At present, compared to our scientific knowledge of how natural biosystems function, we have practically no knowledge of how to engineer biosystems, i.e., how to design, build, repair, maintain, operate, and modify them in a rational and knowledgeable manner. Thus, the EcoCyborg research project was established with the basic intent of making a contribution to the science and engineering of biosystems. / This thesis covers three important arms of study within the overall framework of the EcoCyborg project. The first area is the development and implementation of a workbench for simulation based on composite models. The workbench was designed to accommodate easy integration, synchronization and communication of a number of independent modules. It was developed for use under OS/2 Warp, an operating system that supports multi-process simulation. The functionality of the workbench was tested with a composite model of an EcoCyborg. This composite model contained submodels of an ecosystem, two control systems, and several forcing functions. / The second area is the development and implementation of control systems for biosystems. The control system was intended to guide an ecosystem so that its behavior would best achieve the goals of the controllers which, in this case, were related to the populations of the ecosystem's species. The major part of the work on the control systems was focused on the Pavlovian controller. It mainly covered the investigation of the possibilities to develop and to implement a physiological-level Pavlovian controller. The thesis also presents results from a preliminary investigation on the design and implementation of a cognitive controller. From this, a relatively simple cognitive controller was developed to complement the action of the Pavlovian controller. / The third area is the experimental use of the workbench, and of the Pavlovian and cognitive controllers. For this, ecosystems having various constitutions and their forcing functions were modeled and used in the simulation. Pavlovian controllers with on-off, proportional and proportional plus integral mechanisms were used to control the populations. The cognitive controller was used to maintain minimum population of the various species in the ecosystem. / In general, the workbench that was developed was found suitable to accommodate the simulation of an EcoCyborg composite model. The tools that ware developed for constructing and implementing the Pavlovian controller were tested and found practical and effective for use in constructing Pavlovian controllers of various configurations. The results of the work on the cognitive controller provided useful information for its further development.

Bio-membranes: A Biological Approach to Architecture The desire to introduce an area of study which can potentially inform the field of architecture on a theoretical as well as on a practical level, is the primary aim of this creative project. More specifically, the interest of this work is focused on the identification of useful processes deriving from the world of biology and their utilization in the world of architecture. The designation of an alternative path for perceiving and understanding processing and principles that may be of use in the reconfiguration of various architectural design applications is in quest. In search of a biological model that can potentially inform the field of architecture and provide enough feedback concerning the understanding of "processing" and "principles", biomembrane systems have been designated as the appropriate subject of study. The study and analysis of the structural and functional aspects of the bio-membranes as well as the extraction of useful principles that are derived from this study consist the first part of this work. The second part describes the implementation of these principles into various architectural applications while it challenges existing paradigms and introduces new ways of looking into the realm of architectural theory. / Department of Architecture

Doctorat en Sciences / info:eu-repo/semantics/nonPublished

Oncolytic viruses (OVs) are emerging as a potent therapeutic platform for the treatment of malignant disease. The tumor cells inability to induce antiviral defences in response to a small cytokine known as interferon (IFN) is a common defect exploited by OVs. Heterogeneity in IFN signalling across tumors is therefore a pillar element of resistance to these therapies. I have generated a mathematical model and simulation platform to study the impact of IFN on OV dynamics in normal and cancerous tissues. In the first part of my thesis, I used this model to identify novel OV engineering strategies which could be implemented to overcome IFN based resistance in tumor tissues. From these simulations, it appears that a positive feedback loop, established by virus-mediated expression of an interferon-binding decoy receptor, could increase tumor cytotoxicity without compromising normal cells. The predictions set forth by this model have been validated both qualitatively and quantitatively in in-vitro and in-vivo models using two independent OV strains. This model has subsequently been used to investigate OV attenuation mechanisms, the impact of tumor cell heterogeneity, as well as drug-OV interactions. Following these results, it became apparent that selectivity should equally be observed when overwhelming the cell with a non replicating virus. While normal tissues will clear this pseudo-infection rapidly, owing to their high baseline in antiviral products at the onset of infection, tumor cells with defective anti-viral pathways should not have readily available biomachinery required to degrade this pro-apoptotic signal. Recapitulated by the mathematical model, non-replicating virus-derived particles generated by means of UV irradiation selectively kill tumor cells in cultured cell lines and patient samples, leading to long term cures in murine models. Taken together, this thesis uses a novel mathematical model and simulation platform to understand, design & improve oncolytic virus-based therapeutics.

A broad scope analysis of waterjet cutting systems has been developed using thermodynamics, life cycle analysis, and biological system comparison. The typical assessments associated with mechanical design include measures for performance and thermodynamic efficiency. Further analysis has been conducted using exergy, which is not typically incorporated into design practices. Exergy measures the effectiveness of a process with respect to a base state, usually that of the systems surroundings. Comparing Gibbs free energy of biological processes to exergy efficiency has served to illustrate the need for various levels of comparison. Each biological process used in this comparison correlates to a different type of mechanical process and level of complexity. Overall, biological processes display similar properties to mechanical systems in that simpler systems are more energy efficient. In order to determine accurate efficiency and effectiveness values for a mechanical process, in this case waterjet cutting, a set of thermodynamic models was established to account for energy uses. Various output force and velocity models have been developed and are used here for comparison to assess output efficiencies with "no loss" models used as a lossless base. Experimental testing was then conducted using a simple nozzle and a pressure washer with 2 other diameter nozzles. The most energy efficient system used a turbojet nozzle. It was also the most efficient sustained system with energy inputs. However, it had a much lower exergy efficiency compared to the other systems. This implies that it could be significantly improved by more adequately utilizing the energy provided. An effort to assess the green nature of pressurized water systems was done through use of an Economic Input/Output Life Cycle Analysis (EIO-LCA). The EIO-LCA is designed to assess processes for greenhouse gas emissions and total power consumption across the life of a system. Calculations showed that increases in power consumption result in much higher greenhouse gas emissions per unit time than increases in water consumption. Financial cost however showed an opposite trend due to the much greater cost of water with regard to consumption rates in each system. The most "green" system used only a nozzle with no power consumption.

