VictorJuiz/thesis huggingface dataset:
The physiological mechanisms underlying the osmotic effects on neutrophil function, role of MAPKp38 and the osmotic remodelling of the actin cytoskeleton

Trauma care has progressed significantly in 50 years and new challenges have arisen. Nowadays, patients often die of inflammatory complications rather than from the trauma/hemorrhage itself. Multiple organ failure is the commonest cause of death, and lung, the earliest and commonest organ to fail. Motivated by nascent concepts, we resuscitated rodents in a post-hemorrhage acute lung injury model, with hypertonic saline solution. The increased serum osmolarity attenuated lung damage, mostly by causing a profound, but transient suppression of neutrophil function, which are pivotal in the pathogenesis of post trauma lung failure. In trying to understand the underlying mechanisms, we identified that cell shrinkage alone altered surface expression of adhesion molecules, and impaired adhesive, migratory, oxidative and exocytic neutrophil functions. Earlier studies demonstrating that neutrophil shrinkage caused tyrosine phosphorylation led us to investigate the involvement of stress-activated signaling pathways. We found that shrinkage activated p38, which regulated both the osmotically induced L-selectin shedding and apoptosis. We also identified other osmosensitive kinases, Hck, Syk and Pyk2, that did not mediate the functional outcomes described above. Considering the relevance of the actin cytoskeleton in all suppressed neutrophil functions, we hypothesized its involvement. In fact, shrinkage markedly increased filamentous actin content while abolishing exocytosis of all granules, regardless of the stimulation used. Pharmacological inhibition of osmotic actin polymerization with latrunculin B, restored exocytosis in shrunken cells while induction of polymerization mimicked the effects of hypertonicity under isoosmotic conditions. Impaired chemotaxis, rolling, adhesion, transmigration, respiratory burst and L-selectin shedding were all found to be fully or partially regulated by these cytoskeletal changes. In conclusion, osmotically induced changes in both signaling transduction pathways and actin cytoskeleton are important and common mechanisms accounting for many neutrophil suppressive effects, which will be explored for the management of post-trauma organ failure in an upcoming clinical trial.
Fluid transients and pipeline optimization using genetic algorithms

Millions of dollars are spent each year on water distribution systems. Pipe optimization techniques provide an opportunity for potential savings in costs for water supply systems. These optimization techniques include linear programming, non-linear programming, dynamic programming, enumerative approaches, and genetic algorithms. The former four techniques have been applied to pipe network optimization in the research literature over the last 20 years or so. Genetic algorithms provide a new approach to pipe network optimization. Details of this method are considered in this thesis. A global cost analysis of each component in a water supply system is carried out of the genetic algorithm in order to assess the form of the objective function. Traditionally, the analysis an pipeline systems has focused on the steady state. In the current work, a genetic algorithm optimization model, which uses a probabilistic search procedure that emulates Darwinian natural selection, is coupled with a transient hydraulic simulation model to generate and evaluate trial pipe network designs in search of an optimal solution. A new and powerful penalty function is also developed for pressure violations distinguishing steady state and transient conditions. The genetic algorithm search is applied to a case study which demonstrates its flexibility and the opportunity for significant cost saving offered by this method.
Interaction of cytochrome P450 2C19 with benzodiazepines in vitro: Flunitrazepam identified as a substrate of CYP2C19

Fluintrazepam (Rohypnol$\sp\circler$) is an abused benzodiazepine that has gained notoriety in North America as the "date rape" drug because it causes memory loss and sedation in women who are surreptitiously given the drug. Differences in sensitivity to fluintrazepam are not known. The interaction of various benzodiazepines with cytochrome P450 2C19 and metabolism of flunitrazepam in human liver microsomes were investigated. CYP2C19 is polymorphically expressed in human populations and metabolizes many therapeutically important drugs (e.g., diazepam, omeprazole). 23% of Japanese and 3% of Caucasians lack CYP2C19 activity because of mutations in the gene coding for CY2PC19. We hypothesized that fluintrazepam is metabolized by CYP2C19. Omeprazole was used as the probe drug to characterize CYP2C19 and CYP3A4 activity by quantitating 5-hydroxyomeprazole (5-OHOMP)(CYP2C19) and omeprazole sulphone (CYP3A4) formation. Omeprazole kinetics in African-green monkey liver microsomes were also studied and are comparable to that in human liver. Formation of 5-OHOMP and omeprazole sulphone was inhibited by various benzodiazepines in human and African-green monkey liver microsomes and respective K$\sb{\rm i}$ values determined. (Abstract shortened by UMI.)
Genetic predisposition to ovarian cancer in Ashkenazi Jewish families

