VictorJuiz/thesis huggingface dataset:
Increased free radical generation, as measured by aldehyde-derived peroxidation products, is observed in the heart with chronic iron-overload

Iron-overload cardiomyopathy is a restrictive cardiomyopathy which manifests itself as systolic or diastolic dysfunction secondary to increased deposition of iron in the heart, and is currently the leading cause of cardiovascular mortality worldwide in the second and third decades of life. Nevertheless, the mechanism of chronic iron-induced heart failure remains to be elucidated. The toxicity of iron in biological systems is believed to be attributed to its ability to catalyze an excess generation of free radicals, which can injure all classes of macromolecules. This thesis examined the effects of chronic iron-loading in a murine model, on (a) mortality; (b) selenium-dependent glutathione peroxidase (GPx) activity; (c) free radical-mediated injury to lipid membranes in the heart as quantified by aldehyde-derived peroxidation products, and (d) cardiac function. In addition, the cardioprotective effects of selenium were examined in this model. Lastly, the effects of chelation with desferal or deferiprone (L1) versus no chelation on measures of body iron burden, red cell GPx activity and plasma aldehyde concentrations were examined in patients with beta-thalassemia major and iron-overload. It was found that chronic iron-loading in a murine model resulted in (a) iron deposition in the heart; (b) decreased selenium dependent GPx activity; (c) increased concentrations of aldehydes (hexanal, malondialdehyde, 4-hydroxynonenal); (d) decreased cardiac function, and (e) increased mortality, in comparison with controls. Iron-loaded mice that received supplementation with selenium had decreased total heart concentrations of iron, preservation of GPx activity, decreased concentrations of aldehydes and decreased mortality, in comparison with iron-only treated mice. Non-chelated beta-thalassemia major patients were found to have decreased red cell GPx activity and increased plasma concentrations of aldehydes, in comparison to similar patients chelated with desferal or L1. Although no single mechanism is likely to account for the complex pathophysiology of chronic iron-induced heart failure, these findings provide evidence that the mechanism of injury and dysfunction involves in part free radical mediated-processes. The identification that a deficiency of selenium secondary to chronic iron-overload may offer renewed promise in the clinical management of patients with chronic iron-overload disorders and cardiomyopathy. A conceptual model of chronic iron-overload is presented.
Renal mesangial cell proliferation regulates proteoglycan levels and sulfation

The kidney responds to injury by progression through a series of stages that can lead to healing of the kidney; but when the insult is repetitive these same stages lead to kidney disease. Glomerulonephritis is a common form of human kidney disease that has been studied extensively using rat kidney disease models. We have sought to understand how the stage of compensatory growth of glomerular mesangial cells influences the mesangial cell production of proteoglycans. Proteoglycans may play a role in regulating glomerulonephritis by regulating the proliferation of mesangial cells and the composition of the mesangial matrix. We have observed that for cultured rat renal mesangial cells (RMCs) the proliferative state regulates the levels and sulfation of proteoglycans. In particular, cell layer and medium proteoglycan levels are lower in randomly cycling RMCs than in relatively quiescent RMCs, and one proteoglycan--biglycan--has enhanced sulfation in randomly cycling RMCs compared to quiescent RMCs. The effects on proliferation of biglycan levels and sulfation do not influence the ability of TGF-$\beta$ to increase biglycan mRNA and protein levels, indicating different pathways of regulation. Our results provide more insight into understanding the role of mesangial cell during the proliferative and fibrotic phases of glomerulonephritis.
The catabolism of glucagon-like peptide 2, a novel intestinal growth factor

