VictorJuiz/thesis huggingface dataset:
Microtubules regulate actin microfilament organization and reorganization in the intact and the repairing in vitro aortic endothelial monolayers

This thesis explores an understudied area of endothelial biology, the contribution of microtubules to endothelial integrity and wound repair. This is important because disruption of endothelial integrity and repair leads to initiation and progression of atherosclerosis. We focused on microtubule-microfilament interaction in the in vitro model of endothelial integrity and wound repair. In conclusion, microtubules are important in endothelial biology and pathobiology since they regulate microfilament organization and reorganization via linker proteins to maintain endothelial integrity in confluent monolayers and to regulate directed cell migration during endothelial wound repair. The hypothesis that microtubules organize microfilaments in confluent endothelial monolayers was tested by disrupting the microtubules. This resulted in loss of dense peripheral bands, increase in stress fibers, and associated increase of peripheral focal adhesion proteins. However, when microfilaments were disrupted, microtubules remained unchanged suggesting that microtubules promote endothelial integrity by regulating microfilament organization and their associated cell-substrate and cell-cell adhesion proteins. Microtubules were then hypothesized to interact with microfilaments via linker proteins to regulate endothelial integrity and cell migration. Two linker proteins, IQGAP1 and CLIP-170, were identified which may mediate microtubule-microfilament interaction. When IQGAP1 siRNA was transfected into human aortic endothelial cells, there was 63-76% knockdown of IQGAP1 protein and a delay of wound closure. There was also a delay in microtubule and microfilament reorientation from random to parallel (from 2 to 4 hours) and from parallel to perpendicular (from 8 to 12 hours). However, there were no changes in centrosome redistribution. Studies on the microtubule regulation of microfilament organization were then extended to endothelial cell migration during early wound repair. Microtubules were shown for the first time to undergo a series of changes that were similar to those published for microfilaments. In cells along the wound edge, microtubules remodel from random to parallel then to perpendicular orientations relative to the wound edge. When monolayers were wounded and microtubules disrupted, microfilaments were affected as described above for the confluent monolayer. Following microfilament disruption however, microtubules were still able to undergo the series of changes. Therefore, microtubules are able to remodel independently of microfilaments while microfilament redistribution is dependent on microtubules.
The debate on change of medium of instruction in Hong Kong secondary schools

This thesis explored the heated debate prompted by the 1998 change of medium of instruction from English to Chinese for most Hong Kong Secondary 1 to Secondary 3 students imposed by the Hong Kong government. In order to understand the background of the 1998 change, the history of English education in Hong Kong was briefly examined. Then the thesis looked at the responses of different sectors of Hong Kong society, e.g. parents, teachers, and government officials to the 1998 change as reported in Hong Kong newspaper reports and commentaries. 14 interviews of parents and educators were also conducted to understand the reasoning/rationale behind their views on the issue in detail. At the end of the thesis, the concept of linguistic imperialism was examined to see if it could be appropriately applied to the situation of Hong Kong in relation to the 1998 change.

Keywords: Language policy, China
Education, Secondary, China
Public opinion, China
Language policy, Public opinion
Education, Secondary, Public opinion
Forest values and perceptions of people in northwestern Ontario

In order to contribute to the development of a co-management framework, this study identifies and compares people's forest values. Specifically, we will identify individuals' personal values within each participant group, and their perceptions for why they believe their own group and the other groups might value forests. The methodology used is Conceptual Content Cognitive Mapping, 3CM, which allows individuals to identify their values and to share their perceptions of the other groups' values. Participants include members from the forest industry, environmental groups, Aboriginal communities and the Ontario Ministry of Natural Resources. The study area is northwestern Ontario, which contains Treaty #3, Treaty #9 and Robinson Superior Treaty areas. Data are analyzed to find the dominant forest value themes through hierarchical clustering, resulting in ten value themes. Subsequently, inter-group and intra-group similarities and differences among the rankings of participants' personal values and their perceptions are determined through various non-parametric statistical tests.
"Coming out" as queer Asian youth in Canada: examining cultural narratives of identity and community