Inherited mutations in the BRCA1 and BRCA2 genes confer a high risk for breast and ovarian cancer in certain families. To determine the spectrum of germline BRCA1 and BRCA2 mutations, 51 Ashkenazi Jewish ovarian cancer families of varying risks for developing breast and/or ovarian cancer were analyzed. Recurrent mutations were identified in 31% (15/51) of families. Ten of sixteen (63%) high-risk families were attributed to recurrent mutations (BRCA1 185delAG, 5382insC, and BRCA2 6174delT). Fourteen families harboured BRCA1 mutations, and one family had a BRCA2 mutation. This was significantly greater than the number of carriers in the medium-risk (17%, 3/17) and (13%, 2/15) low-risk families. Additionally, there was a positive association between BRCA1 mutations and the number of ovarian cancers in families, in the presence or absence of a family history of breast cancer.
Murine models of cerebral ischemia, development of a mouse model of global cerebral ischemia; response of GluR2 knockout mice in a model of permanent focal cerebral ischemia

'I. Development of a four-vessel occlusion model of murine global cerebral ischemia: Influence of strain, ischemic duration and reperfusion time'. Cerebral ischemia resulting from cardiac arrest leads to delayed selective neuronal death. A similar pathological outcome is observed in a variety of experimental animal models of global ischemia. However, a reproducible murine model of ischemia resulting in delayed selective neuronal death has yet to be established. Such a model could be applied to transgenic and knockout mice to further elucidate the roles of specific genes and their products in the underlying pathophysiology resulting from cerebral ischemia. ' Purpose'. To develop a model of global cerebral ischemia in the mouse. ' Hypothesis'. Mice subjected to global ischemia produced by a four-vessel occlusion ('4-VO') model will yield the delayed selective death of >90% of pyramidal neurons in the CA1 region of the hippocampus. 'II. Mice lacking GluR2 are NOT more susceptible to focal cerebral ischemia'. The massive influx of Ca2+ ions through neuronal glutamate receptors has been implicated in the pathophysiology of focal cerebral ischemia. AMPA receptor ion channels are composed of heteromeric combinations of four subunits (GluR1, 2, 3 & 4). The inclusion of GluR2 in its composition renders AMPA receptors Ca2+-impermeable. The GluR2 Hypothesis states that cerebral ischemia induces the selective loss of this subunit, and consequently, increases Ca2+-permeability through GluR2-less AMPA receptors. 'Purpose'. We have therefore tested the response of mice lacking this subunit in a model of permanent focal cerebral ischemia. 'Hypothesis'. GluR2(-/-) mutant mice will be more susceptible to ischemic injury resulting from the permanent occlusion of their middle cerebral artery. (Abstract shortened by UMI.)
Nutrient and carbon loading of black spruce containerized seedlings during nursery culture and early outplanting

Loading conifers seedlings with a maximum level of nutrient and carbohydrate reserves during the nursery phase can potentially increase seedling vigor and performance after transplanting to the field. To enhance this integrated practice, black spruce ('Picea mariana' (Mill.) B.S.P.) seedlings were raised under two fertilizer levels (10 mg N seedling-1, representing the conventional regime, and 75 mg N seedling-1 , representing exponential loading regime), and exposed to two levels of CO2 (370 ppm, as ambient, and 800 ppm, as elevated CO2 ) at the end of the nursery phase for 3 weeks. Compared to the conventional fertilization regime, exponential loading induced luxury consumption and increased seedling nutrient reserves substantially. Short-term CO2 enrichment for 3 weeks stimulated photosynthesis and built up carbohydrate reserves in the nutrient-loaded seedlings. However, no significant increase in carbohydrate reserves was observed in the conventional seedlings, due to inadequate nutrient availability. The performance of both nutrient- and carbon-loaded seedlings after planting was tested under greenhouse conditions. Results suggested that combined nutrient and carbon loading practices have high potential in building up seedling nutrient and carbon reserves and that may effectively improve early field performance.
Religious ideals, beliefs and practices in the lives of women during the reign of T'ang Ming Huang

