Refounding of Activity Concept ? Towards a Federative Paradigm for Modeling and Simulation

Journal : Simulation, Transactions of the Society for Modeling and Simulation InternationalInternational audienceCurrently, the widely used notion of activity is increasingly present in computer science. However, because this notion is used in specific contexts, it becomes vague. Here, the notion of activity is scrutinized in various contexts and, accord-ingly, put in perspective. It is discussed through four scientific disciplines: computer science, biology, economics, and epis-temology. The definition of activity usually used in simulation is extended to new qualitative and quantitative definitions. In computer science, biology and economics disciplines, the new simulation activity definition is first applied critically. Then, activity is discussed generally. In epistemology, activity is discussed, in a prospective way, as a possible framework in models of human beliefs and knowledge

Parallélisation et optimisation d'un simulateur de morphogénèse d'organes. Application aux éléments du rein

Depuis plusieurs dizaines d années, la modélisation du vivant est un enjeu majeur qui nécessite de plus en plus de travaux dans le domaine de la simulation. En effet, elle ouvre la porte à toute une palette d applications: l aide à la décision en environnement et en écologie, l aide à l enseignement, l aide à la décision pour les médecins, l aide à la recherche de nouveaux traitements pharmaceutiques et la biologie dite prédictive , etc. Avant de pouvoir aborder un problème, il est nécessaire de pouvoir modéliser de façon précise le système biologique concerné en précisant bien les questions auxquelles devra répondre le modèle. La manipulation et l étude de systèmes complexes, les systèmes biologiques en étant l archétype, pose, de façon générale, des problèmes de modélisation et de simulation. C est dans ce contexte que la société Integrative BioComputing (IBC) développe depuis le début des années 2000 un prototype d une Plateforme Générique de Modélisation et de Simulation(la PGMS) dont le but est de fournir un environnement pour modéliser et simuler plus simplement les processus et les fonctions biologiques d un organisme complet avec les organes le composant. La PGMS étant une plateforme générique encore en phase de développement, elle ne possédait pas les performances nécessaires pour permettre de réaliser la modélisation et la simulation d éléments importants dans des temps suffisamment courts. Il a donc été décidé, afin d améliorer drastiquement les performances de la PGMS, de paralléliser et d optimiser l implémentation de celle-ci; le but étant de permettre la modélisation et la simulation d organes complets dans des temps acceptables. Le travail réalisé au cours de cette thèse a donc consisté à traiter différents aspects de la modélisation et de la simulation de systèmes biologiques afin d accélérer les traitements de ceux-ci. Le traitement le plus gourmand en termes de temps de calcul lors de l exécution de la PGMS, le calcul des champs physicochimiques, a ainsi fait l objet d une étude de faisabilité de sa parallélisation. Parmi les différentes architectures disponibles pour paralléliser une telle application, notre choix s est porté sur l utilisation de GPU (Graphical Processing Unit) à des fins de calculs généralistes aussi couramment appelé GPGPU (General-Purpose computation on Graphics Processing Units). Ce choix a été réalisé du fait, entre autres, du coût réduit du matériel et de sa très grande puissance de calcul brute qui en fait une des architectures de parallélisation les plus accessibles du marché. Les résultats de l étude de faisabilité étant particulièrement concluant, la parallélisation du calcul des champs a ensuite été intégrée à la PGMS. En parallèle, nous avons également mené des travaux d optimisations pour améliorer les performances séquentielles de la PGMS. Le résultat de ces travaux est une augmentation de la vitesse d exécution d un facteur 18,12x sur les simulations les plus longues (passant de 16 minutes pour la simulation non optimisée utilisant un seul cœur CPU à 53 secondes pour la version optimisée utilisant toujours un seul cœur CPU mais aussi un GPU GTX500). L autre aspect majeur traité dans ces travaux a été d améliorer les performances algorithmiques pour la simulation d automates cellulaires en trois dimensions. En effet, ces derniers permettent aussi bien de simuler des comportements biologiques que d implémenter des mécanismes de modélisation tels que les interactions multi-échelles. Le travail de recherche s est essentiellement effectué sur des propositions algorithmiques originales afin d améliorer les simulations réalisées par IBC sur la PGMS. L accélération logicielle, à travers l implémentation de l algorithme Hash Life en trois dimensions, et la parallélisation à l aide de GPGPU ont été étudiées de façon concomitante et ont abouti à des gains très significatifs en temps de calcul.For some years, living matter modeling has been a major challenge which needs more and more research in the simulation field. Indeed, the use of models of living matter have multiple applications: decision making aid in environment or ecology, teaching tools, decision making aid for physician, research aid for new pharmaceutical treatment and predictive biology, etc. But before being able to tackle all these issues, the development of a correct model, able to give answer about specific questions, is needed. Working with complex systems biologic system being the archetype of them raises various modeling and simulation issues. It is in this context that the Integrative BioComputing (IBC) company have been elaborating, since the early 2000s, the prototype of a generic platform for modeling and simulation (PGMS). Its goal is to provide a platform used to easily model and simulate biological process of a full organism, including its organs. Since the PGMS was still in its development stage at the start of my PhD, the application performance prevented the modeling and simulation of large biological components in an acceptable time. Therefore, it has been decide to optimize and parallelize its computation to increase significantly the PGMS performances. The goal was to enable the use of the PGMS to model and simulate full organs in acceptable times. During my PhD, I had to work on various aspects of the modeling and simulation of biological systems to increase their process speed. Since the most costly process during the PGMS execution was the computation of chemical fields, I had to study the opportunity of parallelizing this process. Among the various hardware architectures available to parallelize this application, we chose to use graphical processing units for general purpose computation (GPGPUs). This choice was motivated, beside other reasons, by the low cost of the hardware compared to its massive computation power, making it one of the most affordable parallel architecture on the market. Since the results of the initial feasibility study were conclusive, the parallelization of the fields computation has been integrated into the PGMS. In parallel to this work, I also worked on optimizing the sequential performance of the application. All these works lead to an increase of the software performances achieving a speed-up of 18.12x for the longest simulation (from 16 minutes for the non-optimized version with one CPU core to 53 seconds for the optimized version, still using only one core on the CPU but also a GPU GTX500). The other major aspect of my work was to increase the algorithmic performances for the simulation of three-dimensional cellular automata. In fact, these automata allow the simulation of biological behavior as they can be used to implement various mechanisms of a model such as multi-scale interactions. The research work consisted mainly in proposing original algorithms to improve the simulation provided by IBC on the PGMS. The sequential speed increase, thanks to the three-dimensional Hash Life implementation, and the parallelization on GPGPU has been studied together and achieved major computation time improvement.CLERMONT FD-Bib.électronique (631139902) / SudocSudocFranceF