This thesis examines cultural narratives of identity and community formation in Canada through an analysis of interviews with six self-identified queer Asian youth from the Greater Toronto Area. It critically examines the concept of “coming out” by highlighting the complex and often contradictory positionings that queer Asian youth may find themselves in having to negotiate their identities and subjectivities in different contexts of marginalization. Overall, it argues that “queer Asian youth” are positioned as secondary citizens by the Canadian nation-state. However, this thesis also argues that individuals and communities may take up the category of “queer Asian youth” to contest and characterize the profoundly unstable nature of social categories such as race, class, gender, nation and sexuality.

Keywords: Gays, Identity
Gays, Canada
Lesbians, Identity
Lesbians, Canada
Asians, Canada
Youth, Canada
Coming out (Sexual orientation)
Effects of human milk and formula on the expression of intestinal xenobiotic transporters

Efflux transporters, including P-glycoprotein (MDR1) and MRP2, in the intestine play important roles in decreasing drug bioavailability. Recently, we showed that human milk and formula have different effects on intestinal cytochrome P450 3A4 (CYP3A4), which explains the clinical observation of the significantly faster metabolism of caffeine by formula-fed infants. Since CYP enzymes and MDR1 and MRP2 are sometimes co-regulated, we hypothesize that human milk and formula have different effects on the expression of MDR1 and MRP2. Experiments were conducted using an in vitro cell model, C2BBe1 cells. Both human milk and formula (each at 20%) caused a significant increase in P-gp expression without a concomitant change in mRNA expression. However, 20% of human milk caused a significant increase in both MRP2 mRNA and protein expression, while formula had no effect. Therefore, human milk seems to exert effects on the mRNA expression of MDR1 and MRP2 through different pathways.
A polymer subject to a force: A directed walk model

Our intent is to derive a mathematically rigorous model to qualitatively describe the phase behaviour of a linear homopolymer in to solution subjected to a force. We review and interpret a selection of force-versus-extension curves of macromolecules in solution from the literature. Often, fitting analysis methods rely on theoretical models that are phenomenological in derivation. In our study, we consider a directed walk model of a linear homopolymer in dilute solution in the presence of an applied external force. For this case we determine an exact expression for the generating function in two variables conjugate to the number of steps and an applied external force in the preferred direction of the walk. A more complicated case is the model that has an energy associated with near-neighbour contacts subject to a force. We derive the recurrence relations using combinatorics and determine an exact expression for the generation function in three variables. The asymptotic analysis of the generating function reveals the shape of the singularity diagrams where the critical value was solved exactly and thus identifies the collapse transition of the polymer model. We demonstrate that the model is mathematically rigorous and show that the qualitative description of the polymer model at various temperatures and solvent conditions is in agreement with experimental evidence. The force-extension curve was numerically evaluated where the interacting partially directed walk model shows a second-order phase transition in the presence of an applied force.
Local-spin mutual exclusion algorithms on the DSM model using fetch store objects

We present four local-spin mutual exclusion algorithms on the DSM model using only fetch&store and registers, and prove the correctness of those algorithms. Among those algorithms, two were previously published and the other two were newly developed by us. We also compare relative advantages and disadvantages of these algorithms, and conclude that no algorithm is better than the others in all aspects. Another way to get a local-spin mutual exclusion algorithm on the DSM model is to transform a local-spin mutual exclusion algorithm on the CC model to one on the DSM model. We present the transformation by Anderson and Kim in detail, and address the weakness of the transformation. We also present a simpler transformation that can be applied to the same class of algorithms.
Using graphing calculators in the mathematics classroom: teachers' conceptions and their teaching practices

