VictorJuiz/thesis huggingface dataset:
Understanding the functions of molecular chaperones and thiol oxidoreductases in MHC class I biogenesis

Calnexin (CNX) is a membrane protein of the ER that functions as a molecular chaperone and as a component of the ER quality control machinery. Calreticulin (CRT), a soluble analog of CNX, is thought to possess similar functions but these have never been directly demonstrated. Using a 'Drosophila' expression system and the mouse class I histocompatibility molecule as a model glycoprotein, we found that CRT does possess apparent chaperone and quality control functions, enhancing class I folding and subunit assembly, stabilizing subunits, and impeding export of assembly intermediates from the ER. Indeed, the functions of CNX and CRT were largely interchangeable. We also determined that a soluble form of CNX (residues 1-387) can functionally replace its membrane-bound counterpart. However, the different topological environments of CNX and CRT are important in determining their distinct substrate specificities. CNX and CRT bind to glycoprotein substrates in part through a lectin site specific for monoglucosylated (Glc1Man7-9GlcNAc 2) oligosaccharides. In addition to this lectin-oligosaccharide interaction, ' in vitro' studies have demonstrated that CNX and CRT can also bind to polypeptide segments of both glycosylated and non-glycosylated proteins. We examined whether polypeptide-based interactions occur between CNX and its substrates in cultured cells. We demonstrate that CNX is capable of associating ' in vivo' with a substrate that completely lacks Asn-linked oligosaccharides. We conclude that both lectin-oligosaccharide and polypeptide-based interactions occur between CNX and diverse proteins in such a system and that the strength of the latter interaction varies substantially between protein substrates. ERp57 is a thiol oxidoreductase that binds to CNX and CRT and, at least ' in vitro', can promote disulfide bond formation in glycoproteins that interact with CNX or CRT. As yet, there is no direct information concerning how ERp57 functions in class I biogenesis. By using a heterologous ' Drosophila' expression system, we showed that ERp57 does not affect the formation of the disulfide bond in cells expressing free H chain. Furthermore, the rate of class I molecules folding and assembly with ß2m remains unchanged in the presence of ERp57. These are important findings that challenge the current view of ERp57 function in class I biogenesis.
Temporo-spatial expression of Ets1 and Ets2 transcription factors during murine tooth development

Ets1 and Ets2 belong to the Ets group of transcription factors that show wide spread expression during embryonic development and exhibit discrete mesenchymal and epithelial patterns of expression during organogenesis. The purpose of this study was to map the expression of Ets1 and Ets2 during tooth formation in detail. E10-E20 mouse embryos and postnatal day 1-5 mice were examined using radioactive in situ hybridization. Restricted patterns and varying intensities of Ets1 and Ets2 expression were seen in mesenchymal and epithelial tissues during all stages of tooth formation. Ets1 expression was restricted to the dental papilla mesenchyme, dental sac and developing odontoblasts during early stages of tooth development (bud, cap and bell stages). At differentiation and secretory stages, Ets1 expression was maintained in the dental mesenchyme and its derivatives including odontoblasts. Ets2 expression was noted in the local thickening of oral epithelium, enamel organ, and outer and inner enamel epithelium at early stages of tooth development and was detected in differentiated ameloblasts and odontoblasts during differentiation and secretory stages. RT-PCR analysis confirmed the constitutive expression of Ets1 and Ets2 in odontoblasts. This study documents the expression of Ets1 and Ets2 genes and suggests roles for these transcription factors during tooth development.
Can internal elastic properties of cartilage be measured using MR elastography?

