Statistical Emulation of Neural Simulators: Application to Neocortical L2/3 Large Basket Cells

Many scientific systems are studied using computer codes that simulate the phenomena of interest. Computer simulation enables scientists to study a broad range of possible conditions, generating large quantities of data at a faster rate than the laboratory. Computer models are widespread in neuroscience, where they are used to mimic brain function at different levels. These models offer a variety of new possibilities for the neuroscientist, but also numerous challenges, such as: where to sample the input space for the simulator, how to make sense of the data that is generated, and how to estimate unknown parameters in the model. Statistical emulation can be a valuable complement to simulator-based research. Emulators are able to mimic the simulator, often with a much smaller computational burden and they are especially valuable for parameter estimation, which may require many simulator evaluations. This work compares different statistical models that address these challenges, and applies them to simulations of neocortical L2/3 large basket cells, created and run with the NEURON simulator in the context of the European Human Brain Project. The novelty of our approach is the use of fast empirical emulators, which have the ability to accelerate the optimization process for the simulator and to identify which inputs (in this case, different membrane ion channels) are most influential in affecting simulated features. These contributions are complementary, as knowledge of the important features can further improve the optimization process. Subsequent research, conducted after the process is completed, will gain efficiency by focusing on these inputs.

Object-oriented approach for dynamic system modelling and simulation

Adel Besrour

Software engineering always cares to provide solutions for building applications as close as possible to what they should be, according to the requirements and the final users needs. Systems behavior simulation is a very common application to virtually reproduce and often predict the real-world behavior. Simulation is one of the most operational research tool in a large variety of engineering and scientific domains: Transport, telecommunication, medicine, chemical processes, physics, etc. The complexity of such application is relative to the increasing complexity of the systems. In this context, it is relevant to bring together different tools and formalisms such as markovian chain, Petri nets, etc., to improve the existent approaches and so to answer the simulations performances needs. The principle objective of this thesis is to bring together techniques from software engineering and safety engineering in order to improve the state of the art of modeling and simulation of dynamic systems in the industrial context. In addressing this objective, this work initially involves defining the essential limitations of the used formalisms, methods and tools regarding from one hand the software engineering modeling and simulation techniques and from the other hand the existent risk analysis methodologies. This work is conducted with respect to the problem of danger identification, considering the context of the complex systems behavior and their interaction with the human operator. In software engineering, it is well known that Petri/high-level nets have attractive characteristics to be used in systems simulation and behavior prediction such as the natural graphical representation, and their well-defined semantic. They are well-suited for the description of complex situations with concurrency (interleaving and true concurrency depending on the underlying semantics), conflict and confusion. However, the absence of structuring capabilities has been one of the main criticisms raised against Petri nets/high-level nets. Thus, there have been many attempts to introduce structuring principles in nets of this kind [BCM88] [Kie89] [JR91]. The attractive characteristics of Petri/high-level nets have prompted researchers to enrich these formalisms with object-oriented features. CO-OPN (Concurrent Object-Oriented Petri Net) approach, brings together the power of both Petri/high-level nets and object-orientation techniques, it has been devised so as to offer an adequate framework for the specification and design of large scale concurrent system [BG91]. CO-OPN, as a powerful modeling tool, has been used in a limited way to simulate systems. This work aims to provide a CO-OPN extension to allow a more realistic systems' simulation. Actually, its simulator semantic uses to be a suitable approach for modeling near closed systems and software components, because they need to loose coupling with external world. But, when we model more realistic problems like industrial processes, where human interaction is a relevant event, this approach is not sufficient to catch all system activity attributes. Moreover, the CO-OPN interpretation process does not allow interaction with the object internal states. This work provides a new solution to overcome CO-OPN simulation limitations and a set of prototypes to assist dynamic systems simulations. Furthermore, this work has been conducted in a Risk Analysis (RA) context, a domain where computer-based simulations research are of utmost interest. Actually, classical approaches used to address complex workplace hazard in a limited way, using checklists or sequence models. Moreover, the use of single oriented methods, such as AEA (man-oriented), FMEA (machine oriented) or HAZOP (process oriented), is not satisfactory to overcome the increasing sophistication of industrial processes. The automation of a part of the analysis process as well as the multiple-oriented approach allowed by dynamic modeling may indeed enhance significantly the analysis completeness and reduce the time analyzing time. This work, based on Object Oriented Petri net formalism (CO-OPN), propose an alternative multi-oriented approach where existent methods limitations have been criticized to develop a dynamic model, MORM (Man-machine Occupational Risk Modeling). A real industrial system (metal wire making process) has been specified to implement the different approach steps (system identification, model application, system simulation, system analysis).

