Master's Theses (2009 - )
Permanent URI for this collectionhttps://hdl.handle.net/1807/9947
The School of Graduate Studies (SGS) requires doctoral and masters graduands to submit a thesis written as a required element of their degree program in electronic format.
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SGS intends to house all available digitized Doctoral and Masters theses by U of T graduate students on this site. The current collection is but a small sample of that scholarly work.
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Item Open Access Scaling and Coproduction in Carbon Dioxide Electrocatalysis(2023-03) Nelson, Vivian Elizabeth; Sinton, David; Mechanical and Industrial EngineeringRising anthropogenic carbon dioxide (CO2) emissions are leading to a concerning increase in global temperatures. International efforts such as the 2012 Paris Climate Agreement aim to reduce carbon dioxide (CO2) emissions and limit global warming to 1.5 ̊C higher than pre-industrial levels. One method of reducing emissions is electrochemical carbon dioxide reduction (CO2R), where CO2 is sequestered in useful chemicals and fuels. Much progress has been made recently in increasing the maturity of CO2R technology, but further work needs to be done to increase its industrial viability. This thesis aims to increase the industrial viability of CO2R and investigates key considerations for its industrial deployment. First, a pilot-scale CO2 electrolyzer is designed and evaluated to understand the challenges of performing CO2R at scale. Second, an alternative anodic reaction is developed to create two value streams from a single electrolyzer and lower the plant-gate-levelized cost of production relative to the incumbent process.Item Open Access β3 Integrin PSI Domain Thiol Isomerase Activity: A Novel Role in Blood Coagulation Implications of the L33P Polymorphism(2023-03) Cerenzia, Eric G; Ni, Heyu; PhysiologyαIIbβ3 integrin is the most highly expressed receptor on platelet surface. αIIbβ3 is essential for platelet aggregation. Our lab discovered that the plexin-semaphorin-integrin (PSI) domain of β3 exerts thiol isomerase activity. Monoclonal antibodies binding PSI can inhibit platelet activation, and aggregation. Our work displays that recombinant PSI domain enhanced extrinsic pathway coagulation. Anti PSI-B1 antibody inhibited extrinsic pathway coagulation more than JAN-D1 αIIbβ3 antibody. Anti PSI-B1 antibody inhibited clot retraction significantly more and decreased fibrin branching in scanning electron microscopy relative to other β3 antibodies. This work reveals a thiol isomerase (PSI) that stimulates the activation of coagulation factors through the extrinsic pathway. Furthermore, we have discovered elevated thiol isomerase activity of L33P polymorphism. Anti-PSI domain antibodies are the first inhibitors to target αIIbβ3 at an allosteric site. Typically used αIIbβ3 blockers lead to bleeding risk. Anti-PSI antibodies attenuate platelet aggregation and blood coagulation and are a promising therapeutic agentItem Open Access Gut Microbiome – Mammary Gland MicroRNA Relationships and their Response to Flaxseed in Female Mice(2023-03) Wu, Diana Cheng En; Comelli, Elena M; Thompson, Lilian U; Nutritional SciencesConsumption of flaxseed and its oil and lignan components have been associated with changes during mammary gland development, potentially reducing breast cancer risk in adulthood. The gut microbiota metabolizes flaxseed components and mammary gland microRNA response to flaxseed may be an underlying mechanism. The overall objective of this thesis was to investigate gut microbiota-mammary gland relationships in response to flaxseed and their implications for breast cancer. Thirty-two microRNAs were found to be shared between mammary gland development and breast cancer. Furthermore, a relationship between the gut microbiota and microRNA expression was found. This relationship was altered by flaxseed and its components. Gene targets of the microRNAs altered by flaxseed were found to affect the PI3k-Akt-mTOR pathway. Flaxseed oil altered miRNAs targeting genes related to collagen and ECM pathways. Overall, flaxseed and its components have unique effects on microbiota-microRNA relationships during development, with implications for breast cancer risk in adulthood.Item Open Access Diminished Oarian Reserve caused by Nemp1 Deficiency and DNA Damage in Nemp1-deficient Oocytes(2023-03) Ha, Kyungwon; Jurisicova, Andrea AJ; McNeill, Helen HM; PhysiologyNemp1 is a nuclear envelope protein highly expressed in primordial and primary oocytes. It has been previously evidenced that Nemp1-deficient female mice exhibit severe subfertility and a significant reduction in the ovarian reserve at the onset of puberty. The ovarian reserve of Nemp1/2-deficient females is also affected, yet their fertility is not completely compromised. The purpose of this study is