No description available.

Les microARN sont de petits ARN non codants d'environ 22 nucléotides impliqués dans la régulation de l'expression des gènes. Ils ciblent les régions complémentaires des molécules d'ARN messagers que ces gènes codent et ajustent leurs niveaux de traduction en protéines en fonction des besoins de la cellule. En s'attachant à leurs cibles par complémentarité partielle de leurs séquences, ces deux groupes de molécules d'ARN compétitionnent activement pour former des interactions régulatrices. Par conséquent, prédire quantitativement les concentrations d'équilibres des duplexes formés est une tâche qui doit prendre un compte plusieurs facteurs dont l'affinité pour l'hybridation, la capacité à catalyser la cible, la coopérativité et l'accessibilité de l'ARN cible. Dans le modèle que nous proposons, miRBooking 2.0, chaque interaction possible entre un microARN et un site sur un ARN cible pour former un duplexe est caractérisée par une réaction enzymatique. Une réaction de ce type opère en deux phases : une formation réversible d'un complexe enzyme-substrat, le duplexe microARN-ARN, suivie d'une conversion irréversible du substrat en produit, un ARN cible dégradé, et de la restitution l'enzyme qui pourra participer à une nouvelle réaction. Nous montrons que l'état stationnaire de ce système, qui peut comporter jusqu'à 10 millions d'équations en pratique, est unique et son jacobien possède un très petit nombre de valeurs non-nulles, permettant sa résolution efficace à l'aide d'un solveur linéaire épars. Cette solution nous permet de caractériser précisément ce mécanisme de régulation et d'étudier le rôle des microARN dans un contexte cellulaire donné. Les prédictions obtenues sur un modèle de cellule HeLa corrèlent significativement avec un ensemble de données obtenu expérimentalement et permettent d'expliquer remarquablement les effets de seuil d'expression des gènes. En utilisant ces prédictions comme condition initiale et une méthode d'intégration numérique, nous simulons en temps réel la réponse du système aux changements de conditions expérimentales. Nous appliquons ce modèle pour cibler des éléments impliqués dans la transition épithélio-mésenchymateuse (EMT), un mécanisme biologique permettant aux cellules d'acquérir une mobilité essentielle pour proliférer. En identifiant des éléments transcrits différentiellement entre les conditions épithéliale et mésenchymateuse, nous concevons des microARN synthétiques spécifiques pour interférer avec cette transition. Pour ce faire, nous proposons une méthode basée sur une recherche gloutonne parallèle pour rechercher efficacement l'espace de la séquence du microARN et présentons des résultats préliminaires sur des marqueurs connus de l'EMT. / MicroRNAs are small non-coding RNAs of approximately 22 nucleotide long involved in the regulation of gene expression. They target complementary regions to the RNA transcripts molecules that these genes encode and adjust the concentration according to the needs of the cell. As microRNAs and their RNA targets binds each other with imperfect complementarity, these two groups actively compete to form regulatory interactions. Consequently, attempting to quantitatively predict their equilibrium concentrations is a task that must take several factors into account, including the affinity for hybridization, the ability to catalyze the target, cooperation, and RNA accessibility. In the model we propose, miRBooking 2.0, each possible interaction between a microRNA and a binding site on a target RNA is characterized by an enzymatic reaction. A reaction of this type operates in two phases: a reversible formation of an enzyme-substrate complex, the microRNA-RNA duplex, and an irreversible conversion of the substrate in an RNA degradation product that restores the enzyme which can subsequently participate to other reactions. We show that the stationary state of this system, which can include up to 10 million equations in practice, has a very shallow Jacobian, allowing its efficient resolution using a sparse linear solver. This solution allows us to characterize precisely the mechanism of regulation and to study the role of microRNAs in a given cellular context. Predictions obtained on a HeLa S3 cell model correlate significantly with a set of experimental data obtained experimentally and can remarkably explain the expression threshold effects of genes. Using this solution as an initial condition and an explicit method of numerical integration, we simulate in real time the response of the system to changes of experimental conditions. We apply this model to target elements involved in the Epithelio-Mesenchymal Transition (EMT), an important mechanism of tumours proliferation. By identifying differentially expressed elements between the two conditions, we design synthetic microRNAs to interfere with the transition. To do so, we propose a method based on a parallel greedy best-first search to efficiently crawl the sequence space of the microRNA and present preliminary results on known EMT markers.

