VictorJuiz/thesis huggingface dataset:
Studies of Amino-specific Chemical Tags. Prospects for 19F and 13C Protein NMR and Materials Chemistry

Site-specific chemical tagging of proteins is a precursor to many structurally-focused biological studies by NMR and mass spectrometry. In particular, reductive methylation is a well-known approach to incorporate methyl groups onto lysine and N-terminal amines in proteins. Interestingly, the NMR spectra of reductively dimethylated lysine residues are often complex, due to methyl inequivalence and chemical exchange. Whereas prior studies on small molecules have eluded to some of the underlying exchange processes, the fundamental origins of methyl inequivalence for dimethyllysines have been largely neglected. Furthermore, prior to this thesis, no comprehensive model had been proposed which encapsulates all elements of the exchange phenomena, showing how they are interconnected and give rise to experimentally observed NMR spectra of reductively methylated proteins. The first part of this thesis addresses the methyl exchange for both small molecule substituted dimethylamines and for dimethylamino groups in proteins and should therefore be useful for better understanding methyl spectra of reductively methylated proteins as well as methyl NMR spectra in general. The second half of this thesis is primarily concerned with the application of 19F NMR toward the study of protein chemical exchange as well as the design of novel 19F tags for site-specific labeling of amino acid side chains. The former pertains to a study of exchange between monomeric and oligomeric states of the toxic PrPSc form of the prion protein, which has implications for understanding the mechanisms responsible for aggregation and pathogenesis. The subsequent two chapters describe a computational method for the design of highly-sensitive 19F chemical tags and also introduce a new general bioconjugation strategy for chemically modifying amino groups with reactive indoles, with an emphasis on 19F NMR applications. The final chapters introduce a cross-saturation, spin-diffusion-based technique that allows for the detection of subtle conformational changes in proteins.The methodology described in this thesis extends the repertoire of techniques for designing new chemical tags for NMR applications, for site-specifically labeling proteins, and demonstrates NMR-based approaches to studying disease-relevant chemical exchange processes, characterizing conformational intermediates, and for understanding how biophysical characterization of side chain dynamics and kinetic processes can give insight into structure-function relationships in proteins.

Keywords: Chemical Exchange
Fluorine
Methyl
NMR
Protein
Tagging
Advisor: Prosser, Scott
A Comprehensive Study of Bank Branch Growth Potential and Growth Trends through the Development of a Unique DEA Formulation and a New Restricted DEA Model

DEA has been widely used in branch performance work to evaluate intermediation, profitability and production efficiency. However, traditional modeling approaches fail to assess growth potential and customer retention; two very significant components of a bank's economic health and market stability. To address this issue, this research integrates Operations Research (OR) techniques with DEA methodologies to develop a new formulation for more accurately modeling branch growth from one time period to another. This model was found to be successful in evaluating a branch's growth potential and with the integration of Malmquist Index techniques, and was able to identify growth trends over an extended period of time. In addition, this study introduces a new restricted DEA model that restricts the Most Productive Possibilities Set (MPPS) to a convex subset of non-negative growth units through the restriction of the non-negative intensity variable found in the dual form of DEA. To verify both models and test the validity of the results, several data sets were used, including one provided by one of the Big Five Canadian Banks and one from a large Turkish bank.

Keywords: Bank Branch
Data Envelopment Analysis
Efficiency
Growth
Advisor: Paradi, Joseph C
High-speed Soft-processor Architecture for FPGA Overlays

Field-Programmable Gate Arrays (FPGAs) provide an easier path thanApplication-Specific Integrated Circuits (ASICs) for implementing computingsystems, and generally yield higher performance and lower power than optimizedsoftware running on high-end CPUs. However, designing hardware with FPGAsremains a difficult and time-consuming process, requiring specialized skillsand hours-long CAD processing times. An easier design process abstracts awaythe FPGA via an "overlay architecture", which implements a computing platformupon which we construct the desired system. Soft-processors represent the basecase of overlays, allowing easy software-driven design, but at a large cost inperformance and area. This thesis addresses the performance limitations ofFPGA soft-processors, as building blocks for overlay architectures. We first aim to maximize the usage of FPGA structures by designing Octavo, astrict round-robin multi-threaded soft-processor architecture tailored to theunderlying FPGA and capable of operating at maximal speed. We then scaleOctavo to SIMD and MIMD parallelism by replicating its datapath and connectingOctavo cores in a point-to-point mesh. This scaling creates multi-local logic,which we preserve via logical partitioning to avoid artificial critial pathsintroduced by unnecessary CAD optimizations.We plan ahead for larger Octavo systems by adding support for architecturalextensions, instruction predication, and variable I/O latency. These featuresimprove the efficiency of hardware extensions, eliminate busy-wait loops, andprovide a building block for more efficient code execution.By extracting the flow-control and addressing sub-graphs out of a program'sControl-Data Flow Graph (CDFG), we can execute them in parallel with usefulcomputations using special dedicated hardware units, granting betterperformance than fully unrolled loops without increasing code size.Finally, we benchmark Octavo against the MXP soft vector processor, theNiosII/f scalar soft-processor, and equivalent benchmark implementationswritten in C synthesized with the LegUp High-Level Synthesis (HLS) tool, anddirect Verilog Hardware Description Language (HDL) implementations. Octavo'shigher clock frequency offsets its higher cycle count, performing roughlyon-par with MXP, and within an order of magnitude of the performance of LegUpand Verilog solutions, but with an order of magnitude area penalty.

