VictorJuiz/thesis huggingface dataset:
Coordinated induction of apoptosis and extracellular matrix resorption reverses severe pulmonary vascular disease

Progressive pulmonary vascular disease (PVD) is characterized by smooth muscle cell (SMC) proliferation and migration leading to the formation of occlusive lesions. Reported in this thesis is the co-distribution of the extracellular matrix (ECM) glycoproteins fibronectin with migrating SMC and tenascin-C with proliferating SMCs in pulmonary arteries (PAs) from patients with congenital heart defects and pulmonary hypertension. As tenascin-C is regulated by mechanical stress, we investigated the response of SMCs in the whole vessel using either normal or hypertrophied PAs from piglets and rats embedded in 'attached' versus 'floating' collagen gels. While no difference in medial wall thickness was observed with normal PAs, hypertrophied rat PAs showed increased elastase, matrix metalloproteinase (MMP)-2, tenascin-C, and SMC proliferation correlating with progressive medial thickening. In contrast, reduction of these features on floating collagen was related to induction of SMC apoptosis and loss of excess ECM, causing regression of the thickened media. This response was recapitulated by direct inhibition of either serine elastases or MMPs. However, selective repression of tenascin-C by antisense induced SMC apoptosis and arrested vascular thickening, but failed to induce regression. We related this to the concomitant expansion of a tenascin-independent SMC population which received pro-proliferative signals similar to tenascin-C from an alternative Ãvß3 ligand, osteopontin. Induction of apoptosis and regression by proteinase inhibition was related to the unclustering of ß3 integrins following loss of Ã vß3 ligation to both tenascin-C and osteopontin. The regression of PA medial thickening documented in organ culture was then extended to the intact rat where the reversal of fatal PVD by oral serine elastase inhibitors resulted in normalization of PA pressure and morphometric features. Taken together, these data demonstrate a critical role for ß 3 integrin ligating ECM survival factors, like tenascin-C, in the progression of PVD. Regulating the availability of such factors, through the control of proteinase activity or accessibility of Ãvß3 receptors, may offer novel therapeutic options for this disease.
Collocation, connotation, contamination, analyse sémantique et diachronique des collocations du type adjectif et femme/homme

Cette thèse analyse le fonctionnement des collocations de type adjectif et 'femme'/'homme' présentant un sens différentiel, telles que 'une grandé femme' "une femme grande" et 'un grand homme' "un homme remarquable intellectuellement". Dans un premier temps, et àpartir d'un corpus synchronique, j'observe que les collocations adjectif et ' femme' présentent une connotation sexuelle ou péjorative. Dans un deuxième temps, une étude diachronique me permet de montrer que, quelle que soit la période concernée, cette polarisation sexuelle et/ou péjorative est constante. Me référant aux études antérieures sur les collocations adjectif et nom, je montre que le phénomène précédemment décrit n'avait jamais fait l'objet de recherches. Les autres linguistes s'étaient concentrés sur la différence de sens notée lors de l'antéposition de l'adjectif uniquement. Ils en avaient alors conclu que le glissement syntaxique de l'adjectif devant le nom était la cause de ce changement de sens. Cependant, dans le cas de mes collocations, le rôle du nom--et donc le sens de celui-ci--semble bien être l'origine de la différence de sens observée, et non la position de l'adjectif. Le nom qualifie, dans une certaine mesure, l'adjectif. Selon cette hypothèse, l'origine de la sexualisation des collocations est le sème/fèminin/contenu dans 'femme'; ce sème/féminin/est lui-même marqué du sème/sexué/. Cette hypothèse s'appuie sur des travaux en ancien français de Grisay et al (1969) et en français moderne de Martin-Berthet (1981) qui ont noté la péjoration et la sexualisation des mots du paradigme "être féminin". Je formalise ce phénomène de qualification de l'adjectif par le nom en appliquant les principes élaborés dans le 'Generative lexicon' (Pustejovsky, 1995). Cependant si la linguistique me permet de poser le féminin comme/sexué/, il faut me tourner vers le discours social et historique pour expliquer l'origine de cette sexualisation et de cette péjoration. Je conclus que la péjoration est liée à l'association de la femme au concept tabou qu'est le sexe. Cette association s'est faite au cours des siècles par l'intermédiaire de pratiques discursives qui ont construit le genre féminin à des fins de pouvoir ou d'affirmation.
Autonomous folding of transmembrane helices, characterization of M13 coat protein dimerization motifs in a peptide system

