This thesis investigates the dynamic scheduling of computer communication networks that can be periodically overloaded. Such networks are modelled as mutliclass queueing networks in a slowly changing environment. A hierarchy framework is established to search for a suitable scheduling policy for such networks through its connection with stochastic fluid models. In this work, the dynamic scheduling of a specific multiclass stochastic fluid model is studied first. Then, a bridge between the scheduling of stochastic fluid models and that of the queueing networks in a changing environment is established. In the multiclass stochastic fluid model, the focus is on a system with two fluid classes and a single server whose capacity can be shared arbitrarily among these two classes. The server may be overloaded transiently and it is under a quality of service contract which is indicated by a threshold value of each class. Whenever the fluid level of a certain class is above the designated threshold value, the penalty cost is incurred to the server. The optimal and asymptotically optimal resource allocation policies are specified for such a stochastic fluid model. Afterwards, a connection between the optimization of the queueing networks and that of the stochastic fluid models is established. This connection involves two steps. The first step is to approximate such networks by their corresponding stochastic fluid models with a proper scaling method. The second step is to construct a suitable policy for the queueing network through a successful interpretation of the stochastic fluid model solution, where the interpretation method is provided in this study. The results developed in this thesis facilitate the process of searching for a nearly optimal scheduling policy for queueing networks in a slowly changing environment.

<p><a></a><a>Microbial chemical factories (MCFs) have become an attractive platform for producing valuable drugs, chemicals, and biofuels due to increasing environmental concerns, energy demands, and the difficulties associated with chemically synthesizing complex molecules. However, the potential of using microbes to produce many valuable products has not been fully realized due to low productivity and yields. Production may be enhanced through the dynamic control of metabolic pathways to alleviate metabolic imbalances and toxic product build-up, but very few tools are available to broadly implement this paradigm. I aim to expand this toolbox by developing tunable sensor-regulator devices that act as feedback controllers for toxic intermediate formation by responding to cues of cell health for improved production. Elastin-like polypeptide (ELP) will act as the sensing domain of the controller to indirectly sense toxic metabolite accumulation through changes in intracellular pH. ELPs make ideal sensors since they exhibit a sharp, inverse phase transition to indicators of cellular health such as pH and ionic strength, and external stimuli such as temperature. In this research, a library of ELPs that exhibit pH sensitivity and transition under various conditions was made and purified using a new organic solvent extraction method. It is hypothesized that fusion of ELP to orthogonal transcription factor will allow for the controlled expression of target genes in response to stimuli without disrupting native processes. As proof of concept, an ELP fusion to orthogonal sigma factor was designed to drive the expression of a fluorescent reporter protein. Initial designs successfully alter gene expression by 21% in response to temperature. To improve this response, an alternative feed-forward loop architecture was modelled, which predicted an improved response of 35% and increased ultrasensitivity. Refinement of this design </a>and combinatorial construct libraries will generate various regulators with diverse outputs that may be integrated in bioproduction pathways for improved performance.</p>

The Flexible Low-cost Automated Scaled Highway (FLASH) laboratory at the Virginia Tech Transportation Institute (VTTI) is one of many facilities dedicated to the field of Intelligent Transportation Systems (ITS). The goal of the FLASH lab is to provide small-scale development and implementation of autonomous control strategies for today's vehicles. The current controller used on the scale vehicles is based solely on the kinematics of the system. This body of work was aimed to develop a dynamic control law to enhance the performance of the existing kinematic controller. This control system is intended to automatically maintain the vehicle's alignment on the road as well as keep the speed of the vehicle constant. Implementation of such systems could conceivably reduce driver fatigue by removing nearly all the burden of the driving process from the driver while on the highway. System dynamics of car-like robots with nonholonomic constraints were employed in this research to create a controller for an autonomous path following vehicle. The application of working kinematic and dynamic models describing car-like robotic systems allowed the development of a nonlinear controller. Simulations of the vehicle and controller were done using MATLAB. Comparisons of the kinematic controller and the dynamic controller presented here were also done. In order to make the simulations model the actual system more closely, measures were taken to approximate actual sensor readings. / Master of Science

