VictorJuiz/thesis huggingface dataset:
Molecular Mechanism of Podosome Formation and Proteolytic Function in Human Bronchial Epithelial Cells
Keywords: cell biology
cell migration
cell invasion
protein kinase C
podosome
matrix degradation
invadopodia
lamellipodia
membrane ruffle

In the lung, epithelial cell migration plays a key role in both physiological and pathophysiological conditions. When the respiratory epithelium is injured, the epithelial lining in the respiratory system can be seriously damaged. Spreading and migrating of the surviving cells neighboring a wound are essential for airway epithelial repair. When the repair process is affected, aberrant remodeling may occur, which is important in the pathogenesis of lung diseases. However, in comparison with other cellular and molecular functions in the respiratory system, our understanding on lung epithelial cell migration and invasion is limited. To gain insight into the molecular mechanisms that govern these cellular processes, I asked whether normal (non-cancerous) human airway epithelial cells can form podosomes, a cellular structure discovered from cancer and mesenchymal cells that controls cell migration and invasion. I found that phorbol-12, 13-dibutyrate (PDBu), a protein kinase C (PKC) activator, induced podosome formation in primary normal human bronchial epithelial cells, and in normal human airway epithelial BEAS2B cells. PDBu-induced podosomes were capable of degrading fibronectin-gelatin-sucrose matrix. PDBu also increased the invasiveness of these epithelial cells. I further demonstrated that PDBu-induced podosome formation was mainly mediated through redistribution of conventional PKCs, especially PKCα, from the cytosol to the podosomes, whereas atypical PKCζ played a dominant role in the proteolytic activity of podosomes through recruitment of MMP-9 to podosomes, and MMP-9 secretion and activiation. I also found that that PDBu can activate PI3K/Akt/Src and ERK1/2 and JNK but not p38. PI3K, Akt and Src were critical for podosome formation, whereas ERK1/2 and JNK mediated the proteolytic activity of podosomes via MMP-9 recruitment, gene expression, release and activation without affecting podosome assembly. Podosomes are important for epithelial cell migration and invasion, thus contributing to respiratory epithelial repair and regeneration. My thesis work unveils the molecular mechanisms that regulate podosomal formation and proteolytic function in normal human bronchial epithelial cells. These novel findings may enhance our understanding of cell migration and invasion in lung development and repair. Similar mechanisms may be also applicable to other cell types in distinct organs.
The Activation of Novel Calcium-dependent Pathways Downstream of N-methyl-D-aspartate Receptors
Keywords: ion channels
TRPM2
pannexin
calcium
NMDA receptors

Calcium (Ca2+) influx through N-methyl-D-asparate receptors (NMDARs) is widely held to be the requisite step initiating delayed neuronal death following ischemic stroke. However, blocking NMDARs fails to prevent the accumulation of intracellular Ca2+ ([Ca2+]i) and subsequent neurotoxicity. This suggests that alternate, as yet uncharacterized Ca2+-influx pathways exist in neurons. Transient receptor melastatin 2 (TRPM2) is a Ca2+-permeable member of the transient receptor potential melastatin family of cation channels whose activation by reactive oxygen/nitrogen species (ROS/RNS) and ADP-ribose (ADPR) is linked to cell death. While these channels are broadly expressed in the central nervous system (CNS), the presence of TRPM2 in neurons remains controversial and more specifically, whether they are expressed in neurons of the hippocampus is an open question. Here, I employ a combination of molecular, biochemical and electrophysiological approaches to demonstrate that functional TRPM2 channels are expressed in pyramidal neurons of the hippocampus. Unlike in heterologous expression systems, the ADPR-dependent activation of TRPM2 in neurons required a concomitant rise in [Ca2+]i via either voltage-dependent Ca2+ channels or NMDARs. While short, repeated NMDA applications activated a TRPM2-like current in the absence of exogenous ADPR, sustained NMDA application to hippocampal neurons resulted in the activation of a pannexin1 (Px1) hemichannel. Px1 hemichannels are large conductance, nonjunctional gap junction channels that can be activated following periods of oxygen-glucose deprivation (OGD) in neurons. Activation of Px1 required the influx of Ca2+ through NMDARs. Supplementing the intracellular milieu with adenosine triphosphate (ATP) prevented Px1 activation, suggesting that hemichannels may be activated during periods of mitochondrial dysfunction and metabolic failure. Our findings have potential implications for the treatment of diseases such as cerebral ischemia and Alzheimer’s disease (AD) as they implicate two novel ion channels in the excitotoxic signaling cascade activated downstream of NMDARs.
Red October: Left-Indigenous Struggles in Bolivia, 2000-2005
Keywords: Bolivia
indigenous
left
working class
social movements
neoliberalism
class struggle
Latin America
multiculturalism
Marxism

