VictorJuiz/thesis huggingface dataset:
Platonis Imitator: Cicero’s Reception of Platonic Philosophy
Keywords: Cicero
Plato
Scepticism
Skepticism

This dissertation explores Cicero’s reception of Plato in his late period philosophical works. I argue that Cicero modernizes Platonic philosophy in order to engage with contemporary Hellenistic philosophical debates. Cicero uses a variety of interpretative strategies (translation, historicization, exegesis) to demonstrate that Plato’s doctrines are live options alongside the dominant theories of Hellenistic philosophy. This modernizing approach is consistent with, and an expression of, Cicero’s Academic skepticism: Cicero is not a Platonist; rather he uses Plato dialectically to counter and oppose rival philosophical positions, and ultimately treats Platonic philosophy as an integral part of the Academic’s inquiry after the truth. The first two chapters establish the intellectual context for Cicero’s undertaking by rethinking Cicero’s relationship with his Academic teacher, Antiochus of Ascalon. In Chapter I, I re-evaluate Antiochus’ idiosyncratic view on the history of the Platonic Academy and show that Antiochus’ project is also one of modernization. This provides the relevant background for Chapter II, in which I argue against the view that Cicero takes an ‘Antiochian’ approach to Plato. I establish, through an examination of a debate about the nature of virtue and happiness, that Cicero often employs rival interpretations of Platonic philosophy to challenge Antiochus’ account of the Academy. Chapter III looks at Cicero’s treatments of the Platonic forms. Cicero’s arguments in favor of forms directly counters the Stoic and Antiochian rejections of the forms. While there is no single “theory of forms” in Cicero’s works, there is a family resemblance among his various discussions, each tailored to different argumentative and epistemological contexts. Chapter IV offers an extended examination of the arguments for the immortality of the soul in the first book of the Tusculan Disputations. Here we find Cicero at his most virtuosic as an exegete of Plato, synthesizing elements from a range of Platonic dialogues into a novel Academic defense of immortality. This dissertation, then, shows Cicero to be an independent, creative, and innovative interpreter of Plato. In turn, we gain a better appreciation of both Cicero’s overall philosophical project in his late period works, as well as the central significance of Plato in late Hellenistic philosophy.
Designing Stimuli-Responsive Amino Acid and Peptide Hydrogel Biomaterials as Functional Entrapment Matrices
Keywords: Amino acids
Biomaterials
Hydrogels
Peptides
Supramolecular Chemistry

Supramolecular gels are a fascinating class of soft materials that have attracted significant attention in recent years. Chemical polymer gels have received the most attention but are often limited by their lack of degradability and issues associated with biocompatibility. Physical supramolecular gels are composed of small molecule gelators that assemble into supramolecular network structures; the resulting space is filled with solvent. Peptide-based gels are advantageous as they are composed by small amino acid components and possess reversible supramolecular assemblies through non-covalent interactions in response to various stimuli. The stimuli- responsive properties of these hydrogels allow the design of materials that can be tailored for the purpose of a specific property and function of the gel material depending on the application. Stimuli-responsive peptides that alter properties as a function of pH, redox, temperature, and enzymes offer the potential to create materials with tunable characteristics. Peptide-based gel materials are also particularly attractive in many biomedical applications as they are biocompatible and biodegradable, and they encapsulate solvent similar to that of soft tissues and the extracellular matrix of cells. In this thesis, the stimuli-responsive properties (pH, redox, temperature, and solvent), as well as the biocompatible nature of the peptide gels are highlighted. Dipeptides, peptides bonded to metal scaffolds, peptide amphiphiles, and amino acid amphiphiles are all synthesized and explored for gelation, and fully characterized in terms of their supramolecular behaviour, morphological, and mechanical properties. We explore the properties of gels that are heat sensitive, respond to redox agents, and only gel in a very narrow pH range. The gel compounds are then explored as functional entrapment matrices for catalytic enzymes, as a biomimetic matrix for tissue regeneration, and as an entrapment matrix for drugs in delivery applications. The work in this thesis highlights the usability of these gels as a base matrix and their ability to incorporate and entrap various biomolecules which holds great future promise for the development of biomaterials for many biomedical applications.
Effect of Engineered Nanoparticles-treated Root Canal Biofilm on Macrophage Plasticity and Interactions with Human Periodontal Ligament Fibroblast
Keywords: immunomodulation
Engineered chitosan nanoparticles
Enterococcus faecalis biofilm
macrophage polarization
proteomics
root canal disinfection

