Analysis of directed flow from three-particle correlations
机械工程学专业词汇英语翻译(D)2

diffusion velocity 扩散速度 diffusion viscosity 扩散粘性 diffusion wave 扩散波 diffusion width 扩散宽度 diffusion zone 扩散带 diffusivity of heat 热扩散率 digging 挖掘 digital computer 数字计算机 digitizing 数字化 dihedral angle ⼆⾯⾓ dilatancy 扩容现象 dilatant fluid 胀猎铃 dilatation 膨胀 dilatational fissure 膨胀裂缝 dilatational shock 稀疏激波 dilatational strain 体积应变 dilatational wave 膨胀波 dilatational work 膨胀功 dilatometric curve 膨胀曲线 dilatometry 膨胀测定法 dilute phase flow 稀相怜 dilute phase of fluidization 怜稀相 diluted gas 稀⽓体 dilution factor 稀释因数 dimension theory 量纲理论 dimensional analysis 量纲分析 dimensional equation 量纲⽅程 dimensional formula 量纲公式 dimensional invariance 量纲不变性 dimensional perturbation 尺⼨的扰动 dimensional quantity 量纲量 dimensional transformation 量纲变换 dimensionless ⽆量纲的 dimensionless number ⽆因次数 dimensionless quantity ⽆量纲量 dimensionless specific speed ⽆因次⽐转速 dip 倾斜 diphase 两相的 dipole 偶极⼦ dipole elastic relaxation 偶极⼦弹性弛豫 dipole energy 偶极⼦能量 dipole force 偶极⼦⼒ dipole wave 偶极⼦波 direct control 直接控制 direct dynamic problem 动⼒学直接问题 direct extrusion 正挤压 direct impact 正碰 direct kinematic problem 运动学直接问题 direct load 直接荷载 direct method 直接法 direct motion 顺⾏ direct observation 直接观察 direct sense of motion 运动的直接指向 direct shear test 直剪试验 direct stiffness method 直接刚度法 direct stress 法向应⼒ directed movement 单向运动 directing force 指向⼒ direction ⽅向 direction angle ⽅向⾓ direction cosine ⽅向余弦 direction of action 酌⽅向 direction of rotation 转动⽅向 direction of tension 牵引⽅向 direction of traction 牵引⽅向 directional correlation ⽅向关联 directional dependence ⽅向依赖性 directional stability ⽅向稳定性 directivity ⽅向性 dirichlet neuman's problem 狄利克雷诺埃曼问题 dirichlet problem 狄利克雷问题 dirichlet stability theorem 狄利克雷稳定性定理 disassembly 拆卸 disc 圆盘 discharge 排出 discharge coefficient 量系数 discharge duration curve 量持续曲线 discharge of water 排⽔量 discharge pressure 排放压⼒ discharge rate 瘤速率 discharge regulator 量第器 disconnection 切断 discontinuity 不连续性 discontinuity condition 不连续条件 discontinuity interaction 不连续⾯相互酌 discontinuity layer 不连续层 discontinuity potential 不连续势 discontinuity surface 间断⾯ discontinuity wave 间断波 discontinuous 不连续的 discontinuous flow ⾮连续怜 discontinuous motion 间断运动 discontinuous spectrum 不连续频谱 discontinuous system 不连续系统 discrete 离散的 discrete element method 离散单元法 discrete stochastic process 离散随机过程 discriminant 判别式 discriminator 甄别器鉴相器 disequilibrium ⾮平衡 disk 圆盘 disk damping 圆盘阻尼 dislocation 位错 disorder energy ⽆序化能量 disorder pressure ⽆序压 disorder scattering ⽆规散射 disordered flow ⽆序流 disordered motion ⽆序运动 disorientation 乱取向 dispersed phase 分散相 dispersed shock 分散冲击 dispersion 分散 dispersion coefficient 分散系数 dispersion equation 分散⽅程 dispersion force 弥散⼒ dispersion frequency 分散频率 dispersion hardening 弥散硬化 dispersion interaction 弥散相互酌 dispersion medium 分散介质 dispersion model 分散模型 dispersion relation 分散关系 dispersion surface 弥散⾯ dispersion tensor 频散张量 dispersity 分散性 dispersive wave 弥散波 dispersiveness 分散性 displacement 变位 displacement collision 位移碰撞 displacement coordinate 位移坐标 displacement correction 排⽔量校正 displacement crack 位移裂隙 displacement diagram 变位图 displacement distance 移动距离 displacement field 位移场 displacement flow 排代怜 displacement gradient 位移梯度 displacement law 位移定律 displacement matrix 位移矩阵 displacement method 位移法 displacement of center of gravity 重⼼位移 displacement of equilibrium 平衡的移动 displacement pickup 位移传感器 displacement potential 位移势 displacement resistance 位移阻⼒ displacement sensitivity 位移灵敏度 displacement stream 排代运动 displacement surface 位移⾯ displacement tensor 位移张量 displacement thickness 位移厚度 displacement time graph 位移时间线图 displacement vector 位移⽮量 displacement vector of joint 关节位移⽮量 displacement wave 位移波 disruption 破裂 disruptive 破坏的 dissipated power 耗散功率 dissipation 耗散 dissipation constant 耗散常数 dissipation factor 耗散因数 dissipation of energy 能量的耗散 dissipation of jet 射聊散 dissipation of vorticity 涡旋耗散 dissipation rate 耗散速率 dissipative force 耗散⼒ dissipative function 耗散函数 dissipative process 耗散过程 dissipative stress 耗散应⼒ dissipative system 耗散系统 dissipativity 耗散度 dissociation 离解 dissociation energy 离解能 dissociation equilibrium 离解平衡 dissociation heat 离解热 dissociation potential 离解势 dissociation pressure 离解压 dissociation tension 离解压 dissolution 溶解 dissolution heat 溶解热 dissonance 不谐和 distance control 远距控制 distance from epicenter 震源距 distance of fall 下落距离 distance of visible horizon ⽔平视距 distorted wave 畸变波 distorted wave method 畸变波⽅法 distortion 畸变 distortion energy theory 畸变能理论 distortion factor 畸变因数 distortion matrix 变形矩阵 distortion standard 畸变基准 distortion tensor 畸变张量 distortional component 畸变分量 distortional strain energy 畸变能 distributed load 分布负载 distributed mass 分布质量 distributed moment 分配⼒矩 distributed parameter 分布参数 distributed parameter system 分布参数系统 distributed roughness 分布糙度 distributed source 分布源 distribution 分布 distribution coefficient 分布系数 distribution curve 分布曲线 distribution density 分布密度 distribution factor 分布系数 distribution function 分布函数 distribution law 分布律 distribution of angles of attack 攻⾓分布 distribution of lines of force ⼒线分布 distribution of turbidity 浊度分布 distribution of velocities of flow 临分布 disturbance 扰动 disturbance energy 微扰能 disturbance vortex 扰动涡 disturbation theory 微扰理论 disturbed motion 扰动运动 disturbing force 扰动⼒ disturbing function 扰动函数 disturbing mass 扰动质量 disturbing quantity 扰动量 diurnal motion 周⽇运动 dive 俯冲 divergence 发散 divergence of deformation 形变发散 divergence of fluid 铃散度 divergent flow 发散流 divergent nozzle 扩散形喷管 divergent series 发散级数 divergent wave 发散波 diversion 分流 diversion channel 分⽔渠 diversion dam 分⽔坝 dividing line 分界线 doi edwards theory 陶盖爱德华兹理论 domain 区域 dominant frequency 优势频率 dominant mode 郑 dominant wave 吱 dominant wavelength 吱长 donnell equation 唐奈⽅程 doppler effect 多普勒效应 dot and dash curve 点划线 dot and dash line 点划线 dotted curve 虚线 dotted line 虚线 double amplitude 双幅 double amplitude peak 双幅度峰值 double beam 双重梁 double diffusion 双扩散 double dipole 双偶极⼦ double exposure 双重曝光 double exposure holography 双重曝光全息照相术 double float 双浮标 double force 双⼒ double glide 双重滑移 double helix 双螺旋 double layer 双层 double layer potential 双层势 double lever 双杠杆 double modulation 双重灯 double modulus theory 双模数理论 double pendulum 双摆 double precision arithmetic 双精度运算 double refraction 双折射 double shock diffuser 双激波扩散器 doublet flow 偶极⼦怜 doublet source 双重源 down current 下降⽓流 down surge ⽔⾯下降 downstream 下游 downstream floor 下游护拦 downwash 下洗 downwash velocity 下洗速度 draft 吃⽔ drag 阻⼒ drag acceleration 减速 drag coefficient 阻⼒系数 drag effect 牵制效应 drag flow 阻曳流 drag force 迎⾯阻⼒ drag force of the flow 怜曳⼒ drag head 阻⼒⽔头 drag lift ratio 阻升⽐ drag polar 阻⼒极线 drag reduction 减阻 drain 排⽔管 drain water 排泄⽔ drainage 排⽔ drainage basin 硫 draught 吃⽔ drawing 牵引 drift 漂流 drift compensation 漂移补偿 drift current 漂流 drift energy 漂移能量 drift flow model 漂移怜模型 drift speed 漂移速度 drift velocity 漂移速度 drilling 钻孔 driving force 驱动⼒ driving torque 驱动转矩 drop 下降 drop fall 落滴 drop test 锤辉验 drop weight test 落锤试验 dropping velocity 沉降速度 dropping water 滴⽔ drowned spring ⽔底泉 dry adiabat ⼲绝热线 dry friction ⼲摩擦 dual quaterion 对偶四元数 dual tensor 对偶张量 dual vector 对偶⽮量 duck ⽔上飞机 ductile fracture 韧性断裂 ductile material 延性材料 ductilimeter 延性计 ductilimetry 延度测量法 ductility 延性 duffing equation 杜芬⽅程 duffing method 杜芬法 duffing problem 杜芬问题 dufour effect 迪富尔效应 duhamel integral 杜哈梅积分 dummy load 假负载 duncan chang model 邓肯张模型 durability 耐久性 durability factor 耐久性系数 duration 持续时间 duration of ascent 上升时间 duration of experiment 实验持续时间 duration of test 实验持续时间 dust flow method 尘两法 dye experiment 染⾊柳实验 dye method 染⾊液法 dying oscillation 衰减振荡 dying out 衰灭消失 dynamic accuracy 动态准确度 dynamic action of force ⼒的动态酌 dynamic analogy 动态模拟 dynamic analysis 动态分析 dynamic balancing machine 动平衡机 dynamic boundary condition 动⼒边界条件 dynamic characteristic 动态特性 dynamic coercitivity 动态矫顽磁⼒ dynamic coercive force 动态矫顽磁⼒ dynamic compensation 动态补偿 dynamic compensator 动态补偿器 dynamic condition 动态条件 dynamic consolidation 动⼒固结 dynamic design 动态设计 dynamic elastic modulus 动⼒弹性模量 dynamic elasticity 弹性动⼒学 dynamic equation 动⼒⽅程 dynamic equilibrium 动态平衡 dynamic error 动态误差 dynamic fracture 动⼒断裂 dynamic head 动压头 dynamic height 动⼒⾼度 dynamic hysteresis 动态滞后 dynamic instability 动⼒不稳定 dynamic lift 动升⼒ dynamic load 动⼒负载 dynamic meteorology 动⼒⽓象学 dynamic method 动⼒学⽅法 dynamic model 动⼒模型 dynamic modulus of elasticity 动⼒弹性模量 dynamic parallax 动⼒学视差 dynamic photoelasticity 动态光弹性法 dynamic precision 动态精度 dynamic pressure 动压⼒ dynamic programming 动态规划 dynamic property 动⼒特性 dynamic resistance 动态阻⼒ dynamic response 动态响应 dynamic rigidity 动态刚性 dynamic sensitivity 动态灵敏度 dynamic similarity 动⼒相似 dynamic simulation 动态模拟 dynamic specific speed 动⼒⽐速 dynamic spring constant 动态弹簧常数 dynamic stability 动⼒稳定度 dynamic strain 动应变 dynamic strength 动⼒强度 dynamic stress 动应⼒ dynamic superplasticity 动态超塑性 dynamic system of units 动⼒学单位制 dynamic temperature coefficient 动态温度系数 dynamic temperature difference 动态温差 dynamic test 动⼒试验 dynamic unbalance 动态不平衡 dynamic viscosity 动⼒粘性 dynamical balancing 动⼒平衡 dynamical depth 动⼒深度 dynamical equation of state 动态⽅程 dynamical force 动⼒ dynamical friction 动摩擦 dynamical similarity 动⼒学相似 dynamical system 动⼒系统 dynamical theory of tide 潮汐动⼒学理论 dynamical time ⼒学时 dynamical variables 动⼒学变量 dynamics 动⼒学 dynamometamorphism 动⼒变质酌 dynamometer 测⼒计 dynamometer car 测⼒试验车 dyne 达因。
