VictorJuiz/thesis huggingface dataset:
Bioactivation of trimethoprim, fluperlapine and nevirapine, roles of iminoquinone-type Michael acceptors in idiosyncratic drug reactions

Idiosyncratic drug reactions are significant medical problems for both modern drug therapy and drug development. Although their mechanisms are poorly understood, the involvement of drug reactive metabolites has been generally proposed. Michael acceptors such as quinones, iminoquinones and quinone methides, are common reactive metabolites of many drugs and drug candidates. Trimethoprim is associated with idiosyncratic adverse reactions including liver toxicity and agranulocytosis. We demonstrated that trimethoprim was oxidized by activated human neutrophils, as well as myeloperoxidase (MPO), or HOCl to a reactive iminoquinone methide intermediate with a MH+ ion of m/z 289. In the presence of N-acetyl-L-cysteine (NAC), the reactive intermediate could be trapped as three NAC adducts. Incubation of trimethoprim with isolated hepatic microsomes in presence of NAC gave the same set of TMP-NAC adducts. Immunoblotting studies detected covalent binding of trimethoprim to proteins both 'in vitro' and 'in vivo'. Fluperlapine has been associated with idiosyncratic agranulocytosis in humans. We demonstrated that 7-hydroxyfluperlapine, the major metabolite of fluperlapine, is oxidized by HOCl or by MPO system to a reactive iminoquinone species with a MH+ ion at m/z 324. Using an antibody developed against the drug's analogue, clozapine, we demonstrated that 7-hydroxyfluperlapine could covalently modify human MPO. Furthermore, we demonstrated that 7-hydroxyfluperlapine is metabolized by activated neutrophils to the reactive metabolite that covalently binds to neutrophils. In the presence of NAC or glutathione (GSH), such covalent binding could be inhibited and the NAC or GSH adducts were formed. Nevirapine is associated a high incidence of skin rash, hepatitis and granulocytopenia. We demonstrated that radiolabeled nevirapine covalently bound to activated human neutrophils. Protein binding was also detected when the drug was incubated with MPO in the presence of bovine serum albumin. Oxidized by HOCl, nevirapine formed a reactive intermediate with a molecular ion of m/z 281. This is presumably a reactive quinoneiminium ion and it could be trapped by NAC. The NAC adduct was also detected when 3-hydroxynevirapine, the major metabolite of nevirapine, was metabolized by rat hepatic microsomes in the presence of NAC. Immunoblotting studies detected modified polypeptides in the hepatic cytosol fraction and the skin homogenate from nevirapine-treated rats.
Client-therapist perceptions of helping in psychiatric occupational therapy, a qualitative study

Using an exploratory qualitative approach, data were collected on the perceptions of helping from six psychiatric occupational therapists and two clients of each therapist. Adopting an empowerment theoretical perspective, this study explored the experiences in occupational therapy that clients and their therapists perceive as helpful. In addition, barriers to helping were also examined. Clients and therapists shared many perceptions regarding benefits of the supportive relationship and of valued group dynamics. However, differences emerged with regard to the issues clients named as barriers to helping. These included the concrete problems of poverty, unemployment, social isolation, harmful effects of institutionalization, and stigma. Therapists did acknowledge the sick role as a major barrier but tended to assume a clinical perspective consistent with their training and focused on individual functional skill deficits as areas of concern. This study demonstrated the relevance of an empowerment analysis for helping psychiatric occupational therapy clients.
War, peace and the English curriculum

