VictorJuiz/thesis huggingface dataset:
Empirical analysis of complex wavefields
Keywords: Geophysics.

The principal focus of this thesis is exploring the passive seismic wavefield, including both ambient seismic noise and earthquake ground motion. On the one hand, ambient noise, though appearing to be a nuisance and treated as an unwanted component, has seen flourishing applications in the past decades. However, the discrepancy between the reality of noise properties and theoretical assumptions leads to considerable bias in those applications. A better understanding of the noise wavefield is therefore crucial. One the other hand, significant earthquakes pose continuous threats to human life and habitat. Mitigating seismic hazard demands detailed knowledge of these seismic waves that carry tremendous energy and cause damage. In this thesis, I first give a background introduction on seismic wavefields and the connection between seismic noise and earthquake ground shaking. Then I demon- strate that it's possible to convert the noise data into signals, which can be used to simulate long-period earthquake ground motion. I introduce an improved multi-component C3 method. It enhances the signal-to-noise ratio of the simulation and yields more reliable amplitude estimates. Starting from a puzzling observation, I carefully examine the C3 method and propose a new interpretation of it. Inspired by this insight, I develop a modified signal processing procedure that increases the resolving power of traditional seismic interferometry techniques on relatively sparse networks. I then switch the focus to the coda of repeating earthquakes, which are used to extract velocity perturbations. Studying earthquake coda provides insights into the coda of correlations. The chapter following focuses on the spatial variability of earthquake ground motions by exploring the similarity of earthquake recordings on dense seismic arrays. The spatial coherence revealed from waveform similarity is consistent with that from amplitude measurement
Empirical assessment of practices and bias across diverse research domains
Keywords: Epidemiology and Population Health.

Research today is expensive, time consuming, and low yield. Much work has been done to describe research practices and quantify biases that may contribute to this. However, new ways of conducting research are constantly being proposed. Potential biases may not be as well characterized for these new fields. I aimed to describe the prevalence of practices and potential for biases in three relatively new and fast-growing fields. Specifically, these included: comparative oncology trials in domestic dogs, E-values for sensitivity analysis in observational studies, and machine learning diagnostic tools. Primary research articles were systematically retrieved from literature databases. Data regarding research methodology, reporting, and study results were extracted. In addition to field-specific findings, conserved trends were observed across multiple fields, including a reluctance to report experimental details, a tendency for facile automation in methods and interpretation, and an opportunity to learn from adjacent fields. The present study identifies pitfalls that threaten the validity, generalizability, and clinical value of these three fields of research and provides recommendations for improvement
Enabling gaze-contingent accommodation in presbyopia correction and near-eye displays
Keywords: Electrical Engineering.

Humans rely on several different depth cues to navigate the world around them. Among the most important cues are accommodation (refocus) and vergence (inward and outward rotation). Though accommodation and vergence are neurally linked processes, there are situations in which they fall out of synchrony; specifically, we address two seemingly unrelated issues: presbyopia and virtual and augmented reality (VR/AR). In the former, the crystalline lens within the eye itself loses the ability to accommodate due to it stiffening as a function of age. This stiffening defines presbyopia and occurs in all humans, with diagnosis typically in their late 40s. In the latter case of VR/AR, a viewer is forced to fix their accommodation to the single plane of a display while the display's stereoscopic image encourages their eyes to verge to arbitrary distances to achieve a sense of three dimensionality. In both cases, the viewer is no longer able to accommodate naturally. Traditionally, presbyopia and VR/AR optics have been static, making it difficult to approximate the abilities of the once pliable crystalline lens—inherently trading off acuity, field of view, or stereoacuity in exchange. On the other hand, a more dynamic, gaze-contingent solution requires focus-tunable lenses and eye trackers to properly mimic the accommodation reflex. We built and evaluated gaze-contingent optical systems for use in presbyopia correction and VR/AR, with our solutions outperforming traditional ones on both quantitative and qualitative measures
Engineered biomaterials as intestinal epithelial cell culture platforms
Keywords: Chemical Engineering.