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铁路网络阻塞问题优化建模——流量路由问题说明书

5th International Conference on Civil Engineering and Transportation (ICCET 2015)Railway Network Blocking Problem: An Optimization ModelingFormulation about Flow Routing ProblemHongpeng Ma1, a, Yixiang Yue2, b* and Congli Hao3, c1 School of Traffic and Transportation, Beijing Jiaotong University, Beijing 100044, China2 School of Traffic and Transportation, Beijing Jiaotong University, Beijing 100044, China3 School of Traffic and Transportation, Beijing Jiaotong University, Beijing 100044, Chinaa*****************.cn,b********************,c*****************.cn Keywords: Railroad; Road Network; Blocking Problem; OptimizationAbstract:In this paper, we mainly study on modeling formulation for railway network blocking problem. We propose model formulation for RBP. The objective function of RBP model is to minimize the costs of flow traveling and delay for the train in marshalling station, by deciding which block is built and specifying the assignment of commodities to these blocks, while observing limits on the reclassification capacity at each terminal. The model is solved using GAMS. The model is tested on a real-world railway network located in North of China, the computation results show that the model have the potential to apply and can yield the dramatic railroad’s operating costs saving. IntroductionThe Railway Blocking Problem (RBP) determines how to aggregate a large number of shipments into blocks of shipments as they travel from origins to destinations [1]. In other words, RBP determines which blocks should be built at each yard and what shipments should be placed in the block.Mathematically, RBP is a multi-commodity-flow, network-design, and routing problem. To solve RBP, we need to design the underlying blocking network and to route different commodities on the blocking network to minimize the transportation costs [2]. In RBP, each train will be assigned to a direct block, whose OD is the same as that of the shipment, to avoid unnecessary marshalling and delays. So there are some directed arcs between two terminals that are not necessarily connected by a physical link. However, blocking capacity at each yard, determined by available yard resources (hump yard equipment and shunting yard equipment), limits the maximum number of blocks and maximum car volume that each yard can handle, preventing railroads from assigning direct blocks for all trains. So aiming at delivering the flow with the fewest possible classifications, railroads develop RBP determining which blocks should be built at each yard and what shipments should be placed in each block [3, 4, 5, 6].RBP is one of the most important decision in freight railroads. A good solution of RBP can save railway operation costs of delivering all commodities. And these costs are usually broken down into car-handling costs associated with handling (or blocking) a car and car-miles costs associated with the movement of a car.There are some study about blocking problem of single railway line, Xu [7] proposed a 0-1 programming with the target of minimum balanced using of adaptation capacity and hour of freight train in marshalling station. And Yang [8] proposed 0-1 linear programming model and 0-1 quadratic program model.Compared with single railway line, the reality railroad network is much complicated. For example, number of transport plan about blocking problem in single line railroad is 1048576, but in railway network, the number may be million, even billion. So for complicated railroad network blocking problem, there are very few study in the field. Li [9] proposed Chance Constrained Programming with considering flow, assembly time and volatility of vehicle adaptation extra time consuming. Newton [10] and Newton et al. [11] modeled the blocking problem as a network-design model and formulated it as a MIP. Bodin [12] established Nonlinear Mixed Integer Programming model with the target ofminimum total cost of adaptation and transport, and proposed heuristic decomposition method. Yaghini [13] and Yue [14] proposed Ant Colony Optimization Algorithm to solve the railroad blocking problem.Their approaches focus on determining a near-optimal solution. However, many models only solve blocking problem of single railway network, such as 0-1 linear programming model. And the approaches for RBP can’t guarantee to get optimal solution in any case without considering factors, such as, empty car, flow pathway and service level. So it is very necessary to develop optimization modeling formulation of RBP. Model and Solution MethodNotation. i, j, n, k, q is macroscopic node index. And i, j, n correspond to physical marshalling station in a railway network. k is origin station of commodity and q is destination station of commodity in a railway network. ,i j c is flow transport cost between each pair OD(from station i to station j ), is proportional to mileage between the pair OD. ,i j c can be calculated by any empirical formula according to statistical curve fitting. Conversion coefficient that changing car-hour delay to cost is p, and the value of p is 80 in this study. ,i j m is accumulation delay when the directed block to station j is built in station i . The empirical formulation is shown as equation (1).,,i j i i j m s α=⨯ (1) Where i αis accumulation parameter of marshalling station i , it is a constant derived from statistical analysis by many years record data. ,i j s is number of cars for one train from station i to station j . i t is the save time of car passing station i without reclassification. ,i j u is re-classification capacity from station i to direction j . ,k q d is demand from station k to station q . M is a large number. ,i j b is directed-block index as equation (2).,there is directed block from station to statio 1,0otherwisen i j i j b i j ⎧=∀⎨⎩ (2)There are two decision variables: ,,,i j k q x and ,i j y . ,,,i j k q x is volume from station k to station q shipped using train from station i to station j . ,i j y is 0-1 binary variables as equation (3). ,there is train from station to station 1,0otherwisei j i j j y i ⎧=∀⎨⎩ (3)Formulation of RBP Model. The objective function of RBP model is to minimize the costs of flow traveling and delay for the train in marshalling stations, by deciding which block is built and specifying the assignment of commodities to these blocks, while observing limits on reclassification capacity at each terminal.The formulation of RBP is as follow.,,,,,,,,,,,,,,,,[()]i j k q i j i j i j i j j i j k q k j i j k qi jji k qkz min x c p m y b t x d =⨯+⨯⨯⨯+⨯-∑∑∑∑∑∑ (4)Subject to,,,,,,,i j k q k j j ki qx d u j k -≤∀∑ (5),,,,,,i j k qk qjxd i k q i k =∀=∑, (6),,,,,,,i j k qk qixd j k q j q =∀=∑ (7),,,,,,0,,,,i j k qn i k q jnxx i k q i q i k -=∀≠≠∑∑ (8),,,,,,,i j k q i jx My i j k q ≤∀ (9),,,0,,,i j k q x i j k q ≥∀ (10)The objective function of RBP model is to minimize the total cost consists of flow transport cost in railroad and delay in marshalling station. Constraint (5) is the hard constraint of reclassification capacity of the number of blocking cars satisfied reclassification capacity in every marshalling station. Constraint (6)、(7) and (8) is flow balance constraint. Constraint (9) ensures that if there is no train from station i to station j , volume from station k to station q shipped by train from station i to station j must be zero, which means