VictorJuiz/thesis huggingface dataset:
Targeting extracellular and membrane proteins for degradation via lysosome targeting chimeras

Targeted protein degradation (TPD) is a promising strategy to remove deleterious proteins for therapeutic benefit and to probe biological pathways. The past two decades has witnessed a surge in development of technologies that rely on intracellular machinery to degrade challenging cytosolic targets. However, these TPD platforms leave the majority of extracellular and membrane proteins untouched. To enable degradation of these classes of proteins, we developed lysosome targeting chimeras (LYTACs) as a general strategy to degrade both secreted and membrane-anchored targets as introduced in Chapter 1. The first lysosome targeting chimeras (LYTACs) targeted extracellular and membrane proteins for degradation by bridging a target protein to the lysosome trafficking receptor, cation-independent mannose-6-phosphate receptor (CI-M6PR). Because CI-M6PR has broad tissue distribution, harnessing a receptor with tissue-restricted expression could mitigate off-target effects and allow tissue-specific degradation. In Chapter 2, we developed "GalNAc-LYTACs" that engage the asialoglycoprotein receptor (ASGPR), a liver-specific lysosomal targeting receptor, to degrade extracellular proteins in a cell type-specific manner. Site-specific conjugation and development of homogeneous LYTAC ligands improved the pharmacokinetic profile of GalNAc-LYTACs in vivo. GalNAc-LYTACs represent an avenue for cell-type restricted protein degradation, and additional discovery of recycling receptors with distinct and exclusive localization would expand the range of tissues or cells that LYTACs can target with selectivity. To address this need, we generated a comprehensive map of receptors that traffic from the plasma membrane to the lysosome across different tissues in mice in Chapter 3. Although extracellular degrader technologies have recently expanded the scope of potential therapeutic targets, no prior work has identified cellular features which enable or inhibit membrane protein degradation. Development of LYTACs as therapeutics would greatly benefit from insight into the factors that govern their activity. In Chapter 4, we conducted a genome-wide CRISPR screen to identify modulators of LYTAC-mediated membrane protein degradation. Our findings inform new design strategies for LYTACs with enhanced degradation activity and elucidate fundamental insights of receptor occupancy and trafficking

Keywords: Humanities and Sciences.
Chemistry.
Advisor: Bertozzi Carolyn R.
Du Bois Justin
Long Jonathan Z.
Tatanka Awicagli na Mahpiya Ile Win: An Intergenerational Story of Buffalo Restoration and Lakota Futures

This thesis explores the potential of Buffalo restoration to lead the Lakota people to a healthful Lakota future. Through background and socio-cultural context, storytelling and the intergenerational life-story analysis of the author and her father, and a discussion of medical anthropology and radical hope, this thesis aims to assert Buffalo restoration as mechanism towards realizing a radical reconceptualization of Lakota public health.

Keywords: Indigenous peoples > Social conditions
Indigenous peoples > Politics and government
Indigenous Public Health
Native American Health
Public health
Bison
Bison restoration
Buffalo
Buffalo restoration
Lakota Indians
Cheyenne River Sioux Tribe of the Cheyenne River Reservation
futurism
cultural revitalization
Storytelling
life story
intergenerational
Decolonization
historical trauma
Indian reservations
Text
Capstone
Thesis
Student project report
Advisor: LaFromboise Teresa
Biestman Karen
Technologies for mapping the spatial architecture of complex tissues

Single-cell RNA sequencing (scRNA-seq) is generating an expanding wealth of comprehensive single cell expression profiles of tissues in health and disease, however spatial information is missing and specific cell classes may be systematically under-represented because of difficulty in viably isolating them. The next major challenge is to map how RNA expression is spatially organized, which has been termed spatial transcriptomics. Here, we report a simple strategy to efficiently and inexpensively map inferred cell types based on single-cell sequencing data back into a 3D volume of tissue, a process we call "back-mapping." Our approach begins with a machine-learning algorithm that identifies a minimal panel of moderate to highly expressed transcripts that in combination distinguish every cell type in a scRNA-seq dataset. The target tissue is then fixed and embedded in a physically durable hydrogel that is stained for proteins of interest prior to multiplex in situ hybridization for the transcript panel. These tissues are optically imaged in 3D, single cell profiles generated in an automated fashion, then scRNA-seq classes inferred and displayed in 3D. In many cases it is possible to visualize the cytoplasmic volume of cells to display cytological features based on RNA expression. As a demonstration, we "back-map" the Tabula Muris lung dataset into intact mouse lung and illustrate candidate ligand-receptor interactions between neighboring cells. Using our strategy, biologists can easily and affordably take their single-cell RNA sequencing dataset of their healthy or diseased tissue and generate a map at single-cell resolution map, merely by staining for tens of transcripts

