VictorJuiz/thesis huggingface dataset:
Genome editing with CRISPR/Cas9 to study and treat primary immune regulatory disorders
Keywords: Stem Cell Biology and Regenerative Medicine.

For those living with genetic disease, the advent of gene therapy represents an end to years of repeated treatment and daily disease management. Using gene editing tools, patient cells can be modified to provide long term therapeutic benefit that cures or mitigates disease. In particular, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology allows us to make precise genetic changes to cells for therapeutic benefit. During CRISPR gene editing, single guide RNA (sgRNA) directs Cas9 nuclease to make a double-stranded cut to DNA at a precise location in the genome. A DNA repair cassette delivered by recombinant adeno-associated virus (rAAV) is then inserted at the cut site via homologous recombination. This repair cassette can be designed to contain a therapeutic gene which can be expressed at physiological levels, under the control of endogenous regulatory elements. Monogenic disorders of the blood and immune system are severe diseases with limited therapeutic options. While allogeneic hematopoietic stem cell transplantations (HSCT) have historically been used to treat blood and immune disorders, the rise of CRISPR/Cas9 technology has enabled us to modify a patient's own stem cells for autologous transplantation, thereby circumventing the challenges associated with rejection. Hematopoietic stem and progenitor cells (HSPCs) are particularly amenable to gene therapy because we can isolate, culture, and modify them ex vivo. This dissertation explores CRISPR/Cas9 based gene editing as a new therapeutic modality for two primary immune regulatory disorders caused by mutations in the FOXP3 and IL-10 genes, respectively. The goal of this therapeutic modality is to engraft gene edited patient HSPCs to enable healthy hematopoietic reconstitution, curing the disease. The gene editing strategy was validated through assaying the phenotype and function of edited primary T cells; the engraftment and differentiation potential of edited HSPCs were subsequently confirmed in the NSG-SGM3 humanized mouse model. Further, CRISPR/Cas9 knockout experiments elucidated the mechanisms of dysregulation in specific immune subsets, advancing our understanding of the role of FOXP3 and IL-10 in health and disease. Another aspect of bringing cell and gene therapies to the clinic is the complexity and cost of manufacturing. An understated factor that could expedite patient access to gene therapies is robust and cost-efficient manufacturing processes. The final segment of this dissertation applies a regression-based approach to understand key factors influencing gene editing frequencies in CD4+ T cells. Editing frequencies across varying guide and rAAV concentrations were linked to a cost of raw materials analysis model to provide information on the cost drivers of gene targeting and to predict cost-optimal editing conditions for cell therapy manufacturing
Genre, culture, and affect : music cognition through the lens of computational psychology
Keywords: Music.

Music's isolation from the kinds of survival pressures common in typical natural selection narratives, the social and cultural capital musical preferences confer, and the apparent ubiquity of music across human cultures throughout history make it a potential tool for modeling the structure and development of human society more broadly. Investigating the provenance of musical functionality in both psychological and sociological domains may offer crucial insights into the imperatives common across human cultures. This dissertation aims to start this ambitious project by focusing on the relationship among musical genre, cultural psychology, and computational models of prediction and affect. First, I propose a culture-cognition mediator model of musical functionality, situating music as a crucial link in the mutually constitutive cycle of cultures and selves, and discuss the implications of this model on transdisciplinary music scholarship and the epistemology of musical function. I then discuss experimental and conceptual instantiations of this model in three domains of musical functionality and perception: syncopation, emotion, and genre. These implementations draw on Bayesian probabilistic modeling; theories of affect valuation and mood regulation; and differential topology and computational models of perceptual classification, respectively
Geologic uncertainties in faulted basin models with application to the Norwegian North Sea
Keywords: Geological Sciences.

