毛细管电泳芯片信号分析系统的UML建模研究

集成毛细管电泳芯片(Integrate Cpillary Electrophoresis Chip,ICEC)属于分析型生物芯片,近年来发展迅速。ICEC过程复杂,实现困难,有必要前期通过建模等方式,进行必要的系统设计。统一建模语言(Unified Modeling Language,UML)是一种用来描述系统、构造系统模型的面向对象建模语言,运用UML语言对ICEC信号分析系统进行建模研究,可使ICEC的设计逐步优化,从而最终实现混合物高效分析和分离的目的。本文系统描述UML语言和毛细管电泳芯片工作原理,并介绍运用UML语言对ICEC信号分析系统建模方法。     

人工神经网络在发酵工业中的应用

人工神经网络技术具有很强的非线性映射能力,用于系统的非线性建模,具有无可比拟的优势,广泛应用于发酵过程中培养基的优化和系统建模与控制方面,本主要介绍了人工神经网络的基本原理与使用方法,以及BP神经网络在非线性函数逼近的优点,详细介绍了其在发酵培养基优化,连续搅拌反应器神经网络估计,分批发酵及补料分批发酵过程建模与控制优化中的应用实例。     

仿真领域的持续承诺

随着分子生物学领域的进步,基因组及相关计划的进展,系统生物学逐渐成为生命科学研究中的热点,生物系统方面的建模和仿真也成为目前系统生物学研究引人关注的内容之一。而第一代建模工具在应用的过程中存在许多缺陷,从而导致用户需求和工具建模能力之间存在巨大鸿沟。本文对第一代建模工具存在的问题进行了分析,并简单介绍了可以进行复杂仿真建模的新一代仿真工具。此外,文章对系统生物学的市场模式也进行了探讨。     

细胞信号转导网络的建模

细胞信号转导网络的组织和调控是十分复杂的。目前,结合试验数据,借助计算机建模的方法,进行信号转导网络的研究颤受关注。介绍了信号通路数学建模的步骤、方法,描述了当前信号转导网络建模的不同类型的模型及各自的优缺点。此外,还以G蛋白偶联受体模型为例,详细阐述了模型的层次问题,探讨了信号转导建模所面临的挑战及其未来的发展趋势。     

生态系统服务建模技术研究进展

在生态系统服务评估模型的数量、类型及应用大量增加的背景下,为将生态系统服务评估有效整合到决策中,系统比较、甄别不同建模工具并筛选出适合决策需求的生态系统服务评估和模拟方法尤为必要。因此,归纳并总结了国内外现有的生态系统服务评估模型的建模技术,包括:相关关系法、生物-物理过程法以及专家知识法;分别对其原理、差异、优缺点以及适用性进行了详尽阐释。大多数相关模型侧重于统计关系,相对容易创建和扩展,适用于生态系统服务的初始评估;生物-物理过程模型难以构建且不易获取,但提供了探索人-地系统相互作用和长期变化的有效机制;专家知识法有效结合了多种类型的知识体系,关注人类社会与自然系统之间反馈和交互动态的系统整合,但当评估地点发生变化时难以验证。在此基础上,介绍了基于上述3种建模技术的典型生态系统服务综合评估模型的发展和应用现状。各类建模技术面临着实用性和科学准确性之间的权衡。通过对不同建模技术的梳理与整合分析旨在提升当前生态系统服务研究的决策支撑能力,并为国内相关研究提供参考和借鉴。     

基于熵准则的鲁棒的RBF谷胱甘肽发酵建模

在谷胱甘肽的发酵过程建模中, 当试验数据含有噪音时, 往往会导致模型预测精度和泛化能力的下降。针对该问题, 提出了一种新的基于熵准则的RBF神经网络建模方法。与传统的基于MSE准则函数的建模方法相比, 新方法能从训练样本的整体分布结构来进行模型参数学习, 有效地避免了传统的基于MSE准则的RBF网络的过学习和泛化能力差的缺陷。将该模型应用到实际的谷胱甘肽发酵过程建模中, 实验结果表明: 该方法具有较高的预测精度、泛化能力和良好的鲁棒性, 从而对谷胱甘肽的发酵建模有潜在的应用价值。     

基于熵准则的鲁棒的RBF谷胱甘肽发酵建模

在谷胱甘肽的发酵过程建模中, 当试验数据含有噪音时, 往往会导致模型预测精度和泛化能力的下降。针对该问题, 提出了一种新的基于熵准则的RBF神经网络建模方法。与传统的基于MSE准则函数的建模方法相比, 新方法能从训练样本的整体分布结构来进行模型参数学习, 有效地避免了传统的基于MSE准则的RBF网络的过学习和泛化能力差的缺陷。将该模型应用到实际的谷胱甘肽发酵过程建模中, 实验结果表明: 该方法具有较高的预测精度、泛化能力和良好的鲁棒性, 从而对谷胱甘肽的发酵建模有潜在的应用价值。     

