VictorJuiz/thesis huggingface dataset:
Identification of Targeting Factors Involved in the US2- and US11- Mediated Degradation of Major Histocompatibility Complex Class I Molecules

Human cytomegalovirus uses a variety of mechanisms to evade immune recognition by major histocompatibility complex class I molecules. One mechanism mediated by the immunoevasion proteins US2 and US11 causes rapid disposal of newly synthesized class I molecules by the endoplasmic reticulum-associated degradation pathway. Although several components of this degradation pathway have been identified, evidence suggests that there are still additional host cell proteins that are required by US2 and US11 to target major histocompatibility complex class I molecules for degradation. Two approaches were taken to identify proteins involved in the function of these viral immunoevasion molecules. First was a lentiviral screen for cellular factors involved in US11-mediated degradation. Infection of U373-MG cells expressing US11 with a lentiviral shRNA library and screening for those shRNAs that increased surface class I levels led to the identification of several novel proteins. ERLIN2, PDIA5, DNAJC3, NACA, and SAE1/UBE2I were all shown to impact US11 function and are promising avenues for future research. Second, I identified cyclophilin C, a peptidyl prolyl isomerase of the endoplasmic reticulum, as a component of US2-mediated immune evasion. Cyclophilin C could be co-isolated with US2 and with the class I molecule HLA-A2. Furthermore, it was required at a particular expression level since depletion or overexpression of cyclophilin C impaired the degradation of class I molecules. Overexpression of catalytically inactive cyclophilin C produced a similar effect to the wildtype molecule, suggesting a role in complex formation between US2 and components of the ER-associated degradation machinery, rather than a requirement for peptidyl prolyl isomerase activity. To better characterize the involvement of cyclophilin C in class I degradation, I used LC-MS/MS to detect US2-interacting proteins that were influenced by cyclophilin C expression levels. I identified malectin, P5, and TMEM33 as proteins that increased in association with US2 upon cyclophilin C knockdown. In subsequent validation all were shown to play a functional role in US2 degradation of class I molecules. This was specific to US2 rather than general ER-associated degradation since depletion of these proteins did not impede the degradation of a misfolded substrate, the null Hong Kong variant of Îą1-antitrypsin.

Keywords: Cyclophilin C
ER-Associated Degradation
Human Cytomegalovirus
Major Histocompatibility Complex Class I
US11
US2
Advisor: Williams, David B
Recovery From Depression: How Psychotherapists Come to Know They are Sufficiently Recovered to Practice Competently

Several studies have demonstrated that unprocessed depression amongst psychologists and other mental health therapists can negatively interfere with therapeutic work. While there is a large body of knowledge on both depression and recovery (and in particular, recovery as understood within the wounded healer paradigm), little is known about how these mental health professionals come to know that they have sufficiently recovered from a depressive experience such that the experience now generally aids rather than detracts from their therapeutic work with clients. The present study sought to better understand this aspect of therapist awareness by asking the question: how do mental health therapists come to know they have sufficiently recovered from their depressive experience such that they are now able to provide competent therapy? Participants were ten mental health therapists currently working in the Greater Toronto Area (GTA). Each participant had at least one significant depressive experiences from which they had deemed themselves sufficiently recovered and were therefore able to speak meaningfully about the experience. In-depth interviews were conducted and transcribed, and the data analyzed using a socially constructed grounded theory methodology. Three key themesâ through intrapersonal functioning, through interpersonal relationships, and through client workâ emerged, suggesting that the participants understood that becoming aware of their recovery involved a sense of adaptive shifting in both their personal and professional functioning as well as direct and indirect feedback from a number of important others in their lives. A mid-level theory was generated from these themes. The role of relationships in awareness of recovery had not been previously noted in the literature and as such is a unique contribution to the literature. Broader implications for the field of counselling and clinical psychology are addressed.