Basin modeling is a fundamental physics-governed tool that helps estimate subsurface exploration risks through simulation of basin history in geological time and quantifying the amount of petroleum, or other fluid, e.g., CO2, accumulated in the trap. A common deterministic approach to basin modeling is to define all the required input variables using expert knowledge, geological analogs, log data, or common sense and to produce one or several deterministic basin modeling scenarios. Purely deterministic scenarios may include overlooked hidden geological uncertainties, lack of understanding of the uncertainty, or can be biased due to overconfidence in the ability to estimate the uncertainty. This work explores the semi-deterministic approach to unlocking the impact of several sources of uncertainty typical for faulted hydrocarbon fields in Viking Graben, the Norwegian North Sea, on high-resolution 3D basin modeling results. We simulate multiple high-resolution basin models of the same field using a different combination of uncertain parameters and analyze the simulation results with the help of the multidimensional scaling (MDS) technique. This approach allows us to examine the effect of different combinations of uncertainty parameters on simulation results. Our approach facilitates quick analysis of multiple basin models at once and helps highlight models with such a combination of uncertain parameters, which match geological conceptions of the study area. In addition to exploring the geological uncertainties in 3D basin modeling in Viking Graben, we highlight the problems specific to the current workflows on the seismic interpretation of faults in subsurface exploration. The fault model governs trap geometry, pressure compartmentalization, fluid contacts, and other vital exploration features at the reservoir and the basin scale. Thus, seismic fault interpretation uncertainties can impact basin modeling results. This work proposes a geologically constrained and machine learning-guided seismic fault interpretation workflow. It allows for segmenting structurally consistent faults from noisy automatic seismic fault interpretation output. This output can be a validated fault framework for basin modeling studies. The thesis includes five chapters: a first introduction chapter and three main chapters, followed by a conclusion chapter. Chapter 2 and Chapter 3 employ the MDS technique to analyze multiple basin model simulations with a combination of uncertain parameters. As a result, we choose models with a combination of uncertain parameters that match the study area's geological conceptions. Chapter 4 proposes a workflow to extract a structurally consistent fault model from automatic fault output, e.g., from machine learning using an Approximate Bayesian Framework and modified Hausdorff distance. Three main chapters are separately completed parts of one Ph.D. research combined with the joint scientific idea to explore factors affecting basin modeling results and exploration studies in faulted areas of the Norwegian North Sea
Germany’s Changing ‘Boundary of Belonging’: Anti-Immigrant Attitudes amidst the Refugee Crisis 2015
Keywords: Program in International Relations
Germany
Refugees
Anti-immigrant attitudes
Group threat theory
Migration
Text
Thesis

In 2015 and 2016, more than a million refugees arrived in Germany. How did this ’Refugee Crisis’ impact
native Germans’ understanding of who belongs to the German community and who does not? My thesis
initially establishes that attitudes towards all immigrant groups except refugees improved during the Refugee
Crisis. Why might this be the case? I investigate two potential causal pathways: First, I examine the
impact of county-level exposure to refugees on attitudes towards incumbent immigrant groups using a crosssectional
and a differences-in-differences design. While the cross-sectional analysis indicates that increased
refugee presence on the county-level leads to improved attitudes towards other outgroups, the differences-indifferences
design yields no conclusive findings. Second, I examine whether the national news media coverage
drives the attitudinal shift, by analyzing the salience and sentiment of coverage on various immigrant groups.
I show that the salience of refugees increased during the crisis while the salience of some incumbent groups
decreased. The sentiment analysis yields no significant results with regards to incumbent immigrant groups.
Together these findings suggests that Germany’s “boundary of belonging” shifted to become more inclusive
of non-refugee immigrants as a result of the 2015/2016 refugee inflow. These findings present an important
case study of how a homogenous society’s definitions of inclusion and exclusion adjust in the face of increased
immigration.
Getting around in a byzantine village : social network and financial activities in sixth century Aphrodito
Keywords: Classics.

For more than a century, the papyrological archives from the Byzantine village of Aphrodito have contributed the key evidence for our understanding of socio-economic life in Late Antique Egypt. However, most research still combines evidence from the village with that of Apions' archives from Oxyrhynchus to analyze economic patterns in Late Antiquity. The ﬁnancial activities and conditions in the micro-landscape of Aphrodito are still in want of a dedicated study. My dissertation, accordingly, examines ﬁnancial status and economic activities in Aphrodito through the political structure and the village's social networks. It focuses on two main aspects of village ﬁnancial life- taxation and land tenure. Tax and rental receipts, lease contracts, and account books constitute a major part of the Aphroditan archives. In these documents, villagers' positions in the land market and the ﬁscal system also reﬂected their social, political, and ﬁnancial positions. Related documents, as a result, can be helpful for tracing the transformation of other powers (prestige, bureaucratic authorities, religious power) to ﬁnancial advantages or vice versa in the village context. Instead of analyzing only the political and economic hierarchies, my study relies on social network analysis to tease out how the community of either equal or hierarchical actors assists or limits different social tiers' ﬁnancial capabilities. A detailed study of the interactions of landlords and their managing teams also reveals the mechanisms of both wealth accumulation and estate maintenance. The available strategies of property accumulation and tiers of social hierarchy, I argue, determined the balanced ﬁnancial status of Aphrodito, where no large landlord had the absolute upper hand
Giant magnetoresistive biosensors for point-of-care and personalized pain medicine
Keywords: Materials Science and Engineering.

