VictorJuiz/thesis huggingface dataset:
UDP-glucuronosyltransferases (UGTS) in chemically-initiated toxicity

The majority of xenobiotics and endobiotics are eliminated through glucuronidation catalyzed by the UDP-glucuronosyltransferase ( UGT) superfamily of isozymes. Glucuronidation competes with enzymatic (cytochromes P450, peroxidases) bioactivation which can form potentially toxic reactive intermediates. Since glucuronidation (i.e. elimination), unlike bioactivation, generally is a quantitatively major pathway, UGT deficiencies leading to a decrease in glucuronidation may significantly enhance xenobiotic bioactivation and thus potentially increase xenobiotic-initiated toxicity. This laboratory has previously shown, through 'in vitro' and 'in vivo ' studies, that UGT deficiencies can increase susceptibility to both acetaminophen- and benzo[a]pyrene (B[a]P)-initiated toxicities (cytotoxicity, nephrotoxicity, hepatotoxicity, covalent binding, micronucleus formation). We have now provided the first evidence that 'in vitro ' B[a]P-initiated micronucleus formation, like carcinogenic initiation, is most likely due to enzymatic bioactivation of B[a]P to a reactive intermediate, and that the molecular lesion responsible may be oxidation of DNA and possibly protein (Free Rad. Biol. Med. 23: 579-596, 1997). Furthermore, we have shown for the first time through 'in vitro' and 'in vivo' studies that UGT deficiencies increase toxicological susceptibility to both the potent tobacco-specific carcinogen, 4-(methylntrosamino)-1-(3-pyridyl)-1-butanone (NNK), and the teratogen phenytoin and its major para-hydroxylated metabolite 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH). Micronucleus formation, which may involve reactive oxygen species formation (ROS ) and DNA oxidation initiated by NNK, phenytoin and HPPH was enhanced in both heterozygous (+/j) and homozygous (j/j) UGT-deficient fibroblasts (Cancer Res. 56: 1526-1532, 1996; J. Pharmacol. Exp. Ther. 280: 200-209, 1997). Using salicylate hydroxylation as a measure of hydroxyl radical (·OH) formation, we demonstrated ' in vivo' that peroxidase-catalysed bioactivation of phenytoin and possibly HPPH can initiate ·OH formation (Mol. Pharmacol. 49: 172-181, 1996), and that ·OH formation is increased in phenytoin and HPPH-treated UGT-deficient rats, which are compromised in their ability to glucuronidate these compounds, suggesting a possible mechanism for increased toxicological susceptibility (Proc. 8th International Workshop on Glucuronidation, Abstr. No. 42). In these same rats we have shown that phenytoin-initiated embryotoxicity ('in utero' death) is increased in heterozygous (+/j) UGT-deficient rats compared to UGT-normal (+/+) controls (Toxicol. Sci. 42, Abstr. No. 1288, 1998). These results show that UGT deficiencies can increase xenobiotic-initiated toxicity and therefore suggest that similar UGT deficiencies in the human population may prove to be important determinants of human susceptibility to carcinogenesis and teratogenesis.
Unto my wife I would not be the bride, rich widows and anxious suitors in Thomas Middleton's comedies

This thesis contextualizes the remarrying widow and her suitors in Thomas Middleton's comedies within the social, economic, and sexual concerns surrounding a wealthy widow's remarriage in early seventeenth-century London. While scholars have viewed the early modern construct of the "lusty widow" as a dissuasive tactic of a culture which frowned upon female remarriage, the construct frequently works instead to 'enable' remarriage, re-circulating widows' property back into the male-controlled economy. To an impecunious young man, marrying a prosperous widow was both attractive and threatening, as the wealthier, experienced woman was feared to dominate her husband. To assuage his anxieties over entering this potentially emasculating marriage, the suitor compensated for his threatened masculinity by fantasizing the widow's need of his sexual virility, a fantasy on which the theatre capitalized with comedies eliciting and then managing such anxieties as they celebrated a man's conquest of a widow through her lust. Middleton, who staged seven comic remarrying widows over his career, gradually undermined and mocked this fantasy, exposing the male anxieties beneath it. After an introduction questioning scholarly opinions concerning the early modern English condemnation of female remarriage, Chapter One uses a range of period texts to argue that the idea of a widow's lust helped assuage men's fears that she would prove an ungovernable wife. Chapter Two examines fifteen comedies between 1600 and 1625, showing how fears and desires about widows and remarriage merged with theatrical conventions in the work of Middleton's contemporaries. Chapter Three then analyzes three of Middleton's earliest comedies which conform fairly closely to conventional views of remarrying widows: 'The Phoenix' (1604), 'The Puritan' (1606), and 'Michaelmas Term' (1606). Chapter Four shows how ' A Trick to Catch the Old One' (1605) and 'No Wit', ' No Help Like a Woman's' (1613) begin to expose the male self-interest and anxiety which construct the stereotypes of the widow. The comedies in Chapter Five--'More Dissemblers Besides Women' (1615) and 'The Widow' (1616)--continue this kind of undermining, with 'The Widow' providing Middleton's most explicit exposure of how the theatrical fantasy of the "lusty widow" debases women to assuage the anxieties of men.
Identification of ROM1- and PHR1-interacting proteins in the mammalian photoreceptor

