VictorJuiz/thesis huggingface dataset:
Functional interactions of D1 and D3 dopamine receptors, generation and behavioural assessment of mice lacking both receptors

Dopamine is involved in the control of locomotor activity, reward, cognitive and endocrine functions. Experimental evidence suggests that D1 and D3 dopamine receptors interact in an opposing and synergistic fashion. The objective of this project was to generate mice lacking both receptors in order to investigate D1/D3 receptor interactions in behaviour. D1-/-D3 -/- mice were viable, fertile and showed no gross morphological abnormalities. In a novel open field, they exhibited lower activity than wild-type, D1-/-, and D3-/- mice. D1-/-D3-/- mice performed equally poorly in the rotarod and spatial learning tasks as their D1 -/- littermates. Basal locomotor activity and anxiety-like behaviour were normal in D1-/-D3 -/- mice. Combined deletion of both receptors abolished the exploratory hyperactivity and anxiolytic-like behaviour of the D3 receptor mutant phenotype and further attenuated the low exploratory phenotype of D1 -/- mice. These results suggest an interaction of both receptors in the expression of novelty-induced exploratory behaviour and the need for the presence of intact D1 receptor for the expression of certain behaviours manifested by the D3 receptor mutant phenotype. In addition, the D1 receptor, but not the D3 receptor, is involved in the ability to perform on the rotarod as well as spatial learning.
From ally to menace, Canadian attitudes and policies toward Japanese imperialism, 1929-1939

Few historians consider the 1930s as the formative period of Canada's relations with the Far East. This thesis seeks to redress this neglect by examining Canadian attitudes and policies toward Japanese imperialism from the opening of Canada's legation in Tokyo in 1929 to the outbreak of war in Europe a decade later. These years marked the high point of Canada's business, missionary and diplomatic involvement in the region, a story overlooked by historians. This study will assess the views of Canadian diplomats, missionaries, traders and interest groups to trace the change in Canada's perception toward the Empire of the Sun. During this period, Canadians initially viewed Japan as an imperial ally, its presence in the region as benign as British imperialism elsewhere. By the late 1930s, Japan would be perceived as a potential menace to Canadian security. How and why this change occurred among Canadians concerned by the Far East is the focus of this study. Canada's dealings with Japan during this period reveal much about its own evolving role in world affairs. Seeking to establish itself internationally, the young Dominion opened its third legation in a nation soon to leave this global order. Over the decade, Ottawa looked to London and Washington in formulating its response to growing turbulence in the Far East. While recent scholarship has examined Japanese imperialism during this period, little has been written on Western reaction to it. This thesis provides a case study of how one Western power, albeit a minor one, dealt with an increasingly wayward member of the international community. Historians have overlooked this episode and the insights it provides into the impact of pressure groups and Ottawa's position on collective security. Although European events would dominate Canadian foreign affairs in the 1930s, a consideration of the changing perceptions toward Japan adds a new dimension to our understanding of this period.
Molecular systematics of neotropical deer mice of the Peromyscus mexicanus species group

Mitochondrial DNA sequences of cytochrome 'b', ND3, ND4L, and ND4 were used as phylogenetic markers to re-examine the systematic arrangement of the 'P. mexicanus' species group. Phylogenetic relationships were estimated on the combined sequences using neighbour joining, weighted (6:1) parsimony, and maximum likelihood methods. Contrasting phylogenetic hypotheses of Hooper and Musser (1964, as modified by Huckaby 1980), and Carleton (1989) were tested. Phylogenetic analysis of the mtDNA data most closely approximates Hooper and Musser's (1964) concept of the species group. Within the 'core' ' mexicanus' group, 'P. mexicanus' is not monophyletic, and is segregated into three phylogenetically distinct groups. The nucleotide sequence data supported the polyphyletic arrangement of 'P. nudipes, ' which may be a result of separate invasions from two different ' P. mexicanus' populations. The phylogenetic relationships between the highland taxa including 'P. zarhynchus, P. guatemalensis,' and 'P. grandis' do not conform to any of Huckaby's (1980) three hypotheses, further demonstrating their complex geographical relationships. Phylogenetic evidence suggests that 'P. gymnotis' and members of the western 'P. mexicanus' lineage are conspecific.
Identification and characterization of Gads, a novel hematopoietic-specific adaptor protein, in T cell receptor signaling