Helix-helix interactions between transmembrane (TM) segments are of vital importance to the structure and function of membrane proteins. However, due to technical challenges brought about by the extreme hydrophobic nature of most TM segments, only a handful of membrane proteins structures have been solved at the atomic level. To investigate the feasibility of examining residue-dependent helix-helix interactions between TM segments in a simplified tertiary structure, we compared the thermal behavior of M13 proteins with the corresponding peptide variants. The peptide construct CKKK-TM-KKK, was modeled after a series of hydrophobic Ala-based peptides which were designed to be soluble in both water and membrane environments. The formation of hairpin structure is promoted by the S-S bridges between N-terminal Cys, residues. Statistical analysis of over 5000 entries in TMbase (a database of TM segments at http://ulrec3.unil.ch/pub/tmbase) suggests that over 96% of naturally-occurring TM segments can be incorporated in this generic construct and enable spontaneous membrane insertion. The strength of helix-helix interactions was assessed in terms of the propensity of the peptide/protein to undergo heat induced Ã-helix [right arrow] ß-sheet transition. The three peptide mimics (WT, V29A and V31A) demonstrated thermal stabilities in the same rank and order as the intact M13 proteins, and therefore the relevant helix-helix tertiary contacts am likely preserved in the peptide systems. Molecular dynamics simulations using a global conformation search method confirmed the tight 'two-in-two-out' ('i.e'. two residues in the protein-protein interface followed by two residues in the lipid interactive face) dimerization motif for V31A, consistent with mutagenesis data. The overall results support the notion of TM segments as autonomous folding domains, and suggest that the generic peptide construct provides a viable reductionist system for membrane protein structural and computational analysis.
Immunoreactive p53 protein as a prognostic indicator in ovarian carcinoma

In ovarian carcinoma, the prognostic significance of p53 protein accumulation, usually reflecting p53 gene mutation, remains to be established. Using a sensitive immunofluorometric assay for p53 protein quantification, we evaluated p53 overexpression in relation to patient survival and to clinicopathologic factors including age, stage, grade, histotype, tumor size, and presence of residual tumor. In Cox regression analysis, p53-positive patients exhibited two-fold higher risk for both relapse and death, but at the multivariate level, p53 accumulation was not independently associated with patient outcome. After stratification by factors associated with p53 status and outcome, patients with well or moderately differentiated cancers were shown to have higher risk of relapse (p < 0.01) and death (p < 0.01) when p53 protein accumulation was present. Kaplan-Meier analyses confirmed these findings, which together indicated that mutant p53 protein in ovarian carcinoma is associated with poor prognosis in patients with low grade tumors, early stage, or absence of residual tumor.
The effects of stress on ß1 thyroid hormone receptor immunoreactivity in brain

The goal of this project was to determine whether stressful conditions could produce changes in ß1-like immunoreactivity in rat brain. Three stress models were used. First, social isolation was examined, but produced no changes in ß1-like immunoreactivity in the brain regions examined. Second, uncontrollable foot shock, a model of depression and a more intense form of stress, was utilized but also suggested a lack of plasticity in the ß1 receptor subtype. Third, learned helplessness was used and resulted in increased ß1-like receptor immunoreactivity in the locus coeruleus, cerebellum and superior olivary nucleus. The upregulation of the ß1 receptor subtype in the locus coeruleus is a potentially important finding, since it is a major adrenergic centre and a target for the actions of tricyclic antidepressants (TCAs) suggesting that changes in ß1 like immunoreactivity are not a result of stress per se, but may be associated with differential, depressive-type responses to stress.
A comparison of differences and/or similarities between contract and permanent employees in the workplace

