VictorJuiz/thesis huggingface dataset:
From Genomic Sequencing to Cerebral-Based Weaponry: The New Frontier of the People’s Liberation Army’s Military Technology
Keywords:  Center for International Security and Cooperation
Genomic Sequencing
Academy of Military Medical Sciences
Academy of Military Sciences
Military Technology
Biotechnology
Brain-Computer Interface
Command and Control
Command, Control, Communications, Computers
Cyberspace Agency of China
Chinese Communist Party
China Electronics Technology Corporation
Chinese Military Commission
Defense Advanced Research Projects Agency
Deep Brain Stimulation
Defense Intelligence Agency
Electroencephalogram
Integrated Joint Operations Platform
Intelligence, Surveillance, and Reconnaissance
Military-Civil Fusion
Next-Generation Sequencing
National University of Defense Technology
People’s Liberation Army
People’s Republic of China
Research and Development
State-Owned Enterprise
Strategic Support Force
Science and Technology Commission
Transcranial Magnetoelectric Stimulation
Text
Thesis

The People Republic of China’s 2020 “14th Five Year Plan” – the cornerstone for Chinese national defense posture and economic planning – is the first guiding document to highlight the strategic importance of biotechnology in China’s history. Yet there has been very little awareness or response among U.S. policymakers and experts to the Chinese military’s rapidly evolving biotechnology programs. This thesis is the first study to comprehensively evaluate the scope and status of the People’s Liberation Army’s (PLA) biotechnology capabilities, ranging from emerging biotechnologies to advanced tools already deployed from the Chinese arsenal. To understand the evolution of the PLA’s biotechnology programs and milestones, this thesis collected an original dataset of over 500 open-source Chinese language documents, ranging from Chinese Communist Party (CCP) white papers to Chinese military scientific journals and Chinese news publications. Through two case studies – an investigation of the PLA’s brain-computer interface capabilities and a study of China’s large-scale genomic sequencing programs – this thesis examines the PLA’s strategies for developing and deploying biotechnologies at scale. This analysis first concludes that late-stage partnerships between commercial Chinese biotechnology organizations and military research groups have been an effective avenue for the Chinese military to pursue rapid development of militarized biotechnology. Second, the CCP’s efforts to concentrate technological capabilities under centralized umbrella organizations have proven to be an efficient strategy for deployment. By more fully understanding the PLA’s biotechnology capabilities and deployment strategies, U.S. policymakers and research institutions can work together to better respond to this growing national security risk.
From structure to function : learning principles of tissue behavior from architecture
Keywords: Microbiology and Immunology.

Immunological processes occur in microenvironments; local milieus of cells, molecules and other factors that drive and tune the process of interest. If an immunological process is essential, its microenvironment will develop into a more complex tissue structure. Tissue imaging lets us observe these structures directly and the new wave of highly multiplexed imaging platforms paints their cellular and molecular composition in unprecedented detail. Early highly-multiplexed tissue imaging data revealed that the microenvironments in healthy and diseased tissues were much more diverse and complex than we had anticipated. This presents the opportunity to develop new classes of therapeutics and biomarkers targeting microenvironments rather than molecules. However, first we must improve our ability to interpret the biology underlying the complex structure of tissue microenvironments. We developed a framework for using spatial data to elucidate the specific tissue behavior and misbehavior of disease processes while also learning general principles, such as how tissues reuse useful programs or are co-opted by malignancy. Here, we introduce a theoretical biological model of tissue behavior and an accompanying computational framework, termed Tissue Schematics. We develop and apply this framework in human lymphoid tissue, the immune tumor microenvironment, and autoimmune type 1 diabetes. Lastly, we discuss how the computational analyses will lead to hypothesis-driven experimentation. This framework aids in generating hypotheses surrounding disease origins and avenues for early diagnostics and therapies
From the front line to the living room and back again : pedagogical pleasure in board game play
Keywords: Theater and Performance Studies.

Through an exploration of the pleasure derived from playing Eurogames, a subset of board games that gained popularity in the mid to late 20th century in the geographic West, gaming is a performative act that not only relies upon pedagogical and ideological structures of meaning-making, which influences the way players see and interact with the world around them. Ideologies configure the behaviors of those within and under it, influencing how one constructs their ideas and values. Through an analysis of mechanical and narrative components of the game themselves as well as the theoretical frameworks that surround critical pedagogy, pleasure activism, and ideological value formation, play is essential to understanding the self, the Other, and the world, but within a space dedicated to exploration rather than outcome (i.e. a platform such as Eurogames). Play is often relegated to spaces outside of what the West considers "work" and due to this designation, game play allows people to explore the world around them without the larger ideological frameworks at work outside of the game. Eurogames, through an exploration of how they work upon the psyche and sociality of players, participate in a process where players can instill justice and liberation into the things that we enjoy, the things they find pleasure in. Pleasure, in this sense, is also an activist framework in which players have the potential to create liberatory spaces through an engagement with games, but only within the limitations that both the game and the social world around the game provide. Ultimately, board games, particularly Eurogames, can be analyzed through the lens of pedagogical pleasure in play to explore the ways that these cultural materials participate in performances of social justice, community-building, and equity-making
Full waveform inversion by model extension : a robust method to estimate the seismic propagation velocity in the subsurface from recorded seismograms
Keywords: Geophysics.

