Orchestrated web service applications are highly distributed applications that accomplish business goals by executing services offered by partners. This dependance on partner services allows the development of more flexible, modular applications. For a classical distributed system, correctness can be ensured by statically checking the composition of the components that make up the system against properties of interest. However, in the case of web service applications, there are various conditions that make this type of analysis insufficient. For example, partners can be dynamically discovered, which means that we cannot create a definitive model of the system to analyze. Web service applications can also display new behaviour at execution time, so statically checked properties of the system may not hold throughout the system's lifetime. Due to these limitations of static analysis, this thesis concentrates on the dynamic analysis of web service applications, specifically, by monitoring runtime events. The goal of runtime monitoring is to check whether an application violates a given specification of its behaviour during its execution. The behaviour of the system can be specified in a number of ways, e.g., as a set of temporal properties, assertions or even scenarios. During execution, application events are intercepted and used to determine if the system is violating its specification. Moreover, monitoring the system as it runs provides a chance to recover from an error once a problem has been detected. This is critical in the domain of web service applications, as bugs are potentially exposed to millions of users before they are found/fixed. We present techniques to address several major challenges facing the creation of an industrial-strength runtime monitoring and recovery framework for web service applications. The first milestone for achieving this goal is the creation of an adequate property specification language. This language must be expressive enough to capture the distributed, interactive, and message-driven nature of web service applications, but must also be amenable to efficient runtime monitoring. We propose Web Sequence Diagrams (W-SD), a language that, we feel, meets these criteria. Specifications expressed in W-SD permit the analysis of orchestrations involving multiple partners, from the point of view of the orchestrating service. The second contribution of this thesis is the creation of an industrial-strength online runtime monitoring and recovery framework that is non-intrusive, supports the dynamic discovery of web services, deals with synchronous and asynchronous communication, as well as partner services implemented in different languages. Developers using this framework can specify and efficiently monitor a variety of temporal behaviour. If recovery is enabled, properties are monitored proactively, so this framework allows developers to effortlessly enable error recovery in applications being monitored. The last contribution of this thesis is the development of recovery plans from runtime errors. Given an application path which led to a failure and a monitor which detected it, we have developed various techniques and optimizations that make recovery plan generation feasible in practice. For some of the violations, such plans essentially involve "going back" -- compensating the occurred actions until an alternative behaviour of the application is possible. For other violations, such plans include both "going back" and "re-planning" -- guiding the application towards a desired behaviour.

Pluripotent stem cells have the capacity to develop into different cell lineages and can be manipulated into certain cell types through the use of small molecule inducers. Retinoic acid (RA) signaling through retinoic acid receptors (RAR) and retinoid X receptors (RXR) has the ability to direct lineage determination but has yielded disappointing results in promoting skeletal myogenesis in embryonic stem (ES) cells. RXR is crucial in embryonic development although it is generally considered to act as a silent partner for other nuclear receptors such as RAR. Our findings demonstrate that rexinoid specific signaling enhances skeletal myogenesis and requires β-catenin but not RAR. Moreover, RXR signalling in mouse ES cells can efficiently enhance skeletal myogenesis and closely recapitulates sequential events observed in vivo. Since ES cells closely represent the properties of the developing embryo, efficiently generating skeletal muscle provides a means to further scrutinize signaling pathways in myogenic development in view of developing therapies for muscle related diseases.

The Unified Modeling Language (UML) is a standard language adopted by the Object Management Group (OMG) for writing object-oriented (OO) descriptions of software systems. UML allows the analyst to add class-level and system-level constraints. However, UML does not describe how to check the correctness of these constraints. Recent studies have shown that Symbolic Model Checking can effectively verify large software specifications. In this thesis, we investigate how to use model checking to verify constraints of UML specifications. We describe the process of specifying, translating and verifying UML specifications for an elevator example. We use the Cadence Symbolic Model Verifier (SMV) to verify the system properties. We demonstrate how to write a UML specification that can be easily translated to SMV. We propose a set of rules and guidelines to translate UML specifications to SMV, and then use these to translate a non-trivial UML elevator specification to SMV. We look at errors detected throughout the specification, translation and verification process, to see how well they reveal errors, ambiguities and omissions in the user requirements.

