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

Towards adaptive multi-robot systems: self-organization and self-adaptation

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.The development of complex systems ensembles that operate in uncertain environments is a major challenge. The reason for this is that system designers are not able to fully specify the system during specification and development and before it is being deployed. Natural swarm systems enjoy similar characteristics, yet, being self-adaptive and being able to self-organize, these systems show beneficial emergent behaviour. Similar concepts can be extremely helpful for artificial systems, especially when it comes to multi-robot scenarios, which require such solution in order to be applicable to highly uncertain real world application. In this article, we present a comprehensive overview over state-of-the-art solutions in emergent systems, self-organization, self-adaptation, and robotics. We discuss these approaches in the light of a framework for multi-robot systems and identify similarities, differences missing links and open gaps that have to be addressed in order to make this framework possible

Actor based behavioural simulation as an aid for organisational decision making

Decision-making is a critical activity for most of the modern organizations to stay competitive in rapidly changing business environment. Effective organisational decision-making requires deep understanding of various organisational aspects such as its goals, structure, business-as-usual operational processes, environment where it operates, and inherent characteristics of the change drivers that may impact the organisation. The size of a modern organisation, its socio-technical characteristics, inherent uncertainty, volatile operating environment, and prohibitively high cost of the incorrect decisions make decision-making a challenging endeavor. While the enterprise modelling and simulation technologies have evolved into a mature discipline for understanding a range of engineering, defense and control systems, their application in organisational decision-making is considerably low. Current organisational decision-making approaches that are prevalent in practice are largely qualitative. Moreover, they mostly rely on human experts who are often aided with the primitive technologies such as spreadsheets and visual diagrams. This thesis argues that the existing modelling and simulation technologies are neither suitable to represent organisation and decision artifacts in a comprehensive and machine-interpretable form nor do they comprehensively address the analysis needs. An approach that advances the modelling abstraction and analysis machinery for organisational decision-making is proposed. In particular, this thesis proposes a domain specific language to represent relevant aspects of an organisation for decision-making, establishes the relevance of a bottom-up simulation technique as a means for analysis, and introduces a method to utilise the proposed modelling abstraction, analysis technique, and analysis machinery in an effective and convenient manner

Directional adposition use in English, Swedish and Finnish

Directional adpositions such as to the left of describe where a Figure is in relation to a Ground. English and Swedish directional adpositions refer to the location of a Figure in relation to a Ground, whether both are static or in motion. In contrast, the Finnish directional adpositions edellä (in front of) and jäljessä (behind) solely describe the location of a moving Figure in relation to a moving Ground (Nikanne, 2003). When using directional adpositions, a frame of reference must be assumed for interpreting the meaning of directional adpositions. For example, the meaning of to the left of in English can be based on a relative (speaker or listener based) reference frame or an intrinsic (object based) reference frame (Levinson, 1996). When a Figure and a Ground are both in motion, it is possible for a Figure to be described as being behind or in front of the Ground, even if neither have intrinsic features. As shown by Walker (in preparation), there are good reasons to assume that in the latter case a motion based reference frame is involved. This means that if Finnish speakers would use edellä (in front of) and jäljessä (behind) more frequently in situations where both the Figure and Ground are in motion, a difference in reference frame use between Finnish on one hand and English and Swedish on the other could be expected. We asked native English, Swedish and Finnish speakers’ to select adpositions from a language specific list to describe the location of a Figure relative to a Ground when both were shown to be moving on a computer screen. We were interested in any differences between Finnish, English and Swedish speakers. All languages showed a predominant use of directional spatial adpositions referring to the lexical concepts TO THE LEFT OF, TO THE RIGHT OF, ABOVE and BELOW. There were no differences between the languages in directional adpositions use or reference frame use, including reference frame use based on motion. We conclude that despite differences in the grammars of the languages involved, and potential differences in reference frame system use, the three languages investigated encode Figure location in relation to Ground location in a similar way when both are in motion. Levinson, S. C. (1996). Frames of reference and Molyneux’s question: Crosslingiuistic evidence. In P. Bloom, M.A. Peterson, L. Nadel & M.F. Garrett (Eds.) Language and Space (pp.109-170). Massachusetts: MIT Press. Nikanne, U. (2003). How Finnish postpositions see the axis system. In E. van der Zee & J. Slack (Eds.), Representing direction in language and space. Oxford, UK: Oxford University Press. Walker, C. (in preparation). Motion encoding in language, the use of spatial locatives in a motion context. Unpublished doctoral dissertation, University of Lincoln, Lincoln. United Kingdo

Towards responsive Sensitive Artificial Listeners

This paper describes work in the recently started project SEMAINE, which aims to build a set of Sensitive Artificial Listeners – conversational agents designed to sustain an interaction with a human user despite limited verbal skills, through robust recognition and generation of non-verbal behaviour in real-time, both when the agent is speaking and listening. We report on data collection and on the design of a system architecture in view of real-time responsiveness