Although many selection techniques have been proposed and developed over the years, selection by pointing is perhaps the most popular approach for selection. In 3D interfaces, the laser-pointer metaphor is commonly used, since users only have to point to their target from a distance. However, the task of selecting objects that have a small visible area or that are in highly cluttered environments is hard when using pointing techniques. With both indirect and direct pointing techniques in 3D interfaces, smaller targets require higher levels of pointing precision from the user. In addition, issues such as target occlusion as well as hand and tracker jitter negatively affect user performance. Therefore, requiring the user to perform selection in a single precise step may result in users spending more time to select targets so that they can be more accurate (effect known as the speed-accuracy trade-off). We describe an approach to address this issue, called Progressive Refinement. Instead of performing a single precise selection, users gradually reduce the set of selectable objects to reduce the required precision of the task. This approach, however, has an inherent trade-off when compared to immediate selection techniques. Progressive refinement requires a gradual process of selection, often using multiple steps, although each step can be fast, accurate, and nearly effortless. Immediate techniques, on the other hand, involve a single-step selection that requires effort and may be slower and more error-prone. Therefore, the goal of this work was to explore this trade-off. The research includes the design and evaluation of progressive refinement techniques for 3D interfaces, using both pointing- and gesture-based interfaces for single-object selection and volume selection. Our technique designs and other existing selection techniques that can be classified as progressive refinement were used to create a design space. We designed eight progressive refinement techniques and compared them to the most commonly used techniques (for a baseline comparison) and to other state-of-the-art selection techniques in a total of four empirical studies. Based on the results of the studies, we developed a set of design guidelines that will help other researchers design and use progressive refinement techniques. / Ph. D.

Dissertation (PhD)--University of Stellenbosch, 2007. / ENGLISH ABSTRACT: See full text for abstract / AFRIKAANSE OPSOMMING: Sien volteks vir opsomming

The structures obtained from homology modeling methods are of intermediate resolution 1-3Ã… from true structure. Energy minimization methods allow us to refine the proteins and obtain native like structures. Previous work shows that some of these methods performed well on soluble proteins. So we extended this work on membrane proteins. Prediction of membrane protein structures is a particularly important, since they are important biological drug targets, and since their number is vanishingly small, as a result of the inherent difficulties in working with these molecules experimentally. Hence there is a pressing need for alternative computational protein structure prediction methods. This work tests the ability of common molecular mechanics potential functions (AMBER99/03) and a hybrid knowledge-based potential function (KB_0.1) to refine near-native structures of membrane proteins in vacuo. A web based utility for protein refinement has been developed and deployed based on the KB_0.1 potential to refine proteins.

