Methods in Computational Neurobiology

SYNOPSIS. This paper describes fundamental methodological challengesfaced by computational neuroscience. Modeling strategies intendedfor consolidating extensive knowledge and data into single predictivemodels are inappropriate for much of neuroscience at this stagein its evolution. Instead, models designed to explore the implicationsof guesses or suppositions are more likely to have utility insupporting experimental studies, either by deriving added insightfrom available data or by suggesting experiments that otherwisemight not be performed. Such computational experiments, if theyare to be useful, must be based upon models with a careful balancebetween solid data and supposition. The implications of thisrequirement for two major modeling strategies, simulation modelingand parametric data modeling, are examined.     

Multiscale modeling and mechanics of filamentous actin cytoskeleton

The adaptive structure and functional changes of the actin cytoskeleton are induced by its mechanical behavior at various temporal and spatial scales. In particular, the mechanical behaviors at different scales play important roles in the mechanical functions of various cells, and these multiscale phenomena require clarification. To establish a milestone toward achieving multiscale modeling and simulation, this paper reviews mathematical analyses and simulation methods applied to the mechanics of the filamentous actin cytoskeleton. The actin cytoskeleton demonstrates characteristic behaviors at every temporal and spatial scale, and mathematical models and simulation methods can be applied to each level of actin cytoskeletal structure ranging from the molecular to the network level. This paper considers studies on mathematical models and simulation methods based on the molecular dynamics, coarse-graining, and continuum dynamics approaches. Every temporal and spatial scale of actin cytoskeletal structure is considered, and it is expected that discrete and continuum dynamics ranging from functional expression at the molecular level to macroscopic functional expression at the whole cell level will be developed and applied to multiscale modeling and simulation.     

Modelling and simulation of porcine liver tissue indentation using finite element method and uniaxial stress–strain data

We hypothesize that both compression and elongation stress–strain data should be considered for modeling and simulation of soft tissue indentation. Uniaxial stress–strain data were obtained from in vitro loading experiments of porcine liver tissue. An axisymmetric finite element model was used to simulate liver tissue indentation with tissue material represented by hyperelastic models. The material parameters were derived from uniaxial stress–strain data of compressions, elongations, and combined compression and elongation of porcine liver samples. in vitro indentation tests were used to validate the finite element simulation. Stress–strain data from the simulation with material parameters derived from the combined compression and elongation data match the experimental data best. This is due to its better ability in modeling 3D deformation since the behavior of biological soft tissue under indentation is affected by both its compressive and tensile characteristics. The combined logarithmic and polynomial model is somewhat better than the 5-constant Mooney–Rivlin model as the constitutive model for this indentation simulation.     

Modeling and simulation of biological systems from image data

This essay provides an introduction to the terminology, concepts, methods, and challenges of image‐based modeling in biology. Image‐based modeling and simulation aims at using systematic, quantitative image data to build predictive models of biological systems that can be simulated with a computer. This allows one to disentangle molecular mechanisms from effects of shape and geometry. Questions like “what is the functional role of shape” or “how are biological shapes generated and regulated” can be addressed in the framework of image‐based systems biology. The combination of image quantification, model building, and computer simulation is illustrated here using the example of diffusion in the endoplasmic reticulum.     

软计算在生态模型中的应用

由于生态系统的高度复杂性和非线性以及空间数据采集技术的快速发展,近年来越来越多的软计算方法开始应用到生态模拟中来。软计算是个非常广泛的领域,在模式上主要包括元胞自动机、基于个体和盒式模式等;在方法上代表性的有人工神经网络、模糊数学、遗传算法、混沌理论等。重点介绍元胞自动机和规律方法在生态模型中的应用,具体实例包括种群动态模拟、水华预警和生境栖息地模拟。     

Quantitative modeling of biochemical networks

Today different database systems for molecular structures (genes and proteins) and metabolic pathways are available. All these systems are characterized by the static data representation. For progress in biotechnology the dynamic representation of this data is important. The metabolism can be characterized as a complex biochemical network. Different models for the quantitative simulation of biochemical networks are discussed, but no useful formalization is available. This paper shows that the theory of Petrinets is useful for the quantitative modeling of biochemical networks.     