to identify the window of ovarian reserve reduction and assess for DNA damage leading to POF in Nemp1-deficient females. Follicle counts revealed a significant reduction in the oocyte population at neonatal stages due to excessive oocyte death. Extensive DNA damage and impaired DNA damage sensing were present in the adult Nemp1-deficient oocytes. Additionally, Nemp1-deficient oocytes displayed an increased number of NPBs and compromised chromatin organization. Nemp1/2 deletion partially rescued the extent of DNA damage and chromosomal misalignment exhibited in Nemp1-deficient oocytes.Item Open Access Materials Design and Engineering for Efficient Electrochemical Reduction of Carbon Monoxide(2023-03) Liu, Yanjiang; Sargent, Edward; Electrical and Computer EngineeringCompared with CO2 electroreduction, the electrocatalytic reduction of carbon monoxide (CORR) offers the promise of high overall energy efficiency: it does so by avoiding an undesired side-reaction, that is, the formation of carbonate/bicarbonate when CO2 contacts the alkaline electrolyte used in electrified fuels production. Here, I explore routes to increasing the selectivity of CORR products through materials design and engineering, aided by density functional theory (DFT)-based calculations. Based on these results, I implement an activity-promoting strategy that allows for more selective and active (high current density) conversion of CO into CH4 compared to prior reports. I hypothesized that a C-C coupling disruptor, identified using computational screening, could promote CO protonation and inhibit the production of C2+ molecules. Experimentally, I constructed the predicted optimal electrocatalyst based on a tin-copper catalyst and achieved a CO to-CH¬4 Faradaic efficiency (FE) of (60±3)% at 200 mA·cm−2 in a flow cell. Demonstrating a cascade solid oxide electrolysis cell and membrane electrode assembly (SOEC-MEA) approach, I achieved CO2-to-CH¬4 with a 2.2-fold reduction in energy intensity compared to the currently most efficient previous low-temperature electrocatalytic systems to methane.Item Open Access Data-driven Distributionally Robust Optimization: Intersecting Ambiguity Sets, Performance Analysis and Tractability(2023-03) Tanoumand, Neda; Bodur, Merve; Naoum-Sawaya, Joe; Mechanical and Industrial EngineeringWe consider stochastic programs in which the probability distribution of uncertain parameters is unknown and partial information about it can only be captured from limited data. We use distributionally robust optimization (DRO) to model such problems. As opposed to the commonly used approach for DRO problems that suggests creating an ambiguity set by following a specific procedure, we propose to build it by adopting multiple procedures. Specifically, we design the ambiguity set by intersecting sets that are constructed by different discrepancy-based measures. We derive single-level convex programming reformulations for the resulting two-level DRO problems with various supports, namely, discrete known, univariate, and multivariate supports. We additionally design a cutting-plane algorithm and a relaxation-based technique to tackle computationally challenging DRO problems with multivariate supports. To evaluate the quality of the solutions that our reformulations yield and the performance of these techniques, we conduct experiments on newsvendor and mean-risk portfolio allocation problems.Item Open Access Driver Mutation Discovery in Prostate Cancer Whole Genomes(2020-03) Zhu, Helen; Reimand, Juri; Medical BiophysicsProstate cancer is the most prevalent noncutaneous cancer in men. A new driver discovery method, ActiveDriverWGS, was developed for the analysis of cancer whole genomes and the identification of recurrent SNVs and small indels in protein coding genes and regulatory elements. Here, ActiveDriverWGS was applied to a collection of 569 primary prostate adenocarcinoma whole genomes to find known coding drivers such as SPOP, TP53 and PTEN and novel noncoding driver mutations in active enhancers, promoters and lncRNAs. This analysis was complemented by an examination of recurrent genomic rearrangements in the nuclear genome and recurrent somatic SNVs in the mitochondrial genome. FOXA1 was identified to be a key driver in ~ 17% of samples, abrogated by coding and noncoding simple somatic mutations and structural variation. An integrated analysis was conducted using ActivePathways, revealing pathways affected by multiple types of somatic mutations and potential rare drivers under the statistical threshold of detection.Item Open Access A Digital Database of Trichomycete Fungi and an Investigation of Seasonal Effects on Insect-Trichomycetes Networks(2023-03) Chaudhary, Shalini; Wang, Yan; Ecology and Evolutionary BiologyTrichomycete fungi are gut symbionts of arthropods living in aquatic habitats. The lack of a central platform with accessible collection records and