This study deals with some aspects of the recent changes in employment structure and its effects on workers. For several years, contract employment has increased significantly in both the public and private sectors. The literature has tended to ignore this shift in both employment and corporate structure. This study used qualitative research involving 23 employees: 16 contract and 7 permanent. There were 14 women (the flexibility of contract employment appealed more to women than to men) and 9 men. Interviews took place during a 2-year period. I conducted a follow-up one year later to determine whether any job changes had taken place. The methodology was based on grounded-theory research; the theory emerged from the data for this qualitative study. I compared existing organizational and attitudinal theories about workers and tested their applicability to contract employees. The organizational theories included: The Core vs. Periphery, and the Shamrock Organization. The attitudinal theories included: The Frame of Reference Theory, Partial Inclusion Theory, Discrepancy Theory, the Job Model, the Social Characteristics Model, Life Cycle and Adult Development Theory, and Two-Factor Theory of Job Satisfaction. I found that individuals on contract must deal with financial and emotional insecurities that permanent employees do not have. Contract employees have a different attitude to the workplace and their position in it from permanent employees. The best theoretical fit for organizational theories was the Shamrock Organization model. The best attitude-theory fit was the Life Cycle and Adult Development Theory. Analysis of the interview data also produced 7 themes dealing with contract employee issues: Advantages (1), Employment growth (2), Disadvantages (3), Emotions (4), Identity (5), Insecurity (6), and Telecommuting (7). The themes show the pros and cons of contract employment, identify what contractors describe as their most sensitive issues at work and in their personal lives, comment on what drives the growth in contract employment and how the contract and permanent employees interact as coworkers, and highlight differences between contract and permanent employees in both tangible and emotional terms. On the basis of this material, I make recommendations for employers, permanent employees, unions, employment law makers and educators.
Motivation for success, a new probe for exploring the cognitive, metacognitive and affective profiles of individuals with and without a learning disability

Five studies were investigated in this project aiming to coordinate the study of affective, motivational, metacognitive and cognitive processes that have hitherto been studied in isolation. It aims to extend the phenotypic profiles of selected groups through the use of a new measure of Motivation for Success (MFS). Results suggest that MFS may be useful in diagnosing the presence of psychopathological disorders since individuals with a high MFS, in comparison to those with a low MFS, deviate from the accepted norms associated with verbal concepts related to positive and negative emotions, values and one's self and ideal-self. This study also questions the generality and domain specificity of metacognitive ability suggesting instead that it might be task-dependent. Results suggest that college age students with a Reading Disability may possess superior visual spatial skills and the competence to successfully implement the use of metacognitive strategies on tasks that tap into their abilities, not their disabilities.
Studies of the immune system of HOX11 transgenic mice for lymphoma immunotherapy

We assessed the applicability of dendritic (DC) cell based immunotherapeutic protocols for the treatment of B cell lymphoma, using the HOX11 transgenic mouse model. These mice develop large B cell lymphomas in the spleen. Towards this goal, we analyzed dendritic and T cells from HOX11 mice. Results indicate that HOX11 DCs express normal levels of cell surface molecules and have normal ability to present foreign antigens, while T cells show normal proliferative response to mitogenic stimulation, foreign MHC and OVA protein. In addition, HOX11 derived peptides or lymphoma cell lysates are sufficiently immunogenic to induce specific immune responses in naïve mice. However, HOX11 derived T cells do not show induction of immune responses. Our results suggest that lymphoma development in HOX11 mice is associated with the toleration of lymphoma antigen specific T cells, making HOX11 transgenic mice a good model to develop DC-based immunotherapeutic protocols for the treatment of nonfollicular lymphomas.
Chemoreflex adaptations to hypoxia

This study investigates the role of hypoxia in the context of the chemical control of breathing in humans. A group of 7 volunteers were exposed to isocapnic (eucapnic) hypoxia for 20 minutes, once daily for 14 consecutive days. The same volunteers also repeated these experiments with air substituted for hypoxia in a pseudo-random crossover design. I measured chemoreflex characteristics before and after the exposures using a modified rebreathing method. While not discernible at first, the acute ventilatory response to hypoxia increased with the number of hypoxic exposures so that by the 14th day both the initial increase in ventilation and its subsequent decline were clearly apparent. No changes were observed during the air exposures. Over the 14-day period, the mean ± SEM chemoreflex threshold for all subjects measured before the hypoxic exposures proportionately decreased from 41.7 ± 1.1 mmHg (partial pressure of carbon dioxide) to 38.6 ± 1.0 mmHg. The mean ± SEM chemoreflex threshold increased from 39.7 ± 0.9 mmHg before single hypoxic exposures to 42.1 ± 1.1 mmHg after. Since these changes were only observed during rebreathing tests done while hypoxic, I concluded that peripheral chemoreflex adaptations had occurred.
The effect of flaxseed on the growth and metastasis of human breast cancer cells in athymic nude mice

