Thesis advisor: Mary F. Roberts / There is substantial interest in exploring antibiotic alternatives with a new mode of action due to the increasing rates of bacterial resistance against current antibiotics. Antimicrobial peptides (AMPs) may take up the battle against bacteria in the future because as a result of their membrane-lysis mechanism, it is more difficult for bacteria to develop resistance against AMPs. Although AMPs could preferentially bind to and disrupt negatively charged bacterial membranes through electrostatic and hydrophobic interactions, there is still a great need to further increase the potency and selective toxicity towards bacteria for clinical applications. Herein, we present two strategies to improve the selectivity: light activation and environment-responsive moiety incorporation. Along the way, we also explored the effect of structure stabilization on AMPs action. A well-characterized antimicrobial peptide magainin 2 (mag2) was used as a prototype. Chemical manipulations of mag2 sequence were achieved by incorporation of unnatural amino acids. The selectivity was then tested on liposomes as a membrane model, as well as on bacterial cells and human red blood cells (hRBCs). Different extents of selectivity enhancement were observed from the modified peptides, and within the attempts to illustrate these results, we have gained useful information revealing the membrane-lysis mechanism, which may help us to rationally design and engineer AMPs as therapeutic drugs in the future. / Thesis (MS) — Boston College, 2011. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Presented herein is the development, optimization and mechanistic investigation of an Fe-catalyzed reaction for the Cα-H oxidation of tertiary aliphatic amines to form amides, and related synthetic reactions. Traditional amide synthesis typically involves nucleophilic substitution, and thus produces stoichiometric waste. The need to develop safer, more efficient methodologies for amide synthesis is well documented. The field of transition metal catalysis has made progress toward meeting this synthetic need by developing a variety of transition metal-catalyzed reactions for the oxidation of primary, secondary and benzylic amines. However, tertiary aliphatic Cα-H amine oxidation had not been developed. Guided by literature precedent, and inspired by cytochrome P450, initial investigations involved the evaluation of Fe-based transition metal catalysts with a variety of mono- and bidentate ligands, oxidants and solvents. Ultimately, the ligands picolinic acid and pyridine, the oxidant tert-butyl peroxybenzoate, and water as additive were identified as key players in this catalytic reaction. Through the systematic evaluation of reaction conditions, the Cα-H oxidation of tripropylamine to form N,N-dipropylpropanamide was optimized to afford 63% yield. The Cα-H oxidation of a variety of other amine substrates, including the complex pharmaceutical amines Lidocaine and Donepezil, were optimized to afford amide product in synthetically useful yields. Preliminary mechanistic investigations revealed water to be the source of the O atom in amide formation. Furthermore, these studies suggested that the amine substrate forms an iminium ion after C-H activation, which then undergoes nucleophilic attack by water to form a hemiaminal intermediate. These results allowed us to hypothesize that other nucleophiles, such as CN-, may be used to attack the iminium ion intermediate and thus afford other products. Using slightly modified reaction conditions, this catalytic system was optimized to perform Cα -H cyanation of dimethylaniline. This finding expanded the utility of the reaction as well as supported the mechanistic hypothesis of the presence of an iminium intermediate. Once the Fe/picolinic acid-catalyzed reaction for the Cα-H oxidation of tertiary aliphatic amines was firmly established, detailed mechanistic investigations were conducted using tripropylamine as substrate. Using in-situ IR spectroscopy, the structure of the resting state of the catalyst was probed. These studies revealed that picolinic acid binds to the Fe center in a 1:1 ratio to produce the catalytically active species. Amine substrate as well as water and pyridine were also found to be coordinated to the Fe center. Furthermore, initial rate kinetics were used to establish the dependence of the reaction rate on the concentration of each reaction component. Through these investigations, the kinetic order in each reagent was established and a rate law determined. Additionally, a primary kinetic isotope effect was observed using deuterated substrate, which implicated C-H bond cleavage as the turnover-limiting step in the catalytic cycle. Finally, Eyring studies and oxidant radical probe reactions were conducted, and implicated a concerted 2e- turnover- limiting step. This finding is in contrast to many mechanisms of Fe-catalyzed oxidation reactions found in the literature and allowed us to propose the unprecedented, detailed mechanistic hypothesis described herein. The research presented here establishes an unprecedented amide synthesis methodology through the use of both simple and complex amines. Because this catalytic reaction selectively oxidizes the Cα-H bonds of amines, a high percentage of atoms in the starting material are incorporated into the amide product, and it thus affords a significant increase in atom economy. The mechanistic work offers unique insight into 2e- Fe-oxidation catalysis, and may serve as a foundation for additional optimization, including industrial scale-up.