The intestinal peptide glucagon-like peptide 2 (GLP-2) is a potent intestinotropic hormone. Previous studies have shown that peptides with sequence homology to the N-terminus of GLP-2 (His$\sb1$-Ala$\sb2$), are cleaved and inactivated by dipeptidyl-peptidase IV (DP IV). We therefore hypothesized that DP IV would also target GLP-2. GLP-2$\sp{1-33}$ was degraded to GLP-2$\sp{3-33}$ in serum from normal and DP IV negative rats, by 69 $\pm$ 104% and 39 $\pm$ 26, respectively, while the bioactive analog Gly$\sb2$-GLP-2 was degraded by only 22 $\pm$ 10% (n = 5, P $<$ 0.01 vs controls). In vivo, GLP-2$\sp{1-33}$ was progressively degraded to GLP-2$\sp{3-33}$ over time in control rats, while DP IV negative rats and normal rats injected with GLP-2$\sp{1-33}$ and Gly2-GLP-2, respectively, showed significantly less degradation (n = 3-6, P $<$ 0.01 and P $<$ 0.001, respectively). Pro-boropro, an in vivo inhibitor of DP IV, also significantly decreased degradation of GLP-2 (n = 3, P $<$ 0.05), confirming that DP IV cleaves GLP-2. In contrast, studies using GLP-2 analogs designed to withstand cleavage by neutral endopeptidase, suggested this protease might not cleave GLP-2. Finally a role for the kidney in clearance of GLP-2$\sp{1-33}$ and GLP-2$\sp{3-33}$ from the circulation was demonstrated by analysis of the half-life of immunoreactive GLP-2 in nephrectomized and non-nephrectomized rats (4.76 $\pm$ 0.45 and 2.62 $\pm$ 0.31 min, respectively, n = 3-6, P $<$ 0.001). In conclusion, the results of this study show that the biological effectiveness of GLP-2 is determined by the actions of DP IV, which degrades GLP-2$\sp{1-33}$ to its inactive form, GLP-2$\sp{3-33}$ and the kidney, which clears GLP-2 and its metabolite from the circulation.
Interactions between two Caenorhabditis elegans sex determining proteins: HER-1 and TRA-2A

The free-living soil nematode 'Caenorhabditis elegans' exists in nature as one of two possible sexes, the male or the self-fertile hermaphrodite. Most genes controlling sex determination in 'C. elegans ' have been cloned and sequenced. These genes have been ordered into a signal transduction cascade based on their epistatic interactions. I have uncovered evidence supporting a direct interaction between the proteins encoded by two of the genes in the pathway, 'her-1' and 'tra-2'. This was achieved through binding assays involving immunofluorescent and immunoblotting techniques. The proposed interaction sheds light on the possible mechanisms by which HER-1 negatively regulates the activity of TRA-2A in male development.
Influences of charged and sterically bulky species upon the morphology and structure of preferential aggregates of collagen

Collagen monomers form a variety of aggregates in solution preferentially, depending upon the conditions to which they are subjected. Preferential aggregate morphology was influenced by modifying the surface charge of collagen monomer by reaction with methylglyoxal, resulting in both a decrease in fibrillar diameter and a change in surface characteristics as compared to the well characterized native collagen and shown by atomic force microscopy. By introducing the bulky, negatively charged Ã1-acid glycoprotein, fibrous long spacing collagen was produced, with a greater fibrillar diameter than native collagen, and surface morphology more like the methylglyoxal modified collagen fibrils. Upon addition of the zwitterionic ATP molecule to collagen, segmental long spacing collagen crystallites may be formed. By 31P-NMR, ATP was shown to be bound within the crystallite, probably through some sort of electrostatic interaction. All of these morphological influences have in common the interaction of charges and varying of steric constraints.
Alterations of PTEN in Li-Fraumeni syndrome (LFS) and solid tumors common to the syndrome

In a significant proportion of LFS families the predisposition to cancer cannot be explained by germline 'p53' mutations. Few other genes have been implicated in this syndrome. The 'PTEN' phosphatase tumor suppressor gene is mutated in human cancers observed in LFS; therefore, it is hypothesized that 'PTEN' may be altered in some ' p53'-wild-type families. LFS primary patient lymphocytes, lymphoblastoid cell cultures and common tumors were examined for 'PTEN' alterations. Germline 'PTEN' mutations were not detected, and a novel intronic deletion found in one LFS-C and one LFS-V individual is predicted to be a polymorphism based on an in vitro mRNA processing assay. 'PTEN' is more frequently deleted in brain tumors relative to osteosarcomas and rhabdomyosarcomas, suggesting that 'PTEN' deletion is a rare event in the pathogenesis of sarcomas. Taken together, these observations suggest that 'PTEN ' alterations do not account for cancer in the subset of LFS individuals with wild-type germline 'p53'.
Checking the blind spot, the inevitability of theory in the Ontario secondary school English classroom