The activation of the T cell receptor (TCR) initiates an interconnecting network of signaling pathways that lead to changes in gene transcription which translate to integral T cell responses such as clonal proliferation, differentation and release of cytokines or cytotoxic granules. Research into the molecular mechanisms underlying these responses has led to the discovery of novel transmembrane and cytoplasmic adaptor proteins, which function to coordinate T cell activation at a variety of levels. The work herein centers upon the characterization of a novel hematopoietic-specific cytoplasmic adaptor protein termed Gads, and examines its contribution to TCR signaling. Gads is structurally similar to the Grb2 and Grap adaptor proteins, and contains amino and carboxy terminal SH3 domains flanking a central SH2 domain and a 120 amino acid unique region. While the SH2 domain binds to tyrosine-phosphorylated proteins also known to bind to Grb2 and Grap, such as Bcr-Abl, c-kit, Shc, and LAT, it possesses a unique SH3 domain-binding specificity. Within T cells, Gads mediates interactions with the LAT and SLP-76 adaptor proteins, and is believed to promote crosstalk between these signaling complexes that is required for T cell activation, as assessed by transcription of the 'interleukin-2' gene. Gads also inducibly associates with the serine/threonine kinase HPK1 in response to TCR ligation, and likely contributes to the recruitment of HPK1 to the proximity of the activated TCR. The importance of Gads in TCR signaling ' in vivo' has been highlighted by the recent findings that Gads-deficient mice display impaired thymocyte development and peripheral T cell activation, revealing an essential role for Gads in signaling from both the pre-TCR and mature TCR.
An intelligent metasearch engine for the World Wide Web

Machine learning and information retrieval techniques are applied to metasearch on the World Wide Web as a means of providing user specific relevant documents in response to user queries. A metasearch agent works in conjunction with a user to provide daily sets of relevant documents. Users provide relevance feedback which is incorporated into future results by a choice of machine learning algorithms. Using a fixed ranking method, the algorithms incorporating relevance feedback perform much better than those that do not. Furthermore, using heterogeneous information sources on the World Wide Web is shown to be effective in short and long term usage.
Bioactivation of doxorubicin by human NADPH-cytochrome P450 reductase

Doxorubicin (DOX) is a useful antineoplastic drug with multiple mechanisms of cytotoxicity. One such mechanism involves the reductive bioactivation of the quinone ring to a semi-quinone radical, and subsequent redox-cycling. It is known that rat NADPH-cytochrome P450 reductase (CYPRED) catalyzes DOX reduction and sensitizes human cancer cells to DOX in vitro. The purpose of this investigation was to determine whether human CYPRED also catalyzes DOX reduction. DOX reduction occurred in a human CYPRED cDNA heterologous expression system and also in human liver microsomes. Using a bank of 17 human livers, the rate of microsomal DOX reduction was correlated with CYPRED activity and immunoreactive protein expression. DOX reduction was inhibited by diphenyliodonium chloride, an inhibitor of CYPRED. DOX reduction was not inhibited by carbon monoxide, suggesting that the cytochromes P450 did not catalyze DOX reduction. These results suggest that human CYPRED catalyzes DOX reduction. A mammalian expression vector containing human CYPRED cDNA was constructed for future transfection into breast cancer cells to assess whether sensitivity to DOX will be increased.
Period, power and purpose, understanding compellent threats in the twentieth century

