Physiologically based synthetic models of hepatic disposition

Current Physiologically based pharmacokinetic (PBPK) models are inductive. We present an additional, different approach that is based on the synthetic rather than the inductive approach to modeling and simulation. It relies on object-oriented programming A model of the referent system in its experimental context is synthesized by assembling objects that represent components such as molecules, cells, aspects of tissue architecture, catheters, etc. The single pass perfused rat liver has been well described in evaluating hepatic drug pharmacokinetics (PK) and is the system on which we focus. In silico experiments begin with administration of objects representing actual compounds. Data are collected in a manner analogous to that in the referent PK experiments. The synthetic modeling method allows for recognition and representation of discrete event and discrete time processes, as well as heterogeneity in organization, function, and spatial effects. An application is developed for sucrose and antipyrine, administered separately and together PBPK modeling has made extensive progress in characterizing abstracted PK properties but this has also been its limitation. Now, other important questions and possible extensions emerge. How are these PK properties and the observed behaviors generated? The inherent heuristic limitations of traditional models have hindered getting meaningful, detailed answers to such questions. Synthetic models of the type described here are specifically intended to help answer such questions. Analogous to wet-lab experimental models, they retain their applicability even when broken apart into sub-components. Having and applying this new class of models along with traditional PK modeling methods is expected to increase the productivity of pharmaceutical research at all levels that make use of modeling and simulation.

Agent-based distributed software verification

Despite decades of research, the takeup of formal methods for developing provably correct software in industry remains slow. One reason for this is the high cost of proof construction, an activity that, due to the complexity of the required proofs, is typically carried out using interactive theorem provers. In this paper we propose an agent-oriented architecture for interactive theorem proving with the aim of reducing the user interactions (and thus the cost) of constructing software verification proofs. We describe a prototype implementation of our architecture and discuss its application to a small, but non-trivial case study.

Hybrid knowledge representation in a blackboard KBS for liquid retaining structure design

This paper highlights the importance of design expertise, for designing liquid retaining structures, including subjective judgments and professional experience. Design of liquid retaining structures has special features different from the others. Being more vulnerable to corrosion problem, they have stringent requirements against serviceability limit state of crack. It is the premise of the study to transferring expert knowledge in a computerized blackboard system. Hybrid knowledge representation schemes, including production rules, object-oriented programming, and procedural methods, are employed to express engineering heuristics and standard design knowledge during the development of the knowledge-based system (KBS) for design of liquid retaining structures. This approach renders it possible to take advantages of the characteristics of each method. The system can provide the user with advice on preliminary design, loading specification, optimized configuration selection and detailed design analysis of liquid retaining structure. It would be beneficial to the field of retaining structure design by focusing on the acquisition and organization of expert knowledge through the development of recent artificial intelligence technology. (C) 2003 Elsevier Ltd. All rights reserved.

A conceptual model of personalized virtual learning environments

The Virtual Learning Environment (VLE) is one of the fastest growing areas in educational technology research and development. In order to achieve learning effectiveness, ideal VLEs should be able to identify learning needs and customize solutions, with or without an instructor to supplement instruction. They are called Personalized VLEs (PVLEs). In order to achieve PVLEs success, comprehensive conceptual models corresponding to PVLEs are essential. Such conceptual modeling development is important because it facilitates early detection and correction of system development errors. Therefore, in order to capture the PVLEs knowledge explicitly, this paper focuses on the development of conceptual models for PVLEs, including models of knowledge primitives in terms of learner, curriculum, and situational models, models of VLEs in general pedagogical bases, and particularly, the definition of the ontology of PVLEs on the constructivist pedagogical principle. Based on those comprehensive conceptual models, a prototyped multiagent-based PVLE has been implemented. A field experiment was conducted to investigate the learning achievements by comparing personalized and non-personalized systems. The result indicates that the PVLE we developed under our comprehensive ontology successfully provides significant learning achievements. These comprehensive models also provide a solid knowledge representation framework for PVLEs development practice, guiding the analysis, design, and development of PVLEs. (c) 2005 Elsevier Ltd. All rights reserved.

