VictorJuiz/thesis huggingface dataset:
Actin-perturbing Activity of Treponema denticola Major Outer Sheath Protein (Msp) and Stress Fiber Formation/Stabilization by a Novel Peptide Conjugate Deduced from the Msp Sequence

The major outer sheath protein (Msp) is the most prominent surface antigen of the periodontal pathogen Treponema denticola. It mediates adhesion to extracellular matrix and dysregulation of cytoskeletal homeostasis of host cells. Disassembly of actin filaments and the coincident subcortical de novo synthesis of actin filaments in fibroblasts upon exposure to Msp were investigated with a barbed-end fluorescent labeling method. The functional impact of actin cytoskeleton disorganization was determined with a scratch wound migration assay in fibroblast monolayers and a videomicroscopy migration assay in neutrophils. Msp pretreatment had a significant inhibitory effect on the migration of the fibroblasts across a collagen substratum and inhibited the neutrophil chemotactic migration towards a chemoattractant. In a study originally aimed to find the biologically active domains of Msp that may perturb actin, short peptides were selected from the deduced and predicted surface exposed regions of Msp and investigated for their role in actin dynamics and cell motility. A novel BSA-conjugated peptide (P34BSA) was found serendipitously to induce stress fiber formation and stability in fibroblasts. This activity was found to be mediated by Rho activation and cofilin phosphorylation, which are important tandem signaling pathways in the regulation of a variety of actin-dependent cellular functions. P34BSA was internalized by the cells. Yet, a mechanistic study using low-temperature treatments and depletion of cholesterol with methyl-β-cyclodextrin (MβCD) revealed that P34BSA most likely induces actin stress fiber formation extracellularly through a Rho-dependent signaling pathway. P34BSA induced Rho activation via binding of guanosine nucleotide exchange factor p114RhoGEF to RhoA, one of many exchange factors that have been shown to play a role in activating Rho signaling. Pretreatment with P34BSA partially protected the fibroblasts against the actin-disrupting effects of cytochalasin D and latrunculin B, and the cells maintained most of their actin filaments. P34BSA treatment caused retardation of fibroblast migration on a collagen substratum. It also inhibited the chemotactic movement of neutrophils towards the chemoattractant fMLP. P34 may represent a novel amino acid sequence of a bacterial virulence protein that, when conjugated to BSA, can be used as a chemical reagent to investigate RhoA signaling pathways in host cells.

Keywords: Treponema denticola
Actin dynamics
Advisor: Ellen, Richard P.
Clinical Trials and Treatment Outcomes of Edentulous PatientsTreated with Implant-supported Prosthesis

Since their introduction, the use of endosseous implant for replacements of missing teeth has increased dramatically. To date, however, there is no evidence-based answer to the important clinical question: What implant-supported prosthesis designs provide the best outcomes? Cochrane systematic reviews have been used to critically assess scientific literature, to answer a wide array of questions. This approach was used to focus on implant-related treatment outcomes, including patient-based outcomes. Data showed that in most cases clinical and patient-mediated outcomes did not differ significantly from one another regardless of the prosthesis used. However, long-term prognosis of implant-supported overdentures using magnet attachments may produce inferior outcomes when compared to other attachments. In this dissertation it was shown that long-term results following immediate loading of endosseous implants with overdentures were successful based on biological and clinical parameters, cost to patient, and patient-based outcomes. Moreover, it was noted that well-designed clinical trials evaluating efficacy of immediate loading with fixed prostheses are uncommon. Furthermore, a parallel randomized controlled clinical trial focusing on this issue was carried out. In this trial, the author investigated the effects of immediate and delayed loading of implants with mandibular fixed prostheses. The implant-related outcomes underscore that even when implants are loaded during the healing period (i.e. immediate loading), successful osseointegration can be achieved and maintained. Patients’ satisfaction and oral health-related quality of life indicated that the two loading schemes addressed patient’s need equally.

