VictorJuiz/thesis huggingface dataset:
Exploring the Discourse Attributes of Referential Process in Emotion Focused and Cognitive Behavioural Therapies for Depression

The referential process (RP) refers to the way one’s nonverbal experiences are translated into verbal forms (Bucci, 1993; Bucci, Maskit, & Murphy, 2015). In the context of psychotherapy, three stages of the RP – activation of emotions, symbolization, and reflection – have been presented as a general framework for understanding change (Bucci, 2013). However, most of the studies on RP has been conducted in the context of psychodynamic treatment and in single case designs. Thus, the current study examined the discourse attributes of RP using session transcripts of 40 clients who underwent 16 sessions of cognitive behavioural therapy (CBT) or emotion focused therapy (EFT) for depression.The Discourse Attributes Analysis Program (DAAP; Maskit, Bucci, & Murphy, 2012), a computerized text analysis program that measures the discourse attributes RP, were applied to 80 session transcripts. Given that some therapists had worked with multiple clients and two sessions belonged to each client, Generalized Estimating Equation (GEE) was used to account for the nested structure of the data. The DAAP measures differed between EFT and CBT in the expected ways based on the theories of change that are rooted in each modality: there were more affect words in the EFT transcripts and more reflection words in the CBT transcripts. Overall, the two modalities did not differ in terms of the major measures of RP applied to clients’ and therapists’ speech. This substantiated Bucci (2013)’s theory that RP is an atheoretical framework for understanding change. The study unveiled novel information about specific in-session therapist processes that contribute to clients’ session ratings, as well as their overall treatment outcome. Therapists whose clients belonged to the good outcome group used more concrete, imagistic, specific, and clear language in the highest client rated sessions Additionally, the more that therapists used this style of language and spent more of the sessions doing so, the greater changes their clients perceived from their sessions. These findings imply that it is important for therapists to effectively connect to their experiences and communicate themselves clearly to their clients. Theoretical, clinical, and measurement implications, limitations, and directions for future research are discussed.

Keywords: Cognitive behavioural therapy
Discourse attributes
Emotion focused therapy
Referential process
Advisor: Watson, Jeanne C
Molecular, Metabolic and Functional CD4 T Cell Paralysis Impedes Tumor Control

CD4 T cells are central effectors of anti-cancer immunity and immunotherapy, yet the regulation of CD4 tumor-specific T (TTS) cells is unclear. In this study, we demonstrate that CD4 TTS cells are quickly primed and begin to divide following tumor initiation. However, unlike CD8 TTS cells or exhaustion programming, CD4 TTS cell proliferation is rapidly frozen in place by a functional interplay of regulatory T cells and CTLA4. Together these mechanisms paralyze CD4 TTS cell differentiation, redirecting metabolic circuits, and prohibiting their accumulation in the tumor. Paralysis is actively maintained throughout cancer progression and CD4 TTS cells rapidly resume proliferation and functional differentiation when the suppressive constraints are alleviated. Overcoming their paralysis established long-term tumor control, demonstrating the fundamental necessity of rapidly crippling CD4 TTS cells for tumor progression and their potential importance as therapeutic targets.

Keywords: cancer immunology
CD4 T cells
CTLA4
Tregs
Advisor: Brooks, David G
Strategies for Pharmacological Modulation of Mitophagy

Mitochondrial damage and impaired mitophagy underly the pathogenesis of Parkinson’s disease (PD). Amongst the loci implicated with onset of familial PD are several genes that encode proteins which mediate a common goal: the removal of damaged mitochondria. Mitochondria, like other organelles, are subject to damage, which may affect lipids, DNA or proteins. The level of damage the cell can endure before its survival is compromised exists on a spectrum and there are systems the cell employs to mitigate mitochondrial damage. Pathogenic mutations in PINK1 and PRKN cause early-onset familial PD because they compromise mitophagy, a pathway employed by dopaminergic neurons to handle mitochondrial damage. Since the accumulation of dysfunctional mitochondria produces reactive oxygen species, this further perpetuates damage to lipids, DNA, and proteins in the mitochondrial milieu. Once a critical threshold of damage is crossed, a cell death program is executed leading to loss of dopaminergic neurons in the substantia nigra, the defining pathology in PD. The goal for this work is the identification of small molecules and molecular mechanisms that potentiate the mitophagy pathway, which may be advantageous for dopaminergic neurons susceptible to mitochondrial damage in the context of PD. Importantly, our strategies sought to identify molecules which function without induction of mitochondrial damage and/or apoptosis. The hope is that by bolstering mitophagy, loss of dopaminergic neurons will be slowed, leading to reduced PD-related phenotypes that arise consequently. Fortuitously, several model organisms which reflect PD pathology and systemic characteristics of the disease are available. Molecules that enhance mitophagy were tested in preclinical PD models of mitochondrial damage. This general pipeline led to the identification of ROCK inhibitors and probucol as compounds that enhanced mitophagy and these compounds demonstrably reduced PD-related phenotypes in model organisms reflecting mitochondrial damage. In addition, dissection of the mechanisms through which the molecules function illuminated new aspects of mitophagy and confirmed the idea that mitophagy enhancers may be a viable strategy for the development of PD therapeutics. Additionally, rhomboid-7 negatively regulates basal mitophagy in the dopaminergic neurons of flies. This supports the idea of PARL inhibitors as another class of mitophagy agonists and potential PD therapeutics. Using a robust eye degeneration phenotype, rhomboid-7’s possible epistatic relationships were investigated.

