Morphine induces Beclin 1-and ATG5-dependent autophagy in human neuroblastoma SH-SY5Y cells and in the rat hippocampus

Chronic exposure to morphine can induce drug addiction and neural injury, but the exact mechanism is not fully understood. Here we show that morphine induces autophagy in neuroblastoma SH-SY5Y cells and in the rat hippocampus. Pharmacological approach shows that this effect appears to be mediated by PTX-sensitive G protein-coupled receptors signaling cascade. Morphine increases Beclin 1 expression and reduces the interaction between Beclin 1 and Bcl-2, thus releasing Beclin 1 for its pro-autophagic activity. Bcl-2 overexpression inhibits morphine-induced autophagy, whereas knockdown of Beclin 1 or knockout of ATG5 prevents morphine-induced autophagy. In addition, chronic treatment with morphine induces cell death, which is increased by autophagy inhibition through Beclin 1 RNAi. Our data are the first to reveal that Beclin 1 and ATG5 play key roles in morphine-induced autophagy, which may contribute to morphine-induced neuronal injury.

不同分子量坛紫菜多糖的制备及其抗衰老活性研究

坛紫菜（Porphyra haitanensis），属红藻门（Rhodophyta），红毛菜科（Bangiacease）紫菜属（Porphyra），是我国大规模养殖的重要经济海藻之一，主要产于我国南方沿海如福建、广东、浙江等地。紫菜作为中药，具有“补肾养心，利水消肿”的功效，实验室前期所作的工作表明，坛紫菜多糖具有良好的抗衰老作用。分子量对多糖生物活性有重大影响，本文以福建沿海的坛紫菜为原料，对坛紫菜多糖（P）的降解方法和该紫菜多糖的抗衰老活性与分子量的关系展开了研究。 本论文首次将植物生长发育过程中发生的抗坏血酸和过氧化氢反应体系应用于坛紫菜多糖的降解。抗坏血酸和过氧化氢的浓度及两者的比例是该降解方法的主要影响因素。采用该法制备了分子量分别为50、30、13、8.2和2.7 kD 的P1、P2、 P3、P4和P5五种产品。其中P1、P2和P3产品的红外图谱与原料多糖的红外图谱一致，表明这两种多糖的化学结构在降解过程中并未发生改变，而P4和P5样品的红外图谱显示该样品中出现了少量的羧基。 本论文还首次对各产物进行了抗氧化、免疫调节、抗疲劳、延长寿命、抗老年痴呆等活性的筛选与研究，具体结果如下： 采用化学法对五种降解多糖和原料多糖的抗氧化活性进行研究。结果表明分子量对坛紫菜多糖清除各种自由基能力的影响是不同的。降解之后，坛紫菜多糖清除超氧阴离子的能力有所下降，与金属离子的螯合能力几乎全部丧失，但是多糖清除羟基自由基的能力变化甚微。降解之后，坛紫菜多糖清除有机自由基的能力和还原能力显著提高，随分子量的降低这两种能力明显加强，其中P4样品清除有机自由基能力最强，而分子量最小的P5样品还原能力最突出。 通过测定T、B淋巴细胞增殖率考察了五种降解多糖和原料多糖的免疫调节作用。研究表明：不同分子量坛紫菜多糖均具有免疫调节作用，可显著促进小鼠脾脏T淋巴细胞增殖，显著抑制小鼠脾脏B淋巴细胞增殖。P2和P4样品效果强于其它降解产品和原料。 通过测定小鼠游泳和爬杆时间考察了三种降解多糖P1、P2、P4和原料多糖的耐疲劳作用。研究表明：坛紫菜多糖降解产品耐疲劳作用要优于原料多糖P。P1、P2和P4通过提高小鼠肝糖原储备从而达到显著延长小鼠爬杆时间和负重游泳时间的功效。 通过测定D. melanogaster果蝇寿命、热耐受时间和性活力考察了三种降解多糖P1、P2、P4和原料多糖对寿命及生命活力的影响。研究表明：分子量对坛紫菜多糖对果蝇的寿命和生命活力有很大影响。降解使坛紫菜原料多糖P对果蝇的延长寿命和提高生命活力作用得到加强。在果蝇正常代谢状态下，降解产品中分子量较大的P1和P2作用更显著，而在热应激状态下，降解产品中分子量较小的P4作用更突出。 采用小鼠侧脑室注射Aβ1-40致痴呆模型考察了样品P1改善认知功能的作用。研究表明：P1通过降低皮层和海马组织乙酰胆碱酯酶活性，显著提高乙酰胆碱转移酶的活性，有效改善痴呆小鼠的认知能力，使之水迷宫游泳时间缩短，使避暗潜伏期延长。 为探讨P1样品改善小鼠认知功能的作用机制，本文采用Aβ25-35损伤神经母细胞瘤株SH-SY5Y模型对P1样品的神经细胞的保护作用进行了研究。结果显示低浓度下P1对该损伤模型具有显著保护作用，高浓度下表现出显著的抑制作用。 本文的研究表明坛紫菜多糖在降解之后生物活性得到显著改善。分子量对坛紫菜多糖活性影响很大。总的看来，在体外实验中，分子量越低其体外抗氧化活性和免疫调节作用越显著，但是，在体内实验中，降解产品中分子量最大的P1样品能更有效地改善小鼠疲劳程度、延长果蝇的寿命及热耐受时间，P1样品还能显著改善痴呆小鼠记忆功能。不同分子量坛紫菜多糖体内和体外生物活性的这种差异还需要进行深入研究。