The intestinal epithelium is a tissue structure that is intimately involved in human health, and is awash in an ocean of cue from their surrounding extracellular matrix and from adjacent cell types. In the midst of such an environment, the intestinal epithelium serves an integral purpose as the de facto barrier which orchestrates the dynamic, homeostatic equilibrium between the inside of the organism and the outside world. Unfortunately, diseases involving the gastrointestinal epithelium are all too common in humans. This abundance of digestive diseases has driven the desire to develop engineered models of the intestine, in order to study disease progression in simplified, controlled environments. Polymeric biomaterials are increasingly the focus of approaches to engineer models of the intestinal epithelium. These materials can be coarsely grouped into two main categories: synthetic and naturally-derived materials. In this thesis, strategies are presented which hybridize these synthetic and naturally-derived categories to produce improved models for intestinal epithelial cell culture. The first section of this dissertation details the use of a protein-engineered biomaterial as a culture substrate to improve the physiological accuracy of a commonly used preclinical model of drug absorption. We found that by independently tuning Elastin-Like Protein biomaterial stiffness and the density of a peptide ligand that engaged the mechanotransductive integrin receptors of Caco-2 cells, engineered matrices of lower stiffness and lower integrin-engaging peptide sequences resulted in the formation of Caco-2 monolayers that were more permissive to paracellularly transported drug molecules. The work described in the next section progresses from the 2D model described above, towards models in 3D, while still leveraging the ease and utility of epithelial cell lines. This section of work describes a two-component biomaterial system that is used to create a 3D hydrogel environment in which epithelial cells were encapsulated and cultured, and demonstrates these biomaterials as suitable for Caco-2 and MDCK-II spheroid culture. In the final section of this work, Hyaluronan Elastin-Like Protein (HELP) biomaterials are studied for the 3D culture of human patient-derived intestinal enteroids. This section describes one of the first synthetic, engineered materials for patient-derived enteroid culture, and demonstrates the wide-ranging utility of HELP biomaterials for epithelial organoid culture. In total, this work further solidifies the usefulness of engineered, tunable, and well-defined biomaterials in systematic studies which aim to affect relevant phenomena in intestinal epithelial model systems. The use of HELP biomaterials is the apex of the progression of this work, integrating multiple types of engineered materials, for the 3D culture of a highly physiologically relevant cell type. This material can now be used to study more applied phenomena in the intestinal organoid model system, as a compelling avenue of further study
Engineered biomaterials for therapeutic optimization of cardiovascular interventions
Keywords: Bioengineering.

Ischemic heart disease continues to represent the leading cause of death worldwide, annually accounting for 10 million deaths globally and 1 in 7 deaths in the United States. Current treatment of severe coronary disease and acute myocardial infarction typically relies on reperfusion therapies, including fibrinolytic therapy, percutaneous coronary intervention, and coronary artery bypass grafting. These methods, while successful at restoring macrovascular blood flow after infarction, inadequately address residual microvascular perfusion deficits resulting in cardiomyocyte death, downstream ventricular remodeling, progression to heart failure, and early mortality. Additionally, following myocardial infarction and/or a cardiac operation, patients can develop Dressler's syndrome, or post-cardiac injury syndrome, where inflammation and scarring form cardiac adhesions resulting in increased risks during secondary cardiac operations. This dissertation discusses several projects related to ischemic heart disease and its multiple sequelae. This work demonstrates improved human mesenchymal stem cell (hMSC) culture techniques by culturing hMSCs on chemically oxidized polystyrene substrates. This technology could be utilized in cell therapy applications where timely access to high quantities of hMSCs is difficult due to cell culture constraints. This thesis also examines the use of a photosynthetic oxygen delivery system that rescues the myocardium following acute ischemia. Finally, the use of a dynamically crosslinked polymer-nanoparticle (PNP) hydrogel adhesion barrier is explored for the prevention of cardiac post-operative adhesions or post-cardiac injury syndrome. The PNP hydrogel adhesion barrier significantly reduced adhesions in both rodent and ovine models of cardiac adhesions. These results are expanded to post-operative peritoneal adhesions and result in a significant reduction in peritoneal adhesions following abdominal surgery
Engineering alternative splicing devices for mammalian synthetic biology
Keywords: Bioengineering.