associated ecological metadata has limited ecological investigations of trichomycetes. I developed a database and data visualization web-tool for the exploration of nearly 100 years of previously published collection records. Using collection records from the database, I applied bipartite network methods to examine host-trichomycetes network composition and structure across the seasons. I hypothesized that the composition and structure of these networks would change seasonally. I identified several season-specific taxa as well as significant differences in network composition and structure across seasons. I also found that rewiring contributed more to interaction dissimilarity than turnover. Across all networks, interactions were specialized with insects more specialized than fungi when forming an interaction pair. These findings provide insight into the ecology of these unique interactions and the underlying structure of this system.Item Open Access The Characterization of wact-45, a Novel Small Molecule Tool that Likely Inhibits the Vesicular Acetylcholine Transporter(2019-11) Pyche, Jacob; Roy, Peter J; PharmacologySmall molecule modulators of nervous system function can have utility as therapeutics or as research tools. Thus, the discovery of novel neuromodulators can be of great benefit. Using C. elegans as a model to identify neuroactive compounds, we have uncovered 82 molecules that modulate the egg-laying rate of worms. To assist the characterization of their mechanism of action, I investigated the locomotor phenotypes induced by these compounds. This identified wact-45, a compound that induces a coiler phenotype in worms reminiscent of cholinergic reduction-of-function mutants. Several lines of evidence suggest that wact-45 inhibits the vesicular acetylcholine transporter (VAChT). Notably, wact-45 suppresses the paralysis induced by the acetylcholinesterase inhibitor aldicarb, and mutants that resist the effect of the VAChT inhibitor vesamicol also resist the effects of wact-45. Its potent activity in nematodes and zebrafish suggests that wact-45 has utility as a tool to probe VAChT function in a broad range of species.Item Open Access The Characterization of Cellular and Animal Models of Clear Cell Renal Cell Carcinoma(2022-11) Huang, Richard; Ohh, Michael; Laboratory Medicine and PathobiologyKidney cancer represents one of the most frequently diagnosed malignancies around the world. Most patients present with clear cell renal cell carcinoma (ccRCC), which is often highly resistant to conventional cancer therapeutics when metastatic. Targeted treatments have been developed in the recent decades. However, resistance to therapies, differences in patient responses, and low survival means that more models are required to better understand ccRCC pathogenesis and metastasis. As a result, we used mouse models and single-cell RNA-sequencing to characterize the transcriptional profiles of in vitro, orthotopic, and metastatic models of RCC243, which was recently established from a ccRCC primary tumour. Our findings show that these models form tumours of a clear cell histology in both orthotopic and metastatic settings, and that differential expression exists between the RCC243 models. This highlights the role of the cellular environment, which may influence experimental outcomes and help us better understand disease processes.Item Open Access Developing a 3D Printed High-density Adherent Scaffold Architecture for Large-scale Cardiomyocyte Production(2022-11) Montague Szakaly, Ethan Coulter; Laflamme, Michael A; Laboratory Medicine and PathobiologyThe scalable production of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is a major barrier to their translation as a regenerative therapy for myocardial infarction. Bioreactors like the stirred-tank system are commonly used for large-scale hPSC-CM manufacturing; however these populations typically display an immature phenotype. While maturation can be improved on 2D substrates, conventional 2D formats are not readily amenable to producing billions of cardiomyocytes required for therapeutic applications. Here, we pursued the fabrication of a scalable 3D printed high-density adherent scaffold (HDAS) array for hPSC- CM production. We found that fusion deposition modelling could generate compact scaffolds using common 3D printing materials. 