VictorJuiz/thesis huggingface dataset:
Negotiating Consensus: Reading Time and Space in Nineteenth-century Novels and Popular Print Genres
Keywords: Almanacs
Book history
Nineteenth-century literature
Reading
Space
Time

Traditionally, the realist novel has been associated with representations of homogeneous time and space, continuous with the world of the reader and measurable in objective units of duration or distance. Cued by characters who attend carefully to schedules, positions, and distances, readers and critics have perhaps overlooked the extent to which novelists use time and space not to represent the consensual, the objective, and the real, but to communicate their characters' desires for consensus. This dissertation explores how nineteenth-century novelists have their characters draw upon symbols and language of time and space to articulate feelings, desires, or values that are difficult to voice or explain, as if a language of time and space might be more easily understood than any other kind of language. In Jane Austen's Mansfield Park and Emma, George Eliot's The Mill on the Floss and Middlemarch, and Henry James's The Portrait of a Lady and The Golden Bowl, representations of time and space are sites of contested meaning, involving negotiations between the private feelings of individuals and the conventions of the community. This dissertation also suggests that novelists have characters draw upon time and space to make subversive desires or abstract ideas comprehensible to others partly because two influential print genres--the almanac and the travel handbook--explicitly associated consensus with time and space. However, almanacs also encouraged readers to distinguish between personal and public time, and to reconcile them in the margins of their texts as they read, while travel handbooks prompted similar negotiations regarding the traveller's personal experiences of public spaces. While apparently authoritative, these print genres were actively and diversely used by readers, provocatively paralleling, and perhaps influencing, the nineteenth-century novel's reliance on time and space to represent negotiations between individuals and their communities.
Investigations into UNC-40-Mediated Guidance of Cell Migrations and Cell Extensions
Keywords: Axon guidance
C. elegans
Cell migration
Chemoattraction
DCC
Netrin

The migration of cells and cell extensions is essential for the proper development of an organism. Guidance receptors at the leading edge of migratory cells interpret and translate various environmental stimuli into spatially restricted cytoskeletal modulations that lead to directed membrane extension. To better understand mechanisms of guidance, I study the midline-oriented guidance of specialized muscle membrane projections found in C. elegans called muscle arms. The guidance of muscle arms to the midline depends on a non-canonical UNC-40/DCC pathway that responds to the novel cue MADD-4. UNC-40 is a transmembrane receptor whose canonical ligand is the UNC-6/netrin cue. We have previously shown that downstream effectors of UNC-40 activity in muscle arm extension include UNC-73/RhoGEF, the WAVE actin polymerization complex GEX-2/GEX-3/WVE-1, and members of the focal adhesion complex. Together, these components act in concert to influence actin-based membrane extension to the midline. We found that the EVA-1 transmembrane receptor likely functions as a co-receptor for UNC-40 to respond to MADD-4 for the guidance of muscle arms and axons. EVA-1 is a conserved transmembrane protein with predicted galactose-binding lectin domains. EVA-1 functions in the same pathway as MADD-4, physically interacts with both MADD-4 and UNC-40, and enhances UNC-40's sensitivity to MADD-4. This enhancement is especially important in the presence of UNC-6, because when EVA-1 is absent, we find that UNC-6 interferes with UNC-40's responsiveness to MADD-4. In the absence of UNC-6, UNC-40's responsiveness to MADD-4 is less dependent on EVA-1. By enabling UNC-40 to respond to MADD-4 in the presence of UNC-6, EVA-1 may increase the precision by which UNC-40-directed processes can reach their MADD-4-expressing targets within a field of the UNC-6 guidance cue. I also identified the involvement of integrins in the guidance of muscle arms and axons. I found that integrin likely forms a complex with EVA-1 and UNC-40 to mediate MADD-4 responses. Disruption of integrin suppresses MADD-4 induced axon dorsalization such that the axons extend in a wild type manner, suggesting that integrins play a role in MADD-4 oriented guidance. The function of integrins may provide a mechanistic link between nascent guided membrane and the maintenance of structural support.
Voice as a Memory Cue
Keywords: auditory
evoked potentials
memory