The photoreceptor is a unique neuron in the retina, and its highly specialized organelle, the outer segment, is the site of phototransduction. Elucidation of the molecular basis of outer segment structure and function are two of the main goals of retinal research. Our group has described one major outer segment protein, ROM1, and more recently discovered a second outer segment polypeptide, PHR1, which contains a pleckstrin homology (PH) domain. ROM1 is an essential structural protein of the membranous disks which fill the outer segment. The function of PHR1 is unknown, but the presence of a PH domain suggests that it may be a component of the cytoskeleton or participate in a signalling pathway such as phototransduction. Using the two-hybrid system, I have used the ROM1 C-terminal tail and full-length PHR1 in two different screens to identify ROM1- and PHR1-interacting proteins. The ROM1 C-terminal tail screen has identified five novel putative ROM1-interacting proteins. Four novel cDNA clones encoding putative PHR1-interacting proteins were identified, one of which contains a RING finger domain, a well-known protein-protein binding motif. 'In situ' hybridization revealed that 'PHR1' is expressed in photoreceptor inner segments, the outer plexiform layer, and the ganglion cell layer of the retina. Immunohistochemical analysis indicates that PHR1 is specifically localized to the photoreceptor outer segments and to the plasma membrane of ganglion cells. Retinal PHR1 also migrates more slowly (~37kDa) than predicted (~25kDa), suggesting that PHR1 is post-translationally modified. The proteins which associate with ROM1 and PHR1 in vivo are likely to encode important-components of photoreceptor outer segment structure and function.
Thickness swelling behaviour of oriented strand board

The thickness swelling, spring-back, and swelling stresses of Oriented Strand Board were studied for commercial hot-pressed and experimental steam-injection pressed panels. Samples from the panel centre and edge were divided into top, core, and bottom layers. One panel was subjected to post-manufacturing heat treatment and similarly analysed. Both type of panels showed a J-shaped behaviour where density and swelling behaviour in the surface layers was greatest. However, for steam-injection pressed panels, thickness swell and swelling stress varied linearly from bottom to top. Sampling location showed no effect on swelling behaviour. Swelling stresses in both samples were similar. Swelling was positively correlated to density in hot pressed samples and not correlated in steam-injection pressed samples. Steam-injection pressed samples have higher density, and lower swelling values than hot pressed samples. Considerable reduction in swelling in oriented strandboard was achieved by post-manufacturing heat treatment. The effectiveness of the treatment was time-dependent.
A propos of medieval aesthetics, a historical study of terminology, sources, and textual traditions of commenting on beauty in the thirteenth century

The thesis approaches the textual tradition of commenting on beauty in the thirteenth century from a historical perspective and examines two major issues: the terminology of beauty and the sources of the thirteenth-century texts on beauty. The general organization of the thesis depends on the large amount of precise textual data placed in Appendices One and Two. The individual chapters are built around the interpretation of this material and contain multiple references to the Appendices. In Chapter One the thirteenth-century texts are chosen according to the principles of the continuity of textual tradition and mutual interdependence. Their contents are described, the terms of beauty are selected, and a preliminary list of sources is given. Chapter Two provides an analysis of the historical development of the meanings of the terms of beauty that are used in the thirteenth century. The study centers on the role of the earlier texts in the development of the thirteenth-century meaning of these terms, and examines the question of the historical convergence of their meanings. Chapter Three is devoted to the analysis of the sources of the thirteenth-century discussion of beauty. The Chapter is focused around the two figures whose texts played a major part in the thirteenth-century tradition of commenting on beauty: Cicero and Augustine. The use of these two authors is linked to the two textual traditions that are responsible for the dissemination of their texts related to beauty. The first tradition, which is the source of Cicero's quotations for the thirteenth-century discussion of beauty, is treatises "On the Good" and collections of moral excerpts. The second tradition, which supplied the relevant passages from Augustine, is Collections of Sentences, commentaries on the Sentences of Peter Lombard, and the corresponding sections from the thirteenth-century ' Summae'. Chapter Three is concluded by an examination of several thirteenth-century discussions around the interpretation of sources related to beauty. The thesis makes a contribution to the two areas--terminology and sources of the thirteenth-century discussion of beauty--that were inadequately covered in the previous scholarly literature. It provides another way of looking at the problem of "medieval aesthetics" from a historical perspective that is well supported by textual evidence.
Breast cancer survival by teaching status of the initial treating hospital