Es wurde die Optimierungssoftware SPC-Opt entwickelt, mit welcher sich Aufgaben aus den Bereichen der Formoptimierung sowie der Material- und Formidentifikation bearbeiten lassen. Zur Lösung von Identifikationsproblemen steht eine robuste Implementierung des Levenberg-Marquardt-Fletcher-Verfahrens zur Verfügung. Ergänzt wird dieses durch Line-Search- und Trust-Region-Verfahren, welche sich besonders für Aufgaben der Formoptimierung eignen. Es wurden effiziente Algorithmen zur Approximation der Hesse-Matrix sowie verschiedene Verfahren zur Startparametervariation integriert. Das Programm verfügt über Schnittstellen zur Nutzung von ABAQUS, ANSYS, MSC.MARC, eigenen FEM-Programmen sowie LUA-Skripten. Für Formoptimierungen können geometrische Konturen durch NURBS approximiert und deren Kontrollpunkte als Formparameter genutzt werden. Die Aktualisierung der FEM-Netze entsprechend der Formparameteränderung erfolgt durch ein analytisches Verfahren. Der zweite Schwerpunkt der Arbeit bezieht sich auf die Weiterentwicklung bestehender Verfahren zur Materialparameteridentifikation im Bereich der Gummiwerkstoffe. Hierbei wurde das Konzept der Anpassung anhand bauteilnaher Probekörper entwickelt. Dabei wurde am Beispiel einer Fahrwerksbuchse ein Probekörper entworfen, welcher dem originalen Bauteil zwar ähnlich sieht, jedoch eine deutlich einfachere Geometrie hat. Durch diesen konnte das Verhalten des Bauteils gut approximiert und sichergestellt werden, dass die im Rahmen der Parameteridentifikation durchgeführten FEM-Simulationen sicher konvergieren. Zudem wurden die Nutzerschnittstellen des inelastischen Morph-Stoffgesetz für MSC.MARC und ABAQUS weiterentwickelt, sodass diese nunmehr auch im industriellen Umfeld nutzbar sind. Es konnte nachgewiesen werden, dass die Verwendung bauteilnah identifizierter Parameter zu einer erheblich besseren Abbildung des Materialverhaltens führt als die Verwendung anhand von Standardprobekörpern identifizierter Parameter. Weiterhin zeigte sich, dass vor allem der Einsatz eines Stoffgesetzes mit der Möglichkeit zur Abbildung des charakteristischen Verhaltens von Elastomeren unbedingt erforderlich ist. / Within the scope of this work the optimization software SPC-Opt has been developed to successfully process tasks in the fields of shape optimization and parameter identification. The software includes a robust Levenberg-Marquardt-Fletcher algorithm, several line search and trust region algorithms as well as efficient methods for the approximation of the Hessian matrix. Additionally, procedures for the variation of initial parameters (Design Of Experiments) were implemented. The software includes interfaces to ABAQUS, ANSYS, MSC.MARC, in-house FEM programs and LUA scripts. Within shape optimization problems, geometric shapes are approximated by NURBS and the related control points are employed as design variables. For the update of the FE mesh during the variation of the design variables, a special analytical algorithm is used to preserve the mesh topology. Another focus is related to the further development of existing material parameter identification procedures for rubber materials. Therefor, the concept of component-oriented specimens was developed. Using the example of a bushing, a specimen was designed, which is similar to the original component but has a much simpler geometry. According to this, the behavior of the original component is approximated and the stability of necessary FE simulations is ensured. Additionally, the utilized Model of Rubber Phenomenology (MORPH) is improved in view of the industrial use. It is shown that the identification of material parameters using component-oriented specimens leads to a much better approximation of the original component behaviour than using standard specimens. Additionally, it is shown that the use of a material law which can consider characteritic properties of elastomers, is absolutely necessary.