Keywords: Dental implants
Edentulous
Advisor: Jokstad, Asbjorn
Primary Care Reform: A Case Study of Ontario

This dissertation examines the factors that have the most significant impact on the pace of change in the primary care (PC) sector in Ontario. In Canada, there have been many attempts to improve the PC system through the introduction of a variety of primary care reform (PCR) models. Some say that there is insufficient movement in the PC sector and that it is in a policy gridlock. Others assert that substantial progress has been made and that transformational change is proceeding. This dissertation demonstrates that PCR – the movement from PC to some form of primary health care (PHC) – is multi-dimensional and complex. It identifies the multiple dimensions of PHC and demonstrates that each dimension has implications for the structural relationships between the state and the medical association in the PC sector in Ontario. The framework for this dissertation was derived from three bodies of literature: PC/PHC, neo-institutionalism and professional autonomy. The research design used involves qualitative and quantitative methods, including historical analysis, document analysis, key informant interviews and qualitative data. The case study of PCR in Ontario demonstrates that while there have been some changes in the methods of physician payment and in the organization and delivery of PC, the majority of PCR models have not fundamentally altered the underlying institutional and structural relationships that characterize the sector. This includes the profession’s ability to control the political, economic and clinical aspects of care. Thus, the PCR models that propose the greatest amount of reform – those that alter structural relationships between the state and the medical association in a manner that results in a significant impact on the balance of power in the PC sector- are less likely to be adopted by physicians. This dissertation corroborates that the PCR models that have the greatest impact on professional autonomy are those that remain at the margins of the health care system, whereas the models that have little or no impact on autonomy have been more readily adopted.

Keywords: primary care reform
professional autonomy
neo-institutionalism
key elements
political
technical
primary care
primary health care
ontario
primary care reform models
Advisor: Williams, A. Paul
Digital Microfluidics for Integration of Lab-on-a-Chip Devices

Digital microfluidics is a new technology that permits manipulation of liquid droplets on an array of electrodes. Using this technology, nanoliter to microliter size droplets of different samples and reagents can be dispensed from reservoirs, moved, split, and merged together. Digital microfluidics is poised to become an important and useful tool for biomedical applications because of its capacity to precisely and automatically carry out sequential chemical reactions. In this thesis, a set of tools is presented to accelerate the integration of digital microfluidics into Lab-on-a-Chip platforms for a wide range of applications. An important contribution in this thesis is the development of three rapid prototyping techniques, including the use of laser printing to pattern flexible printed circuit board (PCB) substrates, to make the technology accessible and less expensive. Using these techniques, both digital and channel microfluidic devices can be produced in less than 30 minutes at a minimal cost. These rapid prototyping techniques led to a new method for manipulating liquid droplets on non-planar surfaces. The method, called All Terrain Droplet Actuation (ATDA), was used for several applications, including DNA enrichment by liquid-liquid extraction. ATDA has great potential for the integration of different physico-chemical environments on Lab-on-a-Chip devices. A second important contribution described herein is the development of a new microfluidic format, hybrid microfluidics, which combines digital and channel microfluidics on the same platform. The new hybrid device architecture was used to perform biological sample processing (e.g. enzymatic digestion and fluorescent labeling) followed by electrophoretic separation of the analytes. This new format will facilitate complete automation of Lab-on-a-Chip devices and will eliminate the need for extensive manual sample processing (e.g. pipetting) or expensive robotic stations. Finally, numerical modeling of droplet actuation on single-plate digital microfluidic devices, using electrodynamics, was used to evaluate the droplet actuation forces. Modeling results were verified experimentally using an innovative technique that estimates actuation forces based on resistive forces against droplet motion. The results suggested a list of design tips to produce better devices. It is hoped that the work presented in this thesis will help introduce digital microfluidics to many of the existing Lab-on-a-Chip applications and inspire the development of new ones.