Seismic imaging is an effective method to produce accurate maps of the Earth's subsurface, and has been employed for decades in global seismology, hydrocarbon exploration, geothermal energy production, and more recently CO2 sequestration and monitoring. In complex geological settings, the quality of such maps highly depends on having a reliable seismic velocity model, which can be difficult to obtain. In this thesis, I develop a novel method, namely full waveform inversion by model extension (FWIME), designed to produce accurate acoustic velocity models of the subsurface from seismic recordings when conventional methods fail. I leverage the robust convergence properties of wave-equation migration velocity analysis (WEMVA) with the accuracy and high-resolution nature of acoustic full waveform inversion (FWI) by combining these techniques into a compact, mathematically consistent, and user-friendly workflow. By doing so, I mitigate the need for accurate initial models and the presence of coherent long-offset and/or low-frequency energy within the recorded data, which are difficult and costly to acquire but often necessary for conventional methods to succeed. The novelty of my method resides in the design of a custom loss function and the optimization strategy I develop to pair WEMVA with FWI, which is more efficient and powerful than applying each method separately or sequentially. I illustrate the potential of my proposed method by accurately inverting datasets generated by realistic 2D benchmark models which simulate complex and challenging geological scenarios encountered in field applications. In each scenario, the dataset lacks low-frequency energy and the initial velocity model is inaccurate, which prevents conventional methods from recovering useful solutions. In addition, I develop an efficient 3D numerical implementation of FWIME with the use of general-purpose graphics processing units (GPU) to handle 3D field datasets containing tens of terabytes of information, and to recover billions of unknown parameters. I successfully apply FWIME to a 3D ocean-bottom-node dataset acquired by Shell in the Gulf of Mexico. I show that my method outperforms conventional FWI and manages to improve the velocity model and the resulting subsurface image quality
Functional genomic analysis identifies novel regulators of germline development using flatworm models
Keywords: Bioengineering.

Schistosomes are parasitic flatworms causing one of the most prevalent neglected tropical diseases, schistosomiasis, from which over 250 million people are suffering. With a further 800 million at risk of infection, schistosomiasis imposes a global socioeconomic burden comparable to that of tuberculosis, HIV/AIDS, and malaria. Only a single, partially effective drug is available to treat the disease. These parasites have high fecundity and their eggs are both the transmissible agents and the cause of the infection-associated pathology. Despite the biomedical significance, molecular mechanisms that regulate schistosome reproduction and germline development are only now being understood. Through single-cell RNA sequencing and functional genomic analysis, we first discover that the schistosome germline stem cells (GSCs) derive from a population of somatic stem cells in juvenile parasites. This cell lineage expresses a schistosome specific factor, which we name eled. Through loss-of-function studies, we find that eled prevents the premature differentiation of GSCs. Second, we identify a gene regulatory circuit that balances the output of proliferation and differentiation of the schistosome male GSCs. This program is controlled by onecut, a homeobox transcription factor, and boule, a highly conserved mRNA binding protein essential for germline development in many animals. The germline specific expression of these regulators is conserved in the planarian, the free-living evolutionary cousin of the schistosome, but the function of onecut and boule has been modified to support GSC maintenance. Altogether, my thesis provides important insights to understand the fate regulation and evolutionary adaptation of germline development
Functional neural network surrogates trained on scarce data
Keywords: Energy Resources Engineering.