Dans cette thèse, nous avons travaillé sur le problème de la mise œuvre des plans de contrôle dynamique au sein d'un environnement semi-conducteur multi-produits. Nous nous sommes focalisés sur le compromis entre le rendement et le temps de cycle, la réduction du nombre de contrôles sans valeur ajoutée, et l'optimisation de l'utilisation de la capacité de contrôle. Nous avons commencé par formaliser et généraliser le problème au travers d'une revue de la littérature. Ensuite, nous avons proposé trois principales solutions pour supporter l'implémentation industrielle des plans de contrôle dynamique. La première solution que nous avons proposée est basée sur un indicateur qui permet le traitement d'un très grand volume de données et l'évaluation de plusieurs types de risques avec une très faible consommation des ressources informatiques. La deuxième solution est basée sur des algorithmes d'échantillonnage intelligents que nous avons développés pour permettre le choix en dynamique des meilleurs produits ou lots à contrôler. Et la troisième solution est un programme linéaire mixte en nombres entiers que nous avons développé pour optimiser les paramètres clés qui sont utilisés dans les algorithmes d'échantillonnage dynamique.L'originalité des travaux de cette thèse se trouve dans l'industrialisation des différentes solutions que nous avons proposées. Toutes les solutions ont été validées industriellement et certaines solutions ont été étendues à d'autres sites de la compagnie. Plusieurs perspectives ont été identifiées et offrent ainsi de nombreuses pistes de recherche. / In this thesis, we have worked on the problem of implementing dynamic control plans in a high-mix semiconductor environment. We focused on the trade-off between yield and cycle time, the minimization of the number of controls without added value, and the optimization of the use of inspection capacity. We started our works by formalizing and generalizing the problem through a literature review. Then, we proposed three main solutions to industrially implement dynamic control plan policies. The first solution we proposed is based on an indicator that enables a very large amount of data to be handled and several risk types assessed with little CPU. The second solution is based on smart sampling algorithms we developed to enable the dynamic selection of the best products or lots to control in real time. And the third solution is a mixed-integer linear programming model we developed to optimize the key parameters that are used in the smart sampling algorithms.The originality of this thesis lies in the industrial implementation of the general solutions we proposed. All solutions have been industrially validated and some of the solutions have been extended to other sites of the company. Several perspectives have been highlighted and offer numerous avenues for further works.

Existe um crescente aumento nos gastos mundiais em inovação, com maior participação de áreas como a computação, a eletrônica, a saúde, a área automotiva e a área industrial. Mecanismos diferenciados, assimétricos, tais como o estudado neste trabalho, necessitam de maiores investigações, como a realização de ensaios normatizados. Para se contribuir com esse cenário propõe-se a análise de um sistema robótico, de arquitetura paralela, para experimentos de múltiplas finalidades. O presente trabalho aborda desde a construção de uma máquina paralela de topologia assimétrica, passando por seu controle, até a obtenção de informações sobre essa nova arquitetura. A sua construção é dividida em cinco subsistemas, que se interrelacionam: o mecânico, o elétrico, o de atuação, o de controle e o de interface. Sete estratégias de controle foram comparadas de acordo com os seguintes critérios: a exatidão na trajetória, o comprimento controlável, a dispersão das trajetórias em diferentes períodos de tempo, e o consumo de energia. Os resultados foram gerados por meio de registro, em folha de papel, da trajetória do efetuador da máquina. As curvas geradas foram digitalizadas e comparadas entre si. Os resultados mostraram que os controles dinâmicos podem permitir o funcionamento adequado da máquina, sendo possível, inclusive, velocidades maiores que as observadas no controle descentralizado PID. Neste trabalho em particular, o maior desafio observado foi o valor da menor frequência natural amortecida, que se mostrou baixo e resultou em baixos esforços de controle. Em ordem decrescente, os tipos de controle que apresentaram melhores resultados foram o PID descentralizado, o controle por torque computado com feedforward, e o controle por modos deslizantes, também com feedforward. / There is a steady increase in global spending on innovation, with an increased share of areas such as computing, electronics, health, automotive and industrial area. Differentiated, asymmetric mechanisms, such as the one proposed in this work, need further investigations, such as standardized tests. To contribute to this scenario the analysis of a robotic system, with parallel architecture and for multi-purpose experiments, is proposed. This work covers the construction of a parallel machine with asymmetric topology, its control, and the collection of information on this new architecture. Its construction is divided into five sub-systems, which are interrelated: the mechanical, the electrical, the actuation, the control and its interface. Seven control strategies were compared, according to four criteria. The chosen criteria are the following: track accuracy, stability range, dispersion of the paths at different periods and energy consumption. The results were generated by recording, on a sheet of paper, the trajectory of the machine\'s end-effector. The plots were digitalized and compared. The results showed that the dynamic controls can allow the machine to behave appropriately, even at speeds higher than those with the decentralized PID. The main challenge in this case was the lowest damped frequency, with a low value that resulted in low control efforts. In decreasing order, the best results were achieved with the decentralized PID, the feedforward computed torque control and the feedforward sliding modes control.

