VictorJuiz/thesis huggingface dataset:
The Effect of Articulatory Constraints and Auditory Information on Patterns of Intrusions and Reductions

This dissertation seeks to answer the question whether articulatory constraints and auditory information affect intrusion and reduction errors. These intrusions and reductions of articulatory movement result from a general tendency to stabilize movement coordination. Stabilisation of speech movement coordination is an autonomous self-organizing process. This process, however, can be affected by factors related to articulatory properties and auditory information. To assess how these factors affect movement coordination, three studies were performed. The first study examined differences in articulatory variability in the onsets of word pairs such as cop top and top top. To this end, different phonetic contexts and speaking rate were manipulated. As word pairs like top top are frequently used as control stimuli and word pairs like cop top as experimental stimuli, this study investigated how these two word pairs differ in movement control. The second study examined how constraints on individual articulators, manipulated by phonetic context, and speaking rate affected the number of intrusions and reductions. The third study investigated how these intrusions and reductions were influenced by the presence or absence of auditory information. Movements of the tongue tip, tongue dorsum and lower lip were recorded with electromagnetic articulography. The first study revealed that word pairs with alternating and identical onset consonants differ to such an extent that using identical onset word pairs as control stimuli is not recommended for future error studies. The second study revealed that articulatory constraints resulted in asymmetrical patterns of intrusions: compared to a high back vowel context, a low vowel context resulted in more intrusions in general. In addition, in a front vowel context, the tongue dorsum intruded more frequently than the tongue tip and lower lip. The third study showed that speakers made fewer intrusions without auditory information available than with auditory information available. The results, which are explained within the framework of Articulatory Phonology and Task Dynamics, support the notion that articulatory constraints and auditory information influence coupling strength and movement coordination as reflected in intrusion and reduction patterns.

Keywords: Articulatory Phonology
Auditory information
Coarticulation
Intrusions
Reductions
Task Dynamics
Advisor: Pascal, H. H. M. van Lieshout
Identifying Mediators of Androgen-independent Prostate Cancer Using Mass Spectrometry-based Proteomics

Androgen-deprivation remains the principal therapy for advanced and metastatic prostate cancers. However, some cancer cells are able to survive this treatment and transform themselves to a more aggressive androgen-independent prostate cancer (AIPC). An understanding of the molecular alterations that occur during the progression to androgen-independence is of utmost importance in order to generate effective targeted therapies. Using two different in vitro approaches coupled to high through-put mass spectrometry, we were able to identify numerous potential mediators of AIPC and aggressive prostate cancer. Our first approach using an in vitro cell line model of androgen-independence allowed us to identify enzymes of the ketogenic pathway as elevated in cases of aggressive prostate cancer. Specifically, ACAT1, an enzyme in this pathway, was further validated and shown to be substantially elevated in clinical cases of castration-resistant metastatic prostate cancer. In addition, ACAT1 was found to be an independent tissue-based prognostic marker of biochemical recurrence-free survival. In our second approach we compared the secreted proteomes of androgen independent cell lines (PC3, DU145, PPC1, LNCaP-SF, 22Rv1) to androgen-dependent (LNCaP, VCaP) and normal prostate epithelial (RWPE) cell lines. Of the over 3000 proteins identified in the secretomes, we found more than 100 proteins that were differentially secreted in the androgen independent cell lines. Of these, Protein S (PROS1) was elevated in the secretomes of all the AIPC cell lines and was not detected in the normal or androgen-dependent prostate cancer cell lines. Next, using RT-PCR and immunohistochemistry, we observed significantly higher tissue expression levels of PROS1 in localized high-grade and castrate-resistant metastatic prostate cancer samples compared to normal and low-grade prostate cancer, further indicating its importance in prostate cancer progression. Finally, functional validation revealed that PROS1 increases cell proliferation, migration and viability and thus may play a direct role on prostate cancer biology.Taken together, the results of this research will help in not only increasing the understanding of key molecular alterations and mechanisms by which prostate cancer cells can utilize to gain androgen-independence, and more importantly, aid in the development of new targeted therapies by potentially focusing on blocking or altering specific critical signalling cascades.

