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

Property-Based Testing - The ProTest Project

The ProTest project is an FP7 STREP on property based testing. The purpose of the project is to develop software engineering approaches to improve reliability of service-oriented networks; support fault-finding and diagnosis based on specified properties of the system. And to do so we will build automated tools that will generate and run tests, monitor execution at run-time, and log events for analysis. The Erlang / Open Telecom Platform has been chosen as our initial implementation vehicle due to its robustness and reliability within the telecoms sector. It is noted for its success in the ATM telecoms switches by Ericsson, one of the project partners, as well as for multiple other uses such as in facebook, yahoo etc. In this paper we provide an overview of the project goals, as well as detailing initial progress in developing property based testing techniques and tools for the concurrent functional programming language Erlang

A methodology for full-system power modeling in heterogeneous data centers

The need for energy-awareness in current data centers has encouraged the use of power modeling to estimate their power consumption. However, existing models present noticeable limitations, which make them application-dependent, platform-dependent, inaccurate, or computationally complex. In this paper, we propose a platform-and application-agnostic methodology for full-system power modeling in heterogeneous data centers that overcomes those limitations. It derives a single model per platform, which works with high accuracy for heterogeneous applications with different patterns of resource usage and energy consumption, by systematically selecting a minimum set of resource usage indicators and extracting complex relations among them that capture the impact on energy consumption of all the resources in the system. We demonstrate our methodology by generating power models for heterogeneous platforms with very different power consumption profiles. Our validation experiments with real Cloud applications show that such models provide high accuracy (around 5% of average estimation error).This work is supported by the Spanish Ministry of Economy and Competitiveness under contract TIN2015-65316-P, by the Gener- alitat de Catalunya under contract 2014-SGR-1051, and by the European Commission under FP7-SMARTCITIES-2013 contract 608679 (RenewIT) and FP7-ICT-2013-10 contracts 610874 (AS- CETiC) and 610456 (EuroServer).Peer ReviewedPostprint (author's final draft

Formal Modelling, Testing and Verification of HSA Memory Models using Event-B

The HSA Foundation has produced the HSA Platform System Architecture Specification that goes a long way towards addressing the need for a clear and consistent method for specifying weakly consistent memory. HSA is specified in a natural language which makes it open to multiple ambiguous interpretations and could render bugs in implementations of it in hardware and software. In this paper we present a formal model of HSA which can be used in the development and verification of both concurrent software applications as well as in the development and verification of the HSA-compliant platform itself. We use the Event-B language to build a provably correct hierarchy of models from the most abstract to a detailed refinement of HSA close to implementation level. Our memory models are general in that they represent an arbitrary number of masters, programs and instruction interleavings. We reason about such general models using refinements. Using Rodin tool we are able to model and verify an entire hierarchy of models using proofs to establish that each refinement is correct. We define an automated validation method that allows us to test baseline compliance of the model against a suite of published HSA litmus tests. Once we complete model validation we develop a coverage driven method to extract a richer set of tests from the Event-B model and a user specified coverage model. These tests are used for extensive regression testing of hardware and software systems. Our method of refinement based formal modelling, baseline compliance testing of the model and coverage driven test extraction using the single language of Event-B is a new way to address a key challenge facing the design and verification of multi-core systems.Comment: 9 pages, 10 figure

Reporting an Experience on Design and Implementation of e-Health Systems on Azure Cloud

Electronic Health (e-Health) technology has brought the world with significant transformation from traditional paper-based medical practice to Information and Communication Technologies (ICT)-based systems for automatic management (storage, processing, and archiving) of information. Traditionally e-Health systems have been designed to operate within stovepipes on dedicated networks, physical computers, and locally managed software platforms that make it susceptible to many serious limitations including: 1) lack of on-demand scalability during critical situations; 2) high administrative overheads and costs; and 3) in-efficient resource utilization and energy consumption due to lack of automation. In this paper, we present an approach to migrate the ICT systems in the e-Health sector from traditional in-house Client/Server (C/S) architecture to the virtualised cloud computing environment. To this end, we developed two cloud-based e-Health applications (Medical Practice Management System and Telemedicine Practice System) for demonstrating how cloud services can be leveraged for developing and deploying such applications. The Windows Azure cloud computing platform is selected as an example public cloud platform for our study. We conducted several performance evaluation experiments to understand the Quality Service (QoS) tradeoffs of our applications under variable workload on Azure.Comment: Submitted to third IEEE International Conference on Cloud and Green Computing (CGC 2013

Holistic debugging - enabling instruction set simulation for software quality assurance

We present holistic debugging, a novel method for observing execution of complex and distributed software. It builds on an instruction set simulator, which provides reproducible experiments and non-intrusive probing of state in a distributed system. Instruction set simulators, however, only provide low-level information, so a holistic debugger contains a translation framework that maps this information to higher abstraction level observation tools, such as source code debuggers. We have created Nornir, a proof-of-concept holistic debugger, built on the simulator Simics. For each observed process in the simulated system, Nornir creates an abstraction translation stack, with virtual machine translators that map machine-level storage contents (e.g. physical memory, registers) provided by Simics, to application-level data (e.g. virtual memory contents) by parsing the data structures of operating systems and virtual machines. Nornir includes a modified version of the GNU debugger (GDB), which supports non-intrusive symbolic debugging of distributed applications. Nornir's main interface is a debugger shepherd, a programmable interface that controls multiple debuggers, and allows users to coherently inspect the entire state of heterogeneous, distributed applications. It provides a robust observation platform for construction of new observation tools