Petri Net Siphon Analysis and Network Centrality Measures for Identifying Combination Therapies in Signaling Pathways

Aberrant behavior of biological signaling pathways has been implicated in diseases such as cancers. Therapies have been developed to target proteins in these networks in the hope of curing the illness or bringing about remission. However, identifying targets for drug inhibition that exhibit good therapeutic index has proven to be challenging since signaling pathways have a large number of components and many interconnections such as feedback, crosstalk, and divergence. Unfortunately, some characteristics of these pathways such as redundancy, feedback, and drug resistance reduce the efficacy of single drug target therapy and necessitate the employment of more than one drug to target multiple nodes in the system. However, choosing multiple targets with high therapeutic index poses more challenges since the combinatorial search space could be huge. To cope with the complexity of these systems, computational tools such as ordinary differential equations have been used to successfully model some of these pathways. Regrettably, for building these models, experimentally-measured initial concentrations of the components and rates of reactions are needed which are difficult to obtain, and in very large networks, they may not be available at the moment. Fortunately, there exist other modeling tools, though not as powerful as ordinary differential equations, which do not need the rates and initial conditions to model signaling pathways. Petri net and graph theory are among these tools. In this thesis, we introduce a methodology based on Petri net siphon analysis and graph network centrality measures for identifying prospective targets for single and multiple drug therapies. In this methodology, first, potential targets are identified in the Petri net model of a signaling pathway using siphon analysis. Then, the graph-theoretic centrality measures are employed to prioritize the candidate targets. Also, an algorithm is developed to check whether the candidate targets are able to disable the intended outputs in the graph model of the system or not. We implement structural and dynamical models of ErbB1-Ras-MAPK pathways and use them to assess and evaluate this methodology. The identified drug-targets, single and multiple, correspond to clinically relevant drugs. Overall, the results suggest that this methodology, using siphons and centrality measures, shows promise in identifying and ranking drugs. Since this methodology only uses the structural information of the signaling pathways and does not need initial conditions and dynamical rates, it can be utilized in larger networks.

Bottlenecks detection of track allocation schemes at rail stations by Petri nets

Robustness of the track allocation problem is rarely addressed in literatures and the obtained track allocation schemes (TAS) embody some bottlenecks. Therefore, an approach to detect bottlenecks is needed to support local optimization. First a TAS is transformed to an executable model by Petri nets. Then disturbances analysis is performed using the model and the indicators of the total trains' departure delays are collected to detect bottlenecks when each train suffers a disturbance. Finally, the results of the tests based on a rail hub linking six lines and a TAS about thirty minutes show that the minimum buffer time is 21 seconds and there are two bottlenecks where the buffer times are 57 and 44 seconds respectively, and it indicates that the bottlenecks do not certainly locate at the area where there is minimum buffer time. The proposed approach can further support selection of multi schemes and robustness optimization.

Modeling resource management in the building design process by information constraint Petri nets

The effect of resource management on the building design process directly influences the development cycle time and success of construction projects. This paper presents the information constraint net (ICN) to represent the complex information constraint relations among design activities involved in the building design process. An algorithm is developed to transform the information constraints throughout the ICN into a Petri net model. A resource management model is developed using the ICN to simulate and optimize resource allocation in the design process. An example is provided to justify the proposed model through a simulation analysis of the CPN Tools platform in the detailed structural design. The result demonstrates that the proposed approach can obtain the resource management and optimization needed for shortening the development cycle and optimal allocation of resources.

Graphical simulation of Petri Nets

An interactive graphics package for modeling with Petri Nets has been implemented. It uses the VT-11 graphics terminal supported on the PDP-11/35 computer to draw, execute, analyze, edit and redraw a Petri Net. Each of the above mentioned tasks can be performed by selecting appropriate items from a menu displayed on the screen. Petri Nets with a reasonably large number of nodes can be created and analyzed using this package. The number of nodes supported may be increased by making simple changes in the program. Being interactive, the program seeks information from the user after displaying appropriate messages on the terminal. After completing the Petri Net, it may be executed step by step and the changes in the number of tokens may be observed on the screen, at each place. Some properties of Petri Nets like safety, boundedness, conservation and redundancy can be checked using this package. This package can be used very effectively for modeling asynchronous (concurrent) systems with Petri Nets and simulating the model by “graphical execution.”

