Design and synthesis of type-III mimetics of omega-conotoxin GVIA

Our interest lies in the rational design and synthesis of type-III mimetics of protein and polypeptide structure and function. Our approach involves interactive design of conformationally defined molecular scaffolds that project certain functional groups in a way that mimics the projection of important binding residues as determined in the parent structure. These design principles are discussed and applied to the structurally defined polypeptide, -conotoxin GVIA, which blocks voltage-gated, neuronal N-type calcium channels. These ion channels represent therapeutic targets for the development of new analgesics that can treat chronic pain. It is shown how a discontinuous, 3-residue pharmacophore of GVIA can be mimicked by different molecular scaffolds. It is illustrated how such 1^st generation leads must necessarily be weak and that optimisability must therefore be built-in during the design process.     

Pareto optimality in multiobjective problems

In this study, the optimization theory of Dubovitskii and Milyutin is extended to multiobjective optimization problems, producing new necessary conditions for local Pareto optima. Cones of directions of decrease, cones of feasible directions and a cone of tangent directions, as well as, a new cone of directions of nonincrease play an important role here. The dual cones to the cones of direction of decrease and to the cones of directions of nonincrease are characterized for convex functionals without differentiability, with the aid of their subdifferential, making the optimality theorems applicable. The theory is applied to vector mathematical programming, giving a generalized Fritz John theorem, and other applications are mentioned. It turns out that, under suitable convexity and regularity assumptions, the necessary conditions for local Pareto optima are also necessary and sufficient for global Pareto optimum. With the aid of the theory presented here, a result is obtained for the, so-called, scalarization problem of multiobjective optimization.The author's work in this area is now supported by NIH grants HL 18968 and HL 4664 and NCI contract NO1-CB-5386.     

Fabrication of Channel Waveguides by Photochemical Self-Developing in Doped Sol-Gel Hybrid Glass

Sol-gel derived inorganic-organic hybrid glass (HYBRIMER) films doped with benzildimethylketal (BDK) were prepared. Refractive index and film thickness increase by UV exposure due to photoinduced polymerization and photolocking of high refractive index BDK. This enables the channel waveguides in HYBRIMER film to be fabricated without using a developing process, which is called photochemical self-developing (PSD). The waveguides consist of three layers with under-cladding and over-cladding of undoped HYBRIMER films and core of BDK-doped HYBRIMER film. A 1 × 4 splitter of waveguides was fabricated and demonstrated.     

Ion Channel Behavior of a Supported Bilayer Lipid Membrane Composed of 5,5-Ditetradecyl-2-(2-trimethyl-ammonioethyl)-1,3-dioxane Bromide Modified Glassy Carbon Electrode

A synthetic cationic surfactant, 5, 5-ditetradecyl-2-(2-trimethyl-ammonioethyl)-1, 3-dioxane bromide (DTDB), was used toconstruct a supported bilayer lipid membrane (s-BLM) coatedon an underlying glassy carbon electrode (GCE). Electrochem-ical impedance spectroscopy (EIS), small-angle X-ray diffrac-tion (SAXD) and cyclic voltammetry were used to characterizethe s-BLM. Both EIS and SAXD data indicated that the syn-thetic lipid exists as a well-oriented bilayer in the membrane.     

线上零售商全渠道门店布局密度策略研究

全渠道零售通过整合线上线下发挥协同效应,为零售商和消费者带来价值。但实施全渠道需要更多的成本投入,而合适的线下门店布局是成功的关键。本文基于消费者效用和优化理论,通过零售商和消费者的利益平衡分析,探讨零售商实施全渠道策略下的定价决策、最优门店密度以及相关的全渠道实施的条件。结果表明:全渠道模式的定价与线下不便成本等因素有显著关系;合适的线下门店密度是BOPS策略成功的关键,而最优的密度与与全渠道运营成本系数以及线下门店距离成本难度系数有关,BOPS门店密度大于BOPS+SFS;全渠道策略并不一定有利可图,当线下距离成本效应较低时,BOPS模式优于单一线上销售模式;而BOPS实施成本强度较大或线下距离难度效应较高时,BOPS+SFS则更为可行。     