Keywords: Androgen-independence
Ketogenic Pathway
Prostate Cancer
Protein S
Proteomics
Advisor: Eleftherios, P Diamandis
Clinical, Neuroanatomical, and Neuropsychological Outcomes in Children with Brain Tumors

This thesis utilized diffusion tensor imaging (DTI) and tractography to examine cerebrocerebellar pathway microstructure, as well as medical and demographic data and measures of executive function (EF) to investigate clinical, neurological, and cognitive/behavioral outcomes following treatment for Posterior fossa (PF) tumors. Further, the influence of neurological outcome (i.e. cerebrocerebellar microstructure) on clinical and cognitive/behavioural sequelae was considered. PF tumors account for approximately half of all pediatric central nervous system malignancies and are treated with surgery, radiation, and chemotherapy. With treatment advances, survival rates have improved dramatically though significant late effects (e.g. neurotoxicity and cognitive morbidity) are often observed. Because of tumor location and treatment, damage to the cerebellum and its input/output pathways can occur in patients; this injury may have impact on clinical and cognitive/behavioural outcomes. First, it was found that a higher tumor grade, larger tumor size, and left handedness predicted Cerebellar Mutism Syndrome (CMS), a postoperative disorder present in approximately 25% of children with PF tumors. CMS was also associated with right cerebellar hemispheric white matter damage within the cerebello-thalamo-cerebral pathway - the main cerebellar efferent. Second, using DTI, neuroanatomical identification and segmentation of reciprocal cerebrocerebellar pathways was completed; children treated for PF tumors showed damage to these pathways compared to healthy children - particularly within posterior segments. Third, impairment in EF domains (i.e. cognitive efficiency, planning, working memory, emotion regulation) was observed in children treated for PF tumors relative to healthy children. Microstructure of the cerebello-thalamo-cerebral pathway mediated the effect of treatment for PF tumors on EF outcome, specifically in working memory. This thesis a) provides a schema for CMS risk in children with PF tumors based on medical and neurobiological features; b) shows that treatment for PF tumors put patients at risk for damage to cerebrocerebellar circuitry and this neurological injury, in turn, is associated with working memory impairment; and c) elucidates the role of cerebrocerebellar pathways in connecting brain regions important for speech-language and working memory functions. These findings provide a framework for how individual variance in outcome in patients may occur and can inform the implementation of preventative/mitigative therapies to remedy the adverse effects of treatment.

Advisor: Donald, Mabbott
Characterization of Neuronal Anillin and Borg Protein Localization and Function

Septins are filament-forming proteins that scaffold a host of proteins to their sites offunction. One such protein is anillin, that along with septins, mediates cytokinesis duringcell division. Research to date has focused on characterizing the role of anillin duringcytokinesis. Interestingly, anillin is most highly expressed in the central nervous system,which is in part composed of terminally differentiated, post-mitotic cells, such asneurons. Anillin has been characterized as a mitotic marker in neuronal cells, but perhapsits high expression in the poorly mitotic brain could indicate another, novel role ofanillin. Here we show that not only is anillin present in multiple primary central nervoussystem cells, it is also a smaller isoform of anillin, having an N-terminal truncation. Thetruncated anillin, localizes differently than the better characterized somatic cell anillin,being present in the cytoplasm and largely excluded from the nucleus. In addition, thiscytoplasmic truncated anillin localizes to the phagocytic cup, where it is involved inmediating phagocytosis. Interestingly, brain anillin still localizes to the cleavage furrowdespite its N-terminal truncation, and perhaps its function as an anchor for theactomyosin contractile ring to the cortex, is supplemented by other actin-binding proteincomplexes like the cadherin-catenin complex.The assembly of septin filaments is poorly understood. One of the best candidates forregulating septin filaments are the poorly understood Borg family of proteins that caninduce septin filament polymerization when overexpressed. Here we show that Borgproteins localize to multiple septin-containing structures and are involved in regulatingseptin polymerization into rings. Borg depletion studies also link them to multiple mitoticprocesses, which largely mirrors septin-depletion phenotypes. We also link Borgs toseptin recruitment at the primary cilia. In short, our results show that a novel form ofanillin exists in the brain, and is involved in phagocytosis. In addition, our Borg studiesfurther characterize their roles in septin-dependent phenotypes, as they are required fornormal mitosis progression, and septin recruitment to the ciliary axoneme.

Keywords: borgs
central nervous system
mitosis
phagocytosis
primary cilium
septins
Advisor: William, Trimble
A Generalized Arousal Model of Political Orientation

The majority of psychological theories of political orientation are predicated on the assumption that negatively-valenced emotion enhances conservative belief. In support of this notion, exposure to fear-inducing and disgusting stimuli motivate conservative versus liberal shifts in political beliefs. However, we have recently suggested that research in this area has confounded valence with arousal, which may have led to the premature conclusion that negative valence, rather than arousal more generally, is associated with conservative political beliefs. In a series of 4 studies, we tested the hypothesis that arousal, rather than negative valence per se, promotes conservative orientation. In Studies 1 and 2, experimentally-induced positive as well as negative emotional arousal was associated with enhanced agreement with right-wing political speeches, controlling for baseline political orientation. Studies 3 and 4 used event-related potentials (ERPs) to determine the relationship between political orientation and electrophysiological sensitivity to emotional stimuli. In Study 3, conservatism versus liberalism was associated with heightened feedback-related negativity -- an ERP component thought to index activity in neural regions associated with reward processing -- in response to positive feedback. In Study 4, conservatives, compared to liberals, demonstrated heightened amplitude of the late positive potential (an ERP component that covaries with the motivational salience of stimuli) in response to emotional stimuli, regardless of valence. Taken together, these investigations provide preliminary evidence to support an arousal model of political orientation, which may more accurately portray the psychological motivations underlying conservatism.

