VictorJuiz/thesis huggingface dataset:
Microglia and neurotoxicity: The role of potassium-calcium channels and development of a novel model of microglia activation

Microglia, the resident immune cells of the CNS, are important for orchestrating acute brain inflammation following stroke. Over the past decade, there is growing evidence that microglia K+ channels may play a role in regulating microglia function. In this study, we show that Ca2+ /calmodulin-activated, small-conductance K+ channels (KCNN1/SK1/KCa2.1, KCNN2/SK2/KCa2.2, KCNN3/SK3/KCa2.3 and KCNN4/SK4/KCa3.1) are expressed in rat microglia. In paricular, we found that only KCa3.1 channel mRNA was highly expressed in resting microglia relative to other CNS cells (e.g. astrocytes and neurons), while activated microglia had higher levels KCa2.3 expression. To examine if these channels regulate microglia-induced neurotoxicity, we tested them in co-culture model with LPS-treated microglia and neurons. Interestingly, LPS-activated microglia killed neurons and killing was markedly reduced by specifically blocking either microglia KCa2.3 or KCa3.1 channels. Blocking either KCa3.1 or KCa2.3 channels inhibited LPS-induced iNOS expression and nitric oxide production by microglia. LPS activated p38 mitogen activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) in microglia, and either KCa2.3 or KCa3.1 channel blockade inhibited p38 MAPK phosphorylation, but not NF-kappaB activation. In addition to our in vitro findings, intraocular injections of the KCa3.1 channel blocker TRAM-34 reduced the death of retinal ganglion cells. Together these findings suggest that selective blockade of KCa3.1 or KCa2.3 channels in microglia might provide therapeutic benefits in neurodegenerative disorders. The latter part of this study, we developed an in vitro model of microglia activation that is more relevant to the penumbra region, where microglia can respond to ischemia-stressed neurons. To mimic this in vitro, microglia, grown on porous Transwell(TM) inserts, were activated by oxygen glucose-deprived (OGD) neurons. We found that the OGD-stressed neurons released glutamate, which acted on microglial group II metabotropic glutamate receptors to activate the microglia through NF-kappaB-mediated pathway. Subsequently, we found that these activated microglia killed naive neurons through an apoptotic mechanism, mediated by TNF-alpha. Unlike the earlier LPS model, this killing was not affected by an iNOS inhibitor (SMT) or a peroxynitrite scavenger (FeTmPyP). This novel in vitro model of the ischemic penumbra will be very useful for delineating processes more relevant to neuroinflammation following ischemic stroke.
Role of Neto proteins in hippocampus dependent learning and memory

Neto 1 and Neto 2 are neural-specific proteins with largely overlapping regions of expression in the hippocampus (Ng et al., 2006 submitted). The immunoprecipitation studies demonstrated direct interaction of Neto 1 protein with N-methyl-D-aspartate receptors (NMDAR). NMDA receptors are of vital importance for hippocampus-dependent learning and memory and long term potentiation (LTP). LTP measured at the Schaffer collateral-CA1 was impaired in Neto 1 -/- hippocampal slices. Ng et al., (2006, submitted). Present study demonstrated that Neto 1-/- mice were impaired in hippocampus-dependent contrary to Neto 2-/- mice that showed normal learning in hippocampus dependent tests. It is possible that presence of Neto 1 protein may compensate for the absence of Neto 2 protein, since loss of both Neto 1 and Neto 2 protein in Neto 1-/-2-/- mice resulted in severe deficits in spatial learning which were improved with modulator of the AMPA receptor, CX-546. Thus, Neto proteins serve a role in hippocampus-dependent learning and memory.
"A lot of Indian in his face": The Native American presence in twentieth-century African American autobiography