The Impact of Glucose Variation on Human Astrocytes

Diabetes is a metabolic disorder dysregulating glucose homeostasis. The role of astrocytes in central glucose sensing is poorly understood. But it is recognised they take part in whole-body energy homeostasis, specifically as glucose sensors necessary for the counterregulatory response (CRR) to hypoglycaemia. Iatrogenic hypoglycaemia is the limiting factor to glycaemic control in people with type 1 or type 2 diabetes. Severe hypoglycaemia occurs approximately once per year, whereas, the incidence of minor hypoglycaemia is much greater. Hypoglycaemia impairs awareness of future hypoglycaemia and blunts the CRR, eventually causing hypoglycaemia-associated autonomic failure. The mechanisms of this process are poorly understood. This thesis utilised isolated human astrocytes exposed to acute or recurrent low glucose (RLG) in vitro to mimic glucose variation in diabetes. Cellular responses were characterised of three key astrocyte functions. Firstly, is astrocyte metabolism altered by acute and RLG treatment? Secondly, do isolated human astrocytes become activated by low glucose treatment, and is this affected by RLG? Thirdly, are astrocytic inflammatory pathways altered by acute or RLG? The key findings from this thesis shows for the first time that astrocytic mitochondrial oxidation is increased following RLG, with a concurrent increase in fatty acid dependency but decreased coupling efficiency; glycolytic function is also enhanced. Together, this indicates that astrocytes successfully adapt to low glucose to sustain intracellular nucleotide ratios. Contrary to previous work, these human astrocytes do not respond to low glucose by Ca2+-dependent activation. However, the astrocytes do increase inflammatory cytokine release following acute and RLG. Lastly, for the first time an RNA-sequencing approach has been used to identify low glucose-induced differential gene expression. Together these findings support the argument that astrocytes are sensitive to low glucose and may be important in glucose sensation and the CRR

