Parallel computing offers immense potential to solve large, complex scientific problems. Load imbalance is a major impediment in obtaining high performance by a parallel system. One principal form of parallelism found in scientific applications is data parallelism. Loops without dependencies are data parallel. During the execution of large parallel loops, computational requirements vary due to problem, algorithmic and systemic characteristics. These factors lead to load imbalance which in turn degrades the performance of an application. Over the years, a number of dynamic loop scheduling techniques have been proposed to address one or more of these factors. However, there is no single strategy that works well for different problem domains and system characteristics. Moreover, load balancing during runtime is complicated because of its need for dynamic data redistribution. Therefore, there is a distinct need to integrate the dynamic loop scheduling techniques into a single package and provide them as an application programming interface (API) to the application developer. In recent years, along this direction, a number of dynamic loop scheduling techniques have been integrated into the compiler technologies for shared memory environments. On the other hand, there is no such integrated approach for distributed memory applications. The purpose of this thesis is to present the design, implementation and effectiveness of an integrated approach:the dynamic loop scheduling techniques are integrated into a runtime system for distributed memory architectures. For this purpose, we choose the newly developed parallel runtime environment for multicomputer architecture (PREMA) with its main components: the data movement and control substrate (DMCS) and mobile object layer (MOL). This runtime system has recently been developed and has demonstrated to be one of the most competitive runtime systems for distributed memory architectures. The significance of this work is that the proposed API will enhance the performance of parallel applications by reducing the load imbalance among processors caused by a wide range of factors and will reduce the software developmental cost required for load balancing. With the integration of the scheduling capabilities into the runtime system, its applicability has been expanded. The performance of the API has been evaluated qualitatively and quantitatively. The overhead of the API has been studied analytically and measured experimentally. Three parallel benchmarks including scientific applications of general interest (N-body simulations, automatic quadrature routine and unstructured grid heat solver) were considered for experimentation purpose. Based on the experiments conducted, a cost improvement of up to 76% over the straight forward parallel benchmark has been obtained. For certain application characteristics, the overhead of the runtime system was found to be within 10% of the underlying messaging layer. These results demonstrate that, in large scientific applications it is possible and desirable to combine the rich functionality of a runtime system with the advantages of scheduling techniques to achieve high performance.

Many types of devices based on power converters have been proposed and studied for utility applications. In recent years most of the control systems for these converters have been digital. Unfortunately, such digital controllers, which are often based on a digital signal processor (DSP), are difficult to model in simulation. Thus, hardware prototypes are usually required. This thesis presents a tool for fast prototyping that helps overcome these difficulties. Namely, a hardware-in-the-loop simulation is provided for the digital controller in order to evaluate control algorithms without the voltage source converter and power system. The controller in the loop design methodology is described and the division between the real-time power system model and the hardware controller with an interface is shown. Also, the modulation type, integration time step selection and synchronization between the controller and the real-time system simulation are discussed. The hardware configuration for the real-time simulator and the software implementation of the simulator is discussed. In this thesis an example application of a shunt active compensator following this formal procedure is presented. The active compensator prototyping was first developed in MATLAB/Simulink. Then, following a formal design procedure, the power system was modeled in a digital simulator and the controller was implemented in a digital controller board. Finally, a hardware-in-the-loop test was carried out to validate the performance of the hardware controller for the active compensator. Although the tools and methods presented here are aimed at shunt connected current controller application, they may be generalized for use in the development of any digitally controlled power electronic converter.