if ,=0i j y , there is that ,,,=0i j k q x . Real World Case StudyRailway Network. Based on eight marshalling stations, the railroad network of North China is constructed to calculate as in Fig. 1. All intermediate stations isn’t shown in Fig. 1.Fig. 1.Case of railroad networkThe real world data collected is shown in Table 1, Table 2, Table 3 and Table 4. Station 2 is the center of railway network with five convergence directions, so accumulation delay of station 2 is detailed in Table 2.arrival leave 1 2 3 4 5 6 7 81 0 84 389 832 324 292 693 609 2 84 0 355 798 290 258 659 575 3 389 355 0 1103 465 563 964 874 4 832 798 1103 0 1038 1006 1407 1323 5 324 290 465 1038 0 430 831 536 6 292 258 563 1006 430 0 451 367 7 704 659 964 1537 831 451 0 402 8 609 575 874 1323 536 367 402 0Table 1. Flow transport cost between each pair OD [$/car] departure 1 3 4 5 6 7 8Number of cars of one train of station B[car] 49.3 49.3 52.6 42 41.8 50.5 52.3 Accumulation Parameter of station B[h/car] 9.1 10.1 8.2 9 9.3 10.6 4.1Accumulation delay of station B[h] 449 498 431 378 389 535 215Table 2. Accumulation delay of station 2 station 1 3 4 5 6 7 8Accumulation delay of other stations[h] 550 550 636 600 500 530 530Table 3. Accumulation delay of other marshalling stations station 1 2 3 4 5 6 7 8 t i [h/car] 3 2.9 4 4.7 3 3 4 4reclassificationcapacity[car]Station 2 321 - 651 1110 39 1125 1125 1125Station 6 1125 1125 1125 1125 88 - 700 1100Station 5 500 500 500 500 - 500 500 30 Model Testing and Result Analysis. We use General Algebraic Modeling System (GAMS) [15] to solve MIP model of RBP. And calculation time of RBP solved by GAMS are 30 seconds.To verify feasibility of model of RBP, we solve respectively the RBP with real flow data in 2013 and 2014. And the traffic demand between of each pair OD in 2013 and 2014 is shown in Table 5 and Table 6.Arrival leave 1 2 3 4 5 6 7 81 0 190 70 125 110 10 20 252 150 0 245 20 24 300 153 385 3 272 442 0 160 17 140 130 294 85 405 150 0 9 135 50 185 5 59 140 4 3 0 4 3 06 15 35 230 120 40 0 50 327 11 221 282 138 26 31 0 0 8 40 30 50 490 4 57 0 0 Table 5. Traffic demand between each pair OD in 2013 [car]Arrival leave 1 2 3 4 5 6 7 81 0 190 67 125 106 13 9 342 161 0 231 22 24 315 153 396 3 72 442 0 161 17 131 160 294 89 401 293 0 9 132 49 185 5 59 135 4 3 0 4 3 06 15 36 231 360 40 0 50 327 11 21 282 134 26 30 0 08 38 30 50 505 4 59 0 0 Table 6. Traffic demand between each pair OD in 2014 [car]We use GAMS to solve model of RBP. And the solution is shown in Table 7, Table 8, Table 9 and Table 10.i j k q ,,,i j k q x i j k q ,,,i j k q x i j k q ,,,i j k q x i j k q ,,,i j k q x1 2 1 2 150 2 4 2 4 405 3 2 3 4 150 6 2 6 1 13 1 2 1 4 85 2 4 3 4 150 3 2 3 5 4 6 2 6 2 300 1 2 1 5 59 2 4 5 4 9 3 2 3 8 50 6 2 6 3 140 1 2 1 6 15 2 4 6 4 135 3 6 3 6 230 6 2 6 4 135 1 2 1 7 11 2 4 7 4 50 3 7 3 7 282 6 5 6 5 4 1 2 1 8 40 2 5 1 5 59 4 2 4 1 125 6 5 7 5 3 1 3 1 3 272 2 5 2 5 140 4 2 4 2 20 6 7 5 7 26 2 1 2 1 190 2 5 3 5 4 4 2 4 3 160 6 7 6 7 31 2 1 3 1 70 2 5 4 5 3 4 2 4 5 3 6 8 6 8 57 2 1 4 1 125 2 6 1 6 15 4 6 4 6 120 7 2 7 1 20 2 1 5 1 14 2 6 2 6 35 4 6 4 7 134 7 2 7 2 153 2 1 6 1 13 2 6 4 6 120 4 8 4 8 490 7 2 7 3 130 2 1 7 1 20 2 7 1 7 11 5 1 5 1 96 7 2 7 4 50 21 8 12527 2 722152 5 11476 7 53i j k q ,,,i j k q x i j k q ,,,i j k q x i j k q ,,,i j k q x i j k q ,,,i j k q x 2 3 2 3 442 2 7 4 7 134 5 2 5 2 24 7 6 7 6 50 2 3 4 3 160 2 8 1 8 40 5 2 5 3 17 8 2 8 1 25 2 3 5 3 17 2 8 2 8 30 5 2 5 4 9 8 2 8 2 385 2 3 6 3 140 2 8 3 8 50 5 6 5 6 40 8 2 8 3 29 2 3 7 3 130 3 2 3 1 70 5 6 5 7 26 8 4 8 4 185 2 3 8 3 29 3 2 3 2 245 5 8 5 8 4 8 6 8 6 32 24 1 4 85 - - - - - - - - - - - - - - - Table 7. The Solution of RBP for variable ,,,i j k q x with real flow OD in 2013i j 1 2 3 4 5 6 7 81 0 1 1 0 0 0 0 02 1 0 1 1 1 1 1 13 0 1 0 0 0 1 1 04 0 1 0 0 0 0 0 15 1 1 0 0 0 1 0 16 0 1 0 0 1 0 1 17 0 1 0 0 0 1 0 08 0 1 0 1 0 1 0 0 Table 8. The solution of RBP for variable ,i j y with real flow OD in 2013The objective function value is:2013$5107135z = (11)i j k q ,,,i j k q x i j k q ,,,i j k q x i j k q ,,,i j k q x i j k q ,,,i j k q x 1 2 1 2 161 2 4 2 4 401 3 6 3 6 231 6 2 6 4 132 1 2 1 3 72 2 4 5 4 9 3 7 3 7 282 6 5 6 5 4 1 2 1 4 89 2 4 6 4 132 4 2 4 1 125 6 5 7 5 3 1 2 1 5 59 2 4 7 4 49 4 2 4 2 22 6 7 1 7 11 1 2 1 6 15 2 5 1 5 59 4 2 4 3 161 6 7 2 7 21 1 2 1 7 11 2 5 2 5 135 4 2 4 5 3 6 7 4 7 134 1 2 1 8 38 2 5 3 5 4 4 6 4 6 360 6 7 5 7 26 2 1 2 1 190 2 5 4 5 3 4 6 4 7 134 6 7 6 7 30 2 1 3 1 67 2 6 1 6 15 4 8 4 8 505 6 8 6 8 59 2 1 4 1 125 2 6 1 7 11 5 1 5 1 93 7 2 7 1 9 2 1 5 1 13 2 6 2 6 36 5 2 5 1 13 7 2 7 2 153 2 1 6 1 13 2 6 2 7 21 5 2 5 2 24 7 2 7 4 49 2 1 7 1 9 2 8 1 8 38 5 2 5 3 17 7 3 7 3 160 2 1 8 1 34 2 8 2 8 30 5 2 5 4 9 7 6 7 5 3 2 3 1 3 72 2 8 3 8 50 5 6 5 6 40 7 6 7 6 50 2 3 2 3 442 3 2 3 1 67 5 6 5 7 26 8 2 8 1 34 2 3 4 3 161 3 2 3 2 231 5 8 5 8 4 8 2 8 2 396 2 3 5 3 17 3 2 3 5 4 6 2 6 1 13 8 2 8 3 29 2 3 6 3 131 3 2 3 8 50 6 2 6 2 315 8 4 8 4 185 2 3 8 3 29 3 4 3 4 293 6 2 6 3 131 8 6 8 6 32 2 41 4 89 - - - - - - - - - - - - - - -Table 9.The solution of RBP for variable ,,,i j k q x with real flow OD in 2014 i j 1 2 3 4 5 6 7 81 0 1 0 0 0 0 0 02 1 0 1 1 1 1 0 1 i j 1 234567 83 0 1 0 1 0 1 1 04 0 1 0 0 0 1 0 15 1 1 0 0 0 1 0 16 0 1 0 0 1 0 1 17 0 1 1 0 0 1 0 08 0 1 0 1 0 1 0 0 Table 10. The solution of RBP for variable ,i j y with real flow OD in 2014The objective function value is:2014$5496920z = (12)To verify intuitively feasibility of model, we compare the solution of RBP in 2013 with the solution of RBP in 2014 in Fig. 2. And there are only directed train in Fig. 2.There is a directed train between two stationsPhysical Railway NetworkSolution of RBP in 2014Solution of RBP in 2013StationFig. 2. The solution comparisonComparing the solution of RBP in 2013 and 2014, the feasibility of the model can be verified from the following aspects:1. Some directed trains are canceled.If there are the loss of car-hours and cost, the directed train will be canceled. For example, there are 221 cars per day from station 2 to station 7 in 2013. But there are only 21 cars per day. Because of fewer flow, the directed train will cause the loss of car-hours and cost. So the directed train from station 2 to station 7 is canceled. 2. Some directed trains are built.If the directed block can save car-hours and cost, the directed trains will be built. For example, there are 150 cars per day from station 3 to station 4 in 2013. But there are only 293 cars per day. Because of more flow, the directed train will cause the save of car-hours and cost. So the directed train from 3 to 4 is built.The objective function of RBP model is to minimize the costs of flow traveling and delay for the train in marshalling station. So we need compare the solution with the now using RBP solution in 2014 to verify optimization of model.The flow of transit car with resorting and transit car without resorting of station 2 in 2014 is shown in Table 11 and Table 12.Arrival leave 1 3 4 5 6 7 81 0 32 72 7 9 6 23 3 47 0 61 13 36 43 84 28 79 05 46 17 66 5 5 1 2 0 1 0 0 6 1 19 135 2 0 0 2 7 7 31 52 2 1 0 08 6 1 215 2 1 0 0 Table 11. The flow of transit car with resorting in 2014 [car]Arrival leave 1 2 3 4 5 6 7 81 0 190 35 53 99 4 3 112 161 0 231 22 24 315 153 396 3 25 442 0 1004 95 117 21 4 61 401 214 0 4 86 32 119 5 54 135 3 1 0 3 3 0 6 14 36 212 225 38 0 50 307 4 21 251 82 24 29 0 08 32 30 49 290 2 58 0 0 Table 12. The flow of transit car without resorting in 2014 [car]And the objective function value of real-world in the condition of the same parameters isz (13) $6527430actualCompared with the now using RBP solution in 2014, the optimization of the model can be verified from the following aspects:1. Some directed trains are canceled.The new solution deletes 25 directed trains, saves total 9005 car-hours per day. For example, there are 13 cars per day from station 6 to station 1. Because of a directed block for the flow, there are 500 car-hours about car detention time under accumulation and 38 car-hours of the save time because of transit car without reclassification per day. The directed train from station 6 to station 1 causes the loss of 400 car-hours per day.2. Volume shipped by directed trains are added.The new solution adds volume shipped by directed trains, saves total 3538 car-hours per day.3. Cost Saving.The