The scattering of general SH plane wave by interface crack between two dissimilar viscoelastic bodies

The scattering of general SH plane wave by an interface crack between two dissimilar viscoelastic bodies is studied and the dynamic stress,intensity factor at the crack-tip is computed. The scattering problem can be decomposed into two problems: one is the reflection and refraction problem of general SH plane waves at perfect interface (with no crack); another is the scattering problem due to the existence of crack. For the first problem, the viscoelastic wave equation, displacement and stress continuity conditions across the interface are used to obtain the shear stress distribution at the interface. For the second problem, the integral transformation method is used to reduce the scattering problem into dual integral equations. Then, the dual integral equations are transformed into the Cauchy singular integral equation of first kind by introduction of the crack dislocation density function. Finally, the singular integral equation is solved by Kurtz's piecewise continuous function method. As a consequence, the crack opening displacement and dynamic stress intensity factor are obtained. At the end of the paper, a numerical example is given. The effects of incident angle, incident frequency and viscoelastic material parameters are analyzed. It is found that there is a frequency region for viscoelastic material within which the viscoelastic effects cannot be ignored.

圆夹杂内裂纹对SH波的动力响应

利用特殊函数的Graf加法公式和波函数展开方法得出了圆夹杂内作用集中力的格林函数。根据Bessel函数的渐近性质，对所得格林函数的奇异部分和有界部分进行了分离。利用所得的格林函数和互易定理得出了圆夹杂内裂纹在SH波作用下的散射场。根据裂纹的散射场建立了圆夹杂内裂纹的超奇异积分方程。对超奇异积分方程的数值求解，可得裂纹端点的动应力强度因子。

Steady Patterns of Microparticles Formed by Optical Tweezers

In this paper, we propose a method for forming steady patterns of microparticles in a dispersion using optical tweezers. We demonstrate how to control the congregation of particles in a dispersion and to manually fabricate a pattern, The steady pattern (nay be useful for in-depth research, and the method will have applications in biology and nanotechnology.

Generalized Maugis-Dugdale Model of an Elastic Cylinder in Non-Slipping Adhesive Contact with a Stretched Substrate

We have recently developed a generalized JKR model for non-slipping adhesive contact between an elastic cylinder and a stretched substrate where both tangential and normal tractions are transmitted across the contact interface. Here we extend this model to a generalized Maugis-Dugdale model by adopting a Dugdale-type adhesive interaction law to eliminate the stress singularity near the edge of the contact zone. The non-slipping Maugis-Dugdale model is expected to have a broader range of validity in comparison with the non-slipping JKR model. The solution shares a number of common features with experimentally observed behaviors of cell reorientation on a cyclically stretched substrate.