This thesis interrogates literary interracialism between Native Americans and African Americans in twentieth-century black autobiography. Prefaced by analysis of the slave narrative tradition, my emphasis falls upon autobiography as the most formative genre in Afro-American letters. Ante- and post-bellum narratives offered an evocative platform for public scrutiny, political agitation, and moral suasion. The presence of Native Americans has had a formative but undervalued effect on the politicized self-scrutiny of twentieth-century life writing. Slavery, for instance, was a legacy both endured and perpetuated by Native peoples. The relatively large numbers of Native slaves and the extent of Native slave-owning have not received due recognition by literary historians and critics of black literature. Chapter two examines Richard Wright's Black Boy (1945). I demonstrate how Wright's seemingly minor deployment of the Noble Savage stereotype corresponds to a desire for creative freedom. Here, the quest to establish a legitimate and assertive literary voice in the Deep South during Jim Crow foreshadows the problem of asserting a non-conformist political identity in the McCarthy era. Chapter one explores Langston Hughes' The Big Sea (1940). His quest for racial authenticity uses genealogical hybridity (more specifically, his Metis grandmother's) as his imaginative catalyst. He accentuates her "Indian-ness" in order to construct a differential and essentialized African persona. For Hughes, the ability to negotiate between inchoate identities---Afro-American, Native American, African, and mixed-blood---offered not a liberating choice of selves, but rather a paralyzing anxiety about not belonging anywhere. Although the imaginative function of Natives varies according to the text and author examined, these three autobiographers treat them as conduits for their own negotiation of racial identity. Each uses an interpretation of "Native-ness" to reassess racial alterity and shed light on intellectual and imaginative discourses traditionally separated from, or polarized by, prevailing assumptions by dominant Anglo-American society. Chapter three illuminates Colored People (1994) by public intellectual Henry Louis Gates Jr. Gates' mixed-blood, Afro-Native American uncle embodies and yet reconfigures the popular archetype of the Native-as-Nature's-Child. I evaluate whether this is a pejorative and regressive construction or a nostalgic tribute to a heroic and quintessentially American version of frontier mythmaking.
Exploration of parent involvement and experiences with integrated services

This was a preliminary investigation of parent involvement set in the context of early childhood services based at school sites. The purpose of this study was to examine the roles parents play in their children's education. This study drew on anonymous data obtained from the database of the Toronto First Duty (TFD) pilot project. Semi-structured interviews with four parent focus groups were conducted at four different TFD sites. Thirty-six parents volunteered to participate in the focus group sessions. The results of this study confirmed high levels of involvement of parents who participated in the TFD project. Various forms of parent involvement included communication between themselves and their children, learning at home with their children, and volunteering at school. It is hoped that the findings of this study will be used to serve as a baseline for addressing parent involvement issues and improving service delivery to participating families.

Keywords: Education, Preschool, Parent participation
Education, Preschool, Ontario
Early childhood education, Parent participation
Early childhood education, Ontario
Parents, Services for
Parents, Ontario
Children, Services for
Children, Ontario
School improvement programs, Ontario
Home and school, Ontario
The role of CD36 in the pathophysiology of malaria: validation of a murine model and design of a clinical study

CD36 has been shown to play a central role in phagocytic clearance of Plasmodium falciparum malaria, in cytoadherence of parasitized erythrocytes to endothelium and in maintaining a balanced cytokines state. Significant progress has been made in elucidating C1336-malaria interactions in vitro but an animal model of Plasmodium falciparum does not exist. We have developed and validated a murine malaria model for examining the in vivo role of CD36 in the pathophysiology of severe malaria infection. Accumulating evidence suggests that upregulation of CD36 may be beneficial in P. falciparum infections and may increase phagocytic clearance of P. falciparum malaria, modulate deleterious inflammatory responses to infection and decrease sequestration of malaria parasites in vital organs. This strategy may therefore represent a novel immunomodulatory treatment approach for severe P. falciparum malaria. We have designed a pilot human study to address this issue.
Characterization and dissolution of scale formed during continuous pressure acid leaching of laterites