3D printed substrates were shown to support hPSC-CM attachment and the formation of uniform, contracting monolayers with high purity and viability. Successful attachment inside and retrieval of cells from the HDAS architecture also reveals the potential for 3D printed scaffolds to be applied in future large-scale 2D hPSC-CM manufacturing.Item Open Access Towards a Quantitative Colorimetric Gold Nanoparticle-Based Assay for Measuring ppm and Sub-ppm Aqueous Nitrite Levels(2019-11) Lin, Yuan-Kai; Ramchandran, Arun; Chemical Engineering Applied ChemistryPrior publications and work from our group have demonstrated a colorimetric assay coupling the Griess reaction with gold nanoparticle aggregation to detect the concentration of nitrites. However, a major disadvantage of this assay is it is slow and needs to be conducted at 95oC. This project takes a closer look at the mechanism of aggregation and lower the reaction temperature. The modifications allow the colorimetric measurement of nitrite concentrations exceeding 230 M (10 ppm) at room temperature, greater than 3 M (130 ppb) at 50oC, and potentially as low as about 0.05 M (2 ppb) at 95oC. This work sets the foundation for the development of an accurate, precise, inexpensive and portable nitrite measurement kit.Item Open Access Investigating PLOD2 as a Therapeutic Target to Overcome Metastasis in Radiorecurrent Prostate Cancer(2024-11) Frame, Gavin; Liu, Stanley K; Medical BiophysicsMetastatic relapse of prostate cancer after radiotherapy is a significant cause of prostate cancer- related morbidity and mortality. PLOD2 is a mediator of invasion and metastasis that we identified as being upregulated in our highly aggressive radiorecurrent prostate cancer cell line. This dissertation investigates the role of PLOD2 in driving tumour progression and metastatic potential in radiorecurrent prostate cancer, with particular focus on identifying clinically feasible methods of inhibition. The work herein reveals PLOD2 as a negative prognostic factor associated with biochemical relapse and metastatic disease in prostate cancer patients, driving in vitro invasion, migration, and in vivo extravasation; treatment with the HIF1α inhibitor PX-478 effectively suppresses this metastatic phenotype in radiorecurrent prostate cancer cells. Together, these results demonstrate for the first time the role of PLOD2 in radiorecurrent prostate cancer invasiveness, and point towards its potential as a therapeutic target to reduce metastasis and improve survival outcomes in prostate cancer patients.Item Open Access Online Non-preemptive Resource Constrained Scheduling(2024-11) Fan, Donney; Liang, Ben; Electrical and Computer EngineeringJobs in computing environments have diverse and heterogeneous resource requirements. This thesis presents a study of online, non-preemptive scheduling algorithms for multiple identical machines. In this environment, users send their job requests to be served by these machines, using their resources to satisfy the requests. With multiple requests to serve, the machines need an inherent scheduling objective to optimize. We study the scheduling objectives of the average weighted completion time, the maximum flow time (which is defined as job completion time minus their release time), and the maximum stretch (the ratio of job flow time and its processing time). The key challenge addressed is resource allocation to jobs with non-uniform demands across multiple resource types, such as CPU, memory, and storage. Further, as the thesis studies the online arrival of jobs, their parameters are not revealed to the schedulers until their arrival time. We use the popular competitive ratio to measure the performance of these algorithms. We first propose an online algorithm, termed Multi-Resource Interval Scheduling (MRIS) that achieves a competitive ratio of 8R(1+ϵ) for the average weighted completion time, where R is the number of resource types. To the best of the authors knowledge, this is the first theoretical competitive analysis under the considered system. We further show that the well-known priority queue algorithms can have arbitrarily bad competitive ratios in this setting. In numerical experiments using production workload traces from Microsoft Azure, the proposed algorithm is shown to significantly outperform priority queue algorithms and other state-of-the-art schedulers. Due to stronger lower bounds, we leverage resource augmentation to provide competitive ratio bounds for algorithms for the maximum flow and maximum stretch. In these relaxed models, our algorithms additional resources compared to the optimal algorithms. Using 10R speed augmentation, we provide an algorithm that obtains no greater maximum flow time than the optimal scheduler. We use the previous algorithm as a subroutine to present an approach that achieves a maximum stretch no greater than the optimal scheduler. These algorithms are enabled by interval scheduling paradigms, where the algorithm exercises patience to wait for additional knowledge of job arrivals before committing to scheduling decisions. Although this simple idea is not novel, we use it to obtain competitive ratios for the algorithms presented.Item Open Access Thermoplastic Blends and Composites for High-temperature and High-pressure Applications(2024-11) Cheng, Jackie; Naguib, Hani; Materials Science and EngineeringThis thesis focuses on developing a Polyethylene (PE) and Polyamide (PA) blend tailored for