VictorJuiz/thesis huggingface dataset:
Influencing Oral-nasal Balance in Speech and Song

Oral-nasal balance is dependent on the valving of the velopharyngeal sphincter. This dissertation examined the control and modification of oral-nasal balance in speech and song. Literature was reviewed from the fields of speech science and singing voice pedagogy, which motivated three projects. The first project (Santoni et al., 2018) explored the role of altered nasal signal level feedback on the regulation of oral-nasal balance in singing in trained and untrained singers. Results indicated that all participants showed lower nasalance scores in response to both increased and decreased nasal signal level feedback. The findings implied that trained singers’ internal models for controlling oral-nasal balance may not be as refined as those that guide other vocal parameters. The second project (Santoni et al., 2019) explored the influence of voice focus adjustments (forward and backward vocal tract shape and length modifications) (Boone, 2007; Boone et al., 2010) on the control of oral-nasal balance in typical speakers in speech and song. Results indicated that forward focus led to higher and backward focus to lower nasalance scores. There was one exception wherein one female participant produced lower nasalance scores in forward focus during the nasal stimulus. The results confirmed that voice focus maneuvers influence oral-nasal balance in typical speakers. Findings from project 2 led to the clinical experiment described in project 3. The third project (Santoni, Thaut Bressmann, 2020) explored the influence of voice focus adjustments on the control of oral-nasal balance in speakers with hypernasality in speech and song. Results indicated that for a group of five speakers with hypernasality, forward focus resulted in higher and backward focus resulted in lower nasalance scores. There was one exception wherein one male participant produced lower nasalance scores in forward focus during the nasal stimulus. The results provided preliminary evidence that voice focus maneuvers influence oral-nasal balance in speakers with hypernasality. With further development of the voice focus method, the intervention could become a useful therapeutic approach for speakers with hypernasality.

Keywords: hypernasality
oral-nasal balance
resonance
singing voice pedagogy
speech language pathology
velopharyngeal sphincter
Advisor: Thaut, Michael
Bressmann, Tim
The Precarity of Men: Youth, Masculinity, and Money in a Papua New Guinean Town

This dissertation is a study of uneducated young men (“youths”) in urban Papua New Guinea (PNG). Seeking to move beyond analyses that focus upon the themes of rupture and alienation caused by socio-economic changes that impinge upon young men’s abilities to mature and leave them “stuck” as youth, I deploy both historical and ethnographic data to examine how young men’s lives have been shaped by, and how they in turn shape their lives in the wake of change. Part I of this dissertation explores how the masculine life course and men’s aspirations were recast as local populations were incorporated into the nation state during the colonial era. In particular, I bring attention to the way in which becoming an educated person and living in town became key distinctions that structure post-colonial society. Part II of this dissertation draws upon 24 months of ethnographic research with men who experience the abjection of being forced out of school and turn to several activities: crime, rugby league football, and street sales. These activities provide men with parallel educational trajectories and the ability to claim a place in the city while aligning themselves with core masculine values. Although these activities appear to be a response to exclusion from formal wage labour opportunities, local views of money prevent such an interpretation. Money, I argue, is viewed as an inalienable object that men use as partible complements of their gendered substance, so stolen money or money from rugby (“easy money”), cannot be held, and is instead rapidly spent to re-enter circulation. Instead, men participate in crime and rugby to cultivate “fame,” that is conceived of as the socio-spatial extension of the self through the circulation of “name” and “face.” Although fame is so attractive to men that they may consciously try to prolong their status as youth as they continue to seek it out, this fame is fleeting, and depends upon forsaking social reproduction. “Street sales,” in contrast, allow men to generate a special kind of wealth (“hard work money”) that they can use for provisioning. Through “fathering,” which is predicated upon the flow of material resources to their children, men pass on their name and face to their children. Through partible personhood men thereby transcend death and achieve enduring fame. Attending to men’s practices illustrates how, while social change has made masculine social maturity increasingly disaggregated, men’s core values and desires remain coherent over time, including the desire to cultivate the body, achieve fame, and reproduce themselves socially within a framework of partible personhood. Similarly, examining young men’s actions illustrates how, while young men’s lives are shaped and constrained by broader social processes, being a youth can also be examined as a socially productive period as well.