Endometriose (EM) ist eine häufige gynäkologische Erkrankung, die bei betroffenen Frauen unter anderem mit chronischen Unterleibsschmerzen und Unfruchtbarkeit einhergeht (VALLE 2002). Bisher war es bei den zur Forschung verwendeten Modelltieren für EM (z.B. Rhesusaffe, ZONDERVAN et al. 2004; Weißbüschelaffe, EINSPANIER et al. 2006) nicht möglich festzustellen, ob bei ihnen schmerzhafte Beeinträchtigungen durch die Erkrankung bestehen. Um die Auswirkungen neuer Therapeutika auf das Wohlbefinden der Patientinnen bewerten zu können, werden Methoden benötigt, mit denen EM bedingte Beeinträchtigungen der Modelltiere dargestellt werden können. Daher war es das Ziel dieser Studie, bei einem Primatenmodell für EM, dem Weißbüschelaffen, neue nicht invasive Testsysteme zu etablieren, die zur Darstellung von EM bedingten Schmerzen und Beeinträchtigungen geeignet sind. Unter der Annahme, dass schmerzhafte Erkrankungen das Verhalten (WALLACE et al. 1990), die Beweglichkeit (FLECKNELL 1986) sowie die kognitiven Fähigkeiten (SMITH et al. 2006) der betroffenen Tiere beeinträchtigen können, wurden drei nicht invasive Testsysteme auf ihre Eignung untersucht, Schmerzen bei an EM erkrankten Weißbüschelaffen im Vergleich zu Kontrolltieren darzustellen. Zur Untersuchung des Verhaltens wurde die Videoüberwachung, für die motorischen Fähigkeiten der Futterbaum (modifiziert nach ROBERTS et al. 1993) und für die kognitiven Fähigkeiten der Wisconsin General Test Apparatus (WGTA, HARLOW 1949) sowie der Futterbaum verwendet. Im ersten Abschnitt dieser Studie wurde das Normalverhalten von neun Weißbüschelaffenpaaren per Videokamera über den gesamten Tagesverlauf von zwölf Stunden aufgezeichnet und unter anderem in Bezug auf Aktivität, soziale und eigene Körperpflege sowie Futter- und Wasseraufnahme analysiert. Der Verlauf der Tagesaktivität zeigte drei Maxima zwischen 7:00 und 8:00 Uhr, 11:00 und 12:00 Uhr sowie 14:00 und 15:00 Uhr, dabei war die ansteigende Aktivität als Futtersuchverhalten vor den Mahlzeiten zu werten. Das im ersten Abschnitt der Studie dargestellte Aktivitätsmuster wurde im zweiten Abschnitt verwendet, um die Versuche mit WGTA und Futterbaum besser in den Tagesverlauf der Tiere einzuordnen und darüber ihre Kooperativität zu steigern. Die Tiere führten die Tests immer zur gleichen Tageszeit durch, deshalb wurde somit eine optimale Vergleichbarkeit und Homogenität der Ergebnisse gewährleistet. Bei der Auswertung der Videodokumentation im zweiten Abschnitt dieser Studie zeigte sich, dass erkrankte Weibchen ihren Partner im Gegensatz zu den Kontrolltieren gar nicht pflegen (p=0,029) und die Aktivität der erkrankten Weibchen zwar deutlich, aber nicht signifikant (p=0,057) verringert war. Diese verringerte Aktivität ist möglicherweise ein Hinweis auf Schmerzen der an EM erkrankten Weibchen, während die nicht vorhandene soziale Körperpflege den partnerschaftlichen Problemen betroffener Frauen entsprechen könnte. In den ersten beiden kognitiven Tests mit dem WGTA führten die erkrankten Weibchen signifikant weniger Versuche pro Tag durch als die Kontrolltiere (p=0,006/ p=0,008). Darüber hinaus benötigten die erkrankten Tiere signifikant mehr Versuche, um den ersten Test zu verstehen (p=0,008). Diese Unterschiede zu den Kontrolltieren ließen sich in den folgenden drei Versuchsabschnitten nicht mehr nachweisen. Daraus lässt sich ableiten, dass die Weibchen mit EM sich schlecht auf neue Anforderungen einstellen und sich weniger lange auf eine gestellte Aufgabe konzentrieren können. Nach der International Primatological Society (MC CANN et al. 2007) kann eine verminderte Fähigkeit, sich auf neue Situationen einzustellen, als Anzeichen für Beeinträchtigungen gewertet werden. Bei der Auswertung der Futterbaum Testreihen, in denen sowohl kognitive als auch motorische Fähigkeiten der Tiere mit einer Art „Kletterbaum“ überprüft wurden, ergaben sich demgegenüber keine signifikanten Unterschiede zwischen der EM-Gruppe und den Kontrolltieren. Zusammenfassend eignen sich die Videodokumentation und der WGTA zur Darstellung von Beeinträchtigungen bei an EM erkrankten Weißbüschelaffen. Die beiden Testsysteme können in folgenden pharmakologischen Studien verwendet werden, um erstmals die Auswirkungen neuer Therapeutika auf das Wohlbefinden der Modelltiere zu bewerten. Zusätzlich ermöglichen die Ergebnisse dieser Studie ein Refinement (RUSSELL und BURCH 1959), da die bisher verwendeten invasiven Methoden (Laparoskopie, Laparotomie) zur Bewertung des Verhaltens der EM Läsionen unter einer Therapie ergänzt und sogar ersetzt werden könnten. / Endometriosis (EM) is a common gynecological disease, which is known to cause chronic pelvic pain and infertility in women (VALLE 2002). Up to now, it was not possible to assess, whether the animal models for research (e.g. rhesus macaque, ZONDERVAN et al. 2004; common marmoset, EINSPANIER et al. 2006) suffer from pain or impairments due to the disease. Therefore, new test systems are needed to obtain pain and discomfort in animal models for EM to enable the validation of new therapeutic agents with a view to the patients well being. It was the aim of this study, to establish new non invasive test systems to investigate signs of discomfort in an animal model for EM, the marmoset monkey. Assuming that painful diseases can influence the behaviour (WALLACE et al. 1990), the mobility (FLECKNELL 1986) and the cognitive abilities (SMITH et al. 2006) of animals, three non invasive test systems were reviewed for their ability to detect EM associated pain in common marmosets. They were based on behaviour (videotaping), mobility and exploratory behaviour (food tree, modified after ROBERTS et al. 1993) and cognitive abilities (Wisconsin General Test Apparatus (HARLOW 1949) and food tree). In the first part of this study, the daily activity patterns, allo- and autogrooming as well as water and food intake of nine common marmoset couples were monitored over a 12-hour light phase by video recording. The animals showed a trimodal course of activity per day with maxima from 7:00-8:00h, 11:00-12:00h and 15:00-16:00h. These activity maxima represented foraging behaviour, as they were followed by frequent food intake phases. The knowledge of the daily activity patterns allowed to optimize the experimental conditions for the tasks with the food tree and the Wisconsin General Test Apparatus (WGTA; HARLOW 1949) in the second part of this study. As every animal solved the tasks at the same time of day, the comparability and homogeneity of the results were optimized. By analysing the video documentation in the second part of this study, the females with EM, in contrast to the control females, did not show any social grooming behaviour (p=0.029). Furthermore, their activity level was almost significantly decreased (p=0.057). This reduced activity could indicate towards pain in the diseased females, while the lack of social grooming is similar to partnership problems in diseased women. The WGTA tasks revealed, that the females with EM performed significantly less trials per day in the first two settings (p=0.006/ p=0.008) and needed more trials to solve the first setting than the control animals (p=0.008). Those differences between diseased females and control animals were not detectable in the following three settings of the WGTA tasks. These results demonstrate, that EM affected marmosets have difficulties to concentrate on cognitive tasks and to cope with new situations. According to the International Primatological Society (MC CANN et al. 2007), these difficulties to cope with new situations can be interpreted as signs of distress. The food tree, a kind of jungle gym, was used to assess the animals` cognitive abilities as well as their mobility, but there were no significant differences between the EM diseased females and the control animals. In conclusion, the videotaping and the WGTA are suitable methods to demonstrate signs for impairments due to EM in marmoset monkeys. In following pharmacological studies, both test systems will allow to evaluate the benefit of new therapeutic agents on the animal model`s well being. In addition, the results of this study can help to refine procedures by replacing invasive methods like laparotomy according to the Refinement of RUSSELL and BURCH (1959).