From the approximately 20,000 genes embedded in DNA genomes to the functional proteins they encode for, much of the functional diversity of mammals can be attributed to alternative splicing, a pre-messenger RNA processing mechanism that produces multiple proteins from a single gene through careful arrangement of exons into a final transcript. While synthetic biology harnesses natural sequences refined by genetic evolution to build new functions from modular DNA components in engineered biological systems, few systems have leveraged alternative splicing as a precision tool for genetic control in mammalian systems. Combining the evolved mechanisms of splicing regulation with the ability to produce multiple, distinct proteins from a single gene, alternative splicing in synthetic genetic devices expands our capacity to control mammalian systems for medical, industrial, and biological discovery platforms. We have developed a class of mutually exclusive alternative splicing devices that can express two distinct isoforms based on which one of two internal exons is included in the final RNA molecule. In our efforts to engineer these devices for novel functions to control biological systems, we expanded the functional outputs of our alternative splicing devices using modular protein domains and fluorescent proteins, in addition to updating previous design considerations that limited our initial efforts, such as size and sequence constraints. Our ability to regulate outcomes from alternative splicing devices is important for their use as genetic transcriptional tools for mammalian synthetic biology. We modify our intron framework to support the production of both isoforms at various ratios based on mutations and truncations to consensus elements responsible for alterna- tive splicing. We explored synthetic approaches to controlling isoforms, such as the CRISPR-Cas13 RNA-targeting system and the MS2 protein aptamer, that allowed us to shift splicing patterns in a dynamic fashion. Our strategy to controlling isoform outcomes and protein functionality replicates how evolution evolved RNA splicing for a synthetic alternative splicing device. We present the design, construction, regulation, and versatility of alternative splicing devices. Their unique ability to compress genetic information combined with transcriptional regulation tools, both naturally encoded and artificially introduced, advances the novel mechanism we can harness to engineer biology
Engineering and imaging nonlocal spin dynamics in an optical cavity
Keywords: Physics.

Photon-mediated interactions between atoms coupled to an optical cavity are a powerful tool for engineering entangled states and many-body Hamiltonians. These applications motivate the construction of an optical cavity enabling coherent nonlocal spin interactions, with transverse optical access for high-resolution imaging and addressing of atomic sub-ensembles. Using this apparatus, we implement a nonlocal Heisenberg Hamiltonian, where the relative strength and sign of spin-exchange and Ising couplings are controllable parameters. This tunability enables the demonstration of an interaction-induced protection of spin coherence against single-atom dephasing terms. The optical access afforded by a near-concentric cavity facilitates local control and imaging of the magnetization for Hamiltonian tomography and spatially resolved detection of the spin coherence. Imaging also allows for the first observation of cavity-mediated spin mixing in a spin-1 system, a new mechanism for generating correlated atom pairs. Whereas the single-mode cavity most naturally mediates all-to-all couplings, I will also discuss progress in generalizing to control the distance-dependence of the interactions, with prospects in engineering the spatial structure of entanglement. I furthermore propose and analyze two specific protocols in quantum control enabled by strong and tunable atom-light interactions. I first introduce a protocol that enables entanglement-enhanced measurements near the Heisenberg limit while reducing technical requirements on detection. This is accomplished via an interaction-enhanced readout that relies on reversing the sign of global Ising interactions. Dispersive atom-light interactions also enable heralded schemes, in which a high-fidelity pure state is produced upon probabilistic detection of a single photon. In this context, I show how a time-shaped single-photon pulse can ``paint'' an arbitrary superposition of coherent spin states while avoiding infidelities due to finite cavity linewidth
An engineering approach to uncover interactions between bacteriophages, bacteria and mammalian cells
Keywords: Bioengineering.

The hypothesis driving my thesis is that a major role that bacterial viruses (bacteriophages) may play in the body is to collaborate with the host immune environment to clear a bacterial infection. To probe this question, the existing techniques that can be applied to study bacteria:bacteriophage interactions such as viral particle-based plaque assays are limited to measurements at single points in time and for a bulk population of bacteria and viruses. A relevant experimental model for observing phage-immune interactions will be tripartite: the simultaneous observation of bacteriophages within host bacteria phagocytosed by immune cells. In this thesis, I present three projects that probe how bacteriophages influence the success of bacterial infections of immune cells. In the first, I develop a new method to multiplex the engineering of fluorescent life-cycle reporters into the lysogenic lambda phage. These reporter phages are used to create engineered E. coli lysogens which are infected into macrophages and tracked with live-cell imaging to study prophage induction at the single-cell level. Next, I demonstrate for the first time that prophages induce from phagocytosed E. coli in 20% of the infected macrophages. Furthermore, through a dual bacterial strain infection strategy, I show that the bacteriophages released from one strain of E. coli are functional and can kill other E. coli within the same macrophages. These prophage induction events occur in phagocytosed E. coli at a 26-fold higher frequency than basal levels, suggesting that a factor in the macrophage environment actively triggers the induction process. Finally, through the use of bacterial single gene knockouts, I demonstrate that the PhoP pathway, which responds to outer membrane stress from magnesium limitation, acidic pH and antimicrobial peptides, is involved in the induction process. I identify the mammalian-produced antimicrobial peptide, mCramp1, to be a novel inducer of bacterial prophage induction mediated by PhoP. This thesis suggests several possible new mechanisms by which bacteriophages function to assist the bacterial-killing activity of macrophages
Engineering heterologous hosts for the production and study of fungal lignin-degrading enzymes
Keywords: Chemical Engineering.