This dissertation will examine the socio-legal parameters and the various religious attitudes that influenced the lives of women during the times of Li Lung-chi. Contemporary religious teachings and practices, as well as the lives of women at court will be emphasized. Also of particular interest here is the divergence between the religious ideals and historical reality. This is, therefore, a very broad study of what the three main teachings, Confucianism, Taoism and Buddhism conceived of as the nature of woman, what constituted a good or a bad woman, and what place and role a woman has in life and ritual. There will also be an analysis of the effects of certain women's failure to live up to an assigned set of ideals. For example, there will be some consideration of the aftermath of Wu Hou's use of Buddhism, followed by T'ai-p'ing Kung-chu and Yang Kuei-fei's use of Taoism. The approach in this dissertation is an eclectic one; it uses historical, philosophical and sociological perspectives. The intent is not to offer a comprehensive account; rather, the hope is to achieve two main objectives. First, to render a sketch of the dissonance between the ideals and the practices of the three teachings as represented in their doctrines and philosophies on the one hand, and the behaviour of professed believers like the imperial women and the popular expressions in contemporary religious beliefs and devotional practices on the other. Second, to examine how this dissonance, as reflected in the actions of particular women at court, might have affected the later interpretations and development of the teachings. Entire areas have, therefore, been omitted: for example, the ritual sections concerning women in the dynastic histories, ' Chen-yen' (True Word or Esoteric) practices and their views on women, and the habits and accomplishments of courtesans. The two main approaches are historical and philosophical; sociological observations are built on them. Sources include dynastic and general histories, canonical and apocryphal Buddhist scriptures, moral and philosophical treatises, as well as popular literature. The limits imposed by the source materials will be obvious. Most of the data that is straightforward descriptions of women is limited to the imperial household, the court and the upper classes. Much of the information about the lives of ordinary women can only be inferred, and often unsatisfactorily, from popular literature and prescriptive treatises. In this way, this dissertation can only be an incomplete account of women and religion during the time of T'ang Ming Huang (Brilliant Emperor).
Reproduction, hibernation, and population regulation of arctic ground squirrels (Spermophilus parryii plesius)

Populations of arctic ground squirrels in the boreal forest of the southwest Yukon were studied in order to answer the following questions: (1) What are the mechanisms of population regulation in arctic ground squirrel populations, (2) How does variation among individuals and their environment influence their reproduction and survival, and (3) How does variation in habitat influence hibernating strategies of arctic ground squirrels? In spring 1996, control densities of ground squirrels were 1.6 per ha, and four other populations ranged in density from 3.2 to 30.1 per ha as a result of a 10-year (1987-96) large scale manipulation of food and predators in the boreal forest of the Kluane Boreal Forest Ecosystem Project. When the Kluane project terminated in spring 1996, I measured population densities, reproduction, emigration, and survival in all populations using live-trapping and radio-telemetry techniques until spring 1998. Arctic ground squirrel populations were strongly regulated because all experimental populations declined to control densities within two years after the termination of the experimental manipulations. Two factors proved strongly density-dependent and hence were regulatory: (1) the proportion of females that weaned their litter and (2) overwinter survival. Simultaneous density-independent changes in weaning rate were also detected and were attributed to changes in the previous year's snow accumulation. Female ground squirrels exhibited positive associations of life history traits. Squirrels in better condition at spring emergence were more likely to give birth, wean their litter, survive to the next breeding season, and reproduce once again. Nearly all females who failed during lactation did not survive to the next breeding season. The overwinter survival rate of females that successfully weaned a litter declined at a greater rate with increasing population density than did squirrels that never gave birth, indicating a cost to reproduction. Ground squirrels hibernated distantly (24 m) from their summer burrows in relation to population density and in open or shrubby habitats that were likely to accumulate the most snow. Increased snow accumulation over hibernacula increased the minimum soil temperatures and decreased the rate of mass loss of hibernating squirrels suggesting a selective mechanism for the ability of ground squirrels to identify habitats that minimize their energy expenditure during hibernation.
Women ben purifyid of her childeryn, the purification of women after childbirth in medieval England

This study of the purification of women after childbirth in medieval England undertakes two tasks. First, it recovers and documents the rite of post-partal purification, and the customs surrounding it, as it was practised in England, from the earliest extant references to it originating in the twelfth century, to the publication of the second Edwardian 'Book of Common Prayer' published in 1552. It then examines the ways in which this rite both reflected the communities in which it was practised, and contributed to the shaping of those communities. In order to document the rite, the extant versions of the medieval rite of postpartal purification found in English liturgical books are presented and compared. A variety of non-liturgical sources provides information regarding the customs associated with this rite not recorded in the liturgical books. Informed by three fields of study, the study of popular religion, ritual studies, and gender history, this study then identifies and examines the interactions between and among the various individuals and groups involved in the development and perpetuation of this rite, and the customs surrounding it. First, the relationship between the feast of the Purification and the rite of post-partal purification is examined, illuminating the role this rite played in the ritual life of the community. Then the involvement and investment of various groups within the community is explored. The interaction between clerical perceptions of the rite of purification, and women's own perceptions is examined. In England, not only women in recognised marriages, but the mothers of illegitimate children also participated in this rite. Their participation allows an examination of medieval attitudes towards them. Heads of households are also shown to have contributed towards, and benefited from, this rite and the customs surrounding it. Finally, this study returns to the community as a whole, examining the role the revenues generated by the rite of post-partal purification played in medieval English parish politics. Nine appendices provide excerpts relating to the medieval English practice of post-partal purification from unpublished clerical accounts, churchwarden's accounts, ecclesiastical court records, liturgical books, inquisitions post mortem, and manuals of confession and pastoral care.
The constitution of consciousness, a study in analytic phenomenology