The Unified Modeling Language (UML) is a standard language adopted by the Object Management Group (OMG) for writing object-oriented (OO) descriptions of software systems. UML allows the analyst to add class-level and system-level constraints. However, UML does not describe how to check the correctness of these constraints. Recent studies have shown that Symbolic Model Checking can effectively verify large software specifications. In this thesis, we investigate how to use model checking to verify constraints of UML specifications. We describe the process of specifying, translating and verifying UML specifications for an elevator example. We use the Cadence Symbolic Model Verifier (SMV) to verify the system properties. We demonstrate how to write a UML specification that can be easily translated to SMV. We propose a set of rules and guidelines to translate UML specifications to SMV, and then use these to translate a non-trivial UML elevator specification to SMV. We look at errors detected throughout the specification, translation and verification process, to see how well they reveal errors, ambiguities and omissions in the user requirements.

Although numerous transcription factors (TFs) are expressed by oligodendrocytes (OGs), the role(s) of most of these TFs in oligodendrogenesis remains to be elucidated. One such TF is Hoxa2, which was recently shown to be expressed by O4-positive (+) pro-OGs. Hence, the main objectives of this thesis were to determine the expression profile and function(s) of Hoxa2 during OG development. Immunocytochemical analysis of primary mixed glial cultures demonstrated that Hoxa2 is expressed throughout oligodendrogenesis, diminishing only with the acquisition of a myelinating phenotype. Subsequently, immunohistochemical analysis suggested that Hoxa2 is expressed by migratory oligodendroglial cells in the embryonic spinal cord. However, double immunofluorescent analysis of Hoxa2 transgenic knockout mice showed that OG specification and early maturation proceed normally in the absence of Hoxa2 in the spinal cord. As Hoxa2 is one of 39 murine Hox genes, which exhibit extensive overlapping expression profiles in the spinal cord, we decided to examine the expression of an additional Hox TF, Hoxb4, during OG development. Immunocytochemical analysis of primary mixed glial cultures demonstrated that Hoxb4 is also expressed throughout OG development. Furthermore, comparison of the expression profiles of Hoxb4 and Olig2 suggested that Hoxb4 is expressed by oligodendroglial cells in the spinal cord. Hence, Hoxb4, as well as other Hox TFs could compensate for Hoxa2 in the spinal cord in its absence. As the anterior boundary of most Hox genes has been found to be in the hindbrain or spinal cord, we decided to look at the telencephalon which would be less likely to have compensatory mechanisms. Our results showed that similar to the spinal cord, Hoxa2 is expressed by oligodendroglial cells in the telencephalon. Subsequently, it was found that over-expressing Hoxa2 in CG4 cells, an oligodendroglial cell line derived from the perinatal rat cerebral cortex, impairs their differentiation. In an attempt to determine the mechanism by which it accomplishes this, we examined the expression of polysialylated neural cell adhesion molecule (PSA-NCAM), which has been implicated in this process. Contrary to our expectations, however, it was found that over-expressing Hoxa2 in CG4 cells results in significantly fewer PSA-NCAM+ cells. Hence, the results suggest that Hoxa2s effect on OG differentiation is independent of its effect on PSA-NCAM expression. The expression of Hox genes is enhanced by retinoic acid (RA), which, in turn, both inhibits, as well as promotes OG differentiation. Although the reason for these opposing roles is uncertain, examination of the experimental protocols utilized by different research groups reveals disparities in age, CNS region, as well as RA concentration. As a result, RAs effect on oligodendrogenesis could be stage- and/or concentration-dependent. In order to determine which of these factors could impact RAs effect on OG differentiation we treated CG4 cells with two different concentrations of RA at two distinct time points. The results showed that both factors (concentration and time/stage) can impact RAs effect on CG4 cell differentiation. In an attempt to determine the mechanism by which it accomplishes this, we examined the expression of PSA-NCAM. Contrary to our expectations, the results suggest that RAs effect on CG4 differentiation is independent of its effect on PSA-NCAM expression. The results of this thesis suggest that Hoxa2 and RA could play multiple roles in OG development. Although these roles appear to be similar, further research will be needed to determine whether Hoxa2 acts a downstream effector in the RA signaling pathway in oligodendroglial cells.

