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

A Parallel Mesh-Adaptive Framework for Hyperbolic Conservation Laws

We report on the development of a computational framework for the parallel, mesh-adaptive solution of systems of hyperbolic conservation laws like the time-dependent Euler equations in compressible gas dynamics or Magneto-Hydrodynamics (MHD) and similar models in plasma physics. Local mesh refinement is realized by the recursive bisection of grid blocks along each spatial dimension, implemented numerical schemes include standard finite-differences as well as shock-capturing central schemes, both in connection with Runge-Kutta type integrators. Parallel execution is achieved through a configurable hybrid of POSIX-multi-threading and MPI-distribution with dynamic load balancing. One- two- and three-dimensional test computations for the Euler equations have been carried out and show good parallel scaling behavior. The Racoon framework is currently used to study the formation of singularities in plasmas and fluids.Comment: late submissio

Concurrence-Aware Long Short-Term Sub-Memories for Person-Person Action Recognition

Recently, Long Short-Term Memory (LSTM) has become a popular choice to model individual dynamics for single-person action recognition due to its ability of modeling the temporal information in various ranges of dynamic contexts. However, existing RNN models only focus on capturing the temporal dynamics of the person-person interactions by naively combining the activity dynamics of individuals or modeling them as a whole. This neglects the inter-related dynamics of how person-person interactions change over time. To this end, we propose a novel Concurrence-Aware Long Short-Term Sub-Memories (Co-LSTSM) to model the long-term inter-related dynamics between two interacting people on the bounding boxes covering people. Specifically, for each frame, two sub-memory units store individual motion information, while a concurrent LSTM unit selectively integrates and stores inter-related motion information between interacting people from these two sub-memory units via a new co-memory cell. Experimental results on the BIT and UT datasets show the superiority of Co-LSTSM compared with the state-of-the-art methods

Multiple verification in computational modeling of bone pathologies

We introduce a model checking approach to diagnose the emerging of bone pathologies. The implementation of a new model of bone remodeling in PRISM has led to an interesting characterization of osteoporosis as a defective bone remodeling dynamics with respect to other bone pathologies. Our approach allows to derive three types of model checking-based diagnostic estimators. The first diagnostic measure focuses on the level of bone mineral density, which is currently used in medical practice. In addition, we have introduced a novel diagnostic estimator which uses the full patient clinical record, here simulated using the modeling framework. This estimator detects rapid (months) negative changes in bone mineral density. Independently of the actual bone mineral density, when the decrease occurs rapidly it is important to alarm the patient and monitor him/her more closely to detect insurgence of other bone co-morbidities. A third estimator takes into account the variance of the bone density, which could address the investigation of metabolic syndromes, diabetes and cancer. Our implementation could make use of different logical combinations of these statistical estimators and could incorporate other biomarkers for other systemic co-morbidities (for example diabetes and thalassemia). We are delighted to report that the combination of stochastic modeling with formal methods motivate new diagnostic framework for complex pathologies. In particular our approach takes into consideration important properties of biosystems such as multiscale and self-adaptiveness. The multi-diagnosis could be further expanded, inching towards the complexity of human diseases. Finally, we briefly introduce self-adaptiveness in formal methods which is a key property in the regulative mechanisms of biological systems and well known in other mathematical and engineering areas.Comment: In Proceedings CompMod 2011, arXiv:1109.104

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Department of Energy Engineering (Battery Science and Technology)The continuous throng in demand for high energy density rechargeable batteries innovatively drives technological development in cell design as well as electrochemically active materials. In that perspective metal-free batteries consisting of a flowing seawater as a cathode active material were introduced. However, the electrochemical performance of the seawater battery was restrained by NASICON (Na3Zr2Si2PO12) ceramic solid electrolyte. Here, we demonstrate a new class of fibrous nanomat hard-carbon (FNHC) anode/1D (one-dimensional) bucky paper (1DBP) cathode hybrid electrode architecture in seawater battery based on 1D building block-interweaved hetero-nanomat frameworks. Differently from conventional slurry-cast electrodes, exquisitely designed hybrid hetero-nanomat electrodes are fabricated through concurrent dual electrospraying and electrospinning for the anode, vacuum-assisted infiltration for the cathode. HC nanoparticles are closely embedded in the spatially reinforced polymeric nanofiber/CNT hetero-nanomat skeletons that play a crucial role in constructing 3D-bicontinuous ion/electron transport pathways and allow to eliminate heavy metallic aluminum foil current collectors. Eventually the FNHC/1DBP seawater full cell, driven by aforementioned physicochemical uniqueness, shows exceptional improvement in electrochemical performance (Energy density = 693 Wh kg-1), (Power density = 3341 W kg-1) removing strong stereotype of ceramic solid electrolyte, which beyond those achievable with innovative next generation battery technologies.ope

Modelling and Verification of Multiple UAV Mission Using SMV

Model checking has been used to verify the correctness of digital circuits, security protocols, communication protocols, as they can be modelled by means of finite state transition model. However, modelling the behaviour of hybrid systems like UAVs in a Kripke model is challenging. This work is aimed at capturing the behaviour of an UAV performing cooperative search mission into a Kripke model, so as to verify it against the temporal properties expressed in Computation Tree Logic (CTL). SMV model checker is used for the purpose of model checking

Design Environments for Complex Systems

The paper describes an approach for modeling complex systems by hiding as much formal details as possible from the user, still allowing verification and simulation of the model. The interface is based on UML to make the environment available to the largest audience. To carry out analysis, verification and simulation we automatically extract process algebras specifications from UML models. The results of the analysis is then reflected back in the UML model by annotating diagrams. The formal model includes stochastic information to handle quantitative parameters. We present here the stochastic -calculus and we discuss the implementation of its probabilistic support that allows simulation of processes. We exploit the benefits of our approach in two applicative domains: global computing and systems biology

BlenX-based compositional modeling of complex reaction mechanisms

Molecular interactions are wired in a fascinating way resulting in complex behavior of biological systems. Theoretical modeling provides a useful framework for understanding the dynamics and the function of such networks. The complexity of the biological networks calls for conceptual tools that manage the combinatorial explosion of the set of possible interactions. A suitable conceptual tool to attack complexity is compositionality, already successfully used in the process algebra field to model computer systems. We rely on the BlenX programming language, originated by the beta-binders process calculus, to specify and simulate high-level descriptions of biological circuits. The Gillespie's stochastic framework of BlenX requires the decomposition of phenomenological functions into basic elementary reactions. Systematic unpacking of complex reaction mechanisms into BlenX templates is shown in this study. The estimation/derivation of missing parameters and the challenges emerging from compositional model building in stochastic process algebras are discussed. A biological example on circadian clock is presented as a case study of BlenX compositionality