The focus of this work was the study of scale produced as a by-product from the Falconbridge laterite pressure acid leaching campaigns conducted during the period 2000 to 2002. The objective was twofold: (i) scale characterization, (ii) scale dissolution. The results obtained from the scale characterization studies revealed that alunite formed in fresh water and saline water had the general chemical formula of (H3O)Al3(SO4)2(OH) 6 (hydronium alunite) and NaAl2Fe(SO4)2(OH) 6 (sodium alunite), respectively. In saline water campaigns, Fe substitutes Al within the alunite structure---compared to that of pure hydronium alunite---at an average Al:Fe molar ratio of 2:1. Alunite comprises 67 wt% of the scale mass with hematite, making up the balance. The scale dissolution tests examined the effectiveness of chemicals dissolving scale as a measure of descaling. Two scales were tested, I3 and I6. Maximum dissolution was attained with HCl, instead of H2SO 4 at the most vigorous conditions of 200°C and 0.5m. Also, the dissolution kinetics of I3 were twice as fast as those of I6 due to the five-fold porosity of the former scale. The scale growth rates were found to be highest at the compartment of acid addition. Those obtained from the saline water campaigns were 200% greater than fresh water campaigns.
Correlating UML and source code changes: A first exploration

Design is an important stage in the software development lifecycle which lays a foundation for future implementation. UML class diagrams are a standard language used to represent system design. In this paper, we present and implement metrics for quantifying the change between two successive versions of a UML class diagram. We also use the proposed measures in a case study to explore correlations between model changes and source code changes; the existence of such a correlation is necessary for achieving our future goal of using design changes as early predictors of source code change. The research data for the case study is derived from student projects and our results indicate an absence of a correlation in their data. However, we suspect that atypical aspects of the student projects are skewing the results and further experimentation on different subjects could shed more light on our hypotheses.
Characterization of Nedd4 WW domain - ENaC peptide interactions

Nedd4 is a ubiquitin protein ligase composed of a C2 domain, multiple WW domains and a ubiquitin ligase HECT domain. WW domains are small protein-protein interaction domains that bind a variety of proline-containing sequences. The Nedd4 WW domains bind PY motifs (XPPXY) in the epithelial sodium channel (αβγ-ENaC), an association necessary for Nedd4-mediated regulation of the cell surface stability of the channel. Highlighting the importance of these interactions, mutations of conserved residues in the PY motif of β-ENaC impairs binding to Nedd4 WW domains and causes Liddle syndrome, a hereditary form of hypertension caused by elevated ENaC activity. We have used a multidisciplinary approach to study interactions between the Nedd4 WW domains and PY motif-containing regions of ENaC. Initial studies were focussed on a complex between a fragment of Nedd4 consisting of the second and third WW domains, WW(II+III), and the PY motif-containing region of β-ENaC, the βP2 peptide. Complete resonance assignment of this fragment of Nedd4, as well as the ENaC βP2 peptide, required novel experiments that detect magnetization on the 1Hα nucleus due to the proline-rich content of these molecules. NMR studies on the WW(II+III)-βP2 complex demonstrated a difference in affinity between the WWII and WWIII domains for the βP2 peptide, prompting binding studies on interactions between the individual WW domains of Nedd4 and PY motif-containing regions of ENaC. Differences in affinity of the Nedd4 WWI, WWII and WWIII domains for ENaC were observed, suggesting different in vivo targets for these domains. We then solved the solution structure of a complex between the third WW domain of Nedd4, WWIII, complexed to the βP2 region of ENaC. Only the PY motif and C-terminal residues (PPPNYDSL) are involved in binding to the WW domain. A polyproline type II helical conformation is adopted by the PPPN sequence, while the YDSL sequence forms a helical turn with both the tyrosine and the leucine contacting the WW domain. This structure, along with biochemical data expands our understanding into the mechanisms of WW domain-ligand recognition and the molecular basis of Liddle syndrome.
Monorail for congested downtown Toronto: microscopic analysis of operations and economic feasibility

Inclusion of sustainability elements in the renovation of our infrastructure is important. Improved public transit has been identified as a priority for the overly congested Greater Toronto Area (GTA). This research investigates the technical and economical feasibility of replacing existing shared right-of-way streetcars with a monorail alternative, using the 504 King Streetcar route in downtown Toronto as a case study. A microscopic simulation model for the King Street route has been developed and used in comparing the status quo to the proposed plan. A benefit-cost analysis has been conducted to evaluate whether investing in monorails is justified. A generic core cost benefit analysis model was used. Elements, sub-elements, and influencing factors of cost and benefit have been identified. Microscopic simulation shows that monorail operation is better than Streetcar. Cost-benefit done based on available data, shows that monorail is cost effective.
Psychosocial aspects of decision making for prenatal screening: nuchal translucency scanning as a new screening alternative

