VictorJuiz/thesis huggingface dataset:
Oxygen Regulation of Vascular Smooth Muscle Cell Proliferation and Survival
Keywords: vascular hypoxia
smooth muscle cell proliferation

Arterial smooth muscle cells (SMCs) from the systemic and pulmonary circulations experience a broad range of oxygen concentrations under physiological conditions. The hypoxic response, however, has been inconsistent, with both enhanced proliferation and growth arrest being reported. This variability precludes a definitive conclusion regarding the role of oxygen tension in arterial disease. In the first part of this study, we determined if hypoxia elicits different proliferative and apoptotic responses in human aortic SMCs (HASMCs) incubated under conditions which do or do not result in cellular ATP depletion and whether these effects are relevant to vascular remodeling in vivo. Gene expression profiling was used to identify potential regulatory pathways. In HASMCs incubated at 3% O2, proliferation and progression through G1/S interphase are enhanced. Incubation at 1% O2 reduced proliferation, delayed G1/S transition, increased apoptosis and cellular ATP levels were reduced. In aorta and mesenteric artery from hypoxia exposed rats, both proliferation and apoptosis are increased after 48hrs. p53 and p21expression is differentially affected in HASMCs incubated at 1% and 3% O2. Hypoxia induces a state of enhanced cell turnover, conferring the ability to remodel the vasculature in response to changing tissue metabolic needs while avoiding the accumulation of mutations that may lead to malignant transformation or abnormal vascular structure formation. A unifying hypothesis in which events at the G1/S transition and apoptosis activation are coordinated by effects on p53, p21, their downstream effector genes and regulatory factors is proposed. Differences in the contractile responses of systemic and pulmonary arterial smooth muscle cells to hypoxia are well studied. Differences in proliferation and survival are anticipated because of differences in embryonal cell origin, oxygen concentrations within their respective microenvironments and in cellular energetics but these responses have not been directly compared. In the second part of the study, human pulmonary arterial SMCs (HPASMCs) proliferated at oxygen concentrations which inhibited cell growth in HASMCs. HPASMCs survived and maintained their intracellular ATP levels at levels of hypoxia sufficient to deplete ATP and induce apoptosis in HASMCs. In vivo studies in rats show proliferation and apoptosis in main or branch PASMCs only after 7 days of hypoxia. VSMCs are able to proliferate under hypoxic conditions as long as cellular ATP levels are maintained. HPASMCs have an enhanced capacity to maintain cellular energy status compared to HASMCs and hence their viability is preserved and the proliferative response predominates at lower oxygen concentrations.
Role of Bacterial Effectors SopD and SopB in Pathogenicity of Salmonella enterica serovar Typhimurium.
Keywords: Salmonella
type III secretion
SopD
SopB
SigD
phosphoinositide
phagolysosome fusion
macropinosome
membrane charge
host-pathogen interactions
bacterial invasion

Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that has evolved to take advantage of the eukaryotic host cells it inhabits during infection. It uses bacterial effectors translocated into the host cell cytosol to manipulate host cell machinery and establish a replicative niche. In this thesis I study the function of two of these effectors, SopD and SopB, which have been shown to act cooperatively to induce phenotypes associated with gastroenteritis (fluid secretion and neutrophil influx into the intestinal lumen). In addition to promoting gastroenteritis, SopD has also been implicated in systemic and persistent infection of mice. Although recently implicated in invasion, the precise function of SopD has remained elusive. Here I show that SopD affects membrane dynamics during S. Typhimurium invasion of epithelial cells. SopD promotes membrane sealing and macropinosome formation, events that may have important consequences for efficiency of bacterial cell entry in vivo. Furthermore, we demonstrate that SopD is recruited to the invasion site membranes through the phosphatase activity of SopB, suggesting a mechanism for their cooperative action during induction of gastroenteritis. Unlike SopD, SopB has been a focus of intense research efforts and its role in invasion as a phosphoinositide phosphatase is well documented. However, we have observed that SopB also inhibits fusion of lysosomes with Salmonella-containing vacuoles (SCVs) following invasion. This ability depends on SopB-mediated reduction of negative membrane charge of the SCV during invasion by hydrolysis of the phosphoinositide PI(4,5)P2. Membrane charge alterations driven by SopB result in removal of Rab GTPases from the SCV that depend on electrostatic interactions for their targeting. Two of these Rabs, Rab23 and Rab35 were previously shown to promote phagosome-lysosome fusion. Therefore their removal from the SCV may promote SCV trafficking away from the degradative endocytic pathway of host cells. This represents a new mechanism by which an invasion associated effector controls SCV maturation. Together, this work advances our knowledge of the interaction between S. Typhimurium and its host. This research also suggests a new mechanism by which pathogens other than S. Typhimurium could promote their intracellular survival.
An Investigation of the ca. 2.7 Ga Late Archean Magmatic Event (LAME) in the Superior Province using 1-D Thermal Modelling
Keywords: 2700 Ma
2.7 Ga
thermal model
numerical model
Late Archean
Neoarchean
TTG
tonalite
LAME
Late Archean Magmatic Event
plume
mantle plume
Superior
Abitibi
Archean granite
melting
Archean lithosphere
heat production
greenstone
delamination
crustal thickening
crustal heating

The Late Archean Magmatic Event (LAME), ca. 2.7 Ga, was the greatest crustal addition event in Earth history. My focus is the Superior Province of Canada, where LAME occurred ca. 2.75 – 2.65 Ga. Mantle plumes impinged on the Abitibi subprovince, where ~ 16 km regional thickness of tonalite-trondhjemite-granodiorite (TTG) melt was produced. Granites (sensu stricto) were the last magmatic phase of LAME, with a Superior-wide regional thickness of ~ 1 – 3 km. Assuming a crustal source for both TTG and granites, I use 1-D thermal models to investigate the origin of TTG in the Abitibi subprovince and that of late granites in the Superior Province. Melting curves appropriate to the source of TTG and granites are used to determine the thickness of melt produced in the models. I show that the incorporation of upward melt transfer into a standard model of lower crustal melting may increase the amount of predicted melt by ~ 1/(1-f), where f denotes the fraction of melt that is on average being extracted from the source rocks. Partitioning of heat producing elements between melt and restite reduces the amount of melt produced, but the effect is secondary compared to the increase in melt production through upward melt transfer. For the Abitibi subprovince, I show that the emplacement of a single plume coupled with the emplacement of a 12-km-thick greenstone cover can generate a maximum of ~ 9-km-thickness of TTG melt. However, the emplacement of a series of plumes, each coupled with the emplacement of a 3-km-thick greenstone cover and a 10-km-thick sill results in ~ 20-km-thickness of TTG melt. My model incorporates delamination of restitic eclogite. Finally, I show that late granites in the Superior Province may have resulted from thickening of a crust that had been “pre-heated” during earlier arc activity and that prolonged granitic magmatism observed in some areas of the Superior Province may be explained by late underthrusting of fertile source rocks into deeper and hotter regions of the crust.
Development of Automated Robotic Microassembly for Three-dimensional Microsystems
Keywords: Microassembly
Micromanipulation
Micro-robotics
Automated control
Micro-electromechanical systems

