VictorJuiz/thesis huggingface dataset:
Aboriginal Women in Central Australia, a Preliminary Account

This thesis sets down principles of traditional aboriginal land ownership in Central Australia because political events demonstrate little is known of it. Thus the tabular data has been inserted giving background material from which sites owned by aboriginals are extracted. The problem is to demonstrate that aboriginal women--through the conception sites and their totems--are born equal with men. Three sites have been chosen from these records: Emalk[eta]a, Urumuna and Tu[eta]a. The latter is selected because the introduction of European blood shows that part-white children also inherited land ownership from the aboriginal side of their heritage. The thesis is preliminary study, since when I began this work thirty years ago, I envisaged doing the whole of the Central Australian aboriginal land ownership, both men and women. Due to official opposition it was not to be. This thesis survives as a small yet vital fragment from which generalisations can be made.
The implications of Canadian law for economic approaches to allocating health care resources: The round hole and the square peg

Chapter one explains that the purpose of this thesis is to analyze legal principles at issue when attempts are made to ground allocation policies in economics. Chapter Two examines the ethical values reflected by economics and law. It explores the tensions between the philosophical perspectives of consequentialism and deontology and describes options for bringing normative theories to practice. The purpose of this chapter is to provide the reader with the ethical context of law and economics. Chapter Three describes and analyzes the contribution economics can bring to resource allocation. The chapter addresses four utilitarian based methods of priority setting: cost-minimization analysis, cost-benefit analysis, cost-effectiveness analysis and cost-utility analysis. These are formal methods of comparing costs and consequences of medical interventions to determine whether they are worth funding. Chapter Four examines the legal implications of making allocation decisions according to economic principles. It focuses on the areas where economics and law conflict in relation to resource allocation, the legal theory behind the values at issue in resource allocation and the potential for reconciliation of economic and legal principles. The areas of law focused on are the principles of comprehensiveness, accessibility, public administration, universality and portability under the 'Canada Health Act', the doctrines of legitimate expectations, public interest standing and rules around discretion in administrative law, the right to equality (s.15), available remedies (s.24) and the principles of pressing and substantial, and proportionality (s.1) under the 'Canadian Charter of Rights and Freedoms' (Charter). Chapter Five of the thesis concludes that the legislative objective of making allocation decisions that respect economic principles can be accomplished to the extent that allocation decisions do not violate Canadian law. In recent cases, courts have shown a new willingness to expand the range of issues they are willing to address and consider the legality of government allocation decisions, an area that has traditionally been left to the discretion of government. Evolving case law suggests that allocation policies focusing on consequentialism expressed by economics will have to be compromised if Canadian allocation policy is to accommodate legally binding deonotological values entrenched in law.
HIV gene therapy using nucleases

We are interested in designing RNases for use in HIV gene therapy. In order to develop a "colocalized RNase", Gag-RNase T1 was designed to cleave HIV genomic RNA within viral progeny. Retroviral vectors have been constructed to allow expression of the 'gt1' gene and mutant ' gt1' gene. Gag-RNase T1 was detected by ELISA in transformed ' E. coli' cells with no apparent cytotoxicity; however, it could not be detected in transiently transfected 293-T cells or stable MT4 transductants. Preliminary PCR and RT-PCR analysis of an MT4 cell transductant suggested that a deletion within the proviral DNA was associated with the lack of Gag-RNase T1 production. RNase T1 antibodies were raised in rabbits for specific detection of Gag-RNase T1 or mutant Gag-RNase T1. Also, a cell line producing replication incompetent HIV was constructed for analyzing the mode of inhibition of Gag-RNase T1 or mutant Gag-RNase T1.
Tailoring thermal residual stresses to maximize buckling loads in composite plates