Keywords: conservatism
EEG
ERP
political neuroscience
Political Psychology
social neuroscience
Advisor: Michael, Inzlicht
An Algebraic Approach to Physical-layer Network Coding

Physical-layer network coding (PNC) is a new approach to harnessing interference in wireless networks. Rather than avoiding interference or treating it as noise, PNC enables wireless relays to compute linear functions of the transmitted messages directly from the interfering signals. This allows for concurrent transmissions, thereby increasing network throughput. This dissertation studies a family of the state-of-the-art PNC schemes called compute-and-forward (C). C was originally proposed and studied from an information-theoretic perspective. As such, it typically relies on several strong assumptions: very long block length, almost unbounded complexity, perfect channel state information, and no decoding errors at the relays; its benefit is often analyzed for simple network configurations. The aim of this dissertation is two-fold: first, to relax the above assumptions while preserving the performance of C, and second, to understand the benefit of C in more realistic network scenarios, such as random-access wireless networks.There are four main results in this dissertation. First, an algebraicframework is developed, which establishes a direct connectionbetween C and module theory. This connection allows us tosystematically design lattice codes for C with controlled block length and complexity. In particular, explicit designcriteria are derived, concrete design examples are provided,and it is shown that nominal coding gains from 3 to 7.5dB can be obtained with relatively short block length and reasonable decodingcomplexity. Second, a new C scheme is proposed, which, unlike conventional C schemes, does not require any channel state information (CSI). It is shown that this CSI-free scheme achieves, for a certain class of lattice codes, almost the same throughput as its CSI-enabled counterpart. Third, an end-to-end error control mechanism is designed, which effectively mitigates decoding errors introduced at wireless relays. In particular, the end-to-end error control problem is modeled as a finite-ring matrix channel problem, for which tight capacity bounds and capacity-approaching schemes are provided. The final part of this dissertation studies the benefitof C in random-access wireless networks. In particular, it isshown that C significantly improves the network throughput and delay performance of slotted-ALOHA-based random-access protocols.

Advisor: Frank, R Kschischang
Regulation of ABCG2 Expression in the Lactating Mammary Gland

The Breast Cancer Resistance Protein (ABCG2) is a multidrug efflux transporter that is upregulated in certain drug-resistant cancer cells and in the mammary gland during lactation. It is unclear how ABCG2 is regulated in the lactating mammary gland. This thesis sought to understand the role of prolactin (PRL) and its downstream signalling cascades, and epigenetic mechanisms, in the regulation of ABCG2 expression in the mammary gland during lactation. Using T-47D human breast cancer cells, I showed that PRL upregulated ABCG2, in part, by inducing the recruitment of Signal Transducer and Activator of Transcription-5 (STAT5) to an interferon gamma activation sequence (GAS) motif in the human ABCG2 gene. Pharmacological inhibition of phosphoinositide 3-kinase and mitogen-activated protein kinase signalling further demonstrated the involvement of these pathways in the induction of ABCG2 by prolactin. To further investigate whether STAT5 regulates ABCG2 in vivo, I performed a series of experiments using mammary glands from non-lactating (virgin and forced involution) and lactating mice. These experiments revealed that the E1b alternative mouse Abcg2 mRNA isoform was predominantly expressed and induced in the mouse mammary gland during lactation. Using published STAT5 ChIP-seq datasets and ChIP-qPCR, I showed that STAT5 was bound to multiple regions along the mouse Abcg2 gene during lactation. In particular, one of these STAT5 binding regions, which contains a GAS motif, showed functional activity in luciferase reporter assays. I further investigated epigenetic mechanisms that may regulate Abcg2 in the mouse mammary gland. Despite the presence of a CpG island at the E1b promoter, which when hypermethylated in vitro dramatically reduced promoter activity, the E1b promoter was already hypomethylated in the virgin mammary gland and continued to be hypomethylated during lactation. Analysis of published ChIP-seq data revealed that the E1b promoter region in virgin mouse mammary epithelial cells was already enriched with the open chromatin histone mark H3K4me2 but that there was further accumulation of H3K4me2 during lactation. Collectively, these results suggest that ABCG2 is already poised for expression in the virgin mammary gland and that lactation-associated activation of STAT5, perhaps by prolactin, induces its expression.