The study of human memory often focuses on the benefit of context congruency. In the auditory domain, perhaps the most important context cue is speaker's voice. The present set of auditory experiments was designed to further our understanding of voice as a memory cue. Words were spoken in voices that were congruent on either accent or pitch, both or neither. Voice reinstatement signified maximum congruency and occurred when the same voice spoke the word initially and in a subsequent memory test; voice congruency referred to either accent or pitch being comparable between presentations of a word. These stimuli were chosen to validate and extend earlier models of voice congruency based primarily on variations of pitch between speakers; we investigated multiple salient voice parameters. Experiment 1 found that voice reinstatement aids word and speaker recognition, and that voice congruency partially benefits word recognition. Experiment 2 used a different paradigm and found that voice reinstatement is required to boost word recognition when participants are not given instructions to attend to voice. Experiment 3 provided preliminary evidence that voice reinstatement benefits implicit memory. Experiment 4 examined whether voice effects vary with linguistic background; the benefit of accent congruency to word recognition appears to be augmented in bilinguals of the same language as the accented speaker voice. The first two experiments also utilized event-related potentials (ERPs) to discern the neural correlates underlying the use of voice in memory. Taken together, results indicate that the extent of voice congruency effects, as well as the characterization of ERP modulations reflective of memory components, depends on the task/paradigm used. For example, attention (or some extended processing) is required to observe partial voice congruency effects, while a voice reinstatement benefit appears to be more robust. Finally, this work serves as a starting point for future studies to understand voice congruency in implicit memory and in people with specific language abilities.
Nanotechnology-based Strategies To Enhance Chemo-and Radiation Therapy In Breast Cancer
Keywords: Breast cancer
Chemotherapy
Radiation therapy

A major cause of cancer treatment failure is multidrug resistance (MDR) and radioresistance to standard therapies. Overexpression of ATP-binding cassette (ABC) transport proteins by cancer cells, which actively transport anti-cancer agents (e.g. doxorubicin, Dox) out of the cells against concentration gradients, is a major barrier to effective chemotherapy. Low levels of oxygen in tumors are responsible for radioresistance contributing to the failure of radiation therapy (RT) of solid tumors. This thesis concerns the development and evaluation of three nanoparticle delivery systems for overcoming tumor resistance to chemo- and radiotherapy. System 1: polymer lipid hybrid nanoparticles (PLN), co-loaded with a synergistic combination of anticancer agents Dox and mitomycin C (MMC) (DMsPLN), were found to overcome multiple membrane efflux pumps mediated MDR in vitro. Systemic administration of DMsPLN significantly enhanced therapeutic efficacy in orthotopic tumor models of Dox-sensitive and resistant human breast cancer cells, with low systemic toxicity compared to a clinically used liposomal formulation of Dox. System 2: cyclic Arg-Gly-Asp (RGD), a ligand that binds with αvβ3 intergin receptors preferentially expressed in angiogenic tumor blood vessels and certain cancer cells, was conjugated to DMsPLN. The Integrin-targeted RGD-DMsPLN resulted in a significant reduction in lung metastases of human breast cancer cells without producing drug-associated systemic toxicity as observed in mice treated with free Dox-MMC solutions. System 3: Manganese dioxide nanoparticles (MnO2 NPs) were developed and the reactivity of MnO2 towards peroxides was utilized to regulate the tumor microenvironment in a murine breast tumor. Intratumoral administration of MnO2 NPs simultaneously increased tumor oxygenation by 45%, and tumor pH from pH 6.7 to pH 7.2 by reacting with endogenous H2O2 produced within the tumor. Combination treatment of the tumors with NPs and ionizing radiation significantly inhibited breast tumor growth, increased DNA double strand breaks and cancer cell death as compared to RT alone. The design and application of these three novel nanotechnology platforms, in pharmaceutically acceptable NP formulations, provide promising therapeutic strategies for enhanced chemo- and radiation therapy of breast cancer.
The Design and Use of a High throughput Microscopy Screen to Monitor Transcription Factor Localization in Saccharomyces cerevisiae
Keywords: cerevisiae
kinase
transcription factor