Neural networks (NNs) are often used as surrogates or emulators of partial differential equations (PDEs) that describe the dynamics of complex systems. A virtually negligible computational cost of such surrogates renders them an attractive tool for ensemble-based computation, which requires a large number of repeated PDE solves. Since the latter are also needed to generate sufficient data for NN training, the usefulness of NN-based surrogates hinges on the balance between the training cost and the computational gain stemming from their deployment. To reduce this cost, we propose to use multifidelity simulations in order to increase the amount of data one can generate during the allocated computing time. High-, and low-fidelity images are generated by solving PDEs on fine and coarse meshes, respectively; these multifidelity data are then patched together in the process of training a deep convolutional NN (CNN) using transfer learning. This strategy is further generalized to incorporate three levels of multifidelity data. We use theoretical results for multilevel Monte Carlo to guide our choice of the numbers of simulations (and resultant images) of each kind. This multifidelity training is used to estimate the distribution of a quantity of interest, whose dynamics is governed by a system of nonlinear PDEs with uncertain/random coefficients (e.g., parabolic PDEs governing the dynamics of multiphase flow in heterogeneous porous media). Our numerical experiments demonstrate that a mixture of a comparatively large amount of low-fidelity data and a much smaller amount of high-fidelity data provides an optimal balance between computational speedup and prediction accuracy. When used in the context of uncertainty quantification, our multifidelity strategy is several orders of magnitude faster than either CNN training on high-fidelity images only or Monte Carlo solution of the PDEs. This computational speedup is achieved while preserving the accuracy of the estimators of the distributions of the quantities of interest, as expressed in terms of both the Wasserstein distance and the Kullback--Leibler divergence. To further reduce the cost of data generation, we demonstrate that one can start the CNN training for a new task (a given set of PDEs describing, e.g., reactive transport) from a CNN that was originally trained for a different task (another set of PDEs, e.g., for multiphase flow). Our numerical experiments show that this transfer learning approach yields a considerable speedup when applied to the problem of the estimation of the distribution of a quantity of interest, whose dynamics is prescribed by a system of nonlinear PDEs for advection-dispersion transport in porous media with uncertain/random conductivity field. For a given amount of training data, the method has equal or greater prediction accuracy and generalizability to unseen inputs than a CNN whose training is initialized randomly
Fuzzy Nature of AD Risk Gene Assignments to Brain Cell Types
Keywords:  Department of Biology
Biology
Transcriptomics
Neural networks (Computer science)
GWAS
Cell Type Assignment
Alzheimer's disease
Text
Thesis

As AD pathophysiology remains elusive, risk genes offer valuable information lending clinical and pathophysiological insights into the disease. Assignment of cell type for the AD risk genes proves crucial for understanding underlying pathophysiology. This cell type assignment will often have to be granular, necessitating the use of marker and algorithmic cell type information transfer between datasets. We train and validate a cell type labeling neural network on a scRNA dataset and demonstrate its poor generalization to labeling an snRNA dataset. We extend this analysis to show that for the purpose of assigning cell type labels, markers and the neural network approach respectively lose information when compared to the dataset’s ground truth labels. We systematically analyze these AD risk genes by their cell type assignment, and detail cortical regional effects on cell type assignment. We show that while ANK3, CLU, APP, EPDR1, PLEKHA1, and ICA1 are neuronally dominant in their expression, only CLU, and PLEKHA1 have expression profiles that appear to vary by neuronal subtype. Lastly, we demonstrate that AD candidate drug targets (APOE, GRN) are likely functionally expressed in multiple cell types and thus pose risks, while suggesting other candidates that are functionally expressed in only one cell type.
GABA Antagonism Reduces Sleep Fragmentation and Restores Hourly Sleep in Down Syndrome Model Mice: Pentylenetetrazol as a Therapy for GABAergic Impairment
Keywords:  Department of Biology
Down syndrome
Sleep
Sleep disorders > Treatment
Sleep-wake cycle
Circadian rhythms
GABA
GABA > Antagonists
Memory
Learning disabilities
Intellectual disability
Pharmacology
Text
Thesis

Evidence from animal models supports that Down syndrome (DS) is characterized by excessive GABAergic inhibition in the hippocampus and cortex. Treatment with pentylenetetrazol (PTZ), a non-specific GABAA receptor antagonist, rescues memory and long-term potentiation in DS mouse models only if delivered during mice’s inactive phase. This time-dependent effect suggests that GABAergic dysfunction impairs processes specific to the inactive phase, such as those under sleep or circadian control. However, almost no work in DS has explored how excess GABA modulates sleep or the extent to which sleep deficits mediate characteristic delays. That paucity is notable given the degree of sleep impairments—which include high sleep fragmentation, shorter NREM bouts, and reduced REM—and their potential to explain phenotypes in DS. Using a well-characterized DS mouse model, I administer a seventeen-day course of PTZ p.o. to clarify interactions between GABAergic dysfunction, sleep, and cognitive impairment in DS. I show that in model mice, PTZ treatment reduces sleep fragmentation, lengthens NREM bouts, and increases sleep amount over nine zeitgeber hours. These gains persist one-month post treatment. My findings indicate that GABAergic transmission disrupts sleep quality in DS model mice and that sleep represents a modifiable factor among deficits. Sleep offers a potential mechanism for the cognitive and developmental delays born of GABAergic dysfunction. GABA antagonists demand study as pharmacotherapies for sleep and memory in DS.
Garden From the Concrete Photo Book and Writer's memo
Keywords: Rape in universities and colleges
Asian Americans
Asian American women
Asian American artists
Text
Thesis
Working paper
Photograph
Grey literature
Photographs

In my senior project called “Garden From the Concrete”, I explore how Asian college-aged women survivors’ process of healing from sexual assault while being situated in a red-state through a collaborative photo book. In preparation of the collaborative photo book, I reached out to Asian college-aged women sexual assault survivors in my home-state, which is Oklahoma. I gave the participants the prompt of “Describe your process of healing from sexual assault in a conservative community as an Asian college-aged woman in six pictures.” As photography can provide barriers to entry as it is an expensive hobby, I allowed my collaborators to include any pictures that were financially sustainable for them. As a result of four collaborators (including myself), I gathered film photos and digital photos (from both phone photography and professional camera photography).
Gender differences in pay at the point of hire : causes, consequences, and remediation
Keywords: Business.

