VictorJuiz/thesis huggingface dataset:
Characterization of Epstein-Barr Nuclear Antigen 1 (EBNA1) Effects on Host Cells and its Functional Interaction with the Cellular Kinase CK2

Epstein-Barr virus (EBV) immortalizes host cells as part of its latent mode of infection, and the Epstein-Barr Nuclear Antigen 1 (EBNA1) is essential for establishing EBV latency. In addition to its roles on the EBV genome, increasing evidence suggests that EBNA1 contributes to cell immortalization and survival. The aim of this thesis is to further characterize the effects of EBNA1 on cells. Firstly, I performed a 2D-DiGE proteomic screen on the nuclear proteome of nasopharyngeal carcinoma (NPC) cells with or without EBNA1 expression, and identified several new proteins whose levels were modulated by EBNA1. In addition, I found that stable EBNA1 expression resulted in an accumulation of ROS (reactive oxygen species) in NPC cells, which may be partly due to an EBNA1-induced increase in the transcript and protein levels of NOX1 and NOX2 NADPH oxidases. These findings indicate new ways that EBNA1 can alter the host cell environment and contribute to the development of NPC. EBNA1 exerts multiple effects through interactions with cellular proteins. Here, I also investigated the EBNA1 interaction with the cellular kinase CK2 (Casein Kinase 2), and showed that this interaction is critical for the ability of EBNA1 to disrupt PML (promyelocytic leukemia) nuclear bodies, that mediate tumour suppressor functions and the anti-viral response. Specifically, EBNA1 increases the association of two cellular enzymes, CK2 and USP7 (ubiquitin specific protease 7), with PML nuclear bodies, which leads to the phosphorylation and polyubiqutylation of the PML proteins resulting in their degradation. Lastly, through the characterization of the EBNA1-CK2 interaction, I discovered a novel protein binding pocket in CK2β, containing a KSSR motif, which mediates protein-protein interactions with viral and cellular proteins. The CK2β KSSR motif has the propensity to bind polyserine tracts on EBNA1 as well as on another cellular protein, ARKL1.

Keywords: Epstein Barr Virus
Protein Kinase CK2
Advisor: Frappier, Lori
Optical Spectroscopy of Two-dimensional Electronic Materials

This thesis presents optical studies of several low-dimensional electronic materials. Reflectance, transmittance, ellipsometry and Raman scattering were employed to measure the fundamental excitations of the materials under study. The electrodynamics of BSCCO two-dimensional atomic crystals were investigated as a function of thickness. The thickness dependence of the optical response indicates a tendency of the BSCCO surface to become insulating. Furthermore, the characteristic energy scale of magnetic fluctuations was observed to increase in the atomic crystals. A series of superconducting Cu

Keywords: Mott insulator
optical spectroscopy
Raman
superconductor
Advisor: Burch, Kenneth S.
Electrophysiological Recording of the Brain, Visualization, Prediction, and Interconnectivity

The human brain is a complex network of interconnected neurons. The aim of neuroscience and neuroengineering is to decode the neural activity, visualize it and try to better understand how neurons communicate with each other. This dissertation comprises four contributions to the area. These four topics are discussing how functional relationship between brain activity and movement can be found and whether common features found in different regions are correlated (phase-locked). First, the method of chirplet decomposition offers a new way to visualize the time-frequency content of non-stationary signals with higher resolution than previously possible. The use of Wigner-Ville distribution together with chirplet decomposition allows a clearer visualization in terms of both the temporal and frequency details with detail higher than previously achieved using other methods including Choi-Williams and spectrogram. Second, an improved method of averaging of neural signals over repeated trials is introduced whereby slight variations in the alignment of the neural signal over time is corrected through the use of nonlinear shifts. In earlier studies, time alignment has been performed using linear shift (e.g. alignment with movement onset), but this process alone is not sufficient when the signal timing changes differently over time. To overcome this issue, nonlinear transformations were found to remove any temporal variabilities in the way the task was performed. Third, a multilinear model is demonstrated showing how limb velocity in a reach task can be predicted from neuroelectrical activity. The model, after fitting, suggested that high frequency oscillations have sufficient information for both detection of movement onset and reconstruction of its movement. The use of a linear model reduces the overall computational requirements and simplifies the reconstruction of movement kinematics. Finally, a fourth method involving the measurement of coherence over time reveals how circuits in the basal ganglia communicate with the cortical layers during voluntary movements. This allows investigating the inter-coupling between the sensorimotor cortex and basal ganglia and how cortico-basal ganglia coupling changes with respect to the movement. The association of coherence with power suggests that a coupling in neural activity between the basal ganglia and the cortical region of the brain is required for the execution of voluntary movements. The coherent activity suggests that similar information can be found in two brain regions.