EPFL2005

Computational fluid dynamics for naval engineering problems

Nicola Parolini

The subject of this thesis is the numerical simulation of viscous free-surface flows in naval engineering applications. State-of-the-art numerical methods based on the solution of the Navier-Stokes equations are used to predict the flow around different classes of boats. We investigate the role of the Computational Fluid Dynamics in the design of racing boats, such as America's Cup yachts and Olympic class rowing hull. The mathematical models describing the different aspects of the physical problem, as well as the numerical methods adopted for their solution, are introduced and critically discussed. The different phases of the overall numerical simulation procedure, from grid generation through the solution of the flow equations to the post-processing of the results, are described. We present the numerical simulations that have been performed to investigate the role of different design parameters in the conception of America's Cup yachts and we describe how the results obtained from the simulations are integrated into the overall design process. The free-surface flow around an Olympic rowing boat is also considered. We propose a simplified approach to take into account the effect of the boat dynamics in the prediction of the hydrodynamic forces acting on the boat. Based on the results of the simulations, we propose a new design concept and we investigate its potential benefits on the boat performances. One of the aspects that is found to be not completely satisfactory, within the standard numerical methods adopted, is the modelling of complex free-surface flows. The second part of this thesis is devoted to a more theoretical and methodological investigation of this aspect. In particular, we present and analyse a new numerical method based on the level set approach for the solution of two-fluid flows. The numerical scheme based on a finite element discretization is introduced and different critical aspects of its implementation are discussed. In particular, we present and analyse a new technique for the stabilization of the advection equation associated to the level set problem. Moreover, we propose a new reinitialization procedure for the level set function which plays a crucial role in the accuracy of the algorithm. The convergence properties of this procedure are analysed and comparisons with more standard approaches are presented. Finally, the proposed method has been used to solve a variety of test cases concerning time dependent two-fluid viscous flows. The results of the simulation are presented and discussed.

EPFL2004

Electrical and mechanical activity of the intestine

Mattia Bertschi

The intestine is today still an organ whose mechanisms of functions are not fully understood. The diffculty in its understanding comes from the fact that it is regulated by a complex network of signals of different natures. Granting that a multitude of experimental techniques have brought precious information on the electrophysiological processes associated to the intrisic activity of the intestin, there is still shadow covering over the boundary of knowledge. With a view to sharpening the study of the complex spatio-temporal dynamics of the intrinsic electrical and mechanical activity of the intestine, three different numerical models of intestinal tissue were developed. Of particular interest are the networks of coupled oscillators, exhibiting a mass behavior with marked analogy to the intestinal tissue. The conception of these models were conducted by the handling of effective numerical methods and evaluation of numerical instability and errors. A simplified geometrical model of human colon was also developed, so as to allow a realistic visualization of the simulated results. Experimental measures in vitro and in vivo of an animal model, namely the pig, endorsed us the recordings of intrinsic electrical and mechanical activity of different intestinal segments. The recordings of the mechanical activity were obtained by three different tools: visual inspection, manometry, and Magnet Tracking. The first method implies the use of image processing for the evaluation of intestinal movement. The second one provides local pressure measurements. Only the third method enables noninvasive measurements along the digestive tube. In order to automate the extraction of valuable information contained in the signals recorded by the last method, an approch was proposed based on morphological filtering. These three methods of measure were also used in a parallel study to evaluate the electrical stimulation of the colon, with a goal to find an alternative solution to clasical treatments of chronic constipation. We showed that it is possible to induce local contraction in the cecum with electrical stimulation generated by an implantable device. Computer models guarantee at any time the realization of reproducible simulations of technically dicult, and even impossible, experiments. They compel, nonetheless, a simplification of the physiological reality. So as to validate the computer models, the result of simulations must be treated by particular methods. Electrograms and signals representing the mass movement were computed and faced to observations and real measurements. Simulated electrograms revealed a similarity to those recorded on animal intestines. Numerous resemblances are likewise observable between simulated signals of mass movement and the recordings of Magnet Tracking.

EPFL2005

Computational fluid dynamics for naval engineering problems

Nicola Parolini

EPFL2004

Electrical and mechanical activity of the intestine

Mattia Bertschi

EPFL2005

Object-oriented approach for dynamic system modelling and simulation

Adel Besrour

EPFL2005