This dissertation investigates the process through which gender disparities in pay may arise and be remediated at the point of hire. Chapter 1 provides, for the first time in the literature, a study of initial salary offers across jobs, firms, and industries, in the U.S. between 2017 and 2020. Results demonstrate a persistent gender gap in offers, after controlling for observable differences in human capital, job, firm, and industry characteristics. Chapter 2 continues to investigate the sources of gender disparities in pay. The salary history ban is leveraged as a unique setting to test the role of information in shaping pay disparities among demographic groups. Contrary to the predictions offered by theories of statistical discrimination, the inclusion of productivity-relevant information from prior organizations, such as the inclusion of past salary information, leads to greater, not lesser, gender disparities in pay. Chapter 3 proceeds to reconcile this theoretical puzzle. Findings from twenty-one in-depth, semi-structured interviews with hiring managers reveal that information is not used at the offer stage to infer candidates' quality, as assumed by prior theories of wage-setting, but to infer the amount of leverage candidates may have in offer negotiation. I find that when not knowing job candidates' past salary information, employers extend similarly competitive offers to male and female candidates, out of fear of losing qualified candidates to other potential employers. Collectively, these chapters draw attention to the point of hire as a key source of gender disparities in pay
Genetic and epigenetic identity of centromeres
Keywords: Chemical and Systems Biology.

During cell division genetic material must both be duplicated and segregated into daughter cells. In addition to duplication of the genome during cell division, epigenetic information must also be inherited. This is critical for maintenance of epigenetic states and gene expression profiles. Centromeres mark the site of microtubule attachment during mitosis and are required for proper chromosome segregation. Centromeres are defined epigenetically by the histone H3 variant, CENP-A. Here we provide resources and techniques for studying epigenetic inheritance. We present a novel technique for mapping chromatin associated RNAs genome-wide, ChAR-seq. In efforts to investigate the role of DNA sequence in contributing to vertebrate centromere formation we identify and characterize centromere associated sequences in Xenopus leavis using an alignment independent k-mer based approach that identifies sequence features of repetitive elements in sequencing datasets. Unsatisfied with the lack of techniques for mapping DNA-protein interactions at repetitive regions of the genome we develop a technique that utilizes targeted exogenous adenine methylation to footprint DNA protein interactions that can be read out with long-read sequencing called Directed Methylation with long-read sequencing (DiMeLo-seq). Together these tools and resources allow for more careful study of epigenetic inheritance especially at repetitive regions of the genome
Genetic studies of human evolution
Keywords: Developmental Biology.

Understanding what makes us human and how our species evolved, though enormous questions, present challenges worthy of study. With the advent and availability of genome sequencing for humans and non-human primates, and the technological advances in genetic manipulation and cell culture, we hold more tools than ever before with which to uncover the genetic and molecular basis of human evolution. In this thesis, I describe two complementary approaches to studying the genetic basis of human evolution. In the first, I describe our molecular and genetic studies of a human conserved deletion (hCONDEL584) that drives expression in the developing brain. We show that hCONDEL584 has enhancer activity localized to developing inhibitory interneurons that mimics the expression pattern of nearby gene Nxph1, develop and optimize techniques for further study of hCONDEL584 and Nxph1, recapitulate the human-specific deletion in mice and find differential expression of evolution- and disease-relevant genes in the adult brain, and propose a hypothesized mechanism of human-specific expansion of inhibitory interneurons through the human-specific deletion of enhancers of tumor suppressor genes in the developing brain. In the second approach, I introduce our new cell culture system for genetic mapping of traits divergent across humans and chimpanzees. This system utilizes human and chimpanzee pluripotent stem cells, and fuses them to create auto- and allo-tetraploid cells that we use to study gene expression and regulatory change across humans and chimpanzees. In demonstrating our new system for genetic mapping through panels of deletion lines and a recombinant, we uncover genes subject to species-specific trans-regulation, and propose a candidate species-specific trans-regulator that also has major roles in human neuro-developmental disease. Together, this work represents both forward and reverse genetic approaches to the study of human evolution, uncovers a number of evolutionary and disease-relevant genes and regulatory regions, and contributes to the field a novel system for the mapping of divergent traits across humans and chimpanzees