The effect of tailoring the thermal stresses in composite plates is studied. Traditionally thermal stresses have been seen as a problem that must be minimized to prevent premature failure. While this is a concern, thermal residual stresses can also be used to prestress a composite plate so that the plate resists buckling loads. Numerous numerical studies were performed to determine the effect of various parameters such as the temperature change the plate undergoes, the aspect ratio, boundary conditions and the size and location of stiffeners. Then plates under various loading configurations were optimized to determine the configuration that results in the largest increase in buckling load, and how much improvement is possible for each configuration. The optimized plates were then analyzed neglecting the effects of temperature and it was found that thermal residual stresses had a large effect on the modeled plate's buckling load.
Identification of distinct residues in the carboxyl tail regulating desensitization and internalization of the D¦1 dopamine receptor

In order to investigate the mechanisms underlying agonist induced desensitization and internalization of the D1 dopamine receptor, we used site-directed mutagenesis to remove potential phosphorylation sites in the third intracellular loop and carboxyl tail. Three mutant receptors with serine/threonine residues changed to alanine in the distal carboxyl tail between 431-446 failed to internalize, in comparison to internalization of 25% of the wild-type receptors. As further serine/threonine residues were mutated serially in the carboxyl tail, we demonstrated that substitution of Thr360 in the proximal portion completely abolished desensitization, compared to a 29% decrease in Vmax of the wild-type receptors. Since Thr360 is next to a glutamic acid residue, it represents a potential GRK2 phosphorylation site. These results suggest that desensitization and internalization are regulated by separate and distinct residues within the carboxyl tail, and that GRK2 may be the predominant regulator of rapid agonist induced desensitization of the D1 dopamine receptor.
The effects of life history parameters on the reproductive potential of yellow perch (Perca flavescens) populations

Yellow perch populations in Lake Erie exhibit large yearly fluctuations in year class strength (YCS), with most years showing relatively poor recruitment. For percids, no statistically significant relationship between stock and recruitment has been found. Most research has focussed on various environmental factors to explain the variability in YCS. Of the studies reviewed in the first chapter, variations in YCS could not be explained by variation in any single environmental factor. The second chapter revisited the theoretical equation that spawning stock size is related to recruitment. Yearly variation in the number of mature females in the spawning stock may explain the variability in the YCS of perch. We found that the proportion of fish at age varied annually from 1978-1990, suggesting that intermittent reproduction exists for Lake Erie yellow perch. The third chapter evaluated through a model whether variation in the proportion mature as well as interannual variations in age distributions, size and the associated size-related fecundity could explain the variability in YCS of the yellow perch populations. Variation in the proportion mature could explain a large proportion of the observed YCS, however we could not accurately predict recruitment from the variations in the life history parameters included in the model.
Origin and diversification of neural stem cells during mammalian brain development

Neural stem cells are self-renewing precursor cells that have a fundamental role in generating cellular diversity in the developing mammalian brain. However, the establishment of this unique class of cells during the course of embryogenesis has previously not been characterized. In this thesis, I investigate mammalian neural stem cell ontogenesis using mouse as a model system. First, evidence is presented suggesting that neural stem cell formation is preceded by a primitive neural stem cell stage before the onset of neurogenesis. Primitive neural stem cells display distinct growth factor requirements for the production of progenitor cells and have a broad range of neural and non-neural lineage potential. The transition from primitive neural stem cell to definitive neural stem cell is correlated with an alteration in growth factor dependence and a restriction in multilineage potential. Acquisition of primitive neural stem cell identity is negatively regulated by TGFß signaling proteins, which act to inhibit neural differentiation. Second, results from experiments performed after the onset of neurogenesis reveal that the entire germinal zone is initially composed of a small population of neural stem cells that are critically dependent upon FGF as a stimulus for generating progenitor cells. As neurogenesis proceeds, the FGF-responsive neural stem cell population expands and also gives rise to a distinct EGF-responsive neural stem cell population. A heterogeneous population of FGF- and EGF-responsive neural stem cells (both with self-renewal and multilineage potential) persists in germinal zone compartments throughout the brain. Finally, experiments show that during neurogenesis, neural stem cells and their early progenitors isolated from distinct brain compartments maintain a region-specific pattern of regulatory gene expression in the absence of their in vivo environment. However, this regional specification may not be irreversible and can be altered by local inductive cues. Overall, the results of this research provide the first description of mammalian neural stem cell ontogenesis. An ontogenetic model for the origin and diversification of mammalian neural stem cells is discussed in the context of brain development and adult neural homeostasis. The thesis concludes with an attempt to consolidate what is currently known about stem cell ontogenesis and behavior in various tissues and diverse organisms in order to elucidate the role of stem cells during metazoan evolution.
Anaerobic degradation of linoleic (C¦1¦8:¦2), oleic (C¦1¦8:¦1) and stearic (C¦1¦8:¦0) acids and their inhibitory effects on acidogens, acetogens and methanogens