The intracanal microbes, particularly in proximity to the apical foramen, often result in chronic inflammation of the periapical tissues that might lead to compromised post-treatment healing. Macrophages (MQ), which are major constituents of periapical lesions, respond to microbial factors and exhibit a key role in the pathogenesis as well as the healing of apical periodontitis owing to their functional plasticity. Depending on the microenvironmental cues, they polarize into pro-inflammatory (M1) or anti-inflammatory/pro-wound healing (M2) phenotype. MQ crosstalk with other immune cells and periradicular multipotent cells, such as periodontal ligament fibroblasts (PdLF), via soluble inflammatory signals, to regulate the disease/healing outcomes. Engineered chitosan-based nanoparticles (CSnp) that possess effective antibacterial activities could favorably interact with host cells by virtue of their inherent bioactivity and customized physicochemical properties. Herein, we aimed to (1) understand the influence of residual root canal biofilm on MQ-PdLF interaction, and (2) evaluate the effect of engineered CSnp on modulating residual biofilm-mediated inflammatory response of MQ and their interaction with PdLF. An ex-vivo model of Enterococcus faecalis biofilm in root canals was characterized to evaluate the inflammatory response to untreated versus treated biofilms. Engineered CSnp dispersed in carboxymethyl chitosan (CMCS) resulted in significant reduction of 6-week-old biofilm compared to conventional disinfection (P
Boron Subnaphthalocyanines: The First Unsubstituted Examples, New Boron Lewis Acids, Random Bay Position Halogenation, and Computational Material Screening
Keywords: Borate
Boron
Boron Subnaphthalocyanine
Macrocycle
Materials Chemistry
Organic Electronics

Boron subnaphthalocyanines (BsubNcs) are a class of materials that our lab has shown to be alloyed mixtures of derivatives that are randomly chlorinated in the bay positions, resulting from their formation from boron trichloride. These alloyed mixtures were shown to have a positive influence on the functionality of organic photovoltaics whereby an increase in the amount of bay position chlorination was found to increase power conversion efficiency. The bay position chlorinated BsubNcs were also found to be stable in the ambient environment within organic solar cells which also justified their further development. The alloying of these materials leads to a potentially unique opportunity to tailor the alloyed mixture for a desired application by blending pure or partially separated samples of BsubNcs. Herein we lay the groundwork for achieving this goal. We explore the separation of bay position halogenated (chlorinated and brominated) BsubNcs enabled by their functionalization with phenolic axial moieties. We develop an understanding of the dependence of their physical properties on the frequency of bay position halogenation and developed improved analytical techniques for this class of materials. We also present a new method for the synthesis of BsubNcs that circumvents the generation of bay position halogenated species, resulting in the first examples of pure unsubstituted BsubNcs. To achieve this, we proposed that a non-halide boron based Lewis acid is required, and that a balance of the Lewis acidity of the boron source and the Lewis basicity of the BsubNc precursor can guide the synthesis of BsubNcs. After achieving this desired outcome, we also explored the application of this method for the synthesis of the related boron subphthalocyanines (BsubPcs) and as the macrocycles were formed, we found potential for the broad application of this methodology. A computationally calibrated model to screen key material properties of BsubPcs for their accelerated development was also developed. We uniquely found a method that can achieve this with a standard laptop and software that is free to academia. We anticipate that incorporation of BsubNcs into the model will be possible as the key material properties have been determined for BsubNcs developed in this thesis.
Quantifying Placental Function Using Cardiovascular Magnetic Resonance Imaging
Keywords: Human Pregnancy
Magnetic Resonance Imaging
Maternal Fetal Hemodynamics
Oxygen Transport and Consumption
Placental Function
Sheep Pregnancy