This dissertation provides an analytical framework for understanding the left-indigenous cycle of extra-parliamentary insurrection in Bolivia between 2000 and 2005. It draws from Marxist and indigenous-liberationist theory to challenge the central presuppositions of liberal-institutionalist understandings of contemporary indigenous politics in Latin America, as well as the core tenets of mainstream social movement studies. The central argument is that a specific combination of elaborate infrastructures of class struggle and social-movement unionism, historical traditions of indigenous and working-class radicalism, combined oppositional consciousness, and fierce but insufficient state repression, explain the depth, breadth, and radical character of recent left-indigenous mobilizations in Bolivia. The coalition of insurrectionary social forces in the Gas Wars of 2003 and 2005 was led by indigenous informal workers, acting in concert with formal workers, peasants, and to a smaller degree, middle-class actors. The indigenous informal working classes of the city of El Alto, in particular, utilized an elaborate infrastructure of class struggle in order to overcome structural barriers to collective action and to take up their leading role. The supportive part played by the formal working class was made possible by the political orientation toward social-movement unionism adopted by leading trade-union federations. Radicalized peasants mobilized within the broader alliance through their own rural infrastructure of class struggle. The whole array of worker and peasant social forces drew on longstanding popular cultures of indigenous liberation and revolutionary Marxism which they adapted to the novel context of the twenty-first century. These popular cultures ultimately congealed in a new combined oppositional consciousness, rooted simultaneously in the politics of indigenous resistance and class struggle. This collective consciousness, in turn, strengthened the mobilizing capacities of the popular classes and reinforced the radical character of protest. At key junctures, social movement leaders were able to synthesize oppositional consciousness into a focused collective action frame of nationalizing the natural gas industry. Finally, throughout the left-indigenous cycle, ruthless state repression was nonetheless insufficiently powerful to wipe out opposition altogether and therefore acted only to intensify the scale of protests and radicalize demands still further. The legitimacy of the neoliberal social order and the coercive power required to reproduce it were increasingly called into question as violence against civilians increased.
Nature and the Moral Evolution of Humanity in Nietzsche's "On the Genealogy of Morals"
Keywords: Nietzsche
morality
political philosophy

The dissertation begins by discussing recent critical treatments of Nietzsche in the work of Alasdair MacIntyre and Jürgen Habermas, then gives a brief discussion of the broader scholarly reception of Nietzsche’s political thought. The body of the dissertation proceeds through the text of the Second Essay of Nietzsche’s On the Genealogy of Morals, trying to explicate his account of the origin of political society. The dissertation attempts in the first place to show that the historical narrative Nietzsche offers in the Second Essay is coherent, then to illuminate the details of his account of the rise of political society, and thus of civilized morality (what Nietzsche calls “the bad conscience”), and finally to detail the different stages in the development of the bad conscience. The dissertation lays particular emphasis on determining the relation between what Nietzsche calls ressentiment and the bad conscience. The dissertation also attempts to shed light on Nietzsche’s view of the relation between nature and political society and morality, as he expresses it both in his analysis of the bad conscience and in the somewhat more thematic discussion of this question at the beginning of the Essay.
Participants' Preferences for HIV Prevention Interventions
Keywords: HIV Prevention
Preferences
Interventions