Cartilage has internal variations in molecular structure, composition and possibly mechanical properties depending on position within and location of the tissue within the joint. I have examined the possibility of using MR Elastography as a way to measure the internal variations in elastic properties of cartilage. An apparatus was built to compress cartilage and coils were made to obtain the necessary SNR and resolution. Strain data was obtained in homogeneous gel samples. Changes in strain on the order that would be expected for samples differing in Young's modulus by a factor of 2 were measured. Strain was then measured in Young bovine cartilage samples and found to vary both within the sample and between samples. Cartilage proteoglycans were degraded with trypsin, softening the tissue, and the corresponding increase in strain was measured. Strain images and plots representing variations in elastic properties of cartilage were obtained using MR Elastography.
Constraining the fate of chlorinated ethenes in groundwater systems using stable carbon compound specific isotope analysis

The isotopic effects of subsurface processes on the stable carbon isotopic composition, [delta]13C, of chlorinated ethenes were investigated using Compound Specific Isotope Analysis (CSIA). Headspace analysis was determined to be a robust, simple and effective method for sample preparation and analysis using Gas Chromatography-Combustion-Isotope Ratio Mass Spectrometry (GC-C-IRMS). No significant isotopic fractionation (>0.5 &permil;) was observed during equilibrium volatilization of the chlorinated ethenes from aqueous solution. Further, no significant isotopic fractionation (>0.5 &permil;) was associated with equilibrium sorption of TCE and PCE. These results confirmed the hypothesis that non-degradative, physical subsurface processes would not result in significant isotopic fractionation of the [delta]13C of the chlorinated ethenes. In contrast, degradation of the chlorinated ethenes resulted in large isotopic enrichments of the residual reactant in 13C, consistent with preferential reaction of molecules containing the lighter 12C isotope. This isotopic enrichment could be described by a Rayleigh model enrichment factor ([epsilon]). Rayleigh enrichment factors ([epsilon]) described isotopic fractionation of the chlorinated ethenes during microbial reductive dechlorination of most of the chlorinated ethenes, during abiotic reductive dechlorination of TCE by zero-valent iron, and during aerobic co-metabolic degradation of TCE by toluene ortho-monooxygenase. Enrichment factors varied with specific microbial consortia, with degradation pathway (reductive dechlorination versus aerobic co-metabolism); and for abiotic experiments, with different iron types and surface treatments. The observation of these isotopic enrichment trends indicated that CSIA can provide direct evidence of the occurrence of chlorinated ethene degradation in the field, independent of mass loss due to non-degradative subsurface processes. CSIA was applied at three field sites. These studies confirmed that the [delta] 13CTCE can be conserved at a site where plume geometry is controlled by advective and partitioning processes. Most importantly, they confirmed that CSIA could give direct confirmation of the occurrence of degradation of the chlorinated ethenes at field sites. Therefore CSIA of the [delta] 13C of the chlorinated ethenes represents a powerful tool for the investigation and monitoring of sources and fate of chlorinated ethenes in subsurface systems.
Shoreline residential development and physical habitat influences on fish density at the lake edge of Lake Joseph, Ontario

Fish densities in the littoral fringe zone (0-2.5m offshore, average depth = 0.53m), within a large Central Ontario lake, were investigated with respect to shoreline structure (docks and boathouses) density and physical habitat characteristics. Both categorical (ANOVA) and continuous (multiple linear regression and regression tree) data analysis concluded that coarse woody debris (CWD) was the most important habitat variable for explaining and predicting densities of total forage fish. YOY smallmouth bass, were a notable exception since they appeared to lack a preference for spatially complex habitats. Fish densities in the fringe zone and around shoreline structures, showed that in some areas the addition of shoreline structures can increase forage fish densities. This is probably because the structures add structural complexity which can increase protection from both waves and predators. The habitat created by crib foundations appeared to be of importance in areas in which the CWD has been removed by shoreline residential owners.
Gas plasma polymer surface modification methodologies for the reduction of device related infection

This research attempted to developed materials resistant to device related infection. First, water, ammonia or carbon dioxide plasmas were utilized in a remote microwave plasma (RMP) reactor. Increased hydrophilicity of the surface in water and ammonia plasma treatments was noted. A reduction in colony forming units was noted with water plasma treatment when challenged with ' Pseudomonas aeruginosa' under static flow in the presence of ciprofloxacin. To illustrate the ability of attaching a drug delivery system activation with primary amines was required with ammonia plasma on ethylene treated polyurethane (optimised separately). An optimum using the RMP plasma was found at 408 sccm, 20 W power and 1 minute. Attachment of a drug delivery system through primary amine groups was assessed using isocynate chemistry and a commercial fluroalcohol. Surfaces with the activation registered a fluorine signal proving the feasibility of attaching a drug delivery system through this chemistry.
A robust distrubuted storage system for large information retrieval applications