The objective of this study was to compare survival outcomes of women initially treated at teaching hospitals with those initially treated at community hospitals. The study cohort consisted of 938 women with confirmed node-negative breast cancer randomly selected from among those diagnosed in Ontario in 1991. Cox's proportional hazards model was used to control for the effect of patient and tumour characteristics and treatment received. Crude 5-year survival for women initially treated at teaching and community hospitals was 92.5% and 88.7% respectively (p = 0.067). Among women with tumours <=20mm there was a 53% reduction in relative risk for women initially treated at teaching hospitals as compared to community hospitals, after controlling significant confounders. A significant survival difference was not apparent among women with tumours >20mm. There are a number of possible explanations for thew findings: patient populations may differ with respect to factors not controlled for in the analysis; there may be misclassification of cases with respect to tumour characteristics; or them may be differences in treatments administered.
Biochemical and genetic analysis of excision DNA repair

The integrity of the genetic material is constantly threatened by various DNA damaging agents. Hence, multiple DNA repair pathways have evolved to eliminate damage of different origins. Nucleotide excision repair (NER) is the primary mechanism by which both 'S. cerevisiae' and human cells remove lesions, including those induced by ultraviolet light, that usually cause severe distortions of the DNA helix. I have described a simple protocol for preparing yeast whole cell extracts that can support efficient NER to facilitate biochemical studies of this repair pathway in yeast. This assay reflects ' bona fide' NER as it depends on 'RAD' genes such as ' RAD14' and 'RAD2', which are known to be essential for excision repair. Interestingly, the assay was also dependent on the ' RAD7' and 'RAD16' genes, whose precise roles in NER are uncertain. Using this system, I also demonstrated that yeast replication protein A (Rpa), encoded by the 'rfa'2 gene, is required for NER, since 'rfa2' mutations which confer enhanced UV sensitivity ' in vivo' also resulted in a deficiency in NER 'in vitro'. NER can be divided into two subpathways: global genome repair, which is involved in the repair of both active and inactive genes, and transcription-coupled repair. In the latter subpathway, lesions in the transcribed strands of active genes are more rapidly repaired, but contributions of the transcription machinery to this repair pathway are poorly understood. To determine whether the RNA polymerase elongation factor SII plays a role in excision repair, I examined the effect of deleting the SII gene of 'Saccharomyces cerevisiae'. Lack of SII activity enhanced UV sensitivity, but only in the absence of ' RAD7/16'-dependent global genome repair. This increased UV sensitivity was also seen with RNA polymerase II mutants defective in their response to SII. UV sensitivity was also conferred by other RNA polymerase II mutations that do not affect SII function. Another pathway of excision repair, base excision repair (BER), involves DNA glycosylases that recognize and excise specific types of base damage in DNA, including uracil and thymine glycol. Human uracil DNA glycosylase (UDG) was recently found to interact with the 34 kDa subunit of human RPA. To investigate whether RPA plays a role in BER in yeast and human cells, I set up ' in vitro' BER systems using yeast and HeLa cell extracts. Both of these systems appear capable of performing efficient BER in the presence of several types of lesions. I fractionated HeLa extracts to deplete endogenous RPA and I will test the ability of these fractions to perform BER. (Abstract shortened by UMI.)
The social resources of immigrants, effects on the integration of independent and family class immigrants to Toronto, Canada from South Asia

The central goal of this thesis is to examine the importance of a range of immigrant resources--not only human capital, but also social, financial cultural and psychological resources--in the process of immigrant integration, and to determine how these resources affect the relative success of independent and family class immigrants. Most immigration research conceptualizes integration in objective economic terms to the exclusion of other domains, with a concurrent preoccupation with immigrants' human capital resources; only recently has a competing explanation in the form of social resources emerged, though it remains understated. Using economic and well-being measures of integration, this thesis therefore addresses policy debates about the relative adaptability of these two immigrant classes, and contributes to a theoretically underdeveloped area by extending the definition of integration, and of the integration process, beyond the human capital model. The analysis uses data from the 'South Asian Newcomer Study' collected for this thesis, in which 109 face-to-face interviews were conducted with family and independent class South Asian immigrants. Findings indicate slight differences in human capital resources by immigrant class, though independent class respondents have higher levels of financial and cultural resources. Respondents' network structures vary by class, with family class respondents reporting smaller, more dense, kin-dominated networks, and higher overall levels of social support. In terms of economic integration measures, independent immigrants are more successful, though high levels of certain types of human capital are a liability to achieving economic integration. Moreover, family class respondents' poorer economic performance is linked to the composition of their networks, which disadvantage them in this domain of integration, and not to their human capital levels. Overall, social network and human capital variables are the strongest predictors of economic integration, challenging researchers' preoccupation with the latter. In terms of levels of well-being, family class respondents report higher levels despite poorer economic outcomes; this is explained by their superior levels of social support, which are the strongest predictors in conjunction with a measure of cultural capital. Results support a multidimensional conceptualization of integration that acknowledges the independence of different domains. Theoretical and policy implications are discussed.
The cloning and characterization of two semaphorin genes in Caenorhabditis elegans