Endometriose (EM) ist eine gynäkologische Erkrankung, gekennzeichnet durch chronische Unterbauchschmerzen (Dyspareunie, Dysmenorrhoe) und gilt unbehandelt als einer der Hauptgründe für Infertilität (OLDER 1984). Sie tritt spontan beim Menschen sowie bei höheren nichtmenschlichen Primaten auf und ist bis heute nicht zufriedenstellend therapierbar. Ein geeignetes Tiermodell zur Untersuchung dieser humanrelevanten Erkrankung ist der Weißbüschelaffe (EINSPANIER et al. 2006), welcher auch zur Erforschung neuer Therapieansätze genutzt wird. Bisher erfolgten Therapiestudien im Tiermodell hauptsächlich unter Berücksichtigung von Anzahl und Größe der Endometrioseherde. Diese Angaben geben jedoch keinen Aufschluss über die Schmerzhaftigkeit (BECKER et al. 2004). Eine Beurteilung des Wohlbefindens der Versuchstiere und der therapeutischen Beeinflussung des Schmerzes durch den untersuchten Wirkstoff ist so nicht möglich. Aus diesem Grund sollten in der vorliegenden Arbeit Verhalten und kognitive Fähigkeiten von an EM erkrankten Weißbüschelaffen als Indikator für Beeinträchtigungen, im Rahmen einer EM-Therapie, evaluiert werden. Dazu wurden in einer Basisstudie zunächst nicht invasive Testsysteme zur Beurteilung dieser Parameter etabliert und Unterschiede zwischen erkrankten und gesunden Affen untersucht (ARNOLD et al. 2011; LAMP 2010). Nachfolgend wurden erkrankte Tiere therapiert und mithilfe der zuvor etablierten Systeme erneut mit gesunden und unbehandelten erkrankten Tieren verglichen (ARNOLD und EINSPANIER 2013). Der Wisconsin General Test Apparatus (WGTA, HARLOW 1949) wurde zur Beurteilung kognitiver Leistungen genutzt. Der Futterbaum (modifiziert nach ROBERTS et al. 1993) kam zur Bewertung von Mobilität und räumlichem Erinnerungsvermögen zum Einsatz. Das Verhalten der Tiere konnte mittels versteckter Videoaufzeichnung untersucht werden. Während die Basisstudie zunächst deutliche Reduktionen der sozialen Körperpflege und der Aktivität der erkrankten Tiere im Vergleich zu gesunden Affen hervorbrachte, ergaben sich durch verfeinerte Auswertungsverfahren im Therapieversuch weitere bedeutende Unterschiede im Verhalten unbehandelter erkrankter Affen verglichen mit gesunden und behandelten Artgenossen. Die erkrankten Weibchen übten wiederholt keinerlei soziale Körperpflege gegenüber ihren männlichen Partnertieren aus, zeigten signifikant weniger Komfortverhalten in Form von Aufsuchen der Hängematten und pflegten auch ihr eigenes Fell signifikant weniger als die behandelten Tiere. Weiterhin war die Aktivität der erkrankten Affen noch immer reduziert und sie verbrachten tendenziell mehr Zeit zurückgezogen in ihren Schlafboxen. Die Tiere der Behandlungsgruppe hingegen erreichten in all diesen Parametern ähnliche Werte wie die gesunden Weibchen, was einen positiven Einfluss der Medikation auf das Wohlbefinden der behandelten Affen vermuten lässt. Lediglich das Aufsuchen der Rotlichtquellen war bei den Tieren beider EM-Gruppen reduziert im Vergleich zur gesunden Kontrollgruppe und erwies sich damit als ungeeignet zur Beurteilung eines therapeutischen Einflusses auf das Wohlbefinden der Tiere. Im Gegensatz zu den Verhaltensbeobachtungen, zeigten WGTA und Futterbaum im Therapieversuch keinerlei signifikante Unterschiede zwischen beiden EM-Gruppen und der gesunden Kontrollgruppe auf. Wohingegen in der vorherigen Basisstudie beobachtet wurde, dass erkrankte Weibchen in den ersten Versuchsabschnitten mit dem WGTA signifikant weniger Versuche durchführten und signifikant länger brauchten, um den Versuch zu verstehen als gesunde Weibchen. Diese Schwierigkeit, sich auf neue Aufgaben einzustellen, kann als Anzeichen von Beeinträchtigung angesehen werden (MCCANN et al. 2007). Aufgrund der bereits bekannten Aufgabenstellung im Therapieversuch, erscheint ein Gewöhnungseffekt wahrscheinlich und sollte beim künftigen Einsatz des WGTA vermieden werden. Zusammenfassend ist die Videodokumentation zum Einsatz in Therapiestudien zur Darstellung von Verhaltensänderungen bei Weißbüschelaffen geeignet und zu empfehlen. Gerade bei therapeutischen Studien chronisch schmerzhafter Erkrankungen, sollte die Beurteilung des Verhaltens als Indikator für Beeinträchtigungen vermehrt eingesetzt werden und trägt zum Refinement (RUSSELL und BURCH 1959) der Versuche bei.