In his 1994 call for the creation of a "culture of peace," UNESCO Director-General, Federico Mayor, urged educators to begin a transformation of thinking and practice. From the position that the English curriculum in high schools represents one site for the formation of attitudes towards war and peace, this inquiry looks at the study, historical and current, of war-related literature in English curricula in Ontario high schools, and in several Quaker schools in Canada and the United States. It asks how the English curriculum has played a role in helping to create and sustain a culture that glorifies violence, and that affirms war as inevitable. Finally, it looks for strategies to begin the transformation urged by Mayor. Historically, English Literature studied in Ontario mainstream high schools has established a set of notions--courage, heroism, patriotism, glory, sacrifice and manhood--in a context that accepts war as inevitable and often glorious. Alternative voices have been excluded from literary discourse about war. This exclusion poses a problem, unacknowledged at the secondary school level, to the project of teaching for democracy, which requires access to the widest possible range of perspectives on fundamental issues. Only with such a range will negotiation of textual and contextual meaning constitute an authentic discourse-as-crucible for transformational thinking and practice. Anthologies authorized for use in Ontario mainstream high schools up until the 1970s offered students and teachers a body of works in which there was little, if any, challenge to the dominant cultural attitude towards war. While curricular changes have since occurred on issues of race, gender, and multiculturalism, there has been little substantial change on issues of war. One might expect a different approach to the same literary heritage in the schools of Quakers, a community founded on pacifism. My research, however, shows no curricular discourse on the tension between literature accepting, even promoting war, and the Quaker Peace Testimony. The intersection of the teaching of English and the Quaker Peace Testimony represents a potentially rich site for the development of a challenging curricular discourse, one leading to Mayor's "transformation in thinking and practice."
The relationship of physical activity to risk of testicular cancer

Testicular cancer is the most common cancer among Ontario males aged 25-34, yet few studies have examined the relationship between modifiable factors and testicular cancer risk. Data collected as part of the Enhanced Cancer Surveillance Study were used to examine the relationship between recreational and occupational physical activity at various life periods, including lifetime activity, and risk of testicular cancer. Analysis of 212 cases and 251 controls revealed that relatively high frequency of participation (greater than five times a week) in moderate and strenuous recreational activity in one's mid-teens may have an adverse effect on risk of testicular cancer; moderate or strenuous occupational demands in one's 20's also increased risk of disease. Little difference was seen in the magnitude or significance of the odds ratios between analyses of moderate and strenuous activity separately or between our analyses of total recreational activity, one of which assumed equivalency of moderate and strenuous activity and one of which assigned weights based broadly on MET values. It would appear, then, that it is the frequency of activity at adolescence that is the relevant measure. Increased exposure to androgens as a result of relatively high frequency of participation in physical activity, at a critical period of hormonal balance, may be responsible for the observed adverse effects.
Dystrophin gene regulation in muscle

The identification and characterization of the muscle-promoter and a muscle-specific enhancer within intron I has led to advances in our understanding of dystrophin gene regulation in muscle. However, the sequences identified to date are not sufficient to regulate reporter gene expression in a manner that mimics endogenous dystrophin expression. Evidence that deletion of the muscle promoter can lead to X-linked dilated cardiomyopathy (XLDC) raises additional questions relating to the role of the muscle promoter. The absence of a skeletal muscle phenotype in this patient has been attributed to the up-regulation of non-muscle dystrophin protein isoforms. This thesis examines the role that the intron I enhancer plays in the activation of the brain- and cerebellar Purkinje cell-specific dystrophin promoters and describes a sequence-based approach to search for additional enhancer elements at the 5' end of the dystrophin gene.
99mTc-DADS-digitoxigenin and 99mTc-DADS-digitoxin, Potential Na+, K+-ATPase Based Heart Imaging Agents

Two digitalis-derived 99mTc-chelating ligands, digitoxigenin-DADS and digitoxin-DADS, were synthesized by the Department of Chemistry, McMaster University, as potential Na+, K+-ATPase based heart imaging agents. In order to develop these ligands into radiopharmaceuticals, it was necessary to examine whether they would localize in the heart in a manner similar to the digitalis. Gamma-ray scintigraphy was used to visualize the myocardium. Biodistribution study using guinea pigs yielded a heart/blood ratio of 0.578 ± 0.036 at 10 minutes after the injection. The administration of ouabain decreased it to 0.347 ± 0.039. The results of Na+, K+-ATPase binding assays suggested that both ligands bind to the same binding sites on the enzyme as the digitalis. Bmax values of <math> <f> <rm>2.55*10<sup>-9</sup><fen lp="par">M<rp post="par"></fen> </rm></f> </math> and <math> <f> 2.76<rm><hsp sp="0.265">*10<sup>-9</sup><fen lp="par">M<rp post="par"></fen> </rm></f> </math> and KD values of <math> <f> 1.49*10<sup>-6</sup><fen lp="par"><rm>M</rm><rp post="par"></fen> </f> </math> and <math> <f> 4.71*10<sup>-8</sup><fen lp="par"><rm>M</rm><rp post="par"></fen> </f> </math> for digitoxigenin-DADS and digitoxin-DADS, respectively, were obtained. Non-specific binding was very significant for both ligands. This study showed that 99mTc-chelated digitalis derivatives have the potential to be developed into radiopharmaceuticals for imaging the myocardium in heart diseases.
Explorations in biological atomic force microscopy, using tapping mode under biological buffers to examine polymorphism in RecA protein