Cells and axons require molecules to guide them along stereotypical trajectories towards their target destination. Well-characterized guidance molecules such as the Netrins and the Semaphorins attract and repel migrations over both a long and short-range throughout development. While the Netrins guide the migrations of both cells and axons, the Semaphorins, have been shown to act as axon guidance molecules only. Although the Semaphorins may be required for organ development, immunity, and tumor suppression, their role in these processes is not yet clear. In addition, down-stream-signaling components of the Semaphorin receptors that modulate the actin cytoskeleton during growth cone migration are still unknown. To investigate if the Semaphorins have broad roles throughout development, I cloned and characterized two 'semaphorin' genes in the nematode ' Caenorhabditis elegans'. First, I have used a transgenic approach to demonstrate that 'semaphorin' I may function in the development of the neuromuscular system that regulates defecation. Not only are animals carrying putative dominant-negative transgenes constipated, but 'semaphorin ' I reporters are also expressed in many cells that control defecation. Second, I cloned, characterized, and created a putative null mutation in 'C. elegans' 'semaphorin II' ('ev574 '), that failed to complement previously isolated 'mab-20' mutations, for which the gene had not yet been cloned. That is, 'mab-20 ' encodes 'C. elegans' Semaphorin II. I show that ' mab-20'('ev574') confers errors in axon and cell guidance during migrations. The most penetrant 'mab-20' phenotypes, however, occur within the epidermis during embryonic and larval morphogenesis. These phenotypes can be explained by ectopic contact formation between a small sub-set of epidermal cells during their migrations and rearrangements before and/or during epidermal morphogenesis. These results show for the first time that the Semaphorins can not only guide migrating axons, but cells as well. In addition, the detailed descriptions of the 'semaphorin' mutant phenotypes and a preliminary genetic screen have laid the foundation for further genetic screens to identify components within the Semaphorin pathway. Finally, in pursuing loss-of-function mutations in 'C. elegans semaphorins', I have improved the efficiency and techniques for obtaining Tc1-transposon-mediated mutations. To date, this work has enabled the isolation of over 40 alleles for various laboratories.
Literacy and social identity in a Nunavut community

The problem addressed in this thesis is the relationship between literacy and social identity in the Nunavut community of Igloolik. I used qualitative methods to work with a representative sample of the adult Inuit and non-Native population of this Northern Canadian community during fieldwork in 1990, 1992, and 1993. I found that getting an education (in English), learning the finals (in Inuktitut), and reading and writing traditionally (in Inuktitut) are ways of using literacy that distinguish active biliterates, other younger Inuit, older Inuit, and non-Natives. Active biliterates are able to access resources in the local cash economy because they have got an education and learned the finals, the symbols for syllable-final consonants in written Inuktitut. Other younger Inuit face unemployment if they have not got an education and learned the finals. Older Inuit read and write traditionally but this does not help them to access resources in the cash economy. Non-Natives are employed locally because they have got an education. These differences have emerged in the context of processes in which local Inuit have been sedentarized; the orthography of their language, Inuktitut, has been standardized; and a system of credentialization by grade level has been introduced. These processes reflect in turn the dynamics of the legitimation of the Canadian state in the North and the superimposition of a cash economy onto an economy of structured sharing with kin. Future decisions in literacy planning must take into account the social identities of the residents of Nunavut.
Characterization of fibre suspension flows at papermaking consistencies

Accurate and effective quality control of the manufacture of information grade paper is becoming the primary papermaking concern with the recent and upcoming advances in modern printing technology. An important quality issue, but poorly understood phenomenon, is the interactions between papermaking flow characteristics and the uniformity of fibrous suspensions. To extend knowledge and understanding of these complex interactions, the behavior of a flowing pulp suspension in a grid generated turbulence flow field was experimentally studied and the scale dependency of the suspension uniformity was modeled. A Dynamic Panoramic View technique was developed simultaneously to measure and quantify the suspension local mass variability along the stream-wise direction as well as the transverse direction. The effects of mean flow velocity, concentration, and local flow characteristics on the local mass variability of a representative hardwood kraft pulp were studied. A model was developed to characterize the rate of fibre aggregation in a decaying turbulent flow field. This model was found to be in excellent agreement with experimental data.