Accurate numerical solution of time-dependent, high-dimensional partial differential equations (PDEs) usually requires efficient numerical techniques and massive-scale parallel computing. In this thesis, we implement and evaluate discretization schemes suited for PDEs of higher dimensionality, focusing on high order of accuracy and low computational cost. Spatial discretization is particularly challenging in higher dimensions. The memory requirements for uniform grids quickly grow out of reach even on large-scale parallel computers. We utilize high-order discretization schemes and implement adaptive mesh refinement on structured hyperrectangular domains in order to reduce the required number of grid points and computational work. We allow for anisotropic (non-uniform) refinement by recursive bisection and show how to construct, manage and load balance such grids efficiently. In our numerical examples, we use finite difference schemes to discretize the PDEs. In the adaptive case we show how a stable discretization can be constructed using SBP-SAT operators. However, our adaptive mesh framework is general and other methods of discretization are viable. For integration in time, we implement exponential integrators based on the Lanczos/Arnoldi iterative schemes for eigenvalue approximations. Using adaptive time stepping and a truncated Magnus expansion, we attain high levels of accuracy in the solution at low computational cost. We further investigate alternative implementations of the Lanczos algorithm with reduced communication costs. As an example application problem, we have considered the time-dependent Schrödinger equation (TDSE). We present solvers and results for the solution of the TDSE on equidistant as well as adaptively refined Cartesian grids. / eSSENCE

Due to recent legislation aimed at reducing carbon emissions into the environment through weight reduction, the automotive and aerospace industries are using light alloys such as aluminium silicon (Al–Si) and aluminium zirconium (Al–Zr) instead of steel due to their excellent mechanical properties and low weight to strength ratio. In order to further improve mechanical and metallurgical properties in these alloys, grain refinement is usually used in industry. However, the current and most widely used grain refiner Al–5Ti–B is unable to refine Al–Si alloys with silicon content greater than 3 wt.%., and Al–Zr alloys due to poisoning of the refiner by silicon and zirconium. The Al–5Ti–B refiner also contains larger Al3Ti particles and agglomerates of TiB2 which affect its efficiency and suitability in industrial applications where thin sheets are required. In this study, a new technique which improves the microstructure and efficiency of the Al–5Ti–B refiner has been developed. This involves the reaction of potassium tetrafluoroborate (KBF4) and potassium hexafluorotitanate (K2TiF6) salts at shorter reaction time before ultrasonic processing during solidification. This leads to the formation of a new Al3Ti morphology and de-agglomeration of TiB2 particles which enhances its grain refinement efficiency by 20%. Secondly, through phase diagram analysis of Al grain refining systems and crystallography studies, it was observed that Al3Ti and Al3Nb display similar lattice parameters with atomic misfit of 4.2% and would undergo a peritectic reaction with α-Al at low contact angles. Based on this, and using the duplex nucleation theory and poisoning by Si and Zr, a new quaternary grain refiner containing aluminium, titanium, niobium and boron (Al–4Ti–Nb–B) has been developed. This novel grain refiner has been found to be efficient in Al–Si alloys and Al–Zr, both at laboratory and industrial scales, and to improve the mechanical properties of the alloys despite the presence of Ti in the alloy. It was observed that the addition of Nb to an Al–Ti–B system leads to the formation of solid solution phases of Al3Ti1-xNbx, Al3Nb1-xTx, and (Ti1-xNbx)B2 which prevents poisoning by Si and Zr. Experimental simulations showed that Al3Nb1-xSix rather than Ti(Al1-xSix)3 are formed in Al–Si alloys, and Al3(Ti1-xNbx) and (Al3Ti1-xNbx)B2 phases are formed in Al–Zr alloys rather than Al3(Zrx,Ti1-x), B2(Zrx,Ti1-x) or ZrB2 phases. A new grain refining mechanism, ‘The Quad Nucleation Theory’ based on four nucleation events in Al–4Ti–Nb–B has been proposed. Other newly developed quaternary and ternary novel grain refiners capable of refining aluminium silicon alloys are also presented in this thesis. This includes a novel method of refining Al–Si alloys using phosphorus and niobium.