Background: Ontario has the highest number of HIV positive test reports in Canada. Many of the HIV prevention interventions had a moderate effect on changing unsafe sexual behaviors within the young adult population. Participants’ preferences for such interventions could be a contributing factor to the moderate effect of the prevention interventions. Treatment preference is defined as a positive or negative attitude toward a particular treatment. To date few empirical studies examined preferences for educational and cognitive/behavioral interventions focusing on HIV prevention for young adults. Purpose: The purpose of this study is twofold: to examine participants’ preferences for different types of educational and cognitive/behavioral intervention components for HIV prevention and to explore socio-structural, psychological and intervention related factors that affect participants’ preferences for intervention. Design: The study used a cross-sectional mixed methods design. The data were collected using a face-to-face interview. Structured and open-ended questions were used to inquire about participants’ preferences for intervention. Sample: The sample consisted of 150 young adults ranging in age from 18 to 39 years, and able to speak and read English. The sample was recruited from the Greater Toronto Area. Measures: The measures included an adapted questionnaire to elicit participant preference for intervention, the multi-dimensional locus of control questionnaire, AIDS health locus of control questionnaire and standard demographic questions. Analysis: Descriptive statistics were used to examine preferences for intervention components. Regression analysis was done to explore the relationships between the selected factors and participants’ preferences for intervention. Findings: All 150 participants had a preference for an HIV prevention intervention. In terms of preference for treatment type, 64% preferred an intervention that incorporated a combination of educational and cognitive-behavioral components. Specifically, 23% preferred the intervention to incorporate all three components: educational information, communication skills and goal attainment. In addition, 49% of the participants’ preferred an intervention that incorporated an average of 1-4 sessions lasting 90 minutes in length. Of the socio-structural, psychological and intervention related factors hypothesized to be associated with participants’ preferences for intervention type, components and dose, intervention related factors were found to be the most significant factors related to participants’ preferences. Conclusions: Young adults preferred to have an HIV prevention intervention that encompassed a combination of education and cognitive-behavioral components when given the opportunity to choose their preferred interventions. Providing interventions that are consistent with participants’ preferences is posited as beneficial as it increases the participants’ sense of control, satisfaction with care, adherence to intervention protocol and achievement of desired outcomes.
Improving Breastfeeding Outcomes: A Pilot Randomized Controlled Trial of a Self-efficacy Intervention with Primiparous Mothers
Keywords: breastfeeding
self-efficacy
randomized controlled trial
intervention
pilot study

Breastfeeding is recommended as the optimal source of nutrition for newborns for the first 6 months of life and beyond with the addition of complementary foods. While breastfeeding initiation rates have been increasing, duration rates remain a concern as many women prematurely discontinue due to difficulties encountered rather than maternal choice. In addition, there is a sizable gap between rates of exclusive breastfeeding and current recommendations. Targeting modifiable variables that may be amenable to intervention is one strategy to improve breastfeeding outcomes. One such modifiable variable is breastfeeding self-efficacy. Although research has clearly shown that breastfeeding self-efficacy is predictive of breastfeeding duration and exclusivity, it is unknown whether it can be enhanced to improve breastfeeding outcomes. The purpose of this pilot randomized controlled trial was to examine the feasibility and compliance of a newly developed trial protocol and the acceptability of an intervention to increase breastfeeding self-efficacy in the immediate postpartum period. Secondary outcomes included determining whether there were any trends between groups related to breastfeeding self-efficacy, duration, and exclusivity. Participants included 150 primiparous mothers who were breastfeeding their healthy, full-term infants. Eligible and consenting mothers were randomized to either a control group (standard postpartum care) or an intervention group (standard postpartum care plus the self-efficacy intervention). Participants allocated to the intervention group received three individualized, self-efficacy enhancing sessions with the researcher; two sessions were conducted in hospital, and one was administered via telephone 1 week following hospital discharge. A research assistant blinded to group allocation collected outcome data at 4 and 8 weeks postpartum. The results suggested that the administration of the intervention was feasible and that there was a high degree of protocol compliance; the majority of participants reported that the intervention was beneficial. Secondary outcomes identified that there was a trend among participants in the intervention group to have improved breastfeeding outcomes, including higher rates of breastfeeding self-efficacy, duration, and exclusivity at 4 and 8 weeks postpartum. Preliminary evidence also suggested that the self-efficacy intervention may have assisted to decrease perceptions of insufficient milk supply among the intervention group participants. Overall, the findings from this pilot trial indicated that a larger trial is warranted.
Quantification of Chemical Erosion in the Divertor of the DIII-D Tokamak
Keywords: Plasma
Fusion
Spectroscopy
Hydrocarbon