In the context of control, the motion of a legged robot is very challenging compared with traditional fixed manipulator. Recently, many researches have been conducted to control the motion of legged robot with different techniques. On the other hand, manipulation tasks have been addressed in many applications. These researches solved either the mobility or the manipulation problems, but integrating both properties in one system is still not available. In this thesis, a control algorithm is presented to control both locomotion and manipulation in a six legged robot. Landmines detection process is considered as a case study of this project to accelerate the mine detection operation by performing both walking and scanning simultaneously. In order to qualify the robot to perform more tasks in addition to the walking task, the joint redundancy of the robot is exploited optimally. The tasks are arranged according to their importance to high level of priority and low level of priority. A new task priority redundancy resolution technique is developed to overcome the effect of the algorithmic singularities and the kinematic singularity. The computational aspects of the solution are also considered in view of a real-time implementation. Due to the dynamic changes in the size of the robot motion space, the algorithm has the ability to make a trade-off between the number of achieved tasks and the imposed constraints. Furthermore, an appropriate hierarchy is imposed in order to ensure an accurate decoupling between the executed tasks. The dynamic effect of the arm on the overall performance of the robot is attenuated by reducing the optimisation variables. The effectiveness of the method is evaluated on a Computer Aided Design (CAD) model and the simulations of the whole operation are conducted using MATLAB and SimMechanics.

No description available.

La vision artificielle est un moyen de perception très apprécié en robotique. Les applications les plus courantes de la vision en robotique manipulatrice sont l'estimation de pose et la commande. D'un point de vue conceptuel, l'utilisation de la vision artificielle permet d'améliorer les performances de la commande des robots en termes de précision et de robustesse (vis-à-vis des erreurs sur les paramètres géométriques du robot). De plus, cette mesure est d'autant plus pertinente pour les robots parallèles puisque l'état de ces derniers est généralement mieux défini par la pose de l'effecteur que par les mesures articulaires, traditionnellement utilisées en commande. Cependant, les systèmes de vision classiques ne permettent pas de satisfaire les exigences des commandes hautes performances à cause de leur période d'acquisition et de leur temps de latence trop grands. Pour pallier ce problème, l'approche proposée dans cette thèse est de procéder à une acquisition séquentielle de fenêtres d'intérêt. En effet, le fait de ne transmettre que les régions de l'image contenant les primitives visuelles utiles a pour effet de diminuer la quantité de données à transmettre ce qui permet réduire la période d'acquisition et le temps de latence. De plus, l'acquisition non simultanée des primitives offre la possibilité d'estimer la pose et la vitesse du robot de façon conjointe. Différentes méthodes d'estimation et plusieurs schémas de commandes cinématiques et dynamiques utilisant ce mode d'acquisition ont ainsi été proposés dans ce document. Les résultats expérimentaux obtenus en commande dynamique par vision d'un robot parallèle montrent, pour la première fois, que la commande référencée vision peut être plus performante que la commande articulaire. / Visual sensing is very appreciated in manipulation robotics since it provides measures for pose estimation and robot control. Conceptually, vision allows improving the performance of manipulator robots control from accuracy and robustness (against kinematic parameters errors) points of view. In addition, vision-based control is particularly relevant for parallel robot manipulators. In fact, the state of these robots is usually better described by the pose of their mobile platform than by their articular joints. Thus, the use of vision simplifies the control of parallel robots. However, the typical vision systems do not fulfil the dynamic control constraints on the acquisition frequency and the latency. The approach proposed in this thesis is to perform a sequential acquisition of regions of interest which contain the useful visual features to cut down the data amount to transmit. Thus allows for reducing the acquisition period and latency. In addition, the sequential acquisition allows for estimating both the pose and the velocity of the robot platform. Thanks to this acquisition method, several control laws are proposed. The experimental results show that the performance of the proposed vision based dynamic control laws are, for the first time, better than classical dynamic control.

