Theoretical study of chloroperoxidase catalyzed chlorination of beta-cyclopentanedione and role of water in the chlorination mechanism

Chloroperoxidase (CPO) is a potential biocatalyst for use in asymmetric synthesis. The mechanisms of CPO catalysis are therefore of interest. The halogenation reaction, one of several chemical reactions that CPO catalyzes, is not fully understood and is the subject of this dissertation. The mechanism by which CPO catalyzes halogenation is disputed. It has been postulated that halogenation of substrates occurs at the active site. Alternatively, it has been proposed that hypochlorous acid, produced at the active site via oxidation of chloride, is released prior to reaction, so that halogenation occurs in solution. The free-solution mechanism is supported by the observation that halogenation of most substrates often occurs non-stereospecifically. On the other hand, the enzyme-bound mechanism is supported by the observation that some large substrates undergo halogenation stereospecifically. The major purpose of this research is to compare chlorination of the substrate β-cyclopentanedione in the two environments. One study was of the reaction with limited hydration because such a level of hydration is typical of the active site. For this work, a purely quantum mechanical approach was used. To model the aqueous environment, the limited hydration environment approach is not appropriate. Instead, reaction precursor conformations were obtained from a solvated molecular dynamics simulation, and reaction of potentially reactive molecular encounters was modeled with a hybrid quantum mechanical/molecular mechanical approach. Extensive work developing parameters for small molecules was pre-requisite for the molecular dynamics simulation. It is observed that a limited and optimized (active-site-like) hydration environment leads to a lower energetic barrier than the fully solvated model representative of the aqueous environment at room temperature, suggesting that the stable water network near the active site is likely to facilitate the chlorination mechanism. The influence of the solvent environment on the reaction barrier is critical. It is observed that stabilization of the catalytic water by other solvent molecules lowers the barrier for keto-enol tautomerization. Placement of water molecules is more important than the number of water molecules in such studies. The fully-solvated model demonstrates that reaction proceeds when the instantaneous dynamical water environment is close to optimal for stabilizing the transition state.

Power and thermal aware scheduling for real-time computing systems

Over the past few decades, we have been enjoying tremendous benefits thanks to the revolutionary advancement of computing systems, driven mainly by the remarkable semiconductor technology scaling and the increasingly complicated processor architecture. However, the exponentially increased transistor density has directly led to exponentially increased power consumption and dramatically elevated system temperature, which not only adversely impacts the system's cost, performance and reliability, but also increases the leakage and thus the overall power consumption. Today, the power and thermal issues have posed enormous challenges and threaten to slow down the continuous evolvement of computer technology. Effective power/thermal-aware design techniques are urgently demanded, at all design abstraction levels, from the circuit-level, the logic-level, to the architectural-level and the system-level. ^ In this dissertation, we present our research efforts to employ real-time scheduling techniques to solve the resource-constrained power/thermal-aware, design-optimization problems. In our research, we developed a set of simple yet accurate system-level models to capture the processor's thermal dynamic as well as the interdependency of leakage power consumption, temperature, and supply voltage. Based on these models, we investigated the fundamental principles in power/thermal-aware scheduling, and developed real-time scheduling techniques targeting at a variety of design objectives, including peak temperature minimization, overall energy reduction, and performance maximization. ^ The novelty of this work is that we integrate the cutting-edge research on power and thermal at the circuit and architectural-level into a set of accurate yet simplified system-level models, and are able to conduct system-level analysis and design based on these models. The theoretical study in this work serves as a solid foundation for the guidance of the power/thermal-aware scheduling algorithms development in practical computing systems.^

The usefulness and appropriateness of a federalist perspective as a theoretical construct for the study of government and civics at the secondary level

This dissertation is the formulation of an argument for the incorporation of a liberated federalism perspective as the foundational theoretical construct for the teaching and study of American government and civics at the secondary level. The argument asserts that the history of the nation, in terms of its basic view of government, has developed from a traditional federalist view to a natural rights view. Instruction of government and politics has paralleled that development. The argument further asserts that the current dependence on the natural rights perspective has contributed and helped legitimize, however unintentionally, the excessive levels of individualism, self-absorption, and uncivil behavior that is being experienced in our society today.^ The argumentation follows the dialectic form presented by Hegel of thesis, antithesis, and synthesis. That is, the thesis argues that the traditional federalist perspective would serve as a viable construct for the teaching of government and civics. In this portion of the argument, the republican model of political reality is presented. The antithesis promotes the natural rights perspective and relies on the political systems model for its theoretical approach. Finally, the synthesis argues that a liberated federalism perspective should be the foundational construct. Here, the argument presents its own model as a theoretical construct that is designed to assist teachers and curriculum materials writers in the development of American government and civics lessons and materials. ^

Theoretical Foundations of a Study Examining Adolescent Literature and Rape Myth Acceptance

Adolescents are at the greatest risk for victimization and perpetration of sexual assault. This paper examines the current trends in literacy education which marginalize aesthetic reading experiences and using reader response theory, and argues that young adult literature may provide an opportunity to reduce rape myth acceptance in adolescents.