The International Thermonuclear Experimental Reactor (ITER) is currently designed to use graphite targets in the divertor for power handling and impurity control. Understanding and quantifying chemical sputtering is therefore key to the success of fusion as a clean energy source. The principal goal of this thesis is to design and carry out experiments, then analyze and interpret the results in order to elucidate the role of chemical sputtering in carbon sources in the DIII-D tokamak. A self-contained gas puff system has been designed, constructed, and employed for in-situ study of chemical erosion. The porous plug injector (PPI) releases methane through a porous graphite surface into the divertor plasma at a precisely calibrated rate, minimizing perturbation to local plasma while replicating the immediate environment of methane molecules released from a solid graphite surface more accurately than done previously. For the first time in a tokamak environment, the methane flow rate used in a puffing experiment was the same order of magnitude as that expected from laboratory experiments for intrinsic chemical sputtering. Effective photon efficiencies for injection are reported; results are found to have significant dependencies on surface conditions and the divertor operating regime. The contribution of sputtering processes to sources of C0 and C+ are assessed through measurement of background and incremental spectroscopic emissions of both physically and chemically-released sputtering products and by CI, 910 nm line profile fitting. Comparison of background and incremental emissions of chemically-released products demonstrate a dramatic drop in production of CH in cold and detached conditions. Finally, the chemical erosion yield is calculated in both attached and cold-divertor conditions and found to be much closer to that measured ex-situ in ion beam experiments than previously determined in DII-D. These observations represent a positive result for ITER which will operate at all times with a detached divertor, i.e., a low chemical sputtering yield. Results and analysis techniques presented here point the direction for future experiments with the PPI for study of chemical sputtering in the tokamak edge environment.
Trouble in our Fields: Health and Human Rights among Mexican and Caribbean Migrant Farm Workers in Canada
Keywords: migrant workers
migrant farm workers
seasonal agricultural workers
farmworkers
temporary foreign workers
health
human rights
migration
medical anthropology
Canada
Jamaica
Mexico
occupational health
sexual health
mental health
health care
workers compensation
Seasonal Agricultural Workers Program
structural violence
agriculture

For many years Canada has quietly rationalized importing temporary “low-skilled” migrant labour through managed migration programs to appease industries desiring cheap and flexible labour while avoiding extending citizenship rights to the workers. In an era of international human rights and global competitive markets, the Canadian Seasonal Agricultural Workers Program (SAWP) is often hailed as a “model” and “win-win” solution to migration and labour dilemmas, providing employers with a healthy, just-in-time labour force and workers with various protections such as local labour standards, health care, and compensation. Tracing migrant workers’ lives between Jamaica, Mexico and Canada (with a focus on Ontario’s Niagara Region), this thesis assesses how their structural vulnerability as non-citizens effectively excludes them from many of the rights and norms otherwise expected in Canada. It analyzes how these exclusions are rationalized as permanent “exceptions” to the normal legal, social and political order, and how these infringements affect workers’ lives, rights, and health. Employing critical medical anthropology, workers’ health concerns are used as a lens through which to understand and explore the deeper “pathologies of power” and moral contradictions which underlie this system. Particular areas of focus include workers’ occupational, sexual and reproductive, and mental and emotional health, as well as an assessment of their access to health care and compensation in Canada, Mexico and Jamaica. Working amidst perilous and demanding conditions, in communities where they remain socially and politically excluded, migrant workers in practice remain largely unprotected and their entitlements hard to secure, an enduring indictment of their exclusion from Canada’s “imagined community.” Yet the dynamics of this equation may be changing in light of the recent rise in social and political movements, in which citizenship and related rights have become subject to contestation and redefinition. In analyzing the various dynamics which underlie transnational migration, limit or extend migrants’ rights, and influence the health of migrants across borders, this thesis explores crucial relationships between these themes. Further work is needed to measure these ongoing changes, and to address the myriad health concerns of migrants as they live and work across national borders.
The Regulatory Properties of α5 Subunit-Containing γ-Aminobutyric Acid Subtype A Receptors in Learning and Synaptic Plasticity
Keywords: Learning
GABA
alpha5
fear conditioning