A rigorous analytical method for doubly periodic cylindrical inclusions under longitudinal shear and its application

An infinite elastic solid containing a doubly periodic parallelogrammic array of cylindrical inclusions under longitudinal shear is studied. A rigorous and effective analytical method for exact solution is developed by using Eshelby's equivalent inclusion concept integrated with the new results from the doubly quasi-periodic Riemann boundary value problems. Numerical results show the dependence of the stress concentrations in such heterogeneous materials on the periodic microstructure parameters. The overall longitudinal shear modulus of composites with periodic distributed fibers is also studied. Several problems of practical importance, such as those of doubly periodic holes or rigid inclusions, singly periodic inclusions and single inclusion, are solved or resolved as special cases. The present method can provide benchmark results for other numerical and approximate methods. (C) 2003 Elsevier Ltd. All rights reserved.

Statistics of Turbulence in Benthal Boundary Layers

This paper deals with turbulence behavior inbenthalboundarylayers by means of large eddy simulation (LES). The flow is modeled by moving an infinite plate in an otherwise quiescent water with an oscillatory and a steady velocity components. The oscillatory one aims to simulate wave effect on the flow. A number of large-scale turbulence databases have been established, based on which we have obtained turbulencestatisticsof the boundarylayers, such as Reynolds stress, turbulence intensity, skewness and flatness ofturbulence, and temporal and spatial scales of turbulent bursts, etc. Particular attention is paid to the dependences of those statistics on two nondimensional parameters, namely the Reynolds number and the current-wave velocity ratio defined as the steady current velocity over the oscillatory velocity amplitude. It is found that the Reynolds stress and turbulence intensity profile differently from phase to phase, and exhibit two types of distributions in an oscillatory cycle. One is monotonic occurring during the time when current and wave-induced components are in the same direction, and the other inflectional occurring during the time when current and wave-induced components are in opposite directions. Current component makes an asymmetrical time series of Reynolds stress, as well as turbulence intensity, although the mean velocity series is symmetrical as a sine/cosine function. The skewness and flatness variations suggest that the turbulence distribution is not a normal function but approaches to a normal one with the increasing of Reynolds number and the current-wave velocity ratio as well. As for turbulent bursting, the dimensionless period and the mean area of all bursts per unit bed area tend to increase with Reynolds number and current-wave velocity ratio, rather than being constant as in steady channel flows.

A Breakdown Criterion of Free Molecular Flows and an Optimum Analysis of EBPVD

Two important issues in electron beam physical vapor deposition (EBPVD) are addressed. The first issue is a validity condition of the classical cosine law widely used in the engineering context. This requires a breakdown criterion of the free molecular assumption on which the cosine law is established. Using the analytical solution of free molecular effusion flow, the number of collisions (N-c) for a particle moving from an evaporative source to a substrate is estimated that is proven inversely proportional to the local Knudsen number at the evaporation surface. N-c = 1 is adopted as a breakdown criterion of the free molecular assumption, and it is verified by experimental data and DSMC results. The second issue is how to realize the uniform distributions of thickness and component over a large-area thin film. Our analysis shows that at relatively low evaporation rates the goal is easy achieved through arranging the evaporative source positions properly and rotating the substrate.

The effects of capillary force in micro or nano-indentation

Models describing wet adhesion between indenters and substrates joined by liquid bridges are investigated. The influences of indenter shapes and various parameters of structures on capillary force are focused. In the former, we consider several shapes, such as conical, spherical and truncated conical indenter with a spherical end. In the latter, the effects of the contact angle, the environmental humidity, the gap between the indenter and the substrate, etc. are included. Different dependences of the capillary force on the indenter shapes and the geometric parameters are observed. Most interesting finding is that applying the present results to micro- and nano-indentation experiments shows the size effect in indentation hardness not produced but underestimated by the effects of capillary force.(4 refs)

Subsonic interface crack with crack face contact

A steady-state subsonic interface crack propagating between an elastic solid and a rigid substrate with crack face contact is studied. Two cases with respective to the contact length are considered, i.e., semi-infinite and finite crack face contact. Different from a stationary or an open subsonic interface crack, stress singularity at the crack tip in the present paper is found to be non-oscillatory. Furthermore, in the semi-infinite contact case, the singularity of the stress field near the crack tip is less than 1/2. In the finite contact case, no singularity exists near the crack tip, but less than 1/2 singularity does at the end of the contact zone. In both cases, the singularity depends on the linear contact coefficient and the crack speed. Asymptotic solutions near the crack tip are given and analyzed. In order to satisfy the contact conditions, reasonable region of the linear contact coefficient is found. In addition, the solution predicts a non-zero-energy dissipation rate due to crack face contact.