This thesis concentrates on the application of research I have undertaken in literary theory to a set of problems I encountered in my professional practice as a secondary school English teacher. I argue that, although the last three decades has been a period of much ferment in both the universities and the high schools, the changes that have occurred in these two educational environments have been fundamentally different ones, and that this distinction has largely been overlooked. In most university English classrooms, the traditional New Critical approach to teaching literature has been 'problematized' as a result of challenges from a range of alternative theories. In most high school classrooms, however, the traditional New Critical approach has been ' replaced' by a less traditional Reader Response approach, but most Reader Response classrooms are no more problematized than the New Critical classrooms which preceded them. The failure to distinguish between these two different histories has led, in the high schools, to a situation in which Reader Response Practice has been thought to have solved the major problems inherent in New Critical Practice. I argue, however, that Reader Response practice cannot genuinely solve these problems because it does not address the issue that lies at the centre of New Criticism, which I call the issue of 'what counts'. I argue that Reader Response Practice cannot address this issue because the limits on what counts are determined by theory, and because Reader Response Practice is no more problematized than New Critical Practice, teachers are still positioned so that theory remains in the ' blind spot'. I show how both the 'garden path problem' which characterizes New Critical Practice and the 'interpretation problem ' which characterizes Reader Response Practice are symptoms of an unproblematized classroom. I argue that, in order to solve these problems, classroom practice in the high schools needs to be problematized much like it has been in the universities, so that teachers may check the blind spot and the limits on what counts may be made more explicit and in fact renegotiated. In the last chapter of the thesis, I describe a problematized practice with which I am currently experimenting in my own high school classroom, one which offers a solution to both the 'garden path problem' and the ' interpretation problem'.
The neural basis of the effects of aging on temporal processing in the rat primary auditory cortex

One complaint among the elderly is a difficulty in understanding speech. One factor that may contribute to this, is an age-related deterioration in temporal processing speed, manifested as a decreased ability to process dynamic aspects of speech such as formant transitions. The goal of this study was to explore the neural basis of the effects of aging on auditory temporal processing. A useful stimulus for this investigation is the frequency-modulated (FM) sweep which resembles formant transitions. Extracellular single unit responses were recorded in the auditory cortex (AI) of young and old male Long Evans hooded rats. Tone bursts were presented followed by linear FM sweeps (from low to high and from high to low) at different rates of modulation. Results show that the majority of cells recorded from young rats responded best to fast FM sweeps while those from old rats preferred slower speeds. This suggests a neurophysiological basis for the difference in cortical temporal processing speed between young and old rats for dynamic stimuli.
Differential hydration of protein analogs in D¦2 and H¦2O

The partial molar volumes, V0, and adiabatic compressibilities, KS, of five Ã-amino acids and five oligoglycines have been determined in D2O at 250. In addition, the partial molar volumes, V°, expansibilities, E°, and adiabatic compressibilities, K°S, for a homologous series of eight Ã,[omega]-aminocarboxylic acids in D2O solution have been determined within the temperature range 18 to 55°C. The resulting data have been used to estimate the volume, expansibility, and compressibility contributions of the component aliphatic, polar and charged groups. We used these data to characterize quantitatively the differential hydration properties of charged and hydrophobic groups in D2O and H2O. Our results suggest that the hydration properties of component groups in D2O are measurably distinct from those in H2O in their absolute values and in their temperature dependences. These results represent a step in building up an empirical database of differential volumetric parameters of protein functional groups in D 2O and H2O. Such a database is required for developing a methodology in which insights into the number and chemical nature of solvent-exposed protein groups can be gained from differential volumetric measurements in the absence of structural information.
RNA-binding of LC3 to the AU-rich element of fibronectin mRNA, a structural and functional study