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Loop vectorization is a powerful optimization technique that can significantly boost the runtime of loops. This optimization depends on functional equivalence between the original and optimized code versions, a requirement typically established through the compiler's static analysis. When this condition is not met, the compiler will miss the optimization. The process of manually rewriting the source code to pass an already missed compiler optimization is time-consuming, given the multitude of potential code variations, and demands a high level of expertise, making it impractical in many scenarios. In this work, we propose a novel framework that aims to take the code blocks that the compiler failed to optimize and transform them to another code block that passes the compiler optimization. We develop an algorithm to efficiently search for a code structure that automatically passes the compiler optimization (weakly verified through a correctness test). We focus on loop-vectorize optimization inside OpenMP directives, where the introduction of parallelism adds complexity to the compiler's vectorization task and is shown to hinder optimizations. Furthermore, we introduce a modified version of TSVC, a loop vectorization benchmark in which all original loops are executed within OpenMP directives. Our evaluation shows that our framework enables " loop-vectorize" optimizations that the compiler failed to pass, resulting in a speedup up to 340× in the blocks optimized. Furthermore, applying our tool to HPC benchmark applications, where those applications are already built with optimization and performance in mind, demonstrates that our technique successfully enables extended compiler optimization, thereby accelerating the execution time of the optimized blocks in 15 loops and the entire execution time of the three applications by up to 1.58 times. / Master of Science / Loop vectorization is a powerful technique for improving the performance of specific sections in computer programs known as loops. Particularly, it simultaneously executes instructions of different iterations in a loop, providing a considerable speedup on its runtime due to this parallelism. To apply this optimization, the code needs to meet certain conditions, which are usually checked by the compiler. However, sometimes the compiler cannot verify these conditions, and the optimization fails. Our research introduces a new approach to fix these issues automatically. Normally, fixing the code manually to meet these conditions is time-consuming and requires high expertise. To overcome this, we've developed a tool that can efficiently find ways to make the code satisfy the conditions needed for optimization. Our focus is on a specific type of code that uses OpenMP directives to split the loop on multiple processor cores and runs them simultaneously, where adding this parallelism makes the code more complex for the compiler to optimize. Our tests show that our approach successfully improves the speed of computer programs by enabling optimizations initially missed by the compiler. This results in significant speed improvements for specific parts of the code, sometimes up to 340 times faster. We've also applied our method to well-optimized computer programs, and it still managed to make them run up to 1.58 times faster.

<p> We present a symbolic analysis of a class of while loop programs which can automatically derive a closed-form symbolic expression for the input-output relation embodied in that program.</p> <p> We show that this is especially well-suited to analyzing programs from scientific computation, in particular programs which compute special functions (like Bessel functions) from its Taylor series expansion. Other than making heavy use of algebraic manipulations, as available in any computer algebra system, we also require the use of recurrence relations. It is from these recurrence relations that we derive most of our information.</p> <p> It is important to note that we can often get interesting information about a program (like termination) without requiring closed-form solutions to the recurrences.</p> / Thesis / Master of Science (MSc)

A dynamic real-time optimization (DRTO) formulation with closed-loop prediction is used to coordinate distributed model predictive controllers (MPCs) by rigorously predicting the interaction between the distributed MPCs and full plant response in the DRTO formulation. This results a multi-level optimization problem and that is solved by replacing the MPC quadratic programming subproblems by their equivalent Karush-Kuhn-Tucker (KKT) first-order optimality conditions to yield a single-level mathematical program with complementarity constraints (MPCC). The proposed formulation is able to perform both target tracking and economic optimization with significant performance improvement over decentralized control, and similar performance to centralized MPC. A linear dynamic case study illustrates the performance of the proposed strategy for coordination of distributed MPCs for different levels of plant interaction,. The method is thereafter applied to a nonlinear integrated plant with recycle, where its performance in both set-point target tracking and economic optimization is demonstrated. Subsequently, this study presents two techniques for approximation of the closed-loop prediction within the DRTO formulation - a hybrid closed-loop formulation and an input clipping formulation. The hybrid formulation generates closed-loop predictions for a limited number of time intervals along the DRTO prediction horizon, followed by