Made available in DSpace on 2014-06-12T15:49:26Z (GMT). No. of bitstreams: 1 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2009 / Esta tese trata de um problema muito comum em verificação formal: explosão de estados. O problema desabilita a verificação automática de propriedades através da verificação de modelos. Isto é superado pelo uso de abstração de dados, em que o espaço de estados de umsistema é reduzido usandoumprincípio simples: descartando detalhes de tal forma que o espaço de estados torna-se finito exibindo ainda propriedades desejáveis. Isso habilita o uso de verificacao de modelos, já que o modelo mais simples (abstrato) pode ser usado no lugar do modelo original (concreto). Entretanto, abstrações podem perder propriedades já que o nível de precisão é degradado, para algumas propriedades. Abstrair tipos de dados é, normalmente, uma tarefa não-trivial e requer uma profunda experiência: o usuário deve prover domínios abstratos, uma relacao matemática entre os estados (concreto e abstrato), uma inicialização abstrata, e uma versão abstrata para cada operação. A abordagem proposta nesta tese transfere a maior parte dessa experiência para um procedimento sistemático que calcula relações de abstração. Essas relações são a base para as relações matemáticas entre os estados, como também suas imagens determinam os domínios abstratos (os valores de dados mínimos para preservar propriedades). Também propomos meta-modelos para estabelecer como o sistema abstrato é inicializado e como operações são tornadas fechadas sob os domínios abstratos. Isso elimina o conhecimento requerido do usuário para fornecer as versões abstratas para a inicialização e operações. Os meta-modelos garantem a correspondência entre os sistemas concreto e abstrato. Assim, nós derivamos especificações abstratasa partir de concretas de tal formaque a especificação concreta é mais determinística que a abstrata por construção. Esta é a idéia por trás da teoria sobrejacente de nossa abordagem de abstração de dados: refinamento de dados. A notação adotada é CSPZ uma integração formal das linguagens de especificação CSP e Z. Uma especificação CSPZ tem duas partes: uma parte comportamental (CSP) e outra de dados (Z). O procedimento de cálculo foca na parte de Z, mas os resultados são usados na especificação CSPZ por completo; isso segue da independência de dados da parte de CSP (os dados não podem afetar seu comportamento). Ao final, a verificação automática é obtida pela conversão da especificação CSPZ em CSP puro e em seguida pelo reuso do verificador de modelos padrão de CSP. Nossa abordagem compreende as seguintes tarefas: nós extraímos a parte de Z de uma especificação CSPZ (puramente sintática), calculamos as relações de abstração (através de uma análise sistemática de predicados com uso de ferramenta de suporte), construímos as relações matemáticas entre os estados, os esquemas abstratos (definidos por meta-modelos), e realizamos um pós-processamento na especificação abstrata. A última tarefa pode resultar em alguns ajustes nas relações de abstração. A novidade prática e maior contribuição de nossa abordagem é o cálculo sistemático das das relações de abstração, que são os elementos chave de todas abordagens de abstração de dados que estudamos ao longo dos últimos anos. O refinamento de dados entre o sistema produzido por nossa abordagem e o original (concreto) é a segunda contribuição deste trabalho. O procedimento sistemático é na verdade uma técnica de análise de predicado que usa as restrições sobre os dados para determinar seus valores mínimos que são suficientes para preservar o comportamento do sistema. Isso evita a execução (concreta ou simbólica) do sistema analisado. Os passos produzem mapeamentos que revelam alguns elementos cruciais: o espaço de estados abstrato e as relações matemáticas entre ele e o espaço de estados concreto. Essas relações são usadas para construir o sistema abstrato seguindo o formato estabelecido pelos meta-modelos. As limitações de nossa abordagem são também discutidas. Nós aplicamos a abordagem a alguns exemplos também analisados por outras técnicas da literatura. Discutimos também sobre trabalhos relacionados procurando destacar vantagens, desvantagens e aspectos complementares. Finalmente, apresentamos nossas conclusões e futuras direções para este trabalho