No description available.

This paper reviews most frequently used computational modelling approaches and formal verification techniques in computational biology. The paper also compares a number of model checking tools and software suits used in analysing biological systems and biochemical networks and verifiying a wide range of biological properties.

No description available.

Deux systèmes biologiques distincts, les muscles squelettiques et les sites d'adhésion de cellules kératocytes en mouvement, sont considérés dans un même cadre en raison de la similitude profonde de leur structure et de leur fonctionnalité. La réponse passive de l'un et de l'autre peut être modélisée à l'aide d'un grand nombre d'unités multi-stables couplées par des interactions à longue portée, et exposées à un désordre spatial fixé et un bruit thermique/mécanique. Les interactions à longue portée dans de tels systèmes conduisent à une synchronisation malgré les fluctuations temporelles et spatiales. Bien que les deux systèmes biologiques considérés présentent des différences structurelles importantes, nous montrons que l'on peut identifier une structure de verre de spin sous-jacente commune. À la lumière de cette analogie, ces systèmes vivants semblent être proches de points critiques et, à cet égard, le désordre gelé, reflétant l’incommensurabilité stérique des unités parallèles, peut être fonctionnel. Un autre paramètre important fixant la réponse est la rigidité interne du système qui couple les unités entre elles. / Two biological systems, a half-sarcomere of a skeletal muscle and an adhesive cluster of a crawling keratocyte, are considered in parallel because of the deep similarity in their structure and functionality. Their passive response can be modeled by a large number of multi-stable units coupled through long-range interactions, frustrated by quenched disorder and exposed to thermal noise. In such systems, long-range interactions lead to synchronization, defying temporal and spatial fluctuations. We use a mean-field description to obtain analytic results and elucidate the remarkable ensemble-dependence of the mechanical behavior of such systems in the thermodynamic limit. Despite important structural differences between muscle cross-bridges and adhesive binders, one can identify a common underlying spin glass structure, which we fully exploit in this work. Our study suggests that the muscle machinery is fine-tuned to operate near criticality, and we argue that in this respect the quenched disorder, reflecting here steric incommensuration, may be functional. We use the analogy between cell detachment and thermal fracture of disordered solids to study the statistics of fluctuations during cellular adhesion. We relate the obtained results to recent observations of intermittent behavior involved in cell debonding, also suggesting near-criticality. In addition to the study of the equilibrium properties of adhesive clusters, we also present the first results on their kinetic behavior in the presence of time-dependent loading.

Plusieurs types d’expérimentation existent pour étudier et comprendre les systèmes biologiques. Dans ces travaux, nous nous intéressons à la simulation in silico, c’est-à-dire à la simulation numérique de modèles sur un ordinateur. Les systèmes biologiques sont composés d’entités, à la fois nombreuses et variées, en interaction les unes avec les autres. Ainsi, ils peuvent être modélisés par l’intermédiaire de deux approches complémentaires : l’approche population-centrée et l’approche individu-centrée. Face à la multitude et à la variété des phénomènes composant les systèmes biologiques, il nous semble pertinent de coupler ces deux approches pour obtenir une modélisation mixte. En outre, en raison de la quantité conséquente d’informations que représente l’ensemble des entités et des interactions à modéliser, la simulation numérique des systèmes biologiques est particulièrement coûteuse en temps de calcul informatique. Ainsi, dans ce mémoire, nous proposons des solutions techniques de parallélisation permettant d’exploiter au mieux les performances offertes par les architectures multicoeur et multiprocesseur et les architectures graphiques pour la simulation de systèmes biologiques à base de modélisations mixtes. Nous appliquons nos travaux au domaine de la coagulation du sang et plus particulièrement à l’étude de la cinétique biochimique à l’échelle microscopique ainsi qu’à la simulation d’un vaisseau sanguin virtuel. Ces deux applications nous permettent d’évaluer les performances offertes par les solutions techniques de parallélisation que nous proposons, ainsi que leur pertinence dans le cadre de la simulation des systèmes biologiques. / Several types of experimentation exist to study and understand biological systems. Inthis document, we take an interest in in silico simulation, i.e. numerical simulation ofmodels on a computer. Biological systems are made of many various entities, interactingwith each other. Therefore, they can be modeled by two complementary approaches: thepopulation-based approach and the individual-based one. Because of the multitude anddiversity of the phenomena constituting biological systems, we find the coupling of thesetwo approaches relevant to provide a hybrid modelisation. Moreover, because of the hugequantity of data that the entities and interactions represent, numerical simulation of biologicalsystems is especially computationaly intensive. This is why, in this document, we proposeparallel computing methods to take advantage of the performances offered by multicore andmultiprocessor architectures and by graphical ones for the simulation of biological systemsusing hybrid modelisations. We apply our work to blood coagulation and especially to thestudy of biochemical kinetics at the microscopic scale and the simulation of a virtual bloodvessel. These two applications enable us to assess both the performances obtained by theparallel computing methods we proposed and their relevance for biological systems simulation.