Effluents from many food processing industries contain fats and oils in addition to carbohydrates and proteins. Long chain fatty acids (LCFAs), a hydrolysis byproduct of fats and oils, are difficult to degrade and are inhibitory to anaerobic organisms. These acids are degraded via ß-oxidation but the compound initiating the mechanism has not been clearly identified. Although LCFAs inhibit aceticlastic methanogenesis their effects on acidogenesis, acetogenesis and hydrogenotrophic methanogenesis have not been well studied. This study assessed the degradability of linoleic (C18:2), oleic (C18:1) and stearic (C18:0) acids and determined their inhibitory effects on anaerobic organisms in 160 mL serum bottles. Degradation and inhibition studies were conducted using 10, 30, 50 and 100 mg·L-1 LCFA. Inhibition studies using glucose, butyrate and acetate (each at 100 mg·L-1) and hydrogen (10.1 kPa) investigated the effects of the three LCFAs on acidogens, acetogens, aceticlastic methanogens and hydrogenotrophic methanogens. Unsaturated C18 LCFAs were degraded to shorter chain LCFAs however, no LCFA byproducts were detected as intermediates during the degradation of stearic (C18:0) acid. Palmitic (C16:0) and myristic (C 14:0) acids were produced from linoleic (C18:2) acid at all concentrations examined and in cultures receiving more than 10 mg·L -1 oleic (C18:1) acid. In cultures receiving 100 mg·L-1 linoleic (C18:2) acid, both oleic (C18:1) and palmitoleic (C16:1) acids were detected. Acidogenesis was affected by the presence of LCFAs and synergistic inhibitory effects of all three acids on acetogenesis were observed. Hydrogenotrophic methanogenic inhibition was observed and aceticlastic methanogens were inhibited at all LCFA concentrations examined. In cultures fed with linoleic (C 18:2) and oleic (C18:1) acids, inhibition of acetate methanogenesis was concentration dependent but for cultures receiving stearic (C18:0 ) acid, the effect was independent of concentration. In comparison to stearic (C18:0) acid, linoleic (C18:2 ) and oleic (C18:1) acids were degraded faster. Therefore, the design of a full-scale system will depend on the SRT for the more slowly degrading LCFA. LCFAs affected glucose and butyrate degradation. Hence, in effluents containing carbohydrate and LCFAs mixtures, the degradation of carbohydrate monomers will be affected. In comparison to oleic (C18:1) acid, greater aceticlastic inhibition was observed for cultures receiving linoleic (C18:2) acid. Thus, it is recommended a two-stage process, acetogenic followed by methanogenic, be used to minimize the inhibition.
Cell cycle regulation in epithelial cell senescence and in response to TGF-ß