土壤-植物-大气连续体水热、CO2通量估算模型研究进展

土壤-植物-大气连续体(SPAC)水热、CO2通量的准确估算对理解陆地和大气的物质和能量交换过程有着重要意义.重点阐述了基于过程的土壤-植物-大气连续体水热、CO2通量模型,综述了统计模型、综合模型及基于遥感的模型的发展过程.其中水热通量统计模型包括基于温度和湿度以及基于温度和辐射的方法;CO2通量统计模型包括基于气候因子或蒸散因子以及基于光能利用率的方法.水热通量过程模型包括大叶、双源、多源和多层的水热传输物理模型;CO2通量过程模型包括叶片尺度及由大叶、双叶和多层方法扩展到冠层尺度的生理生态模型以及光合-蒸腾耦合模型.综合模型包括生物物理模型、生物化学模型和生物地理模型.统计模型形式简单,资料易得,对大范围的水热通量模拟具有指导意义;过程模型准确的揭示了水热和CO2通量传输的物理和生理过程,是大尺度综合模型的基础.未来生态系统水热、CO2通量估算模型将集成各种技术手段进行多尺度网络观测和大尺度机理模拟.     

Managing the environmental problem of seawater intrusion in coastal aquifers through simulation–optimization modeling

The seawater intrusion is a widespread environmental problem of coastal aquifers where more than two third of the world’s population lives. The indiscriminate and unplanned groundwater withdrawal for fulfilling the growing freshwater needs of coastal regions causes this problem. Computer-based models are useful tools for achieving the optimal solution of seawater intrusion management problems. Various simulation and optimization modeling approaches have been used to solve the problems. Optimization approaches have been shown to be of great importance when combined with simulation models. A review on the combined applications of simulation and optimization modeling for the seawater intrusion management of the coastal aquifers are done and is presented in this paper. The reviews revealed that the simulation–optimization modeling approach is very suitable for achieving an optimal solution of seawater intrusion management problems even with a large number of variables. It is recommended that the future research should be directed toward improving the long-term hydraulic assessment by collecting and analyzing widespread spatial data, which can be done by increasing the observation and monitoring networks. The coupling of socioeconomic aspects in the seawater intrusion modeling would be another aspect which could be included in the future studies.     

Modeling and simulation: tools for metabolic engineering.

Mathematical modeling is one of the key methodologies of metabolic engineering. Based on a given metabolic model different computational tools for the simulation, data evaluation, systems analysis, prediction, design and optimization of metabolic systems have been developed. The currently used metabolic modeling approaches can be subdivided into structural models, stoichiometric models, carbon flux models, stationary and nonstationary mechanistic models and models with gene regulation. However, the power of a model strongly depends on its basic modeling assumptions, the simplifications made and the data sources used. Model validation turns out to be particularly difficult for metabolic systems. The different modeling approaches are critically reviewed with respect to their potential and benefits for the metabolic engineering cycle. Several tools that have emerged from the different modeling approaches including structural pathway synthesis, stoichiometric pathway analysis, metabolic flux analysis, metabolic control analysis, optimization of regulatory architectures and the evaluation of rapid sampling experiments are discussed.     

Simulation of the cardiovascular system using equivalent electronic system

This paper describes simulation of the cardiovascular system using a complex electronic circuit. In this study we have taken a slightly different approach to the modeling of the system and tried to advance existing electrical models by increasing more segments and parameters. The model consists of 42 segments representing the arterial system. Anatomical and physiological data for circuit parameters have been extracted from medical articles and textbooks. The frequency of heart is 1 Hz and the system operates in steady state condition. Each artery is modeled by one capacitor, resistor and inductor. The left and right ventricles are modeled using AC power suppliers and diodes. The results of the simulation including pressure and volume graphs exhibit operation of the cardiovascular system under normal condition. The results of the simulation have been compared with the relevant experimental observation and are in good agreement with them.     