Cellular signalling networks control gene expression by modulating the activities of transcription factors through regulatory mechanisms that affect their transactivation or transrepression potential, DNA-binding affinity, localization, or abundance. This regulation often requires the site-specific phosphorylation of the transcription factor by a kinase. I have developed a high throughput microscopy screen and used it to monitor the nucleo-cytoplasmic distribution and abundance of 122 different GFP-tagged transcription factors in 84 different Saccharomyces cerevisae kinase mutant backgrounds and in wild type cells after exposure to eight different environmental stress conditions that modulate kinase signalling pathways. Thirty one GFP-tagged transcription factors exhibited changes in localization or abundance, mostly in response to an acute exposure to environmental stress rather than to the chronic loss of a non-essential kinase. These screens revealed that the Yero88c transcriptional repressor, which was not previously known to undergo changes in localization, translocates from the cytoplasm to the nucleus in response to multiple environmental stresses; its paralog, Yblo54w, displayed similar behavior. Yero88c and Yblo54w are known to repress the transcription of ribosome biogenesis (Ribi) genes in response to environmental stress and the downregulation of the TORC1 or PKA signalling pathways (Lippman Broach, 2009). I show that the nuclear accumulation of Yero88c and Yblo54w is inhibited by TORC1 and PKA signalling. Further analysis implicates the kinase Sch9 and the Tap42-associated phosphatase complexes in the regulation of Yero88c localization by TORC1. Serine-to-alanine substitutions at six putative PKA/Sch9 consensus phosphoacceptor sites in its sequence causes Yero88c to localize to the nucleus constitutively. These data suggest that under optimal growth conditions PKA and Sch9 phosphorylate Yero88c causing it to localize to the cytosol, whereas the activation of TORC1-regulated phosphatases in response to stress induces the dephosphorylation and nuclear accumulation of Yero88c resulting in the repression of Ribi genes and the attenuation of cell growth.
Transcranial Adaptive Beamforming via Ultrasonic Phased Arrays and its Application to 3D Imaging of Certain Types of Head Injuries
Keywords: Adaptive beamforming
Phase aberration
Phased array
Transcranial
Ultrasonic imaging

A new adaptive beamforming method for ultrasonic imaging via small-aperture phased arrays through composite layered structures, such as human skull, is developed. If there is a scattering layer between the phased array and the imaged volume, acoustic phase aberration and wave refraction at undulating interfaces between the barrier and the rest of the propagation media can cause significant distortion of an ultrasonic image pattern produced by conventional beamforming techniques. This distortion takes the form of defocusing the ultrasonic field transmitted through the skull and causes loss of resolution, overall degradation of image quality and generation of non-informative final sonograms. To compensate for the phase aberration and refractional effects, an adaptive beamforming algorithm is developed and examined. After accurately assessing the skull's local geometry and sound speed, the method calculates a new timing scheme to refocus the distorted beam at its original location. The procedure is in fact a construction of a matched filter that automatically adapts the transmission and reception patterns of the phased array to the local geometry and acoustical properties of the skull and cancels its distorting effects. Results of numerical simulations, developed to accommodate and verify the proposed theory, are provided and discussed. The simulation results are verified experimentally by applying the method on realistic human skull phantoms in water immersion setups. The developed adaptive beamforming algorithms were implemented on an open-platform phased array controller and a lab prototype of the imaging system was delivered. Results of 2D and 3D adaptive imaging through skull phantoms via 2MHz linear and matrix phased arrays are presented.
Investigating the Effect of Vesicular Acetylcholine Transporter Expression on Central and Peripheral Function
Keywords: acetylcholine
ChAT
choline acetyltransferase
cholinergic
neurotransmitter
VAChT

