examples are present to reveal the different kinds of tan- gential movement modes varied with the normal impulse during collision.

关键词： multi-rigid body, impact, friction.

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