RecA fibrils in physiological conditions have been successfully imaged using Tapping Mode atomic force microscopy. This represents the first time images of RecA have been obtained without drying, freezing and/or exposure to high vacuum conditions. While previously observed structures--the monomer, the hexamer, the short rod--were seen, a new type of fibril was also observed. This mini-fibril is narrower in diameter than the standard fibril, and occurs in three distinct morphologies: aperiodic, 100-nm periodic, and 150-nm periodic. In addition, much longer rods are observed, and appear curved and even circular.
The regulation of intracellular calcium ion concentration and mitochondrial function by cyclosporin A, a putative mechanism for the pathogenesis of gingival overgrowth

Gingival overgrowth is associated with loss of homeostasis of collagen metabolism subsequent to the administration of several drugs, including the immunosuppressant cyclosporin A. Currently, the mechanisms by which CsA induces gingival overgrowth have not been resolved. My hypothesis is that the induction of gingival overgrowth by cyclosporin A (CsA) involves the deregulation of collagen turnover due to a disturbance of calcium utilization in the mitochondria of gingival fibroblasts. CsA (10nM) inhibited collagen bead phagocytosis (2-fold; p < 0.05) in cultured human gingival fibroblasts (HGF) and Rat2 cells. Thapsigargin (Tg; 1 [mu]M; p < 0.01) and carbonyl cyanide 'm'-chlorophenyl hydrazone (CCCP; 10 [mu]M; p < 0.02) also inhibited phagocytosis of collagen beads, indicating the importance of mitochondrial function in phagocytosis. Collagen-coated beads (CCB) induced equivalent increases of intracellular calcium [Ca2+], in HGF and Rat2 cells. Tg inhibited the collagen-bead induced [Ca2+]i response 3.7-fold. Pre-treatment with CsA inhibited collagen-induced [Ca2+]i and [Ca2+]SERCA responses. Collagen bead-induced phagocytosis induced a time-dependent decrease in [Ca2+]mito in both Rat2 cells and Rat2 cells pre-treated with CsA. CsA prevented the loss of mitochondrial membrane potential of cells in suspension indicating that CsA was indeed acting upon the mitochondrial permeability transition pore (MPTP). Phagocytosis was decreased in mitochondria-depleted Rat2 cells compared to Rat2 cells by 2-fold (p < 0.05) and by at least 2-fold when they were pre-treated with CsA (p < 0.05). Collectively, these data indicate that CsA acts at an intracellular locus where it: (i) inhibits calcium flux through the MPTP; (ii) inhibits calcium exchange between the SERCA and mitochondria; and (iii) inhibits collagen phagocytosis through a mitochondrial-dependent, calcium-regulated pathway. Future work could focus on how the interaction of mitochondria and SERCA calcium stores contributes to the anti-phagocytic activity of CsA.
Development of a 6 DOF reconfigurable gripper for flexible fixtureless assembly

In this thesis, a six degrees-of-freedom reconfigurable gripper is designed and built for implementation of flexible fixtureless assembly. Flexible fixtureless assembly is a novel technique in which traditional fixtures used in automotive assembly industries are eliminated by the use of multi-finger grippers. The gripper developed in this thesis is capable of precisely picking up parts of different geometries, rigidly holding the parts in space, and choosing different grasping points while allowing sufficient clearance for welding gun. The overall design procedure includes the conceptual, configuration and parametric design stage. A three-finger gripper is developed, each of which has two movable joints and two frictionless point-contacts with the grasped part. Finite element analysis is carried out to simulate deflections of the components under load. Finally, the workspace and the kinematic model of the reconfigurable gripper have been computed. The reconfigurable gripper is proved to achieve the objectives of this thesis.
Strategies of survival, meditations on a Jewish subjectivity