应用于PLC控制程序的Petri网执行模型

在现有的工业控制系统中经常使用PLC实现顺序控制、定时等功能.控制程序经常需要执行同步操作且输入开关量的触发时机具有不确定性,因此无法充分描述真实的执行过程.为此提出下述解决方法:首先在控制程序的编译阶段,使用Petri网建立网模型以表示程序执行逻辑,其次在控制程序的执行阶段,根据程序真实执行状况动态运行上述网模型,当程序运行结束时网模型停止执行,由此判断程序中存在的逻辑错误.

Nonautonomous elementary net systems and their application to programmable logic control

In this paper, a novel approach to Petri net modeling of programmable logic controller (PLC) programs is presented. The modeling approach is a simple extension of elementary net systems, and a graphical design tool that supports the use of this modeling approach is provided. A key characteristic of the model is that the binary sensory inputs and binary actuation outputs of the PLC are explicitly represented. This leads to the following two improvements: outputs are unambiguous, and interaction patterns are more clearly represented in the graphical form. The use of this modeling approach produces programs that are simple, lightweight, and portable. The approach is demonstrated by applying it to the development of a control module for a MonTech Positioning Station. © 2008 IEEE.

Petri网可达性的综合判定法

Petri网标识的可达性判定问题是进行Petri网分析的基础,而传统的判定方法并不能确保所得结果的可靠性.在揭示Petri网可达性问题的实质之后,讨论了在标识图的同一连通域内标识可达性的判定问题,进而在分析相关原理的基础上提出了一种有效判定Petri网标识可达性的综合判定法.此判定方法综合多种传统判定方法的优点,结合Gr鯾ner基理论,确保了对Petri网标识可达性进行判定所得结果的可靠性.

基于Petri网的Web服务流程建模方法研究

随着网络应用的蓬勃发展,Web服务越来越普及。在实际应用中,往往需要对已有Web服务进行集成。目前通常的企业Web服务集成过程,都是先根据企业的业务流程建立相应的Web服务流程模型,再由此建立应用系统。而目前已有的建模手段的共同问题是：无法确保模型的正确性和与具体业务的紧密吻合。该文提出一种基于Petri网的Web服务流程建模方法。该建模方法通过将Petri网引入建模过程弥补了原建模过程中无法直观感受模型的不足,通过建立一套完备的形式化定义保证了建立模型的正确性,通过将紧同步随机Petri网引入建模过程可以更好的描述实际业务。通过使用该方法, 可以很好地解决现在Web流程建模过程中存在的问题。此方法也为其他领域中的流程建模仿真提供了一种很好的解决问题的方法和思路。

基于有色Petri网的Web服务组合建模与分析

形式化定义了Web服务组合过程中的5种基本逻辑结构,并采用有色Petri网表示,然后将其抽象为服务的代数运算;在此基础上,提出了经过服务运算后得到的服务的性质及组合服务的构造方法;最后通过实例分析,说明该建模方法可以保证组合的服务是正确且可终止的。

基于有限状态机与Petri网的系统分析与设计

从系统组成、功能需求和体系结构方面介绍了航天器空间对接仿真系统的实时多任务控制系统,基于有限状态机和Petri网方法对其进行了单任务级和多任务级的分析建模,并以此为基础完成系统的详细设计,其中应用分叉和资源共享模型实现了系统的同步和互斥问题。实际应用中应用工程化和模块化的方法完成系统设计,系统运行性能良好。试验证明这种分析设计方法合理可行。

基于Petri网的Web数据库访问的建模研究

本文针对多用户访问Web数据库的过程进行了分析并提出改进思路,然后利用带抑止弧的扩充Petri网对改进后的访问过程进行建模。

基于时延Petri网的多UUV系统的任务分配策略

针对多水下机器人(unmanned underwater vehicle,UUV)系统动态任务分配问题展开研究,在对系统的体系结构和任务分配机制进行分析的基础上,利用时延 Petri 网理论对系统的任务分配进行建模,提出了一种新的任务分配策略:群体协调层采用集中式任务分配策略,由主 UUV 将任务实时下达给各从 UUV;监控规划层采用基于适应度的分布式任务分配方式,充分发挥各异构 UUV 自身的智能。仿真结果验证了模型的合理性和任务分配策略的有效性。