Keywords: efficiency
FPGA
multi-threading
overlay
parallelism
soft-processor
Advisor: Anderson, Jason H.
The Present Participle as a Marker of Style and Authorship in Old English Biblical Translation

This dissertation investigates evidence of multiple authorship in the Old English Hexateuch translation of Genesis and in the Old English Gospels by examining how the translations render the Latin present participle into Old English. These are two of the longest extant Old English texts, and there is growing scholarly recognition that both may be products of multiple authorship; however, the translators, except one in Genesis, are anonymous, and the number and locations of shifts in authorship are widely disputed. Past scholarship has employed qualitative, philological evidence, counted features possibly indicating shifts in authorship, and variously proposed breaks between and within texts, but qualitative studies have not fully exploited the present participle as a marker, and quantitative results have not been verified with statistical tests. This dissertation addresses these gaps by conducting a full inventory of Latin present participles in the Old English Genesis and the Old English Gospels, identifying how they are rendered into Old English, and then categorizing them by case and position. The dissertation then applies a statistical "proportion test" to search for the locations of statistically significant shifts in the rate of translating the Latin present participle with its OE counterpart, both overall and in several subcategories. Last, the study engages in qualitative syntactic and philological analysis to evaluate breaks indicated by the proportion test. The results independently corroborate previously asserted textual breaks in Genesis and the Old English Gospels with new syntactic and statistical evidence, revise an existing theory of intra-textual shift in the OE Matthew, and detect evidence of other intra-textual shifts not previously asserted in scholarship. These results also suggest Old English biblical translators engaged in interpretation and authorship, not merely mechanical translation. The study's approaches further explore how traditional and non-traditional methods of authorship attribution can investigate a wide variety of authorship problems.

Keywords: attribution
authorship
Old English Gospels
present participles
syntax
translation
Advisor: Townsend, David
A Methodology for the Optimal Design of Linear Ultrasonic Actuators

Linear ultrasonic motors (LUSMs) are a type of piezoelectric actuator that can achieve closed-loop positioning accuracy in the nanometre range. The operating principle of the LUSM is based on two stages of energy conversion. First, the converse piezoelectric effect is used to generate resonant vibrations in the stator body. Then, linear motion is induced through frictional contact with a moving stage. A primary challenge facing the design of LUSMs is the ability to accurately evaluate actuator-based output performance parameters in a simulated environment. This challenge limits the use of these parameters in computer-aided design optimizations. Furthermore, this issue has led to a heavy emphasis on the stator design, where the scope is limited to the mechanical design aspect of the first stage of energy conversion. To address these issues, the overall objective of this thesis is to develop an LUSM design methodology that is capable of optimizing an LUSM configuration with respect to actuator-based performance specifications by accounting for both stages of energy conversion in its operation. By fully considering the input-output relationships in both stages of energy conversion from mechanical and electrical viewpoints, the proposed design methodology is capable of further improving the actuator output performance parameters in terms of the output force and power densities. In this work, a novel LUSM performance evaluation and design optimization methodology is developed. The primary contribution of this methodology is its ability to evaluate both stator-based and actuator-based performance parameters in a single design stage under contact conditions found in the stator-operating environment. This approach allows the design optimization of LUSMs to be performed with respect to the actuator output performance parameters. The performance evaluation and optimization approach enables the improvement of the LUSM output performance parameters through the application of non-sinusoidal periodic excitation voltage signals in driving the LUSM stator. Two actuation approaches were considered: the application of a square-wave excitation voltage and the application of an excitation voltage yielding a square-wave-based stator driving tip trajectory. The higher harmonics of the square wave were able to excite additional resonant modes in the stator. Performance analysis and extensive finite element-based simulations indicated significant improvements compared to sinusoidal excitation signals in terms of output force and power.