Keywords: Knowing processes
Recovery
Therapist competence
Therapist depression
Wounded healer
Advisor: Moodley, Roy
Sectarianism from Below: Youth Politics in Post-war Lebanon

In this dissertation I examine why sectarianism persists among Lebanese youth. While much of the literature on communal conflict focuses on macro-level factors and elite-based explanations, I look to different, finer, levels of analysis for a fuller picture of how communal dynamics are reproduced, and why they persist—even where the literature would expect to find them lacking, such as among educated, economically secure young Lebanese, in western-oriented universities, or civil society movements. I argue that youth themselves, and particularly the young partisans of Lebanon’s political parties, play an active role in the reproduction and rejuvenation of sectarian political dynamics ‘from below.’ The networking, strategies, and activities of youth within their political spheres constitute a ‘feedback mechanism’ operating at the grassroots to reproduce Lebanon’s particular sectarian institutional configuration. I contend that youth not only contribute to the reproduction of sectarianism, they also help to adapt it and rejuvenate its appeal among their peers. I examine three spheres of youth politics: the university campus; youth-led civil society movements; and youth wings of political parties. I find that far from being the ‘blind followers’ of manipulative elites depicted in the literature, partisan youth act with more autonomy than is often assumed; generating new culture, styles, and social networks—all of which are imbued with sectarian affiliation. I also show that the politics of Lebanese youth are complex, ambivalent, and sometimes contradictory. Youth pursue multiple agendas—not only sectarian ones. In some cases, partisan youth even challenge their sect-based parties to develop more transparent, democratic institutions. Their efforts, however, get shut-down by political elites. Thus, while youth enjoy relative autonomy within their own political realms, the closer they come to the power of Lebanon’s elites, the more limited it becomes. This study contributes to debates on path dependency, the persistence of communal categories, and challenges dichotomous conceptions of youth politics. To understand the political role of youth as more than simply the “hope” or “threat” for democracy, I argue we must look closely at the politics of everyday life and grassroots realms, and take youth seriously as political actors in their own right.

Keywords: Ethnicity
Lebanon
Sectarianism
Students
Youth
Youth Politics
Advisor: Sandbrook, Richard
A.F. Büsching and the Place of Geographical Knowledge in the German Enlightenment, c. 1740 - 1800

This dissertation places geographical knowledge and practice in the German Enlightenment (Aufklärung). I illustrate something of geography’s constitutive sites and practical making by discussing the life and work of Anton Friedrich Büsching (1724–93), who made his name as one of the foremost geographers in the German lands and Europe through his Neue Erdbeschreibung (Hamburg, 1754–92), and through his geographical periodicals. I consider Büsching’s geographical project and its social, political and scientific contexts in three articles. The first concerns the making of geographical knowledge ‘at home’ in the context of Büsching’s geography of Asia (Hamburg, 1768) and the Royal Danish Expedition to Arabia (1761–67) organised by Johann David Michaelis. I illustrate how Büsching and Michaelis sought to integrate knowledge of the study and the field in ways that allowed them to produce more accurate knowledge of Asia’s geography, and to legitimate the credibility of textual critique in the study. I argue that understanding the relations between the constitution of the study as an analytic site and the evaluation of knowledge from the field is crucial for understanding the making of Enlightenment geography. The second article concerns the place of geography in print, and focusses on Büsching’s ‘learned newspaper’, the Wöchentliche Nachrichten (Berlin, 1773–87). I argue his periodical played a central role in reshaping the moral economy of geographical knowledge in the later eighteenth century, and show that the periodicity and materiality of the periodical genre transformed the character of geography’s authors and audiences in the Aufklärung. The final article discusses the place of politics in German geography. I argue that geography was politicised through inscriptive practices of authorship, correspondence and learned journalism, and through practices of mapping and education. Moreover, I contend that that Büsching’s geographical project was politicised through his work on the geography of the Holy Roman Empire and through his periodicals, because these works were a means for improving geo–literacy, and for engendering a sense of pride in both ‘Germany’ as a cultural nation and in Frederick II’s Prussia. Collectively, the dissertation demonstrates the centrality of Büsching’s geographical project to the making of geography in the Aufklärung.

Keywords: Book history
Enlightenment
Germany
Historical geography
History of geography
Periodicals
Advisor: Ruddick, Susan M
The Role of Fat-tails, Multiple Variance components, and Pricing Kernels in Option Pricing

