VictorJuiz/thesis huggingface dataset:
Lung Defects Contribute to Respiratory Symptoms in a Mecp2-mutant Mouse Model of Rett Syndrome
Keywords: Lipid metabolism
MECP2
Pulmonary function
Pulmonary surfactant
Rett syndrome
Translational medicine

Rett syndrome (RTT) is a progressive neuro-metabolic disorder caused by mutations in the X-linked gene, methyl-CpG-binding protein 2 (MECP2). After a period of seemingly normal post-natal development, RTT patients experience a developmental regression, consisting of loss of acquired verbal and motor skills, stereotypic hand movements, respiratory abnormalities, and seizures. Respiratory impairment causes up to 80% of premature patient death; despite this, lung pathology in RTT is understudied and respiratory symptoms are currently attributed to neuronal loss of MECP2. To study the Mecp2-deficient lung, we utilized a Mecp2-mutant mouse model that recapitulates many features of RTT. I found striking lipid metabolism abnormalities in the lungs of Mecp2-mutant mice, including increased cholesterol and triglycerides and decreased phosphatidylcholines. My single cell RNA-sequencing and chromatin immunoprecipitation experiments showed that lipogenesis is increased due to decreased binding of the nuclear repressor coreceptor 1/2 (NCOR1/2) complex in the promoters of its target genes in the absence of MECP2, leading to their upregulation. I also showed that lung AE2 cell-specific depletion of Mecp2 is sufficient to cause lung lipid metabolism abnormalities and respiratory symptoms. In contrast, hindbrain neuron-specific deletion of Mecp2, which removes Mecp2 from the neuronal respiratory control center, imparted a different respiratory phenotype. RNA-sequencing of the Mecp2-deficient lung revealed decreased expression of key extracellular matrix (ECM) genes; consistently, I found alveolar tissue degradation and bronchiolar enlargement in Mecp2-mutant mice. Consistent with these findings, Mecp2-mutant mice have altered pulmonary function. Finally, we treated whole body metabolism in Mecp2-mutant mice using lipid-modulating compounds, including statins and liver X receptor (LXR) agonists; both improved neurological and respiratory symptoms, suggesting clinical utility. Altogether, these findings implicate key functions of Mecp2 in the lung and highlight the importance of studying non-neuronal aspects of RTT. Our findings will aid in developing treatments and clinical recommendations for RTT patients.
Uberizing the Legal Profession? Three Essays on Lawyers in Digital Platform-based Legal Services
Keywords: lawyers
online gig work
professional autonomy
professional identity
professional status
professional stratification

Using a set of data from an Internet-based legal service platform in China, this thesis examines the impacts of digital platform-based legal services on lawyers and their work. With interview data with lawyers actively working on this platform, Chapter 1 finds that supplementary income and flexibility are the two major motives for lawyers to engage in platform work. Nevertheless, when working online, lawyers face lower intra-professional status and lower professional autonomy. Despite its growth, the digital legal market is imposing a minimal threat to the traditional legal market due to the lack of interference in labour supply and demand between these two markets.Building on the concept of “counter-institutional identity”, Chapter 2 uses a grounded theory approach to develop a theoretical model that explores the processes of the emergence of identity threats and lawyers’ coping tactics as they work on this platform, a work setting that opposes the dominant norms in the legal field. I find that identity threats emerge when lawyers’ existing professional identity is challenged by counter-institutional work features. Moreover, some lawyers are able to restructure their professional identity to adapt to the counter-institutional work, while some are prone to protect their old identity and resist changes. Individuals’ belief in professional dynamism, the belief that the legal profession is and will be experiencing constant changes, underlies the divergence between identity restructuring and protection. Chapter 3 examines the ways in which technology-driven innovations impact professional stratification in digital platform-based legal services. With topic modeling to uncover the platform work content and thereby locate the involved lawyers’ market positioning, this study finds that digital platform-based services are dominated by low-status personal legal work. No evidence is found for higher levels of activity among young and female lawyers on this platform, suggesting that digital platform-based practices may not enlarge the disparities between demographic groups of lawyers. Moreover, digital legal work provides more equal opportunities for disadvantaged lawyers: young lawyers have earnings advantages over older lawyers and a gender earnings gap is not observed.
Queering App-propriate Behaviours: The Affective Politics of Gay Social-sexual Applications in Toronto, Canada
Keywords: affect theory
gay men
internet
poststructuralism
queer theory
socio-sexual applications