This study investigated teachers' conceptions of mathematics and their teaching practices with respect to the use of graphing calculators in their mathematics classrooms. Case studies on three teacher participants were developed using quantitative and qualitative data that consisted of self-assessments on beliefs in mathematics, observations, surveys on professional and personal technology use, and semi-structured interviews. All three teachers viewed mathematics as a dynamic field, emphasized understanding concepts as opposed to mechanical procedures, and preferred the construction and understanding of the concept over the memorization of procedures. All three teachers were willing to use graphing calculators in the mathematics classroom and all three had a similar goal of attempting to use the graphing calculators to eliminate mechanical processing time and enhance their students' ability to construct their own learning. The evidence from the study suggests that these teacher's practices, with respect to the use of graphing calculators in the mathematics classroom, are influenced by how proficient their students are at using this technology and how accessible the technology is. There were five major findings from the study: (1) if the mechanics of operating a graphing calculator involve at least as much mental effort as the mechanics involved in pencil and paper work, then using the graphing calculator will not free up students so that they can concentrate on constructing their own knowledge and understanding of mathematical concepts or solving more complex problems; (2) when mechanical operating issues are overcome, introducing graphing calculators into the mathematics classroom aids teachers in helping students construct their own mathematical knowledge by allowing all students to begin at a common starting point; (3) to obtain the full benefits of having students learn with the graphing calculators in the mathematics classroom, teachers must require students to use the graphing calculators when they are being evaluated; (4) teachers will determine for themselves where graphing calculators can be most appropriately used in the curriculum; and (5) teachers require strategies that will allow them to successfully deal with managing the day-to-day difficulties involved in using technological instruments such as the graphing calculator in the classroom. Implications for future study include how we can help those teachers inexperienced with the use of technology to incorporate the use of technology in their classrooms, how we need to address the need for consistent teaching practices throughout the intermediate, secondary and post-secondary levels, and how future case studies can be coded to reflect more precisely the language used by teachers to question students in the classroom. Suggestions for educators to consider when using graphing calculators in the mathematics classroom are given at the end of the study.

Keywords: Graphic calculators
Mathematics, Study and teaching
Mathematics teachers, Attitudes
Functional expression of multidrug resistance transporters, P-glycoprotein and the breast cancer resistance protein, in brain cellular compartments

Multidrug resistance (MDR) is a clinical obstacle often encountered during pharmacological treatment of a variety of neurological disorders that include HIV neuropathy, brain neoplasia, and epilepsy. The expression of ATP-binding cassette (ABC) efflux transporters at the blood-brain barrier (BBB) may play a role in restricting permeability and accumulation of xenobiotics and therapeutics into the brain. Glial cells (microglia, astrocytes) are pathologically involved in these neurological disorders and are drug cellular targets. The goal of this Ph. D. project was to investigate the subcellular localization, protein/gene expression and activity of P-glycoprotein (P-gp) and BCRP that may confer MDR in brain compartments using well-characterized in vitro brain culture systems. P-gp gene/protein expression were detected in rat brain microvessel endothelial cells (RBE4) and a continuous rat brain microglia cell line (MLS-9). BCRP gene/protein expression were detected in RBE4, MLS-9 and primary cultures of human brain microvessel cells, rat astrocytes and microglia but at low levels compared to BCRP over-expressing MCF-MX100 cells. P-gp was localized along the plasma/nuclear membranes and plasmalemmal vesicles in RBE4, MLS-9 and in situ in rat brain capillaries by electron microscopy using C219, MRK16, MAB-448 monoclonal antibodies. Fluorescence microscopy using BXP-21 and BXP-53 monoclonal antibodies did not localize BCRP to the plasma membrane compared to MCF-MX100 in all brain compartments. Cellular accumulation of 3H-digoxin in the presence of P-gp inhibitors shows P-gp activity in RBE4 and MLS-9 cells. In addition, protease inhibitors are inhibitors and substrates for P-gp in RBE4 and MLS-9 cells. Compared to MCF-MX100 cells, BCRP transport of 3H-mitoxantrone and fluorescent pheophorbideA was not detected in our brain cultures. In conclusion, our results suggest a multi-level model of drug resistance in brain compartments at the plasma and intracellular membranes. The functional expression of P-gp in RBE4 and MLS-9 cells suggests an important role in restricting the permeability of drugs across the BBB as well as restricting drug accumulation in cellular targets within brain parenchyma. Low expression and lack of BCRP activity in our brain cultures, paralleling recent in situ and in vivo studies, suggests that BCRP, unlike P-gp, may not serve a protective role, at least in non-diseased brain.
The association of DNA viruses and childhood cancers

