Engineering simulations for cancer systems biology

Computer simulation can be used to inform in vivo and in vitro experimentation, enabling rapid, low-cost hypothesis generation and directing experimental design in order to test those hypotheses. In this way, in silico models become a scientific instrument for investigation, and so should be developed to high standards, be carefully calibrated and their findings presented in such that they may be reproduced. Here, we outline a framework that supports developing simulations as scientific instruments, and we select cancer systems biology as an exemplar domain, with a particular focus on cellular signalling models. We consider the challenges of lack of data, incomplete knowledge and modelling in the context of a rapidly changing knowledge base. Our framework comprises a process to clearly separate scientific and engineering concerns in model and simulation development, and an argumentation approach to documenting models for rigorous way of recording assumptions and knowledge gaps. We propose interactive, dynamic visualisation tools to enable the biological community to interact with cellular signalling models directly for experimental design. There is a mismatch in scale between these cellular models and tissue structures that are affected by tumours, and bridging this gap requires substantial computational resource. We present concurrent programming as a technology to link scales without losing important details through model simplification. We discuss the value of combining this technology, interactive visualisation, argumentation and model separation to support development of multi-scale models that represent biologically plausible cells arranged in biologically plausible structures that model cell behaviour, interactions and response to therapeutic interventions

Simplification of UML/OCL schemas for efficient reasoning

Ensuring the correctness of a conceptual schema is an essential task in order to avoid the propagation of errors during software development. The kind of reasoning required to perform such task is known to be exponential for UML class diagrams alone and even harder when considering OCL constraints. Motivated by this issue, we propose an innovative method aimed at removing constraints and other UML elements of the schema to obtain a simplified one that preserve the same reasoning outcomes. In this way, we can reason about the correctness of the initial artifact by reasoning on a simplified version of it. Thus, the efficiency of the reasoning process is significantly improved. In addition, since our method is independent from the reasoning engine used, any reasoning method may benefit from it.Peer ReviewedPostprint (author's final draft

Enhancing the EAST-ADL error model with HiP-HOPS semantics

EAST-ADL is a domain-specific modelling language for the engineering of automotive embedded systems. The language has abstractions that enable engineers to capture a variety of information about design in the course of the lifecycle — from requirements to detailed design of hardware and software architectures. The specification of the EAST-ADL language includes an error model extension which documents language structures that allow potential failures of design elements to be specified locally. The effects of these failures are then later assessed in the context of the architecture design. To provide this type of useful assessment, a language and a specification are not enough; a compiler-like tool that can read and operate on a system specification together with its error model is needed. In this paper we integrate the error model of EAST-ADL with the precise semantics of HiP-HOPS — a state-of-the-art tool that enables dependability analysis and optimization of design models. We present the integration concept between EAST-ADL structure and HiP-HOPS error propagation logic and its transformation into the HiP-HOPS model. Source and destination models are represented using the corresponding XML formats. The connection of these two models at tool level enables practical EAST-ADL designs of embedded automotive systems to be analysed in terms of dependability, i.e. safety, reliability and availability. In addition, the information encoded in the error model can be re-used across different contexts of application with the associated benefits for cost reduction, simplification, and rationalisation of dependability assessments in complex engineering designs

An overview of very high level software design methods

Very High Level design methods emphasize automatic transfer of requirements to formal design specifications, and/or may concentrate on automatic transformation of formal design specifications that include some semantic information of the system into machine executable form. Very high level design methods range from general domain independent methods to approaches implementable for specific applications or domains. Applying AI techniques, abstract programming methods, domain heuristics, software engineering tools, library-based programming and other methods different approaches for higher level software design are being developed. Though one finds that a given approach does not always fall exactly in any specific class, this paper provides a classification for very high level design methods including examples for each class. These methods are analyzed and compared based on their basic approaches, strengths and feasibility for future expansion toward automatic development of software systems

The Construction of Verification Models for Embedded Systems

The usefulness of verification hinges on the quality of the verification model. Verification is useful if it increases our confidence that an artefact bahaves as expected. As modelling inherently contains non-formal elements, the qualityof models cannot be captured by purely formal means. Still, we argue that modelling is not an act of irrationalism and unpredictable geniality, but follows rational arguments, that often remain implicit. In this paper we try to identify the tacit rationalism in the model construction as performed by most people doing modelling for verification. By explicating the different phases, arguments, and design decisions in the model construction, we try to develop guidelines that help to improve the process of model construction and the quality of models

Mapping Big Data into Knowledge Space with Cognitive Cyber-Infrastructure

Big data research has attracted great attention in science, technology, industry and society. It is developing with the evolving scientific paradigm, the fourth industrial revolution, and the transformational innovation of technologies. However, its nature and fundamental challenge have not been recognized, and its own methodology has not been formed. This paper explores and answers the following questions: What is big data? What are the basic methods for representing, managing and analyzing big data? What is the relationship between big data and knowledge? Can we find a mapping from big data into knowledge space? What kind of infrastructure is required to support not only big data management and analysis but also knowledge discovery, sharing and management? What is the relationship between big data and science paradigm? What is the nature and fundamental challenge of big data computing? A multi-dimensional perspective is presented toward a methodology of big data computing.Comment: 59 page

The SP theory of intelligence: benefits and applications

This article describes existing and expected benefits of the "SP theory of intelligence", and some potential applications. The theory aims to simplify and integrate ideas across artificial intelligence, mainstream computing, and human perception and cognition, with information compression as a unifying theme. It combines conceptual simplicity with descriptive and explanatory power across several areas of computing and cognition. In the "SP machine" -- an expression of the SP theory which is currently realized in the form of a computer model -- there is potential for an overall simplification of computing systems, including software. The SP theory promises deeper insights and better solutions in several areas of application including, most notably, unsupervised learning, natural language processing, autonomous robots, computer vision, intelligent databases, software engineering, information compression, medical diagnosis and big data. There is also potential in areas such as the semantic web, bioinformatics, structuring of documents, the detection of computer viruses, data fusion, new kinds of computer, and the development of scientific theories. The theory promises seamless integration of structures and functions within and between different areas of application. The potential value, worldwide, of these benefits and applications is at least $190 billion each year. Further development would be facilitated by the creation of a high-parallel, open-source version of the SP machine, available to researchers everywhere.Comment: arXiv admin note: substantial text overlap with arXiv:1212.022

The development of a program analysis environment for Ada

A unit level, Ada software module testing system, called Query Utility Environment for Software Testing of Ada (QUEST/Ada), is described. The project calls for the design and development of a prototype system. QUEST/Ada design began with a definition of the overall system structure and a description of component dependencies. The project team was divided into three groups to resolve the preliminary designs of the parser/scanner: the test data generator, and the test coverage analyzer. The Phase 1 report is a working document from which the system documentation will evolve. It provides history, a guide to report sections, a literature review, the definition of the system structure and high level interfaces, descriptions of the prototype scope, the three major components, and the plan for the remainder of the project. The appendices include specifications, statistics, two papers derived from the current research, a preliminary users' manual, and the proposal and work plan for Phase 2