Currently, there is an opioid epidemic sweeping the United States of America, as well as many countries around the world, resulting in more annual opioid overdose deaths in the USA than deaths from firearms or automobile accidents. One common pathway for opioids entering the hands of opioid naïve individuals is through the prescription of opioids for postoperative pain management, which can develop into opioid misuse and chronic opioid use. Recent advances in point-of-care (POC) technologies offer an opportunity to combat the epidemic through innovations in pain medicine, reducing the need for prescription opioids through the careful management of pain pre- and post- operatively. Using versatile and multiplexable giant magnetoresistive biosensor arrays, we demonstrate two tools which can enable clinicians to proactively optimize opioid delivery postoperatively through POC opioid monitoring and reduce opioid use through targeted referrals for non-pharmacological adjuvant treatments like hypnosis. The first tool demonstrates that giant magnetoresistive (GMR) nanosensors offer a quantitative, sensitive, and rapid solution for low-cost, sample-to-answer opioid detection at the POC. We utilized the robust nature of GMR nanosensors by developing a competitive morphine assay and characterizing it in saliva, blood, and plasma. We then implemented the assay on a fully automated POC GMR platform and demonstrated its duality to detect either morphine or hydromorphone using only 180μl of direct saliva without the need for pre-processing. The second tool developed in this work addresses the need for targeted hypnosis referrals for pain treatment, known as hypnotic analgesia. Through our work, inexpensive genotyping of 4 single nucleotide polymorphisms (SNPs) in the catechol-o-methyltransferase (COMT) gene was performed using giant magnetoresistive biosensors to determine if hypnotizable individuals can be identified for targeted hypnosis referrals. We show that this tool is 100% accurate compared with pyrosequencing, and we use it to genotype three cohorts of patient samples involved in hypnosis studies. Using this same 4-SNP COMT genotyping tool, we then investigated phenotypes of hypnotizability, which may modulate the benefit of hypnosis treatments due to the heterogeneity of experience of hypnosis between individuals. We propose this heterogeneity is underpinned by limitations in the mechanistic understanding of variants of hypnotizability phenotypes, and we investigate if genetic differences in COMT activity is a mechanism for the divergence of hypnotizability phenotypes via cognitive-behavioral assessments in an exploratory study. These results together suggest that optimal COMT diplotypes may be associated with the inwardly attentive phenotype of hypnotizability, and that the 4-SNP COMT GMR assay may be able to be used to differentiate the two phenotypes of hypnotizability. Finally, we demonstrate how the 4-SNP COMT genotyping assay can be translated to the POC in two different formats
Gimme Shelter: Habitat Use of Lizards in a Warming Arid City
Keywords:  Department of Biology
Biology
Ecology
Herpetology
Lizards
Climatic changes
Global warming
Wildlife conservation
Habitat conservation
Biodiversity conservation
Urbanization
Urban ecology (Biology)
Arizona
Arizona > Pima County
Arizona > Tucson
North America > Sonoran Desert
Text
Thesis

Lizards are highly vulnerable to climate change. Modeling studies have predicted that over one third of the world’s lizard populations are expected to go extinct within the next sixty years as elevated temperatures reduce the time available for critical activities such as foraging and reproduction. This effect likely varies between habitats and may be exacerbated in urban areas, which often experience temperatures several degrees warmer than their surroundings. Understanding the interactive effects of habitat and temperature on lizard activity is therefore essential to lizard conservation in urban settings. In this study, I analyze the results of 819 lizard surveys conducted in multiple habitats over 21 years in the warming desert city of Tucson, Arizona. I document elevated abundances of several lizard species in forested and riprap habitats relative to nearby open areas. I also show that at least three out of Tucson’s five most common lizard species are active at different temperatures in different habitats. Activity is generally high at low temperatures in riprap, intermediate temperatures in open habitats, and high temperatures in forested habitats, with important species-specific variability. In particular, I show that forested habitats promote higher activity than open habitats at elevated temperatures for at least one terrestrial species vulnerable to climate warming. I suggest that heterogeneous urban habitats can facilitate continuous lizard activity across a range of air temperatures, which is critical to ameliorate the effects of ongoing and future climate warming on lizard populations.
Global Human Rights in Domestic Movements: The American Queer Liberation Movement and LGBTQ Rights as “Human Rights”
Keywords: LGBTQ Rights
Global human rights
Civil rights movements
Text
Thesis