Keywords: Masculinity
Men
Money
Papua New Guinea
Youth
Advisor: Wardlow, Holly
Uncovering the Neural Pathways Mediating the Bladder-inhibitory Effects of Percutaneous Tibial Nerve Stimulation: A Novel Approach to Treating Overactive Bladder

Each year, millions of Canadians suffer from the debilitating effects of overactive bladder (OAB) resulting in profound socio-economic costs. Various treatment algorithms, such as behavioral therapies and pharmacotherapies have been introduced to counter the unwanted results of this disorder. Such treatments are, however, modest in their effectiveness. An alternative to conventional therapies, neuromodulation, is proven efficient in reducing OAB symptoms. However, it’s the invasiveness and the surgical cost (e.g., sacral nerve stimulation – SNS), which precludes it as a first line of treatment in the algorithm of incontinence care. Consequently, percutaneous tibial nerve stimulation (PTNS) was introduced as a less-invasive yet effective therapy for treating OAB symptoms. In PTNS, clinical efficacy is achieved by repeatedly applying electrical stimulation through a percutaneous needle electrode, which is used to target the tibial nerve (TN). However, the lack of rationale for using the set stimulation parameters (20 Hz coupled with intensities below the motor threshold), the need for repeated treatments to maintain the therapeutic effects as well as the inconsistent response rates pose a major barrier to its widespread use. The focus of this work is therefore, to rationalize the lack of consistency in the bladder-inhibitory output following standard TNS techniques. In particular, we investigated the role of saphenous nerve (SAFN), largest cutaneous branch of the femoral nerve which, intercedes with the anatomical point of PTNS delivery, in modulating bladder function. This project uses well-established animal models to explore and systematically characterize the effects of TNS and SAFNS on bladder function and is divided into three main aims. The first aim focuses on rationalizing the inconsistency in response rates observed during non-selective TNS approaches by optimizing the role of stimulation parameters. The second aim targets the investigation of SAFN afferents in inhibiting bladder activity in a continuous urodynamic model. Finally, the last aim validates the consistency of SAFN-evoked bladder inhibitory reflexes at high stimulation amplitudes and its role in the development of a model for underactive bladder (UAB). Together, these results improve our understanding of the neural network underlying the therapeutic output of PTNS and the role of SAFN afferents within the urodynamic circuitry.

Keywords: Bladder
Neuromodulation
Saphenous Nerve
Tibial Nerve
Advisor: Yoo, Paul B
The Sensual Body and Artistic Prowess in Netherlandish Painting ca. 1540â 1570

In the middle of the sixteenth century, Netherlandish painters turned their attention toward the sensual nude. The leading contemporaries of Pieter Bruegel, including Frans Floris, Willem Key, Jan Massys, Maerten van Heemskerck, and Michiel Coxcie, favoured subjects that allowed them to elaborate their respective approaches to the ideal body. Artistsâ deliberate attention to the visual and tactile qualities of their painted figures had affective and artistic aims: painters sought to cultivate empathetic responses in their viewers while simultaneously asserting their individual brands. These artists also favoured subjects that presented the sensual nude as a problemâ an object for erotic delectation and one that could raise salient social concerns around gender, love, and coupling. An important feature of the paintings in this study is the way they orchestrate the possibility for contrasting points of view, thus complicating attempts to derive unequivocal interpretations. Indeed, contemporary rederijker drama, public festivity, vernacular literature and poetry, authoritative classical texts, and prints from across Europe suggest the range of issues that might have been projected onto Netherlandish depictions of the nude. While little is known of the patrons of such works, the scale, quality, and erudite subject matter point to a relatively affluent and educated class of individual; we know, for example, that Frans Florisâ s nudes were collected by Antoine Perrenot de Granvelle, a Habsburg official and the Bishop of Arras, and by the wealthy Antwerp financier, Nicholas Jonghelinck. Such patrons were as attracted by the visceral, affective qualities of the sensual body as they were by the opportunities it gave to display their erudition. They also valued how the leading artists adapted the fashionable formal vocabulary of antiquity and post-Raphaelesque figure painting to Netherlandish thematic demands and artistic traditions. By allowing their works to negotiate between the international and the local, Frans Floris and his contemporaries were active participants in a discourse on the sensual nude that had regional relevance and pan-European purchase. This very prominent and prestigious image category must be better integrated into art historical narratives of Netherlandish painting and Renaissance art.

