VictorJuiz/thesis huggingface dataset:
Cytokine signal transduction responses in epithelial cells to gastrointestinal bacterial pathogens

Lastly, I delineated host and bacterial mechanisms involved in EHEC-mediated suppression of Stat1. Bacterial, but not host cell, protein synthesis, adhesion to host cells, and generation of a soluble factor(s) after bacterial contact with host cells are all involved. Sucrose density gradient fractionation showed that EHEC disrupts IFNgamma receptor chain alpha association with cholesterol-enriched membrane microdomains, and immunolabelling confirmed altered subcellular localization. Overall, a combination of host cell-derived and bacterial factors is associated with suppression of Stat1 activation. The bacterial enteropathogens Helicobacter pylori and enterohemorrhagic Escherichia coli (EHEC) O157:H7 cause considerable morbidity and mortality in humans. To establish infection and elicit disease, these bacteria modulate host epithelial cell signal transduction, but the precise mechanisms remain unclear. Some microbes inhibit cytokine-induced Janus kinase and signal transducer and activator of transcription (Jak-Stat) pathways important to host immunity. Accordingly, the objectives of my research were: (1) to determine if H. pylori and EHEC suppress cytokine-induced Stat signalling in epithelial cells in vitro, and (2) to delineate both bacterial and host cell mechanisms involved. In summary, these studies demonstrate, for the first time, that bacterial enteropathogens suppress cytokine-induced signal transduction pathways in gastrointestinal epithelial cells. This could represent a unique immune evasion strategy employed by these bacteria. First, I determined that H. pylori infection of gastric epithelial cells suppressed interleukin (IL)-4-induced Stat6 activation. Complementary techniques showed infection inhibits IL-4-induced Stat6 tyrosine phosphorylation, DNA-binding, and nuclear translocation independent of bacterial virulence factors CagA, CagE, and VacA. IL-4 receptor and Jak1 expression were unaffected. Moreover, H. pylori suppressed IFN-gamma (IFNgamma)-induced Stat1 tyrosine phosphorylation. These findings indicate that H. pylori suppression of cytokine signalling could influence disease outcome. Next, I showed that EHEC O157:H7 suppresses IFNgamma-induced Stat1 DNA-binding, tyrosine phosphorylation, but not nuclear translocation, in colonic epithelial cells. Stat1 suppression required live bacteria, but was independent of Shiga-like toxins, intimin, type III secretion, or plasmid-encoded factors. Functionally, EHEC suppressed IFNgamma-inducible expression of a Stat1-dependent gene. Furthermore, EHEC serotype O113:H21 also suppressed Stat1 activation, but enteropathogenic E. coli or commensal E. coli did not. Together with the H. pylori results, this indicates that specific pathogens suppress cytokine signalling.
Cloning and characterization of mammalian MUS81a junction-cleaving nickase

The DNA damage response network has been shown to contribute to tumor suppression by maintaining genomic integrity. Many components of these pathways have been conserved across evolution. Most prominent of which is the novel cell cycle checkpoint/DNA damage repair protein Mus81. Initial studies in yeast identified Mus81 as interacting with Rad54 and Chk2. Recently Mus81 and its partner Eme1 (members of the XPF-ERCC1 subfamily) were shown to possess a junction-resolving activity. Junctions are mostly formed following replication fork regression, or during DNA damage repair. Here we show that transcriptional regulation of Mus81 occurs in a p53-dependent manner. We also show that mice deficient in Mus81 develop to maturity in a C57BL6/J background. Embryonic fibroblasts, T-cells, and B-cells deficient in Mus81 show a marked decrease in proliferative ability supporting Mus81's role in replication fork maintenance. Additionally, homozygous TB cells are sensitive to UV and MMC supporting the role of Mus81 in DNA damage repair. Finally, Mus81 is dispensable for the immune compartment and its overexpression is not enough to elicit a phenotype in Drosophila eyes.
Identification of a novel diagnostic marker for viral myocarditis using cDNA microarrays