This thesis presents the development of cardiovascular MRI methods for assessing placental oxygen exchange using a combination of human and sheep studies. An “inputs and outputs” approach was designed based on MRI measurements of blood flow and oxygen content to determine oxygen transport in the major placental vessels, which has previously only been possible using invasive techniques not suitable for human studies. The basis of the methodology relies on MRI blood oximetry, which uses magnetic properties of blood (T2) to derive oxygen saturation (SO2). MRI oximetry was validated in pregnant sheep, confirming the fidelity of the T2-SO2 relationship in-utero. The combination of MRI oximetry with vessel flow was applied to measure placental-fetal oxygen transport in normal pregnant sheep. The findings were in agreement with existing reference data obtained using invasive techniques, providing further validation of the approach, which was then applied in human pregnancies. Our results confirmed that streaming exists in the human fetal circulation, whereby the metabolically active heart and brain are supplied with blood with a higher oxygen content than the blood returning to the placenta via the right heart and main pulmonary artery (68±10% vs. 49±9%, P
Cell Division Compromises Epithelial Cell Polarity and Drives Tumor Progression
Keywords: cancer
cell division
cell polarity
EMT
mitosis
tumourigenesis

Epithelia are the predominant tissue type of the animal body and form major components of most organs. As with all tissues, the formation of epithelia during development and their stem cell-based renewal requires cell division. This presents a problem as dividing epithelial cells transiently lose apical-basal polarity, which could compromise epithelial integrity. How epithelial cells respond to challenges arising from cell division is not understood. To better understand the mechanisms of polarization and the impact of cell division on epithelial integrity, I have carried out a screen to identify novel epithelial polarity determinants. I evaluated the relationship between cell division and epithelial cell polarity using Drosophila embryos and imaginal discs as model systems. I conducted a screen to find novel genes required for the normal distribution of the apical determinant Crumbs (Crb), which revealed shrub, srpk, and the cell cycle regulator fizzy (Cdc20), as genes that are required for normal polarity. Embryonic mutants of fzy, which leads to an arrest at metaphase, confirms the transient loss in epithelial cell polarity during cell division. This led to an in-depth analysis of the impact of cell division on epithelial cell polarity. Reducing cell division suppressed the mutant phenotypes of polarity genes, arguing that cell division significantly challenges epithelial polarity suggesting a higher requirement for the function of polarity regulators. I then investigated epithelia where loss of polarity proteins such as Crb have no adverse consequences in a wildtype background. I found that accelerating cell division in such epithelia caused a loss of polarity and neoplastic tumor growth. Moreover, neoplastic growth is strongly enhanced when accelerated division is combined with a loss of Crb. Interestingly, neoplastic growth as well as the loss of epithelial cell polarity observed in polarity mutants can be rescued by blocking cell division. My findings indicate that the process of cell division not only increases tumor mass but also compromises epithelial polarity to drive tumor progression.
A “Shocking” Investigation into Life on Mars: Examination of the Structural and Chemical Effects of Shock in Hydrous Phases in Martian Meteorites
Keywords: Mars
Meteorites

