VictorJuiz/thesis huggingface dataset:
Allogeneic Double Negative T cell Therapy as a Novel Treatment for AML Patients
Keywords: acute myeloid leukemia
adoptive T cell therapy
Double negative T cell
T cell

Allogeneic bone marrow transplantation (allo-BMT) is a potentially curative treatment for high-risk leukemia patients. However, a high disease relapse rate caused by residual disease and an associated toxicity such as graft-vs.-host disease (GvHD) remain as major issues that hamper recipients' survival. Many forms of immunosuppressants to control GvHD increase the risk of disease relapse, and therefore, there is an unmet need for a treatment that can target chemotherapy-resistant blasts with low off-tumor toxicity. Approaches to prevent GvHD while maintaining or enhancing graft-versus-leukemia (GvL) are the ‘Holy Grail’ for allo-BMT patients. CD3+ CD4- CD8- double negative T cell (DNT) is an unconventional mature T cell subset found in periphery. In this thesis, I have developed a method to expand therapeutically-relevant numbers of clinical-grade DNTs obtained from healthy donors (HDs) and extensively characterized them. I demonstrated that ex vivo expanded HD-DNTs target an array of leukemic cell lines and primary AML cells including chemotherapy-resistant patient samples in vitro and significantly reduce the leukemia load in patient-derived xenograft (PDX) models. Unlike CD4+ and CD8+ conventional T (Tconv) cells, DNTs do not attack normal allogeneic cells and normal xenogeneic tissues in vitro and in xenograft models. Further, potentials of using allogeneic DNTs as an off-the-shelf adoptive cell therapy have been demonstrated herein, including resistance to host-versus-graft (HvG) rejection and lack of GvHD-inducing activities. Interestingly, allogeneic DNTs effectively suppressed proliferation of Tconv cells and prevented priming of CD8+ T cells against allogeneic antigens, and infusion of DNTs with human peripheral blood mononuclear cells (PBMCs) into mice suppressed xenogeneic GvHD caused by Tconv cells. Notably, co-infusion of DNTs and PBMC into leukemia-bearing recipient eradicated the disease while suppressing tissue damage caused by Tconv cells. Collectively, in this thesis, I have developed a novel form of a cellular therapy for leukemia patients that has potentials to be used as an off-the-shelf treatment as a monotherapy or as a follow-up therapy to allo-BMT.
The Politics of Passing: Disabled and Mad Students’ Experiences of Disclosure in Higher Education
Keywords: crip
disability
mad
new materialism
post-qualitative
students

This dissertation explores disabled and mad students experiences of disclosure in higher education from a Deleuzian new materialist perspective. This theoretical orientation conceptualized students’ movements through the university as rhizomatic, and included passing, moving into the middle, and coming out. The author argues that these movements create an affective politics within the university that can change and rearrange the university in meaningful ways for individuals with embodied differences. The author organizes the relationship between students and the university using la paperson’s (2017) idea that there are two competing machinic-desires operating within higher education. In this thesis, these desires are defined as eugenic and crip. Eugenic desires operate within the university and construct assemblages with eugenic ends and are operationalized by the disclosure process. Crip desires, on the other hand are a passional understanding of disability and madness as multiplicity (rather than a binary) that can build the university anew. Crip desires are constituted by disabled and mad students and create assemblages that deterritorialize the university. The impact of disclosure was made clear by the 17 disabled and mad participants who shared stories of disclosure’s affective violence (when registering as a “student with a disability,” or disclosing to faculty or staff, and petitioning a grade or a course). The author argues that disclosure produces violence in higher education because it reduces embodied differences to biomedical and psychiatric explanations – often limiting disability/madness from becoming anything other. However, there are other ways that students speak about disability and move in-between identities that allow for a different understanding of disability and madness to emerge. When students come out-crip, they story difference rather than disclose disability, and therefore, create new conditions for how access might be arranged. The author argues that a more complex understanding of students’ movements and actions as rhizomatic reveals that they are engaged in micropolitical work with identity that can create small and slow cracks in the university. In asking participants to imagine a different university, this project engages in a thinking-resistance that works towards actualizing different conditions for learning in higher education.
The Relationship Between Calcite Mass and Coccolith Morphology in the Coccolithophore Family Noelaerhabdaceae
Keywords: Calcite production
Coccolithophores
Full field retardation estimation
Michel-Lévy chart
Ocean acidification
Polarized light microscopy