Flaxseed (FS), with high levels of the lignan, secoisolariciresinal diglycoside (SDG), and Ã-linolenic acid (ALA)-rich flaxseed oil (FSO), was tested for its ability to inhibit the growth and metastasis of MDA-MB-43 human breast cancer cells in athymic nude mice. FS (10% wt/wt) fed to CLR-nu/nu mice inhibited early tumour growth but not lung metastasis. In NCR-nu/nu mice, 5% and 10%FS had no significant effect on primary tumour growth, whereas 15%FS tended to be stimulatory. All FS diets reduced the number of recurrent tumours, but 10% and 15%FS yielded the smallest and largest mean tumour sizes, respectively. 10%FS produced the lowest number of total metastases, whereas in the lung, 5%FS increased all metastasis growth parameters and 15%FS increased the mean area per metastasis. FSO and SDG at the level found in 15%FS affected tumour growth and metastasis in an opposite manner to 15%FS. In NCR-nu/nu mice with established tumours, 10%FS suppressed lymph node metastasis. Overall, the effect of FS on MDA-MB-435 tumour growth and metastasis depends on the mouse strain, level of FS, and experimental design.
Blues before sunrise, rowing at the University of Toronto

The University of Toronto Rowing Club (UTRC) has existed, with several lapses, since 1897. After a failed attempt in 1880, students were able to organize under the auspices of the Argonaut Rowing Club and renowned sculler Ned Hanlan. Following the First World War, coach Tommy Loudon turned out formidable Varsity crews whose successes included an Olympic silver medal and several wins at the Royal Canadian Henley Regatta and the Toronto-McGill boat race. After a twenty-year absence, rowing returned to the University of Toronto in the 1960s, guided once more by the Argonaut Rowing Club. Since the 1970s, students have assumed greater responsibility for the direction of the UTRC. In the past twenty-five years the club has attracted a large number of women and has become one of the University's largest sports teams. Over the course of its history the UTRC has shifted from the core to the periphery of public and university policy. Before the Second World War, and even into the 1960s, the rowers benefited from their amateur status, gaining extensive recognition and financial support from administrators, businessmen and politicians. In the past thirty years however, few resources have been allocated to the UTRC, which has been run on a shoestring budget by student-athletes and alumni volunteers. Nevertheless, while the prospects for competitive success have diminished, rowing has remained an important formative experience for generations of students at the University of Toronto.
Effects of modafinil on physiological and perceptual responses during exercise

Modafinil (M) belongs to a new class of drugs which elicit "arousal" properties similar to amphetamines, but with less potent side-effects. One aim of this study was to confirm that acute treatment with M (4mg$\cdot$kg$\sp{-1}$) would have an ergogenic effect on high intensity exercise performance. Eight males cycled to exhaustion at 85% VO$\sb2$ max after both M and placebo (P) treatments, using a double-blind experimental design. M prolonged time to exhaustion by 10-15%. The mechanism responsible for this effect is most likely related to a mechanism of action in the CNS that enhanced the level of arousal and vigilance. A second objective was to assess whether M would cause an overconfidence effect (i.e. a self-appraised overestimation of actual performance abilities) and enhanced cognitive performance. Seventeen subjects who participated in this experiment were randomly treated with M and P after familiarization trials. M did not cause an overconfidence effect, nor show any disturbance in self-monitoring ability. Moreover, M significantly shortened reaction time and consequently enhanced cognitive efficiency. In conclusion, M was well tolerated and had positive effects on physical and cognitive performance.
A genetic analysis of the role of neuralized in the notch and EGFR pathways of Drosophila melanogaster