Keywords: mitophagy
Parkinson's disease
Advisor: McQuibban, Angus
Energy Level Alignment at Organic Semiconductor Interfaces

Organic semiconductors are promising materials for future generations of light-weight and flexible electronic devices. Several distinct functional organic semiconducting layers are usually stacked together to create a variety of devices such as organic light emitting diodes and organic solar cells. The relative alignment of each layer’s frontier molecular orbital energies with those in its adjacent layers is critical in dictating a device’s performance and functionality. With a rapidly increasing number of new functional organic semiconducting layers in modern devices, the energy level alignment (ELA) at organic-organic interfaces is becoming an increasingly crucial aspect in material selections and device design. Despite of this, there is still lack of a general scientific guideline in charting interface energy levels at such interfaces. In this thesis, a comprehensive experimental study is conducted on several dozens of organic heterointerfaces by using photoelectron spectroscopy. Broad sets of molecules having a diverse range of electronic and geometric structures were carefully selected. After correcting variables such as molecular orientation-dependent ionization energies, a general energy level alignment rule for charting interface energy levels (energy offsets and charge-transfer dipoles) over three distinct regions was found. This universal energy level alignment rule covers a wide achievable range of frontier orbital energies at organic heterojunctions, and is expected to provide a master guide in selection of new materials for fabricating future generations of superior organic semiconductor devices.

Keywords: energy level alignment
molecular orientations
organic electronics
organic heterojunctions
Advisor: Lu, Zheng-Hong
Spectralities at the Protest Chronotope: Venezuela’s Colectivos and the Opposition Social Imaginary

To talk about the 2014 and 2017 anti-government protests in Venezuela is to contend with the colectivos. According to media and NGO reports, Venezuela’s political opposition, and anti-government protesters, colectivos played a vital role in helping to ensure the survival of the government of President Nicolás Maduro during both waves of months-long unrest. In these accounts, colectivos were the shock troops of the Bolivarian Revolution, conducting widespread acts of unchecked violence and intimidation against anti-government protesters and activists, often rivaling and even surpassing official state authorities in both effectiveness and brutality. These accounts of Venezuela’s colectivos stand in contrast not only to how the groups tend to operate in the country, but also obscure their complex history and their shifting relationship with the Venezuelan state.My dissertation provides a qualitative exploration of this contrast by drawing from semi-structured interviews with anti-government protesters, as well as from open source visual data from protests. Through this approach, I place the contrast between Venezuela’s colectivos as they exist today and how they exist in media, NGO reports, and opposition narratives within the context of the union cívico-militar, the overarching ideological ordering structure of Venezuela. In doing so, I argue that opposition protesters drew from and contributed to an “opposition social imaginary”: that is, a shared set of normative beliefs and values in which colectivos hold a place shaped in part by decades-old race-and-class prejudices endemic to Venezuelan society. I argue that this imaginary is the source of the commonplace depictions of colectivo members as violent, fanatical, and remorseless. Finally, I argue that whereas this imaginary ascribes a highly collaborative relationship to colectivos and the Venezuelan state, no such relationship is needed for groups like colectivos and other non-state actors to antagonize anti-government demonstrators at protests. Rather, it is the particularities of the space and time of the protest that engender ad hoc, tenuous, collaborative arrangements between state and non-state actors.