Robotic microassembly is a process to leverage intelligent micro-robotic technologies to manipulate and assemble three-dimensional complex micro-electromechanical systems (MEMS) from a set of simple-functional microparts or subsystems. As the development of micro and nano-technologies has progressed in recent years, complex and highly integrated micro-devices are required. Microassembly will certainly play an important role in the fabrication of the next generation of MEMS devices. This work provides advances in robotic microassembly of complex three-dimensional MEMS devices. The following key technologies in robotic microassembly are studied in this research: (i) the design of micro-fasteners with high accuracy, high mechanical strength, and reliable electrical connection, (ii) the development of a microassembly strategy that permits the manipulation of microparts with multiple degrees of freedom (DOFs) and high accuracy, (iii) fully automated microassembly based on computer vision, (iv) micro-force sensor design for microassembly. An adhesive mechanical micro-fastener is developed to assemble micro-devices. Hybrid microassembly strategy, which consists of pick-and-place and pushing-based manipulations, is employed to assemble three-dimensional micro-devices with high flexibility and high accuracy. Novel three-dimensional rotary MEMS mirrors have been successfully assembled using the proposed micro-fastener and manipulation strategy. Fully automatic pick-and-place microassembly is successfully developed based on visual servo control. A vision-based contact sensor is developed and applied to automatic micro-joining tasks. Experimental results show that automatic microassembly has achieved sub-micron accuracy, high efficiency, and high success rate. This work has provided an effective approach to construct the next generation of MEMS devices with high performance, high efficiency, and low cost.
Efficient Simulation, Accurate Sensitivity Analysis and Reliable Parameter Estimation for Delay Differential Equations
Keywords: Delay Differential Equations
Sensitivity Analysis
Parameter Estimation
Discontinuous Ordinary Differential Equations
Runge-Kutta Methods
Linear Multistep Methods

Delay differential equations (DDEs) are a class of differential equations that have received considerable recent attention and been shown to model many real life problems, traditionally formulated as systems of ordinary differential equations (ODEs), more naturally and more accurately. Ideally a DDE modeling package should provide facilities for approximating the solution, performing a sensitivity analysis and estimating unknown parameters. In this thesis we propose new techniques for efficient simulation, accurate sensitivity analysis and reliable parameter estimation of DDEs. We propose a new framework for designing a delay differential equation (DDE) solver which works with any supplied initial value problem (IVP) solver that is based on a general linear method (GLM) and can provide dense output. This is done by treating a general DDE as a special example of a discontinuous IVP. We identify a precise process for the numerical techniques used when solving the implicit equations that arise on a time step, such as when the underlying IVP solver is implicit or the delay vanishes. We introduce an equation governing the dynamics of sensitivities for the most general system of parametric DDEs. Then, having a similar view as the simulation (DDEs as discontinuous ODEs), we introduce a formula for finding the size of jumps that appear at discontinuity points when the sensitivity equations are integrated. This leads to an algorithm which can compute sensitivities for various kind of parameters very accurately. We also develop an algorithm for reliable parameter identification of DDEs. We propose a method for adding extra constraints to the optimization problem, changing a possibly non-smooth optimization to a smooth problem. These constraints are effectively handled using information from the simulator and the sensitivity analyzer. Finally, we discuss the structure of our evolving modeling package DDEM. We present a process that has been used for incorporating existing codes to reduce the implementation time. We discuss the object-oriented paradigm as a way of having a manageable design with reusable and customizable components. The package is programmed in C++ and provides a user-friendly calling sequences. The numerical results are very encouraging and show the effectiveness of the techniques.
Two Theorems of Dye in the Almost Continuous Category
Keywords: orbit equivalence
ergodic theory

This thesis studies orbit equivalence in the almost continuous setting. Recently A. del Junco and A. Sahin obtained an almost continuous version of Dye’s theorem. They proved that any two ergodic measure-preserving homeomorphisms of Polish spaces are almost continuously orbit equivalent. One purpose of this thesis is to extend their result to all free actions of countable amenable groups. We also show that the cocycles associated with the constructed orbit equivalence are almost continuous. In the second part of the thesis we obtain an analogue of Dye’s reconstruction theorem for etale equivalence relations in the almost continuous setting. We introduce topological full groups of etale equivalence relations and show that if the topological full groups are isomorphic, then the equivalence relations are almost continuously orbit equivalent.
Detailed Modeling of Soot Formation/Oxidation in Laminar Coflow Diffusion Flames
Keywords: Soot Formation
Numerical Simulation
Aggregate Fragmentation
Parallel Computing
Laminar Coflow Diffusion Flame