Cholinergic neurons use the neurotransmitter acetylcholine extensively throughout the central and peripheral nervous systems. During normal and pathological aging (i.e. Alzheimer's disease) cholinergic neurotransmission decreases, particularly in the basal forebrain which supplies the cortex and hippocampus with cholinergic input. This thesis investigates the effect of vesicular acetylcholine transporter (VAChT) overexpression on cholinergic function. The biochemical characteristics of cholinergic neurons following VAChT overexpression were measured and the behaviour phenotype of these animals was evaluated. Furthermore, the effect of lifelong VAChT overexpression on the age-related impairment of hippocampal structure and function was determined. No overt differences in the expression levels of presynaptic cholinergic transcripts and proteins were observed following VAChT overexpression in mice. With this absence of presynaptic compensation, acetylcholine release in the hippocampus was found to be significantly elevated. While this increased level of acetylcholine release was not sufficient to significantly modify peripheral function, we observed behavioural phenotypes conducive to central cholinergic action. VAChT overexpressing mice exhibited decreased locomotion and enhanced response to novelty in the open field. In addition, these mice displayed a release of exploratory inhibition. These data support the ability of VAChT to modulate cholinergic tone and central cholinergic function. Using a model of normal aging, VAChT overexpression was found to enhance dendritic ramification in newborn neurons of the hippocampus. An improvement of the precision of spatial memory acquisition was also observed in aged mice overexpressing VAChT. These data provide direct immunohistological evidence that VAChT overexpression augments dendritic expansion in the hippocampus and that VAChT contributes to improved precision of hippocampal-dependant spatial memory. In conclusion, this thesis demonstrates that VAChT overexpression augments central cholinergic function related to locomotion, response to novelty and hippocampal structure and that these features may in part contribute to superior spatial memory during aging.
Characterizing the Role of Dietary Antioxidants as Immune-enhancing Molecules in Larval Anurans
Keywords: Antioxdants
Diet
Larval anurans
Self-medication

The effects of stress (disruption of homeostasis) and stressors (factors that cause changes in homeostasis) and their impacts on animal health, physiology, behaviour and fitness have received enormous attention within the scientific community. From an evolutionary stand point, understanding the way in which animals cope with stress or how stress tolerance has evolved is important, as chronic stress can lead to loss of fitness. From an ecological stand point, identifying stressors within the environment and understanding how additive stressor effects can impact the way in which animals cope is crucial for understanding population declines and or possible extinctions. One coping mechanism used by some animal taxa is diet. When consumed, dietary antioxidants (secondary metabolites produced by plants) can provide protection from oxidative damage that can result from exposure to stressors. My dissertation focuses on the effects of these compounds on tadpole immune function. I choose to focus on tadpoles, as populations of numerous amphibian species are declining worldwide and some have gone extinct. In addition, tadpoles, which are strictly aquatic, are exposed to a wide variety of both abiotic and biotic stressors. I focus on three areas of study: 1) the effect of dietary antioxidants and natural stressors on immune function; 2) whether or not tadpoles detect these compounds in their food and whether or not they have the ability to self-medicate; 3) a potential trade-off between immune function and antipredator defense mediated by dietary antioxidants and the environmental availability of these compounds in natural tadpole habitats. My work will contribute to the field of ecology and amphibian biology by investigating the effects of these potentially beneficial compounds and the effects on amphibian immune function, in an attempt to determine if there are any natural immune enhancers to help amphibian's combat mortality via immunosuppression.
α-Melanocyte Stimulating Hormone Prevents GABAergic Loss and Improves Cognitive Function in Alzheimer's Disease
Keywords: alpha-melanocyte stimulating hormone
Alzheimer's disease
cognitive function
GABAergic system
somatostatin