Keywords: Digital microfluidics
electrowetting
Lab on a chip
droplet manipulation
Advisor: Wheeler, Aaron
Metamaterial-Inspired CMOS Tunable Microwave Integrated Circuits For Steerable Antenna Arrays

This thesis presents the design of radio-frequency (RF) tunable active inductors (TAIs) with independent inductance (L) and quality factor (Q) tuning capability, and their application in the design of RF tunable phase shifters and directional couplers for wireless transceivers. The independent L and Q tuning is achieved using a modided gyrator-C architecture with an additional feedback element. A general framework is developed for this Q- enhancement technique making it applicable to any gyrator-C based TAI. The design of a 1.5V, grounded, 0.13um CMOS TAI is presented. The proposed circuit achieves a 0.8nH-11.7nH tuning range at 2GHz, with a peak-Q in excess of 100. Furthermore, printed and integrated versions of tunable positive/negative refractive index (PRI /NRI) phase shifters, are presented in this thesis. The printed phase shifters are comprised of a microstrip transmission-line (TL) loaded with varactors and TAIs, which, when tuned together, extends the phase tuning range and produces a low return loss. In contrast, the integrated phase shifters utilize lumped L-C sections in place of the TLs, which allows for a single MMIC implementation. Detailed experimental results are presented in the thesis. As an example, the printed design achieves a phase of -40 to +34 degrees at 2.5GHz. As another application for the TAI, a reconfigurable CMOS directional coupler is presented in this thesis. The proposed coupler allows electronic control over the coupling coefficient, and the operating frequency while insuring a low return loss and high isolation. Moreover, it allows switching between forward and backward operation. These features, combined together, would allow using the coupler as a duplexer to connect a transmitter and a receiver to a single antenna. Finally, a planar electronically steerable patch array is presented. The 4-element array uses the tunable PRI/NRI phase shifters to center its radiation about the broadside direction. This also minimizes the main beam squinting across the operating bandwidth. The feed network of the array uses impedance transformers, which allow identical interstage phase shifters. The proposed antenna array is capable of continuously steering its main beam from -27 to +22 degrees of the broadside direction with a gain of 8.4dBi at 2.4GHz.

Keywords: tunable active inductors
phase shifters
directional couplers
steerable antenna arrays
metamaterials
CMOS MMIC
Advisor: Eleftheriades, George V.
earPod: Efficient Hierarchical Eyes-free Menu Selection

The research in this dissertation developed and evaluated a new method for menuing interaction that is intended to be better suited than current methods with respect to mobile eyes-free scenarios. The earPod prototype was developed and then evaluated in a series of four experiments. In the first two experiments, earPod was first compared against an iPod-like (visual) interface and then against a fuller set of competitive techniques that included dual vs. single modality presentations, audio vs. visual modalities, and radial vs. linear mappings. The third experiment consisted of a longitudinal study designed to understand the learning patterns that occurred with these techniques. The fourth experiment examined performance in a conventional (single task) desktop setting and in a driving simulator (i.e., a dual task situation where participants carried out the driving task while interacting with the mobile device). The results of these experiments, comparing earPod with an iPod-like visual linear menu technique on fixed-sized static menus, indicated that earPod is comparable both in terms of speed and accuracy. Thus it seems likely that earPod should be an effective and efficient eyes-free menu selection technique. The comprehensive 3x2 study implemented in Experiment 2 showed that the benefit of earPod was largely due to the radial menu style design. While performance using it was comparable in both speed and accuracy with the visual linear menus, its performance was slower than for a visual radial style menu. In the multi-task simulated driving condition in Experiment 4, where concurrent tasks competed for visual attention, the eyes-free earPod interface was found to be beneficial in improving performance with respect to the safety related driving parameters of following distance and lateral movement in the lane. Thus auditory feedback appears to mitigate some of the risk associated with menu selection while driving. Overall, the results indicated that not only should earPod menuing be able to provide safer interaction in dual task settings, but also that, with sufficient training, audio only menu selection using innovative techniques such as those employed by earPod can be competitive with visual menuing systems even in desktop settings.