objective function value of formulation of RBP model is 5496920. And the objective function value of real-world in the condition of the same parameters is 6527430. Total cost saving is 1030510.4. Traffic flow adjustments.The solution considers the balance of railway line. And some flows in busy railway line are adjusted to other rail lines to improve whole network efficiency. Such as, in existing RBP solution in 2014, the flow from station 5 to station 6 pass station 2 with reclassification operation. But in solution of RBP model, a directed block between station 5 and station 6 is built to make full use of railway between station 5 and station 6.ConclusionsThis paper mainly focuses on Railway Blocking Problem in a network. We consider both transport cost and delay on marshaling station; and use GAMS to solve it. We give a case of 8 marshaling stations to test the model on the real world data. In the case, solution by our method can decrease 55% of car-hours and 16% of cost per day. In the meantime, we can optimize traffic flow to improve efficiency of the whole network. It is sure that our proposed models are effective, efficient and potential for application in a real world railway network.References[1] M Yaghini, et.al. Solving railroad blocking problem using ant colony optimization algorithm [J]. Applied Mathematical Modelling, 35(2011) 5579-5591.[2] R.K. Ahuja, et.al. Solving Real-Life Railroad Blocking Problems [J]. Interfaces, 37(2007) 404-419.[3] M Yaghinia and R Akhavan. Multicommodity Network Design Problem in Rail Freight Transportation Planning [J]. Procedia - Social and Behavioral Sciences, 43(2012) 728-739.[4] C Barnhart, et.al. Railroad Blocking: A Network Design Application [J]. Operations Research, 48(2000) 603-614.[5] Ahuja, et.al. Network Models in Railroad planning and scheduling [J]. Operation Research, 1(2005) 54-101.[6] A Balakrishnan, et.al. A Dual-ascent Procedure for Large-scale Uncapacitated Network Design [J]. Operations Research, 73(1989) 716-740.[7] H.Xu, et al. Study on the Model and Algorithm of the Formation Plan of Single Group Trains at Technical Service Stations (In Chinese) [J]. Journal of the China Railway Society, 28(2006) 12-17.[8] S.Yang, et al. An Artificial Neural Network Method for Marshalling Plan (In Chinese) [J]. Journal of Changsha Railway University, 20(2002) 79-84.[9] X.Li. Study on Optimization of Marshalling Plan and Flow Path Based on Uncertain Parameters (In Chinese) [D]. Southwest Jiaotong University, 2002.[10] H.N. Newton. Network Design under Budget Constraints with Application to the Railroad Blocking Problem [D]. Auburn University, 1996.[11] H.N. Newton, et.al. Constructing Railroad Blocking Plans to Minimize Handling Costs [J]. Transportation Science, 32(1998) 330-345.[12] L.Bodin, et.al. A Model for the Blocking of Trains [J]. Transportation Research Part B Methodological, 14(1980) 115-120.[13] M.Yaghini, et.al. Solving Railroad Blocking Problem Using Ant Colony Optimization Algorithm [J]. Applied Mathematical Modelling, 35(2011) 5579-5591.[14] Y.Yue, et.al. Multi-route Railroad Blocking Problem by Improved Model and Ant Colony Algorithm Real World [J]. Computers & Industrial Engineering, 60(2011) 34-42.[15] A.Brooke, et.al. GAMS Language Guide. 2006.。
Acta Biochim Biophys Sin-2012-Ma-948-56

Original ArticleA new recombinant pituitary adenylate cyclase-activating peptide-derived peptide efficiently promotes glucose uptake and glucose-dependent insulin secretionYi Ma,Tianjie Luo,Wenna Xu,Zulu Ye,and An Hong*Department of Cell Biology,Institute of Biological Medicine,Jinan University,Guangzhou510632,China*Correspondence address.Tel:þ86-20-85223266;Fax:þ86-20-85221983;E-mail:makesi8866@The recombinant peptide,DBAYL,a promising thera-peutic peptide for type2diabetes,is a new,potent,and highly selective agonist for VPAC2generated through site-directed mutagenesis based on sequence alignments of pi-tuitary adenylate cyclase-activating peptide(PACAP), vasoactive intestinal peptide(VIP),and related analogs. The recombinant DBAYL was used to evaluate its effect and mechanism in blood glucose metabolism and utiliza-tion.As much as28.9mg recombinant DBAYL peptide with purity over98%can be obtained from1l of Luria-Bertani medium culture by the method established in this study and the prepared DBAYL with four mutations (N10Q,V18L,N29Q,and M added to the N-terminal) were much more stable than BAY55-9837.The half-life of recombinant DBAYL was about25folds compared with that of BAY55-9837in vitro.The bioactivity assay of DBAYL showed that it displaced[125I]PACAP38and [125I]VIP from VPAC2with a half-maximal inhibitory concentration of48.4+6.9and47.1+4.9nM,respective-ly,which were significantly lower than that of BAY55-9837,one established VPAC2agonists.DBAYL enhances the cAMP accumulation in CHO cells expressing human VPAC2with a half-maximal stimulatory concentration (EC50)of0.68nM,whereas the receptor potency of DBAYL at human VPAC1(EC50of737nM)was only1/1083 of that at human VPAC2,and DBAYL had no activity toward human PAC1receptor.Western blot analysis of the key proteins of insulin receptor signaling pathway:insulin re-ceptor substrate1(IRS-1)and glucose transporter4 (GLUT4)indicated that the DBAYL could significantly induce the insulin-stimulated IRS-1and GLUT4expression more efficiently than BAY55-9837and VIP in adipocytes. Compared with BAY55-9837and PACAP38,the recombinant peptide DBAYL can more efficiently promote insulin release and decrease plasma glucose level in Institute of Cancer Research(ICR)mice.These results suggested that DBAYL could efficiently improve glucose uptake and glucose-depend-ent insulin secretion by VPAC2-mediated effect.Keywords pituitary adenylate cyclase-activating peptide; type2diabetes;insulin;VPAC2-mediated effect;recombinant peptideReceived:June29,2012Accepted:August6,2012 IntroductionPituitary adenylate cyclase-activating polypeptide(PACAP) is a member of the superfamily of metabolic,neuroendo-crine,and neurotransmitter peptide hormones and belongs to the secretin,glucagons,and vasoactive intestinal peptide (VIP)family[1,2].PACAP exists as either a38-amino acid (PACAP38)or27-amino acid(PACAP27)peptide. PACAP27corresponds to the N-terminal27-amino acid portion of PACAP38and exhibits the same biological activ-ity as PACAP38[3,4].The action of PACAP is mediated through three G protein-coupled receptors,PAC1,VPAC1, and VPAC2.PAC1receptor exhibits high affinity for PACAP38and PACAP27,but much lower affinity for VIP. VPAC1and VPAC2receptors exhibit similar high affinity for PACAP38,PACAP27,and VIP[5].PACAP is widely distributed in the brain and peripheral organs,notably in the endocrine pancreas,gonads,respiratory,and urogenital tracts,which has been shown to have effects on many pathological states including Parkinson’s disease[6],dia-betes[7,8],ischemia[9],traumatic injury[10],immuno-logical disorders[11,12],myeloma kidney injury,and so on [13].Most of these neuroprotective actions of PACAP are mediated through the selective PAC1receptor whereas the effects on peripheral organs often involve VPAC1or VPAC2receptor.PACAP has been shown to increase insulin secretion from the pancreas through VPAC2recep-tor[14,15].But the role of PACAP in the control of glucose homeostasis is complex,because it also plays a role in increasing glucagon and catecholamine secretion,which increases glucose output from the liver through VPAC1-mediated effect[16].Therefore,PACAP derivative asActa Biochim Biophys Sin2012,44:948–956|ªThe Author2012.Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences.DOI:10.1093/abbs/gms078.Acta Biochim Biophys Sin(2012)|Volume44|Issue11|Page948 at Jinan University on November 16, 2014 / Downloaded fromVPAC2-specific agonist,which would stimulate glucose-dependent insulin secretion from pancreatic b-cell without leading to increased glucose production by the liver could be used for clinical treatment of type2diabetes. Development of BAY55-9837,an established highly select-ive VPAC2agonist,as a potential peptide therapeutic for the treatment of type2diabetes was limited by its poor peptide stability[14].To overcome the limitation,the re-combinant peptide DBAYL with32amino acids was designed and generated through site-directed mutagenesis by gene-recombination technology.The recombinant DBAYL (N10Q,V18L,N29Q,and M added to the N-terminal)were much more stable than BAY55-9837.DBAYL enhances the cAMP accumulation in VPAC2-CHO cells with higher bio-activity than BAY55-9837.DBAYL could more efficiently induce the expression of the key proteins of insulin receptor signaling pathway including insulin receptor substrate1 (IRS1)and glucose transporter4(GLUT4)than BAY55-9837in adipocytes[17,18].In addition,DBAYL treatment increased the insulin-stimulated GLUT4translocation to the plasma membrane.Corresponding to these results,glucose uptake activity of differentiated3T3-L1adipocytes treated with DBAYL were significantly improved,which was better than BAY55-9837.Thus,insulin signal transduction was more efficiently improved by DBAYL through VPAC2-mediated effect. DBAYL,a novel recombinant PACAP-derived peptide,as highly selective agonist for VPAC2,can hopefully be a peptide therapeutic for type2diabetes through efficiently promoting glucose uptake and glucose-dependent insulin secretion.Materials and MethodsMaterialsChitin beads and the plasmid pKYB-MCS were purchased from New England Biolabs(NEB,Ipswich,USA). Escherichia coli strain ER2566was kept in our laboratory. All the restriction enzymes were purchased from New England Biolabs.T4DNA ligase was obtained from TaKaRa (Dalian,China).Synthetic peptides were purchased from Sinoasis Pharmaceuticals(Guangzhou,China).Primer syn-thesis and DNA sequencing were performed by Invitrogen Company,Guangzhou Branch(Guangzhou,China).VPAC2-CHO cell line was constructed in our laboratory.3T3-L1 adipocytes were provided by Dr Zhang WJ(College of Life Sciences,Wuhan University,Wuhan,China). Construction and identification of the expression plasmid pKY-DBAYLThe DBAYL gene was designed according to the bias of E.coli for the codons to ensure its high expression.The gene was synthesized and amplified in two steps asdescribed previously[7]using three oligonucleotides primers:F1:50-GGTGGTCATATGCATAGCGATGCGGT GTTTACCGATCAGTATACCCGTCTGCGTAAA-30,con-taining an Nde I site(underlined);F2:50-CAGATATT TTTTCGCCGCCAGCTGTTTACGCAGACGGGT-30;F3:50-CCACCATGCTCTTCCGCAATAACGTTTCTGTTTAA TGCTCTGCAGATATTTTTT-30,containing an Sap I site (underlined);GGTGGT at the50end of F1and CCACCAat the50end of F3are the protecting bases.After polymer-ase chain reaction(PCR)products were purified by thePCR clean-up kit(Qiagen,Hilden,Germany)and digestedwith Nde I and Sap I,the DNA fragment was directly ligatedto a gel-purified Nde I/Sap I digested pKYB-MCS vector (NEB)to yield the expression plasmid pKY-DBAYL.pKY-DBAYL containing DBAYL gene was confirmed byDNA sequencing using the T7promoter as the sequencingprimer(Fig.1).Expression of fusion proteinThe recombinant expression vector pKY-DBAYL was transformed into the E.coli strain ER2566with the opti-mized procedure[19].Briefly,the cells were grown at378Cto a density of OD600¼0.8and induced by adding isopro-pyl b-D-thiogalactoside to a final concentration of0.5mM.Figure1The constructed recombinant expression vectorpKY-DBAYL(A)The amino acid sequence of RBAYL and rBAY.(B)The construction map of the expression plasmid pKY-DBAYL.PACAP-derived peptide promotes glucose uptake and glucose-dependent insulin secretionActa Biochim Biophys Sin(2012)|Volume44|Issue11|Page949at Jinan University on November 16, 2014/Downloaded fromThe induced cells were incubated for6h at358C and col-lected by centrifugation at10,621g for20min.Sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)was used to identify the expression of the fusion protein.The cell pellet was resuspended in buffer A con-taining20mM Tris-HCl(pH8.0),500mM NaCl, and1mM EDTA by gentle shaking for20min,and then disrupted with JN-3000PLUS low-temperature ultra-high-pressure continuous flow cell crusher(JNBIO, Guangzhou,China)at the following conditions:diluted bac-teria concentration of18%by buffer A,crushing pressure of 1700bar and cooling temperature of38C.The lysate was then centrifuged at10,621g for30min at48C and the supernatant was subjected to purification and preparation of target peptide by chitin beads affinity chromatography. Preparation and identification of the recombinant peptide DBAYLThe supernatant(1.5l)was passed through a column (4.5cmÂ20cm)packed with25ml chitin beads at a flow rate of0.5ml/min.After the supernatant was loaded on the column,the flow rate was raised to2ml/min and the column was thoroughly washed with more than10bed volume of buffer A.Then80ml of buffer B containing 20mM Tris-HCl(pH8.0),500mM NaCl,1mM EDTA, and100mM b-mercaptoethanol was then quickly passed through the column to distribute b-mercaptoethanol evenly throughout the resin and the column flow was stopped.The column was incubated at258C for24h.Fractions contain-ing DBAYL were obtained by eluting the column with buffer A.Then the recombinant peptide DBAYL was puri-fied and prepared by reverse-phase high-performance liquid chromatography(HPLC)system using4.6mmÂ150mm 300SB-C18Sep-Pak column(Agilent Technologies, Beijing,China)through gradient elution with increasing concentration of acetonitrile from2%to55%for45min at 1ml/min.The eluate containing DBAYL was dried by ly-ophilization.Prepared DBAYL at a final concentration of 1mg/ml in45%acetonitrile containing0.1%trifluoroacetic acid was analyzed by4000Q TRAP electrospray ionization-mass spectrometry(ESI-MS;Applied Biosystems,Foster City,USA).Peptide concentrations were determined by com-paring the OD280values of peptide stock solutions in the assay buffer with the predicted extinction coefficient[20]. Stability assayDBAYL,BAY55-9837,PACAP38,or VIP at a final concen-tration of1mg/ml in20mM sodium phosphate buffer(pH 8.0)containing150mM sodium chloride were incubated at 378C.At different time points,samples were collected and analyzed by liquid chromatography mass spectrometry,a rapid and sensitive method to detect degradation of polypep-tide in these formulations.A2-ml sample was injected into HPLC-ESI-MS system containing 1.0mmÂ150mm300 SB-C18Sep-Pak(Agilent Technologies,Santa Clara,USA) column and analyzed under the condition of increasing con-centration of acetonitrile from2%to55%for55min at 0.05ml/min by HPLC-ESI-MS system.Competition receptor binding assayThe potential of DBAYL to displace[125I]PACAP38 and[125I]VIP by competitively binding to the human VPAC2receptor was examined in VPAC2-CHO cell mem-brane prepared previously[7].Briefly,10mg of membrane was incubated with0.1nM[125I]PACAP38(Phoenix Pharmaceuticals,Mountain View,USA)or[125I]VIP (PerkinElmer Life and Analytical Sciences,Boston,USA) in the presence of increasing concentrations of DBAYL peptide,in a total volume of100ml of20mM HEPES (pH7.4)containing150mM NaCl,0.5%BSA,2mM MgCl2,and0.1mg/ml bacitracin at378C.After being incu-bated for20min,the membrane was collected on GF/C filters pretreated with0.1%polyethylenimine.The filters were washed with25mM cold Na3PO4containing1% BSA and counted on a gamma counter.Non-specific binding was defined as the residual binding in the presence of1mM recombinant PACAP38(i.e.rPACAP38)or VIP and was always,20%of the total binding.The assay of PACAP38,VIP,and BAY55-9837were taken as the positive controls.