In this thesis I pursue two major goals. I develop an account of constitution to describe how we can be directed towards objects in our mental episodes. In doing so, I use results of Husserlian phenomenology and put them into the context of contemporary analytic philosophy of mind, thus taking an approach that can be best described as 'analytic phenomenology.' In the first chapter I argue that a strong emphasis on the differences between mind and world, as we find it in Descartes, for example, creates an unbridgeable gap between them. Two main strategies of contemporary philosophy of mind, reductionism and eliminativism, are reactions to, rather than rejections of, this distinction. I propose that an account of constitution can provide a perspective that acknowledges, but does not overemphasize, the differences between the mental and the physical. In the second chapter I outline the history of the notion of 'constitution.' In contrasting the positions of Husserl and Haugeland I present the main features of constitution. Then I develop an account of constitution, according to which the objects, towards which we are directed, and the mental episodes, in which we are directed towards them, are constituted. I argue that constitution requires a holistic background. Using Husserl's analyses of time consciousness I describe how this background can shape the content of an occurrent mental episode. I show that establishing this background rests on our biological makeup and environment, on passive processes of association, and on the social group in which we grow up. In the fourth chapter I concentrate on the social aspect of constitution. I argue that we learn to constitute various kinds of mental episodes through social practices, mainly through acquisition of language, and that anti-individualism allows for phenomenological analysis. Finally, I discuss whether constitution entails idealism. I use a late-Wittgensteinian argument to show that metaphysical realism and idealism are unintelligible positions. I conclude that the claim that constitution implies transcendental idealism depends on the assumption that we can meaningfully distinguish between the object as it is in itself and the constituted object.
Street architecture, nineteenth-century urban buildings and the British architectural profession

"Street Architecture", a phrase used by British architectural writers from the 1820s, described stylish small-scale residential and commercial urban buildings that no longer adhered to urban vernacular norms. These buildings determined much of the architectural character of modern metropolises, and therefore street architecture was one of the most conspicuous aspects of nineteenth-century modernity. For a century prior to World War I the term found its way into most British monographs, essays, editorials and addresses on the subject of contemporary architecture. Street architecture posed problems that elicited a variety of responses, yet patterns do emerge. The unregulated nature of nineteenth-century urban architecture created streetscapes comprised of racy individualistic buildings, many of which affronted architectural propriety. When irregularly composed streets were deemed a relief from the so-called monotony of Georgian streets, or a by-product of the "Battle of the Styles", their variety was Picturesque and therefore respectable. However, much of this complexity was also understood as mercantile rivalry that made commercial buildings compete with one another in scale and ostentation. Writers who defended the dignity of the architectural profession objected to buildings that appealed to the public in the service of business interests. The discipline of urban planning was founded early in the twentieth century, in large part because government seemed poised to determine the character of all future urban architecture. Anticipating this opportunity, British architects-turned-planners envisioned remaking London in the image of Paris. Those who adopted Beaux-arts ideals, and even planners committed to Picturesque principles of design in Garden Cities and Suburbs, interpreted Victorian architectural exuberance as exclusively pandering to crass commercialism, and demanded that streets be composed of modest, dignified buildings. Planners argued for new city architecture that did not cater to popular taste. In the event, urban architecture remained undisciplined and "street architecture" disappeared from planners' lexicon. But the history of the term exposes the contest between architects and the city that shaped planning theory in Britain in the first half of the twentieth century. It also illuminates the vitality of debate occasioned by the unprecedented growth of nineteenth-century metropolises, which professional interests ultimately obscured.
Dietary hydroxycinnamic acids, phase I and Phase II metabolism

Plant phenolics have been found to exert many beneficial health effects. Much is known about their beneficial health effects, but very little is known about their metabolism. The largest group of plant phenolics in the diet are the hydroxycinnamic acids (e.g., chlorogenic acid, caffeic acid, ferulic acid). Mass and UV spectral analyses have been used to show that caffeic, chlorogenic, and dihydrocaffeic acids were metabolized by phase I enzymes to form a reactive 'ortho'-quinone, which in turn formed various conjugates with glutathione. The 'ortho'-quinone formed also underwent further oxidation in the presence of H2O 2/O2 to form a hydroxylated product and possibly its ' para'-quinone oxidation product. The phase II conjugating enzyme catechol ' O'-methyltransferase also catalyzed the 3-'O'-methylation of caffeic, chlorogenic and dihydrocaffeic acids, while CYP 1A1/2 catalyzed an 'O'-demethylation of ferulic acid and dihydroferulic acid. Hepatocytes also catalyzed the reduction of caffeic acid to dihydrocaffeic acid.