an open-loop optimal control formulation extended to rest of the horizon. The input clipping formulation utilizes an unconstrained MPC optimization formulation for each distributed MPC, coupled with the application of an input saturation mechanism. The performance of the approximation techniques is evaluated through application to case studies based on linear and nonlinear dynamic plant models respectively. The approximation techniques are demonstrated to be more computationally efficient than than the rigorous counterpart without significant loss in performance. The performance of the proposed DRTO formulation can be further improved by the introduction of nonlinearity. The nonlinear dynamic plant model is firstly introduced in the DRTO formulation while maintaining the linear formulation for the distributed MPCs. The performance of resulting formulation is demonstrated and compared against the linear counterpart. The nonlinear MPC formulation is then included in both lower-level control implementation and DRTO formulation. By reformulating the Lagrangian of the nonlinear MPC optimization subproblems, the nonlinear MPC formulation is successfully implemented in the DRTO formulation. The performance of such DRTO formulation is further improved and shown using a nonlinear case study. The conclusion of this study is summarized and the potential directions of this research such as large-scale applications, variation of MPC implementations, and robust model-based control are outlined and explained in the end. / Thesis / Master of Applied Science (MASc)

Caenorhabditis elegans es un nematodo de vida libre utilizado como organismo modelo en diferentes disciplinas de la ciencia. Su tamaño reducido, plan corporal anatómicamente simple, ciclo de vida corto y amplio repertorio de comportamientos, lo han transformado en un organismo muy útil en investigación. Además, emerge como un modelo de interés en la industria farmacéutica para realizar ensayos in vivo rápidos y económicos, y para la detección de compuestos con actividad biológica. C. elegans comparte características fisiológicas y farmacológicas con nematodos parásitos y además es sensible a la mayoría de las drogas antiparasitarias que se utilizan en el hombre y en los animales. Dado que es difícil trabajar con nematodos parásitos en el laboratorio, C. elegans ha emergido como un excelente modelo de nematodo parásito y ha contribuido al conocimiento de los mecanismos de acción de diversos fármacos. C. elegans cuenta con la mayor familia de receptores Cys-loop. En sus músculos, posee tres receptores Cys-loop principales: dos receptores nicotínicos (nAChRs), el L-AChR y el N-AChR, y el receptor de GABA, UNC-49. Los nAChRs median la contracción de los músculos de la pared del cuerpo mientras que los receptores de GABA median la relajación muscular, permitiendo el movimiento sinusoidal típico del nematodo. Estos receptores son los blancos moleculares de drogas antihelmínticas. El levamisol, actuando como agonista del L-AChR, genera contracción sostenida de los músculos y finalmente la parálisis espástica del nematodo. La piperazina, actuando como agonista de los receptores de GABA, genera relajación muscular y parálisis flácida. Otros receptores Cys-loop presentes en el nematodo también son blancos de fármacos antihelmínticos. El receptor de glutamato permeable a cloruro (GluCl) presente en neuronas y células musculares es el blanco molecular de la ivermectina (IVM), uno de los antiparasitarios más utilizados a nivel mundial. En cuanto a los receptores Cys-loop, C. elegans no es más diferente a los nematodos parásitos de lo que cada especie individual de parásito lo es de otra. Esto se evidencia en la amplia diversidad de subunidades que generan receptores Cys-loop con diferente composición y propiedades farmacológicas en los nematodos y cuyas bases moleculares no se comprenden completamente. En esta Tesis se utilizó a C. elegans como modelo de nematodo parásito. Se estudiaron las propiedades antihelmínticas y los blancos de acción de diferentes compuestos químicos a través de ensayos de comportamiento. Para determinar sus mecanismos de acción se realizaron registros electrofisiológicos de corrientes unitarias y macroscópicas sobre receptores presentes en células musculares de C. elegans o expresados heterologamente en células de mamífero. En el Capítulo 1 se estudió el befenio, un antihelmíntico colinérgico cuyo modo de acción no se conocía completamente. Mediante ensayos de comportamiento se determinó que befenio genera parálisis espástica en nematodos salvajes adultos jóvenes. Utilizando cepas mutantes se determinó que el L-AChR es el blanco molecular involucrado en la actividad paralizante de befenio. Estos resultados sugieren que no existiría un receptor específico para befenio en los músculos de C. elegans. Cuando befenio fue combinado con levamisol el efecto paralizante fue aditivo. Esto es de importancia ya que la combinación de drogas es una buena estrategia para reducir la resistencia en nematodos parásitos. A nivel molecular, mediante registros de canal único, se determinó que befenio activa el L-AChR de C. elegans tanto en larvas L1 como L2, y a mayores concentraciones, actúa como un bloqueador de canal abierto de dicho receptor. Los estudios de docking molecular mostraron que befenio se une al sitio de unión ortostérico del agonista y forma las interacciones cation-π requeridas para la activación del receptor. Estos resultados podrían explicar la alta eficacia para activar el L-AChR. La selectividad de befenio por el nAChR muscular de mamífero fue estudiada mediante registros de canal único y de corrientes