VictorJuiz/thesis huggingface dataset:
Stabilized discretizations for fluid flows and coupled poromechanics
Keywords: Engineering.

In this thesis we develop various stabilized spatial discretizations for fluid flow problems and coupled poromechanics. We start by considering isogeometric collocation methods, which have arisen as an efficient alternative to Galerkin discretizations for high-order simulations of mechanics. We wish to apply theses schemes to incompressible flow problems, which requires the development of appropriate stabilization strategies. The classical SUPG method is extended to a collocation setting, which stabilizes spline collocation schemes in highly advective regimes. Simultaneously, we show that PSPG stabilization allows one to collocation mixed problems with an equal-order scheme. We show that these stabilizations are effective are removing instabilities while also retaining the inherent high-order accuracy of spline collocation methods when applied to the scalar advection, incompressible Stokes, and incompressible Navier-Stokes equations. Continuing the focus on isogeometric collocation methods, we move on to consider applications in compressible flows. Stabilization strategies are again needed, in this case so that the scheme can handle shocks. We extend a residual-based, artificial viscosity method for this purpose, and we develop a projection-inspired alternative to SUPG stabilization. Results on a variety of conservation laws show the robustness of the stabilized scheme, again without sacrificing accuracy on smooth problems. We then turn away from isogeometric collocation methods and pure fluid flow problems. The latter half of the thesis considers coupled poromechanics, or the coupled problem of flow through a deformable porous media. We consider spatial discretization using a coupled finite element - finite volume approach using piecewise linear and piecewise constant representations for mechanics and flow, respectively. While commonly used in practice, this discretization choice will exhibit pressure instabilities as undrained conditions are approached due to a lack of inf-sup stability. We show that pressure jump stabilization is effective at removing spurious pressure oscillations that appear in the nearly undrained burden regions when simulating CO2 sequestration, and study numerical properties such as the proper selection of stabilization constants for different meshes. Finally, we consider the performance of iteratively, or sequentially, coupled schemes for poromechanics when undrained regions are present. We clarify the relationship between fractional step schemes and the inf-sup condition, and in particular note that the fact that sequential schemes do not form or invert the full saddle-point matrix at any point is not enough to conclude that spurious pressure oscillations will not appear. However, pressure jump stabilization can be trivially extended to the fixed-stress method considered, and this both removes spurious pressure oscillations and improves the efficiency of the scheme.
Strontium clock atom interferometry for fundamental physics
Keywords: Humanities and Sciences.
Physics.

Clock atom interferometers, quantum sensors based on the interference of atomic matter-waves excited by resonant pulses of light, show promise for measurements of industrial use as well as tests of fundamental physics. The fundamental advance of clock atom interferometry is the use of optical transitions with exceptional lifetime as the basis of the interferometer, giving new capabilities to what has become a standard technique. Although they are already showing performance that by some metrics surpasses the best devices using conventional matter-wave optics, more development is required for clock atom interferometers to be deployed in next-generation sensors. This thesis documents the development of two future experiments that aim to apply clock atom interferometry to questions in fundamental physics. The QMATCH experiment is designed to measure the electric charge of nominally neutral atoms beyond the limits of the best classical tests, using the scalar Aharonov-Bohm effect. MAGIS-100, currently under construction at Fermilab, is a 100 m-scale atom interferometer that aims to search for ultralight dark matter and to serve as a pathfinder for future gravitational wave observatories based on clock atom interferometry. In addition, this thesis reports a novel technique for matter-wave optics in alkaline earth atoms, exciting the 3P0 clock state of bosonic Sr-88 using a novel three-photon process in a collinear geometry.
A structural and functional investigation of inhibitory synaptic transmission
Keywords: Medicine.
Structural Biology.

Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter of the mammalian central nervous system. Neurons release GABA to shunt or prevent action potentials from propagating in target cells, and this process is critical to providing a dynamic regulation of overall neural circuitry. Chapter 1: I briefly introduce neurotransmission and focus on inhibitory neurotransmission mediated by GABA signaling. Chapter 2: I describe the development of an anti-vGAT recombinant Fab domain used to purify intact inhibitory GABA SVs from mouse brains and the subsequent structural characterization of these vesicles using electron microscopy. I also describe the use of these vesicles in a functional assay that directly probes the membrane association and membrane fusion of GABA synaptic vesicles. The results in this chapter have been published in the journal Current Research in Physiology in their special edition issue on neurotransmitter transporters. Chapter 3: Following the success of the vGAT Fab domain in purifying GABASVs, I describe the development of a molecular toolbox for the isolation and study of other types of vesicular neurotransmitter transporters and SVs using the recombinant Fab domain approach. The results shared in this chapter are preliminary, and the work is ongoing. Chapter 4: I use the recombinant anti-vGAT Fab domain to isolate detergent-solubilized vGAT from rat brains for structural characterization via CryoEM. The results shared in this chapter are preliminary, and the work is ongoing. Chapter 5: I describe an orthogonal structural characterization of purified GABA synaptic vesicles using high-resolution CryoEM. More specifically, the structure of the native vacuolar ATPase was investigated in the context of GABA SV membranes to determine its direct binding partners. The results shared in this chapter are preliminary, and the work is ongoing.
Systems and synthetic biology approaches enable first-principles models of transcription in human cells
Keywords: Engineering.
Bioengineering.