To determine when and if habitable environments existed on Mars, accurate measurements of the volatile and isotopic compositions of hydrous phases in martian meteorites are essential. However, past studies on these phases have routinely overlooked one of the most fundamental properties of martian meteorites — they are all inherently shocked, experiencing extreme pressure and temperature (P-T) conditions during impact and ejection from the martian surface. These intense P-T conditions are known to induce volatile loss and isotopic disturbances. Thus, if shock-induced chemical alteration is not properly accounted for, past interpretations about water and life on Mars based on measurements from hydrous phases may be misconstrued. As such, the objective of this thesis is to determine how shock deformation has affected the structure and chemistry of the three most common hydrous phases in martian meteorites (apatite, merrillite, and iddingsite) using detailed microstructural and petrographic analyses. Microstructural electron backscatter diffraction analyses of apatite and merrillite in martian meteorites reveals these minerals experienced localized shock-induced P-T conditions high enough to alter their primary martian water contents; with the first in-situ evidence of shock-dehydrogenation in phosphate minerals revealed by correlative electron energy loss spectroscopy. This evidence of shock-induced chemical alteration also indicates that unshocked phosphate minerals on Mars would dissolve faster in water-rock interactions, supplying more bio-available phosphorus for potential life than previously estimated. Additionally, the complex microstructures observed in the phosphate minerals, even in “low-shock” meteorites, suggests that their original H-isotope compositions may have also been altered by shock, necessitating re-evaluation of past models of Mars’ atmospheric evolution based on these H-isotope measurements. Finally, through detailed petrographic examination of shock features, it is inferred that iddingsite alteration in a terrestrially weathered martian meteorite was produced on Mars via water-rich deuteric alteration. The microstructural and petrographic analyses carried out in this thesis reveal significant shock-induced structural and chemical alteration of hydrous phases in martian meteorites, and new evidence of water-rich magmatism on Mars (deuteric iddingsite). These results indicate that past approximations of water and phosphorous abundances on Mars are likely underestimates, suggesting that habitable conditions for potential martian life were more prevalent than previously assumed.
The 'Grey Area' of Consent: Understanding the Psychosocial Impacts of Trauma on Sexual Consent
Keywords: Consent Education
Gender-based Violence
Sexual Consent
Sexual Violence
Sexuality Education
Trauma-Informed Practice

In recent years, sexual consent education has proliferated and arguably become the most popular way of preventing gender-based violence (GBV), particularly on post-secondary campuses. However, mainstream consent programming applies a reductive conception of consent and lacks a trauma-informed lens. The concept of consent that much programming relies upon is binary (‘Yes’/‘No’) and obscures ongoing yet preventable harm in the ‘grey area’ of consent. This disproportionately impacts youth trauma survivors as they are more than twice as likely to be sexually (re)victimized compared to their peers without trauma histories; moreover, the psychosocial impacts of trauma, such as substance dependence, dissociation, or hypersexuality, refuse a binary model of consent. To explore these phenomena, I interviewed 8 diverse undergraduate students at the University of Toronto who self-identify as trauma survivors. Using intersectional feminist theory and critical trauma studies as a theoretical framework, the project provides an evidentiary and conceptual basis for rethinking consent education with a trauma-informed approach. I found that trauma survivors were able to shed light on more complex conceptualizations of consent because they could not subscribe to, or fit their experiences into, a neatly packaged version of ‘healthy,’ consensual sexual experience. Participants in the study said that they were previously taught that consent is the key to positive, healthy sexual experiences—as if bad or regrettable sex could be abolished through consent—and this message did not reflect their lived experiences. The awkwardness, ambiguity, or ambivalence that may arise out of subjective sexual experiences, and not just those of survivors of trauma, remains an understudied, critical gap in consent education. This study contributes to the evidence that we must attend to the grey areas of sex and harm in order to understand more nuanced dynamics for negotiating mutually pleasurable, ethical sex, as well as the more insidious and uncontested manifestations of GBV. By recognizing the limits of contemporary consent discourses, we can expand visions of sexual justice and prioritize talk of mutuality, interdependence, and compassion in order to foster a greater sexual ethic of care.
Neurostructural, Neurofunctional, and Neurocognitive Correlates of Cannabis Use in Adolescents with Bipolar Disorder
Keywords: Adolescents
Bipolar Disorder
Cannabis
Neurocognitive
Neurofunctional
Neurostructural