Keywords: earPod
Human Computer Interaction
Computer Science
Interactive Techniques
Advisor: Chignell, Mark
Nontradable Market Index and Its Derivatives

The S&P 500 Index is a leading indicator of U.S. equities and is meant to reflect the risk and return on the U.S. stock market. Many derivatives based on the S&P 500 are available to investors. The S&P 500 Futures of the Chicago Mercantile Exchange and the S&P 500 Index Options of the Chicago Board Options Exchange are both actively traded. My thesis argues that the S&P 500 Index is only a summary statistic designed to reflect the evolution of the stock market. It is not the value of a self-financed tradable portfolio, and its modifications do not coincide with changes of the value of any mimicking portfolio, due to the particular way the S&P 500 Index is computed and maintained. Therefore, the Spot-Futures Parity and the Put-Call Parity do not hold for the S&P 500 Index and its derivatives. Furthermore, its derivatives cannot be priced by using the standard option pricing models, which assume that the underlying asset is tradable. Chapter One analyzes why the S&P 500 Index does not represent the value of a self-financed tradable portfolio and why it cannot be replaced by the value of a tracker such as the SPDR. In particular, we show that the nonlinear and extreme risk dynamics of the SPDR and of the S&P 500 Index are very different. Chapter Two provides empirical evidence that the non-tradability of the S&P 500 Index can explain the Put-Call Parity deviations. Even after controlling for the liquidity risk of the options, we find that the Put-Call Parity implied dividends depend significantly on the option strike. In Chapter Three, we develop an affine multi-factor model to price coherently various derivatives such as forwards and futures written on the S&P 500 Index, and European put and call options written on the S&P 500 Index and on the S&P 500 futures. We consider the cases when the underlying asset is self-financed and tradable and when it is not, and show the difference between them. When the underlying asset is self-financed and tradable, an additional arbitrage condition has to be introduced and implies additional parameter restrictions.

Keywords: Nontradable Market Index and Its Derivatives
Advisor: Gourieroux, Christian
A Biophysical Characterization of Phagolysosome Acidification

Specialized cells of the innate immune system, such as macrophages, employ lysosomal enzymes, together with cationic peptides and reactive oxygen intermediates, to eliminate invading microorganisms ensnared within phagosomes. The effectiveness of this impressive armamentarium is potentiated by the acid pH generated by the vacuolar-type ATPase (V-ATPase). The determinants of the luminal pH of phagosomes and of the lysosomes they fuse with are not completely understood, but the V-ATPase is known to be electrogenic and net accumulation of protons requires charge compensation. For this reason, counter-ion pathways are thought to serve a central role in the control of acidification. It has generally been assumed that a parallel anion influx accompanies proton pumping to dissipate the voltage that tends to build up. In fact, impaired chloride channel activity in cystic fibrosis has been proposed to underlie the defective phagolysosome acidification and microbial killing reported in lung macrophages. In the first part of this thesis, I devised methods to dialyze the lumen of lysosomes in intact cells, while monitoring lysosomal pH, in order to assess the individual contribution of counter-ions to acidification. Surprisingly, anions were found to be completely dispensable for proton pumping, whereas the presence of permeant cations in the lysosomal lumen was essential. Accordingly, defects in lysosomal anion permeability cannot explain the impaired microbicidal capacity of phagocytes in cystic fibrosis. Even though counter-ion permeation pathways exist, dissipation of the electrical contribution of the V-ATPase may not be complete. If present, a transmembrane potential would alter the rate and extent of proton accumulation in phagosomes and lysosomes. However, no estimates of the voltage across the phagosomes were available. To overcome this deficiency, in the second part of this thesis, I describe a noninvasive procedure to estimate the voltage across the phagosome using fluorescence resonance energy transfer. This novel approach, in combination with organellar pH measurements, demonstrated that proton pumping is not limited by counter-ion permeability.