基于SWISS-MODEL的蛋白质三维结构建模

蛋白质的三级结构预测可通过同源建模、Threading和TOPITS等方法进行,但同源建模是应用最为广泛的方法。SWISS-MODEL正是一个基于同源建模的蛋白质结构服务器。它与ExPASy网站和DeepView程序是紧密相联系的。该文重点介绍SWISS-MODEL的提交方式、建模的步骤、结果的评估和应用程序等。     

分子模拟在门冬酰胺酶Ⅱ表面呈现多肽技术中的应用

简要地介绍了表面呈现技术和组合酶技术的应用以及发展前景,描述了一种应用分子建模系统辅助进行抗动脉粥样硬化的嵌合酶疫苗的构建过程。门冬酰胺酶活力测定结果证明,嵌合酶的空间结构和活性位点均能够依照设计要求保留。提供了一种生物信息学手段在组合生物合成领域中的应用方法。     

基于R的结构方程模型在生态学中的应用

结构方程模型已经成为当前生态数据分析的主要方法之一。与其他多变量统计方法不同,结构方程模型的建模过程由理论假设驱动,且可以同时量化多个变量间的直接和间接因果关系。然而,由于结构方程模型引入国内生态学领域的时间相对较短,研究者经常在实际应用中遇到各种问题,各种使用错误也屡见不鲜。对此,本文系统阐述了结构方程模型的建模原理、建模流程、模型评价、模型修正等方面内容,并且结合具体研究案例介绍了结构方程模型分析的两个主流R包—lavaan和piecewiseSEM。其中,lavaan可以分析纳入了潜变量的结构方程模型,piecewiseSEM则可以解决各观测数据不独立以及响应变量残差不满足多元正态分布等问题。本文将有助于研究者准确理解结构方程模型并能扩大其在生态学中的应用。     

蛋白质结构与功能研究中的分子模拟技术

分子模拟技术为蛋白质的研究提供了一种崭新的手段,在理论上解决了结构预测和功能分析以及蛋白质工程实施方面所面临的难题。它在蛋白质的结构预测和模建工作中占有举足轻重的地位,实现了生物技术与计算机技术的完美结合。本文简要阐述了该技术的基本步骤和工作原理,并以目前应用最广的生物大分子领域的商品化分子模拟软件Accelrys公司基于Linux系统开发的InsightII为例,介绍了相关程序模块的功能和作用,同时结合该技术在蛋白质的结构预测和模建、结构与功能关系分析、分子设计等过程中的开发与应用,加以具体说明和展望。     

Modeling high-biomass-density cell recycle fermentors

Since intrinsic models, which take into account cell volume fraction, follow from proper application of the law of conservation of mass to a multiphase system, the intrinsic modeling approach should be used whenever biomass occupies a significant volume fraction of the culture. A recent report(11) offers the first comparison of intrinsic and nonintrinsic model predictions to actual experimental data gathered from a high-density yeast recycle fermentor. Here, the analysis of Jarzebski et al.(11) has been carried further to show that the improper nonintrinsic model predicts a steady-state culture glucose concentration that differs from that given by the fundamentally correct intrinsic model by over 60% at the optimal, bleed stream flow rate. In addition, a revised formulation for an intrinsic ethanol mass balance is presented.     

Modeling of heat transfer in whole-body hyperthermia

The therapeutic application of whole-body hyperthermia, whereby the body temperature is for a short time raised to 43–44°C is currently considered quite promising. However, body temperature above 42°C also raises the risks associated with hemodynamic instability and arrhythmia. A model of heat transfer is built to improve the efficacy and safety of the immersion-convection technique of whole-body hyperthermia. The model takes into account the changes in skin blood flow and the dynamics of heart rate depending on body temperature. It adequately reflects the processes of heating in the organism and can be used to calculate the heat distribution in the body.     

基于AnyBodyTM技术的人体运动建模方法

人体运动的建模与仿真是当今运动生物力学研究的一个热点.利用数值模型研究人体的运动规律,是人体运动研究的一个重要手段和有效工具.其关键技术在于应用逆向运动学方法求解人体运动,并获取人体运动中各个肌肉力学上技术参数.文中主要探讨基于AnyBodyTM System软件人体运动仿真的建模方法来研究人体运动力学规律,结合The AnyBodyTM system对人体运动具体应用,说明The AnyBodyTM system技术在人体运动仿真领域的优势.     

An Object-Oriented Approach for Flexible Manufacturing Control Systems Analysis and Design Using the Unified Modeling Language

In reacting to global competition and rapidly changing customer demands, industrial business organizations have developed a strong interest in flexible automation. The aim of flexible automation focuses on achieving agility in handling uncertainties from internal or external environments. Modeling complex structures, promoting reuse, and shortening the development time cycle are particularly significant aspects in the analysis and design of CIM systems, where heterogeneous elements have to be integrated in a complex control architecture. The design methodology for FMS control software involves the abstraction of an FMS and the estimation of the system performances. The aim of this activity is to suggest the optimal configuration of an FMS for given specifications, through simulation tools. In the software engineering field, object-oriented (OO) approaches have proven to be a powerful technique with respect to such aspects. The unified modeling language (UML), by using OO design methodologies, can offer reusability, extendibility, and modifiability in software design. Also, it bridges the gap that exists between the OO analysis and design area and the area of OO programming by creating an integrative metamodel of OO concepts. The specific goal of this paper is to formulate a new methodology for developing reusable, extendible, and modifiable control software for an FMS in an object-oriented environment. It is demonstrated that, with few diagrams, UML can be used to model such systems without being associated with other modeling tools.     