This dissertation is a quantitative analysis of 125 cases of compellent threats 1919-1990. The author explains that the study is intended to test the conventional, 'realpolitik' based explanations for how states targeted by compellent threats respond to the demands made of them. After discussing the inadequacies of previous attempts to understand the nature of threats in international relations, the author outlines the hypotheses being tested. In the substantive chapter, the author discusses his findings. ' Realpolitik' explanations, largely rooted in rational models of state behaviour, prove to be inadequate in explaining the historical record. Though, as predicted, the powerful initiator states did tend to be more successful in their use of threats, this success did not depend on the weakness of the targeted state. Therefore, the relative power of the states involved had no relationship to the outcome of the encounter. Other hypothesized variables, such as the nature of the demands being made, or the nature of the threats being issued, had no effect on the outcome of the encounters. The author concludes with a discussion of the implications for these findings and how the presented research can be refined. The author explains how his findings differ from previous findings in this field, and why the choices made in methodology can have serious implications for the validity of the results presented. The author defends his choices, and concludes that though the dissertation is only presented as a first step towards understanding compellence, it offers a fruitful starting point for further research in this area.
Risk factors associated with lead in Toronto tapwater and residents' tapwater use behaviours, a pilot study

Tapwater lead concentrations ([PbW]) in 25 lead pipe and 25 non-lead pipe serviced households were measured to determine whether service line material affected [PbW]. The effect of temperature, flushing, and a variety of physical factors on [PbW] were also studied and an estimate of per capita lead intake was made from questionnaire household tapwater consumption data. Overnight standing samples were collected from the kitchen cold and hot water tap and then a further sample was collected from each tap after five minutes of flushing. Samples were analyzed by ICP-MS. Data on the plumbing system were recorded and a questionnaire on tapwater consumption administered. The mean pooled (lead and nonlead serviced) [PbW] was 5.5 ± 7.0 [mu]g/L. Sixteen households (75% lead pipe serviced, 25% nonlead pipe) exceeded the Ministry of Environment and Energy's maximum acceptable concentration guideline of 10 [mu]g Pb/L. Both service line material and flushing significantly influenced pooled [PbW]. Multiple linear regression on pooled [PbW] data showed that length of service line, kitchen pipe material and soldering, and time since last plumbing renovation were also significant influences on [PbW]. Two adult consumption estimates--2.5 ± 1.7 L tapwater/day/capita and 6.1 ± 11.1 [mu]g Fb/day/capita were calculated based on the demographic/consumption questionnaire. Recommendations are made for corrective measures including replacement of City and household lead plumbing materials and tapwater flushing prior to consumption.
Multi-Sense Artificial Awareness

In the process of exploring multi-sense artificial awareness systems, a multi-camera vision algorithm and an iterative spatial probability based sound localization system were developed. The multi-camera vision algorithm uses spatial probability maps to combine the results of the individual cameras in a simple and efficient manner. The sound localization system uses an iterative technique that increases the accuracy of the localization while maintaining a high localization rate. It can correctly localize objects in noisy environments with a signal to noise ratio as low as 0 dB. The sound localization system also uses spatial probability maps for the integration of the results of multiple microphones. Spatial probability maps also serve as the basis for the integration of vision and sound localization. An integrated vision and sound localization (IVSL) system was implemented and it was discovered that the integration of the two senses results in increased accuracy and robustness.
Fault diagnosis of a heat exchanger system using unknown input observers

In this thesis, the fault diagnosis of a heat exchanger system, consisting of two heat exchangers in series, is investigated. The system, modeled by ten first-order nonlinear differential equations, has three unknown disturbances and three output measurements. The goal is to determine the degradation levels in heat exchangers based on the sizes of the residuals generated via unknown input observers. The residuals must be robust against disturbances and sensitive to the degradation. It is proved that this is only achievable when the number of output measurements is greater than that of disturbances. Therefore, either some of the disturbances must be eliminated or more sensors must be installed. With one of the disturbances assumed constant, the degradation in the first heat exchanger can be determined accurately with reasonable precision. The addition of one more sensor results in a more precise diagnosis of the first heat exchanger. The degradation in the second heat exchanger can be determined when a second sensor is added, but the diagnosis is crude and only eighty percent accurate at best.
The effect of insulin delivery route on hepatic lipid and glucose metabolism in streptozotocin-diabetic rats