Advisor: Wong, Willy
Image-guided Predictions of Liposome Transport in Solid Tumours

Due to the ability to preferentially accumulate and deliver drug payloads to solid tumours, liposomes have emerged as an exciting therapeutic strategy for cancer therapy. Unfortunately, the initial excitement was dampened by limited clinical results, where only negligible increases in patient survival following liposome therapy have been observed. What are the reasons for the limited clinical efficacy? Is the nanoparticle formulation optimal? Is the enhanced permeability and retention effect overstated? What are the barriers limiting the delivery of drugs to cancer cells? What is the optimal dosing and treatment schedule? Addressing these questions requires developing quantitative tools to understand the behaviour of liposomes in vivo, such as pharmacokinetics, biodistribution, intra-tumoural accumulation, and drug release. Central to each of these questions is the concept of transport - the collection of biophysical processes responsible for the delivery of molecules to tissues. Understanding transport means understanding the crucial links between the spatio-temporal accumulation of liposomes, the physicochemical properties of liposomes, and properties of the tumour microenvironment. In this thesis, a biophysical mathematical transport model is developed that when used in combination with non-invasive imaging methods can predict liposome transport in solid tumours. The mathematical transport framework is validated in its ability to predict the bulk and intra-tumoural accumulation of liposomes based on biophysical transport properties of solid tumours. Furthermore, novel imaging methods are developed and used to elucidate the crucial links between transport barriers and spatial heterogeneity in liposome accumulation. Finally, methods are presented to integrate quantitative imaging and mathematical modelling such that an accurate prediction of liposome transport in solid tumours is possible. In summary, this thesis presents and validates an image-guided mathematical framework that can be used to guide the rational application of liposomes for the treatment of solid tumours.

Keywords: Drug Delivery
Imaging
Liposomes
Transport
Advisor: Jaffray, David A
Mantle Dynamics Following Supercontinent Formation

This thesis presents mantle convection numerical simulations of supercontinent formation. Approximately 300 million years ago, through the large-scale subduction of oceanic sea floor, continental material amalgamated to form the supercontinent Pangea. For 100 million years after its formation, Pangea remained relatively stationary, and subduction of oceanic material featured on its margins. The present-day location of the continents is due to the rifting apart of Pangea, with supercontinent dispersal being characterized by increased volcanic activity linked to the generation of deep mantle plumes. The work presented here investigates the thermal evolution of mantle dynamics (e.g., mantle temperatures and sub-continental plumes) following the formation of a supercontinent. Specifically, continental insulation and continental margin subduction are analyzed. Continental material, as compared to oceanic material, inhibits heat flow from the mantle. Previous numerical simulations have shown that the formation of a stationary supercontinent would elevate sub-continental mantle temperatures due to the effect of continental insulation, leading to the break-up of the continent. By modelling a vigorously convecting mantle that features thermally and mechanically distinct continental and oceanic plates, this study shows the effect of continental insulation on the mantle to be minimal. However, the formation of a supercontinent results in sub-continental plume formation due to the re-positioning of subduction zones to the margins of the continent. Accordingly, it is demonstrated that continental insulation is not a significant factor in producing sub-supercontinent plumes but that subduction patterns control the location and timing of upwelling formation. A theme throughout the thesis is an inquiry into why geodynamic studies would produce different results. Mantle viscosity, Rayleigh number, continental size, continental insulation, and oceanic plate boundary evolution are explored in over 600 2D and over 20 3D numerical simulations to better understand how modelling method affects conclusions on mantle convection studies. The results from this thesis show that the failure to model tectonic plates, a high vigour of convection, and a (pseudo) temperature-dependent viscosity would distort the role of mantle plumes, continent insulation, and subduction in the thermal evolution of mantle dynamics.