Guaranteeing the quality of multidimensional analysis in data warehouses of simulation results: Application to pesticide transfer data produced by the MACRO model

Currently, the vital impact of environmental pollution on economic, social and health dimensions has been recognized. The need for theoretical and implementation frameworks for the acquisition, modeling and analysis of environmental data as well as tools to conceive and validate scenarios is becoming increasingly important. For these reasons, different environmental simulation models have been developed. Researchers and stakeholders need efficient tools to store, display, compare and analyze data that are produced by simulation models. One common way to manage simulation results is to use text files; however, text files make it difficult to explore the data. Spreadsheet tools (e.g., OpenOffice, MS Excel) can help to display and analyze model results, but they are not suitable for very large volumes of information. Recently, some studies have shown the feasibility of using Data Warehouse (DW) and On-Line Analytical Processing (OLAP) technologies to store model results and to facilitate model visualization, analysis and comparisons. These technologies allow model users to easily produce graphical reports and charts. In this paper, we address the analysis of pesticide transfer simulation results by warehousing and OLAPing data, for which the data results from the MACRO simulation model. This model simulates hydrological transfers of pesticides at the plot scale. We demonstrate how the simulation results can be managed using DW technologies. We also demonstrate how the use of integrity constraints can improve OLAP analysis. These constraints are used to maintain the quality of the warehoused data as well as to maintain the aggregations and queries, which will lead to better analysis, conclusions and decisions.     

Population genetics models of local ancestry

Migrations have played an important role in shaping the genetic diversity of human populations. Understanding genomic data thus requires careful modeling of historical gene flow. Here we consider the effect of relatively recent population structure and gene flow and interpret genomes of individuals that have ancestry from multiple source populations as mosaics of segments originating from each population. This article describes general and tractable models for local ancestry patterns with a focus on the length distribution of continuous ancestry tracts and the variance in total ancestry proportions among individuals. The models offer improved agreement with Wright-Fisher simulation data when compared to the state-of-the art and can be used to infer time-dependent migration rates from multiple populations. Considering HapMap African-American (ASW) data, we find that a model with two distinct phases of "European" gene flow significantly improves the modeling of both tract lengths and ancestry variances.     

Modeling of Sugar Crystallization through Knowledge Integration

This paper reports on the comparison of three modeling approaches that were applied to a fed batch evaporative sugar crystallization process. They are termed white box, black box, and grey box modeling strategies, which reflects the level of physical transparency and understanding of the model. White box models represent the traditional modeling approach, based on modeling by first principles. Black box models rely on recorded process data and knowledge collected during the normal process operation. Among various tools in this group an artificial neural networks (ANN) approach is adopted in this paper. The grey box model is obtained from a combination of first principles modeling, based on mass, energy and population balances, with an ANN to approximate three kinetic parameters ‐‐ crystal growth rate, nucleation rate and the agglomeration kernel. The results have shown that the hybrid modeling approach outperformed the other aforementioned modeling strategies.     

Rigid-body modeling of knee cartilage and meniscus using experimental pressure-strain curves

Rigid-body knee models have gained popularity thanks to computational speed and ease of setup compared to finite element models—showing exciting potential for clinical patient-specific models in the future. However, Rigid-body studies in general have encountered difficulty in modeling cartilage and especially meniscus material properties, often relying on computationally costly optimization techniques. This paper presents two new methods to alleviate the difficulty—one to define model contact pressure and one to define meniscus internal forces—and is the first to our knowledge to use experimental pressure-strain curves from the literature to simulate cartilage and meniscus behavior in a rigid body model. This paper describes the methodology to derive the proof of concept model and preliminary results from a gait simulation based on ISO 14243-1.     