The Coxsackievirus B3 (CVB3) serotype is the leading cause of viral myocarditis. Presently, the Dallas Criteria is the gold standard for diagnosis. In the present study, we utilized microarrays to search for differentially expressed genes between CVB3-infected mice and control mice in order to identify novel diagnostic targets. A/J mice were infected with 10pfu of CVB3. Total RNA was extracted from heart tissue and analyzed by cDNA microarray. The Aldo-Keto Reductase AKR1C13 gene was found to have the greatest degree of upregulation following reverse labeling (Floor Flip) and was independently confirmed using real time RT-PCR. Microarray conducted on blood samples also showed AKR1C13 to be upregulated. Microarrays conducted on AB and MI mice showed no change in the expression of AKR1C13. AKR1C4 occupies the syntenic region of AKR1C13 in the human genome and was shown to be upregulated in human biopsy samples of myocarditis when examined by RT-PCR. We have identified the Aldo-Keto Reductase AYR1C4 gene as a possible candidate for use as a diagnostic tool in human myocarditis.
Studies on hematopoietic malignancies using recombinant diphtheria toxin-growth factor fusion proteins

Studies on the interactions of hematopoietic growth factors and their target cells are limited by the heterogeneous nature of hematopoietic cells, low cell surface receptor densities and complex interactions with other factors. It has been recently demonstrated that the cell receptor binding domain of several naturally occurring toxins may be replaced by growth factor sequences in order to generate targeted cytotoxins. In this thesis, the cytotoxicity of two recombinant hematopoietic growth factor fusion toxins has been investigated. A recombinant diphtheria toxin (DT)-granulocyte colony-stimulating factor (G-CSF) fusion protein was produced. The approximately 70,000 Dalton fusion protein shared immunologic determinants with both DT and G-CSF, and retained the enzymatic activity characteristic of DT and receptor specificity of G-CSF. DAB486-G-CSF was cytotoxic towards G-CSF-responsive malignant blast cells derived from patients with acute myeloblastic leukemia. As fusion of G-CSF to non-toxic DT sequences results in a 400-fold reduction in the ability of the growth factor to stimulate normal bone marrow colony formation, reduced functioning of the cell receptor binding domain limits DAB486-G-CSF-mediated toxicity. The cytotoxicity of a recombinant DT-related interleukin-6 (IL-6) fusion protein towards myeloma cell lines was also investigated. DAB389-IL-6 was specifically cytotoxic towards U266 myeloma cells: protein synthesis and methylcellulose colony formation were inhibited by low (10−11 to 10−9 M) doses of the IL-6 fusion toxin. Brief (150 minute) exposure in suspension culture reduced clonogenic cells by approximately 99%, and a molar excess of recombinant human (rh) IL-6 reversed the inhibitory effect on colony growth. Six other cell lines displayed variable sensitivity to DAB389-IL-6 in a clonogenic assay, ranging from dose-dependent inhibition (OCI-My 5), to inhibition preceded by stimulation at low doses (OCI-My 4) or to no specific inhibition (OCI-My 1, -My 2, -My 3 and -My 7). Colony formation by DAB389-IL-6 sensitive, but not insensitive, cell lines was either stimulated (U266, OCI-My 4) or inhibited (OCI-My 5) by rhIL-6. Expression of cell surface receptors for IL-6 was not sufficient to predict sensitivity to cell killing by DAB389-IL-6. Specific cell surface binding sites for IL-6 were detected on U266 and OCI-My 5 cells, as well as on IL-6 fusion toxin-resistant OCI-My 1 and -My 7 cells. The demonstration that U266 myeloma colony formation may be selectively eliminated in the presence of normal bone marrow granulocyte, erythroid and mixed granulocyte/erythroid colonies points toward the potential use of DAB389-IL-6 for the selective elimination of certain IL-6 receptor expressing malignant cells from mixed cell populations
Francesco algarotti and francesco milizia: architectural and dramatic theorists of the Italian enlightenment