Keywords: Continental insulation
Mantle convection
Mantle plume
Pangea
Subduction zones
Supercontinent
Advisor: Lowman, Julian P
Circuits for Blind ADC-based CDRs and Frequency Detectors

This thesis presents three contributions in the area of clock and data recovery (CDR). Two of these three contributions focus on the design of frequency detection mechanisms for reference-less half-rate clock and data recovery circuits, while the third one focuses on the design of blind ADC-based CDRs. While conventional CDR architectures for phase and frequency detection are dual loop, the interaction between the frequency detection loop and the phase detection loop can interfere with phase locking. Furthermore, the frequency detector, typically deactivated after lock, occupies area. This thesis introduces two new architectures for reference-less CDRs which perform frequency detection by adjusting the phase error of the phase detector. This enables the phase detector to deal with frequency offset, as well as phase offset. The feasibility of these two 10Gb/s CDRs are demonstrated through chip fabrications in Fujitsu 65nm CMOS technology and measurement results. The third contribution of this thesis is in the area of blind ADC-based CDRs. While the design simplicity of these CDRs significantly reduces their time to market, their high power consumption limits their application. This thesis studies the architecture of these CDRs with the goal of minimizing their power consumption. We will show that for a given analog power consumption, the optimum oversampling ratio is 2.8 (~3). The digital CDR is also redesigned to lower the power consumption of digital equalization. A 5Gb/s CDR was fabricated in Fujitsu 65nm CMOS technology and measurement results show a factor of 2 of power reduction, with improved performance.

Keywords: Analog to Digital Converter
Clock and data recovery
Equalization
Frequency detector
SerDes
Wireline
Advisor: Sheikholeslami, Ali
The Lyrics of Zhou Bangyan (1056-1121): In Between Popular and Elite Cultures

Successfully synthesizing all previous styles of the lyric, or ci, Zhou Bangyan’s (1056-1121) poems oscillate between contrasting qualities in regard to aesthetics (ya and su), generic development (zheng and bian), circulation (musicality and textuality), and literary value (assumed female voice and male voice, lyrical mode and narrative mode, and the explicit and the implicit). These qualities emerged during the evolution of the lyric genre from common songs to a specialized and elegant form of art. This evolution, promoted by the interaction of popular culture and elite tradition, paralleled the canonization of the lyric genre. Therefore, to investigate Zhou Bangyan’s lyrics, I situate them within these contrasting qualities; in doing so, I attempt to demonstrate the uniqueness and significance of Zhou Bangyan’s poems in the development and canonization of the lyric genre. This dissertation contains six chapters. Chapter One outlines the six pairs of contrasting qualities associated with popular culture and literati tradition that existed in the course of the development of the lyric genre. These contrasting qualities serve as the overall framework for discussing Zhou Bangyan’s lyrics in the following chapters. Chapter Two studies Zhou Bangyan’s life, with a focus on how biographical factors shaped his perspective about the lyric genre. Chapter Three examines various methods through which Zhou Bangyan’s lyrics were circulated during the Song Dynasty, including through the performance of singing girls, anthologies compiled by the literati, and prosodic manuals of lyric meters annotated by musicians. Chapter Four focuses on the issue of lyrical voice, demonstrating how Zhou Bangyan deviated from the assumed female persona tradition by writing lyrics from the viewpoint of a male. It also analyzes the absence of the lyrical self in some of Zhou Bangyan’s lyrics on objects. Chapter Five studies how Zhou Bangyan explored the narrative mode generally found in common songs and how he developed complicated narrative techniques typical of literati lyrics. The last chapter investigates Zhou Bangyan’s lyrics with a focus on lyric structure, temporal sequence, point of view, and intertextuality, revealing the emphasis of these lyrics on an implicit style.