[K15,R16,L27]VIP(1–7)/GRF(8–27),a VPAC1-specific agonist,was used as the negative control in the receptor binding assay[21].Each assay was per-formed at least three times.Assay of cAMP accumulation induced by DBAYL Human PACAP receptor-transfected cells,VPAC1-CHO, VPAC2-CHO,and PAC1-CHO cells,cultured in the Dulbecco’s modified Eagle’s medium at378C were scraped off with rubber policeman and washed with PBS twice. The density of the cells was adjusted to2Â106cells/ml. DBAYL or rPACAP38was added to the500-ml cell sus-pension,and the concentrations of the peptide were ranged from1Â10212to1Â1025M.The mixtures were incu-bated at378C for5min,then two volumes of0.2M HCl was added,and the mixtures were incubated at room tem-perature for another20min.Cells were lysed by pipetting up and down until the suspension was homogeneous.The precipitate was removed by centrifugation at225g for 10min,and the supernatant was transferred into test tube and cAMP concentrations were measured by using the cyclic AMP enzyme immunoassay kit(Cayman Chemical Company,Ann Arbor,USA).Western blot analysis of IRS-1and GLUT4induced by DBAYLCell culture and induction of3T3-L1adipocytes were carried out as described previously[22].DifferentiatedPACAP-derived peptide promotes glucose uptake and glucose-dependent insulin secretionActa Biochim Biophys Sin(2012)|Volume44|Issue11|Page950 at Jinan University on November 16, 2014 / Downloaded from3T3-L1adipocytes were incubated with100nM insulin for 20min[23].After being washed twice with PBS buffer, differentiated3T3-L1adipocytes were cultured for48h in medium,respectively,containing0and1m M of DBAYL, BAY55-9837or VIP.Then the total protein was extracted. After the total protein was separated by12%SDS-PAGE and transferred onto poly(vinylidene difluoride)membranes (Immobilon P;Millipore,Billerica,USA),the membranes were incubated with the IRS-1rabbit mAb(Cell Signaling Technology,Boston,USA)or anti-GLUT4antibody(Santa Cruz Biotechnology,Santa Cruz,USA)for2h at room temperature.The horseradish peroxide(HRP)-conjugated goat-anti-rabbit IgG(Immunology Consultants Laboratory, Portland,USA)or sheep-anti-mouse HRP-IgG(BioFX Laboratories,Owings Mills,USA)was used as the second antibody.Protein bands were visualized by using an ECL kit(Santa Cruz Biotechnology)and densitometric analysis of the results of western blot was performed with image analysis software[24].To evaluate the effect of DBAYL on GLUT4translocat-ing to the plasma membrane,differentiated3T3-L1adipo-cytes were incubated with100nM insulin for20min.After being washed twice with PBS buffer,differentiated3T3-L1 adipocytes were cultured for48h in medium containing 1m M of DBAYL.Another experiment group that differen-tiated3T3-L1adipocytes were cultured for48h in medium containing1m M of DBAYL without insulin treatment to determine whether the manner of the DBAYL effect on GLUT4translocating to the plasma membrane is insulin-dependent or non-insulin-dependent.Then plasma membrane lawns were prepared by sonic-ation as described previously[25].GLUT4contents of the plasma membrane lawns were determined by immunoblot-ting using anti-GLUT4antibody performed with an ECL kit. Effect of DBAYL on glucose uptake activity Differentiated3T3-L1adipocytes were incubated with 100nM insulin for20min[23].After being washed twice with PBS buffer,the3T3-L1adipocytes were cultured for 48h in medium,respectively,containing0,1,and5m M of DBAYL or BAY55-9837.The glucose level of the cell culture supernatants was determined with Glucose assay kit-glucose oxidase method(Applygen Technologies Inc., Beijing,China).Effect of DBAYL on insulin release and glucose disposal in ICR miceEighteen male ICR mice weighing25–30g were housed at room temperature on a12/12h light/dark cycle.ICR mice fasted over-night(12h)and were randomly divided into three groups according to their weight(six per group).The prepared DBAYL(0.5m g/kg)that is dissolved in the normal saline was intraperitoneally injected into the ICRmice and10min later,glucose dissolved in distilled water(2g/kg)was given to ICR mice by gavage.The experimen-tal groups with the same dose or volume of BAY55-9837and rPACAP38were as positive controls and the groupswith normal saline as a negative control.At15min after gavage,blood samples were collected from the tail vein andthe plasma glucose levels were determined using OneTouchUltra Meter(Johnson&Johnson,Johnson,USA)and the plasma insulin was measured using RIA kit(Linco Research,Charles,USA)in the First Affiliated Hospital ofJinan University(Guangzhou,China).ResultsExpression and preparation for DBAYLThe fusion proteins consisting of target peptide-,intein-and chitin-binding domain(i.e.DBAYL-intein-CBD)were expressed through a recombinant peptide expression vector,pKY-DBAYL,in E.coli strain ER2566.The fusion pro-teins were purified using chitin affinity column.The cleav-age of intein was induced by b-mercaptoethanol and thetarget peptide,DBAYL was released.Then the recombin-ant peptide DBAYL was further purified and prepared by reverse phase HPLC system.About28.9mg of recombin-ant DBAYL peptide over98%of purity can be obtainedfrom1l of Luria-Bertani medium.The prepared DBAYLwas analyzed and identified by ESI-MS.Figure2 showed that the molecular weight of DBAYL fromESI-MS was3916.6Da,which was consistent with the theoretical value(3916.5Da).The purity of prepared DBAYL was over98%by the analytical HPLC determin-ation method.Peptide stability improved by site-directed mutagenesisThe recombinant DBAYL was tested together withBAY55-9837,PACAP38,and VIP for stability at378C in20mM sodium phosphate buffer(pH8.0)containing150mM sodium chloride.After4weeks at378C,the main peptide peaks for BAY55-9837,PACAP38,and VIP were remarkably diminished and the slower migrating peak emerged,probably as a result of peptide degradation.Onthe other hand,DBAYL exhibited dramatic improvementin stability,losing only7.7%of the main peak.The sta-bility data in4weeks showed that the half-life of recom-binant DBAYL was about25folds compared with that ofBAY55-9837in vitro,and the half-life of wild-type PACAP38and VIP is slightly shorter than the BAY55-9837in vitro(Fig.3).DBAY L selectively binding to VPAC2receptorHuman VPAC2receptor-transfected cells,and VPAC2-CHO cells,were used for competition receptor binding petition binding of[125I]PACAP38or[125I]VIPPACAP-derived peptide promotes glucose uptake and glucose-dependent insulin secretionActa Biochim Biophys Sin(2012)|Volume44|Issue11|Page951at Jinan University on November 16, 2014/Downloaded fromon membranes purified from CHO cells identified DBAYL as a VPAC2-selective peptide (Fig.4).DBAYL competi-tively displaced [125I]PACAP38from VPAC2,with a half-maximal inhibitory concentration (IC50)of 48.4+6.9nM,and the IC50of the recombinant PACAP38,VIP,and BAY55-9837were 18.1+5.3,21.2+4.0,and 68.3+8.1nM,respectively [Fig.4(A)].DBAYL competitively displaced [125I]VIP from VPAC2with an IC50of 47.1+4.9nM,and the IC50for rPACAP38,VIP,and BAY55-9837at human VPAC2were 19.7+4.9,18.0+2.6,and 70.3+3.7nM,respectively [Fig.4(B)].Whereas the IC50for VIP(1–7)/GRF(8–27),an established human VPAC1-specific agonist,at human VPAC2was over 20m M.These results showed that DBAYL could competi-tively displace [125I]PACAP38and [125I]VIP by binding to human VPAC2receptor in VPAC2-CHO cells.In two com-petition receptor-binding experiments,the IC50of DBAYL was significantly lower than that of BAY55-9837,the established VPAC2-specific agonist.Receptor potency of DBAYL at PACAP receptors subtypesThe accumulation of cAMP in human PACAP receptor-transfected cells (VPAC1-CHO,VPAC2-CHO,andPAC1-Figure 2The ESI-MS of the prepared recombinant DBAYL Prepared DBAYL at 1mg/ml in 45%acetonitrile containing 0.1%TFA was analyzedby electrospray ionization time-of-flight massspectrometry.Figure 3Stability analysis of peptides at 1mg/ml in aqueous solution during incubation at 378C Sample (2-ml)was injected into HPLC-ESI-MS system and analyzed under the condition of increasing concentration of acetonitrile from 2%to 55%for 55min at 0.05ml/min.PACAP-derived peptide promotes glucose uptake and glucose-dependent insulin secretionActa Biochim Biophys Sin (2012)|Volume 44|Issue 11|Page 952at Jinan University on November 16, 2014/Downloaded fromCHO cells)was used as an index of the agonist activity.DBAYL was a potent agonist for the VPAC2receptor with a half-maximal stimulatory concentration (EC50)of 0.68nM.However,the receptor potency of DBAYL at human VPAC1(EC50of 737nM;Fig.5)was only 1/1083of that at human VPAC2,and DBAYL had no activity toward human PAC1receptor.Three receptors subtypes are both activated by rPACAP38.rPACAP38was a potent agonist at human PAC1with an EC50of 0.57nM,and the EC50for rPACAP38at human VPAC1and VPAC2receptor were 0.97and 0.99nM,respect-ively (Fig.5).These results showed that DBAYL was a VPAC2-spcific agonist with high potency and bioactivity,whereas rPACAP38could active human PAC1,VPAC1,and VPAC2receptor with different affinity.In vitro effects of DBAYL on the key proteins in insulin receptor signaling pathwayThe expression levels of IRS1,a key and essential protein for insulin signal transduction and GLUT4,an important rate-limiting factor of the glucose transport,were signifi-cantly increased in differentiated 3T3-L1adipocytes treated with DBAYL.Figure 6(A)showed that the insulin-stimulated IRS1and GLUT4expression levels in differentiated 