VictorJuiz/thesis huggingface dataset:
Investigation of CSF1-CSF1R Signaling in AML-Bone Marrow Stromal Cell Interactions
Keywords: Acute Myeloid Leukemia
Bone Marrow Stroma
Cell Signaling
CSF1-CSF1R
Tumour microenvironment

Acute myeloid leukemia (AML) is a highly heterogeneous and growth factor-dependent disease. Colony stimulating factor 1 (CSF1) is a cytokine produced by bone marrow (BM) stromal cells that directs the differentiation and growth of myeloid cell precursors into monocytes and macrophages. Human CSF1 (hCSF1) exists as a soluble/secreted (hCSF1-sol), and a transmembrane (hCSF1-mem) isoform. CSF1 acts on the CSF1 receptor (CSF1R), which is expressed on mononuclear phagocytic cells. In this study, the CSF1-CSF1R ligand-receptor pair was investigated in the context of AML-stromal cell interactions. Analysis of cell surface CSF1R protein levels revealed that a subset of AML patient samples express high levels of CSF1R (CSF1Rhigh), and that these patients have shorter overall survival (OS) times compared to patients with low CSF1R expression (CSF1Rlow). In examining the CSF1-CSF1R interaction experimentally, the long-term growth and survival of CSF1Rhigh AML cells was supported by MS-5 stromal cells expressing human CSF1 (hCSF1) in co-culture experiments. MS-5 cells expressing the membrane-bound form of CSF1 (hCSF1-mem) in particular led to significant increases in AML cell numbers and adhesion to stroma, compared to cells co-cultured with MS-5 empty vector (EV) or hCSF1-sol cells. Co-culture of AML cells with MS-5 hCSF1-mem cells led to activation of mTOR signaling in AML cells as observed through increases in pS6, increased expression of the hematopoietic stem cell markers CD34 and c-Kit on AML cells, and distinct changes in the cytokine profiles of both AML and stromal cells. Further to this, deletion of the PDZ domain binding motif (PDBM) at the C-terminal end of CSF1 ligand in MS-5 stromal cells led to decreased stromal support of AML cells, and reduced mTOR pathway activation. The interaction between CSF1 and CSF1R mediates supportive effects between AML and stromal cells by fostering bilateral intracellular and intercellular signaling changes. As such, targeting the CSF1-CSF1R interaction may prove to be an effective therapeutic strategy to overcome and compromise the protective and supportive role of the BM niche in AML disease pathogenesis.
Optimal Design of Multi-user Distributed Massive MIMO Systems
Keywords: 5G
Distributed antenna systems
Massive MIMO
RAN design

This thesis studies two fundamental challenges facing the optimal deployment of distributed massive multiple-input multiple-output (DM-MIMO) systems: (1) the need for the optimal design of the locations of the remote-radio-heads (RRHs) and (2) the issue of non-reciprocal uplink/downlink channels and their impact on the performance of DM-MIMO systems. The radio access network in a DM-MIMO system consists of several RRHs, each equipped with one or more antennas, scattered throughout the coverage area. To reap the potential benefits of DM-MIMO systems, the locations of these RRHs need to be carefully optimized. The majority of this thesis is dedicated to the optimal RRH placement for DM-MIMO systems, investigating this problem from different aspects. We first consider the RRH location optimization to maximize the average downlink rate. Two variants of the harmonic clustering algorithm (HCA) are proposed to obtain the locations of the RRHs in both homogeneous and non-homogeneous propagation settings. Afterwards, this thesis proposes a framework using signal-to-leakage-and-noise ratio (SLNR) for RRH placement. The SLNR-based RAN design approach demonstrates promising gains in the average throughput of the system, however, this comes at the cost of performance degradation at the cell-edge users. Alternatively, this thesis also considers the cell-edge rate maximization problem for RRH placement. An optimization framework based on an approximation of the probability distribution of the downlink rate is proposed. This approach is capable of outperforming the HCA placement in terms of the cell-edge rate. As a last step towards optimal RRH placement, this thesis considers a scenario where the positions of the RRHs are to be selected from a discrete set of possible locations. Two efficient solutions based on sequential decision making formulation and Monte-Carlo tree search are proposed to tackle the RRH location selection problem. The last part of this thesis investigates the impacts of non-reciprocal uplink/downlink channels on the performance of DM-MIMO systems operating in time-division-duplexing mode. Accurate expressions for downlink rate are obtained illustrating the degrading effects of the residual non-reciprocity on the achievable throughput. Finally, a robust downlink beamforming method is proposed which is capable of mitigating the impacts of the non-reciprocal channels.
Microfluidic and Nanofluidic Study of Solvent-based Unconventional Hydrocarbon Processes
Keywords: Bitumen
Microfluidics
Nanofluidics
Shale oil
Solvent based EOR