Existem métodos de integração de equações algébrico diferenciais não lineares (DAEs) considerados clássicos pela literatura. Porém, neste trabalho, através uma abordagem geométrica, apresenta-se um método de integração de DAEs. Tal método é inspirado na teoria de desacoplamento de sistemas não lineares explícitos, quando se considera que as saídas são restrições algébricas. Neste caso, a DAE pode ser identificada como dinâmica zero. O resultado principal desta abordagem é que, dada uma DAE, sob certas condições, é possível a construção de um sistema explícito, de tal maneira, que as soluções desse sistema explícito convergem para as soluções da DAE. / Classical methods for numerical integration of diferential algebraic equations (DAEs) can be formal in the literature. In this work, using a diferential geometric approach, a numerical method of integration of DAEs is established. This method is inspired in the decoupling theory of nonlinear explicit systems, when one considers that the outputs are algebraic constraints. The main result is the construction of an explicit system, whose solutions converge to the solutions of the DAE.

No description available.

In this thesis, we study numerical analysis for random processes and fields. We investigate the behavior of the approximation accuracy for specific linear methods based on a finite number of observations. Furthermore, we propose techniques for optimizing performance of the methods for particular classes of random functions. The thesis consists of an introductory survey of the subject and related theory and four papers (A-D). In paper A, we study a Hermite spline approximation of quadratic mean continuous and differentiable random processes with an isolated point singularity. We consider a piecewise polynomial approximation combining two different Hermite interpolation splines for the interval adjacent to the singularity point and for the remaining part. For locally stationary random processes, sequences of sampling designs eliminating asymptotically the effect of the singularity are constructed. In Paper B, we focus on approximation of quadratic mean continuous real-valued random fields by a multivariate piecewise linear interpolator based on a finite number of observations placed on a hyperrectangular grid. We extend the concept of local stationarity to random fields and for the fields from this class, we provide an exact asymptotics for the approximation accuracy. Some asymptotic optimization results are also provided. In Paper C, we investigate numerical approximation of integrals (quadrature) of random functions over the unit hypercube. We study the asymptotics of a stratified Monte Carlo quadrature based on a finite number of randomly chosen observations in strata generated by a hyperrectangular grid. For the locally stationary random fields (introduced in Paper B), we derive exact asymptotic results together with some optimization methods. Moreover, for a certain class of random functions with an isolated singularity, we construct a sequence of designs eliminating the effect of the singularity. In Paper D, we consider a Monte Carlo pricing method for arithmetic Asian options. An estimator is constructed using a piecewise constant approximation of an underlying asset price process. For a wide class of Lévy market models, we provide upper bounds for the discretization error and the variance of the estimator. We construct an algorithm for accurate simulations with controlled discretization and Monte Carlo errors, andobtain the estimates of the option price with a predetermined accuracy at a given confidence level. Additionally, for the Black-Scholes model, we optimize the performance of the estimator by using a suitable variance reduction technique.

