VictorJuiz/thesis huggingface dataset:
GABA Antagonism Reduces Sleep Fragmentation and Restores Hourly Sleep in Down Syndrome Model Mice: Pentylenetetrazol as a Therapy for GABAergic Impairment

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.

Keywords:  Department of Biology
Down syndrome
Sleep
Sleep disorders > Treatment
Sleep-wake cycle
Circadian rhythms
GABA
GABA > Antagonists
Memory
Learning disabilities
Intellectual disability
Pharmacology
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Thesis
Advisor: Heller H. Craig
Zeitzer Jamie
Garden From the Concrete Photo Book and Writer's memo

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).

Keywords: Rape in universities and colleges
Asian Americans
Asian American women
Asian American artists
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Thesis
Working paper
Photograph
Grey literature
Photographs
Gender differences in pay at the point of hire : causes, consequences, and remediation

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

Keywords: Business.
Advisor: Sorensen Jesper B.
Sterling Adina
Goldberg Amir
Genetic and epigenetic features of cell-free DNA for the early detection of lung cancer

Lung cancer remains the leading cause of cancer deaths, due largely to the late stage at diagnosis for most patients. Patients diagnosed earlier and with smaller tumors have higher rates of survival, but current screening paradigms have low uptake. Here, we aim to develop blood-based assays to increase the number of people screened for lung cancer. To do this, we focus on cell-free DNA (cfDNA), or the short fragments of DNA found in the plasma compartment of the blood, which in patients with cancer can contain DNA shed directly from the malignant tumor cells. This circulating tumor DNA, or ctDNA, features tumor-specific mutations and epigenetic alterations, making it a promising biomarker for cancer. First, we aim to leverage genetic features of cfDNA to discriminate lung cancer samples from healthy ones, and develop a Lung Cancer Likelihood in Plasma (Lung-CLiP) model which can robustly discriminate early-stage lung cancer patients from risk-matched controls. Next, we aim to develop a novel method that harnesses epigenetic features of cfDNA for early lung cancer detection. We focus on DNA methylation, which is broadly dysregulated in cancer. We identify hundreds of loci at which methylation states distinguish non-small cell lung cancer (NSCLC) from healthy blood and lung samples, and using these regions we identify features of cfDNA methylation that distinguish patients from controls. A LASSO logistic regression model trained on these features shows stage-dependent sensitivity, suggesting biological plausibility, and outperforms a leading commercial method for Stage I tumors. Integration of genetic and epigenetic features may achieve optimal performance, and we aim to test that strategy in the near future

Advisor: Alizadeh Ash
Diehn Maximilian
Pollack Jonathan D.
Salzman Julia
Sherlock Gavin
Genetic and epigenetic identity of centromeres

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

Keywords: Chemical and Systems Biology.
Advisor: Straight Aaron
Cimprich Karlene
Jarosz Daniel
Wysocka Joanna
Genetic studies of human evolution

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

Keywords: Developmental Biology.
Advisor: Kingsley David M. (David Mark)
Boettiger Alistair
Fuller Margaret T.
Luo Liqun
Genome editing with CRISPR/Cas9 to study and treat primary immune regulatory disorders

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

Keywords: Stem Cell Biology and Regenerative Medicine.
Advisor: Bacchetta Rosa 
Maltzman Jonathan
Porteus Matthew H.
Roncarolo Maria-Grazia
Wright John Fraser
Genre, culture, and affect : music cognition through the lens of computational psychology

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

Keywords: Music.
Advisor: Berger Jonathan
Fujioka Takako
Kronengold Charles (Charles Stewart)
Tsai Jeanne Ling
Germany’s Changing ‘Boundary of Belonging’: Anti-Immigrant Attitudes amidst the Refugee Crisis 2015

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.

Keywords: Program in International Relations
Germany
Refugees
Anti-immigrant attitudes
Group threat theory
Migration
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Thesis
Advisor: Fouka Vasiliki
Getting around in a byzantine village : social network and financial activities in sixth century Aphrodito

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

Keywords: Classics.
Advisor: Scheidel Walter
Fournet Jean-Luc
Morris Ian
Saller Richard P.
Woytek Bernhard
Gimme Shelter: Habitat Use of Lizards in a Warming Arid City

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.

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
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Thesis
Advisor: Dirzo Rodolfo
O'Connell Lauren
McFadden Tyler
Rosen Philip
Global Human Rights in Domestic Movements: The American Queer Liberation Movement and LGBTQ Rights as “Human Rights”

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.

Keywords: LGBTQ Rights
Global human rights
Civil rights movements
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Thesis