Unconventional resources such as tight oil and bitumen do not yield to conventional production processes and are difficult to produce economically. The use of solvents to extract unconventional resources has shown promise and has potential to enable efficient production while overcoming the limitations of the current processes. However, adding a solvent phase adds further complexity to a physical system that is already poorly understood, with multicomponent mixtures within multiscale micro- and nano-confined geometries. While conventional laboratory testing methods can provide some insight, they do not resolve the critical physical/chemical mechanisms at the pore-scale. Over the past few years, microfluidic approaches have been increasingly applied in the energy sector, and particularly in oil and gas. In contrast to conventional methods, microfluidics can provide direct visualization of pore-scale dynamics during extraction processes and generate fast and accurate phase data for the fluids under reservoir-relevant temperatures, pressures, and scales. In this thesis, a new generation of high-temperature and high-pressure microfluidic and nanofluidic devices are developed for the study of solvent-based unconventional resources recovery methods. For bitumen extraction, both pure solvent and solvent-steam co-injection methods are studied using a glass-glass micromodel at reservoir relevant temperature and pressure. To investigate asphaltene precipitation and deposition resulting from solvent-bitumen interactions during solvent-based extraction processes, a silicon-glass microfluidic device is developed. To improve the practicality of silicon-glass microfluidic based methods for such applications, a new approach was developed whereby the device yield per wafer was increased by one to two orders of magnitude, rendering these otherwise expensive microfluidic systems effectively disposable. This new approach was tested in application to immiscible flooding for heavy oil production, and a CO2 capture fluid with successful tests at pressures up to 80 bar. Lastly, these methods were extended to the nanoscale and applied to measure the first contact miscibility pressure of CO2 and oil under nano-confinement for enhanced oil recovery implications in tight and shale oil reservoirs. Collectively, these contributions provide insight into solvent-based recovery methods for unconventional resources by levering the precision, robustness, and optical access provided by microfluidics and nanofluidics.
Androgen Receptor and Histone Variant H2A.Z Interact to Regulate Fear Memory and Memory-related Gene Transcription
Keywords: Androgen receptor
Epigenetics
Fear memory
H2A.Z
Histone variant
Sex difference