Anthropogenic CO2 emissions into the atmosphere are taken up by the ocean, leading to a decrease in pH and CaCO3 saturation state in a process called ocean acidification. Ocean acidification is thought to affect several marine calcifying groups, including the coccolithophores. Field studies on potential changes in coccolithophore calcification due to ocean acidification often rely on the coccolith as a proxy for calcification. Such research, however, is limited by researchers applying different approaches for estimating coccolith mass with little knowledge on how the different approaches relate to each other. Furthermore, several studies rely on flawed methodology to estimate coccolith mass from its interference colours produced under polarized light. In this thesis, a published method for estimating coccolith mass under circular polarized light (the CPR-method) was revised. These revisions addressed several important limitations with the CPR-method by rendering a revised and accurate Michel-Lévy chart, developing a colour management routine applicable to oil objectives, and using polymer films of known and low (~30nm) retardation for calibration to reduce polarization aberrations. After these limitations were addressed, coccoliths could be measured with unprecedented accuracy (±0:007 μm for thickness and ±~15-20% for mass). The CPR-method was then applied to plankton samples collected near the Canary Islands in January and September 1997. Relative abundance, coccolith thickness, and coccolith mass of different morphotypes of the coccolithophore species Emiliania huxleyi were evaluated, and the study revealed that "overcalcified" Type A coccoliths in September were lighter and thinner than "normally calcified" Type A coccoliths in January, and the thickness difference between Type A and Group B coccoliths was furthermore highly variable between samples. This result has important implications for several studies which have used E. huxleyi morphotypes as a proxy for coccolithophore calcification. The CPR-method was also applied to E. huxleyi and Gephyrocapsa oceanica strains cultured under different salinity conditions to evaluate the relationship between coccolith length and thickness. The study found that coccolith length and thickness were not related in E. huxleyi, and caution is therefore needed before using the ks model to estimate coccolith mass from length.
Analysis of Apical Vesicle Trafficking in Drosophila Photoreceptor Cells
Keywords: Crumbs
Drosophila
Eyes shut
Photoreceptor cells
Polarized protein trafficking
Rhodopsin

Vesicle trafficking is an essential process required for a multitude of cell behaviors, including cell signaling and membrane polarization. Problems in vesicle trafficking have been linked to many human diseases. I investigated the mechanisms of vesicle trafficking of apical proteins in Drosophila photoreceptor cells (PRCs). Individual ommatidia in the Drosophila compound eye house 8 PRCs that surround a matrix filled lumen, called the interrhabdomeral space (IRS). My goal was to further clarify the mechanisms that control vesicle trafficking of apical proteins including the photopigment Rhodopsin1 (Rh1), which localizes to the rhabdomere, the apical determinant Crumbs (Crb), which is enriched at the stalk membrane, and the proteoglycan Eyes shut (Eys), which is secreted into the IRS. Rh1, Crb, and Eys are critical for proper PRC development, and are linked to retinal degenerative disease in humans and flies. Therefore, in addition to furthering our understanding of polarized trafficking in a model epithelial cell, my research has implications for understanding human retinal diseases. I performed RNAi and dominant-negative-based genetic screens to assess the function of 240 trafficking-related genes in apical trafficking of Rh1, Crb, and Eys. I identified 28 attractive candidates and further analyzed 5. I found that (i) the Arf GEF protein Sec71 is required for biosynthetic traffic of both apical and basolateral proteins, that (ii) the exocyst complex and the motor protein dynein promote the secretion of Eys and Rh1, and that (iii) the syntaxin Avalanche is involved in the endocytosis of Rh1, Crb, and Eys. In addition, I executed an in depth analysis of the small GTPase Rab19, which has not been characterized to date. Using CRISPR/Cas9 I produced a Rab19 null mutant that caused light-dependent PRC degeneration. My data suggest that degeneration is due to cytoplasmic accumulation of Rh1 in PRCs following light exposure as a result of a defect in Rh1 recycling.
A Decolonial Analysis of Student Success in Nigerian Secondary Schools
Keywords: Colonial Schooling in Contemporary Africa
Colonial Schooling in Contemporary Nigeria
Education and Development in Africa
Student Experiences in Nigeria
Student Success in Nigeria
Youth Education in Nigeria