Real-time systems such as medical devices, surgical robots, and microprocessors are safety- critical applications that have hard timing constraint. The correctness of real-time systems is important as the failure may result in severe consequences such as loss of money, time and human life. These real-time systems have software to control their behavior. Typically, these software have source code which is converted to object code and then executed in safety-critical embedded devices. Therefore, it is important to ensure that both source code and object code are error-free. When dealing with safety-critical systems, formal verification techniques have laid the foundation for ensuring software correctness. Refinement based technique in formal verification can be used for the verification of real- time interrupt-driven object code. This dissertation presents an automated tool that verifies the functional and timing correctness of real-time interrupt-driven object code programs. The tool has been developed in three stages. In the first stage, a novel timed refinement procedure that checks for timing properties has been developed and applied on six case studies. The required model and an abstraction technique were generated manually. The results indicate that the proposed abstraction technique reduces the size of the implementation model by at least four orders of magnitude. In the second stage, the proposed abstraction technique has been automated. This technique has been applied to thirty different case studies. The results indicate that the automated abstraction technique can easily reduce the model size, which would in turn significantly reduce the verification time. In the final stage, two new automated algorithms are proposed which would check the functional properties through safety and liveness. These algorithms were applied to the same thirty case studies. The results indicate that the functional verification can be performed in less than a second for the reduced model. The benefits of automating the verification process for real-time interrupt-driven object code include: 1) the overall size of the implementation model has reduced significantly; 2) the verification is within a reasonable time; 3) can be applied multiple times in the system development process. / Several parts of this dissertation was funded by a grant from the United States Government and the generous support of the American people through the United States Department of State and the United States Agency for International Development (USAID) under the Pakistan – U.S. Science & Technology Cooperation Program. The contents do not necessarily reflect the views of the United States Government.

Formal verification methods have been shown to be very effective in finding corner-case bugs and ensuring the safety of embedded software systems. The use of formal verification requires a specification, which is typically a high-level mathematical model that defines the correct behavior of the system to be verified. However, embedded software requirements are typically described in natural language. Transforming these requirements into formal specifications is currently a big gap. While there is some work in this area, we proposed solutions to address this gap in the context of refinement-based verification, a class of formal methods that have shown to be effective for embedded object code verification. The proposed approach also addresses both functional and timing requirements and has been demonstrated in the context of safety requirements for software control of infusion pumps. The next step in the verification process is to develop the refinement map, which is a mapping function that can relate an implementation state (in this context, the state of the object code program to be verified) with the specification state. Actually, constructing refinement maps often requires deep understanding and intuitions about the specification and implementation, it is shown very difficult to construct refinement maps manually. To go over this obstacle, the construction of refinement maps should be automated. As a first step toward the automation process, we manually developed refinement maps for various safety properties concerning the software control operation of infusion pumps. In addition, we identified possible generic templates for the construction of refinement maps. Recently, synthesizing procedures of refinement maps for functional and timing specifications are proposed. The proposed work develops a process that significantly increases the automation in the generation of these refinement maps. The refinement maps can then be used for refinement-based verification. This automation procedure has been successfully applied on the transformed safety requirements in the first part of our work. This approach is based on the identified generic refinement map templates which can be increased in the future as the application required.