Sex hormones are potent regulators of memory, but the role of androgen receptors in males is poorly characterized compared to the role of estrogens in females. Thus, the goal of my thesis is to characterize the role of AR in fear memory and the mechanistic basis of this effect in male mice. In Chapter 2, I utilized transgenic male mice that overexpress the androgen receptor (AR) to elucidate its effects on fear memory. I showed that AR overexpression impairs fear memory and that this effect is regulated by circulating androgens. Moreover, I showed that AR regulates the expression of several memory-related genes, including the epigenetic memory suppressor, histone H2A.Z. Our lab previously identified the histone variant H2A.Z as a negative modulator of fear memory through its effects on transcription. Given that AR is a transcription factor that interacts with H2A.Z in prostate cancer, I next characterized the functional and mechanistic interaction between the two. In Chapters 4 and 5, I used inducible-conditional H2A.Z knockout mice to delete the two genes (H2afz and H2afv) that encode H2A.Z in excitatory neurons in adult mice. I showed that simultaneous deletion of both H2A.Z-encoding genes enhanced fear memory, which extends our prior findings that virally-mediated depletion of H2afz alone enhances memory. Next, I showed that H2A.Z deletion blocked the effects of androgen receptor manipulation on fear memory, suggesting that AR and H2A.Z interact at a functional level. To test the mechanistic basis of this interaction, I utilized cultured hippocampal neurons to show that manipulating AR activation alters H2A.Z binding to DNA, suggesting that AR regulates behaviour through H2A.Z. Given its interaction with AR, I next investigated whether H2A.Z deletion produces unique effects in males and females. In contrast to males, H2A.Z deletion did not enhance fear memory in females, but it did serve as a protective factor against stress-enhanced fear memory (a PTSD-modeling paradigm). Overall, these data suggest that AR and H2A.Z interact at the chromatin level to regulate fear memory and that interactions with sex hormones may produce sex-specific effects of H2A.Z on fear memory.
Risk Factor Epidemiology and Predictive Modelling Approaches to Understanding Chronic Disease Incidence
Keywords: CDPoRT
Chronic disease
Lifestyle risk factors
Prediction modelling
Royston-Parmar model

The chronic disease burden is a public health priority with most Canadian adults having chronic disease. Addressing this burden is a complex task requiring multiple stakeholders, including researchers. While researchers have traditionally studied chronic diseases individually “in silos”, studying multiple chronic diseases together is important because the results provide a comprehensive understanding of the overall health of the individual and the population. This dissertation contributes to the field of chronic disease research by elucidating the relationships between a person’s first chronic disease with shared lifestyle risk factors and applying this knowledge to create a predictive tool. To enable fresh perspectives about chronic disease incidence, various survival analysis techniques were applied. The first objective examined the relationships between shared lifestyle risk factors and the incidence of first chronic disease at a given age over the life course. This study found that most individuals will develop chronic disease prior to death, and heavy, daily smoking was the most important lifestyle factor for chronic disease incidence at a given age. The second objective focused on the Royston-Parmar model and its application for prognostic modelling in health research. The study found that this relatively new model was suited for prediction but has not been widely adopted for health research. The third objective developed and validated the Chronic Disease Population Risk Tool (CDPoRT), a population risk algorithm that predicted the incidence of multiple chronic diseases simultaneously over a ten-year period in the general adult population using routinely-collected data. The end product was a tool that consistently demonstrated strong predictive performance in estimating chronic disease risk. Overall, the studies capitalized on representative health survey data linked to administrative data to study the relationships between shared lifestyle risk factors and multiple chronic diseases, and leveraged these findings to create CDPoRT using traditional and novel survival analysis methods.
Psychological Meme Science
Keywords: agent-based modeling
computational social science
election campaigns
memes
social networks
urban legends

Memes are ideas, often represented using media, with the special characteristics of being repeatable and adaptable. Memes impact our lives in material ways, influencing political systems and propagating the stories our shared culture is built from. When propagated via online social networks, the massive scale at which memes operate is without precedent. However, the meme does not act on its own; it is only by human activity that memes are created and proliferated. This dissertation will tackle a series of research questions surrounding the scientific study of humans and memes from a psychological perspective. This work begins with the observation that science is a social enterprise and scientific ideas spread as memes. The first chapter of this dissertation applies social network methods to the global scientific collaboration network in order to build a map of beliefs about systems of humans and memes. The next chapter examines a hierarchical democratic phenomenon - the online campaign preceding an election - in order to determine the appropriate analytical scope for investigating complex systems of political memes. The final chapter presents a method for translating regression models from the psychological literature into computational social simulations using agent-based models. A computational social simulation of urban legends is then built, replicating a study from the literature and then extending it to examine the effect of social network topology upon the propagation of urban legends. Humans and memes, together, constitute a complex system that offers new methodological tools to study the human condition.
Optoelectronic Investigations of Colloidal Quantum Dot Solar Cells
Keywords: Colloidal quantum dots
Optoelectronics
Photovoltaics
Renewable energy
Solar cells