Through a mixed-methods research approach, this thesis investigates how Nigerian secondary schools are preparing Nigerian youth for decolonial social leadership. Specifically, the main research question is: To what extent are Nigerian secondary school students prepared to engage in and contribute to the political, economic, and cultural development of their communities without reproducing coloniality? This question was investigated by: critically analyzing Nigeria’s education policy documents, conducting surveys with 768 students across the six geo-political zones in Nigeria, and interviewing 30 of the surveyed students. The data show that the Nigerian secondary school system is not preparing students for decolonial social leadership. Specifically, students are being educated through a banking education model that measures their success through socially disconnected high stakes examinations. The study shows that the education system: violates poorer students, especially vulnerable female students, perpetuates oppressive social understandings amongst students, reproduces oppressive social hierarchies, and divides students along class and ethnic lines. Also, students are educated in a way that intellectually estranges them from: their immediate social environments, the diverse social issues in their communities and their contested communal social histories. Put together, coloniality is being reproduced in the schooling experiences of students in seven distinct ways. To position Nigeria’s education system towards developing a new generation of decolonial-inclusive leaders, the thesis argues for a complete system overhaul guided by a decolonial theoretical lens. Specifically, the thesis recommends a shift from its current Eurocentric, adult centered and managerial orientation towards a multi-centric, student-centered and decolonial approach to schooling. This recommended approach involves reduced high stakes examinations and the adoption of communal/formative forms of assessment, the use of a trans-disciplinary curriculum, privileging problem-based teaching and learning methods, and a commitment to nurturing the unique passion/talents of every Nigerian student.
Biochemical and Biophysical Analyses of the DNA Packaging Protein Machine the Bacteriophage HK97
Keywords: Bacteriophage
HK97
NMR
Protein Purification
Structural Biology
terminase

Packaging of DNA into the phage head requires the action of a terminase complex, which is comprised of a small terminase (TerS in HK97) subunit and a large terminase subunit (TerL in HK97). TerS binds the phage DNA and regulates the activity of TerL. TerL possesses nuclease and ATPase activities needed to generate a genome-length unit of phage DNA from a DNA concatemer and to translocate the mature DNA into the phage head. In the bacteriophage HK97, an HNH endonuclease, gp74, is also involved in phage head packaging. HNH endonucleases are proteins which bind and digest DNA in the presence of divalent metal cofactors. Gp74 enhances the activity of the terminase enzymes toward the phage DNA substrate, and this activity is dependent on an intact HNH motif. Mutation of the metal binding residue in the HNH motif abrogates the gp74-mediated enhancement of terminase function and inhibits phage formation. Work in this thesis addresses the molecular mechanism by which gp74 enhances terminase activity. Using NMR spectroscopy, I have shown that gp74 possesses a helical insertion in its HNH motif that affects its metal binding capability. Further, I have shown that the helical insert is involved in gp74-mediated enhancement of DNA digestion by the terminase enzymes. Finally, the helical insert is also necessary for phage formation. The biochemical experiments examining how wild type and gp74 mutants affect terminase functions required purified samples of the individual terminase subunits. Thus, part of this thesis also describes methods I developed to purify HK97 terminase proteins such that they are soluble in solution and functional. My studies involving gp74, TerS, and TerL have enhanced our understanding regarding the molecular basis by which cofactors (e.g. gp74) regulate the activities of terminases that are needed for DNA packaging and phage maturation.
Characterizing the Role of Neural Dynamics in the Treatment of Depression
Keywords: Depression
Electroconvulsive Therapy
Electroencephalography
Escitalopram
Magnetic Seizure Therapy
Predicting Treatment Response