Synaptic plasticity, which is thought to represent the neuronal substrate for learning and memory is influenced by the degree of GABAergic inhibitory tone. In particular, γ-aminobutyric acid subtype A receptors (GABAARs), which mediate the majority of inhibitory neurotransmission in the mammalian brain regulate learning and plasticity. In these studies I examined a subpopulation of α5 subunit-containing GABAA receptors (α5GABAARs), which are preferentially expressed in the hippocampus, to determine whether they have a specific role in memory processes. I hypothesized that α5GABAAR-activity constrains hippocampus-dependent learning and CA1 synaptic plasticity. The main research objective of this thesis was to investigate the electrophysiological changes within the hippocampus that accompany genetic and pharmacological targeting of α5GABAARs and how these changes impact behaviour. I found that the general anesthetic etomidate enhanced a tonic inhibitory conductance generated by α5GABAARs, and this action correlated with an impairment of long-term potentiation (LTP) and hippocampus-dependent memory performance for fear-associated memory and spatial navigation. Mice with a genetic deletion of the α5 subunit gene (Gabra5–/–) were resistant to the LTP- and memory-impairing effects of etomidate. Additionally, the LTP- and memory-impairing effects of etomidate were rescued by pharmacologically inhibiting α5GABAARs. Genetic and pharmacological inhibition of α5GABAARs enhanced associative learning in trace fear but not contextual fear conditioning tasks. Interestingly, genetic deletion and pharmacological inhibition of α5GABAARs did not result in the common adverse side-effects associated with non-selective inhibition of GABAARs such as anxiogenesis or seizures. Further, I found that blocking the tonic inhibition generated by α5GABAARs lowered the threshold for LTP, such that lower stimulation frequencies enhanced LTP. Synaptic changes within this frequency band were modified independently of phasic GABAAR inhibition. Inhibiting the α5GABAAR-dependent membrane conductance was associated with an increase in the depolarizing envelope during 10 Hz stimulation. These experiments provide new insights into the in vitro and in vivo physiology of α5GABAARs and suggest that a tonic inhibition generated by α5GABAARs constrains learning and glutamate plasticity through regulation of the membrane’s electrical properties.
Dimension Groups and C*-algebras Associated to Multidimensional Continued Fractions
Keywords: dimension group
C*-algebra
continued fraction
multidimensional continued fraction

Thirty years ago, Effros and Shen classified the simple dimension groups with rank two. Every such group is parametrized by an irrational number, and can be constructed as an inductive limit using that number's continued fraction expansion. There is a natural generalization of continued fractions to higher dimensions, and this invites the following question: What dimension groups correspond to multidimensional continued fractions? We describe this class of groups and show how some properties of a continued fraction are reflected in the structure of its dimension group. We also consider a related issue: an Effros-Shen group has been shown to arise in a natural way from the tail equivalence relation on a certain sequence space. We describe a more general class of sequence spaces to which this construction can be applied to obtain other dimension groups, including dimension groups corresponding to multidimensional continued fractions.