During neointima formation in the fetal ductus arteriosus (DA) and in diseased coronary arteries, migration of smooth muscle cells (SMC) is modulated by upregulation of fibronectin (FN). This involves increased translation of FN mRNA when microtubule-associated protein 1 light chain 3 (LC3) binds an AU-rich element (ARE) in the 3' untranslated region (3'UTR) of FN mRNA. We now investigate how LC3 binds to the ARE by generating LC3 peptides and mutant LC3, followed by northwestern (NW) immunoblotting and electrophoretic mobility shift assay (EMSA). The positive charge of 3 arginine residues (the arginine-rich motif)(ARM) appears critical for LC3-ARE binding. The significance of this motif in regulating FN mRNA translation is demonstrated by stably-transfecting wild-type (WT) vs mutant LC3 into LC3-null HT1080 human fibrosarcoma cells and observing increased fibronectin with wild-type LC3 only, associated with an elongated, slower growing phenotype.
The role of the AMPA receptor GluR2 subunit in anesthetic neurodepression and excitotoxic cell death

The AMPA subtype of glutamate receptor mediates fast excitatory neurotransmission. This ligand-gated ionotropic receptor is composed of multiple subunits (GluR1, GluR2, GluR3, and GluR4). In particular, the GluR2 subunit is present in the majority of AMPA receptors in the forebrain and imparts reduced calcium permeability, insensitivity to polyamine inhibition, sensitivity to barbiturate inhibition and influences the localization of these receptors to the synapse. The objective of this thesis was to determine the importance of the GluR2 subunit in physiological, pharmacological, and pathophysiological processes. Specifically, the roles of the AMPA receptor GluR2 subunit in anesthetic-induced neurodepression, excitatory neurotransmission, and neuronal excitotoxicity were investigated. 'In vitro' electrophysiological studies revealed a decreased potency of barbiturates for the inhibition of GluR2-deficient AMPA receptors. In contrast, behavioral studies demonstrated that GluR2 null mutant (-/-) mice were more sensitive to pentobarbital than wildtype (+/+) mice. These results suggest that the inhibition of AMPA receptors does not contribute to the neurodepressive effects of barbiturates in this mouse model. These findings were corroborated by behavioral studies demonstrating that the (-/-) mice were also more sensitive to volatile anesthetics, which do not appreciably inhibit AMPA receptors. Therefore, the inhibition of AMPA receptors does not underlie anesthetic-mediated neurodepression. Instead, we postulated that a reduced excitatory neurotransmission in (-/-) mice renders then more sensitive to general anesthetics. A reduced excitatory neurotransmission 'in vitro' was demonstrated by the decrease in the fast component of evoked excitatory postsynaptic current (EPSC) recorded from (-/-) hippocampal slice. In contrast, AMPA receptor-mediated miniature EPSCs in cultured (-/-) hippocampal neurons were unaltered, suggesting that a normal AMPA receptor complement exists at synapses activated by the spontaneous release of glutamate. The increased kainate-evoked current density measures in (-/-) neurons were suggestive of an enhanced expression of extrasynaptic AMPA receptors. These results are consistent with a reduced localization of GluR2-deficient AMPA receptors to some synapses. In addition, kainate excitotoxicity was studied in the and (-/-) mice. 'In vitro' and 'in vivo' experiments demonstrated unchanged neuronal death, despite increased calcium influx into (-/-) hippocampal cultured neurons. In summary, absence of the GluR2 subunit contributes to a reduced synaptic neurotransmission and increased anesthetic-induced neurodepression, without enhancing excitotoxic neuronal injury.
From watchful eye to bureaucratic formality, the evaluation of teacher performance in Ontario from 1870 to 1999

This document presents a synthesis of trends from 1870 to 1999 in teacher evaluation in the Ontario school system which includes four eras which overlap each other and are not so fixed as these rough time frames might suggest: the "inspection era" (1870s-1900s); the "scientific evaluation" era (1920s-1930s); the "humanist assessment" era (1960s-early 1970s); and the "business oriented, back to basics" performance review era of the 1990s. It is argued that explicit and implicit purposes of teacher evaluation have not significantly changed and that classroom observation is still the main source of data in evaluating teacher effectiveness. An examination follows of 20 teacher reports dating from 1982-1998, from one Ontario school board. Issues in the data include: the effect of gender in the report, the lack of consistent use of criteria, the non-critical tone of the reports and the use of questionable criteria. The author concludes with a review of new research advocating increased teacher autonomy along with a critique of the conservative political climate that resists progressive changes.