The binding of multiple transcription factors (TFs) to genomic enhancers activates gene expression in mammalian cells. However, the molecular details that link enhancer sequence to TF binding, promoter state, and gene expression levels remain opaque. We applied single-molecule footprinting (SMF) to measure the simultaneous occupancy of TFs, nucleosomes, and components of the transcription machinery on engineered enhancer/promoter constructs with variable numbers of TF binding sites for both a synthetic and an endogenous TF. We find that activation domains enhance a TF's capacity to compete with nucleosomes for binding to DNA in a BAF-dependent manner, TF binding on nucleosome-free DNA is consistent with independent binding between TFs, and average TF occupancy linearly contributes to promoter activation rates. We also decompose TF strength into separable binding and activation terms, which can be tuned and perturbed independently. Finally, we develop thermodynamic and kinetic models that quantitatively predict both the binding microstates observed at the enhancer and subsequent time-dependent gene expression. Chapters 2-4 provide a template for quantitative dissection of distinct contributors to gene activation, including the activity of chromatin remodelers, TF activation domains, chromatin acetylation, TF concentration, TF binding affinity, and TF binding site configuration. Chapter 5 demonstrates how novel large serine recombinases can facilitate highly controlled and fast parallel DNA reporter assays by integrating linear DNA library members into landing pads. Chapter 6 characterizes how transcriptional run-on between two tandem genes can lead to unexpected gene expression dynamics in synthetic gene systems. Taken together, this thesis provides novel biological insights and tools to advance understanding and engineering of gene expression in human cells.
Three essays on international trade and innovation
Keywords: Humanities and Sciences.
Economics.

This dissertation consists of three essays spanning the topics of international trade and innovation, with specific attention to their underlying legal institutions. In the first chapter, I address the role of non-uniform trade policy in a world where firms are known to be heterogeneous. Since much firm-level policy occurs unilaterally and outside of negotiated most-favored nation tariff rates, exploring governments' strategic incentives in sequential-move environments is of interest. Compared to an existing heterogeneous-firm model with non-uniform tariffs, I add simplifying functional form assumptions that then allow me to add strategic behavior into the model. In particular, I allow one country to act as a Stackelberg leader in setting trade taxes, and I find that it always elects to impose a tax, and that the tax is larger than it would be if the follower were not expected to respond. I also discuss the specific policy avenues that are available to governments for levying non-uniform tariffs on firms and relate the situations in which these avenues may be used to forces and incentives in my model. In the second chapter, joint with Lisa Ouellette, I turn to innovation policy and consider the market for vaccines. We review and synthesize research from a broad array of disciplines including economics, law, and public health, documenting the outsized benefits of vaccines juxtaposed with a seemingly anemic development pipeline. Vaccines have many attributes that are understood in the economic literature to limit the rents that a monopolist can extract. Most importantly, they are durable goods, and they are preventatives. Starting from this understanding, we argue that market-based innovation incentives, such as patents, will under-provide such goods relative to goods without these properties, even though the social benefit of such goods may be far greater. In the third chapter, I consider international patenting flows and leverage the European Patent Office's DOCDB database, which contains detailed international patent bibliographic data, to consider patent application filings as a measure of knowledge diffusion and domestic knowledge production. After describing the international patenting regime and the incentives that drive it, I document a clear relationship between a country's market size and both its domestic knowledge production and its reception of foreign knowledge diffusion. I also find that, although bilateral patent flows resemble bilateral trade flows in that they increase with the size of the source and destination countries, distance does not play as clear a role in moderating patent flows as it does with trade in goods.
Tools for coronary MR angiography : non-cartesian trajectories and motion-corrected reconstructions
Keywords: Engineering.
Bioengineering.

