Altering the substrate specificity of proteases is a powerful process with possible applications in many areas of therapeutics as well as proteomics. Although the field is still developing, several proteases have been successfully engineered to recognize novel substrates. Previously in our laboratory, eight highly active OmpT variants were engineered with novel catalytic sites. The present study examined the roles of several residues surrounding the active site of OmpT while attempting to use rational design to modulate fine specificity enough to create a novel protease that prefers phosphotyrosine containing substrates relative to sulfotyrosine or unmodified tyrosine residues. In particular, a previously engineered sulfotyrosine-specific OmpT variant (Varadarajan et al., 2008) was the starting point for rationally designing fifteen new OmpT variants in an attempt to create a highly active protease that would selectively cleave phosphotyrosine substrates. Our design approach was to mimic the most selective phosphoryl-specific enzymes and binding proteins by increasing positive charge around the active site. Sulfonyl esters have a net overall charge of -1 near neutral pH, while phosphate monoesters have a net overall charge of -2. Selected active site residues were mutated by site-directed mutagenesis to lysine, arginine, and histidine. The catalytic activities and substrate specificities of each variant were characterized. Although several variants displayed altered substrate specificity, none preferred phosphotyrosine over sulfotyrosine containing peptides. Taken together, our results have underscored the subtle nature of protease substrate specificity and how elusive it can be to engineer fine specificity. Apparently, phosphotyrosine specific variants were not possible within the context of our starting sulfotyrosine specific OmpT derivative mutated to have single amino acid changes chosen on the basis of differential charge interactions. / text

This dissertation consists of three essays on Economic Growth. The first essay introduces directed technical change in a growth model with environmental constraints. The final good is produced from ”dirty” and ”clean” inputs. We show that when inputs are sufficiently substitutable, sustainable growth can be achieved with temporary taxes/subsidies that redirect innovation towards clean inputs; and that delay in intervention is costly as it later necessitates a longer transition phase with slow growth. The second essay explains how unilateral environmental policies undertaken by a group of committed countries can ensure sustainable growth in the presence of directed technical change. There are two countries and two tradeable goods: a nonpolluting good and a polluting one, which, itself, is produced with a clean and a dirty input. Innovation can be targeted at the non-polluting sector, at clean or at dirty technologies. I show that sustainable growth can generally not be achieved by unilateral carbon taxes but can be achieved by a temporary unilateral combination of clean research subsidies and a tariff. I characterize the first best policy, the world optimal policy under the constraint that one country must be in laissez-faire, and the optimal policy from the viewpoint of a single country. The third essay shows that long-term relationships, which reduce the static costs associated with low contractibility, create dynamic inefficiencies. We consider the repeated interaction between final good producers and intermediate input suppliers, where the provision of the intermediate input is non contractible. Producer/supplier pairs can be good matches or bad matches (featuring lower productivity). We build a ”cooperative” equilibrium that features cooperation in good matches without any collusion amongst suppliers. We contrast this set-up with the Nash equilibrium where cooperation is precluded and a contractible setting. Every period one supplier has the opportunity to innovate. We show that innovations need to be larger to break up existing relationships in the cooperative case than in the contractible and Nash cases. The rate of innovation in the cooperative case is lower than in the contractible case, and can be lower than in the Nash case. / Economics

Nature employs complex networks of protein-tailoring enzymes to effect the post-translational modification of proteins in vivo. By comparison, modern chemical methods rely upon either nonspecific labeling techniques or upon the genetic incorporation of bioorthogonal handles. To develop truly robust bioconjugates it is necessary to develop methods which possess the exquisite activity and specificity observed in biological catalysts. One attractive strategy to achieve this is the engineering of protein-tailoring enzymes possessing user-defined specificity and high catalytic efficiency. / Chemistry and Chemical Biology

We present a methodology for exploiting shared-memory parallelism within matrix computations by expressing linear algebra algorithms as directed acyclic graphs. Our solution involves a separation of concerns that completely hides the exploitation of parallelism from the code that implements the linear algebra algorithms. This approach to the problem is fundamentally different since we also address the issue of programmability instead of strictly focusing on parallelization. Using the separation of concerns, we present a framework for analyzing and developing scheduling algorithms and heuristics for this problem domain. As such, we develop a theory and practice of scheduling concepts for matrix computations in this dissertation. / text

The purpose of this research is to describe and analyze the public relations elements of Mothers Against Drunk Driving’s campaign to prevent underage drinking. The focus will be Mothers Against Drunk Driving (MADD) and its current communication strategies and possible future initiatives. An analysis of underage drinking in the United States provides the necessary background for MADD’s change in its prior mission statement and goals. The public relations strategies of MADD will be analyzed through the characteristics of organizational excellence, models of public relations and focus principally on the factors for self-directed change. After discussing the basic foundations of MADD’s current campaign, an analysis of underage drinking on college campuses explains the need for a separate campaign for the college community. The results of MADD’s public relations and campaign will be discussed in closing. / text

