Robust handling of non‐linear constraints for GA optimization of aerodynamic shapes

A new approach to the robust handling of non‐linear constraints for GAs (genetic algorithms) optimization is proposed. A specific feature of the approach consists of the change in the conventional search strategy by employing search paths which pass through both feasible and infeasible points (contrary to the traditional approach where only feasible points may be included in a path). The method (driven by full Navier–Stokes computations) was applied to the problem of multiobjective optimization of aerodynamic shapes subject to various geometrical and aerodynamic constraints. The results demonstrated that the method retains high robustness of conventional GAs while keeping CFD computational volume to an acceptable level, which allowed the algorithm to be used in a demanding engineering environment. Copyright © 2004 John Wiley & Sons, Ltd.     

Non-protein amino acids in peptide design

An overview of the use of non-protein amino acids in the design of conformationally well-defined peptides, based on work from the author’s laboratory, is discussed. The crystal structures of several designed oligopeptides illustrate the useα-aminoisobutyric acid (Aib) in the construction of helices, D-amino acids in the design of helix termination segments and^DPro-Xxx segments for nucleating ofβ-hairpin structures.β- andγ-amino acid residues have been used to expand the range of designed polypeptide structures. Dedicated to Professor C N R Rao on his 70th birthday     

Numerical simulation and experimental validation of heat transfer within rotating flows for three‐dimensional non‐axisymmetric,turbulent conditions

A control volume type numerical methodology for the analysis of steady three‐dimensional rotating flows with heat transfer, in both laminar and turbulent conditions, is implemented and experimentally tested. Non‐axisymmetric momentum and heat transfer phenomena are allowed for. Turbulent transport is alternatively represented through three existing versions of the k–ε model that were adjusted to take into account the turbulence anisotropy promoted by rotation, streamline curvature and thermal buoyancy. Their relative performance is evaluated by comparison of calculated local and global heat balances with those obtained through measurements in a laboratory device. A modified version of the Lam and Bremhorst, low Reynolds number model is seen to give the best results. A preliminary analysis focused on the flow structure and the transfer of heat is reported. Copyright © 2002 John Wiley & Sons, Ltd.     

宁波城市设计的若干思考与建议

通过探讨城市设计概念的形成过程和历史积淀，阐明其在城市建设中的意义，并运用城市设计的理论与分析方法，针对目前宁波城市大规模的规划、设计、改造现象，提出若干思考与建议．     

微型硅谐振式力传感器的振动分析

介绍了谐振式力传感器的工作原理，并从理论上和实验上对中科院合肥智能所研制的第一代微型硅谐振梁（３×０．４×０．０４５ｍｍ＾３）式测力传感器进行了全面的振动分析，所得结构为其进一步优化设计提供了科学根据，文中使用的实验分析方法，为其它微小物体的动态和识别提供了一条有效途径。     

An application of factorial design to the development of fused silica capillary columns

Stationary phase crosslinking conditions for fused silica capillary columns were optimized with the use of a factorial design experiment. This experimental strategy was chosen because it provided for the determination of two-factor interactions. A predictive model was developed for the desired chromatographic performance parameters as a function of the variables of the crosslinking reaction. Confirmatory experiments proved the usefulness of the mathematical model which resulted in the production of capillary columns of superior performance with significant improvements in reproducibility.     

The optimization of silica gel synthesis from chemical bottle waste using response surface methodology

To reduce the amount of hazardous chemical bottle waste in the environment, we report the optimization research of silica extraction in chemical bottle waste into silica gel. Alkali fusion and sol–gel process were utilised to prepare silica gel effectively. The alkali fusion process was carried out by adding sodium hydroxide to produce sodium silicate. Afterwards, silica gel was prepared by the sol–gel method using hydrochloric acid. Box-Behnken Design (BBD) was applied to Optimisation factors the poptimiseactors affecting the silica recovery. The factors that optimised mass ratio, particle size, and temperature. The optimum recovery of silica gel was obtained by SiO₂: NaOH mass ratio of 1:3, the particle size of 63–74 µm, and a temperature of 800 °C. The purity of silica gel optimum is 63.74% characterised using X-ray fluorescence. The structure of silica gel is the appearance of amorphous peaks at 2θ 20-30° characterised using an x-ray diffractogram. The silica gel surface was characterises using scanning electron microscopy-energy dispersive x-ray. It showed an irregular surface and characteristic showed that silica gel had a radius of 15.74 nm and a specific surface area of 297.08 m².     