In Alzheimer's disease (AD), the appropriate excitatory/inhibitory balance required for memory formation is impaired. In order to elucidate deficits in the inhibitory gamma-aminobutyric acid (GABA)-ergic system in AD and to establish a link between GABAergic dysfunction and cognition, the TgCRND8 mouse model of AD was utilized. TgCRND8 mice with established amyloid beta peptide (Abeta) pathology exhibit spatial memory deficits and altered anxiety. Concomitant with behavioural changes, GABAergic deficits are observed in the hippocampus. The GABAergic marker glutamic acid decarboxylase 67 (GAD67) mRNA and protein levels in the hippocampus as well as the number of GAD67+ GABAergic cells in the CA1 region of the hippocampus are significantly decreased. However, at this stage of Abeta pathology, the number of ChAT+ cholinergic cells in the septum remains unchanged, suggesting that cholinergic cells may not underlie behavioural deficits. The GABAergic loss may represent an early target in AD disease progression. By increasing inhibition, the physiological excitatory/inhibitory balance in the brain may be restored resulting in normal function. I found that the neuropeptide, alpha-melanocyte stimulating hormone (alpha-MSH), prevents the loss of GAD67 mRNA, protein levels and GAD67+ cells in the CA1 region of the hippocampus. In particular, alpha-MSH protects the loss of the somatostatin (SST) expressing subtype of GAD67+ inhibitory interneurons. SST is reduced in the CSF and brain of AD patients and SST levels are correlated with cognitive function. By preserving hippocampal GAD67+ cells, especially the SST+ subtype, alpha-MSH improved spatial memory in TgCRND8 mice and prevented changes in anxiety independent of altering Abeta; peptide load in the brain. alpha-MSH modulated the excitatory/inhibitory balance in the brain by restoring GABAergic inhibition and as a result, improved cognition in TgCRND8 mice.
Locating Diaspora: Afro-Caribbean Migrations and the Transnational Dialectics of Race and Community in North America, 1910-1929
Keywords: Afro-Caribbean
Diaspora
Migration
North America
Race
Transnational

This dissertation examines the migration of West Indians from the Anglophone Caribbean to the U.S. and Canada in the early twentieth century. It focuses on the transnational negotiations of racial community and conceptions of blackness, a process enacted through Afro-Caribbean migration networks and the encounters between peoples of African descent in North America. The comparative element considers how conceptions of race, and specifically blackness, were differently constituted and expressed among communities in three different locales: New York, Montreal, and Toronto. The transnational dimension illuminates the connective elements between those sites and the mediation of ethnic and national difference among black Canadians, Americans, and West Indians. It proposes three scales by which to analyze formations of community and diasporic conceptions of race in North America. The first scale of analysis is the nation. In their migrations, Afro-Caribbean immigrants encountered different constructions of blackness within the respective national contexts; black peoples themselves expressed multiple and sometimes conflicting identifications with nation, state, and empire in Canada and the U.S. Second, this dissertation evaluates communities at the local level, identifying the characteristics of urban sites that framed the West Indian experience and the formulations of racial communities therein. The third scale of analysis is the transnational. Here, it focuses on how different expressions of race in the respective local and national contexts were mobilized between sites and across space, and how the terms of blackness traveled and translated across geographic, political, and cultural borders. Ultimately, this dissertation illustrates the process and practice of diaspora among peoples in the respective U.S. and Canadian cities, and their transnational engagements with a broader racial community. In the early twentieth century, the category of blackness had increasing resonance among an otherwise diverse, disparate, and ethnically heterogeneous community. Diasporic blackness was rooted in the North American experience, and routed through West Indian migration networks between New York, Toronto, and Montreal. It not only incorporated differences among peoples of African descent, it was contingent upon them. As a result of these cross-border encounters and interactions, racial, ethnic, and national communities were remade through diaspora.
Using Quantitative Synthetic Genetic Interaction Profiling in Escherichia coli to Investigate Bacterial Protein Synthesis
Keywords: conditional rewiring
genetic interaction
protein synthesis
ribosome biogenesis
synthetic genetic array
translational fidelity

Bacterial protein synthesis depends on the coordination of a complex, multi-component machinery that processes ribosomal RNA, assembles ribosomes, and translates diverse messenger RNA transcripts to meet changing physiological and environmental demands. Despite decades of detailed investigations, which enabled basic mechanistic understanding of the core translation processes, the global functional connectivity and component memberships of this central system and its relationship to other biological pathways had remained unclear. Physical interaction data can suggest the biological roles and associations of gene products, but only genetic interaction (GI) screens can truly reveal pathway-level functional dependencies. For my Thesis, I performed quantitative