Keywords: Design methodology
Excitation voltage
Linear ultrasonic motors
Piezoelectricity
Vibrations
Advisor: Mills, James K
Benhabib, Beno
Fanconi Anemia Signalling and Mus81-Eme1 Operate in Distinct Pathways to Facilitate in Utero Development and Crosslink Repair

One of the most detrimental types of DNA damage are covalent linkages between opposing DNA strands called crosslinks. One major pathway that plays a role in repair of crosslink damage is mutated in Fanconi Anemia (FA), a hereditary syndrome characterized by bone marrow failure, congenital abnormalities and cancer susceptibility. FA patient cells demonstrate hypersensitivity to crosslinking agents and inhibitors of DNA replication; however, mouse models of FA do not typically mimic the human FA phenotype. Mus81Eme1 is an endonuclease that also has been shown to facilitate crosslink repair by cleaving DNA ahead of crosslinks. It is uncertain whether Mus81Eme1 and the FA pathway act in parallel to repair crosslinks or are epistatic. To examine this, we developed a mouse model deficient in FA pathway signalling (

Advisor: McPherson, J. Peter
Grant, Denis M
A Matrix-free Algorithm for Multidisciplinary Design Optimization

Multidisciplinary design optimization (MDO) is an approach to engineering design that exploits the coupling between components or knowledge disciplines in a complex system to improve the final product. In aircraft design, MDO methods can be used to simultaneously design the outer shape of the aircraft and the internal structure, taking into account the complex interaction between the aerodynamic forces and the structural flexibility. Efficient strategies are needed to solve such design optimization problems and guarantee convergence to an optimal design.This work begins with a comprehensive review of MDO problem formulations and solution algorithms. First, a fundamental MDO problem formulation is defined from which other formulations may be obtained through simple transformations. Using these fundamental problem formulations, decomposition methods from the literature are reviewed and classified. All MDO methods are presented in a unified mathematical notation to facilitate greater understanding. In addition, a novel set of diagrams, called extended design structure matrices, are used to simultaneously visualize both data communication and process flow between the many software components of each method. For aerostructural design optimization, modern decomposition-based MDO methods cannot efficiently handle the tight coupling between the aerodynamic and structural states. This fact motivates the exploration of methods that can reduce the computational cost. A particular structure in the direct and adjoint methods for gradient computation motivates the idea of a matrix-free optimization method. A simple matrix-free optimizer is developed based on the augmented Lagrangian algorithm. This new matrix-free optimizer is tested on two structural optimization problems and one aerostructural optimization problem. The results indicate that the matrix-free optimizer is able to efficiently solve structural and multidisciplinary design problems with thousands of variables and constraints. On the aerostructural test problem formulated with thousands of constraints, the matrix-free optimizer is estimated to reduce the total computational time by up to 90% compared to conventional optimizers.

Keywords: aerostructural optimization
matrix-free
MDO architectures
multidisciplinary design optimization (MDO)
nonlinear optimization
Advisor: Martins, Joaquim R R A
Tipping Points to Institutional Care for Persons Living with Dementia: Analyzing the Policy Trajectory in Ontario

Most people, if given a choice, would remain in their own home and community as they age. This desire does not diminish for persons living with dementia (PLWD), yet many end up prematurely or inappropriately in residential long-term care (LTC), or waiting in a hospital bed for placement. While institutional care is valuable for those in need of high intensity care, it is ill-suited for those with lower intensity care needs. Premature or inappropriate placement of PLWD is not good for individuals (PLWD and their caregivers), or for the system (inappropriate use of resources), yet occurs in part because PLWD often have multiple complex, ongoing health and social needs; however, this thesis argues that it also is a result of care systems focused on episodic, curative care, and by fragmented services that are ill-equipped to support PLWD safely and cost-effectively in the community.While much policy analysis has focused on demand side issues (e.g., an aging population, dementia projections and needs), this research addresses supply side factors - particularly local system capacity to provide needed community-based care options for PLWD to live safely and cost-effectively in the community for as long as possible. It uses Neo-institutionalism, a high-level theory drawn from political science, to explore the historical and policy legacies for community based care of PLWD and predict what one would expect to see in the future if Ontario remains on the same familiar path. It also uses a Balance of Care (BoC) simulation methodology to explore what the system will actually provide PLWD to age safely at home. The conceptual and applied approaches combined are expected to provide a greater understanding of the policy trajectory for home and community care, its impact on current resource allocation decisions at the local level in Ontario and the potential for H and concerted health and social care interventions to help offset the growing healthcare costs for high intensity users of the system like PLWD.