This thesis presents an architecture and design for a Robust Distributed Storage System (RDSS) targeted at digital library, multimedia, and information retrieval applications, and implemented on networks of low-cost workstations or personal computers. In particular, the system addresses problems associated with managing large distributed indices in the context of these applications. The RDSS provides a framework for scaling a single-node server to create a reliable distributed system. In addition to performance benefits achieved by distributing these applications, the RDSS provides efficient data mirroring, on-line failure recovery, and node management.
Regulation of fibronectin synthesis by nitric oxide dependent phosphorylation of LC3 and by a map kinase dependent mechanism

Intimal cushion formation in the fetal ductus arteriosus (DA) requires fibronectin (FN)-dependent smooth muscle cell (SMC) migration. Nitric Oxide (NO) mediates increased FN mRNA translation in DA SMC through phosphorylation and binding of LC3, a microtubule-associated protein, to an AU rich element in the 3' UTR of FN mRNA. To investigate the mechanism whereby NO regulates LC3 phosphorylation, we assessed the influence of kinase inhibitors on FN synthesis. While extracellular signal-regulated kinase inhibition suppressed FN synthesis, this was not related to reduced LC3-mediated FN mRNA translation. We then sought to determine the specific NO-dependent phosphorylation site using an LC3 tagged green fluorescent protein (GFP) construct, transfected into DA SMC. In contrast to the perinuclear and microtubule associated distribution of native LC3, immunofluorescence was observed in vacuoles in LC3-GFP transfected cells and was increased by NO. Western immunoblotting revealed a truncated phosphorylated LC3-GFP, explaining the vacuolar distribution.
Bayesian empirical applications of generalized stochastic volatility models

This dissertation examines three empirical finance applications of univariate, multivariate and generalized specifications of discrete-time stochastic volatility (SV) models. These models are applied on daily stock index return data from the Toronto Stock Exchange. The SV parameters are estimated by implementing existing Bayesian Markov Chain Monte Carlo (MCMC) econometric methods. The main objective of the dissertation is to assess the ability of stochastic volatility to (i) forecast the daily conditional variances and covariances implied by daily returns, and (ii) hedge against adverse return movements. Models of stochastic volatility are designed to parsimoniously capture the time-series properties of daily returns, notably the asymmetry, fat tails and persistence of the conditional and unconditional distributions. The dissertation examines the conditional dynamics implied by all relevant SV specifications, computes one-step ahead volatility forecasts, and assesses the contribution of stochastic volatility to risk management.
The Orlando Furioso in print, 1516-1542, an historical study and a descriptive bibliography

The aim of this dissertation is to reconstruct the history of Ludovico Ariosto's 'Orlando Furioso' as a material object from the 'editio princeps' of 1516 to Gabriele Giolito's edition of 1542. The analysis is based on the physical evidence derived from the direct examination of extant copies of the thirty-six editions that appeared during the period under consideration. My primary concern is the evolution of the formal presentation of the 'Furioso', and specifically the physical features of format, layout, illustration, decoration, and size and styles of type. The Introduction sets out the methodological bases of the dissertation, namely historical bibliography for Part I, and analytical and descriptive bibliography for Part II; it also provides a survey of previous work on the subject. Although I have drawn to some extent on these prior studies, the application of Anglo-American bibliographical techniques to the early editions of the 'Furioso' represents an original contribution to the scholarship on Ariosto's work. The five sections of Part I examine the major phases in the physical history of the 'Furioso' to 1542: the three editions published in Ferrara during Ariosto's lifetime; the commercial success achieved by the work from 1524 to 1531; the first illustrated editions by Nicolò Zoppino; the other much-imitated formula, inaugurated by Francesco Bindoni and Maffeo Pasini in 1535, of including commentaries designed to aid the reader; Giolito's integration of illustration and commentary, and the consequent redefinition of the 'Furioso''s physical form. Part II is a descriptive bibliography of the thirty-six editions examined. It is designed to provide a detailed, technical basis for Part I, and it also functions independently as a standard against which copies in addition to those examined here may be analyzed. The dissertation includes a short list of the editions and a glossary of bibliographical terms.
Enzyme mediated degradation of L-phenylalanine based segmented polyurethaneureas