Understanding the mechanisms and nature of tumour heterogeneity is a key focus of current cancer research. Tumour heterogeneity can arise from clonal evolution and/or differentiation. This thesis investigated the role of methylation in dynamic regulation of CD24 based heterogeneity in colorectal cancer cell lines. First, E-Cadherin variation between the cell lines LS174T and LS180 was investigated to find out whether E-Cadherin had any causal role in the difference in lumen formation between these two cell lines derived from the same tumour. These studies found no evidence of a causal role of E-Cadherin. However, morphological heterogeneity in LS174T was observed during the E-Cadherin study, suggesting that this cell line might be a mixture of two different clones. Single cell sorting by FACS allowed to isolate and establish these clones which were stable in the culture for long enough (until passage ~30) to allow their characterisations. Between the two clones, the CD24⁺ clone (named the LS174T_Clone 1^CD24+) was found to have shorter doubling time (23 hours) than the CD24- clone (named the LS174T_Clone 2CD24-; 30 hours). When cultured in matrigel, the LS174T_Clone 1^CD24+ showed higher clonogenicity (Chapter 4). Microarray analysis further revealed differences in gene expression including LAPTM4B, CXCR4, TGFIB and IL8 between these clones. Interestingly, when maintained for a long time in culture (around passage 50, which is equivalent to ~7 months), CD24 expression went through a gradual change in these clones, which became more evident from subclones of LS174T_Clone 2^CD24- (Chapter 6) and clones from another CRC cell line SW480 (chapter 5 and 6). To understand the mechanism of this dynamic change in the expression of CD24, it was first shown that no mutation could be responsible for this phenomenon. This suggested that promoter methylation of CD24 might be the mechanism of the observed dynamic changes in CD24 expression. Bisulfite (BS) modification of DNA from the LS174T clones and CD24 differentially expressing CRC cell lines (such as CD24- cell lines: CC20, RKO vs CD24+ cell lines: DLD1, NCIH716) followed by Sanger sequencing showed that direct methylation of seven CpG positions in the CD24 promoter region Chr6:106975560-106975834 is strongly correlated with the expression of CD24. Further subcloning and sequencing revealed that changes in the methylation of only two out of the seven CpG positions might be the main contributor to the CD24 expression differences. This is the first evidence of direct methylation-mediated regulation of CD24, showing, more broadly, how methylation can contribute to and maintain dynamic heterogeneity in cancer cells. Finally, a mixed culture experiment with the CD24+ and CD24- clones was conducted to test a simple mathematical model, which aimed to explain the interaction between the clones that are stably present in the LS174T cell line (Chapter 7). Altogether, these experiments suggest that genes such as REG1A (an inducer of angiogenesis) might be expressed because of synergistic interactions between the clones, whereas CXCR4 and TFF2 might be involved in a receptor-ligand complementary relationship. These findings have set a ground for future studies to confirm such interactions between co-existing subpopulations within a heterogeneous milieu of cancer cells.

Existe um crescente aumento nos gastos mundiais em inovação, com maior participação de áreas como a computação, a eletrônica, a saúde, a área automotiva e a área industrial. Mecanismos diferenciados, assimétricos, tais como o estudado neste trabalho, necessitam de maiores investigações, como a realização de ensaios normatizados. Para se contribuir com esse cenário propõe-se a análise de um sistema robótico, de arquitetura paralela, para experimentos de múltiplas finalidades. O presente trabalho aborda desde a construção de uma máquina paralela de topologia assimétrica, passando por seu controle, até a obtenção de informações sobre essa nova arquitetura. A sua construção é dividida em cinco subsistemas, que se interrelacionam: o mecânico, o elétrico, o de atuação, o de controle e o de interface. Sete estratégias de controle foram comparadas de acordo com os seguintes critérios: a exatidão na trajetória, o comprimento controlável, a dispersão das trajetórias em diferentes períodos de tempo, e o consumo de energia. Os resultados foram gerados por meio de registro, em folha de papel, da trajetória do efetuador da máquina. As curvas geradas foram digitalizadas e comparadas entre si. Os resultados mostraram que os controles dinâmicos podem permitir o funcionamento adequado da máquina, sendo possível, inclusive, velocidades maiores que as observadas no controle descentralizado PID. Neste trabalho em particular, o maior desafio observado foi o valor da menor frequência natural amortecida, que se mostrou baixo e resultou em baixos esforços de controle. Em ordem decrescente, os tipos de controle que apresentaram melhores resultados foram o PID descentralizado, o controle por torque computado com feedforward, e o controle por modos deslizantes, também com feedforward. / There is a steady increase in global spending on innovation, with an increased share of areas such as computing, electronics, health, automotive and industrial area. Differentiated, asymmetric mechanisms, such as the one proposed in this work, need further investigations, such as standardized tests. To contribute to this scenario the analysis of a robotic system, with parallel architecture and for multi-purpose experiments, is proposed. This work covers the construction of a parallel machine with asymmetric topology, its control, and the collection of information on this new architecture. Its construction is divided into five sub-systems, which are interrelated: the mechanical, the electrical, the actuation, the control and its interface. Seven control strategies were compared, according to four criteria. The chosen criteria are the following: track accuracy, stability range, dispersion of the paths at different periods and energy consumption. The results were generated by recording, on a sheet of paper, the trajectory of the machine\'s end-effector. The plots were digitalized and compared. The results showed that the dynamic controls can allow the machine to behave appropriately, even at speeds higher than those with the decentralized PID. The main challenge in this case was the lowest damped frequency, with a low value that resulted in low control efforts. In decreasing order, the best results were achieved with the decentralized PID, the feedforward computed torque control and the feedforward sliding modes control.