My dissertation, composed of two chapters, explores the pricing of index and individual equity options contracts. These chapters make three modeling choices on (i) state variables, (ii) return innovations and (iii) the pricing kernel, and answer the question about what we can learn from stocks and options data. Both chapters specify a variance-dependent pricing kernel, which allows non-monotonicity when projected onto returns. While first chapter employs Inverse Gaussian distribution to capture fat-tailed dynamics of returns, second chapter chooses to model distribution of returns as a normal shock plus Compound Poisson jumps. Regarding the state variables, Chapter 1 uses long-run and short-run variance components, whereas Chapter 2 defines normal and jump variance components as the state variables. The first chapter nests multiple volatility components, fat tails and a variance-dependent pricing kernel in a single option model and compare their contribution to describing returns and option data. All three features lead to statistically significant model improvements. A variance-dependent pricing kernel is economically most important and improves option fit by 17% on average and more so for two-factor models. A second volatility component improves the option fit by 9% on average. Fat tails improve option fit by just over 4% on average, but more so when a variance-dependent pricing kernel is applied. Overall these three model features are complements rather than substitutes: the importance of one feature increases in conjunction with the others. Focusing on individual equity options, second chapter develops a new factor model that explores (i) if a separate beta for market jumps is needed, (ii) cross-sectional differences in jump betas of stocks, and (iii) the role of jump betas in explaining equity option prices. Differentiating between normal beta and jump beta, the model predicts that a stock with higher sensitivity to market jumps (normal shocks) have higher out-of-the-money (at-the-money) option prices. The results show that jump betas are needed to adequately explain equity options.

Advisor: Christoffersen, Peter
Illuminating Urban Grime: The Atmospheric Impact of Urban Grime Photochemistry

Deposition and subsequent processing of atmospheric species on impervious surfaces leads to the formation of surface films. Most abundant in urban environments, these films, sometimes referred to as â urban grimeâ , are thought to mediate environmental processing of species through adding an additional compartment into which species can partition, facilitating transfer of atmospheric species into surface water and promoting heterogeneous reactions. In this thesis, real urban grime samples are collected and used to investigate composition, growth characteristics, and reactivity of the less studied inorganic fraction of the film. Some of the reactions that we propose include the photochemical formation of nitrogen oxides, the formation of ClNO2 from grime chloride and the re-emission of ammonia from grime. The particular focus is urban grime photochemistry as a possible daytime source of HONO to the atmosphere. While surface nitrate/HNO3 photolysis has been previously suggested as a HONO source, it has not been previously studied using real environmental surfaces. Using a combination of laboratory and field photochemical experiments it has been found that grime nitrate undergoes photolysis to form gas phase nitrogen oxides at a rate faster than has previously been reported for aqueous nitrate, gas-phase HNO3 and surface deposited HNO3 on clean glass. This chemistry is dependent on relative humidity and only involves a fraction of extractable grime nitrate. Based on these studies, urban grime photochemistry was explored as a source of HONO using a box model. The magnitude and temporal variation of this HONO source depend on the photochemical properties of the precursor including rate constant and wavelength dependence of its absorption cross-section, the source and rate of accumulation of the precursor as well as other factors such as latitude, season.

Keywords: Atmospheric Chemistry
Nitrate
Photolysis
Urban Grime
Advisor: Donaldson, D J
Syntactic Categories Informing Variationist Analysis: The Case of English Copy-raising

This thesis uncovers and investigates of two levels of syntactic change progressing in tandem in Canadian English. One involves the complementizers (Rooryck 2000:48; López-Couso and Méndez-Naya 2012a) that link perception verbs to finite subordinate clauses, e.g. It seems (like/as if/as though/that/Ø) she's getting better quickly. The predominant variant in Canadian English is like (López-Couso and Méndez-Naya 2012; Brook 2011a, 2014) – an incoming form that now represents 68.2 percent of comparative complementizers across corpora of sociolinguistic interviews from Ontario (Tagliamonte 2003-06, 2006, 2007-10, 2010-13, 2013; Tagliamonte and Denis 2014). Looking beyond the variable context, as per Aaron (2010), suggests that a second, broader change is occurring. The entire seem* like structure is overtaking Subject-to-Subject raising (seem* to VP). Younger speakers are increasingly saying It/she seems like she’s getting better quickly rather than She seems to be getting better quickly. I find that the key variationist concept of orderly heterogeneity (Weinreich et al. 1968) applies readily to the covarying syntactic constructions despite their abstract nature. I also address the question of whether one level of change has led to the other. A methodologically comparable corpus from York, England (Tagliamonte 1996-1998, 1998) shows a low proportion of like (13.2 percent) and no broader-level change; I hypothesize that the broader-level shift depends on a certain threshold of like in the community grammar. Since like, unlike its remaining covariants, allows copy-raising (Rogers 1974, Horn 1981, Asudeh 2002, Asudeh and Toivonen 2007, Gisborne 2010, inter alia), it gives speakers the choice of a matrix NP or matrix expletive subject. Experimental/acquisitional research indicates that these two options correspond to different evidential/epistemic values (Rett and Hyams 2014); I argue that with a high proportion of like they together comprise a clear, streamlined binary system that makes Subject-to-Subject raising much less useful in comparison, accounting for its emerging decline.