Keywords: Teachers
Rating of
History
Enseignants
Évaluation
Histoire
Efficient online algorithms for multicasting with bandwidth and delay guarantees

This work proposes a novel paradigm for online multicasting with bandwidth and delay guarantees. We first address the issue of online maintenance of multicast tress, namely the case where the topology of the multicast network is confined to trees. Next, motivated by examples that demonstrate the inefficiency of tree-bead multicast graphs, we waive this requirement. Instead, multicast information is delivered to the participants by means of dedicated virtual circuits. Our solutions observe the following guidelines: (i) Satisfaction of bandwidth and delay requirements imposed by individual users; (ii) Feasibility with respect to constraints such as the capacity of links; (iii) Online handling of join/leave requests; (iv) Dual objectives, i.e., maximization of total admitted users while keeping the overall cost sufficiently small; (v) Performance guarantees related to the cost incurred by each admitted user; (vi) Provably low time-complexity; and (vii) Efficient reclaiming of resources. Previous research has failed to comply with several of the above specifications.
Comparing angiographic coronary revascularization strategies, a "natural" experiment

Objective. To compare rates of clinical restenosis between routine angioplasty and coronary stenting in the real world. Design. A retrospective cohort analysis comparing markers of clinical restenosis between patients exposed to liberal and conservative coronary stenting policies. Setting. At a tertiary care, high-volume Canadian institution, patients who underwent percutaneous coronary interventions were captured in a database. Patients. Individuals undergoing angiographic revascularization during a period of economic restraint (the 'conservative' group (C)) from January 1 to February 28 1996, were compared to a before and after cohort, where coronary stent use was at 'usual', higher levels (the liberal group (L), November 1 to Nov 30, 1995 (L1), and April 1 to May 31(L2) 1996). Follow up. Data was gathered retrospectively. The endpoint was the first of any of the following within nine months: death, MI, CABG, repeat PTCA, or repeat coronary angiography. Results. There was no difference in clinical restenosis rates between conservative (N = 147) and liberal (N = 232) groups: 34.7% vs 37.9% respectively, p = 0.524 (OR C/L = 0.915, 95% CI (0.694-1.206)). Conclusions. At our institution, a conservative stenting policy did not result a higher clinical restenosis rate than that of a liberal policy.
A model of cancer immunotherapy via immunoencapsulation of gene-modified tumour cells

Tumour antigen was delivered simultaneously with cytokine utilizing a subcutaneously implantable microencapsulation device. It was hypothesized that animals bearing encapsulated cytokine secreting tumour cells would demonstrate a survival benefit vs control animals after tumour challenge. Tumour lines included B9/BM1 myeloma. (Balb/c), MCA-38 colon carcinoma, and MMB leukemia (C57BL/6). Cytokines included interleukin-12. (IL-12), granulocyte-monocyte colony stimulating factor (GM-CSF), and soluble Flt3 ligand (sFlt3L). ' In vivo' devices contained viable B9/BM1 tumour up to 70 days, 145 days for MCA-38, and 166 days for MMB. Device secreted IL-12 was detectable for seven weeks 'in vitro' and 3 weeks 'in vivo'. Challenge experiments demonstrated no survival advantage for groups bearing B9/BM1 or MCA-38 encapsulated cells. In animals bearing encapsulated MMB cells no differences amongst lymphocyte subsets, nor in CTL cytotoxicity against MMB cells, were detected. Animals implanted with encapsulated IL-12 gene modified cells before MMB turnour challenge did display a trend towards increased survival.