In den letzten Jahrzehnten hat sich auf dem Gebiet der phänomenologischen Metallplastizität eine schleichende Revolution vollzogen. Dank der gestiegenen Rechenleistung, in Kombination mit ausgereiften numerischen Algorithmen, sind viele technisch relevante Problemstellungen einer zuverlässigen numerischen Analyse zugänglich gemacht worden. Beispielsweise ermöglicht die Metallumformsimulation, als häufigste Anwendung der Plastizitätstheorie, eine Analyse des Eigenspannungszustandes und der Rückfederung in plastisch umgeformten Halbzeugen und Bauteilen. Solche Simulationen sind für die Planung energie- und ressourceneffizienter Herstellungsprozesse sowie für die Ausnutzung der plastischen Tragfähigkeitsreserven von großer Bedeutung. Die Crashtest-Simulation ist die zweithäufigste Anwendung, die in der Automobilindustrie und auch zunehmend im Flugzeugbau eingesetzt wird. Aus der Notwendigkeit, das Verhalten metallischer Werkstoffe auf Bauteilebene hinreichend genau zu beschreiben, resultiert die Motivation für eine breit angelegte Studie zur Materialmodellierung. Dabei führt die beträchtliche Anzahl unterschiedlicher Phänomene und Effekte, die berücksichtigt werden müssen, zu einer großen Vielfalt von Materialmodellen. Da die Lösung komplizierter praktischer Probleme mit einem sehr großen numerischen Aufwand verbunden ist, wird der vorteilhafte phänomenologische Zugang bevorzugt. Bei der Konzeption von neuen phänomenologischen Materialmodellen müssen folgende Aspekte beachtet werden: die Genauigkeit bei der Beschreibung des Materialverhaltens; die Stabilität und Robustheit von zugehörigen numerischen Algorithmen; die numerische Effizienz; die zuverlässige Parameteridentifikation für einen möglichst großen Anwendbarkeitsbereich; die Anschaulichkeit und Einfachheit des Materialmodells. Im Allgemeinen stehen diese Anforderungen an ein "gutes Materialmodell" zwar in einem gewissen Widerspruch zueinander, bilden andererseits aber das Grundgerüst für eine systematische Studie. Obwohl sich die vorliegende Arbeit vordergründig an erfahrene Spezialisten im Bereich der Kontinuumsmechanik wendet, sind die darin präsentierten Modelle und Algorithmen auch für praktisch tätige Berechnungsingenieure von Interesse. / In the last decades, a creeping revolution was taking place in the area of the phenomenological metal plasticity. Due to the increased computational power, combined with refined numerical algorithms, many of technically relevant problems are now available for the numerical analysis. In particular, the metal forming simulation is a typical application of the metal plasticity. It enables the analysis of the residual stresses and spring back phenomena in plastically deformed workpieces and components. Such analysis is advantageous for planning of energy and resource-efficient manufacturing and for exploitation of plastic reserves of bearing capacity. The crash test simulation is the second most common application of metal plasticity, highly celebrated in the automotive industry and gaining increasing popularity in the aircraft industry. The need for sufficiently accurate description of metal behaviour on the macroscale motivates wide-ranging studies on material modelling. The large number of different effects and phenomena contributes to the large manifold of material models. The current work deals with the phenomenological approach, due to its great suitability for the solution of practical problems. The following aspects should be taken into account upon the construction of new phenomenological models: the accurate description of the material behaviour, the stability and robustness of the corresponding numerical algorithms, the numerical efficiency, the reliable parameter identification for a sufficiently large application area, the clearness and simplicity of the material models. In general, these requirements imposed on a "good material model" contradict each other. In this work, however, they are complimentary to each other and build a framework for a systematic study. Although this work is written primarily for experts on the continuum mechanics, the presented models and algorithms can be of interest for practically working engineers.

The main objectives of this research are (a) to develop advanced simulation methods for voltage-recovery phenomena using improved, realistic system models and accurate solution techniques and (b) to develop methods for the mitigation of problems related to slow voltage recovery. Therefore, this work concentrates on the areas of voltage-recovery analysis in electric power systems, dynamic load modeling with emphasis on induction-motor models, dynamic simulation with emphasis on the numerical integration methods, and optimal allocation and operation of static and dynamic VAr resources. In the first part of this work, a general framework for power-system analysis is presented the main characteristics of which are (a) the utilization of full three-phase models and (b) the use of a "quadratized" mathematical formulation, which models the system under study as a set of mathematical equations of order no more than two. The modeling approach is essentially the same for steady-state, quasi-steady-state, and dynamic analysis. Furthermore, a new approach for time-domain transient simulation of electric power systems and dynamical systems, in general, is introduced in this research. The new methodology has been named quadratic integration method. The method is based on a numerical integration scheme that assumes that the system states vary quadraticaly within an integration time step. Accurate modeling and simulation of voltage-recovery phenomena allows the development of mitigation methodologies via the optimal allocation and operation of static and dynamic VAr resources over the planning horizon. This problem is solved with successive dynamic programming techniques with the following two innovations: (a) the states at each stage (candidate solutions) are obtained with static and dynamic (trajectory) sensitivity analysis and (b) each candidate solution is evaluated by considering the optimal operation of installed static and dynamic VAr sources utilizing concepts from the theory of applied optimal control and trajectory optimization.

Existem métodos de integração de equações algébrico diferenciais não lineares (DAEs) considerados clássicos pela literatura. Porém, neste trabalho, através uma abordagem geométrica, apresenta-se um método de integração de DAEs. Tal método é inspirado na teoria de desacoplamento de sistemas não lineares explícitos, quando se considera que as saídas são restrições algébricas. Neste caso, a DAE pode ser identificada como dinâmica zero. O resultado principal desta abordagem é que, dada uma DAE, sob certas condições, é possível a construção de um sistema explícito, de tal maneira, que as soluções desse sistema explícito convergem para as soluções da DAE. / Classical methods for numerical integration of diferential algebraic equations (DAEs) can be formal in the literature. In this work, using a diferential geometric approach, a numerical method of integration of DAEs is established. This method is inspired in the decoupling theory of nonlinear explicit systems, when one considers that the outputs are algebraic constraints. The main result is the construction of an explicit system, whose solutions converge to the solutions of the DAE.