Keywords: Dementia Care
Dementia Policy
Health Policy
Home and Community Care
Homecare
Neo-institutionalism
Advisor: Williams, Paul
Applications of Digital Microfluidics for the Extraction and Analysis of Small Molecules from Solid Samples

Digital microfluidics (DMF) has emerged as a valuable technology that may be useful in the goal of realizing true lab-on-a-chip (LOC) or total micro analysis systems (µTAS). DMF is a relatively new microscale liquid-handling technique in which droplets of fluid are manipulated on a flat, two-dimensional array of electrodes coated with a hydrophobic insulator. Droplet movement is driven by the application of electric potentials to successive electrodes, enabling a droplet to be dispensed from a reservoir, merged, mixed and split. One of the strengths of DMF when compared to channel microfluidics is the ease with which DMF can process solid samples, and incorporate solid materials into sample preparation work-flows without the risk of clogging.This thesis describes the exploration of digital microfluidics as a tool for working with solid samples and matrices. Chapter two describes the first method useful for analyzing multiple hormones in dried blood. This method broadens the scope and breadth of information available from the analysis of dried blood spotted directly onto device. Chapter three describes the first method for applying digital microfluidics towards the analysis of pharmaceuticals from blood spotted onto filter paper - dried blood spots (DBS). The DMF method is compared to the traditional macroscale method employed by collaborators at GlaxoSmithKline. Chapter four describes the first combination of DMF and miniature mass spectrometry (MS). This newly developed, automated, multiplexed, and portable platform was designed for the extraction of illicit drugs from dried urine, and is designed to replace the traditional two-tiered urine analysis system with a one-tiered total analysis system. Chapter five describes a new method for on-chip solvent optimization using a design of experiment. Using this system, C18-coated magnetic beads were incorporated onto device, enabling the first instance of fractionation on a DMF device. Finally, chapter six summarizes the principles and concepts derived from this work, and concludes with a look forward to future applications of digital microfluidics as a tool to handle solid samples and matrices.

Keywords: Digital Microfluidics
Dried Blood Spot
Hormones
Sample Preparation
Solid Phase Extraction
Urine Analysis
Advisor: Wheeler, Aaron R
Decentralized Coordination Control for Dynamic Multiagent Systems

Engineered networks such as power grids, communication networks and logistics operations are becoming increasingly interdependent and comprised of intelligent components that are capable of autonomously processing and influencing their local environment, as well as interacting with other such components. These emerging capabilities are poised to enable unprecedented efficiency gains across previously disparate application domains. Fully harnessing this potential is contingent in part on our ability to effect coordinated local interactions among such components, ensuring their optimal collective behavior. In this thesis we formulate several Decentralized Coordination Control Problems (DCCPs) for networked multiagent systems involving either static or dynamic agents. We propose that Consensus Optimization (CO) methods constitute a viable foundation for the synthesis of coordination control strategies that address large classes of DCCPs. In order to understand both the potential and the limitations of such strategies, we develop a new framework for the convergence analysis of general CO schemes. In contrast with existing analytic approaches, our framework is based on powerful system-theoretic techniques enabling the study of DCCP scenarios in which the agent dynamics interact with those of the CO algorithm itself, thereby affecting its performance. Aside from fulfilling its intended purpose, our analytic viewpoint also leads to the relaxation of several standard assumptions imposed on numerical CO algorithms, and suggests a methodical approach to deriving conditions under which existing centralized optimization methods can be decentralized. In addition, we propose the Reduced Consensus Optimization (RCO) algorithm -- a streamlined variant of CO which is more innately suited to the DCCP context. Agents implementing RCO generally need not be aware of the network size and topology, and the overall processing and communication overhead associated with agent coordination may be substantially reduced relative to CO. On the basis of RCO, we propose a methodology for the design of decentralized content caching strategies in information-centric networks.

Keywords: Consensus Optimization
Control Theory
Cooperative Systems
Coordination Control
Decentralized Optimization
Multiagent Systems
Advisor: Pavel, Lacra
Development of Helper-dependent Adenoviral Vectors for Gene Therapy for Inherited Retinal Diseases

There have been significant advancements in the field of retinal gene therapy in the past decade. In particular, therapeutic efficacy has been achieved in three separate human clinical trials using adeno-associated viruses (AAV) to treat a type of Leber's congenital amaurosis caused by

Keywords: ABCA4
eye diseases
gene therapy
helper-dependent adenoviral vector
Stargardt's disease
subretinal gene delivery
Advisor: Hu, Jim