粘弹性材料界面裂纹的瞬态响应和散射研究

本文研究粘弹性材料界面裂纹对冲击载荷的瞬态响应和对广义平面波的稳态散射。相对于已有广泛研究的弹性材料裂纹瞬态响应和稳态散射问题，本文的研究有三个突出特点：1）粘弹性材料；2）界面裂纹；3）广义平面波入射。粘弹性材料界面裂纹对冲击载荷的瞬态响应和对广义平面波的散射尚无开展研究，本文在弹性材料相应问题的研究基础上，首先开展了这一问题的研究。对于冲击载荷下粘弹性界面裂纹的瞬态响应问题，利用Laplace积分变换方法，将粘弹性材料卷积型本构方程转化为Laplace变换域内的代数型本构方程，从而可以在Laplace变换域内象处理弹性材料的冲击响应一样，将相应的混合边值问题归结为关于裂纹张开位移COD的对偶积分方程，并进一步引入裂纹位错密度函数CDD （Crack Dislocation Density），将对偶积分方程化成关于CDD的奇异积分方程（SIE）。用数值方法求解奇异积分方程得到变换域内的动应力强度因子数值解，最后利用Laplace积分逆变换数值方法得到时间域内的动应力强度因子的时间响应。理论分析考虑了两种裂纹模型，即Griffith界面裂纹和柱面圆弧型界面裂纹。考虑的载荷包括反平面冲击载荷和平面冲击载荷。对于平面冲击载荷，通过对裂尖应力场的奇性分析，首次发现粘弹性界面裂纹裂尖动应力场奇性指数不是常数0.5，而是与震荡指数一样依赖材料参数。针对反平面冲击载荷给出了一个算例，计算了裂尖动应力强度因子的时间响应，并与弹性材料的结果作了比较，发现粘弹性效应的影响不仅使过冲击峰值降低，而且使峰值点后移。粘性效应较大时，过冲击现象甚至不出现。关于粘弹性界面裂纹对广东省义平面波的散射问题，首先研究广义平面波在无裂纹存在的理想界面的反射和透射，再研究由于界面裂纹的存在而产生的附加散射场。利用粘弹性材料的复模量理论，可将粘弹性材料的卷积型相构方程化成频率域内的代数型本构方程。类似弹性平面波的处理，在频率域内将问题最终归结为关于裂纹位错密度CDD的奇异积分方程。数值方法求解奇异积分方程即可得到频率域内的散射场，并进而得到裂尖动应力强度因子和远场位移型函数和散射截面。理论分析考虑了两种裂纹模型：Griffith界面裂纹和柱面圆弧型界面裂纹。研究的入射波有广义的SH波和P波。对于广义平面P波入射的情况，通过对裂尖应力场的奇性分析，同样发现粘弹性界面裂纹裂尖动应力场奇性指数不地常数0.5，而是与震荡指数一样依赖于材料参数。对柱面裂纹散射远场的渐近分析，发现远场位移和应力除含有几何衰减因子外，都含有一个材料衰减速因子。散射截面由于材料衰减因子的存在也成为依赖散射半径的量。为了使散射截面仍有意义，文中提出一种修正办法。对Griffith界面裂纹，给出了一个广义平面SH波入射的算例；对柱面界面裂纹，给出了一个广义平面P波入射的算例。计算了不同入射角和入射频率下裂纹的张开位移和动就应力强度因子，并分析了其依赖关系。求解奇异积分方程的数值方法和Laplace积分逆变换数值方法是本文的基本数值方法。本文对这两种方法作了大量的调研和系统的研究。在对比分析的基础上，对现有的各种方法从原理，适用范围，计数效率，优势及特点进行了归纳总结。并尝试了奇异积分方程的最新数值方法--分片连续函数法，证实了其适用性和方便性．