Disaster support and recovery generally involve highly irregular and dangerous environments. Modular robots are a salient solution to support search and rescue efforts but are still limited to do their reliance on a rigid structure design. To enhance flexibility and resilience to damage, a soft-body interconnection mechanism for self-reconfigurable modular robotic systems has been developed. The soft-body interconnection mechanism utilizes elastomeric polymers instead of a rigid body. Hence, it is capable of deforming under extreme loads without damage. This thesis presents the work completed towards the realization of a soft-body interconnection mechanism. The functional requirements of the soft-body mechanism were broken down into two separate modules for extension and capture. An initial simulation demonstrated the inability of using a simulated model made of hypo-elastic materials as a basis for design. Hence, an iterative design process was used to develop an initial extension and capture soft-body mechanisms that conformed to the desired performance parameters. An empirical study which varied multiple structural parameters was then completed with the initial extension and capture soft-body mechanisms as a basis for the modified designs. The data from the study was correlated with measured performance data with resulted in diagrams useful for the optimal design of soft-body extension and capture mechanisms. The use of the diagrams for design was demonstrated in the design and development of a soft-body interconnection mechanism for an in-house designed small hard shell modular robot system.

by Dong Sun. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (p. 116-121). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Doctor of Philosophy (Economics) / Auctions are an ancient economic institution. Since Vickrey (1961), the development of auction theory has lead to an extremely detailed description of the often desirable characteristics of these simple selling procedures, in the process explaining their enduring popularity. Given the pervasiveness of auctions, the question of how a seller should engineer the rules of these mechanisms to maximize her own profits is a central issue in the organization of markets. The seminal paper of Myerson (1981) shows that when facing buyers with Independent Private Values (IPVs) a standard auction with a specifically selected reserve price (or prices) is optimal, that is, maximizes a seller's expected profits among all conceivable selling mechanisms. In this model, it is assumed that the buyers have perfect information as to the existence of gains from trade. We shall argue that the consequences of this assumption for the design of the optimal auction are not well understood, which motivates our analysis. The three essays of this thesis relax the `known seller valuation' assumption by examining the optimal auction program when the seller (and principal) holds private information representing her reservation value for the good. In the first essay we provide an original technique for comparing ex ante expected profits across mechanisms for a seller facing N>1 potential buyers when all traders hold private information. Our technique addresses mechanisms that cannot be ranked point-by-point through their allocation rules using the Revenue Equivalence Theorem. We find conditions such that the seller's expected profits increase in the slope of each buyer's allocation probability function. This provides new intuition for the fact that a principal does not benefit from holding private information under risk neutrality. Monopoly pricing induces steep probability functions so the seller/principal benefits from announcing a fixed price, and implicitly her private information. An application is presented for the well known k double auction of the bilateral trade literature. In the second and third essays of this thesis, we extend the above framework to allow for informational externalities. Specifically, we allow for the situation in which the seller's private information represents a common value component in buyers' valuations. Thus the seller's private information (say regarding the quality of the good) is of interest to bidders independently of any strategic effects. In recent work Cai, Riley and Ye (2007) have demonstrated that a seller who holds private information about the quality of a good faces an extra consideration in designing an auction; the reserve price signals information to bidders. In a separating equilibrium signalling is costly in the sense that reserves are higher than would be optimal under complete information. We examine the returns to the seller in an English auction from using different types of secret reserve regimes. We find that immediate disclosure of a reserve is preferable to announcement after the auction in the form of a take-it-or-leave-it offer to the winning bidder. Sale occurs less often during the auction for a given reserve price strategy under secret reserve regimes, which increases the incentive for the seller to report more favourable information though the reserve price offer. Separating equilibria involving later announcement therefore generate even lower expected profits to the seller (signalling is more costly) than under immediate disclosure. In the third essay we compare the benchmark signalling equilibrium of immediate disclosure to a screening regime which we call the Right of Refusal. In this extreme form of a secret reserve the seller never announces the reserve price, she simply accepts or rejects the auction price. We find that the Right of Refusal dominates immediate disclosure if the seller's valuation is a sufficient statistic for the private information of interest. Thus a seller with market-relevant private preference information can benefit from not exercising monopoly price setting power. The result also provides conditions under which a competitive screening equilibrium is more efficient than a signalling mechanism. Broadly speaking, screening is better when the common value aspect in the preferences of the informed and uninformed parties are `aligned', and potential gains from trade to the uninformed party are significant. We believe this conclusion to be of particular interest to the design of privatization schemes.

Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Graduation date: 1998

Failure mechanisms observed in electromigration (EM) stressed dual damascene Cu/SiO₂ interconnects trees were studied and simulated. Failure sites with ‘melt patch’ or ‘crater’ are common for test structures in the top metal layer, though the occurrence of such failure modes probably depends on the passivation layer thickness. Interconnects that were EM stressed for a short time and then stressed with increasing current to induce Joule heating in the line had similar failure sites to lines that were stressed to failure under standard EM conditions. This shows that some failure mechanisms during EM could be assisted by Joule heating effect. / Singapore-MIT Alliance (SMA)

Thesis (Ph. D.)--Carnegie-Mellon University, 1984. / Bibliography: p. 260-266.

In recent years, extensive studies of many interesting aspects of online community dynamics promoted a better understanding of this area. One of the most challenging problems facing builders of online communities is the design of incentive mechanisms that can ensure user participation. However, running online community experiments in the real world is expensive, and requires a great deal of motivation from users. In this thesis two major approaches are explored: system dynamics modeling and agent-based modeling, to simulate the overall behaviours of participants in online communities. Although these models are developed by using two different methodologies, both of them can provide insights into the user motivation process, incentive mechanism evaluation and community development. The target online community for my study is called Comtella, which is used in several senior Computer Science classes in the Department of Computer Science, University of Saskatchewan. Simulation models for the Comtella online community have been developed and the simulation results are useful to provide future directions for incentive mechanism improvement.