Advisor: Jauregui, Beatrice
Practice Patterns and Health Outcomes of Adjuvant Oxaliplatin Chemotherapy for Colorectal Cancer

INTRODUCTION: Oxaliplatin-containing adjuvant chemotherapy improves survival for stage III colon cancer. Yet it is not without harms, most commonly dose-dependent peripheral neuropathy. The 2018 International Duration Evaluation of Adjuvant Chemotherapy (IDEA) trial sought to determine the optimal duration of adjuvant therapy by evaluating the non-inferiority (NI) of 3 versus 6 months of treatment. The 3-year disease-free survival probability was 74.6% in the 3-month group versus 75.5% in the 6-month group (HR 1.07, 95% CI 1.00-1.15; pNI = 0.11). There remain open questions regarding how these findings changed practice, whether these outcomes are obtained in the general population, and – given oxaliplatin-induced neuropathy – the relationship between treatment duration and post-treatment falls. METHODS: We leveraged linked administrative and population-based datasets held at ICES to conduct three retrospective cohort studies of patients with stage III colon cancer in Ontario, Canada. First, we employed interrupted time series regression and mixed models to evaluate the association between IDEA’s publication and prescribed treatment durations. Second, we utilized overlap propensity score-weighted survival models to determine the relationship between treatment duration and mortality. Third, we again used weighted survival models to examine the association between treatment duration and fall-related injury. RESULTS: IDEA’s publication was associated with a 16.4% (95% CI 12.5-20.3%) absolute increase in patients treated with ≤50% of a 6-month course of therapy. Between-prescriber variation strongly influenced treatment duration in the post-IDEA period (median odds ratio 2.10 [95% CI 1.73-3.18] for short-duration treatment). Treatment with 50% of a 6-month course of therapy was associated with a HR of 1.13 (95% CI 0.88-1.47) for overall mortality versus >85% of a 6-month course of therapy. Meanwhile, treatment with >85% of a 6-month course of therapy conferred a HR of 0.84 (95% CI 0.62-1.13) for fall-related injury. CONCLUSION: Although IDEA could not conclude non-inferiority of 3 to 6 months of adjuvant therapy, the trial rapidly shifted clinical practice while introducing greater provider-level practice variation. While intuitive concerns about the relationship between oxaliplatin and fall-related injury are not borne out in the data, evidence from routine practice solidifies that treatment duration is a preference-sensitive decision involving a tradeoff between survival and toxicity.

Keywords: chemotherapy
colorectal cancer
neuropathy
non-inferiority
oxaliplatin
practice variation
Advisor: Baxter, Nancy N
Modeling Poteomes of Neurodevelopment and Disease in Human Cerebral Organoids

Understanding the molecular programs orchestrating human neuronal maturation remains one of the final frontiers in neuroscience. Neurogenesis during human brain development is a tightly organized and highly critical process, wherein the differentiation of neural progenitor cells to mature neurons produces the full complement of neurons required for an adult brain. These stages follow very stereotypical spatiotemporal patterns with different regions of the subventricular zone forming distinct neuronal subtypes before transitioning to gliogenesis later in development. While much of our current understanding of brain development and function is based upon a long history of observational and functional studies in animal models and static human autopsy tissue, the uniqueness of the human brain suggests the need for alternative ways to more accurately model human physiological processes. To expand our insight and systems-level understanding of human neuronal differentiation and maturation, I utilized proteomic assays to probe the neurobiology driving maturation of human neuronal populations using the rapidly evolving tridimensional system of brain organoids. By leveraging mass spectrometry-based proteomics to molecularly profile precursor and neuronal niches of human-derived organoids, I developed an approach which can be used to study temporal and cell-type-specific protein dynamics in developing cerebral organoids. This unique resource served as a valuable tool to nominate previously unappreciated genes in neurodevelopment and disease, such as RUVBL2, which was conserved between precursor compartments of brain organoids and human fetal tissue. In addition to these spatially- defined proteomes, this work also revealed numerous proteins within the doublecortin (DCX)+ neuronal cell compartment with timepoint-specific expression patterns. Among these proteins, I uncovered the potential role of FABP7 in neurogenesis and highlighted its common clinical phenotypes and molecular mechanisms in patients with neurodevelopmental disorders. Together, the goal of this work is to highlight a generalizable approach to study dynamic spatiotemporal changes in the post-transcriptional molecular landscape of developing cerebral organoids offering valuable insight into critical pathways and candidates setting up brain development and disease.