A knowledge-based system for liquid retaining structure design with blackboard architecture

Owing to the high degree of vulnerability of liquid retaining structures to corrosion problems, there are stringent requirements in its design against cracking. In this paper, a prototype knowledge-based system is developed and implemented for the design of liquid retaining structures based on the blackboard architecture. A commercially available expert system shell VISUAL RULE STUDIO working as an ActiveX Designer under the VISUAL BASIC programming environment is employed. Hybrid knowledge representation approach with production rules and procedural methods under object-oriented programming are used to represent the engineering heuristics and design knowledge of this domain. It is demonstrated that the blackboard architecture is capable of integrating different knowledge together in an effective manner. The system is tailored to give advice to users regarding preliminary design, loading specification and optimized configuration selection of this type of structure. An example of application is given to illustrate the capabilities of the prototype system in transferring knowledge on liquid retaining structure to novice engineers. (C) 2004 Elsevier Ltd. All rights reserved.

Tool support for executable documentation of Java class hierarchies

While object-oriented programming offers great solutions for today's software developers, this success has created difficult problems in class documentation and testing. In Java, two tools provide assistance: Javadoc allows class interface documentation to be embedded as code comments and JUnit supports unit testing by providing assert constructs and a test framework. This paper describes JUnitDoc, an integration of Javadoc and JUnit, which provides better support for class documentation and testing. With JUnitDoc, test cases are embedded in Javadoc comments and used as both examples for documentation and test cases for quality assurance. JUnitDoc extracts the test cases for use in HTML files serving as class documentation and in JUnit drivers for class testing. To address the difficult problem of testing inheritance hierarchies, JUnitDoc provides a novel solution in the form of a parallel test hierarchy. A small controlled experiment compares the readability of JUnitDoc documentation to formal documentation written in Object-Z. Copyright (c) 2005 John Wiley & Sons, Ltd.

Dealing with non-determinism in testing concurrent java components

The testing of concurrent software components can be difficult due to the inherent non-determinism present in these components. For example, if the same test case is run multiple times, it may produce different results. This non-determinism may lead to problems with determining expected outputs. In this paper, we present and discuss several possible solutions to this problem in the context of testing concurrent Java components using the ConAn testing tool. We then present a recent extension to the tool that provides a general solution to this problem that is sufficient to deal with the level of non-determinism that we have encountered in testing over 20 components with ConAn. © 2005 IEEE

Modelling Java concurrency with Object-Z

In this paper, we present a formal model of Java concurrency using the Object-Z specification language. This model captures the Java thread synchronization concepts of locking, blocking, waiting and notification. In the model, we take a viewpoints approach, first capturing the role of the objects and threads, and then taking a system view where we capture the way the objects and threads cooperate and communicate. As a simple illustration of how the model can, in general be applied, we use Object-Z inheritance to integrate the model with the classical producer-consumer system to create a specification directly incorporating the Java concurrency constructs.

A classification of concurrency failures in java components

The Java programming language supports concurrency. Concurrent programs are hard to test due to their inherent non-determinism. This paper presents a classification of concurrency failures that is based on a model of Java concurrency. The model and failure classification is used to justify coverage of synchronization primitives of concurrent components. This is achieved by constructing concurrency flow graphs for each method call. A producer-consumer monitor is used to demonstrate how the approach can be used to measure coverage of concurrency primitives and thereby assist in determining test sequences for deterministic execution.

Animation of object-z specifications using a Z animator

We discuss a methodology for animating the Object-Z specification language using a Z animation environment. Central to the process is the introduction of a framework to handle dynamic instantiation of objects and management of object references. Particular focus is placed upon building the animation environment through pre-existing tools, and a case study is presented that implements the proposed framework using a shallow encoding in the Possum Z animator. The animation of Object-Z using Z is both automated and made transparent to the user through the use of a software tool named O-zone.

Embedding defeasible logic into logic programming

Defeasible reasoning is a simple but efficient approach to nonmonotonic reasoning that has recently attracted considerable interest and that has found various applications. Defeasible logic and its variants are an important family of defeasible reasoning methods. So far no relationship has been established between defeasible logic and mainstream nonmonotonic reasoning approaches. In this paper we establish close links to known semantics of logic programs. In particular, we give a translation of a defeasible theory D into a meta-program P(D). We show that under a condition of decisiveness, the defeasible consequences of D correspond exactly to the sceptical conclusions of P(D) under the stable model semantics. Without decisiveness, the result holds only in one direction (all defeasible consequences of D are included in all stable models of P(D)). If we wish a complete embedding for the general case, we need to use the Kunen semantics of P(D), instead.