In the early part of the eighteenth century, in Venice, Carlo Lodoli, a scholar-priest, established an early argument for functionalism in art with his call for a general reform of the architectural design practices of his day. There has been much debate, in light of the French hegemony in theories of art during the period, as to the originality of Lodoli's concepts. Among Lodoli's many disciples stand two, Francesco Algarotti (1712–64) and Francesco Milizia (1725–98), both of whom became famous for their interpretations and applications of Lodoli's functionalist approach in a number of treatises published throughout the middle of the century. The similarities in, and far-reaching success of their treatises, argues for the existence and importance of a school of thought that can be considered representative of the Italian Enlightenment. The purpose of this thesis is to examine the ways in which Algarotti and Milizia applied a new functionalist artistic criticism to what they perceived as one of their society's oldest and most important institutions: the theatre. Both men viewed the representational qualities inherent in the arts as something vital to the well-being of society and, in their respective treatises, Saggio sopra l'opera in musica (1755) and Del Teatro (1772), they brought their architecturally conceived sense of order to bear on analyses of the theatre as a physical space and as an event. This thesis analyzes Algarotti's and Milizia's dissection of the theatre event and their creation of rules meant to guide the process of design and production thereby returning the practice of theatre to its original function of creating utility and pleasure.
Palaeopathology of the temporal bone in chilean populations

The purpose of this thesis is to understand the evolution of the epidemiologic pattern of four ear pathologies (i.e. congenital malformations-atresia of the external acoustic meatus; tumours-exostosis; otitis media, and otosclerosis) in Chilean Native populations, based on the possible correlation between palaeopathological findings and the observed prevalences these otologic pathologies have among contemporary Native Americans. Within this framework, the main objectives of this study are: (1) to evaluate the differences and similarities between the otopathologic patterns of prehistoric and historic Chilean Native populations, and establish possible causes of continuities or discontinuities between these models; (2) establish the possible causal agents of these pathologies and their eventual associated effects; to determine, if possible, the relative risk of these pathologies; and (3) to develop a palaeoepidemiological model of otologic pathologies for Chile's Native populations. The populations examined consider prehistoric and historic groups from different latitudes and altitudes. Three pathologies (congenital disorders, tumours, and otosclerosis) are evaluated directly (i.e. macroscopically) and only otitis media is assessed indirectly (i.e. radiologically). Nonparametric tests are used to evaluate the degree of relationship between diseases and sex, altitude, and latitude. The results of this study confirm the reported prevalence of tumours-exostosis in northern coastal populations but demonstrate their non-existence in southern coastal groups. The implications of this latter finding are discussed. The absence of otosclerotic cases corroborate what has been observed in other Native American groups. Congenital disorders although absent in our samples seem to have been present in prehistoric and historic times. The lack of findings in the groups studied is evaluated in relation to reported cases from neighboring populations. Traces of infectious middle ear disease (i.e. otitis media) are clearly demonstrated by means of radiology. Incidences of pneumatized temporal bones in coastal and highland populations suggest the existence of both intrinsic and extrensic factors in the high prevalence of otitis in ancient Native Chilean groups. Tentative explanations for these incidences are discussed. However, the lack of modern data hampers comparisons between past and present prevalences.
The effects of prior heat shock on in vitro muscle contractile properties at 20 degrees C and 42 degrees C

Acutely, temperatures >40°C adversely affect muscle function. It was of interest to determine if the increased Hsp content induced by a pre-exposure to heat could reduce this fatigue. A 15 min heat-shock was given to the right hindlimb, with the left hindlimb serving as a contralateral control, and separate animals as full controls. Forty Sprague Dawley rats, 21–28d old, were separated into two 1-limb heat-shocked groups and two control groups, each stimulated at 42 and 20°C. EDL and SOL muscles were removed 24h later and the contractile properties assessed in vitro. Muscles were twitched and brought to tetanus every 5 min up to 30 min, at which time, they were exposed to a 6 min fatigue protocol. Muscles stimulated at 42°C fatigued earlier than muscles stimulated at 20°C, with heat-shock not reducing fatigue. These results suggest that following a 24h heat-shock of 42°C for 15 min, contractile performance does not improve at 20 or 42°C when compared to contralateral controls and full controls.
Reliability assessment of measures used in HIV lipodystrophy