Dynamic Landscapes, Stability and Ecological Modeling

The image of a ball rolling along a series of hills and valleys is an effective heuristic by which to communicate stability concepts in ecology. However, the dynamics of this landscape model have little to do with ecological systems. Other landscape representations, however, are possible. These include the particle on an energy landscape, the potential landscape, and the Lyapunov function landscape. I discuss the dynamics that these representations admit, and the application of each to ecological modeling and the analysis and representation of stability. CWP is a Postdoctoral Fellow with the Oak Ridge Institute for Science and Education     

Modeling of loops in protein structures

Comparative protein structure prediction is limited mostly by the errors in alignment and loop modeling. We describe here a new automated modeling technique that significantly improves the accuracy of loop predictions in protein structures. The positions of all nonhydrogen atoms of the loop are optimized in a fixed environment with respect to a pseudo energy function. The energy is a sum of many spatial restraints that include the bond length, bond angle, and improper dihedral angle terms from the CHARMM-22 force field, statistical preferences for the main-chain and side-chain dihedral angles, and statistical preferences for nonbonded atomic contacts that depend on the two atom types, their distance through space, and separation in sequence. The energy function is optimized with the method of conjugate gradients combined with molecular dynamics and simulated annealing. Typically, the predicted loop conformation corresponds to the lowest energy conformation among 500 independent optimizations. Predictions were made for 40 loops of known structure at each length from 1 to 14 residues. The accuracy of loop predictions is evaluated as a function of thoroughness of conformational sampling, loop length, and structural properties of native loops. When accuracy is measured by local superposition of the model on the native loop, 100, 90, and 30% of 4-, 8-, and 12-residue loop predictions, respectively, had <2 A RMSD error for the mainchain N, C(alpha), C, and O atoms; the average accuracies were 0.59 +/- 0.05, 1.16 +/- 0.10, and 2.61 +/- 0.16 A, respectively. To simulate real comparative modeling problems, the method was also evaluated by predicting loops of known structure in only approximately correct environments with errors typical of comparative modeling without misalignment. When the RMSD distortion of the main-chain stem atoms is 2.5 A, the average loop prediction error increased by 180, 25, and 3% for 4-, 8-, and 12-residue loops, respectively. The accuracy of the lowest energy prediction for a given loop can be estimated from the structural variability among a number of low energy predictions. The relative value of the present method is gauged by (1) comparing it with one of the most successful previously described methods, and (2) describing its accuracy in recent blind predictions of protein structure. Finally, it is shown that the average accuracy of prediction is limited primarily by the accuracy of the energy function rather than by the extent of conformational sampling.     

Modeling long-term compost application effects on nitrate leaching

Application of compost to agricultural soils may be beneficial for crop production by increasing soil fertility and supplying plant nutrients, however, any raise of the soil organic matter content may increase the potential for unintended groundwater contamination by nitrate leaching. In this paper, the effect of long-term compost applications on nitrate leaching, soil organic matter content, and crop production is analyzed using results of simulation scenarios for agricultural sites with loamy and sandy soils. Simulations were carried out using the Danish Nitrogen Simulation System (DAISY) which describes the nitrogen balance in a one-dimensional soil-plant-atmosphere system and considers compost type and application rate as well as management and cropping practice. Estimations of hydraulic and solute transport parameters are based on pedotransfer functions. Data from a 4.5-year period of field experiments with compost applications in northern Germany as well as from laboratory experiments with compost amended soil are used for model calibration. Simulation results suggest that: (i) with respect to nitrogen turnover the differences between compost types (i.e., non-matured and matured) are small compared to site-specific properties (i.e., soil temperature and water balance) and management practices (i.e., crop rotation) when considering a compost application period of 50 years; (ii) with respect to nitrate leaching the effect of different compost application scenarios is highly sensitive at the sand and relatively small at the loam site; and (iii) relatively high crop yields and acceptably low nitrate concentrations in the drainage water are obtained at the sand site when applying a combination of 10 t compost/ha/yr and soil- N_min adjusted mineral nitrogen additions of about 20 kg/ha/yr to a winter-grain dominated crop rotation. Further optimization may be possible by applying reduced rates of the (economically interesting) non-matured compost. This revised version was published online in June 2006 with corrections to the Cover Date. This revised version was published online in June 2006 with corrections to the Cover Date. This revised version was published online in June 2006 with corrections to the Cover Date.     

Standardizing clinical trials workflow representation in UML for international site comparison

Background

With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper''s objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML.

Methods

Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software.

Results

Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses'' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities.

Conclusions

This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative analysis of international clinical trials workflows.