Cellular proliferation is tightly controlled by a family of cell cycle regulators that function to ensure the orderly completion of each phase of the cell cycle. The cell cycle regulators consist of a repertoire of kinases, the cyclin dependent kinases (cdks), their partner cyclins and two families of cdk inhibitors. In the course of this thesis, I investigated the manner by which these cell cycle regulators function to mediate an arrest of cellular proliferation in response to anti-proliferative signals. The signals that I investigated were those elicited by TGF-ß, an anti-mitogenic cytokine, and by cellular senescence. My studies utilizing a human mammary epithelial cell model demonstrated an increase in both the steady state level and stability of a cdk inhibitor, p15INK4B, in response to TGF-ß. The increase in the steady state level of p15 was mirrored by an increase in its association with cdk4 and cdk6 complexes. The increase in p15 binding to these complexes was accompanied by a loss of cyclin D1 association to both cdk4 and cdk6 complexes, which resulted in their subsequent loss of kinase activity. An absence of kinase activity from these cell cycle complexes served to arrest cellular proliferation at the G1/S phase of the cell cycle in response to TGF-ß. The proliferative capacity of normal cells is limited to a finite capacity due to the constraints imposed by cellular senescence. My investigations into the manner by which cell cycle regulators mediate the senescence arrest yielded different results in two model systems: human mammary epithelial cells (HMEC) and human prostatic epithelial cells (HPEC). In HMEC, a loss of expression of 'Cdc25A', a cell cycle phosphatase, at senescence served to contribute towards a loss of cyclin E/cdk2 activity. However, in HPEC, p16INK4A steady state levels increased and correlated with an increase in its binding to both cdk4 and cdk6 complexes. The subsequent loss of cyclin D1 association that accompanied the increased p16 binding served to suggest a role for p16 in the inhibition of these complexes. In contrast to studies in senescent fibroblasts, no increase in the steady state level or association of p21 to target cdk complexes was observed.
Properties and occurrence of lipids in extracellular polymeric substances (EPS) of activated sludge flocs

The objective of this study was to improve our understanding of the composition of extracellular polymeric substances (EPS), particularly lipids, and their influence on floc structure and surface chemistry of microbial flocs. Total carbohydrates and lipids were the dominant components in capsular EPS extracted from the microbial floc grown in reactors at different sludge retention time (SRT), followed by humics, protein, acidic polysaccharides and DNA. The relative hydrophobicity of microbial floc was affected by SRT. Sludge surfaces at higher SRTs (16 and 20 days) were more hydrophobic than those at lower SRTs (4 and 9 days). Lipids comprised about 31% of the total EPS content extracted from microbial floc with different SRTs. The strong correlation between the concentration of lipids; in slime and capsular EPS, improved emulsification properties of EPS, and sludge retention time all indicate the importance of lipids in influencing the surface activity of floc.
Characterization of the mu opioid receptor desensitization mechanisms in a heterologous expression system

Endogenous opioids play an important role in a variety of physiological processes and mediate their actions through at least three distinct subtypes of cell surface receptors: mu, kappa and delta. The mu opioid receptor is considered to be the major target for the production of analgesia and the development of drug tolerance and dependence. Receptor desensitization has been considered to play important role in opioid tolerance. However, understanding mu opioid receptor desensitization mechanisms using rat brain tissues or cell lines has been difficult because of the presence of multiple subtypes of opioid receptor. This thesis documents the mechanisms of desensitization of the mu opioid receptor expressed in Chinese hamster ovary cells without interference caused by the presence of other opioid receptor subtypes. In this cell line, the mu opioid receptor was desensitized after 1hr exposure to the opioid peptide, DAMGO, largely by the loss of receptors from the cell surface without affecting the affinity or proportion of agonist-detected high affinity sites. Using site-directed mutagenesis, the structural determinants for this agonist-induced functional desensitization was determined to be threonine 394 preceded by an acidic amino acid in the cytoplasmic tail, presumably serving as a primary phosphorylation site for G protein coupled receptor kinase. However, mu opioid receptor down-regulation with an agonist treatment appears to be governed by two distinct pathways. One was G protein-dependent, GRK-dependent, and the other was G protein-independent but tyrosine kinase-dependent. In addition, the mu opioid receptor was shown to be a direct substrate for protein tyrosine kinase. Unlike other prototypic G protein coupled receptor, G protein coupling to the mu opioid receptor was tighter and resistant to agonist-induced G protein uncoupling from the mu opioid receptor. The persistent G protein coupling property of the mu opioid receptor with agonist exposure is partially determined by the intracellular regions of the receptor with contributions from multiple transmembrane domains. Taken together, these findings establish that the agonist-induced mu opioid receptor desensitization is mediated by receptor down-regulation rather than G protein uncoupling from the receptor and that multiple domains of the receptor contribute to its tight coupling to G protein and resistance to agonist-induced dissociation.
Understanding the function of endoglin through the generation and characterization of endoglin deficient mice and the study of patients with hereditary hemorrhagic telangiectasia