The first goal of this thesis is to develop and validate a modeling tool into which fundamental combustion chemistry and aerosol dynamics theory are implemented for investigating soot formation/oxidation in multi-dimensional laminar coflow diffusion flames taking into account soot polydispersity and fractal-like aggregate structure. The second goal is to use the tool to study soot aggregate formation/oxidation in experimentally studied laminar coflow diffusion flames to advance the understanding of soot aggregate formation/oxidation mechanism. The first part of the thesis deals with the large CPU time problem when detailed models are coupled together. Using the domain decomposition method, a high performance parallel flame code is successfully developed. An advanced sectional aerosol dynamics model which can model fractal-like aggregate structure is successfully implemented into the parallel flame code. The performance of the parallel code is demonstrated through its application to the modeling of soot formation/oxidation in a laminar coflow CH4/air diffusion flame. The parallel efficiency reaches as high as 83%. The second part of the thesis numerically explores soot aggregate formation in a laminar coflow C2H4/air diffusion flame using detailed PAH-based combustion chemistry and a PAH-based soot formation/oxidation model. Compared to the measured data, flame temperature, axial velocity, C2H2 and OH concentrations, soot volume fraction, the average diameter and the number density of primary particles are reasonably well predicted. However, it is very challenging to predict effectively the average degree of particle aggregation. To do so, particle-particle and fluid-particle interactions that may cause non-unitary soot coagulation efficiency need to be considered. The original coagulation model is enhanced in this thesis to accommodate soot coagulation efficiency. Different types of soot coagulation efficiency are numerically investigated. It is found that a simple adjustment of soot coagulation efficiency from 100% to 20% provides good predictions on soot aggregate structure as well as flame properties. In the third part of the thesis, the effects of oxidation-driven soot aggregate fragmentation on aggregate structure and soot oxidation rate are studied. Three fragmentation models with different fragmentation patterns are developed and implemented into the sectional aerosol dynamics model. The implementation of oxidation-driven aggregate fragmentation significantly improves the prediction of soot aggregate structure in the soot oxidation region.
Linker-based Lecithin Microemulsions as Transdermal Drug Delivery Systems
Keywords: lecithin microemulsions
transdermal drug delivery

The interest in microemulsions as transdermal delivery systems have been motivated by their large surface area for mass transfer, their high solubilization capacity of hydrophobic actives, and their ability to improve skin penetration. Lecithins (mixtures of phospholipids similar to those find in the skin) have been proposed as ideal surfactants in microemulsions due to their skin compatibility. Unfortunately, their incorporation into microemulsions used to require toxic medium-chain alcohols or viscous polymeric co-surfactants. Recently, microemulsion-base “green solvents” were formulated with lecithin and linker molecules. The main objective of this dissertation was to test this concept of linker-based lecithin microemulsions in transdermal delivery. In the first part of this study, linker-based lecithin formulations were developed using soybean lecithin as main surfactant, sorbitol monooleate as lipophilic linker, and caprylic acid/sodium caprylate as hydrophilic linkers. These additives, at the suggested concentration, are safe for cosmetic and pharmaceutical applications. The low toxicity of these formulations was confirmed in cultured human skin tissues. The solubilization and permeation of a common anaesthetic, lidocaine, was evaluated. The concept of “skin” permeability was introduced to account for the differences in solvent-skin partition when comparing different delivery systems. The linker-based lecithin microemulsion produced a substantial absorption of lidocaine into the skin, when compared to a conventional pentanol-lecithin microemulsion. The second part of this study takes advantage of the lidocaine adsorbed in the skin with the linker-based lecithin microemulsion as reservoir for in situ skin patches. The in situ patches were able to release 90% of the lidocaine over 24 hours, which is comparable to the release profile obtained from conventional polymer or gel-based patches. In the third part of this work, the role of surfactant droplets on the transport of lidocaine was studied. A mass balance model that accounted for mass transfer and partition coefficients was introduced. The parameters generated from the model confirm that in most cases the transport through the skin limits the overall penetration of lidocaine. Besides the conventional diffusion mechanism, the results suggest that surfactant droplets, carrying lidocaine, also penetrate into the skin and contribute to the accumulation of the lidocaine in the skin.
Development of a Flat Panel Detector with Avalanche Gain for Interventional Radiology
Keywords: interventional radiology
flat panel detector
flat panel imager
avalanche multiplication
amorphous selenium
fluoroscopy