macroscópicas. Se determinó que befenio activa el nAChR pero actúa como un agonista muy débil y un bloqueador de canal potente. Según estudios de docking molecular, befenio generaría las interacciones necesarias para la activación solamente en uno de los dos sitios ortostéricos del receptor. Esto explicaría su baja eficacia en receptores de mamífero con respecto a los receptores de nematodos. Cepas mutantes de C. elegans que carecen de la subunidad LEV-8 podrían contener LAChRs formados por la subunidad ACR-8 en su reemplazo. Estos L-AChRs imitan un receptor de nematodo parásito, como el receptor de H. contortus, cuya subunidad ACR-8 podría mediar la actividad de befenio. Mediante ensayos de comportamiento con la cepa mutante se determinó que la subunidad ACR-8 no es requerida para el efecto paralizante de befenio en C. elegans. A nivel de canal único, los receptores que carecen de la subunidad LEV-8 también fueron activados por befenio y dicha droga, al igual que ACh, indujo una rápida desensibilización del receptor. En el Capítulo 2 se estudiaron tres terpenoides, carvacrol, timol y eugenol, presentes en plantas. Mediante ensayos de comportamiento utilizando nematodos salvajes, se determinó que los terpenoides paralizan rápidamente a C. elegans. El orden de potencia de parálisis fue: carvacrol>timol>eugenol. Las larvas fueron más sensibles que los nematodos adultos jóvenes. Además, los compuestos inhibieron irreversiblemente la eclosión de los huevos con el mismo orden de potencia. Estos hallazgos indican que los terpenoides producen efectos antihelmínticos a corto y largo plazo. Se evaluaron tres combinaciones de drogas: timol/levamisol, timol/piperazina y timol/ivermectina. El efecto paralizante de la combinación timol/levamisol fue sinérgico y dicha combinación también fue efectiva en la inhibición de la eclosión de huevos. Mediante ensayos de comportamiento con nematodos mutantes se determinó que los L-AChRs y los receptores de GABA son los blancos moleculares de los terpenoides. Los registros de corrientes macroscópicas revelaron que los compuestos no son capaces de activar los receptores, pero inhiben las corrientes evocadas por los agonistas. En registros de canal único, los terpenoides disminuyeron la actividad de L-AChRs generada por ACh y levamisol, redujeron la frecuencia de aperturas del L-AChR e indujeron un componente de estado cerrado más prolongado. Sin embargo, no afectaron las propiedades del canal como la conductancia y la duración de apertura. El análisis global indicó que los terpenoides ejercen su efecto antihelmíntico actuando como antagonistas no competitivos del L-AChR. En el Capítulo 3 se estudió la doxepinona, considerada una estructura química privilegiada. Mediante ensayos de comportamiento se demostró que la doxepinona ejerce su acción paralizante sobre nematodos salvajes adultos jóvenes actuando a través el GluCl, el blanco molecular de la IVM. Este compuesto sintético generó parálisis estacionaria en nematodos salvajes. La IVM actúa sobre GluCls presentes en la faringe del nematodo e inhibe el bombeo faríngeo. Doxepinona también redujo la velocidad de bombeo faríngeo en nematodos salvajes y el efecto fue mediado por los GluCls. Mediante registros de corrientes macroscópicas se caracterizaron las corrientes del receptor heteromérico GluCl α 1/GluClß de C. elegans evocadas por el agonista glutamato. Se determinó que la doxepinona no es un agonista de dicho receptor ya que no es capaz de activarlo. Mediante diferentes protocolos de aplicación de drogas, se determinó que la doxepinona actúa como un inhibidor alostérico de los GluCls. Se propuso a la inhibición del GluCl como un nuevo mecanismo antihelmíntico. En resumen, en esta Tesis Doctoral, utilizando a C. elegans como modelo de nematodo parásito, se identificaron los sitios y se descifraron los mecanismos de acción molecular de diferentes compuestos químicos, con actividad antihelmíntica. / Caenorhabditis elegans is a free-living nematode used as a model organism in different science disciplines. Its reduced size, anatomically simple body plan, short life cycle and broad repertoire of behaviours have turned it in a useful organism for research. It also emerges as an interesting model in the pharmaceutical industry for fast and cheap in vivo assays and for the detection of compounds with biological activity. C. elegans shares pharmacological and physiological characteristics with parasitic nematodes and is sensitive to most antiparasitic drugs used in humans and animals. Given that parasitic nematodes are difficult to work with in the laboratory, C. elegans has emerged as an excellent parasitic model and has contributed to the understanding of mechanisms of action of anthelmintic drugs. C. elegans has the largest Cys-loop receptor family. In its muscle, it has three main Cysloop receptors: two nicotinic receptors (nAChRs), L-AChR and N-AChR, and the UNC-49 GABA receptor. nAChRs mediate body wall muscle contraction while GABA receptors mediate muscle relaxation, thus allowing the typical sinusoidal movement of the nematode. These receptors are the molecular targets of anthelmintic drugs. Levamisole, acting as an L-AChR agonist, generates sustained muscle contraction which ends in spastic paralysis of the nematode. Piperazine, by acting as an agonist of GABA receptors, generates muscle relaxation and flaccid paralysis. Other Cys-loop receptors in the nematode are also targets of anthelmintic drugs. The glutamate-activated chloride channel (GluCl) present in neurons and muscle cells is the molecular target of ivermectin (IVM), which is one of the most used antiparasitic drug