Advisor: Diamandis, Phedias
Online Learning and Optimization in Communication Networks

In this thesis, I propose new online learning and optimization approaches to evaluate and design communication networks by investigating unknown system variation, feedback delay, and communication efficiency over time. The results of this thesis provide new analytical insights and design guidelines that will help to improve future communication networks. In the first part of this thesis, we consider periodic decision updates for constrained Online Convex Optimization (OCO). This is motivated by many practical wireless communication systems, which only permit a fixed decision update over multiple time slots, while the environment changes between the decision epochs. We propose an efficient online algorithm, which employs a periodic virtual queue together with aggregated gradient descent for decision updates. We evaluate the performance of theproposed algorithm in a large-scale multi-antenna system shared by multiple wireless service providers. In the second part of this thesis, we study OCO with long-term constraints in the presence of multi-slot feedback delay. We propose an efficient online algorithm, which uses a double regularization together with a penalty mechanism on the long-term constraint violation, to tackle the asynchrony between information feedback and decision updates. We apply the proposed algorithm to solve a general network resource allocation problem. In the third part of this thesis, we exploit over-the-air computation to jointly optimize the training of the global model and the analog aggregation of the local models over time for federated learning (FL). We propose an efficient algorithm to adaptively update the local and global models based on the time-varying communication environment. The trained model is both channel- and power-aware, and it is in closed form incurring low computational complexity. We derive performance bounds on both the computation and communication performance metrics. In the last part of this thesis, we encourage temporal similarity in the decision sequence over time to control the communication overhead in online distributed optimization. We propose an efficient algorithm, which uses a tunable virtual queue together with a modified Lyapunov drift analysis to jointly consider computation and communication over time. We apply the proposed algorithm to enable communication-efficient FL.

Keywords: Distributed Computation
Mobile Communications
Networked Systems
Online Learning
Stochastic Optimization
Advisor: Liang, Ben
Dong, Min
Common Ownership in Syndicated Loan Markets and Disclosure of Mutual Fund Performance

This dissertation investigates the role of financial institutions, which are important external capital providers for firms and exert significant influence on various aspects of corporate behaviors. In Chapter 1, I examine the impact of interconnections among institutional investors on credit markets. In Chapter 2, I study the disclosure practices of mutual funds.Chapter 1 studies whether economic interconnectedness among contracting parties is associated with reduced agency frictions in debt contracting. Using common ownership (CO) among lenders to identify economic connections and a strict research design, I document that when CO between a participant lender and lead lenders is higher, the participant takes a larger share of the loan. The inferences are robust to using financial institution mergers as plausibly exogenous variation in CO and to controlling for alternative mechanisms. In addition, I show that the effect of horizontal CO on the loan structure is more salient when incentives for tacit coordination are stronger. Finally, I find that risk-taking incentives in managerial compensation decrease with vertical CO between the borrower and lead lenders, suggesting that compensation contracts may serve as a plausible channel by which vertical CO reduces agency frictions. Chapter 2 investigates the disclosure of mutual fund performance by focusing on S&P 500 index funds. My examination is motivated by a new SEC rule to promote clear and concise disclosure for fund investors. Based on the guidance and requirements in the SEC rule, I develop a custom measure of information density of management discussion of fund performance (MDFP) in annual shareholder reports. I define information density as the number of facts required by the SEC final rules scaled by the length of the MDFP, showing the extent to which fund managers deliver key information within a reasonable length of text. I provide evidence that information density predicts future fund flows and reduces investors’ reliance on past fund performance. Further, investors rely more on fund disclosure instead of past performance when the economic uncertainty is lower and when the relative importance of fund disclosures is higher (i.e., signals of past performance are weaker and disclosure of performance is more credible).

Advisor: Hope, Ole-Kristian O
The Real Subalgebras of $\mathfrak{so}_4(\mathbb{C})$ and $G_{2(2)}$

Classifying the subalgebras of a simple Lie algebra is a pursuit that stretches back to the work of Cartan on representations of simple Lie algebras. Mal'cev, in classifying orthogonal and symplectic representations of simple Lie algebras also found the semisimple subalgebras of $B_n, C_n,$ and $D_n$. Following that, Dynkin and Minchenko classified the semisimple subalgebras of the complex exceptional Lie algebras. We investigate the real subalgebras of a number of rank 2 Lie algebras: $\mathfrak{so}_4(\mathbb{C})$, its real forms, and the split real form of $G_2$, $G_{2(2)}$. In this thesis, we classify the real subalgebras of these Lie algebras up to inner automorphism (i.e., up to the adjoint action of the corresponding Lie group). For the matrix algebras above, we largely proceed with the help of copious amounts of linear algebra. For $G_{2(2)}$, we take advantage of the Cartan decomposition $G_{2(2)} = \mathfrak{k} \oplus \mathfrak{p}$, where $\mathfrak{k}$ is a compact subalgebra, to identify the semisimple and Levi-decomposable subalgebras of $G_{2(2)}$. To find the solvable subalgebras, we use the classifications of semisimple and nilpotent elements of $G_{2(2)}$, as well as our own classification of Jordan elements, to build nilpotent and solvable subalgebras.

Keywords: conjugacy
representations
subalgebras
Advisor: Repka, Joe