high-temperature and high-pressure applications. Chapter 2 systematically investigated the impact of compatibilizer and weight percentage on blend miscibility and morphology. Mechanical and barrier properties of the blends were comprehensively characterized at elevated temperatures to assess their suitability for demanding thermal environments. Chapter 3 introduces an innovative method to enhance interfacial stress transfer in these blends by strategically localizing graphene nanoplatelets at the blend interface. This approach minimizes the required nanofiller content compared to traditional melt blending methods while achieving significant enhancements in mechanical performance. The findings underscore the effectiveness of this novel technique in improving the blend's mechanical strength and durability under extreme conditions. Overall, this research advances the development of PE/PA blends for industrial applications requiring robust performance in high-temperature and high-pressure settings.Item Open Access Healthcare Providers’ Perspectives on the Use of Teledentistry in Supporting Oral Healthcare of First Nations Children in Northern Ontario(2024-11) Arshat, Natalie; Lawrence, Herenia P; DentistryHealthcare Providers’ Perspectives on the Use of Teledentistry in Supporting Oral Healthcare of First Nations Children in Northern Ontario Natalie Arshat Master of ScienceFaculty of Dentistry University of Toronto 2024 AbstractObjective: Understand the perspectives of community-based healthcare workers in remote Indigenous (First Nations) communities in Northern Ontario on the potential benefits of teledentistry to improve access to pediatric dental care. Methods: A qualitative descriptive study design was used to elaborate on the experiences of community health providers who serve under the Weeneebayko Area Health Authority in Moose Factory, Ontario. Participants interviewed included healthcare providers and community health representatives. Semi-structured, one-on-one interviews were conducted virtually April and September of 2023. Thematic analysis was applied to interview transcripts which were then organized and categorized into recurring themes. Results: Participants interviewed included dental professionals (dentists, assistants, and hygienists), nurses, and a paramedic, all of whom had experience delivering care within the coastal communities of James and Hudson Bay, Ontario. Themes that emerged included: teledentistry as a means of communication between remote dental experts and community-based health providers, supporting more favourable connections between providers and patients, mitigating the use of resources and burden on staff and patients, and as a support mechanism for decision-making amongst nurses. The interviewees also described challenges associated with managing acute pediatric dental cases with intermittent access to dentists. The idea of teledentistry, particularly the store-and-forward vs. real-time examination form, was received favourably by all participants interviewed. Conclusion: The study findings suggest that teledentistry has a beneficial role to play in supporting healthcare providers serving remote First Nations communities where access to and sustainability of dental care is a current challenge. The favoured response to access to technology, whether in an asynchronous or synchronous manner, reflects that this innovative medium could aid in addressing the management of the considerable levels of oral disease among the pediatric population.Item Open Access Investigating beta inducible growth hormone 3 (BIGH3) as a mediator of fibrosis in inflammatory bowel disease(2024-11) Visser, Grace Victoria; Philpott, Dana J; Buechler, Matthew B; ImmunologyInflammatory bowel diseases (IBD) are characterized by chronic inflammation and development of fibrosis. Current therapeutics attempt to address inflammation, while fibrotic areas are surgically removed. Fibrosis is caused by excessive production of extracellular matrix (ECM) by activated fibroblasts. Fibroblast activation and ECM expression is mainly driven by transforming growth factor beta (TGFß) signaling. This project sought to identify a “co-factor” to TGFß, meaning a protein that acts synergistically in fibrosis with TGFß. One candidate is beta-inducible growth hormone 3 (BIGH3), which has been associated with increased collagen from lung fibroblasts and increased expression in patients with fibrotic IBD. BIGH3’s mechanistic role in colon fibrosis is previously unexplored. Following acute administration of dextran sulfate sodium (DSS) in drinking water, mice lacking BIGH3 (Bigh3-/-) did not exhibit differences from wildtype in inflammatory indicators. To assess fibrosis during chronic disease, three cycles of DSS were administered. Bigh3-/- colons did not show differences from wildtype in fibrosis scoring, however they showed increased inflammatory indicators. This suggested