Keywords: Antwerp
Erotics
Nude
Renaissance
Senses
Advisor: Kavaler, Ethan Matt
Uncovering ‘Cryptic’ Natural Products from Streptomyces Bacteria

The Streptomyces bacteria produce natural products that have potent biological activity against other organisms: 60% of our antibiotics are derived from this source. Genome sequencing reveals genes for many more. One view in the field is that these “cryptic” metabolites could serve as badly needed antibiotics for antibiotic resistant infections. However, many of them are produced at too low yields for structural and mechanistic characterization. The top priority is finding broadly applicable approaches to enhancing the yields of these molecules. To address this, I took advantage of a conserved regulator of specialized metabolism to develop a generally applicable tool, called AfsQ1*, that heterologously induces many specialized metabolic genes. Using this technology, I developed two antibiotic discovery screens. First, I identified afsQ1*-induced antibacterial activities and purified the active agents. This led to the discovery of the antibiotic siamycin-I, a potent inhibitor of antibiotic resistant Gram-Positive bacteria. I demonstrated that this compound targets the lipid-II component of cell wall biogenesis, the first of this class of molecules to do so. The second approach used comparative metabolomics to identify afsQ1*-induced novel masses. By NMR I identified a new pepticinnamin analogue, whose family are inhibitors of an eukaryotic post-translational modification called farnesylation. Farnesyl transferase inhibitors were previously investigated (unsuccessfully) as anticancer medicines. I demonstrate, however, that they are candidates for antifungal therapy, because they block morphological switching- a key virulence trait in lower fungi. This work suggests a new paradigm in antifungal therapy. Finally, I dissect an interaction between Lactobacillus reuteri and C. albicans. When co-cultured together C. albicans cannot undergo filamentous growth and I found that this inhibition is molecule-mediated. 1-acetyl β-carboline is the active metabolite isolated from L. reuteri and I found that its production is prevalent throughout the Lactobacillus genera. I also synthesized a new β-carboline analogue for future clinical trials.

Keywords: Antibiotics
Cryptic Metabolites
Microbial Interactions
Natural Products
Secondary Metabolism
Streptomyces
Advisor: Nodwell, Justin
Defining Delivery Pathways of Nanoparticles

The goal of nanomedicine is to use nanoparticles to carry drugs to specific target site in the body. For cancer nanomedicine, a recent meta-analysis showed that only 0.7% of the injected nanoparticles reach the tumour. To address this delivery inefficiency, it is important to examine each biological barrier to determine its impact on delivery. In this thesis, first the body was modelled as a series of barriers that nanoparticles need to overcome successively in order to access the target site. The model shows that the number and strength of barriers limits what is available to be delivered. The macrophages of the liver can sequester up to 99% of the injected nanoparticles, and thus are the biggest barrier for targeted delivery. Next, clodronate-liposomes were used to remove the liver macrophages and showed that both nanoparticle tumour delivery and hepatobiliary elimination can be improved. Specifically, nanoparticle tumour delivery can be increased up to 50× and hepatobiliary elimination up to 10×. Removal of the liver macrophages then allowed the exploration of other secondary barriers to delivery such as tumour pathophysiology and the liver sinusoidal endothelium. Together, these studies define concepts and strategies that can improve nanoparticle delivery and reduce unwanted bioaccumulation to pave the way for their clinical translation and regulatory approval.