HIV-Lipodystrophy (HIV LD) describes a syndrome of body fat redistribution and metabolic abnormalities recognized in HIV-positive individuals receiving treatment. A standardized, reliable definition of HIV LD is needed to better study the epidemiology and for evaluation of potential treatments. This thesis examines the reproducibility of three measures commonly used in evaluating HIV LD: the Carr Lipodystrophy Questionnaire (LQ), body part circumferences, and DEXA estimations of body fat, and examines the correlation between LQ and DEXA. For the LQ, reproducibility was moderate to good for test-retest comparisons, but only fair to moderate for most items in inter-physician and patient-physician comparisons. Body circumferences and DEXA showed good reproducibility. Correlations between DEXA and the LQ were significant in some anatomical areas; however this was clouded by the weak reproducibility of the LQ. Standardized scoring instructions may help improve reproducibility of the LQ and allow more meaningful comparisons with DEXA.
The orthodontic and surgical treatment of dental anomalies in children with complete unilateral cleft lip and palate at SickKids Hospital, Toronto, Canada

This was a retrospective study of 116 children with non-syndromic complete unilateral cleft lip and palate (CUCLP). The presence and morphology of the lateral incisors on the cleft and noncleft sides and the second premolars were determined using serial radiographs, photographs and case histories. The orthodontic, surgical and/or prosthetic procedures rendered in the area of the cleft were recorded and analyzed. Cleft-side lateral incisors were rarely present at the conclusion of orthodontic and surgical treatment of CUCLP. In most cases there was agenesis. When present they were often abnormal in size, shape and bone support and were commonly extracted in favor of canine substitution. Following bone grafting the canine was advanced by orthodontics or segmental surgery. Prosthetic options were less common.
Memory for associative information in younger and older adults

The present series of experiments examined how aging and divided attention influence memory for item and associative information in a variety of contexts. Previous research has suggested that one reason for older adults' poorer episodic memory is an impairment in processing and retaining associative information. To examine this, older adults, younger adults, and younger adults under various divided attention conditions studied unrelated word pairs for a later recognition memory test of both single words and different combinations of word pairs (Experiments 1--3). Both older and younger divided attention adults performed less well than the full attention group, with the deficit in associative information being greater than the deficit in item information. In addition, a differentially greater associative impairment was found for the older adults, as shown by their heightened tendency to make false alarm responses to re-paired (conjunction) distracters. These findings are interpreted in a dual-process model of recognition memory, in which older adults rely more on familiarity rather than recollection when processing associative information. The ability to remember other types of associative information was further examined by using cued recall tests of associative memory that varied in terms of the degree of specificity. In these experiments (Experiments 4--6), participants studied items that were paired with either related or unrelated units of information, as well as specific numerical information (either quantity or price information). Although older adults had the greatest difficulty remembering specific arbitrary associations, this impairment was reduced when associations were made meaningful (as a result of expertise) or contained a certain degree of schematic support. These results are discussed in terms of how prior knowledge and evaluative processing can influence associative memory, and suggest that a framework of associative memory that emphasizes different levels of associative specificity is necessary to interpret how older adults access associative information. The overall pattern of results imply that observations of age-related differences in memory for associative information depend on differences in available attentional resources, grain size (degree of precision) analyses at both encoding and retrieval, schematic support, and the meaningfulness and specificity of the association.
Reconceiving discretion: from discretion as power to discretion as dialogue