Endoglin, (CD105), an integral membrane glycoprotein, is a member of the TGF-ß receptor superfamily. It is expressed at high levels on vascular endothelium and also found in several human hematopoietic cells. Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder associated with mutations in the 'Endoglin' gene, leading to loss of a functional allele (haploinsufficiency). To define the role of endoglin in normal and pathological blood vessel formation, we first investigated its expression in vascular endothelium of HHT patients. We then generated ' Endoglin' deficient mice and analyzed their vascular and immune systems. The haploinsufficiency model proposed for HHT was first based on ' in vitro' experiments. This thesis further confirms this model. It demonstrates that all blood vessels of HHT1 patients express reduced endoglin ' in situ', and that severe lesions such as arteriovenous malformations (AVMs) are not attributed to loss of heterozygosity. To generate an animal model for BHT and ascertain the role of endoglin in development, we generated mice lacking one and two copies of the gene. We show that 'Endoglin' null embryos die at gestational day 10.0-10.5 due to defects in vessel and heart development suggesting that endoglin is critical for both angiogenesis and heart valve formation. Some mice expressing a single allele of 'Endoglin' spontaneously developed clinical signs of HHT. The analysis of disease onset and progression revealed that clinical manifestations were heterogeneous, leading to severe vascular abnormalities and fatal hemorrhages. Our results demonstrate that the HHT mouse model reproduces well the heterogeneous phenotype of the human disease. The data suggest that in addition to reduced expression of endoglin, modifier genes can contribute to heterogeneity and severity of HHT. As expression of a single allele of 'Endoglin' leads to a vascular disorder, we investigated if it could alter the immune system of ' Endoglin' heterozygous mice. We show that reduced endoglin expression either on vascular endothelium or on subsets of hematopoietic cells leads to alteration of T and B lymphocyte homeostasis.
Evaluation of the OneChip reconfigurable processor

The concept of a reconfigurable processor comes from the idea of having a general-purpose processor coupled with some reconfigurable resources that allow implementation of custom application-specific instructions. This thesis describes 'OneChip', a third generation reconfigurable processor architecture that integrates a Reconfigurable Functional Unit (RFU) into a superscalar Reduced Instruction Set Computer (RISC) processor's pipeline. The architecture allows dynamic scheduling and dynamic reconfiguration. To evaluate the performance of the OneChip architecture, several off-the-shelf software applications were compiled and executed on 'Sim-OneChip', an architecture simulator for OneChip which includes a software environment for programming the system. The architecture is compared to a similar one but without dynamic scheduling and without an RFU. OneChip achieves a performance improvement and shows a speedup range from 2.16 up to 32.02 for the different applications and data sizes used.
On the crashworthiness of foam-filled ultralight automotive structures

In this thesis, a novel 'layered' model for simulating the quasi-static and dynamic collapse of foam-filled ultralight aluminium structures using three-dimensional elasto-plastic finite element analysis is presented. Specifically, the quasi-static and dynamic axial collapse of foam-filled box columns is investigated. The column was modelled using shell elements, while the filler foam was modelled as a series of solid layers with a shear-stress failure criterion, which ties the layers together. This method enabled the simulation of the shear rupture of the foam, as observed in the extensive mechanical testing carried out in support of this study. The interface between the filler and the tube was modelled using an automatic contact algorithm, which incorporates the penalty method. The finite element analysis consisted of two investigations. In the first, aluminium columns of varying dimensions filled with aluminium foam of varying densities undergoing quasi-static axial crushing were examined. The effect of foam density, wall thickness and width of the column on energy absorption was evaluated and discussed. In the second, the same geometry was explored under dynamic impact loading. (Abstract shortened by UMI.)