Background. New prenatal screening techniques increase women's options, but may complicate decision making. One such new option is nuchal translucency scanning (NTS), a non-invasive, first-trimester ultrasound screening approach. Objectives. (1) To evaluate the effects of a psychoeducational intervention; (2 & 3) To determine whether social and psychological factors associated with a desire to undergo prenatal testing, and factors associated with difficult decision making, predict the decision to undergo invasive testing; (4) to build a predictive model of the choice for invasive testing; (5) to evaluate whether psychological sequelae change, following group genetic counseling, and then again after NT-adjusted risks are received; (6) to determine whether reassuring NT-adjusted risks decrease the uptake rate of invasive prenatal testing. Sample. A consecutive series of 271 women attending a late maternal age clinic in a Canadian teaching hospital. Method. Baseline measures were used to assess psychological status, sociodemographic characteristics, and level of knowledge about prenatal diagnosis. Women were then exposed to a psychoeducational intervention, after which levels of knowledge, anxiety, risk perception, and decisional conflict were retested. For women who elected NTS and had reassuring results, measures were re-administered after adjusted risks were communicated. Analyses: Scores from social and psychological measures were analyzed using analyses of variance. Multiple regression analysis was used to assess the relative importance of the social and psychological predictors on the choice for invasive testing. Results. Knowledge increased, and decisional conflict decreased, after group genetic counseling. Predictors of invasive testing were: desire to know about fetal health; having discussed prenatal diagnosis with one's health practitioner; risk attitude, and choice of screening tests and screening results. Decisional conflict, anxiety and risk perception decreased after reassuring NTS results. Of the women who underwent NTS alone, 78% elected invasive testing. Uptake decreased to 8% when women also had reassuring maternal serum screening (MSS) results. Summary. Social and psychological factors play an integral role in women's decisions about prenatal testing. Women of advanced maternal age are willing to undergo NTS alone, but many are unwilling to forgo the certainty afforded by invasive testing. The effects of consistently reassuring screening results are worthy of further investigation.
Characterization of anoxia-tolerance and circadian changes in 70kD heat shock proteins in the three-spot wrasse

We studied the anoxia-tolerance of the three-spot wrasse (Halichoeres trimaculatus) which burrows into the sand nightly. The sand was determined to be anoxic and the wrasse survived 12h of forced anoxia at 29C. Liver glycogen content was high, comparable to other anoxia-tolerant species, and tissue [lactate] increased significantly but to lower levels than expected. It appears that high glycogen storage and metabolic depression are two strategies employed by the wrasse. The inducible heat shock protein 72 (Hsp72) was not detected in liver, heart, white muscle or gill during anoxic burial or during 12h of forced anoxia. However, Hsp72 expression was detected in liver of sand deprived fish, suggesting that the absence of sand may be a stressful. Fluctuations during a 24h cycle in white muscle, liver, and gill glucose concentration, white muscle lactate concentration and Hsp73 expression in white muscle suggest that there may be circadian variation in these compounds.
Role of protein tyrosine phosphatase MEG2 in phagocytosis: Modulation by phosphatidylinositol-3,4,5-trisphosphate and Rab28

PTP-MEG2, a cytosolic protein-tyrosine-phosphatase (PTP) containing a Sec14 homology lipid-binding domain, may be an important regulator of vesicle fusion events. PTP-MEG2 was previously shown to localize in granules, secretory vesicle membranes and associated with nascent phagosomes. However, little is known about the molecular mechanisms whereby MEG2 regulates vesicle fusion. We speculate that PTP-MEG2 specifically binds to and is activated by PIP3 in nascent phagosomes and thereby regulates signaling events that control vesicle fusion during phagocytosis that enable maturation of the phagosome. In this thesis, we examined the functional significance of the Sec14 lipid-binding domain related to regulation of the intracellular localization and activity of PTP-MEG2. We determined that the phosphatase activity of MEG2 is enhanced by phosphatidylinoisitol 3,4,5-trisphosphate (PIP3) and this interaction is mediated through its Secl4 homology domain. In Fcgamma (Fcgamma) receptor-mediated phagocytosis, PTP-MEG2 is recruited to nascent phagosomes and colocalizes with PIP3, as determined using a fluorescent reporter construct containing the pleckstrin homology domain of AKT (AKT-PH). We identified two MEG2 binding partners, N-ethylmaleimide-sensitive factor (NSF) and GTPase Rab28, which are both substrates of MEG2 and localized to nascent phagosomes.
Identification of Rheb protein-protein interactions