Two important parameters in the development and use of degradable biomaterials are related to the potential toxicity of the degradation products and the rate of material degradation when placed in the human body. This research focused on determining the degradation products from degradable segmented polyurethaneureas synthesized using LDI; a chain extender based on L-phenylalanine; and [epsilon]-polycaprolactone or polyethylene oxide. L-phenylalanine residues were incorporated into the polyurethane backbone in order to introduce sites for enzyme-mediated degradation. The polyurethanes were characterized using GPC and elemental analysis. Degradation studies were carried out by incubating the polyurethanes for 8 weeks in tris buffered solutions containing chymotrypsin at 37°C and pH 8. Degradation was assessed by HPLC and MS. Three degradation products associated with the hard segment of the polyurethane were isolated and their chemical structures were determined. The study concludes that the hard segment region containing the amino-acids is effectively cleaved by the enzyme.
A model to predict the effects of air-water gas exchange on lindane concentration in Lake Ontario

DYRESM, a one-dimensional model that predicts the vertical temperature distribution in lakes, was modified to include concentrations of soluble chemicals resulting from air-water gas transfer. The new model was applied to Lake Ontario to determine concentrations of the pesticide Lindane for several scenarios over one to four year periods. Air-water gas exchange was found to be a dominant process affecting Lindane concentration in Lake Ontario. Lindane's solubility was the most important factor for determining the direction of gas flux. Predictions from a baseline simulation for the International Field Year on the Great Lakes (1972-1973) were similar to measured concentrations of approximately 0.4 $ng\ L\sp{-1}$ during the summer months and 0.3 $ng\ L\sp{-1}$ during the winter. Lindane was determined to be deposited by air-water gas exchange in spring and summer, and volatilized in autumn and winter, with a net annual deposit to Lake Ontario.
Modulation of oscillatory activity in inhibitory neuronal networks by anesthetics, the role of receptor desensitization

Anesthetics significantly alter inhibitory signalling in the brain, and oscillatory activity in inhibitory networks in the CNS can play an important role in supporting the cognitive processes disrupted by anesthetics. The aim of this study is to identify a dynamic mechanism for the disruption of oscillatory network activity by anesthetics that may explain the impairment in cognitive function seen with these drugs. The effect of anesthetic modulation of IPSPs on network activity is examined using model neurons connected by GABAergic synapses. The results show that the anesthetics propofol and midazolam can both disrupt synchronous activity in these networks, but the mechanisms differ based on the differential effects on the kinetics of deactivation and desensitization of inhibitory signals seen with these two drugs. The results illustrate that the interplay between kinetics at the synapse and their resultant effects on network dynamics is a complex, non-linear relationship that requires a theoretical analysis.
Speechio delle rare e virtuose donne, the role of the female interlocutor in the sixteenth-century dialogues on love