In conversation with affect theory, queer theory, and relevant social scientific literature, this thesis investigates the affective and feeling politics of gay socio-sexual applications (GSSAs). Specifically, this thesis investigates how GBQ men’s understandings of emotional connections—a term used in GSSAs, such as Grindr, to advertise the potentialities of such applications—are involved in the socio-sexual politics and constitution of normative gay men’s sexual subjectivities online and how online outreach workers and social service workers are implicated in and involved with such politics. Applying a feminist poststructural affect theory lens, this thesis uses Jackson and Mazzei’s (2011) process of “plugging-in” with different poststructural theories, such as Michel Foucault’s (1991) governmentality, Julia Kristeva’s (1982) abjection, and Sara Ahmed’s (2004a, 2004b, 2010a, 2010b) affective economies and promises of happiness to analyze what I term “fractions” of data. In the first data chapter, I apply Foucault’s theorization of governmentality to argue that subjects learn to navigate GSSAs through discourses of emotional regulation and restraint, while analyzing the politics of “emotional risk.” In the second data chapter, I apply Kristeva’s (1982) theorization of abjection to argue that the abjection of others and the abjection of the “self” take place within GSSAs through the rejection of emotional dependency upon others, romantic love, as well as the aspiration for neoliberal norms of individuality. In my third data chapter, I apply Sara Ahmed’s (2004a, 2004b, 2010a, 2010b) work on the promises of happiness and affective economies to argue that GSSAs promote certain affective economies of confidence and self-assuredness whereby subjects are encouraged to perform neoliberal subjectivities through promises of self-pleasure. In particular, I note how GSSAs, such as Grindr, hold differing “promises” for individuals that keep subjects bound to them and using them, even if they might seek to disconnect from such applications. Within each data chapter, I write a Deleuzian “intermezzo” section in reflection on my experiences in what I term “thinking/feeling/writing” within the affective assemblages of my research project. I close with a very un-final not-conclusion that articulates some further thoughts for online outreach as well as my own becomings within my research.
Creativity as Intra-action: Relational Entanglement and Creative Becoming within the Space of Schooling
Keywords: Creativity
Ethnographic Research
Philosophy of Education
Relational Sociology
Social Justice Education
Social Theory

This thesis explores creativity as a relational process of entangled becoming and develops a relational theory of creativity as intra-action (Barad, 2007) which is then put to work to conduct an analysis of everyday creation within the space of schooling. Engaging with central debates in new materialism and posthumanism this thesis explores the intra-active entanglements at the heart of everyday schooling. An intra-active approach to creativity foregrounds how the material and the discursive, the human and the nonhuman, are ongoingly entangled in processes of co-creation and attunement (Ingold, 2017a) throughout everyday life culminating in larger processes of worldmaking (Goodman, 1978).This perspective is developed in contrast with the prevalent view of creativity as a human-centred ability or instrument for success; a view that is central to both human capital and neoliberal approaches creativity. This prevalent view, I argue, ultimately distorts and obscures the rich creative dynamism at the heart of everyday intra-active entanglements. Integrating classroom observations, interviews, and a craft activity, in this research I seek to better understand What types of intra-active entanglements characterize the space of schooling? How are students intra-actively entangled in the material-discursive reconfiguration of the world within the space of schooling? And what kinds of new and alternative realities become possible as a result of these differential entanglements? Through a meticulous analysis of the intra-activity central to schooling, this research illustrates that young people participate in significant intra-active processes of co-creation renegotiating the basic outlines of the material-discursive in subtle ways. Equally, however, despite this rich intra-activity, the participants in this study consistently characterized their own creative processes as relatively inconsequential, failing to measure up to the standard of ‘real’ creativity. This analysis demonstrates how the radical reimagination of everyday space as relational and intra-active can reveal important processes that often remain unheeded. It suggests the need for an alternative discursive framework that challenges the individualistic and instrumental while forefronting the powerful possibilities of everyday becoming latent in the material-discursive entanglements central to schooling.
The Utility of Brain Imaging to Advance Clinical Decision Making for Trigeminal Neuralgia
Keywords: Diffusion Tensor Imaging
Neurosurgery
Pain
Tractography
Treatment Response
Trigeminal Neuralgia