Keywords: Zhou Bangyan
song lyrics
the Song Dynasty
Advisor: Sanders, Graham
Frozen Landscapes, Dynamic Skills: An Ethnoarchaeological Study of Inuit Kayaking Enskilment and the Perception of the Environment in Greenland

This dissertation is an ethnoarchaeological study of kayaking – a skill that has been practiced by Inuit in the Eastern Arctic since the first Thule migrants explored and settled the region around 1250 A.D. In this project, I aim to better understand the archaeological record of Inuit culture by working closely with a community in Greenland that builds kayaks and practices traditional hunting skills. Although kayaking is no longer a primary mode of subsistence, the community finds meaning in the persistence of the skill because it is an important mechanism of intergenerational experience, and because it contains types of cultural and environmental knowledge that can only exist through practice. The community is specifically focused on the physicality of enskilment – the process through which individuals develop unique capacities for awareness and response through environmentally situated practice. Through enskilment, kayakers attune their senses to subtleties and nuances of the environment which would not otherwise be apparent, and they embody a heritage of resilience and creative responsiveness in both the natural and social environment. Drawing on three field seasons of ethnoarchaeological fieldwork, I document the process through which individuals become skilled kayakers and explore the constitution of the kayaking community through practice. As demonstrated in this dissertation, the acquisition of skill in kayaking is not a passive process where knowledge is simply handed from one generation to the other. This is an important observation for archaeologists who study the past through the interpretation of material culture. It will be argued that understanding the impermanence and inherent creativity through which environmentally situated knowledge is re-grown in the experiences of each generation allows for more nuanced archaeological narratives which emphasize skilled practice on the part individuals as causative agents at work in the deeper history of Inuit culture.

Keywords: Arctic Archaeology
Enskilment
Advisor: Friesen, Max
Il quarto libro dell'Eneide in scena: studio filologico e critico della Dido in Cartagine (1524) di Alessandro Pazzi de' Medici

This thesis is a commented critical edition of Alessandro Pazzi de’ Medici’s Dido in Cartagine (1524). It is based on the premise that there still exists a significant lacuna in the field of Italian Renaissance tragedy. Notwithstanding the importance attributed by many critics to Italian Cinquecento tragedy, we nonetheless do not have reliable editions of many of these works. Italian Renaissance tragedy has been for the greater part perceived as a minor literary genre, particularly when compared with comic theatre or with contemporary English and French drama. Pazzi was a Florentine scholar, educated both in Latin and Greek. Most of the tragedies written in the early sixteenth century were translations or rewritings of Greek tragedies, while Dido in Cartagine is a play that deals with a Roman subject. It is an original dramatization of Dido’s suicide after Aeneas abandons her. The main source is therefore the fourth book of Virgil’s Aeneid. The dissertation is comprised of an introduction, four chapters, the text of Dido in Cartagine, the critical apparatus, an appendix, and a bibliography. Chapter 1 introduces Pazzi and his works. Chapter 2. a. deals with the issue of representing death on Italian Renaissance stages. Chapter 2. b. is a study of Dido’s theatrical dimension. Chapter 3 opens the philological section of the thesis: it provides the description of the original manuscript and of its printed editions, the transcription criteria according to modern methods in textual criticism, and a table of linguistic sources used for the philological footnotes of the text. Chapter 4 presents the fourth book of the Aeneid in Latin with the first full translation in vernacular on parallel page. The text of the tragedy follows, annotated with philological and critical footnotes, and accompanied by the critical apparatus, which provides the readings, accepted as original and correct, and the variants of the 16th-century proofreader as well as the ones of the Solerti printed edition of 1887. In the appendix, readers can analyze Andrea Lancia’s compendium of the fourth book of the Aeneid. The thesis closes with a works cited section.