Keywords: Cancer
Drug delivery
Elimination
Kupffer Cells
Liver
Nanoparticles
Advisor: Chan, Warren CW
Control and Operation of the Battery-enabled Direct-current Fast Charging Station for Electric Vehicles

This dissertation presents, develops, and evaluates a system architecture and its control structure that mitigates impact of the Electric Vehicles’ (EVs) Direct-Current Fast-Charging (DCFC) station on its host weak Alternating Current (AC) grid. The DCFC station includes multiple DCFC units, a Battery Energy Storage System (BESS), a solar-Photovoltaic (PV) system, and a grid-interface Voltage-Sourced Converter (VSC). The proposed control system, i.e., combination of Local Controllers (LCs) and Supervisory Controller (SC) contains the station dynamics within the station and thus prevents dynamic impact of the DCFC units and other internal sources, such as solar-PV generation, on the host grid. Unlike a conventional station, this enables interfacing the proposed DCFC station to the legacy AC distribution grid, irrespective of the grid weakness and technical limits. A discrete-event control-based Supervisory Controller (SC) for the DCFC station is synthesized, evaluated, and verified to (i) limit the station’s power based on grid-imposed requirements, (ii) coordinate operation of controllable units within the station, (iii) operate the station in either grid-connected mode or islanded mode, and (iv) dynamically adjust power flows inside the station between grid, PV unit, DCFC units, and BESS to satisfy the EVs charging requirements and when applicable charge BESS or export PV power to the grid. Time-domain simulation results, in PLECS software platform, are presented to assess the dynamic performance of the proposed SC subject to various discrete events/transitions. The results demonstrate robustness of the proposed control system to large-signal disturbances and discrete events/transitions. The proposed control system performance, i.e., LCs and SC, is experimentally validated using a two-layer real-time control Hardware-in-the-Loop (HIL) setup. The power circuit of the DCFC station is simulated in real-time in OPAL-RT platform. The LCs and the SC of the DCFC station are implemented in industrial CompactRIO (cRIO) controller and a Programmable Logic Controller (PLC) PLCnext-controller, respectively. The control system performance is tested in case of islanded and grid-connected modes of operation of the station, subject to various disturbances and SC transitions, to verify the functionality of the implemented controls and readiness for final deployment and field tests.

Keywords: DC Fast Charging
DC Microgrids
Discrete-Event Systems
Electric Vehicles
Supervisory Control
Weak AC-grid
Advisor: Iravani, Reza
Determinants of Statin Drug Sensitivity in Mevalonate-dependent Cancers

Statins are widely prescribed cholesterol-lowering drugs that inhibit HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate pathway. Several lines of evidence support that certain tumours depend on the mevalonate pathway for growth and survival and are vulnerable to statins. However, if statins are to be successfully repurposed for the personalized treatment of cancer, we must identify biomarkers that can predict which patients might benefit from the addition of a statin to their treatment regimen, and how best to administer these drugs in combination with other agents to maximize therapeutic responses. Herein, the research objectives were to elucidate novel determinants of statin drug sensitivity in different tumour types, and further characterize the molecular mechanism(s) by which statins induce cancer cell death. To this end, we demonstrated that prostate tumours overexpress HMGCR, and that high HMGCR protein expression is associated with poor prognosis. Interestingly, however, not all prostate cancer cells were sensitive to statin-mediated HMGCR inhibition at physiologically-achievable concentrations. We further identified that statin-sensitive prostate cancer cells were impaired in their ability to activate a sterol-regulated feedback loop in response to statin exposure. Notably, in statin-insensitive prostate cancer cells, where this sterol-regulated feedback loop was intact, the clinically-approved drug dipyridamole was found to inhibit this response and sensitize cells to statin-induced apoptosis. In an independent malignancy, multiple myeloma, we identified that cells positive for the t(4;14) chromosomal translocation were particularly vulnerable to mevalonate pathway inhibition. Statin treatment induced a robust integrated stress response in t(4;14)-positive cells, which was exacerbated by co-treatment with the proteasome inhibitor bortezomib. Moreover, statin treatment synergized with bortezomib to induce apoptosis in t(4;14)-positive cells, providing strong rationale to combine these two clinically-approved agents for the treatment of t(4;14)-positive disease. Taken together, the work presented in this thesis reveals two promising opportunities for the repurposing of statins, as single agents or in combination with additional, clinically-approved drugs, to treat distinct mevalonate-dependent cancers. Since statins are already approved for the prevention of cardiovascular disease, and are available as generic drugs, they offer an immediate, safe and affordable opportunity to improve cancer patient care and treatment outcomes.