Approximately 15% of human cancers can be attributed to viral infections. Polyomaviruses including simian virus 40, JC virus and BK virus, have been repeatedly isolated from various human brain tumours. However due to inconsistent findings, the etiologic role of polyomaviruses in brain tumours remains controversial. Human papillomaviruses (HPV) are an established causative agent of cervical cancers. Several studies suggested vertical transmission of HPV, suggesting that fetal exposure to HPV may contribute to childhood malignancy such as leukemia. Based on the aforementioned, we searched in 48 childhood brain tumour samples and 36 leukemia samples for the presence of polyomaviruses and HPV by PCR analysis, respectively. No viral DNA was detected in all samples by our highly sensitive 'neat and spike' PCR assay. Therefore, polyomaviruses probably do not play a major role in the pathogenesis of childhood brain tumours, and HPV is unlikely to be an etiological factor in childhood leukemia.
Modulation of dopamine transporter function through protein interactions

The dopamine transporter is a presynaptic protein found near dopaminergic synapses and plays a major role in the clearance of dopamine from the synapse through a reuptake mechanism. Because dopamine transporter function plays a key role in the general tone of dopaminergic synapses, the regulation of the transporter itself plays a vital role in the dopaminergic system. Previous studies suggest protein trafficking may be, a robust mechanism of dopamine transporter regulation, therefore the identification of proteins involved in dopamine transporter localization will have great significance towards understanding both normal and aberrant dopaminergic neurotransmission. Towards this end, we have identified several different proteins that interact and modify dopamine transporter function, including α-synuclein. Cells coexpressing α-synuclein and the dopamine transporter exhibited a 50% increase in dopamine transporter-mediated dopamine uptake. Furthermore, the increase in dopamine transporter activity corresponded to increased cell surface transporter localization. Yeast 2-hybrid, co-immunoprecipitation and GST-fusion protein experiments revealed a direct interaction between the dopamine transporter and α-synuclein. The last 23 amino acids of the dopamine transporter carboxyl tail and the non amyloid-β component domain of α-synuclein were critical for this interaction. The coexpression of these two proteins also promoted dopamine-induced apoptosis suggesting a possible pathophysiological implication for the interaction between the dopamine transporter and α-synuclein. In addition to α-synuclein, we have identified PDZ proteins and the D2 receptor as potential dopamine transporter-interacting proteins. These interactions were confirmed through co-immunoprecipitation studies. Coexpression of the dopamine transporter with PSD-95/SAP90 or SAP102, resulted in an increase in dopamine uptake. Similarly, dopamine transporter and D2 receptor coexpression increased dopamine transporter activity. For each interaction, the increase in dopamine transporter activity correlated with an increase of dopamine transporters on the cell surface. Taken together, these studies identify potential components of dopamine transporter regulation, possibly mediated by altering dopamine transporter trafficking/localization. These dopamine transporter-interacting proteins may provide pathways through which the dopamine transporter can respond to different stimuli. The clarification of these interactions will provide significant contributions towards creating a heuristic framework by which the dopamine transporter is involved in both normal and dysfunctional states of the dopaminergic system.
Extrusion processing of low-bulk density, microcellular, open-cell thermoplastic foams