The effect of differential hepatic insulinization induced by chronic insulin treatment via the intraperitoneal versus the subcutaneous route on hepatic lipid and glucose metabolism was examined in streptozotocin (STZ) induced diabetic rats. Rats were divided into 4 groups: (1) Normal control (N); (2) STZ-diabetic control (D); (3) STZ-diabetic, treated intraperitoneally (IP) with insulin; and (4) STZ-diabetic, treated subcutaneously (SC) with insulin. Hepatic insulinization was 2-fold greater in IP compared to SC (p $<$ 0.05). TGSR was decreased in D (p $<$ 0.05) and normalized following insulin treatment regardless of route. Liver acetyl-CoA carboxylase (ACC) activity was normal but fatty acid synthase (FAS) was decreased in D (p $<$ 0.05). ACC and FAS were normal in both insulin treated groups. Hepatic glucokinase (GK) activity was significantly decreased in D (p $<$ 0.001), partially restored in D (p $<$ 0.05) and higher in IP (p $<$ 0.05) compared to N. Glucose 6-phosphatase (G6Pase) activity was increased in D (p $<$ 0.05) and normalized in IP and SC. The results indicate that chronic insulin treatment by either the IP or the SC route results in normal hepatic triglyceride secretion. Chronic IP treatment results in enzyme levels that reflect improved glucose metabolism compared to SC.
The function of alternatively spliced isoforms of dystrophin

The Duchenne Muscular Dystrophy gene encodes multiple isoforms of dystrophin generated by different promoters and by alternative splicing events at the 3' end of the transcript. Alternative splicing of the penultimate exon 78 produces two structurally different C-termini in the protein. Usage of the two dystrophin C-termini is tissue-specific, developmentally regulated, and highly conserved across species. Work in this thesis began to characterize the functional significance of the two C-termini of dystrophin by creating targeted mice specifically mutated so as to constitutively use only one of the two C-termini (Chapter II). In addition, the yeast-two hybrid system was used to identify novel dystrophin interacting proteins that bind to the mainly hydrophobic exon-79 encoded C-terminus of dystrophin (Chapter III). Lastly, the full-length cDNA sequences encoding the novel family of CAPS proteins (calcium-dependent activator protein for secretion), first identified in the two-hybrid screen, were obtained (Chapter IV). Human expression profiles indicated that CAPS-1 is a neural/endocrine specific protein while CAPS-2 is expressed ubiquitously.
A tool for a formal refinement method

A 'formal refinement method' is a method of constructing correct programs and proving program correct: one constructs a program the way one would perform stepwise refinement, except that specifications are formal and refinements are justified by theorems. Thus, the program and its proof of correctness are developed in parallel, which is mentally easier than developing the program and the proof separately. A major problem with the actual use of formal refinement methods is that, when carried out on paper, they could be mundane, tedious, error-prone, and hard to edit. We build a computer tool for using Hehner's theory, a formal refinement method. It combines the advantages of both the syntax-directed editor <math> <f> <ty>Math<hsp sp="-0.167"><hsp sp="-0.167"><hsp sp="-0.167"><in align="c"> </in><hsp sp="-0.167"><hsp sp="-0.167">pad</ty></f> </math> of Backhouse et al. and the proof checker driven Refinement Calculator of Butler et al.: an editor aware of the recursive operator-operand structure of expressions, with computer proof assistant support behind. The computer will do the mundane chore, and correcting mistakes and making changes will be convenient.
Distributed-in-space glutathione conjugation kinetics of ethacrynic acid in liver