Lignin is the second-most abundant biopolymer on Earth and has significant potential as a renewable source for commodity chemicals yet remains vastly underutilized. The lack of an established route to lignin deconstruction means that the primary value of industrial lignin by-products is heat and electricity by incineration. Molecular decomposition of lignin would yield derivatives with economic value in chemical and material applications typically reliant on petroleum. Biological catabolism of lignin by wood-decaying basidiomycete fungi is widespread in nature and presents scalable and renewable means of its deconstruction under mild conditions. However, basidiomycete fungi remain genetically intractable and challenging to cultivate rapidly, limiting their utility in the industrial production of lignin-degrading enzymes. Efficient heterologous production of basidiomycete lignin-degrading enzymes has also proven elusive, hampering efforts toward engineering a biochemical route to the valorization of lignin. In this dissertation, I present efforts aimed at overcoming this major obstacle in the field of lignin degradation. I demonstrate that, despite extensive optimization, the model yeast host Saccharomyces cerevisiae is unable to produce most of the lignin-degrading enzymes tested, especially the main agents of fungal lignin degradation, heme peroxidases. In contrast, the model plant host Nicotiana benthamiana natively produces heme peroxidases for cell wall biogenesis, and I found that this host is well-suited for heterologous production of fungal lignin-degrading peroxidases as well as the majority of lignin-degrading enzymes tested. This approach enabled assay of these enzymes in different combinations on a model lignin dimer, revealing different modes of action. Finally, I describe identification of two null mutants of S. cerevisiae that exhibit increased secretion of multiple fungal lignin-degrading peroxidases. This work represents a significant advance in the development of a biochemical route to lignin valorization, with implications for the understanding of biological lignin degradation as well as of factors required for successful production of proteins in heterologous hosts
Engineering novel peptide agonists of the glucagon-like peptide-1 receptor
Keywords: Chemical and Systems Biology.

Understanding the molecular operations of G-protein coupled receptors and their ligands is a central goal in the project of understanding human physiology and altering it with pharmacological agents to improve human health. Receptors in GPCR class B have pharmacological and structural features that are distinct among GPCRs because they are evolutionarily adapted to bind and respond to short, alpha-helical peptide ligands instead of small molecule ligands. The glucagon-like peptide-1 receptor (GLP-1R) is a class B G-protein coupled receptor and diabetes drug target expressed mainly in the pancreatic β-cells that, when activated by its agonist GLP-1 after a meal, triggers insulin secretion and β-cell survival and proliferation. The best-studied agonist peptides, GLP-1 and exendin-4, share sequence homology at their N-terminal region; however, modifications to this region that can be tolerated are not fully understood. In this work, I have used combinatorial peptide screening coupled with chemical exploration with non-canonical amino acid substitutions to find novel and highly active GLP-1R agonists with altered N-terminal composition and to explore the principles that govern peptide activity
The engineering of sentiment and desire : unraveling the aestheticized politics of ideotainment in China
Keywords: Communication.

We are entering into a post-truth era where the divide between propaganda, news, and entertainment is increasingly blurred. With the aid of social media, propaganda seeps into the interstices of everyday life and becomes pervasive, unobtrusive, and ambient. This is especially the case in authoritarian regimes. My dissertation investigates the shifting paradigm of propaganda in China, particularly an emerging trend on social media known as ideotainment, in which ideological messages are packaged in entertaining forms such as hiphop songs, short videos, photo-editing apps, and interactive mini-games. Much of the ideotainment content is produced and/or promoted by state-run media in China. Through case studies of viral ideotainment campaigns (with up to several billion page views) and interviews with their producers in Chinese state-run outlets in 2018 and 2019, this dissertation reveals how the Party-state appropriates digital technologies and popular culture genres to reinforce the legitimacy of the political regime, incorporating entertainment and the logic of play into a process of ideological subjectification that taps into netizens' nationalist sentiment and materialistic desires. It also traces the continuity and discontinuity between the Chinese Communist Party's pre-digital propaganda arts since 1930s and social media-based ideotainment in the current era. On the one hand, this dissertation documents the Party's long tradition in utilizing cultural entertainment as a means of propaganda that thrives on different media forms and technologies; on the other hand, it examines how media convergence in China over the past decade has afforded new possibilities for the innovation of propaganda and thought work. This dissertation makes both theoretical and empirical contributions to propaganda studies, China studies, and digital journalism studies