X-ray coronary angiography remains the predominant technique for coronary artery examination, yet it exposes both patients and operators to ionizing radiation and is invasive. Despite strong demand for non-invasive and safer alternatives, the clinical adoption of coronary MR angiography has been slow. The primary challenges in coronary MR angiography are its prolonged scan time and limited resolution. Because coronary arteries often follow tortuous paths and have relatively small diameters, high resolving power is required. Additionally, whole-heart imaging is preferred over target-volume methods, as it reduces operator dependency. Achieving large volumetric coverage at high resolution demands collecting a significant amount of data. However, continuous myocardial movement restricts data collection to specific cardiac cycles, necessitating the segmented data acquisition over multiple heartbeats. Consequently, coronary MR angiography is slow and susceptible to both respiratory and cardiac motion. This dissertation introduces several tools for coronary MR angiography categorized into non-Cartesian trajectory design and non-rigid motion-corrected reconstruction. Non-Cartesian trajectories often exhibit higher sampling efficiency and greater robustness against undersampling compared to traditional rectilinear approaches, making them particularly useful for reducing the overall scan duration. Because non-rigid models capture a wide range of transformations, non-rigid motion-corrected reconstruction reduces resolution loss due to respiratory and cardiac motion.
Toward preventing traumatic brain injury : evaluation and design of modern helmet technologies
Keywords: Engineering.
Bioengineering.

Traumatic brain injury is a prominent global health issue affecting tens of millions of humans per year. Contact sports, in particular, present a particularly high risk of concussion (a form of mild traumatic brain injury) as well as repeated, subconcussive head impacts that can accumulate over a lifetime and are associated with development of neurodegenerative diseases in later life. This dissertation seeks to determine the efficacy of modern head protective technologies being utilized to reduce the risk of brain injury, with a specific focus on American football athletes. First, an instrumented mouthguard device was used in a field study to determine the factors affecting the severity of head impacts experienced in American football athletes, ultimately finding that significant differences in impact severity could not be detected between two existing helmet models on the field. Therefore, three modern devices that represent dramatic changes to helmet technology were evaluated to determine how they could improve impact safety. Using a large-scale test methodology that simulates impacts using the head, neck, and torso of two anthropomorphic test devices, the first technology explored was one that couples a helmet and shoulder pads as one unified piece of protective equipment. Next, both laboratory and field data were collected to determine the efficacy of a widely adopted padded helmet shell cover. While these first two technologies seek to improve safety by making additions to existing helmet technology, soft hydraulic shock absorbers were explored as a means of replacing existing helmet components to improve safety. A physical prototype of a wearable hydraulic shock absorber was developed, tested alongside existing state-of-the-art helmet shock absorbers, and implemented into a full helmet system for impact testing. Finally, a finite element model of an American football helmet comprised entirely of liquid shock absorbers was developed and evaluated alongside existing helmet models for its performance under impact loading representative of concussive and subconcussive impacts. The results of this research demonstrate the promise, and limitations, of modern helmet technologies targeted towards preventing traumatic brain injury.
A transcriptional switch underlies the pro-and anti-inflammatory activities of afucosylated and sialylated IGG glycoforms
Keywords: Medicine.

Antibodies play a crucial role in bridging the gap between the innate and adaptive immune systems by serving as a link that connects these two components of the immune response. They recognize specific antigens on pathogens, facilitating recognition and response by innate immune cells. Additionally, antibodies contribute to immunological memory, allowing the adaptive immune system to mount a faster and more specific response upon re-exposure to the same pathogen. This coordination enhances the overall effectiveness of the immune defense against infections. IgG Fc glycosylation serves as a mechanism to enhance the versatility of antibody function by altering its affinity for specific activating and inhibitory Fc-gamma receptors. This, in turn, regulates Fc-mediated effector functions and influences the innate immune response directed toward target pathogens. However, the precise impact of different IgG glycoforms on immunity in frequently infected sites, such as the lungs, remains unclear. In Chapter I, I review the literature regarding IgG Fc glycosylation, Fc-gamma receptor functions, and the impact of both on human disease outcomes. In Chapter 2, my colleagues and I use mass spectrometry to identify specific IgG glycoforms that correlate with COVID-19 disease trajectories. We identify a correlation between afucosylated IgG abundance and more severe disease outcomes as well as an enrichment of sialylated IgG in protected patient populations. In Chapter 3, we investigate how these glycoforms impact the local immune response within the lungs of Fc-gamma receptor-humanized mice at the functional and transcriptional levels. We identify the transcription factors NF-κB and REST as likely regulators of immune complex-mediated inflammation within the lung. Altogether, we identify a transcriptional switch that underlies the pro- and anti-inflammatory activity of afucosylated and sialylated IgG in the lung mediated by the transcription factors NF-κB and REST that may have relevance in human disease.
Untouchable : on the cultural politics of hands in Modern China
Keywords: Humanities and Sciences.
East Asian Languages and Cultures.