Colloidal quantum dots (CQDs) are solar photovoltaic materials synthesized and processed as an ink, a potential advantage in scaling manufacture. The power conversion efficiency (PCE) of CQD solar cells has progressed well in recent years, from under 4% in 2010 to 13% today. In this thesis I seek to understand further and improve the CQD solid at both the materials and device levels with the goal of maximizing power conversion efficiency. I begin by developing an analytical model for the design and realization of optically-enhanced infrared CQD solar cells: here I focus on devices intended to operate as the junction behind a silicon solar cell collecting otherwise-unabsorbed infrared light. This optical strategy leads to a record peak external quantum efficiency of 60% in the infrared in devices employing ~100 nm-thick active layers. Next I present an optical model that uses experimental inputs from spectroscopic ellipsometry, and calculations based on the transfer matrix method, to obtain, for the first time, the spatial distribution of photocurrent losses in CQD solar cells operando. I then deploy this capability to observe depletion widths and interfacial energy barriers in operating CQD devices. Moving from photocurrent to photovoltage investigations, I then provide a model to quantify the impact of CQD size distributions on absorption and photoluminescence spectra, and that allows prediction of voltage losses, low-energy absorption tails, and the Stokes shift. These results provide physical insight into CQD absorption and photoluminescence spectra; and offer a quantitative picture of open-circuit voltage losses in CQD solar cells. They indicate that suppressing deep trap states is the most promising path forward in improving CQD solar cell performance. I then develop spectrally-tailored infrared solar cells that lever the engineering of ensembles of CQDs, achieving a record of 1% additional power points on top of a silicon cell’s efficiency. The studies herein improve understanding of the operating principles of CQD solar cells and offer quantitative guidance to chemists, materials scientists and engineers towards improved syntheses, processes, and designs.
Variation in the Initial Mass Function of Nearby Galaxies: Instrumentation and Observations
Keywords: Astronomical Instrumentation
Extragalactic Astronomy
Initial Mass Function
Integral Field Spectrograph
Near-Infrared
Star Formation

Galaxies are a fundamental structural unit of the Universe, where the vast majority of stars form and reside. Investigating the underlying mechanisms that direct the formation of stellar populations is key to furthering our understanding of how galaxies evolve. One major ingredient of a stellar population is the initial mass function (IMF), which describes distribution of stellar masses that arise from a star forming event. This thesis presents two projects to further our knowledge of the IMF: an observational near-infrared study of the IMF in early type galaxies, and the development and commissioning of the Wide Integral Field Infrared Spectrograph (WIFIS). Recent measurements of the IMF, traditionally considered to be universal, in nearby massive early type galaxies have revealed an overabundance of low-mass stars. In this thesis, we detail a pilot study using integral field spectroscopy to characterize the IMF and other stellar population parameters of M85 and M87 by comparing a novel set of near-infrared gravity-sensitive absorption features to stellar population synthesis models. Adopting modern statistical analysis methods, we find that the IMF slopes are much steeper in the massive M87 than in M85, where the IMF is similar to the Milky Way. The IMF slopes are efficiently constrained by the near-infrared spectral features, opening a path for further studies into the IMF of nearby galaxies using these new diagnostics. WIFIS is an integral field spectrograph that delivers an unparalleled combination of field size and near-infrared spectral coverage. We present the development of WIFIS, from laboratory assembly to on-sky instrument performance. Furthermore, we detail the optomechanical design and development of two critical WIFIS subsystems, a Calibration Unit that enables flat fielding and wavelength calibration, and a Guider Camera, which provides guiding and target acquisition capabilities. Presently, WIFIS is operating successfully and is conducting an extragalactic survey to characterize the properties of nearby stellar populations. As part of this survey, we conduct a preliminary investigation into the IMFs of M85 and M87 using WIFIS and find evidence for a radially varying IMF, while confirming the capability of WIFIS to deliver scientifically rigorous spectroscopy.
Teacher Collaboration for Mandated Accreditation: A Case Study of Evaluating the International Baccalaureate Diploma Program
Keywords: Accreditation
International Baccalaureate Diploma Program
Program Evaluation
Teacher Collaboration