For her capstone project, Natalie Adams-Menendez studied the ways in which the American LGBT Rights Movement for queer liberation was and continues to be influenced by the Global Human Rights Movement, as well as the manner in which the concept of “human rights” has become integral to modern queer rights advocacy. Her research included reviewing scholarly articles, examining current advocacy organizations, exploring historically queer neighborhoods of San Francisco and Washington, D.C., and attending community protests and events. Through her findings, Natalie aims to untangle the past and present of the American LGBTQ Rights Movement and gain critical knowledge about the future and potential of its relationship with the Global Human Rights Movement. She hopes this insight will serve as the foundation for her post-graduate career work towards advocating LGBTQ rights as human rights, both domestically and abroad.
Student project deposited by department for archival purposes. Original work unavailable for public download due to permission restriction preferences of the author.
Glucose-6-phosphate dehydrogenase in health and disease and a therapeutic strategy for glucose-6-phosphate dehydrogenase deficiency
Keywords: Chemical and Systems Biology.

Glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, is critical for a variety of cellular processes and mutations in the G6PD gene can cause G6PD deficiency -- a genetic trait present in ~300-500 million people worldwide. Currently, G6PD deficiency is most known for causing hemolytic anemia; however, it has been associated with other chronic disorders and there are no therapeutics for G6PD deficiency. Here, the role of G6PD in health and disease, past treatment strategies, and potential pharmacological pathways and drug targets are discussed. The lack of therapeutics and drug discovery efforts for G6PD deficiency motivated our lab to conduct a high throughput screen where we identified a small molecule activator of G6PD, which works by stabilizing the structural NADP+ and dimer. My work aimed to understand how loss of structural NADP+ binding affected the homo-oligomeric properties and function of G6PD and whether oligomer stabilization could be used as a therapeutic strategy for G6PD deficiency. Here, I found that loss of structural NADP+ induces structural changes in the G6PD dimer, which prevents tetramer formation. By introducing non-native cysteines at the oligomeric interfaces of G6PD, I found that the tetramer is the more active and stable form of wild type G6PD. Furthermore, I found that stabilization of the dimer and tetramer improved activity for select G6PD variants and that favoring the tetramer stabilized the enzyme to a greater extent than the dimer. Since enzyme activity and stability are major determinants of pathogenicity, my study suggests a small molecule which stabilizes the tetramer may be beneficial for treatment of G6PD deficiency related disorders and encourages the pursuit of such novel compounds. Foreseeable challenges and future research directions pertaining to these findings conclude my dissertation
Goldi-ox : mixing metals and valences in halide perovskites
Keywords: Chemistry.

Throughout my PhD, I have explored and expanded the vast and diverse class of metal-halide perovskites. These extended semiconducting solids can be prepared by aqueous syntheses at near-ambient temperatures and offer myriad applications, the most prominent of which is as high-efficiency solar absorbers in photovoltaic cells. My work has focused on understanding and controlling the optical and electronic effects of combining different metals and distinct oxidation states of the same metal in both known and novel halide perovskites. The perovskite Cs2AgBiBr6 represents one promising nontoxic alternative to the toxic Pb-based perovskites, such as (CH3NH3)PbI3, but it has a large bandgap energy that makes it impractical for use as a high-efficiency single-junction solar absorber. I showed that mixing Sn into Cs2AgBiBr6 reduced the bandgap in a fully nontoxic composition. Using a host of experimental techniques complemented by calculations, I uncovered the structural, electronic, and optical consequences of the complex mechanism of Sn substitution in Cs2AgBiBr6. This study demonstrated the ability to tune the electronic structure of perovskites by mixing metals in a nontoxic composition, opening the door to a wider diversity of methods to manipulate the electronic structures of perovskites. I expanded the family of halide perovskites by discovering and characterizing the new family of gold-cage perovskites, an unprecedented structure with no known analog. This structure, with the general formula Cs8AuIII4MIIIX23 (M = In3+, Sb3+, Bi3+; X = Cl-, Br-, I-), combines zero- and three-dimensional sublattices and features ordering of the homovalent Au3+ and M3+ metals, a rare phenomenon only observed in one other halide perovskite. Furthermore, I demonstrated that the visible light absorption could be tuned across a wide range by changing the M3+ metal and by mixing in Au1+. This work added a new member to the impressive array of halide-perovskite structures and demonstrated tunability of the electronic structure, thereby helping to solidify the promise of studying unique perovskite structures. I further diversified halide perovskites with new structure types that stabilize unusual oxidation states of metals in well-defined mixed-valence solids that are stable to ambient conditions. In addition to rigorously confirming the oxidation state assignments using a slew of characterization techniques, I investigated the optical, electronic transport, and magnetic properties of these unique perovskites. This work expands the small family of mixed-valence 3D halide perovskites to bolster the promise of novel perovskite architectures to incorporate new metals and metals with unusual oxidation states