The factors affecting the hepatocellular glutathione (GSH) conjugation of ethacrynic acid (EA), a model substrate, in the formation of the glutathione adduct EA-SG were assessed for their influence on local GSH conjugation rates from the inlet to the outlet of the liver. These included plasma protein binding, sinusoidal uptake, spontaneous and enzyme-catalyzed conjugation, co-substrate (GSH) availability and EA-SG efflux at canalicular and sinusoidal membranes and their zonation within the acinus. The spontaneous coupling of EA with GSH was rapid, whereas the 'in vitro' conjugation catalyzed by the glutathione 'S'-transferases (GSTs) in rat liver was even faster. The conjugation rates greatly exceeded the EA uptake rate by saturable and non-saturable processes in isolated rat hepatocytes. When these ' in vitro' data were viewed with respect to events in whole liver (single-pass perfused rat liver), transport and not GSH conjugation was found to be rate-limiting in the rapid conversion of EA to EA-SG. In studies with isolated, enriched periportal and perivenous hepatocytes, EA uptake and EA-SG efflux were functionally similar among hepatocytes throughout the acinus. However, a shallow and increasing (portal to venous) GST activity gradient was observed in rat liver. When these zonal, uptake and metabolic 'in vitro' data were utilized to predict EA disposition in liver perfusions in the presence and absence of bovine serum albumin (BSA), a series compartment model was found to be most consistent with data obtained in the absence of albumin. The model predicted both a temporal and zonal depletion of GSH among hepatocytes and a change in the rate-limiting step with increasing perfusion time from uptake to co-substrate availability. The model was less capable of predicting the influence of high albumin protein binding on uptake and metabolism, unless a role of BSA in facilitating drug uptake was assumed. This investigation showed for the first time that, in addition to metabolic enzymes, flow and substrate binding, other important factors such as zonal transport, co-substrate, and GSH conjugate efflux further influence the distributed-in-space processing of acceptor substrates in GSH conjugation.
Environmental life cycle cost analysis, a review of economic, energy and green house gas emission impacts of asphalt and concrete pavements

Life cycle cost analysis has increasingly become an integral part of most decision-making processes for large infrastructure projects throughout the world. The evaluation of asphalt and concrete pavements has always been based on the lowest cost alternative either in terms of initial costs or life cycle costs. However, these costs do not account for any potential impact such alternatives may have on the environment. The objective of this report is to evaluate the various potential impacts asphalt and concrete pavements have on the environment. This analysis is not a complete Life Cycle Assessment (LCA) of asphalt and concrete pavements. The evaluation is considered a scoped LCA, which includes the detailed analysis of economic, energy and GHG emission values related to pavement construction.
p53 gene status and chemosensitivity of childhood acute lymphoblastic leukemia cells to antinoneoplastic agents

The role of p53 as a determinant of sensitivity to antineoplastic agents in six childhood acute lymphoblastic leukemia cell fines was investigated. Adriamycin (ADR)-sensitive cell lines were found to have wild-type (wt) p53, whereas resistant cell lines contained mutations in the gene. Following ADR treatment, wt but not mutant p53 was increased in a time- and dose-dependent manner. The cell cycle distribution of cells with wt p53 was unchanged after ADR treatment; however, G1 was significantly reduced (p < 0.0001) in cells expressing mutant p53. Furthermore, apoptosis was detected in 43 to 66% of cells with wt p53 but in only 8 to 13% of those with mutant gene. p53 mutations also correlated with resistance to daunorubicin, but not to methotrexate, vincristine, or dexamethasone. These results suggest that p53 gene status and the ability of p53 to induce apoptosis may be important determinants of sensitivity to ADR and daunorubicin in ALL cells.
Writing to Learn: The Effect of an Intentional Learning Environment and the Measurement of Reflective Processes

Five grade 5-6 classes, two control and three experimental, participated in a study of reflective processes in written composition. The experimental classrooms use a computer system designed to support intentional learning (CSILE). This system may facilitate the development of reflection in writing because it is designed to support student control over learning. Opinion essays written for the study were rated on 13 dimensions using a 3-point scale. The expected advantage on essay scores for the CSILE group resulted but was not statistically significant. An additional investigation of the factors underlying the 13 dimensions was completed. Results suggest factors of essay quality (coherence and style) can be differentiated from a reflection factor. A comparison of experimental and control groups on factor scores resulted in a significant advantage for the experimental group only on the reflection factor. Moderate inter-rater reliability on factor scores, however, necessitates caution in interpreting this result.