This thesis is a reflective analysis of Jewish responses to anti-Jewish prejudice in Post World War II Toronto and an examination of the literature of various Jewish academics and a number of the author's family members, including herself. Krieger concludes that Jewish self-hatred is both a concern of the scholars and laypeople, leading some to contemplate or attempt to "pass" unnoticed in the Christian-"mainstream" society. The goal of this dissertation is to challenge monolithic, ahistorical and simplistic discussions of the concept of "white privilege". The history of anti-Jewish prejudice indicates that Jews have been and continue to be treated differently from other [Christian] whites. Secondly, this thesis is intended to address the lack of knowledge among most non-Jews with regard to the history of anti-Jewish oppression and its negative psychological effects on Jews, and to challenge the current notion that Jews are not oppressed.
A comparative approach to quantify the influence of smallmouth bass predation and habitat complexity on the structure of littoral fish assemblages

Fish assemblages were studied to compare trapping methods and distance sampling and to determine the impact of smallmouth bass ('Micropterus dolomieu') predation and habitat complexity on the structure of littoral fish communities. I found these techniques to be independently selective, however traps provided more repeatable relative abundance estimates. Both sampling methods were required for confidence in presence-absence data. Although species richness did not differ between lakes with or without piscivorous fish, species composition and abundance did. I was able to identify two distinct fish assemblages, one with small-bodied species and one with large-bodied centrarchids. Lakes with predators did not contain or had reduced abundance of vulnerable species. Species in these same lakes with predators were more abundant yet smaller in complex compared to simple habitats. These results highlight the need to focus on the conservation of native species by preventing the introduction of piscivores and loss of habitat in lakes.
The impacts of comorbidity on health outcomes and health care utilization in the Canadian population

This thesis examined the prevalence and impacts of comorbidity of specific combinations of chronic conditions, using data from the 1994/95 Canadian National Population Health Survey. All pairs of the following conditions were studied for their associations with long-term disability, poor self-reported health, and general practitioner (GP) visits, using probabilities and relative risks: allergies, arthritis, back problems, diabetes, heart disease, and high blood pressure. People with comorbid musculoskeletal conditions and heart disease or diabetes were at increased risk of reporting long-term disability and poor self-reported health, while comorbid high blood pressure or allergies had negligible effects. High blood pressure was only important as a comorbid condition for GP visits. While effects for pairs were usually greater than effects for single conditions, the combined effects were often less than additive. The results demonstrate that a simple summation of chronic conditions does not accurately describe their combined impacts, and that studies which give equal weighting to all conditions may be misleading.
Viacheslav Ivanov's Eros, a critical study

This dissertation is a study of the main themes and structure of the book 'Eros,' a collection of thirty-three lyric poems written in 1906 by Viacheslav Ivanovich Ivanov (1866-1949). The collection is among other things the account of Ivanov's attempt to stimulate a poetic renewal through an erotic association between himself, his wife Lidiia Ivanova, and the younger poet Sergei Gorodetskii. Ivanov renders the affair in terms of a Dionysian visitation, which ends tragically and yet provides a catharsis and the promise of spiritual and creative rebirth. An example of the conjunction of seemingly incompatible influences from Friedrich Nietzsche and Vladimir Solov'ev, 'Eros' is examined in the context of the "mystical anarchist" movement of 1906, as the extreme expression of Ivanov's Promethean impulses, and as a poetic rendering of theories of Platonic eros that were current in the literary soirées of the period. An expression of Ivanov's syncretic "myth" of unity, the lyric cycle is also considered in light of Ivanov's theories of the roots of the drama and the Dionysian dithyramb. 'Eros' is read as an example of Russian Symbolist "life-creation," ('zhiznetvorchestvo') in which the boundaries between life and art are deliberately blurred.
Internal kinematics of CFRS galaxies at z  0.6