Keywords: Lysosome
Phagosome
pH
Microscopy
Macrophage
CFTR
Advisor: Grinstein, Sergio
VLSI Implementation of Digital Signal Processing Algorithms for MIMO/SISO Systems

The efficient high-throughput VLSI implementation of near-optimal multiple-input multiple-output (MIMO) detectors for 4x4 MIMO systems in high-order quadrature amplitude modulation (QAM) schemes has been a major challenge in the literature. To address this challenge, this thesis introduces a novel scalable pipelined VLSI architecture for a 4x4 64-QAM MIMO receiver based on K-Best lattice decoders. The key contribution is a means of expanding/visiting the intermediate nodes of the search tree on-demand, rather than exhaustively along with three types of distributed sorters operating in a pipelined structure. The combined expansion and sorting cores are able to find the K best candidates in K clock cycles. The proposed architecture has a fixed critical path independent of the constellation order, on-demand expansion scheme, efficient distributed sorters, and is scalable to a higher number of antennas/constellation orders. Fabricated in 0.13um CMOS, it operates at a significantly higher throughput (5.8x better) than currently reported schemes and occupies 0.95 mm2 core area. Operating at 282 MHz clock frequency, it dissipates 135 mW at 1.3 V supply with no performance loss. It achieves an SNR-independent decoding throughput of 675 Mbps satisfying the requirements of IEEE 802.16m and Long Term Evolution (LTE) systems. The measurements confirm that this design consumes 3.0x less energy/bit compared to the previous best design.

Keywords: ASIC Implementation
K-Best MIMO Detector
Sequential Monte Carlo
Lattice Reduction
Advisor: Gulak, P. Glenn
Beyond Chronic Rejection: Tissue Remodelling in Obliterative Bronchiolitis after Lung Transplantation

The long-term success of lung transplantation has been challenged by chronic graft dysfunction, which is manifested as obliterative bronchiolitis (OB). We demonstrated that allograft airway fibrosis is a dynamic process of tissue remodelling, in which cellular and matrix components dynamically change before or after complete obliteration of the airway lumen. This dynamic process was associated with changes in expression and activity of matrix metalloproteinases (MMPs). The early inflammatory phase was associated with MMP-dependent migration of blood-borne fibrocytes, which highly express MMP-9 and MMP-12. ‘Established’ fibrosis was associated with MMP-2 and MMP-14 expressed by myofibroblasts in both human OB lesions and their animal models. In established allograft airway fibrosis, general MMP inhibition resulted in apoptosis of myofibroblasts in vivo and in vitro, while low-doses of MMP-inhibitor treatment induced upregulation of MMP-2, increased collagenolytic activity, and significantly decreased myofibroblasts and collagen. The dynamic process of tissue remodelling in established allograft airway fibrosis was supported by underlying continuous alloimmune responses, in particular, direct T-cell-myofibroblast contact. iii Modulation of tissue remodelling using a low-dose MMP inhibitor in combination with cyclosporine induced partial regression of fibrosis after its establishment. We further demonstrated the mechanism of alloimmune responses unique to the lung. Human and animal studies demonstrated that bronchioles develop de novo lymphoid tissue characterized by formation of high endothelial venules and homing of effector memory T-cells. A following study demonstrated the important role of local immunological memory maintained by the intrapulmonary lymphoid tissue in exerting effector function in allograft rejection. Collectively, the present studies support the hypothesis that tissue remodelling is an important mechanism of allograft airway fibrosis. Regulation of tissue remodelling and underlying tissue injury is important not only to arrest aberrant remodelling of allograft airways but likely to reverse aberrant remodelling and to regenerate normal tissue architecture in airways after lung transplantation.

Keywords: Lung transplantation
chronic rejection
Advisor: Keshavjee, Shaf