According to some scholars, the middle years of the sixteenth century represent a period of "feminism" within the Italian literary tradition. This is a remarkable assertion that has yet to be fully investigated. Focusing on a group of "minor" texts of the period, specifically dialogues on love, this dissertation traces a particular character, the female interlocutor engaged in discussions on love. The principal dialogues analyzed in this study are by Leone Ebreo, Sperone Speroni, Tullia d'Aragona, Giuseppe Betussi, Marcantonio Piccolomini, and Girolamo Bargagli. All of these works are documentary in nature and therefore serve as reflections of social phenomena. Thus the female interlocutor can be approached, not just as an interesting literary figure, but also as the reflection of an historical figure. Much critical attention has been focused on the more famous dialogues of the period, Pietro Bembo's 'Gli Asolani' and Baldassare Castiglione's 'Il libro del cortegiano', and on the generally passive nature of the female interlocutors in these works. In contrast, the minor dialogues on love have only rarely been the object of study. Within a particular category of love dialogues, however, intellectually engaged female characters are portrayed. By tracing the emergence of a female voice and the use of a genre that was uniquely capable of presenting that voice, namely, dialogue, this study is an attempt to shed light on the role that women played in an intellectual and cultural environment steeped in Neoplatonic theories of love. The ways in which the female literary figure transcends conventional restrictions governing women's behavior are discussed, as are the limitations within which the figure is depicted. Furthermore, drawing from recent studies on dialogue by Virginia Cox, Olga Zorzi Pugliese, Francesco Tateo, and Nuccio Ordine, I examine the presentation of female characters while recognizing the unique hermeneutical demands of the genre. The methodologies of these critics and their innovative approach to Renaissance dialogues aid in understanding the success of this genre in the period, and therefore provide the critical tools for an investigation of the female interlocutor.
The role of Epstein-Barr virus in oncogenesis

Epstein-Barr virus (EBV), the human herpesvirus 4, is a ubiquitous pathogen associated with a wide spectrum of human epithelial and lymphoid malignancies, including nasopharyngeal carcinoma (NPC), Hodgkin's disease, and immunoblastic lymphomas of immunocompromised hosts. I have sought to understand the role of EBV in oncogenesis through both clinical and basic science studies. NPC, a tumor endemic in Pacific Rim countries, is difficult to diagnose early with consequently poor prognosis. In a Phase I clinical trial, the promise of nasopharyngeal brush biopsies for the detection of EBV DNA as an early diagnostic of NPC was developed and tested. EBV genomic DNA sequences were detected using a multiplex polymerase chain reaction system. Predominantly Asian patients with various otolaryngological conditions (n = 178, 21 with NPC) underwent nasopharyngeal brush biopsy. Demonstration of EBV DNA in nasopharyngeal brush biopsy specimens detected NPC with a sensitivity of at least 90% and a specificity of approximately 99%. The promise of this technique as a possible ambulatory screening strategy in high-risk populations has resulted in its progression to a large Phase II trial in the U.S.A., Canada, and Asia. EBV efficiently infects and growth-transforms human B lymphocytes ' in vitro'. To understand this growth transformation process, I have used a cDNA subtraction strategy for identification of EBV-induced genes in freshly infected B cells. I cloned and characterized a new cellular C 2H2 (Krûppel-type) zinc finger gene, 'ZNF EB', which maps to 18q12, a region with mutations in numerous, predominantly hemopoietic malignancies, RT-PCR analyses show that ZNF EB transcripts are transiently induced in B cells activated by crosslinking surface immunoglobulin or by mitogen, and are highly expressed in B cells (both lines and acutely infected cells) that support EBV latent infection. Preliminary studies show that ZNFEB may be a downstream effector of the EBV latent membrane protein 1. Importantly, when ZNFEB expression is inhibited through antisense-mediated mRNA degradation, EBV-induced B cell proliferation is abrogated. These data suggest that ZNFEB is a critical player in the EBV-mediated growth transformation of B lymphocytes.
Frictional resistance evaluation of orthodontic brackets and archwires with sliding mechanics using quantified simulation of canine retraction

The purpose of this study was to evaluate by quantitative analysis the frictional resistance of bracket/archwire combinations using an experimental canine retraction model capable of tipping and uprighting to approximate orthodontic tooth movements representative of sliding mechanics. The friction testing apparatus for this study was comprised of an Instron testing machine apparatus, a load cell, and a servomotor interface for second order bracket control. This study demonstrated significant effects for bracket type, archwire type, archwire size, and archwire shape, as well as pair-wise interactions for bracket type/archwire type, bracket type/archwire size, bracket type/archwire shape, archwire type/archwire size, archwire type/archwire shape, and archwire size/archwire shape.