Capture-évolution-éjection de particules par des systèmes binaires (étoile-planète, étoile binaire, étoile-trou noir supermassif, trou noir binaire, ...). Dans une première partie, en utilisant une généralisation de l'application de Kepler, nous décrivons, au travers du cas de 1P/Halley, la dynamique chaotique des comètes dans le système solaire. Le système binaire, alors considéré, est composé du Soleil et de Jupiter. L'application symplectique utilisée permet de rendre compte des différentes caractéristiques de la dynamique : trajectoires chaotiques, îlots invariants de KAM associés aux résonances avec le mouvement orbital de Jupiter,... Nous avons déterminé de façon exacte et semi-analytique l'énergie échangée (fonction kick) entre le système solaire et la comète de Halley à chaque passage au périhélie. Cette fonction kick est la somme des contributions des problèmes à trois corps Soleil-planète-comète associés aux 8 planètes du système solaire. Nous avons montré que chacune de ces contributions peut être décomposée en un terme keplerien associé au potentiel gravitationnel de la planète et un terme dipolaire dû au mouvement du soleil autour du centre de masse du système solaire. Dans une deuxième partie, nous avons utilisé la généralisation de l'application de Kepler pour étudier la capture de particules de matière noire au sein des systèmes binaires. La section efficace de capture a été calculée et montre que la capture à longue portée est bien plus efficace que la capture due aux rencontres proches. Nous montrons également l'importance de la vitesse de rotation du système binaire dans le processus de capture. Notamment, un système binaire en rotation ultrarapide accumulera en son sein une densité de matière jusqu'à 10^4 fois celle du flot de matière le traversant. Dans la dernière partie, en intégrant les équations du mouvement du problème à trois corps restreint plan, nous avons étudié l'éjection des particules capturées par un système binaire. Dans le cas d'un système binaire dont les deux corps sont de masses comparables, alors que la majorité des particules sont éjectées immédiatement, nous montrons, sur les sections de Poincaré, que la trace des particules restant indéfiniment aux abords du système binaire forme une structure fractale caractéristique d'un répulseur étrange associé à un système chaotique ouvert. Cette structure fractale, également présente dans l'espace réel, a une forme de spirale à deux bras partageant des similitudes avec les structures spiralées des galaxies comme la nôtre. / This work is devoted to the study of the restricted 3-body problem and particularly to the capture-evolution-ejection process of particles by binary systems (star-planet, binary star, star-supermassive black hole, binary black hole, ...). First, using a generalized Kepler map, we describe, through the case of 1P/Halley, the chaotic dynamics of comets in the Solar System. The here considered binary system is the couple Sun-Jupiter. The symplectic application we use allows us to depict the main characteristics of the dynamics: chaotic trajectories, KAM islands associated to resonances with Jupiter orbital motion, ... We determine exactly and semi-analytically the exchange of energy (kick function) between the Solar System and 1P/Halley at its passage at perihelion. This kick function is the sum of the contributions of 3-body problems Sun-planet-comet associated to the eight planets. We show that each one of these contributions can be split in a keplerian term associated to the planet gravitational potential and a dipolar term due to the Sun movement around Solar System center of mass. We also use the generalized Kepler map to study the capture of dark matter particles by binary systems. We derive the capture cross section showing that long range capture is far more efficient than close encounter induced capture. We show the importance of the rotation velocity of the binary in the capture process. Particularly, a binary system with an ultrafast rotation velocity accumulates a density of captured matter up to 10^4 times the density of the incoming flow of matter. Finally, by direct integration of the planar restricted 3-body problem equations of motion, we study the ejection of particles initially captured by a binary system. In the case of a binary with two components of comparable masses, although almost all the particles are immediately ejected, we show, on Poincaré sections, that the trace of remaining particles in the vicinity of the binary form a fractal structure associated to a strange repeller associated to chaotic open systems. This fractal structure, also present in real space, has a shape of two arm spiral sharing similarities with spiral structures observed in galaxies such as the Milky Way.