Selecting an appropriate treatment for patients with depression is challenging for several reasons. There is no clear understanding on (i) the pathophysiology of depression, (ii) heterogeneity in depression, and (iii) targets for successful treatment outcome. As such, although treatments for depression are effective, their average efficacy seems to be poor. It is widely accepted that seizures induced in the brain are highly effective for severe, treatment-resistant cases of depression. Seizures are also known to impact the dynamics of neural activity. Based on this knowledge, we investigated whether treatments for depression impact neural dynamics for therapeutic efficacy. We also evaluated whether measures of neural dynamics can predict response. Seizure therapy (electroconvulsive therapy and magnetic seizure therapy) and pharmacotherapy (escitalopram) were studied. It is hypothesized that modulations of neural dynamics in several frequencies, timescales, regions and networks, previously shown to be affected in depression, are associated with therapeutic outcome. These modulations are also hypothesized to be distinct from modulations associated with non-response. In this work, measures of neural dynamics were derived from power spectral density analysis, multiscale entropy analysis and microstate analysis of resting-state, eyes-closed EEG data. Results suggest that successful seizure therapy potentially impacts several characteristics of neural dynamics for therapeutic efficacy. In responders of seizure therapy, modulation of neural dynamics was observed in regions (posterior cingulate cortex, precuneus, occipital pole) and networks (salience, fronto-parietal) previously known to be impaired in depression. In responders of escitalopram, modulation of neural dynamics was observed after 2 weeks into the 8-week course of escitalopram treatment. These changes were observed in regions known to be impaired in depression (posterior cingulate cortex, precuneus, posterior cingulate cortex) but not within networks. In non-responders of escitalopram, an early modulation of neural dynamics (i.e., baseline to 2 weeks) was observed. Finally, using measures of neural dynamics, prediction of response to escitalopram achieved an accuracy of 83.2%. Knowledge from this work will guide the development of antidepressant response prediction tools and potentially improve treatment efficacy in depression.
Hybrid Bioactive Nanoparticles for Modulation of Tumor Microenvironment and Enhancing Radiation and Chemotherapy Efficacy
Keywords: Breast and prostate cancer
Chemotherapy
nanoparticles
Radiation therapy
Tumor hypoxia
Tumor Microenvironment

Tumor microenvironment (TME) abnormalities are recognized as the main obstacle in treating solid tumors and are responsible for the failures in cancer therapies via promoting tumor cell growth, invasion, resistance to radiation and chemotherapy (CT), and escape from immune surveillance. To tackle interplay of multiple TME factors, our team has previously designed novel hybrid manganese dioxide nanoparticles (MDNPs) with the high reactivity and specificity toward H2O2 for the simultaneous and sustained production of O2 and regulation of pH to modulate the TME. Here, we propose a new multimodal strategy by utilizing MDNPs to remodel the TME, suppress drug and radiation resistance factors, reverse immunosuppressive conditions, and enhance treatment efficacy. Results from this thesis reveal the high potential of MDNPs in quenching reactive oxygen species (ROS) (e.g. H2O2), decreasing HIF1α, and lowering hypoxia level in the tumor. In comparison to radiation therapy (RT) alone, the combination of MDNPs and RT promoted cell death and decreased cancer cell proliferation in tumor-bearing animals. Survival studies not only resulted in significant increase in median survival time for breast and prostate tumor-bearing animals treated with the combination MDNPs + RT, but also achieved curative III treatment. It was further observed that MDNPs could modulate TME, reflected in downregulation of drug resistance factors and enhanced cellular uptake and anti-cancer activity of doxorubicin (DOX). The combination therapy with MDNPs and DOX also stimulated adaptive antitumor immunity and decreased immunosuppression, resulting up to 60% complete tumor regression in breast tumor-bearing mice. The high in vivo tolerability and stability of the nanoparticles, the simplicity of administration and effectiveness of the MDNPs on CT and RT are key elements that will make this system highly translational. Such results suggest that the new multimodal combination therapies are a simple yet powerful approach to treat solid tumors. Further, it was shown that the polymer-lipid nanoparticle (PLN) formulation developed by our team has a transformable behaviour in physiological condition, enabling higher intracellular uptake in vitro and intratumoral accumulation and penetration in-vivo of DOX when compared to liposomal or free solution of DOX. The findings in this thesis verify that transformable PLN system offers a unique platform and a novel approach for more effective drug transportation to the tumor.
Transgressive Nature. Beyond the Frame: Images of Vegetal Nature Across the Arts in Northern Renaissance Europe
Keywords: Astwerk
early modern
forest
frame
nature
vernacular