The internal kinematics of a galaxy are closely related to its dynamical mass, and can help place constraints an the type of galaxy that is being observed; in particular, different types of galaxies show characteristic scaling relations of size and velocity width [sigma]'v', or rotation velocity 'Vrot'. In principle, these scaling relations provide clues about the nature of a galaxy independently of any changes in luminosity or morphology that may be caused by bursts of star formation. This thesis is based on a study of the internal kinematics of luminous starforming galaxies in the 0 < 'z' < 0.8 range, with the aim of investigating the nature of the blue galaxies which cause the largest changes in the luminosity function at 'z' >= 0.5. New kinematic data are analysed for a sample of 30 galaxies from the Canada-France Redshift Survey, most of them with rest-frame ('U' - ' V')'AB' <= 1/2. Unlike most previous studies, target galaxies were selected 'regardless' of size and morphology, from a well-studied magnitude-limited survey (the CFRS). Our sample is therefore representative of the most rapidly changing 1/3 of the galaxy population in the 0 < 'z' < 0.8 range. The 17 galaxies at ' z' > 0.45 have sizes (from HST images) and velocity widths [sigma]' v' (from emission lines) similar to those of typical local Irregular galaxies or very small late-type Spiral galaxies. This is consistent with their morphologies (Brinchmann et al. 1998) and rest-frame colors; however, these galaxies are as bright as the brightest local Irregular galaxies, and roughly 2 magnitudes brighter than typical Irregular galaxies known nearby. We conclude that the increase in the number density of luminous blue galaxies at 'z' >= 0.5 is mainly due to a population of small and unusually-bright late-type galaxies. This could be caused by either an increase in luminosity of some fraction of the population of small galaxies, by an increase in the number density of said population, or by a combination of both density and luminosity evolution.
Transplacental pharmacology and toxicology of morphine in humans, in vitro and in vivo studies

'Purpose'. To investigate the effects of morphine on the placenta and on fetal response. 'Methods'. Placentas from uncomplicated term pregnancies were obtained after vaginal delivery or cesarean section. The treatment groups were morphine and morphine-naloxone. A chorionic vein and artery supplying a single, peripheral cotyledon were cannulated for perfusion. Morphine, antipyrine, lactate, glucose, human chorionic gonadotropin, oxygen consumption, perfusion pressures, and pH gradient were measured. Women with singleton pregnancies, requiring fetal blood sampling (FBS), between 21 and 39 weeks gestation, were assigned to the study or control groups based on placental location, fetal position, and pre-FBS extent of fetal movement. Only study patients received 10 or 15 mg of morphine. Pre- and post-procedure maternal vital signs, biophysical profile score (BPS), and Doppler indices were measured. Maternal and cord blood was drawn for morphine analysis. ' Results'. The rate of morphine transfer across the placenta was 0.73 ± 0.44 and 0.69 ± 0.26 ng/mL/min in the morphine (n = 4) and morphine-naloxone (n = 5) perfusion experiments, respectively (p = 0.89). The mean fetal-to-maternal transfer ratio was 0.31 ± 0.27 (morphine) and 0.27 ± 0.24 (morphine-naloxone) (p = 0.66). The clearance of morphine was 0.89 ± 0.40 (morphine) and 0.87 ± 0.27 mL/min (morphine-naloxone) (p = 0.92). The morphine:antipyrine clearance index was 0.63 ± 0.08 (morphine) and 0.64 ± 0.26 (morphine-naloxone) (p = 0.99). Morphine was retained by and released from all placentas. The mean morphine dose (n = 10) was 0.16 ± 0.02 mg/kg Mean maternal and cord morphine levels were 41.8 ± 14.6 and 25.5 ± 11.6 ng/mL, respectively. The fetal-to-maternal ratio was 0.61 ± 0.20. After morphine exposure, there was a mean 3.2 point decrease in the BPS (p < 0.05). A significant positive trend was measured when biophase morphine was correlated with the S/D ratio, RI and PI. 'Conclusions'. Morphine transfers across the placenta, unaffecting placental viability or barrier integrity. Naloxone does not alter morphine transplacental kinetics. Placental retention and release of morphine prolongs fetal exposure. Morphine affects fetal response as indicated by a decreased BPS. The correlation between the biophase morphine and the Doppler indices suggests that morphine functions as a vasoconstrictor of the placental vasculature.
Lateral Current Injection lasers and the Integrated Split-Electrode Laser Modulator

Lateral Current Injection (LCI) lasers and the Integrated Split-Electrode Laser Modulators (SELM) are fabricated in the GaAs/AlxGa1-x As/In0.1Ga0.9As material system. The effect of lateral leakage current on the threshold current of LCI devices is studied in detail. The simulation results based on a simple, but informative modeling of temperature dependence of threshold current are compared against experimental results to further advance the understanding of internal operation mechanism of LCI devices. The SELM is successfully fabricated and its concept proven. Modulation and output extinction measurements show the SELM is working in the way that it is intended. Consideration of the rate equations reveals the potentially superior modulation characteristics of the SELM, which awaits to be proven experimentally.