Keywords: Drug repurposing
Mevalonate pathway
Personalized medicine
Statins
Tumour metabolism
Advisor: Penn, Linda Z
Role of microRNA-27B-3P in the Regulation of Key Extracellular Matrix Markers in the Synovium during Osteoarthritis

Synovial fibrosis, characterized by excessive accumulation of extra-cellular matrix (ECM), is a key pathology contributing to joint destruction associated with Osteoarthritis (OA). microRNAs (miRNAs) are small non-coding RNAs that play key roles in various pathophysiological processes. We have previously shown that miR-27b-3p is abundantly expressed in the OA synovium and elevated in the synovial fluid of patients with late-stage knee OA. However, the exact role of miR-27b-3p in the regulation of ECM in the OA synovium is largely unknown. Hence, my PhD thesis project aimed to determine the role of miR-27b-3p in the regulation of ECM components in the synovium during OA. I first show that miR-27b-3p is prominently expressed in the human OA synovial lining and increased in late-stage knee OA compared to early-stage radiographic knee OA. I further show that miR-27b-3p is highly expressed in the synovial lining and fibrocartilage of a surgery-induced mouse model of knee OA. To decipher the role of miR-27b-3p in the regulation of synovial ECM, I transfected primary human OA fibroblast like synoviocytes (FLS, major synovial cells) with miR-27b-3p-mimic and subjected to ECM-specific qPCR array. Profiling the expression of 84 ECM genes in OA-FLS showed that miR-27b-3p-mimic significantly increases the expression of key ECM genes including pro-collagen-Type-I (COL1A1), A-disintegrin-and-metalloproteinase-with-thrombospondin-motifs-8 (ADAMTS8), Thrombospondin-1 (THBS1), Fibronectin-1 (FN1), Collagen-type-V-alpha-1 (COL5A1) and Collagen-type-XIV-alpha-1 (COL14A1). MiR-27b-3p-mimic also markedly increased COL1A1 protein expression as well as migration of OA-FLS. Integrative computational analysis of identified ECM genes predicted a closed relationship between miR-27b-3p signaling and ADAMTS8. To functionally evaluate this, I silenced ADAMTS8 by siRNA in miR-27b-3p-mimic transfected OA-FLS. Results showed that ADAMTS8 silencing attenuated the increased expression of COL14A1, COL5A1 and FN1 without any significant effect on COL1A1 and THSB1 expression in OA-FLS, suggesting that regulation of COL14A1, COL5A1 and FN1 expression by miR-27b-3p may in part be mediated by ADAMTS8. Finally, I performed RNA sequencing on miR-27b-3p-mimic transfected OA-FLS to profile the transcriptome of miR-27b-3p in FLS during OA. Overall, this study provides a crucial evidence on the role of miR-27b-3p in the regulation of key ECM markers in the OA synovium.

Keywords: ADAMTS8
Collagen
Extracellular Matrix
microRNA
Osteoarthritis
Synovitis
Advisor: Kapoor, Mohit