Nature became a significant object of attention in the early modern era. Images of plant life changed significantly in the arts and architecture of Northern Europe near the beginning of the sixteenth century. Representations of branches, vines, and other botanical material become more prominent, proliferating in every medium. As designs based on nature became a field for creative innovation, botanical material sometimes transgresses the role of marginal ornament, and natural settings appear in new contexts. Other studies tend to either disregard plant ornament or they argue that landscape became a central subject in northern art but connect its origins and impetus to sources in ancient Rome and early modern Italy. Rather than seeking connections with Italy, this study demonstrates the impact of other factors, arguing that the changes in representing trees and plants reflect cultural shifts, including changes in knowledge production and religious thought. A consideration of the factors that concerned vernacular culture, as well as humanists, provides insights that deepen our understanding of early modern art. Nature could serve as a representational strategy to visualize these concerns. The broad and contradictory significances that natural imagery carried made it an ideal vehicle to express the concerns of northern European culture in a time of religious reform. Nature's polyvalency may suggest alternate points of view, enabling the work as a whole to participate in current themes of discourse and debate. This project examines the inventive uses of plant imagery, and demonstrates the impact of its cultural contexts. The geographical context is from the Alsace to the Czech Republic, the Low Countries, and especially the German-speaking lands. Some works were produced by renowned artists, while others are little known in North America. This study addresses the roles nature played in early modern visual culture, in ways not yet addressed by other scholars.
A Different Shade of Grey: Intimacies of Older Filipino Gay Men in Canada
Keywords: ageing
bakla
Filipino
older adults
queer

This dissertation is a qualitative study, which examined the experiences of intimacy of the older Filipino gay men in Canada. These group of men identify as bakla, which is the Filipino term for queer or non-normative gender and sexual identity, practices, and performances. I specifically investigated how older bakla engage and express their intimacies with the three significant groups of people in their lives, namely, their sexual partner, their family or bloodrelated kin, and their friends. The purpose of such inquiry was to understand the relationship dynamics that older bakla have with these three groups. Such significant figures are the potential sources of social and emotional support of the older bakla. Intersectionality theory from a queer diasporic–feminist gerontological lens informed the study that takes into account the social location of the informants in terms of sexuality and gender, race, diaspora, age, and class. In this study, I used both participant observations and in-depth interviews as the main methods of data collection. These methods were informed by a culturally-grounded approach, called kuwento, a Filipino version of storytelling. This type of storytelling allowed the informants of the study to articulate their experiences in a manner that was comfortable, accessible, and convenient for them. Using grounded theory for data analysis, older bakla revealed a different experience of iii intimacy with their significant others. A story of difference exists, because they do not necessarily resonate to the dominant stories of aging. Their stories of intimacies offer critique of the norms and dominant discourses of identity. As well, older bakla’s intimacies illuminate their sense of agency in negotiating the norms of gender, sexuality, ageing, class, diaspora, and race that have marginalized and oppressed their beings and subjectivities. In the conclusion, I discuss how their intimacies with significant others, which are conditioned by uncertainty, impact their well-being and ageing bodies and how these informed critical social work education and practice. This study offers important contributions to the field of gerontological social work, sexuality and queer studies, migration and transnationalism, and anti-oppressive epistemologies.