A number of interventional procedures such as cardiac catheterization, angiography and the deployment of endovascular devices are routinely performed using x-ray fluoroscopy. To minimize the patient’s exposure to ionizing radiation, each fluoroscopic image is acquired using a very low x-ray exposure (~ 1 uR at the detector). At such an exposure, most semiconductor-based digital flat panel detectors (FPD) are not x-ray quantum noise limited (QNL) due to the presence of electronic noise which substantially degrades their imaging performance. The goal of this thesis was to investigate how a FPD based on amorphous selenium (a-Se) with internal avalanche multiplication gain could be used for QNL fluoroscopic imaging at the lowest clinical exposures while satisfying all of the requirements of a FPD for interventional radiology. Towards this end, it was first determined whether a-Se can reliably provide avalanche multiplication gain in the solid-state. An experimental method was developed which enabled the application of sufficiently large electric field strengths across the a-Se. This method resulted in avalanche gains as high as 10000 at an applied field of 105 V/um using optical excitation. This was the first time such high avalanche gains have been reported in a solid-state detector based on an amorphous material. Secondly, it was investigated how the solid-state a-Se avalanche detector could be used to image X-rays at diagnostic radiographic energies (~ 75 kVp). A dual-layered direct-conversion FPD architecture was proposed. It consisted of an x-ray drift region and a charge avalanche multiplication region and was found to eliminate depth-dependent gain fluctuation noise. It was shown that electric field strength non-uniformities in the a-Se do not degrade the detective quantum efficiency (DQE). Lastly, it was determined whether the solid-state a-Se avalanche detector satisfies all of the requirements of interventional radiology. Experimental results have shown that the total noise produced by the detector is negligible and that QNL operation at the lowest fluoroscopic exposures is indeed possible without any adverse effects occurring at much larger radiographic exposures. In conclusion, no fundamental obstacles were found preventing the use of avalanche a-Se in next-generation solid-state QNL FPDs for use in interventional radiology.
Music as The Between: The Idea of Meeting in Existence, Music and Education
Keywords: music
meeting
existence
education
aesthetics
philosophy
meaning

As a violinist, teacher, and thinker, I am concerned to articulate the relevance of music to the lives of my audience, my students and myself. But my concern is not merely to describe the meanings that people experience when they engage music. Rather, I am interested in constituting the musical relevance that each of us must actualize as we work to make our lives vital and meaningful. Accordingly, in my study I articulate in philosophical, yet practical, terms, a particular attitude of musical engagement that I call meeting. Grounded in Martin Buber’s idea of human existence as I-Thou, my conception of meeting has a specific character. Each side of the meeting must meet itself in its work to constitute the adequacy of its engagement with the other as it must meet with the other in its work to constitute the adequacy of its engagement with itself. It follows that the essence of human meeting is not merely the “reality” – physical, cultural, intellectual – of people who come together. Rather, the essence is their self-critical thought that is created as they share their lives with each other. The focus, then, is not the meeting’s outcome but rather the meeting itself insofar as it constitutes mutual understanding, communication and love. Thus, at the heart of my study, I constitute music in the same way, not as a physical or cultural “reality,” but rather as the meeting between music and musical participant that demands that each – music and participant – attend to self and other. The idea that music’s whole being is meeting has profound implications for how we conceive of music education. Accordingly, the ultimate purpose of my study is to bring my ideas of musical meeting to bear upon how we teach and learn music in the classroom.