Recently, the small GTPase Rheb was shown to regulate cell growth signaling. The regulation of Rheb and its interaction with other signaling pathways are not fully understood. To help answer these questions, a yeast two-hybrid screen of a mouse brain cDNA library was performed using Rheb as bait. 120 candidate polypeptides were initially isolated. Further analysis eliminated false positives and identified 3 putative Rheb-interactors, adenylate cyclase 9 (AC9), ribosomal protein L22-like 1 (RpL2211), and exchange protein directly activated by cAMP 2 (Epac2). To confirm and further characterize these interactions, affinity chromatography and immunofluorescence experiments were performed. While neither candidate interactor bound Rheb under tested conditions, these proteins may still be physiological Rheb interactors. The discovery of novel Rheb interaction partners is important for elucidating Rheb's function and molecular mechanism. If subsequent studies identify AC9, RpL2211, or Epac2 as Rheb interactors this work will contribute to their body of evidence.
Evaluation of a biodegradable scaffold for the treatment of a diaphyseal bone defect of the tibia

The aim of this study was to compare angiogenesis and osteogenesis occurring within a bone defect of the tibia treated using autograft or a biodegradable bone scaffold. A diaphyseal tibia defect was created in a canine model and fixed with a statically locked intramedullary nail. Three treatment groups were studied: (1) defect empty, (2) defect treated with autograft, and (3) defect treated with scaffold. Samples were perfused with a barium compound to assess angiogenesis. Samples were analyzed using radiographs, Micro CT, brightfield microscopy and fluorescent microscopy. Extensive reaming was found to adversely affect angiogenesis and osteogenesis within an untreated tibial defect. Nonunion between osteotomy sites and intervening bone graft was observed in many of the defect sites treated with acute autogenous bone grafting. Use of a biodegradable scaffold was shown to enhance angiogenesis and osteogenesis at the osteotomy sites in this canine tibial defect model.
Do doctors follow the provincial and national guidelines for the management of low grade cervical smear abnormalities? A retrospective population-based cohort study

This paper addresses whether management of Ontario women with low grade cervical smear abnormalities, ASCUS and LSIL, is consistent with national and provincial guideline recommendations. Using an administrative laboratory database, Cytobase, compliance rates with guideline recommendations are calculated for this population for the year 1999. 29,384 women were diagnosed with a low grade cervical abnormality on a pap smear. 16% of women with a diagnosis of LSIL and 24% of women with a diagnosis of ASCUS were managed according to guideline recommendations. 48% of women with a diagnosis of LSIL and 42% of women with a diagnosis of ASCUS did not have any follow up as captured by Cytobase. A community based pilot project was also carried out utilizing a computer generated reminder placed on the pap smear report as a method of implementation of guideline recommendations to determine the feasibility of this strategy in a randomized controlled trial.
The effects of repeated yohimbine on the extinction and reinstatement of cocaine seeking

Acute exposure to the pharmacological stressor yohimbine (YOH) reinstates drug seeking in rats. The present thesis investigated whether repeated exposure to YOH, given either during or following extinction training, affects the time-course of extinction and magnitude of subsequent YOH-induced reinstatement. Rats trained to self-administer cocaine were given 5 days of extinction training. YOH/VEH animals were injected with YOH (1.25 mg/kg, i.p.) prior to, and vehicle (VEH) following, daily extinction training; VEH/YOH animals were injected in the opposite order. VEH/VEH animals were injected with VEH both before and after daily extinction training. Following additional extinction training in the absence of YOH, animals were tested for reinstatement to a YOH challenge (1.25 mg/kg, i.p.). YOH/VEH animals showed an initial resistance to extinction and a marked attenuation in reinstatement responding relative to other animals. These findings demonstrate that repeated stress exposure can modulate both extinction and reinstatement of drug seeking.