that BIGH3 did not affect histological signs of fibrosis but might have regulate colon inflammation. Understanding how inflammation and fibrosis are regulated in the colon will inform development of “co-factor” therapeutics.Item Open Access Code, Consciousness, and Composition: AI Ethics and Human-AI Co-Created Works(2024-11) Bayoumi, Aziza; Ratto, Matt; Information StudiesThe scope of current AI ethics discussions is limited, largely focusing on normative ethical codes rather than the ethical issues that arise in relationships between humans and specific kinds of AI. My research counters this trend by analysing writing co-created by LLMs and human authors. These pieces are “Ghosts” by Vauhini Vara and ChatGPT, “According to Alice” and “Hello World!” by Sheila Heti and a ChaiAI chatbot, and “Not the Only One” by Stephanie Dinkins, using a bot of her own making. By analyzing works of memoir and autofiction, my research presents distinct moments where the self is being constructed in collaboration with chatbots. I read these works through concepts from Critical Posthumanism and Narrative Ethics. These theoretical frameworks allow me to situate my work outside of human-centric ways of thinking about ethics, to better appreciate the agency that the chatbots are enacting in the conversation, and to explore the impact of this agency on the authors’ perceptions of themselves.Item Open Access In Differential Privacy, There is Truth: Evaluating PATE with Monte Carlo Adversaries(2024-11) Wang, Jiaqi; Papernot, Nicolas NP; Lie, David DL; Electrical and Computer EngineeringThe shift from centralized to decentralized machine learning (ML) addresses privacy concerns associated with centralized data collection. A prominent approach for learning from decentralized data is the Private Aggregation of Teacher Ensembles, or PATE, which aggregates the predictions of a collection of teacher models. Aggregation is performed through a noised voting mechanism to reveal a collective prediction for the ensemble while providing differential privacy guarantees for the training data of each teacher model. PATE’s differential privacy guarantees protect only against adversaries that observe a bounded number of predictions. PATE provides virtually no privacy guarantees in the realistic setting where an adversary is allowed to query the system continuously. However, the prospects of such an attack have never been evaluated. We contribute to the first study on the confidentiality and privacy guarantees provided by PATE. We devise and implement an attack using Monte Carlo sampling to recover the votes submitted by participants of the PATE protocol, thus breaking PATE’s confidentiality guarantees. Surprisingly, we also show that our adversary is more successful in recovering voting information when the vote-aggregation mechanism introduces noise with a larger variance. Because differential privacy generally benefits from noise with greater variance, this reveals a tension between achieving confidentiality and differential privacy in collaborative learning settings. Next, we observe that PATE and its myriad variants assume that protocol participants, who contribute model votes, are honest. We evaluate scenarios where they can be corrupted by the attacker, and find that attacks become drastically more potent as the attacker is able to control more participants. Robustly defending against the attacks reported in this paper is non-trivial, and is likely to result in a significantly reduced utility of PATE.Item Open Access A Comparison of Short-Term Treatment Outcomes with Non-extraction and Extraction Orthodontic Treatment Modalities in Borderline Class I and Mild Class II Malocclusions(2024-11) Vu, Wendy; Daskalogiannakis, John; Posluns, James; DentistryExtraction (EX) and non-extraction (NEX) decisions impact various treatment outcomes, including soft tissue and incisor positions. Increasing desirability for more protrusive lips requires for an update in esthetic preferences. Borderline cases are critical when attempting to discern EX and NEX treatment effects. This retrospective study used Discriminant Analysis to identify 30 EX and 30 NEX borderline cases, analyzing soft tissue, incisor, and occlusal changes. Assessment of profile and incisor inclination preferences were conducted by 90 laypeople (LP), 40 orthodontists (OR), and 40 general dentists (GP). EX cases showed increased nasolabial angle, more ideal overbite, and lip and incisor retraction, with no significant differences in molar relationship and overjet. Linear regression of survey results indicated OR preference for EX profiles, GP preference for NEX profiles, and all groups favouring more upright incisors. LP’s preferences more aligned with GP. Conflicting GP preferences emerged, desiring protrusive lips and acute nasolabial angle (NEX-associated), yet more strongly preferring upright incisors (EX-associated).