Trigeminal neuralgia (TN) is a devastating chronic pain disorder, characterized by extremely severe, recurrent, lancinating attacks of unilateral facial pain. While the diagnosis and treatment of TN primarily focuses on neurovascular compression of the trigeminal nerve at the root entry zone, other etiological factors and therapeutic strategies exist. Understanding the different subtypes of TN and who best responds to treatment is an important, unmet challenge in the field. Advances in brain imaging techniques, in particular diffusion tensor imaging (DTI), have offered a non-invasive, in vivo avenue to study TN and its pathophysiology. Importantly, these techniques may serve as an objective, clinically translatable tool to guide treatment decision making in the clinic. Therefore, the overall goal of this thesis is to demonstrate the utility of brain imaging to advance clinical decision making for TN patients. In Study 1, I determine whether early, post-treatment DTI metrics at the radiosurgical target can predict long-term clinical response in TN patients. In Study 2, I define a new subtype of treatment-refractory TN and investigate its clinical and neuroimaging features. Lastly, in Study 3, I examine the relationship between brainstem trigeminal fiber microstructure and treatment response across different subtypes of TN. I found that 1) early, post-treatment target DTI metrics can predict long-term clinical response in TN patients treated with radiosurgery, 2) a new, unique subtype of TN can be defined for patients who present with a single pontine lesion and are refractory to surgical management, and 3) abnormalities in the brainstem trigeminal fiber microstructure is a key characteristic of treatment non-response across a large cohort of TN subtypes. In conclusion, this thesis demonstrates the significance of advanced brain imaging in the clinical setting to optimize treatment decision making and elucidates the mechanisms that underlie treatment response in the TN population.
Systems for CO2 Utilization: Property Measurement and Electrocatalytic Conversion
Keywords: Carbon dioxide utilization
CO2 reduction
Electrocatalysis
Microfluidics
Phase properties
Renewable energy

Carbon dioxide (CO2) emissions account for approximately 80% of anthropogenic contributions to greenhouse gas emissions and there is a growing need for CO2 utilization strategies. CO2 at supercritical conditions can be employed as a green solvent for extractions and separations, or can be injected in the subsurface for storage. CO2 can also be used as a reactant, a raw material to be converted into valuable chemicals via electrocatalysis. It is likely that all such approaches are needed, and more, to substantially reduce greenhouse gas emissions. The study of the physical and chemical properties of CO2 informs these climate-critical CO2 mitigation approaches. Understanding the CO2 phase behavior of complex fluid mixtures – liquid, gas, supercritical – at different thermodynamic conditions is essential to many industrial and chemical processes. In this work a phase behavior measuring chip was developed that can simultaneously determine the phase behavior of fluids at multiple combinations of temperature and pressure within the application’s scope. This phase chip testing method demonstrated a hundredfold decrease in the processing time comparing to the current industrial testing processes while maintaining experimental resolution and high accuracy (Chapter 3). At the same time, this work provides a platform for exploring CO2 mixture phase behavior, interface behavior, and mass transport. Electrochemical reduction of CO2 to valuable liquid fuels and chemical feedstocks is a sustainable approach to intermittent electricity utilization. Gas diffusion heterogeneous reaction electrodes facilitate effective CO2 mass transport to the catalyst, enabling electrolyzers to operate at the current densities required for industrial deployment. However, the complex interactions between a solid catalyst, liquid electrolyte, and gas reagents of heterogeneous electrodes significantly influence the CO2 reduction reaction (CO2RR) performance. This work focuses on CO2 local availabilities/pressure (Chapter 4), microstructure wetting capabilities (Chapter 4), pH distribution (Chapter 5), and electromigration (Chapter 5) with the goal of improving the performance of the CO2 reduction reaction (CO2RR) in practical systems. Together these efforts improve efficiencies, selectivities, and current densities of CO2 electrocatalytic systems, and advance the field of CO2 utilization more generally.
Predictive Impact of Rare Genomic Copy Number Variations in Infant Siblings of Individuals with Autism Spectrum Disorder
Keywords: Autism Spectrum Disorder
Copy Number Variation
Microarray
Whole Genome Sequencing

Autism Spectrum Disorder (ASD) is a prevalent neurodevelopmental disorder characterized by social communication deficits and the display of restrictive, repetitive behaviors. Given the extensive genetic landscape of ASD, profiling genetic risk in individuals with a higher probability of developing the disorder due to family history would complement the observation of behavioral markers in infancy and assist in diagnosing ASD early in development when therapeutic interventions would be most beneficial. In this work, I present the first copy number variant (CNV) analysis in 288 prospectively recruited infant sibling cohort from 253 families as part of the Baby Sibling Research Consortium. By age 3, 103 siblings (35.8%) were diagnosed with ASD and 54 (18.8%) were developing atypically. Thirteen siblings had CNVs at ASD-relevant loci: 6 with ASD, 5 atypically developing, and 2 typically developing. Eleven of 157 infant siblings (7%) with a confirmed ASD diagnosis or who were deemed atypically developing at 36 months of age had a genetic finding that would have been predictive of their developmental outcome. Within these families, an ASD-related CNV in a sibling has a positive predictive value (PPV) for ASD or atypical development of 0.83. Most notably, I identified a 90 kb deletion of the third exon of PTCHD1-AS, located on chromosome X (Xp22.11), in 3 related male siblings with ASD. I present genomic and phenotypic data for 109 males and 45 females with disruptive variants in PTCHD1 obtained from ASD and clinical genetic datasets. Investigation of their phenotypes revealed that males with exclusive disruptions of the lncRNA present with an increased frequency of ASD and a Broader Autism Phenotype (BAP) and fewer comorbidities than males with deletions spanning the upstream protein coding gene PTCHD1. To further study the function of this gene, I have identified the syntenic transcript in the mouse brain and profiled its isoforms. Expression analysis on various brain regions identified highest expression in the mouse cortex, in early development (post-natal day 7). I have generated 3 mouselines with disruptions of Ptchd1-as, of which one is currently being characterized as part of a collaborative effort to uncover the function of this lncRNA.
Path Following Control for Multiple Quadrotors Carrying A Rigid-body Slung Payload
Keywords: Multi-body dynamics
Nonlinear control
Quadrotor
Robust control