Keywords: British English
Canadian English
copy-raising
dialectology
language change
syntax
Advisor: Tagliamonte, Sali A.
The Effects of Latent Categories on Product Performance: Discovery, Identification and Firm Strategy in the Context of the Motion Picture Industry

My dissertation, composed of three chapters, explores the effect of product categories, as revealed by consumers' online rental behavior, on firm performance and strategy in the movie industry. Research in sociology suggests that sorting products into cognitive categories matters for performance, but empirical studies find an inconsistent relationship between category-spanning and performance. Importantly, they do not establish the causality of this hypothesized relationship. To address these issues, the first chapter empirically identifies the relationship between category-spanning and movie performance, based on a measure of latent category coherence, entitled latent similarity, which is adapted from Zuckerman (2004). This represents a departure from existing research that relies on third-party categories to measure category-spanning, as this may not capture how consumers categorize. I evaluate a movie's latent similarity from consumers' movie rental patterns on Amazon Instant Video, which are observable in movies' "Customers who rented this also rented..." co-rental lists. The idea behind the measure is that if all of a movie's co-rentals cross-reference each other (forming closed set), then that movie has a high latent similarity measure, suggesting it is in a clear category. I find a strong positive relationship between the measure and performance, and I provide causal evidence through an identification strategy composed of instrumental variable and control function. The second chapter explores what exactly the latent similarity measure is picking up. I identify the latent categories implied by the Amazon rental data through clustering algorithms. Then, I employ topic modeling to show that the derived categories differ in the extent to which their movies share common attributes, and I develop a theoretical model to explain how consumer preferences can lead to these differences. The third chapter is an empirical investigation of studio strategies regarding their movies' category-spanning, exploring the role played by studio type in this decision. My dissertation has several contributions. First, it provides causal evidence that variation in category coherence affects performance. Second, it provides several methodological innovations for strategy in (1) adapting the Zuckerman measure to use with novel digital data, and (2) applying machine learning tools to identify and describe latent product categories.

Keywords: big data
categories
movies
strategy
Advisor: Ryall, Michael
Mixed-Signal Architectures for Spectrum Sensing

The radio spectrum is subject to temporal and geographic variations and measurements indicate low utilization below 6GHz. In response, the Federal Communications Commission sent a notice of proposed rulemaking to facilitate cognitive radio use in the licensed digital television bands. Cognitive radios identify unused spectrum segments for data transmission while minimizing interference with licensed radios. Spectrum sensing is the enabling technology and detects the presence of a signal within a frequency band. Mixed-signal architectures offer potential power savings by performing signal detection in the analog domain, significantly reducing the analog-to-digital converter (ADC) sampling rate. The integrating mixer is a novel mixed-signal architecture for spectrum sensing that is based on the short-time Fourier transform (STFT). The architecture consists of a folded double balanced mixer with capacitive loads that implements current-domain windowing in the first stage while downconversion mixing and integration is implemented in the second stage. A load capacitor array enables integration with programmable time constant. A prototype was designed and fabricated in IBM's 0.13Âľm CMOS process. The measured results indicate an average dynamic range (DR) of 24.2dB over a 2.2GHz bandwidth (BW) with a power dissipation of 1.55mW. The integrating mixer architecture is extended by utilizing binary-weighted load capacitors, which integrates the STFT signal and acts as the sampling capacitors for a successive approximation register (SAR) ADC. An array of folded mixers are utilized to remove current restrictions on the selection of the window function, which improves side-lobe reduction and fall off in the frequency domain. A prototype was designed and fabricated in IBM's 0.13Âľm CMOS process. The measured results indicate an average DR of 26.8dB over a 1.25GHz BW. The integrated SAR ADC achieves a peak signal-to-noise-and-distortion ratio of 45.4dB at a sampling frequency of 200kHz for an effective number of bits of 7.25. The power dissipation is 0.88mW for a full quadrature implementation. In comparison to recent spectrum sensing implementations, the integrating mixer prototypes achieve the lowest power dissipation while obtaining a DR that falls within the reported range. The prototypes are well suited for integration within low power cognitive radio transceivers that target portable IEEE 802.22 applications.

Keywords: Cognitive Radio
Energy Detection
Short-time Fourier Transform
Spectrum Sensing
Advisor: Chan Carusone, Anthony