The Unified Modeling Language (UML) is widely used by software engineers as the basis of analysis and design in software development. However, UML ignores human factors in the course of software development because of its strong emphasis on the internal structure and functionality of the application. This thesis presents a method of mapping human-computer interaction (HCI) requirement specifications generated by usability engineering (UE) methodologies (e.g. Putting Usability First (PUF)) into UML specifications. These two sets of requirement specification are specified, using Extensible Markup Language (XML) so that HCI requirement specifications can be integrated into UML ones. A Mapping Tool was developed to facilitate the creation of mappings between PUF XML tags and XMI tags. The Mapping Tool was used to create mappings between PUF and UML requirement specifications. This mapping process and its outputs were evaluated to demonstrate that the tool worked. The results of the evaluation show that the HCI requirement specification represented by the PUF XML tags can improve the UML specification by adding them into the XMI tags.

In mesoscale manufacturing desired dimensional and surface characteristics are defined, but edge conditions are not specified in design. The final edge conditions that exist in mesoscale objects are created not only by the manufacturing process but, because of their size, also by part handling procedures. In these parts, the concern is not only with burrs, which can be formed by some mesoscale manufacturing processes, but also with the shape and size of the edge. These properties are critically important as the edge can constitute a large percentage of the smallest features of mesoscale objects. Undefined edge geometry can result in measurement, assembly, and operational difficulties. Due to the potential problems caused by edge conditions, it is desirable to have the ability to measure and characterize the edge conditions of parts. This thesis considers mesoscale measurement tools to provide an edge measurement tool recommendation based on edge size and properties. A set of analysis techniques is developed to determine the size and shape of the measured edge, locate any local inconsistencies such as burrs or dents, and track trends in calculated parameters as a function of edge position. Additionally, a standard method for communicating design requirements is suggested in order to differentiate between acceptable and unacceptable edges.

De nos jours, la réalisation d'un système électronique hétérogène composé de différents sous-systèmes (logiciel, matériel, mécanique, etc..), démarre par une spécification de haut niveau qui est ensuite divisée en différentes parties modélisées en différents langages. Ces nouvelles méthodes requièrent donc de nouvelles techniques d'aide à la conception et de validation afin de réduire le temps de mise sur le marché. La vérification par simulation de tels systèmes consiste à simuler conjointement les différentes parties du système en utilisant les simulateurs appropriés à leur type de modélisation. Ce type de simulation appelé cosimulation doit être réalisable à tous les niveaux de la spécification. Le sujet de cette thèse consiste à étudier un outil de validation par cosimulation. Cet outil doit pouvoir vérifier un système complet tout au long de son flot de conception par simulation à l'aide de simulateurs concurrentiels communicants. Chaque partie du système est simulée, éventuellement sur une machine distante pour respecter la délocalisation des groupes de travail, mais surtout par un simulateur spécifique à son domaine d'application. La cosimulation multiniveaux peut être de deux types. Le premier est la cosimulation fonctionnelle. Elle permet une validation de l'interconnexion des sous-systèmes entre eux. Le second est la cosimulation temporelle. Elle permet d'ajouter à la cosimulation fonctionnelle une synchronisation en temps des différents simulateurs. L'interface de cosimulation a été utilisée avec succès sur des applications industrielles, tout particulièrement sur des exemples du monde automobile chez PSA (Peugeot-Citroën). Au niveau multilangage, elle permet actuellement d'inclure des langages tels que SDL, COSSAP, MATLAB, SABER, VHDL et le C, bénéficiant ainsi d'une variété de langages pour la spécification.

Two new specification tests for overidentifying restrictions proposed by Hahn and Hausman (2002:b) are here tested and compared to the classical Sargan test. Power properties are found to be very similar in overall performance, while Sargan generally has better size than the new tests. Also, size is distorted for one of the new tests, thus a tendency to reject prevails. In addition, sometimes severe bias is found which affects the tests’ performances, something that differs from earlier studies.

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