worldwide. Considering Cys-loop receptors, C. elegans is no more dissimilar to parasitic nematodes than each individual species of parasite is to another. This results from the wide subunit diversity that generates Cys-loop receptors with different compositions and pharmacological properties among nematodes; the molecular basis of this diversity remains not fully understood. In this Thesis, C. elegans was used as parasitic nematode model. The anthelmintic properties and molecular targets of different chemical compounds were studied through behavioural assays. To determine their mechanisms of action, electrophysiological recordings, single-channel and macroscopic current recordings, were carried out in C. elegans muscle cells or in mammalian cells heterologously expressing the receptor under study. In Chapter 1 bephenium was studied. It is a cholinergic anthelmintic drug whose mechanism of action was not fully understood. Through behavioural assays it was determined that bephenium generates spastic paralysis in young adult wild-type worms. By using different mutant strains, it was determined that L-AChR is the molecular target involved in the paralyzing activity of bephenium. The results suggested that there may not be a specific receptor for bephenium in C. elegans muscle. When bephenium was combined with levamisole, the paralyzing effects were additive; which is of significance since drug combination is a good strategy to reduce resistance in parasitic nematodes. At the molecular level, through single channel recordings, it was determined that bephenium activates L-AChR in larvae L1 and L2 C. elegans. At higher concentrations, it acted as an L-AChR open channel blocker. Molecular docking studies showed that bephenium binds to the orthostetic agonist binding site and forms the cation-π interactions required for receptor activation. This result may explain the high efficacy for L-AChR activation. Bephenium selectivity for the mammalian muscle nAChR was studied through singlechannel and macroscopic current recordings. Bephenium activated nAChRs, but it acted as a very weak agonist and a potent channel blocker. According to the molecular docking studies, bephenium would generate the necessary interactions for activation only in one of the two orthosteric sites of the receptor. This may explain the low efficacy in the mammalian receptor with respect to nematode receptors. C. elegans mutant strains that lack LEV-8 subunit may have L-AChRs containing the spare ACR-8 subunit in its replacement. These L-AChRs may mimic those in certain nematode parasites, like the H. contortus receptor, for which it was suggested that its ACR-8 subunit may mediate bephenium activity. Through behavioural assays in the mutant strain, it was determined that the ACR-8 subunit is not required for the paralyzing effects of bephenium on C. elegans. At the single channel level, the receptors that lack LEV-8 subunit were similarly activated by bephenium. Bephenium, like ACh, induced fast receptor desensitization. In the Chapter 2 terpenoids present in plants (carvacrol, thymol and eugenol) were studied. Through behavioural assays in wild-type nematodes, it was determined that terpenoids produced fast paralysis of the worms. The paralyzing potency order was: carvacrol > thymol > eugenol. The larvae were more sensitive than young adults. Also, the compounds irreversibly inhibited egg hatching with the same potency order. These findings indicate that terpenoids generate short- and long-term anthelmintic effects. Three drug combinations were evaluated: thymol/levamisole, thymol/piperazine and thymol/ivermectin. The paralyzing effect of thymol/levamisole combination was synergic, and this combination was effective in the inhibition of egg hatching too. Through behavioural assays in mutant nematodes, it was determined that L-AChRs and GABA receptors are the molecular targets of the terpenoids. The macroscopic current recordings revealed that the compounds could not activate the receptors but inhibited the currents evoked by the agonists. In single channel recordings, terpenoids reduced L-AChR activity generated by ACh and levamisole, reduced the frequency of L-AChR openings and induced a longer closed state component. However, terpenoids did not affect channel properties, such as conductance and open duration. The global analysis indicated that, terpenoids exert their anthelmintic effect, acting as L-AChR non-competitive antagonists. In the Chapter 3, doxepinone was studied. Doxepinone is considered a privileged chemical structure. Through behavioural assays, it was demonstrated that doxepinone exert the paralyzing action in wild-type young adult worms acting through GluCls, which are the molecular targets of IVM. The synthetic compound generated stationary paralysis on wild-type worms. IVM acts on nematode pharyngeal GluCls and inhibits pharyngeal pumping. Doxepinone also reduced the pharyngeal pumping rate in wild-type worms and the effect was mediated by GluCls. Through macroscopic current recordings, the responses of GluCl α1/GluClß receptors of C. elegans evoked by the agonist glutamate were characterized. It was determined that doxepinone is not a GluCl agonist because it is not capable of activating the receptor. Through different drug application protocols, it was determined that doxepinone acts as an allosteric inhibitor of GluCls. The inhibition of GluCls was proposed as a new anthelmintic mechanism. In summary, in this Doctoral Thesis, using C. elegans as a model of parasitic nematode, the target sites and mechanisms of action of different chemical compounds with anthelmintic activity were deciphered.