This qualitative case study investigates how teachers work together to complete the evaluation for a mandated accreditation of a program at one school. Specifically, the study describes the participants’ experiences of completing the evaluation, the effects of the evaluation on a school’s program as perceived by the participants, and the future of program evaluation. Qualitative data were collected in the form of document review, participant survey and interviews of evaluation team members. The evidence from the study shows that the majority of participants find the evaluation of the program transformative for their practices. Five major findings as suggested by the case study can be summarized as follows: (1) participants in this study find that their perceptions of completing the evaluation are influenced by the context of the specific school, their own experience with the given program, the personal relationships that exist between the leadership team and the teachers and among teaching colleagues, and the larger community of stakeholders situated in a specific culture; (2) the freedom to change practices and determine what is needed for the given school is crucial in how participants view the impact of an evaluation; (3) respondents’ perceptions of the intentions and abilities of the internal evaluation leaders may have some effect on how they view their evaluation experiences; (4) participants express the desire to determine what aspect of their program is most useful for them to evaluate, when to gather what data, and how to report their findings to their networks; and (5) participants argue that self-assessment is a regular function of continuous performance monitoring and a natural part of the learning climate where professional conversations lead to change. Implications from this study suggest that the context of the evaluation and the individual characteristics of the teachers can have an effect on how they perceive the collaboration required for the evaluation and how much value they place on engaging in these mandated processes. School leadership needs to establish a learning climate that supports the collaborative professional development of teachers. Suggestions for areas of further research are included at the end of the study.
Working with an Accent: The Aesthetic Labour of International Teaching Assistants in Ontario Universities
Keywords: accent
aesthetic labour
internationalization
international teaching assistants (ITAs)
narrative inquiry
universities

International teaching assistants (ITAs) in North American English-medium universities often work with an accent. In one sense, to work with an accent entails doing one’s work while having an aural stigma. This is due to the increased likelihood that students and other university stakeholders perceive ITAs’ foreign-accented English as difficult to understand. The purported problem of their foreign accents can thus create additional facets in working with an accent such as working with the idea of how to change an accent and performing (around) it in order to be viewed as effective workers. All of this work can be considered a type of aesthetic labour in that ITAs need to develop the right sound for their professional duties. Based on a narrative inquiry of the experiences of 14 ITAs working in various universities in Ontario, Canada, this thesis explores how they conceptualize and execute aesthetic labour. Specifically, it details their perceptions of a satisfactory aural aesthetic for work as well as the extent to which they incorporate this aesthetic in discussions about their professional practices. Regarding the first research objective, the ITAs understood a satisfactory accent in linguistic, racial, and professional terms. Indeed, an accent could sound “native” or “nonnative,” become “whitened” or remain racialized, and match or not match one’s work (environment). In terms of taking up these perceptions in their professional practices, which took the general form of working on or around an accent, the ITAs’ prior views on aural aesthetics were upheld and/or tempered by contextual factors in their universities. On the immediate level, the above findings provide suggestions for changes to existing forms of ITA training, which tend to ignore the knowledge of ITAs and fail to prepare them to effectively communicate according to the specificities of their work environments. More broadly, the findings are useful in highlighting how accents are not stable individual traits, but rather, malleable tools that help workers negotiate intercultural encounters in a range of professional settings. Therefore, this study counters research that frames the ITA accent as an inherent problem needing to be rectified for a homogeneous audience.