Using MapReduce Streaming for Distributed Life Simulation on the Cloud

Distributed software simulations are indispensable in the study of large-scale life models but often require the use of technically complex lower-level distributed computing frameworks, such as MPI. We propose to overcome the complexity challenge by applying the emerging MapReduce (MR) model to distributed life simulations and by running such simulations on the cloud. Technically, we design optimized MR streaming algorithms for discrete and continuous versions of Conway’s life according to a general MR streaming pattern. We chose life because it is simple enough as a testbed for MR’s applicability to a-life simulations and general enough to make our results applicable to various lattice-based a-life models. We implement and empirically evaluate our algorithms’ performance on Amazon’s Elastic MR cloud. Our experiments demonstrate that a single MR optimization technique called strip partitioning can reduce the execution time of continuous life simulations by 64%. To the best of our knowledge, we are the first to propose and evaluate MR streaming algorithms for lattice-based simulations. Our algorithms can serve as prototypes in the development of novel MR simulation algorithms for large-scale lattice-based a-life models.https://digitalcommons.chapman.edu/scs_books/1014/thumbnail.jp

Graduate and Undergraduate Catalog, 2014-2015

Eastern Washington University\u27s course catalog for the 2014-2015 academic year.https://dc.ewu.edu/catalogs/1001/thumbnail.jp

Examination of myocardial electrophysiology using novel panoramic optical mapping techniques

Optical mapping of voltage signals has revolutionised the field and study of cardiac electrophysiology by providing the means to visualise changes in electrical activity at a high temporal and spatial resolution from the cellular to the whole heart level under both normal and disease conditions. The aim of this thesis was to develop a novel method of panoramic optical mapping using a single camera and to study myocardial electrophysiology in isolated Langendorff-perfused rabbit hearts. First, proper procedures for selection, filtering and analysis of the optical data recorded from the panoramic optical mapping system were established. This work was followed by extensive characterisation of the electrical activity across the epicardial surface of the preparation investigating time and heart dependent effects. In an initial study, features of epicardial electrophysiology were examined as the temperature of the heart was reduced below physiological values. This manoeuvre was chosen to mimic the temperatures experienced during various levels of hypothermia in vivo, a condition known to promote arrhythmias. The facility for panoramic optical mapping allowed the extent of changes in conduction timing and pattern of ventricular activation and repolarisation to be assessed. In the main experimental section, changes in epicardial electrical activity were assessed under various pacing conditions in both normal hearts and in a rabbit model of chronic MI. In these experiments, there was significant changes in the pattern of electrical activation corresponding with the changes in pacing regime. These experiments demonstrated a negative correlation between activation time and APD, which was not maintained during ventricular pacing. This suggests that activation pattern is not the sole determinant of action potential duration in intact hearts. Lastly, a realistic 3D computational model of the rabbit left ventricle was developed to simulate the passive and active mechanical properties of the heart. The aim of this model was to infer further information from the experimental optical mapping studies. In future, it would be feasible to gain insight into the electrical and mechanical performance of the heart by simulating experimental pacing conditions in the model