Organic nitrates such as glyceryl trinitrate (GTN) are commonly used to treat myocardial ischemia and congestive heart failure. GTN is proposed to act as a prodrug that requires bioactivation for pharmacological activity. However, continuous administration results in tolerance development, limiting its clinical usefulness. Aldehyde dehydrogenase 2 (ALDH2) has been proposed to be the primary enzyme responsible for GTN bioactivation, and ALDH2 inactivation has been proposed as the sole basis of nitrate tolerance. In the present study, we utilized an in vivo GTN tolerance model to investigate the role of ALDH2 in GTN bioactivation and tolerance. We assessed changes in ALDH2 protein, mRNA and activity levels in rat blood vessels during chronic GTN exposure (0.4 mg/hr for 6, 12, 24 and 48 hr) in relation to changes in vasodilator responses to GTN. A time-dependent decrease in both ALDH2 expression and activity occurred (80% in tolerant veins and 30% in tolerant arteries after 48 hrs exposure to GTN), concomitant with decreased vasodilator responses to GTN. However, after a 24 hr drug-free period following 48 hr GTN exposure, the vasodilator responses to GTN had returned to control values, whereas ALDH2 expression and activity were still markedly depressed. The dissociation between reduced ALDH2 activity and expression, and the duration of the impaired vasodilator responses to GTN in nitrate-tolerant blood vessels, suggest factors other than changes in ALDH2-mediated GTN bioactivation contribute to nitrate tolerance. / Thesis (Master, Pharmacology & Toxicology) -- Queen's University, 2008-10-03 16:14:49.313

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Knowing the root cause of why an Integrated Circuit (1C) device fails to function properly is the key to provide the corrective measures to increase the yield and shorten the time to market. In recent years, electrical fault diagnosis method has received growing attention due to the effective and indispensable guiding role it plays in modern fault localization practice when physical measures are more and more confined by the shrinking feature size and condensed internal structure. While most of the fault diagnosis tools are based on gate level fault models, many faults are actually at the transistor level (the intra-gate fault). This thesis provides an innovative method to diagnose the intra-gate faults. It covers a wide range of different types of intra-gate faults. The method extends the capability of gate level fault diagnosis tools to the intra-gate domain by building connections with these intra-gate faults to particular types of gate level faults. Intra-gate faults are transformed to gate level representations so that they can be diagnosed directly by the widely available and well developed gate level diagnosis tools. Real diagnosis of intra-gate faults from wafer data and physical failure analysis photos are provided as solid proofs of the effectiveness of this method.

With the expansion of computer networks, activities involving computer communication are becoming more and more distributed. Such distribution can include processing, control, data, network management, and security. Although distribution can improve the reliability of a system by replicating components, sometimes an increase in distribution can introduce some undesirable faults. To reduce the risks of introducing, and to improve the chances of removing and tolerating faults when distributing applications, it is important that distributed systems are implemented in an organized way. As in sequential programming, complexity in distributed, in particular parallel, program development can be managed by providing appropriate programming language constructs. Language constructs can help both by supporting encapsulation so as to prevent unwanted interactions between program components and by providing higher-level abstractions that reduce programmer effort by allowing compilers to handle mundane, error-prone aspects of parallel program implementation. A language construct that supports encapsulation of interactions between multiple parties (objects or processes) is referred in the literature as multiparty interaction. In a multiparty interaction, several parties somehow "come together" to produce an intermediate and temporary combined state, use this state to execute some activity, and then leave the interaction and continue their normal execution. There has been a lot of work in the past years on multiparty interaction, but most of it has been concerned with synchronisation, or handshaking, between parties rather than the encapsulation of several activities executed in parallel by the interaction participants. The programmer is therefore left responsible for ensuring that the processes involved in a cooperative activity do not interfere with, or suffer interference from, other processes not involved in the activity. Furthermore, none of this work has discussed the provision of features that would facilitate the design of multiparty interactions that are expected to cope with faults - whether in the environment that the computer system has to deal with, in the operation of the underlying computer hardware or software, or in the design of the processes that are involved in the interaction. In this thesis the concept of multiparty interaction is integrated with the concept of exception handling in concurrent activities. The final result is a language in which the concept of multiparty interaction is extended by providing it with a mechanism to handle concurrent exceptions. This extended concept is called dependable multiparty interaction. The features and requirements for multiparty interaction and exception handling provided in a set of languages surveyed in this thesis, are integrated to describe the new dependable multiparty interaction construct. Additionally, object-oriented architectures for dependable multiparty interactions are described, and a full implementation of one of the architectures is provided. This implementation is then applied to a set of case studies. The case studies show how dependable multiparty interactions can be used to design and implement a safety-critical system, a multiparty programming abstraction, and a parallel computation model.

Thesis (Ph. D.)--Duke University, 2008.

Thesis (Ph. D.)--University of Texas at Austin, 2004. / Supervisor: Delbert Tesar. Vita. Includes bibliographical references.