考虑传统双渠道和BOPS双渠道的消费者和零售商决策研究

本论文在全渠道零售的BOPS模式下,考虑允许退货研究消费者渠道选择问题。首先研究传统双渠道和实施BOPS的双渠道下的消费者和零售商决策。然后加入退货设定,对二者的决策进行重新研究和对比分析。研究发现:不考虑退货的情况下,引入BOPS模式能够提升实体店对零售商及消费者的吸引力;退货情况下,引入BOPS使消费者更愿意选择线下购买和销售,但不一定总能带来销售总量的增加;实施BOPS时,退货允许让零售商更愿意在实体店销售,同时消费者的购买渠道选择也变得复杂。     

E-供应链竞争下自营品牌商的第三方零售渠道引入与定价策略

基于电商平台销售渠道的多样性,决策是否引入第三方零售渠道是自营品牌商在现实的E-供应链竞争中常常面临的重要难题。在多渠道竞争环境下,构建由两个自营品牌商和一个电商平台组成的E-供应链系统。考虑品牌商不引入、单一品牌商引入与两个品牌商均引入第三方零售渠道三种情形,分别建立Stackelberg博弈模型并求解,分析了平台佣金、消费者的自营零售渠道偏好和交叉价格弹性系数等因素对第三方零售渠道引入及E-供应链各成员最优策略的影响。研究表明:不同的交叉价格弹性系数和消费者自营渠道偏好对第三方零售渠道引入策略具有差异性,且两个品牌商均引入第三方零售渠道对电商平台最有利。此外,平台佣金、消费者自营渠道偏好和交叉价格弹性系数对自营、第三方商品的定价以及电商平台、品牌商的利润具有重要影响。     

On the Non-Adaptive Zero-Error Capacity of the Discrete Memoryless Two-Way Channel

We study the problem of communicating over a discrete memoryless two-way channel using non-adaptive schemes, under a zero probability of error criterion. We derive single-letter inner and outer bounds for the zero-error capacity region, based on random coding, linear programming, linear codes, and the asymptotic spectrum of graphs. Among others, we provide a single-letter outer bound based on a combination of Shannon’s vanishing-error capacity region and a two-way analogue of the linear programming bound for point-to-point channels, which, in contrast to the one-way case, is generally better than both. Moreover, we establish an outer bound for the zero-error capacity region of a two-way channel via the asymptotic spectrum of graphs, and show that this bound can be achieved in certain cases.     

Compact finite difference schemes on non‐uniform meshes. Application to direct numerical simulations of compressible flows

In this paper, the development of a fourth‐ (respectively third‐) order compact scheme for the approximation of first (respectively second) derivatives on non‐uniform meshes is studied. A full inclusion of metrics in the coefficients of the compact scheme is proposed, instead of methods using Jacobian transformation. In the second part, an analysis of the numerical scheme is presented. A numerical analysis of truncation errors, a Fourier analysis completed by stability calculations in terms of both semi‐ and fully discrete eigenvalue problems are presented. In those eigenvalue problems, the pure convection equation for the first derivative, and the pure diffusion equation for the second derivative are considered. The last part of this paper is dedicated to an application of the numerical method to the simulation of a compressible flow requiring variable mesh size: the direct numerical simulation of compressible turbulent channel flow. Present results are compared with both experimental and other numerical (DNS) data in the literature. The effects of compressibility and acoustic waves on the turbulent flow structure are discussed. Copyright © 1999 John Wiley & Sons, Ltd.     

Explicit finite volume non‐oscillatory schemes for 2D transient free‐surface flows

A class of high‐resolution non‐oscillatory shock‐capturing Roe, TVD and ENO explicit schemes in finite volume approach are presented for the computation of 2D unsteady rapidly varied open channel flows. In order to apply these schemes to simulate the hydraulic phenomena in field, the Strang‐type operator splitting technique is adopted to treat the flow with bottom slope and friction terms. Verifications of the proposed schemes are made by comparison with analytical solutions or experimental data, and very good agreements are obtained. To illustrate the efficiency and stability of the present algorithms, four typical problems of rapidly varied flows are solved and the results of different schemes are compared. It is demonstrated that the proposed method is accurate, robust and highly stable even in the flows with very strong discontinuites, which need no tuning of any adjustable parameter, such as artificial viscosity coefficient, as other methods do, and is a reliable mathematical modeling for 2D practical hydraulic engineering applications. Copyright © 1999 John Wiley & Sons, Ltd.