Keywords: Italian
Renaissance
Theater
Tragedy
Philology
Advisor: Lettieri, Michael
Sheer Force of Will: A Will Theory of Contract

In the intellectual history of contract law, one enduring idea is the “will theory”: the idea that the law of contract merely reflects the will or choice of the contracting parties. In the common law (as in the civilian tradition), this idea remains both influential and controversial. Almost all lawyers, judges, and scholars accept that the will of the parties must play some role in explaining contract law. However, they debate how encompassing, and how acceptable, that role is: the extent to which the will theory “fits” the legal doctrine that it purports to explain, and whether it provides a satisfactory justification for the institution of contract. In these debates the participants often talk past each other, because in the current scholarship there is no developed conception of what a will theory should look like. Instead, the will theory has been defined in large part by implication, through the attacks of critics who assume it is susceptible to their objections. This aim of this dissertation is to show that a will theory, formulated with appropriate precision, can explain and justify the core of the common law of contract. We can understand contractual obligation as arising through the sheer force of the contracting parties’ will.

Keywords: contract
Advisor: Benson, Peter
Genome-Wide Analysis of Translation in the Early Drosophila Embryo

Regulation of translation plays an essential role in Drosophila embryogenesis, as loss or misexpression of regulatory proteins can cause lethal development defects. As a result of its importance in these early developmental events, there has been considerable study of translation in the early embryo. Here, I complement those studies with an investigation into translation on a genome-wide scale. In chapter 2, I describe my development and optimization of polysome-gradient protocols to study translation in the mature oocyte and early embryo on a genome-wide scale. In chapter 3, I combine the protocols developed in chapter 2 with microarray analysis to study the role of Smaug, a sequence specific RNA-binding protein, in regulating translation on a genome-wide scale. Comparisons of the list of mRNAs that co-immunoprecipitate with Smaug with those that are translationally repressed by Smaug and those that are degraded by Smaug, suggests that Smaug directly regulates the translation and stability of a large number of mRNAs in the early embryo. I also developed a new algorithm to search for Smaug binding sites, which are called Smaug Recognition Elements (SREs), in mRNAs. The presence of SREs was shown to predict Smaug binding and translational regulation. Taken together these data indicate that Smaug plays a direct and global role in regulating the translation and stability of a large fraction of the mRNAs in the early Drosophila embryo.

Keywords: Smaug
mRNA
translation
Gene Regulation
Advisor: Smibert, Craig
Priming the Brain for Recovery from Stroke: The Role of Aerobic Exercise as an Adjunct to Upper-limb Therapy

Following a stroke, the majority of individuals are left with residual deficits and there is a need to continue to improve strategies to augment recovery. This dissertation explores the approach of optimizing central nervous system conditions using aerobic exercise prior to task training. In healthy individuals a single session of aerobic exercise influences arousal and attention however, it is unknown if these effects translate to a stroke population. Further, little is known about the effect of a single bout of aerobic exercise on subsequent skill adaptation. Therefore, the main objectives of this thesis were to investigate the effect of a single bout of aerobic exercise on: (1) CNS arousal and attention in a stroke population; and, (2) short-term skill adaptation in healthy individuals and those who have suffered a stroke. Overall, for individuals recovering from a stroke, CNS arousal may be augmented as indicated by faster reaction times in some conditions and consistently faster movement times across conditions following exercise. However, attention did not appear to be influenced by the exercise bout as reaction time variability was unchanged in study 1 and absolute change was comparable across tasks with differing attentional demands in study 2. While exercise positively enhanced short-term adaptation in healthy individuals, for individuals recovering from stroke the exercise bout did not appear to benefit upper-limb movement adaptation compared to a control condition. This dissertation highlights the potential for using exercise to influence CNS state after stroke, though results revealed significant between and within-subject variability in this population. Future work should progress to evaluating the longitudinal multi-session effects of pairing aerobic exercise with ecologically valid task training to determine if the observed single session benefits augment neurorehabilitation and aid long-term recovery from stroke.

Keywords: exercise
neuroscience
physiotherapy
stroke
upper-limb
Advisor: McIlroy, William E
Roy, Eric A