基于模型的景观格局与生态过程研究

景观格局与生态过程关系的研究是景观生态学的主要特色和理论核心之一。模型可以充分利用实验和观测数据并综合不同时间和空间尺度上的信息提炼规律或揭示内在机制,模拟景观格局与生态过程的动态与相互关系,成为景观生态学研究的有力工具。结合研究实例,总结了基于模型的景观格局研究、生态过程研究和格局-过程关系研究的发展现状和薄弱环节,同时探讨了通过构建耦合模型研究格局-过程相互关系的途径。总结了景观模型研究亟待发展的领域与发展趋势。     

The hermeneutics of ecological simulation

Computer simulation has become important in ecological modeling, but there have been few assessments on how complex simulation models differ from more traditional analytic models. In Part I of this paper, I review the challenges faced in complex ecological modeling and how models have been used to gain theoretical purchase for understanding natural systems. I compare the use of traditional analytic simulation models and point how that the two methods require different kinds of practical engagement. I examine a case study of three models from the insect resistance literature in transgenic crops to illustrate and explore differences in analytic and computer simulation models. I argue that analyzing simulation models has been often inappropriately managed with expectations derived from handling analytic models. In Part II, I look at simulation as a hermeneutic practice. I argue that simulation models are a practice or techné. I the explore five aspects of philosophical hermeneutics that may be useful in complex ecological simulation: (1) an openness to multiple perspectives allowing multiple levels of scientific pluralism, (2) the hermeneutic circle, a back and forth in active communication among both modelers and ecologists; (3) the recognition of human factors and the nature of human practices as such, including recognizing the role of judgments and choices in the modeling enterprise; (4) the importance of play in modeling; (5) the non-closed nature of hermeneutic engagement, continued dialogue, and recognizing the situatedness, incompleteness, and tentative nature of simulation models.

State space modeling of yeast gene expression dynamics

Combined interaction of all the genes forms a central part of the functional system of a cell. Thus, especially the data-based modeling of the gene expression network is currently one of the main challenges in the field of systems biology. However, the problem is an extremely high-dimensional and complex one, so that normal identification methods are usually not applicable specially if aiming at dynamic models. We propose in this paper a subspace identification approach, which is well suited for high-dimensional system modeling and the presented modified version can also handle the underdetermined case with less data samples than variables (genes). The algorithm is applied to two public stress-response data sets collected from yeast Saccharomyces cerevisiae. The obtained dynamic state space model is tested by comparing the simulation results with the measured data. It is shown that the identified model can relatively well describe the dynamics of the general stress-related changes in the expression of the complete yeast genome. However, it seems inevitable that more precise modeling of the dynamics of the whole genome would require experiments especially designed for systemic modeling.     

Evaluation of Tools for Modeling Manufacturing Systems Design with Multiple Levels of Detail

This paper presents an investigation of simulation packages regarding their ability to model business processes related to manufacturing systems. Three simulation packages are investigated: VS7, SIMAN/CINEMA IV, and SIMFACTORY II.5. These packages are evaluated with regard to their capabily of modeling problems related to the manufacturing systems design (MSD) framework, which involves different levels of detail: the conceptual modeling level and the detailed design level. The investigation is based on a case study related to manufacturing systems. The main objective of this investigation is to examine the manufacturing simulation packages and their ability to offer variable detail modeling. Research findings suggest that no simulation environment offers sufficiently flexible facilities for the variable detailed modeling of manufacturing systems design. The paper proposes a method for systems entity classification to increase the levels of detail in an effective manner without duplication of data collection and model building efforts.     

Phenomenological and molecular-level Petri net modeling and simulation of long-term potentiation

Petri net-based modeling methods have been used in many research projects to represent biological systems. Among these, the hybrid functional Petri net (HFPN) was developed especially for biological modeling in order to provide biologists with a more intuitive Petri net-based method. In the literature, HFPNs are used to represent kinetic models at the molecular level. We present two models of long-term potentiation previously represented by differential equations which we have transformed into HFPN models: a phenomenological synapse model and a molecular-level model of the CaMKII regulation pathway. Through simulation, we obtained results similar to those of previous studies using these models. Our results open the way to a new type of modeling for systems biology where HFPNs are used to combine different levels of abstraction within one model. This approach can be useful in fully modeling a system at the molecular level when kinetic data is missing or when a full study of a system at the molecular level it is not within the scope of the research.