Adolescents with bipolar disorder (BD) have high rates of cannabis use, and cannabis use is associated with increased symptom severity and treatment resistance in BD. However, few studies have examined the association of cannabis use with neurostructure, neurofunction, and/or neurocognition in adolescent BD. As societal perceptions of cannabis benefits are increasing alongside decreasing perception of harm, addressing this gap is imperative. This thesis examines the neurostructural, neurofunctional, and neurocognitive correlates of cannabis use in adolescent BD. The over-arching hypothesis was that cannabis use in adolescents with BD would be associated with brain structure, brain function, and neurocognition. Structural and functional neuroimaging was completed using magnetic resonance imaging (MRI). Vertex-wise analysis revealed significant group effects on brain structure in frontal and parietal regions. Adolescents with BD and cannabis use (BDCB+) exhibited larger volume and surface area (SA) in parietal regions, and smaller thickness in frontal regions, relative to healthy controls (HC) and adolescents with BD and no cannabis use (BDCB−). BDCB− had smaller volume, SA, and thickness in parietal and frontal regions relative to HC. Resting state functional connectivity (rsFC) seed-to-voxel analyses revealed three significant clusters. First, rsFC between the left nucleus accumbens (NAc) seed and left superior parietal lobe was negative in the BDCB- group and positive in the HC group. Second, rsFC between the right orbitofrontal cortex (OFC) seed and right lateral occipital cortex was positive in the BDCB+ and negative in the BDCB- and HC groups. Finally, rsFC between the right OFC seed and right occipital pole was positive in the BDCB+ group and negative in the BDCB- group. Neurocognition was examined using a computerized automated test battery. There were between-group differences on tests of visuo-spatial working memory and sustained attention. Working memory scores were significantly impaired in BDCB+ relative to HC, and sustained attention was significantly impaired in BDCB- relative to HC. This thesis emphasizes the importance of integrating brain-based research to further elucidate clinical and behavioural attributes that manifest in adolescents with mood disorders. This study is the first step in understanding the brain-based origins of clinically relevant symptoms associated with cannabis use in adolescents with BD.
Elucidating the Role of FGF and RA Signaling during Pancreatic Differentiation using hPSC
Keywords: Beta Cells
Diabetes
Fibroblast Growth Factor
Pancreas
Retinoic Acid
Stem Cells

Type 1 Diabetes is an auto-immune disease that results in the destruction of insulin-producing β-cells. Human pluripotent stem cells (hPSCs) can be differentiated to NKX6-1+PDX1+ pancreatic progenitors (PPs) and to NKX6-1+CPEP+ β-like cells in vitro, offering a potential source of cells for therapy. Although PPs are in clinical trials and β-like cells have been approved for clinical trials, recent publications demonstrated that both populations contain cells of non-pancreatic lineages. This suggests that pancreatic specification may require further optimization, and that the markers the field uses to guide differentiation may be inadequate. In this thesis, I set out to elucidate the role of FGF and RA signalling upon pancreatic specification, with the goal to improve β-cell differentiation. In Chapter 4, I used chemical and genetic tools to demonstrate that FGFR3 activation at stage 3 of differentiation inhibited PDX1+ Endoderm induction through the MEK/ERK signaling pathway. Impaired PDX1 specification was accompanied by a decrease in PPs and β-like cells and increase in the frequency of PDX1-SOX2+ cells. As a result, stage 4 cultures failed to generate pancreatic grafts in vivo and instead generated teratomas. Notably, FGFR and MEK inhibition during endocrine induction enhanced β-cell differentiation. In Chapter 5, I demonstrated that retinoid signaling during stage 3 influenced the efficiency and purity of PPs and β-like cells. Surprisingly, retinoid treatment at stage 3 was not required for PDX1 induction, however, it was necessary for efficient PP specification. Importantly, I demonstrated that treatment with the RA precursor retinol at stage 3 was superior to RA as it generated fewer CDX2+ cells and higher percentages of β-like cells. Consistent with these findings, I showed that the RA synthesizing enzyme, ALDH, was expressed by PDX1+ endoderm and PPs and sorting for ALDH+ using ALDEFLUOR, enriched for a population expressing higher NEUROG3 levels compared to unsorted cells. Based on these data, I proposed that ALDH could be used to mark endocrine competent PPs. Together, the knowledge from this thesis advances the field by providing strategies to improve current β cell differentiation protocols and by identifying markers that could be used to monitor PP purity and β-cell differentiation.