3T3-L1adipo-cytes treated with DBAYL were 3.1and 2.9folds,respect-ively,of that in blank control group without DBAYL treatment.The effects of increasing IRS1and GLUT4ex-pression by DBAYL were significantly stronger than VIP and BAY55-9837.Simultaneously,GLUT4of translocating to the plasma membrane was significantly increased in differentiated 3T3-L1adipocytes treated with DBAYL.Figure 6(B)Figure 5Induced cAMP accumulation by DBAYL or PACAP38in CHO-VPAC2,CHO-VPAC1,and CHO-PAC1cells Results are expressed as the percentage of maximum cAMP accumulation by PACAP38.Data are the mean of three separateexperiments.Figure 6Effect of DBAYL on IRS-1and GLUT4protein expression (A)and GLUT4translocation (B)in 3T3-L1adipocytes Results of changes of GLUT4level by densitometric analysis.2,control group;þ,positive group;P ,0.01,(A):DBAYL(þ)group compared with DBAYL(2)group;(B):DBAYL(þ)/Insulin(þ)group compared with DBAYL(2)/Insulin(2)group;P ,0.05,(A):DBAYL(þ)group compared with BAY55-9837(þ)group or VIP(þ)group;(B):DBAYL(þ)/Insulin(2)group compared with DBAYL(2)/Insulin(2)group;DBAYL(þ)/Insulin(þ)group compared with DBAYL(2)/Insulin(þ)group.Figure 4Displacement of [125I]PACAP38(A)or [125I]VIP (B)by DBAYL,rPACAP38,VIP,BAY55-9837,and VIP(1–7)/GRF(8–27)in membranes purified from CHO cells expressing human VPAC2The results are expressed as percentage of maximum binding to [125I]PACAP38or [125I]VIP.PACAP-derived peptide promotes glucose uptake and glucose-dependent insulin secretionActa Biochim Biophys Sin (2012)|Volume 44|Issue 11|Page 953at Jinan University on November 16, 2014/Downloaded fromshowed that DBAYL treatment and combined treatment of insulin plus DBAYL significantly increased the GLUT4translocation to the plasma membrane by 51%,which was agreed well with the glucose uptake results.Lower doses of insulin could also increase GLUT4translocation,and com-bined treatment of insulin plus DBAYL could more effect-ively promote GLUT4translocation to the plasma membrane.As a VPAC2-specific agonist,DBAYL may sig-nificantly increase the GLUT4translocation to the plasma membrane in a non-insulin-dependent manner,and DBAYL had the biological synergistic effect with insulin on GLUT4translocation.DBAYL promoted glucose uptake activity of differentiated 3T3-L1adipocytesGlucose uptake activity of differentiated 3T3-L1adipocytes treated with different concentrations of DBAYL was all sig-nificantly improved in different degrees.Figure 7showed that 1and 5m M of DBAYL increased glucose uptake of differen-tiated 3T3-L1adipocytes by 43%and 49%,respectively.Improvement effect of DBAYL was better than BAY55-9837at the same concentration.As shown in Fig.7,1and 5m M of BAY55-9837increased glucose uptake of differ-entiated 3T3-L1adipocytes by 16%and 34%,respectively.In vivo effects of DBAYL on insulin release and glucose disposal in ICR miceAs shown in Table 1,compared with normal saline group,recombinant DBAYL (0.5m g/kg)obviously promoted the insulin release and decreased the level of plasma glucose after giving glucose by gavage in ICR mice.Furthermore,the results showed that the biological effects of DBAYL were significantly better than BAY55-9837and rPACAP38.Because of acting on three receptors subtypes,rPACAP38can not effectively decreased the plasma glucose level of ICR mice after glucose gavage.DiscussionAt present,the main approach to treat type 2diabetes is to maintain euglycemia through administration of sulfonylurea drugs that increase insulin levels or by injecting insulin itself.Both therapies produce significant bouts of hypoglycemia,because their onset of action is independent of the prevailing level of glucose.New therapies that retain or enhance glucose-dependent insulin secretion would be a significant advance,since they would avoid the risk of hypoglycemia.PACAP could activate both VPAC1and VPAC2.VPAC2activation enhances glucose disposal by stimulating insulin secretion while VPAC1activation elevates hepatic glucose output [26].Wild-type PACAP could not effective-ly lower blood sugar in vivo because the increase in glucose production may offset the increase in insulin secre-tion.Therefore,clinical treatment of diabetes requires a VPAC2-specific agonist that would enhance pancreatic b cell insulin release without causing increased glucose pro-duction [27].VPAC2-specific agonists such as BAY55-9837,Ro25-1553,and hexanoyl-VIP (C6-VIP)produced by chemical synthesis have been demonstrated to induce insulin secretion from b cells in a glucose-dependent manner [28].In this report,we provide a novel gene recombinant PACAP-derived peptide that is a VPAC2-specific agonist with high stability.Our previous studies had shown that BAY55-9837and some other polypeptides had potential in-stability due to either oxidation or deamidation because of several certain amino acid composition [7,19].Stability ana-lysis showed that the prepared DBAYL with four mutations (N10Q,V18L,N29Q,and M added to the N-terminus)were much more stable than BAY55-9837,wild-type PACAP,and VIP.DBAYL lost only 7.7%of the main peak during the 4-week incubation at 378C,and the half-life of DBAYL was about 25folds compared with that of BAY55-9837in vitro .Compared with three previously studied VPAC2agonists,BAY55-9837,hexanoyl-VIP (C6-VIP),and Ro 25-1553[14,18],or wild-type PACAP and VIP,there was one methio-nine at the N-terminus of the recombinant DBAYL,which may effectively close the N-terminal sequence H-S-that is highly sensitive to the dipeptidyl peptidase IV that widely exists in organism.And closing of enzyme-sensitive sequences at the N-terminus may improve the stability and half-life of the peptide in vivo.From bioactivity assay of DBAYL,the methionine at the N-terminus should have no effect on the high flexibility of the N-terminal region of DBAYL,and the receptor potency of DBAYL at human VPAC2maintains highly selective activity.Except for the methionine at the N-terminus of DBAYL,other three muta-tions (N10Q,V18L,and N29Q)were simultaneously intro-duced into the peptide sequence by DNA recombination to avoid deamidation and improve the soluble (data notshown).Figure 7Effect of DBAYL or BAY55-9837on glucose uptake in differentiated 3T3-L1adipocytes Data are shown as the mean +SE of three independent experiments.*P ,0.05and **P ,0.01vs.DBAYL or BAY55-9837treatment (0m M).PACAP-derived peptide promotes glucose uptake and glucose-dependent insulin secretionActa Biochim Biophys Sin (2012)|Volume 44|Issue 11|Page 954at Jinan University on November 16, 2014/Downloaded from。
电气专业英语课文翻译

An electric circuit (or network) is an interconnection of physical electrical device. The purpose of electric circuits is to distribute and convert energy into some other forms. Accordingly, the basic circuit components are an energy source (or sources), an energy converter (or converters) and conductors connecting them.电路(或者网络)是物理电气设备的一种互相连接。
电路的目的是为了将能量分配和转换到另外一种形式中。
因此,基本的电路元件包括电源、电能转换器以及连接它们的导体。
An energy source (a primary or secondary cell, a generator and the like) converts chemical, mechanical, thermal or some other forms of energy into electric energy. An energy converter, also called load (such as a lamp, heating appliance or electric motor), converts electric energy into light, heat, mechanical work and so on.电源(原生电池或者再生电池、发电机等类似装备)将化学能量、机械能量,热能或者其他形式的能量转换成电能。
电能转换器(也称为负载,如灯泡、电热器或者电动机)将电能转换成光、热、机械运动等等。
Analysis_of_DC-Link_Capacitor_Losses_in

15
200
Capacitor Losses (W)
2-L / NPC Casc H-Br 150
ESR (mOhms)
10
100
5
50
0 10
2
10
3
10
4
10
5
Frequency (Hz)
Fig. 1. ESR – frequency characteristic of a 4.7mF / 450V capacitor [5].
2 P = ∑ RC ( f h ) ⋅ I h , rms h
(1)
Losses affect the capacitor lifetime, since they cause heat dissipation and thermal stress. A factor KRipple is used by capacitor manufacturers to quantify the effect of current ripple on capacitor lifetime.
II.
CAPACITOR ESR CHARACTERISTICS
The Equivalent Series Resistance of a DC-link capacitor varies with the frequency of the capacitor current. A typical ESR – frequency characteristic is illustrated in Fig. 1 [5]. In case that more than one current harmonics h, with rms values Ih,rms and frequencies fh flow through the capacitor, the losses P occurring on the capacitor’s ESR can be calculated using equation (1) below, where RC(fh) stands for the value of ESR at frequency fh.