The 'neuralized' gene of 'Drosophila melanogaster' is thought to be a member of the neurogenic signalling pathway involved in the development of the embryonic and adult nervous systems. Overexpressing 'neuralized' during development causes dominant phenotypes in the eye, notum and wing of adults. These phenotypes include the production of extra and misplaced bristles in the eye, an increase in the number of notal microchaetae and decrease in macrochaetae, and deletion of portions of wing veins. These dominant phenotypes were used to screen a deficiency kit for modifiers of 'neuralized.' The screen identified deficiencies which uncovered members of both the neurogenic and the EGFR signalling pathways. This interaction was confirmed by directly testing alleles of genes in both pathways for the ability to modify the 'neuralized' overexpression phenotype. It appears that 'neuralized' could play a role in both of these pathways. Biochemical tools to test these interactions have been produced.
Protein interactions involved in human gene regulation

Protein-protein interactions are important both for basal transcription and for the regulation of transcription. The core transcription machinery consists of a set of proteins, the general transcription factors, plus the multisubunit enzyme RNA polymerase II. The general transcription factors interact with each other and with RNA polymerase II to enable the polymerase to produce mRNAs. This process is regulated in cells by activator and repressor proteins that increase or decrease respectively the rate of transcription. Activators and repressors have been shown to function through interactions with various other proteins involved in transcription such as the general transcription factors and transcriptional cofactors. In order to increase our understanding of how the core transcription machinery works and how it is regulated, protein interactions among proteins involved in transcription must be identified and characterized. Chapters 2 and 3 of this thesis describe the identification of proteins that interact with the Wilms' tumour suppressor protein, WT1. WT1 is a transcriptional regulator that is able to activate and repress transcription. In chapter 2, a yeast two-hybrid screen is used to screen for cDNAs encoding proteins that interact with amino acids 182 to 295 of WT1. This region of WT1 has been implicated in both activation and repression of transcription. One interacting protein was found: the 90 kD heat shock protein, hsp90. Hsp90 was also able to bind to this region of WT1 'in vitro'. In chapter 3, protein affinity chromatography is used to identify an interaction between amino acids 182 to 295 of WT1 and the general transcription factor IIB. Both alternatively spliced isoforms of WT1 bind TFIIB. In 'in vitro' transcription reactions, addition of amino acids 182 to 295 of WT1 results in inhibition of transcription, which is reversed by the addition of recombinant TFIIB. Using gel mobility shift assays to examine the formation of the pre-initiation complex, WT1 was found to inhibit formation of a TFIIF-TFIIB-TBP-promoter complex, but not a TFIIB-TBP-promoter complex. This result suggests that the interaction between WT1 and TFIIB may be involved in transcriptional repression by WT1. Chapter 4 examines the interactions of two elongation factors, TFIIS and Elongin A, with the RNA polymerase II holoenzyme. An interaction was identified between each of these elongation factors and the general transcription factor IIB. The amino-terminus of each factor, which is sufficient for the interaction with RNA polymerase II holoenzyme, was also sufficient to bind TFIIB. The site of interaction on TFIIB was mapped to amino acids 100 to 240. TFIIB was found to compete with TFIIS for binding to the RNA polymerase II holoenzyme. This suggests that TFIIB can mediate the interaction between these elongation factors and holoenzyme.
On the development of block-ciphers and pseudo-random function generators using the composition and XOR operators

We attempt to provide evidence for the security of block-ciphers which are constructed by taking the composition and exclusive or of non-secure function generators. We provide this evidence by showing that such construction can be used to combine partially secure pseudo-random, function generators into generators with stronger security properties than any of their constituents. We extend results of Luby and Rackoff, and show that there are constructions based on the composition and &square; operators which can be used to combine 1 - [delta] secure pseudo-random permutation and function generators, where 0 < [delta] < 1, to achieve a <math> <f> 1-<fr><nu>1</nu><de><lim align="r"><op><rf>log</rf></op><ul><rm> c</rm></ul></lim><mit>n</mit></de></fr></f> </math> secure generator, for any c > 0. We then give the first proof that there is a natural construction which combines together 1 > [delta] secure function generators to form a pseudo-random function generator.