Novel robust path-following flight controllers for quadrotors carrying a tethered payload are extensively studied from the perspective of dynamic modelling, control design, and experimental verification. By using multiple quadrotors to cooperatively carry a payload, their payload capacities can be significantly boosted. The number of vehicles can be adjusted according to the weight of the payload, resulting in a flexible and efficient use of drone resources. The presented model development starts from a single quadrotor with a point-mass payload to multiple quadrotors with a rigid-body payload. The payload is towed by quadrotors with cables. The systems are decomposed into the payload subsystem and the quadrotor attitude subsystem by assuming the cable is tethered at the center of mass of each quadrotor. The controller designs are then developed for a single quadrotor with a point-mass payload, followed by controller of multiple quadrotors with a rigid-body payload. Both controllers resemble a cascade form in structure. The outer loop offers a robust path-following controller that stabilizes the payload subsystem by assuming the lift vector of each quadrotor can point instantaneously to a given direction. An uncertainty and disturbance estimator is designed to estimate and eliminate the lumped disturbances caused by exogenous wind and parameter imperfection. The inner loop, on the other hand, is an attitude tracker implemented on each quadrotor to follow a reference attitude generated by the outer-loop controller. The overall stability of the complete system is proven using the Lyapunov method and the Reduction Theorem. Aside from the analytical control law, a model predictive controller (MPC) method is also studied and implemented on quadrotor for cooperative slung payload delivery. The MPC method utilizes the equivalent damping force from the previous controller as the baseline stabilizing inner loop. The linearized closed-loop model is then calculated. Finally, the optimum controller is calculated after a prediction horizon and a cost function are defined. The MPC scheme achieves better performance and requires less parameter tuning. Extensive simulations and experiments show that the controller designs are capable of stabilizing the payload under model imperfection and exogenous disturbances simultaneously.
On the Generation of Theta Rhythms in the Hippocampus
Keywords: biophysical modelling
computational neuroscience
hippocampus
inhibitory classes
local field potentials
theta rhythms

A prevalent local field potential (LFP) rhythm in the CA1 hippocampus associated with memory processing and spatial navigation is the (3-12 Hz) theta oscillation. Theta rhythms emerge intrinsically in an in vitro whole hippocampus preparation. This system makes it possible to assess the contribution of different cell types, a problem that remains unresolved, in the absence of state-dependent confounding factors typically encountered in vivo. To decipher the theta generation mechanism we leverage insights from minimal models in application to biologically detailed ones. We extract a piece of a previously published full CA1 model, the segment model, on which we test minimal model hypotheses. We distinguish the pyramidal (PYR) cells as the theta rhythm initiators whose activity is regularized by inhibitory cells supporting an ‘inhibition-based tuning’ mechanism. We find a strong correlation between the PYR cell input currents and the resulting theta frequency, establishing that the intrinsic PYR cell properties underpin frequency characteristics. We analyze contributions of external drives and find that strongest theta responses are generated by the hippocampus CA3 while weakest responses are induced by inputs from the CA1. Subsequently we turn our attention to the full CA1 model and explain the theta activities it produces according to our gathered insights. We demonstrate that the termination of PYR cell theta bursts relies on sequential activation of distinct inhibitory cell classes. Two main types of inhibitory cells have been considered particularly important for the generation of theta rhythms, the parvalbumin-positive (PV+) and the somatostatin positive (SOM+) cells. Having demonstrated the importance of PV+ cells in theta generation, we turn to the SOM+ oriens lacunosum-moleculare (OLM) cells, a heavily studied cell class whose role is still unclear. We find that OLM cells regulate the robustness of the LFP laminar polarity profile without affecting average power, a robust response that depends on co-activation of distal inhibition and basal excitation. Finally, we estimate the spatial extent of the theta LFP, and predict that about 22,000 PYR cells participate in intrinsic theta generation. The work presented in this thesis provides a cellular-based foundation from which in vivo theta activities can be explored.