This dissertation explores the representation of touch and tactile culture in modern Chinese literature, film, and visual culture. The project investigates the many powers invested in human hands through narrative, taking a particular interest in the discourses that contribute to the construction of "untouchable" people and groups at various historical junctures. I argue that hands and protocols of touch are situated at the crux of major ideological and political tensions from the early Republican era to the new millennium. By examining how contentions about labor, sexuality, modernity, and national survival are played out in discourses of hands, my analysis offers fresh readings of seminal cultural texts and interrogates existing assumptions about intimacy and alienation in the modern era. This project not only contributes to the China field's emerging interest in sensory experience—which has been mostly limited to discussions of visuality, sound, and taste—but also opens up a new vista for sustained future inquiry about how tactility interacts with sight, taste, scent, and sound in a comprehensive aesthetic discourse of the body.
Using foundation models to learn how to represent electronic health records
Keywords: Engineering.

The invention and use of electronic health records has enabled new applications of machine learning in the field of healthcare. One particularly important application is the use of machine learning to predict the risk of a variety of clinical outcomes given electronic health records. However, training machine learning models on electronic health records is often challenging due to limited data set sizes and the intrinsic complexity of electronic health record data. In this dissertation, I propose and validate the use of foundation models as a way to learn representations for electronic health records, taking advantage of the longitudinal structure of medical record data to learn transferable representations. These representations can then be used to improve our ability to predict patient risk, achieving superior ranking performance, increased robustness across both time and space, and better label efficiency.
Waste monitoring and management for improved water quality and soil health
Keywords: Engineering.

Good water quality and soil health are fundamentally important to planetary (human and environmental) health, which poor waste management practises can jeopardize. Waste monitoring and management strategies can impact and influence water quality and soil health. The research in this dissertation examines these in specific contexts, with a specific focus on community needs. In so doing, it aims to contribute to achieving Sustainable Development Goals (SDGs) related to zero hunger, clean water and sanitation, responsible consumption and production, and life on land. This thesis consists of three research chapters. Chapter 2 investigates fecal contamination of stored water supplies in rural Kenyan households, identifying ruminant feces as a significant source and elucidating transmission pathways. Chapter 3 explores the production of soil amendment biochar from cacao husks in Malaysia, optimizing reactor designs and characterizing biochar properties. Chapter 4 examines the impact of biochar on soil and cacao sapling growth, which demonstrated mixed results but revealed potential benefits and areas for improvement. The findings in this dissertation underscore the importance of community-centered approaches and highlight the complexity of ensuring that waste management ultimately does remediate and ameliorate water quality and soil health. Recommendations for future research include exploring the conceptual models underpinning the research to ensure that each link of the causal chain is rigorously examined such that risks are adequately quantified, processed improved, or expenditure and effort towards interventions justified. Ultimately, the dissertation emphasizes the value of holistic, locally informed solutions to address environmental degradation and promote sustainable development. While the research presents promising avenues for enhancing water and soil quality, it underscores the need for careful consideration of unintended consequences and community perspectives in advancing sustainable development goals.
Wavefunction-based simulations : dynamics of quantum many-body systems
Keywords: Humanities and Sciences.
Applied Physics.

Many exotic phases of matter, such as quantum spin liquid (QSL) and high temperature superconductivity, are associated with strong correlations between constituent particles. Yet theoretical analysis is largely hindered by the strong interactions. Numeric simulations, although facing the challenge of exponential complexity, have provided valuable theoretical insights and connections to experiments. In this work, I present wavefunction-based numerical methods to study strongly correlated systems with an emphasis on dynamics, which can provide extra information about the excitations in the system, connect theoretical modeling with experimental spectroscopies and can reveal interactions in the system. After an overview, I will first discuss characterizations of the QSL on a triangular lattice through dynamical spin structure factor and Raman scattering. The QSL phase shows distinct spectral features, among which a prominent chiral excitation in Raman spectra signals proximity to chiral ordering. I then present the study of salient spectral features observed in recent angle resolved photoemission spectroscopy experiment on a one-dimensional cuprate. These spectral features can be well reproduced by adding extended electron-phonon couplings, which enhances superconducting pairing correlations in 1D and may help the establishment of superconductivity in 2D. Finally, I present a time-dependent nonequilibrium study and show cuprates superconductivity could potentially be enhanced via laser driven photodoping. I conclude with some ideas to go beyond the results presented in this thesis.