In order to promote a deeper understanding of the cell opening behavior during foaming, a failure analysis of a cell wall was performed according to the Considere and Failure criteria using the uniaxial experimental data of a polymer melt. A theoretical approach to prediction of the cell wall rupture moment was proposed using two adjacent cubic-shaped cells. This concept was further extended to arrive at an estimation of the minimum threshold diameter of a foam extrudate to produce an open-cell foam structure. A continuous extrusion process for the manufacture of low-density, microcellular, open-cell thermoplastic foams is presented using a single-screw tandem extrusion foaming system. Fundamental studies have been conducted to investigate the effects of various processing parameters and materials compositions on the basic properties (i.e., extensional behavior, solubility, diffusivity, and initial foam extrudate shape) of plastic melts and melt/gas solutions that influence the cell morphologies of thermoplastic foams. The observed phenomena were essential in understanding and devising the processing strategies to achieve a desired foam structure. Based on the fundamental studies, this thesis presents the basic strategies for promoting a low-density, microcellular, open-cell thermoplastic foam. The effects of polymer blending, additives, processing temperature, blowing agent content, die geometry, and surface quenching on the final foam morphologies were thoroughly investigated to verify the proposed strategies. By tailoring the material compositions and processing conditions, low-density (>10 fold), microcellular (109 cells/cm 3), open-cell (>95%) thermoplastic foams were successfully achieved. Furthermore, a procedure for estimating gas loss from a foam structure was proposed in order to understand the effect of gas loss during open-cell content measurement using a gas pycnometer, and the corresponding open-cell content errors were calculated.
An investigation of cytochrome P450 2B6 in smoking: Expression, regulation and clinical outcomes

Introduction. The CYP2B6 enzyme is expressed in human brain and liver. CYP2B6 metabolizes clinical drugs (e.g. bupropion, a smoking cessation drug), drugs of abuse (e.g. nicotine), toxins (e.g. cigarette smoke nitrosamines) and endogenous compounds (e.g. serotonin and testosterone). CYP2B6 is genetically polymorphic and variations resulting in decreased enzyme activity may alter clinical responses. The expression and regulation of CYP2B6 protein in human brain is of interest as it may affect the central metabolism of CYP2B6 substrates. Methods. We investigated the effect of the decreased function CYP2B6*6 allele in a bupropion-mediated smoking cessation clinical trial. We also investigated the constitutive expression of brain CYP2B6 protein and its induction by nicotine and phenobarbital in African Green monkeys. Results. In the clinical trial, there was a significant drug by genotype interaction (OR=2.97, CI=1.05-8.40, p=0.04). Specifically, the CYP2B6* 6 group had higher abstinence rates with bupropion than placebo (32.5% vs. 14.3%, p=0.01) compared to the CYP2B6*1 group which had high abstinence rates with both the bupropion and placebo treatment (31.0% vs 31.6%, p=0.93). In addition, the CYP2B6* 6 group maintained their abstinence rates to the 6 month follow-up whereas the abstinence rates in the CYP2B6*1 group decreased over time. This suggests that the CYP2B6 genotype may be involved in novel smoking cessation effects. In monkeys, constitutive brain CYP2B6 was expressed in a region- and cell type-specific manner. Chronic nicotine and phenobarbital treatment resulted in significant increases in brain CYP2B6 protein levels which were also region- and cell type-specific. This demonstrates that brain CYP2B6 is inducible and may result in increased metabolism of CYP2B6 substrates, such as bupropion and serotonin, in specific brain regions and cell types. Conclusion. Genetic variation in CYP2B6 affects smoking cessation outcomes which may be mediated by CYP2B6 expression in the brain. CYP2B6 protein is expressed in monkey brain and is inducible. These studies show that CYP2B6 may have a novel role in the brain. The metabolism of centrally-acting substrates in the brain is of interest as it may affect the levels of clinical drugs and endogenous neuroactive compounds.