A focus group study of fourteen University of Saskatchewan second to fourth year humanities and social science undergraduate students was conducted in the fall of 2011. The purpose of the research was to determine how students learn about library resources and services. Findings indicate that the participants often use a variety of informal, self-directed and information sharing strategies. Seeking help from professors, peers, friends, and family members is a common practice. Convenience, familiarity, and perceived knowledge are key factors that determine who and how these students learn about the library. Formal instruction and seeking assistance from librarians did not resonate for participants as a typical approach for learning about the library. The author suggests that undergraduate students engage in informal learning and information sharing as many ‘adult learners’ do, similar to an employment setting. The library, within the formal educational structure, lends itself to a more informal learning context. The study concludes that libraries must continue to develop resources, services, and innovative programs that support students’ informal learning styles, while also providing formal instruction as part of the undergraduate curriculum ensuring students are exposed early on to core foundational skills that contribute to their success as informal and self-directed learners.

Much confusion surrounds the term 'self-directed learning', which presently describes a process, a goal, a teaching technique, and an outcome of that teaching. As a process, the literature concentrates mainly on how individuals learn, with little reference to groups that can be as selfdirected as individuals. The purposes of this study were: (a) to reduce conceptual confusion by creating a typology distinguishing different processes of self-directed learning; (b) to explore the phenomenon of group self-directed learning; and (c) to illustrate the effect of environment on learning, and the complex learning dynamics in group settings. This project arose somewhat differently from typical doctoral research. Data from two unrelated field studies conducted for other purposes, completed before this thesis work began, each illustrated self-directed groups learning informally in the contexts of community action and innovative small workplaces. A subsequent review of the literature indicated a lack of attention to this form of group learning, and the field studies were then re-analyzed from this perspective. As a result of the literature review and data re-analysis (1) a typology emerged from the literature review that divides the process of self-directed learning into three forms, each of which is context sensitive but between which learners can continually move back and forth; (2) it appears that the term 'autodidactic' can apply to specific groups which are both self-organized and self-directed in their learning efforts; and (3) that the term 'autodidaxy' as presently defined is as conceptually confusing as the term 'self-directed learning'. This confusion is reduced by the typology proposed by this thesis. Minor findings indicate two continuing problems. The first is reluctance by some to accord non-credentialed learning the value it deserves, and the second is the difficulty often encountered in transferring knowledge from the site of learning to the site of application. This study concludes that 'informalizing' some formal curricula, and encouraging self-directed learning at all levels and in all contexts, may provide some of the tools necessary for living and learning in the twenty-first century.

We study a directed network design problem called the $k$-$(S,T)$-connectivity problem; we design and analyze approximation algorithms and give hardness results. For each positive integer $k$, the minimum cost $k$-vertex connected spanning subgraph problem is a special case of the $k$-$(S,T)$-connectivity problem. We defer precise statements of the problem and of our results to the introduction. For $k=1$, we call the problem the $(S,T)$-connectivity problem. We study three variants of the problem: the standard $(S,T)$-connectivity problem, the relaxed $(S,T)$-connectivity problem, and the unrestricted $(S,T)$-connectivity problem. We give hardness results for these three variants. We design a $2$-approximation algorithm for the standard $(S,T)$-connectivity problem. We design tight approximation algorithms for the relaxed $(S,T)$-connectivity problem and one of its special cases. For any $k$, we give an $O(\log k\log n)$-approximation algorithm, where $n$ denotes the number of vertices. The approximation guarantee almost matches the best approximation guarantee known for the minimum cost $k$-vertex connected spanning subgraph problem which is $O(\log k\log\frac{n}{n-k})$ due to Nutov in 2009.

In Ontario, the organs of deceased donors are usually allocated to those recipients who are ranked highest on the province’s waiting list for transplant surgery. However, on rare occasion, a donor, or the donor’s family, will request that an organ be given to a designated recipient or designated group of recipients. The ethical acceptability of these so-called “directed donations” of organs from deceased donors is debated in the transplant literature. The purpose of this study was to elicit the views of a group of transplant professionals in Ontario on the question, “Under what circumstances, if any, should a donor or the donor’s family be allowed to choose the recipient of the organ?” Qualitative in-depth interviews were conducted with 14 Ontario transplant professionals from a range of clinical disciplines. An analysis of these interviews revealed several practical and ethical considerations that the transplant professionals believed to be important in assessing the acceptability of directed donations.

In Ontario, the organs of deceased donors are usually allocated to those recipients who are ranked highest on the province’s waiting list for transplant surgery. However, on rare occasion, a donor, or the donor’s family, will request that an organ be given to a designated recipient or designated group of recipients. The ethical acceptability of these so-called “directed donations” of organs from deceased donors is debated in the transplant literature. The purpose of this study was to elicit the views of a group of transplant professionals in Ontario on the question, “Under what circumstances, if any, should a donor or the donor’s family be allowed to choose the recipient of the organ?” Qualitative in-depth interviews were conducted with 14 Ontario transplant professionals from a range of clinical disciplines. An analysis of these interviews revealed several practical and ethical considerations that the transplant professionals believed to be important in assessing the acceptability of directed donations.