化工原理英文教材流体流动的基本方程Basic equations of fluid flow

F Mb Ma
The momentum flow rate M of a fluid tream having a mass flow rate m and all moving at a velocity u equals mu
F mub ua
It is true if the velocity u is an average velocity at the cross section.
Ma a
Mb b
Assuming that the flow is steady and flows in the x direction.
The sum of forces acting in the x direction equals the difference between the momentum leaving with the fluid per unit time and that brought in per unit time by the fluid or
If u varies from point to point in the cross section of stream, however, the total momentum flow does not equal the product of mass flow rate and average velocity
the component of the gravity in the direction of flow
Fg cos A 0
From this equation, noting that A=bL and Fg=ρrLbg
So
Ram air fan motor cooling

专利名称:Ram air fan motor cooling发明人:Hipsky, Harold W.,Colson, Darryl A.申请号:EP11174373.8申请日:20110718公开号:EP2409919A3公开日:20140226专利内容由知识产权出版社提供专利附图:摘要:A ram air fan assembly (10) includes a ram air fan (12) disposed at a fan inlet (14)and a ram air fan motor (20) operably connected to the ram air fan (12). A blower (46) is operably connected to the ram air fan (12) and is configured to redirect a cooling flow(32) across the ram air fan motor (20) from a substantially axially directed flow to asubstantially radially directed flow thereby increasing the cooling flow (32) across the ram air fan motor (20). A method of cooling a ram air fan assembly (10) includes urging a cooling flow (32) toward the ram air fan motor (20) and is directed across the ram air fan motor (20) thus removing thermal energy from the ram air fan motor (20). The cooling flow (32) proceeds across a blower (46) operably connected to the ram air fan motor (20), thus directing the cooling flow (32) substantially radially outwardly toward the fan inlet (14).申请人:Hamilton Sundstrand Corporation地址:One Hamilton Road Windsor Locks, CT 06096-1010 US国籍:US代理机构:Leckey, David Herbert更多信息请下载全文后查看。
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a r X i v :n u c l -t h /0208014v 1 8 A u g 20021Analysis of directed flow from three-particle correlationsN.Borghini a ∗,P.M.Dinh b and J.-Y.Ollitrault baService de Physique Th´e orique,CP225,Universit´e Libre de Bruxelles,B-1050Brussels bService de Physique Th´e orique,CEA-Saclay,F-91191Gif-sur-Yvette cedexWe present a new method for analysing directed flow,based on a three-particle az-imuthal correlation.It is less biased by nonflow correlations than two-particle methods,and requires less statistics than four-particle methods.It is illustrated on NA49data.1.INTRODUCTIONThe measurement of the successive harmonics of azimuthal correlations in a heavy ion collision [1],v n ≡ e in (φ−ΦR ),where ΦR is the impact parameter direction,is of paramount importance,since it yields information on the medium created in the collision.In particular,a novel behaviour has been predicted for the first harmonic v 1,the so-called directed flow ,at ultrarelativistic energies [2].However,the analysis of directed flow at these energies is highly nontrivial,because v 1is very small.Thus,methods based on an analysis of two-particle azimuthal correlations [3]are likely to be biased by “nonflow”two-particle correlations:quantum (HBT)correlations between identical particles and correlations due to global momentum conservation have been shown to be important at SPS [4],while correlations due to minijets may be large at RHIC [5].On the other hand,methods relying on four-particle correlations [6],which are free from this bias,are plagued by a lack of statistics due to the smallness of v 1,although they give good results for the analysis of elliptic flow v 2(see Sec.2).To remedy these shortcomings,we proposed a new method of v 1analysis [7],based on the measurement of a mixed three-particle correlation,which involves both v 1and v 2:ei (φa +φb −2φc )≃(v 1)2v 2,(1)where φa ,φb ,and φc denote the azimuths of three particles belonging to the same event,and the average runs over triplets of particles emitted in the collision,and over events.Once v 2has been obtained from a separate analysis,this equation yields (v 1)2v 2,thus v 1.Here,we apply this method to NA49data on Pb-Pb collisions at 158A GeV.Results obtained using the “standard”flow analysis are given in Ref.[8].In our method,the first step in the analysis is the measurement of a reference v 2.Then,an equation analogous to Eq.1yields an estimate of the integrated v 1,i.e.,its average value over some phase space region.Finally,restricting φ1in Eq.1to a small (p T ,y )bin allows one to obtain2more detailed,differential measurements of v1as a function of transverse momentum or rapidity.2.ELLIPTIC FLOW FROM2,4,6,8-PARTICLE CORRELATIONSAs stated in the introduction,our method of analysis of directedflow v1requires the preliminary knowledge of an estimate of the ellipticflow v2,integrated over some phase space region.Of course,this estimate must be obtained by analysing the same sample of events from which one wants to extract v1.In practice,the average over phase space is a weighted average:w2v2 ≡ w2e2i(φ−ΦR) ,(2) where w2is the chosen weight.In order to reduce statisticalfluctuations,w2must be larger for particles with stronger ellipticflow.The value of w2v2 is obtained using the cumulant method described in Ref.[6]:one can extract estimates of w2v2 from cumulants of multi-(2-,4-,6-...)particle correlations. While two-particle methods are equivalent to the standardflow analysis,higher orders are essentially free from nonflow effects.They werefirst used in analysing data obtained by the STAR Collaboration at RHIC[9].In Fig.1,we present application of the method to NA49data,and show the dimen-sionless quantityv2≡ w2v2(w2)2,(3)as a function of centrality for charged particles,where we have used w2=p T.We display estimates using cumulants of two-,four-,six-,and even eight-particle correlations[6], as well as the corresponding quantity for charged pions obtained from the“standard”subevent method[3].It is quite remarkable that the four-,six-,and eight-particle estimates all agree:this supports the idea that they are indeed free from nonflow effects,and correspond to a genuine collective motion in the direction of the impact parameter.Moreover,these multiparticle estimates show a slight discrepancy with the two-particle values,as expected if nonflow correlations are sizable[6].Please note that the statistical uncertainties on high order cumulants remain reasonably small,especially for midcentral collisions.In the following,our reference ellipticflow value will preferably be the estimate from the four-particle cumulant,which is a priori the most reliable since it is free from nonflow correlations and has a smaller statistical error than higher order estimates.3.INTEGRATED DIRECTED FLOW FROM2,3,4-PARTICLE CORRE-LATIONSThe next step in the analysis is to determine the average value of directedflow over some phase space region.As in the case of ellipticflow,we perform a weighted average w1v1 ≡ w1e i(φ−ΦR) ,(4)3 where stronger weight is given to particles with stronger directedflow.In the NA49 analysis,we used a rapidity dependent weight w1=y−y CM,where y CM is the centre-of-mass rapidity.This weighted average is obtained from the following three-particle correlation:w1(a)w1(b)w2(c)e i(φa+φb−2φc) = w1v1 2 w2v2 ,(5)where w2is the same as in ing the value of w2v2 obtained in Sec.2,we thus derive w1v1 ,up to a global sign.In practice,the left-hand side of Eq.5is constructed using a generating function for-malism detailed in Ref.[7].This procedure is a very efficient way to sum over all pos-sible triplets of particles,and also to remove automatically the effects of slight detector anisotropies.The method was applied to NA49data.In Fig.2,we present as a function of centrality the dimensionless quantity v1≡ w1v1 /4Figs.3and 4together with two two-particle estimates,either uncorrected or corrected for the effect of momentum conservation [10].At high p T ,v 1from three-particle correlations is consistent with the two-particle value corrected for momentum conservation,but significantly lower than the uncorrected one.This shows that correlations from momentum conservation,which are large,are automati-cally removed in our method.This is also reflected by the behaviour at midrapidity,where v 1vanishes,as it should by symmetry,while the uncorrected two-particle estimate does not.The three-particle estimate also vanishes more smoothly at p T =0than two-particle estimates which may be biased by HBT correlations [4].Figure 3.Directed flow v 1of charged pionsas a function of transverse momentum for midcentral Pb-Pb collisions at 158A GeV.Figure 4.Directed flow v 1of charged pi-ons as a function of y −y CM for midcentral collisions.Open points are reflected with respect to midrapidity.ACKNOWLEDGEMENTSWe thank the NA49Collaboration for permission to use their data.REFERENCES 1.S.Voloshin and Y.Zhang,Z.Phys.C 70(1996)665.2.R.J.M.Snellings et al.,Phys.Rev.Lett.84(2000)2803.3.P.Danielewicz and G.Odyniec,Phys.Lett.B 157(1985)146.4.P.M.Dinh,N.Borghini and J.-Y.Ollitrault,Phys.Lett.B 477(2000)51;N.Borghini,P.M.Dinh and J.-Y.Ollitrault,Phys.Rev.C 62(2000)034902.5.Y.V.Kovchegov and K.L.Tuchin,hep-ph/0203213.6.N.Borghini,P.M.Dinh and J.-Y.Ollitrault,Phys.Rev.C 64(2001)054901;nucl-ex/0110016.7.N.Borghini,P.M.Dinh and J.-Y.Ollitrault,Phys.Rev.C 66(2002)014905.8. A.Wetzler,these proceedings.9. A.H.Tang,hep-ex/0108029;C.Adler et al.[STAR Collaboration],nucl-ex/0206001.10.N.Borghini et al.,Phys.Rev.C 66(2002)014901.。