Factor Xa: Simulation studies with an eye to inhibitor design

Factor Xa is a serine protease which activates thrombin and plays a key regulatory role in the blood-coagulation cascade. Factor Xa is at the crossroads of the extrinsic and intrinsic pathways of coagulation and, hence, has become an important target for the design of anti-thrombotics (inhibitors). It is not known to be involved in other processes than hemostasis and its binding site is different to that of other serine proteases, thus facilitating selective inhibition. The design of high-affinity selective inhibitors of factor Xa requires knowledge of the structural and dynamical characteristics of its active site. The three-dimensional structure of factor Xa was resolved by X-ray crystallography and refined at 2.2 Å resolution by Padmanabhan and collaborators. In this article we present results from molecular dynamics simulations of the catalytic domain of factor Xa in aqueous solution. The simulations were performed to characterise the mobility and flexibility of the residues delimiting the unoccupied binding site of the enzyme, and to determine hydrogen bonding propensities (with protein and with solvent atoms) of those residues in the active site that could interact with a substrate or a potential inhibitor. The simulation data is aimed at facilitating the design of high-affinity selective inhibitors of factor Xa.     

Functionality map analysis of the active site cleft of human thrombin

Summary The Multiple Copy Simultaneous Search methodology has been used to construct functionality maps for an extended region of human thrombin, including the active site. This method allows the determination of energetically favorable positions and orientations for functional groups defined by the user on the three-dimensional surface of a protein. The positions of 10 functional group sites are compared with those of corresponding groups of four thrombin-inhibitor complexes. Many, but not all features, of known thrombin inhibitors are reproduced by the method. The results indicate that certain aspects of the binding modes of these inhibitors are not optimal. In addition, suggestions are made for improving binding by interaction with functional group sites on the thrombin surface that are not used by the thrombin inhibitors. Abbreviations: MCSS, multiple copy simultaneous search; PPACK, d-phenylalanyl-l-propyl-l-arginine chloromethane; NAPAP, N -(2-naphthylsulfonylglycyl)-d-para-amidinophenylalanylpiperidine; argatroban, (2R,4R)-4-methyl-1-[N -(3-methyl-1,2,3,4-tetrahydro-8-quinolinylsulfonyl)-l-arginyl]-2-piperidine carboxylic acid; rms, root mean square. The thrombin residues are numbered according to the chymotrypsin-based numbering by Bode et al. [8]. P1, P2, P3, etc., denote the peptide inhibitor residues on the amino-terminal side of the scissile peptide bond, and S1, S2, S3, etc., the corresponding subsites of thrombin     

An Experimental Design Approach to Quantitative Expression for Quality Control of a Multicomponent Antidiabetic Formulation by the HILIC Method

A rapid and reproducible hydrophilic liquid chromatography (HILIC) process was established for concomitant determination of remogliflozin etabonate (RE), vildagliptin (VD), and metformin (MF) in a formulation. A face-centered central composite experimental design was employed to optimize and predict the chromatographic condition by statistically studying the surface response model and design space with desirability close to one. A HILIC column with a simple mobile phase of acetonitrile (65% v/v) and 20 mM phosphate buffer (35% v/v, pH 6, controlled with orthophosphoric acid) was used to separate RE, VD, and MF. RE, VD, and MF were separated in 3.6 min using an isocratic mode mobile phase flow at a flow rate of 1.4 mL at room temperature, and the analytes were examined by recording the absorption at 210 nm. The developed HILIC method was thoroughly validated for all parameters recommended by ICH, and linearity was observed in the ranges 20–150 µg/mL, 10–75 µg/mL, and 50–750 µg/mL for RE, VD, and MF, respectively, along with excellent regression coefficients (r² > 0.999). The calculated percentage relative deviation and relative error ascertained the precision and accuracy of the method. The selectivity and accuracy were further confirmed by the high percentage recovery of added standard drugs to the formulation using the standard addition technique. The robustness of the HILIC processes was confirmed by developing a half-normal probability plot and Pareto chart, as the slight variation of a single factor had no significant influence on the assay outcomes. Utilization of the optimized HILIC procedure for concurrent quantification of RE, VD, and MF in solid dosage forms showed accurate and reproducible results. Hence, the fast HILIC method can be regularly employed for the quality assurance of pharmaceutical preparations comprising RE, VD, and MF.