Keywords: ABCG2
BCRP
epigenetics
lactation
prolactin
Stat5
Advisor: Shinya, Ito
Growing up in Families that Foster: Exploring the (E)motions of Young Adult Sons and Daughters of Foster Parents

Foster care is designed to provide safety and security for maltreated children through a temporary, transitional home placement where a healing experience can occur through family-based care. Development of relationships and connections are encouraged between foster family members and the foster child. One of these relationships is with the sons and daughters of foster parents (herein sons/daughters). The central aim of this exploratory study was to explore the emotions of sons/daughters and how they cope with their fostering experiences. Theoretical sampling was used until theoretical sufficiency was obtained at 15 participants who were young adult sons/daughters (18-33 years) who temporarily or permanently resided outside of the current, public foster homes in Ontario. This cross-sectional, qualitative research design was descriptive and interpretative in nature through a constructivist grounded theory approach. Data collection methods included open-ended interviews, demographic questionnaires, object sharing, photographing the object, photo-feedback, and memo-writing. Initial coding, focused coding, memo-writing, theoretical sorting, and diagramming were used to analyze the data. Emerging codes and concepts within the textual data and photographs were input and analyzed using Dedoose, an evidence-informed web application data management system. Analysis of findings using a neuroscience lens, led to the identification of a foster schema - 'you can get attached, but only up until a certain point' for sons/daughters. Repeated exposure to foster siblings arriving in sons/daughters' homes, living with them, and then leaving resulted in the participating sons/daughters being apprehensive and cautious about developing relationships with new foster siblings. This fostering schema was also applied to non-fostering relationships with friends and romantic partners, as young adults. To regulate their emotions, sons/daughters tended to rely on strong, stable, and supportive relationships with their mothers. Recommendations are discussed relating to child welfare service delivery, research, and policy.

Keywords: emotions
foster care
foster siblings
grounded theory
neuroscience
sons and daughters of foster parents
Advisor: Robert, MacFadden
Mircofluidic Systems for High-throughput Biophysical Characterization of Single Cells

Biophysical (mechanical and electrical) properties of living cells have been proven to play important roles in the regulation of various biological activities at the molecular and cellular level, and can serve as promising label-free markers of cells' physiological states. In the past two decades, a number of research tools have been developed for understanding the association between biophysical property changes of biological cells and human diseases; however, technical challenges of realizing high-throughput, robust and easy-to-perform measurements on single-cell biophysical properties have yet to be solved. This thesis focuses on the development, testing and modeling of microfluidic platforms for biophysical characterization of single cells.The proposed microfluidic system for biophysical characterization of red blood cells (RBCs) achieved a speed of 100-150 cells/second and was capable of quantifying multiple parameters as mechanical and electrical signatures of each RBC including transit time, impedance amplitude ratio, and impedance phase increase. In comparison with previously reported microfluidic devices for single RBC biophysical measurement, this system has a higher throughout, higher signal to noise ratio, and the capability of performing multi-parameter measurements. The microfluidic device consisting of two stages of microchannels was also developed for measuring mechanical opacity to mitigate the coupled effect of cell size/volume and deformability. The stiffness/deformability changes of lymphocytes in chronic lymphocytic leukemia (CLL) patients were, for the first time, studied using this system.In order to extract the inherent electrical properties of cells, electrical and geometrical models are developed to interpret the impedance data and to determine the specific membrane capacitance and cytoplasm conductivity of individual cells. Results from testing 3,249 AML-2 cells and 3,398 HL-60 cells reveal different specific membrane capacitance and cytoplasm conductivity values between AML-2 and HL-60 cells. The results also demonstrate that the quantification of specific membrane capacitance and cytoplasm conductivity can enhance cell classification results since these parameters contain information additional to cell size.The progressive deformability changes during blood banking/storage were studied using a microfluidic system. High-speed imaging (5,000 frames/sec) captures the dynamic deformation behavior of the cells, and together with automated image analysis, enables the characterization of over 1,000 RBCs within 3 minutes. Multiple parameters including deformation index (DI), time constant (shape recovery rate), and RBC circularity were quantified. Compared to previous studies on stored RBC deformability, our results include a significantly higher number of cells (>1,000 cells/sample vs. a few to tens of cells/sample) and, for the first time, reveal deformation changes of stored RBCs when traveling through human-capillary-like microchannels.

Keywords: Biophysics
Biosensors
High-throughput
Microfluidics
Advisor: Yu, Sun