This thesis articulates, and contrasts, the two conceptions of discretion that inform the case law on administrative discretion in Canadian law: discretion "as power" and discretion "as dialogue". I suggest that the latter conception provides the best explanation for the progressive trend which developed in the law of discretion over the last twenty-five years, whereby courts devised procedural and substantive constraints on the exercise of discretion while endorsing a posture of deference towards that kind of decision-making power. Moreover, I argue that the normative foundations for that conception of discretion can be found in a combination a relational theory exemplified in writings by J. Nedelsky, a democratic theory of the kind expressed by H. Richardson, and a vulnerability theory, articulated by J. Handler and L. Sossin. I argue further that a view of discretion as dialogue is justified under an attractive understanding of the rule of law and consequently contributes to the recognition of the legitimacy of the administrative state. Finally, my conception of discretion as dialogue favours the realisation of the legitimate projects of the welfare state while at the same time recognising a role for the rule of law in government.

Keywords: Administrative discretion, Canada
Judicial review of administrative acts, Canada
Judicial discretion, Canada
Characterization of novel abiotic stress associated genes in Arabidopsis thaliana using a systems biology approach

Approximately 50% of the 28000 genes in Arabidopsis thaliana have function ascribed to them by traditional homology-based annotation methods. The goal of this study was to begin to biologically characterize genes that were predicted from in-house and publicly-available large-scale gene expression data sets from many different treatments and conditions using machine learning algorithms to be involved in abiotic stress responses. The role of candidate genes with unknown function was elucidated using bioinformatics and in planta using gene knock-out studies. Results implicate At1g16850, LEA-LIKE 1, as part of the plant's mechanism for acclimation response during periods of cold and salt stress. In addition, LEA-LIKE 1 possibly plays a role in seed development and viability.
Peacekeepers in the sand: Canada and the United Nations Emergency Force

Should the success of a peacekeeping mission be determined by the length of time the peace is kept, or the lasting initiatives of peace that are created? Judged by the former, the United Nations' first major attempt at a peacekeeping force was a substantial achievement. The United Nations Emergency Force (UNEF) eased tensions and kept peace in the Middle East for over a decade. However, when judged by the latter criterion---the ability to create a lasting peace rather than merely observe a ceasefire---the entirety of the mission must be taken into account. Here the UN's report card is less stellar. UNEF's hasty withdrawal in particular, and the United Nations' inability to even imagine, let alone actively manage, peacekeeping's retreat, paved the way for the decade-delayed conclusion of hostilities between Israel and Egypt in the form of the Six Day War. This thesis provides a comprehensive examination of Canada's political and military involvement in UNEF from 1956 to 1967. For ten and a half years, UNEF was able to keep the peace along the Egyptian-Israeli border, and Canada played a large role in these efforts. Yet the subsequent myth of Canada's valour and success in international peacekeeping misrepresents the historical reality from whence it came. Much has been written about the creation of UNEF, a little about UNEF's withdrawal, yet next to nothing pertaining to the middle years. Examining Canada's participation in UNEF in its entirety not only provides historical precision, but also helps to more accurately evaluate current peacekeeping efforts. As the UN's first major peacekeeping undertaking, UNEF faced tremendous challenges in its creation, in its ongoing funding, and during day-to-day life on the ground. In meeting these challenges with varying degrees of success, UNEF taught three important lessons: Peacekeeping is inherently difficult---even more so without a clear mandate and stable funding from the outset; Canada needs to critically assess its participation in each peacekeeping operation; and peacekeeping is nothing without parallel peacemaking.
The effect of individualized pulmonary rehabilitation after moderate or severe exacerbation in individuals with chronic obstructive pulmonary disease

Purpose. This study was to characterize acute exacerbations (AEs) in terms of health-related quality of life (HRQL) and functional exercise capacity in individuals with chronic obstructive pulmonary disease (COPD) following pulmonary rehabilitation (PR), and examine the feasibility of abbreviated PR after AEs. Methods. Sixty subjects had baselines measures after PR. Those experiencing exacerbations were randomized into two groups. The treatment group attended a 3-week intervention. Results. Thirty-four subjects were randomized. Baseline six-minute walk (6MW) was 66m lower (p