Keywords: Medicine.
Biochemistry.
Advisor: Harbury Pehr
Krasnow Mark
Rohatgi Rajat
Temporal regulation of DNA replication at the G1/S transition of the cell cycle

A fundamental challenge in cell division is replicating genomic DNA once and only once each cell cycle, such that daughter cells faithfully inherit their genome. In eukaryotes, duplicating DNA precisely once is critically dependent on separating DNA replication into two distinct stages: "origin licensing" during G1 phase, and "origin firing" during S phase. During origin licensing, cells demarcate future sites of DNA synthesis by loading inactive MCM helicases onto origins of replication. At the start of S phase, cells begin origin firing, whereby replication factors are recruited to the inactive helicases to form the active CMG helicases and replication forks that duplicate DNA. Critically, licensing is inhibited once DNA synthesis starts, such that newly synthesized DNA cannot be re-licensed. Failure to coordinate these processes can lead to re-replication of DNA, in which DNA is copied more than once within a single cell cycle, causing DNA damage and genome instability and ultimately can produce the mutations underlying diseases such as cancer. This dissertation describes work done to understand the regulation and signaling which coordinates G1 phase origin licensing and S phase origin firing. In human cells, inhibition of licensing in S phase centers around inhibition of licensing factor CDT1 starting from S phase entry. However, the E3 ubiquitin ligase CRL4Cdt2 only starts to degrade the licensing factor CDT1 after origin firing, raising the question of how cells prevent re-replication before CDT1 is fully degraded. Using quantitative microscopy and in vitro reconstituted human DNA replication, we show that CDT1 inhibits DNA synthesis during an overlap period when CDT1 is still present after origin firing. CDT1 inhibits DNA synthesis by suppressing CMG helicase progression at replication forks, and DNA synthesis commences once CDT1 is degraded. Thus, in contrast to the prevailing model that human cells prevent re-replication by strictly separating licensing from firing, licensing and firing overlap, and cells instead separate licensing from DNA synthesis.

Keywords: Medicine.
Chemical and Systems Biology.
Advisor: Ferrell James Ellsworth
Meyer Tobias
Cimprich Karlene
Testimonial Advertisements and Willingness to Pay: The Role of Gender and Presentation

This paper investigates the impact of video and text testimonials on willingness to pay
(WTP). An experiment is run eliciting WTP for three different ungendered products
where participants see a photo of the product and either a male or female video testi-
monial, a text testimonial, or no testimonial. We find that the female video testimonial
significantly decreases WTP, while the male video testimonial and the text testimonial
have approximately no effect. Additionally, the text testimonial leads to a significantly
higher retention of factual information presented as compared to the video testimonial
treatment. These results support the hypothesis that consumers’ engagement in video
testimonials is more focused on the presenter than the product.

Keywords: Advertising
Willingness to pay
Sex
Text
Thesis
Advisor: Bernheim B. Douglas
The Afternoon Fun Economy

Using GPS data gathered from 2019 to 2022, this paper analyzes the effect Covid-19 and
Work from Home (WFH) had on consumption decisions, specifically in relation to golfing
activity. Integrating thousands of geospatial polygons with vehicular and mobile GPS data, this
paper finds strong growth in golfing throughout Covid-19 and subsequently after. Similarly, the
temporal and daily distribution of golfing trips underwent significant changes, exhibiting growth
midweek and midday. To contextualize these trends against WFH, I conducted a regression over
a fixed panel of golfers active from 2019 to 2021 to identify the effect income and remote job
postings had on golfing growth. Based on the evidence presented in this paper, I find WFH to be
the likely culprit behind the growth in golfing and the change in weekly and daily patterns.

Keywords: WFH
Geospatial data
Alternative data
Leisure
Consumption (Economics)
Text
Thesis
Advisor: Bloom Nicholas
The concept of music in the Shakespearean corpus: an exploration of neoplatonic ideas of music in Shakespeare (1996)

Part One surveys the major musical concepts of the English Renaissance and their relationship to the Platonic tradition. The main body of the thesis (Part Two) consists of a systematic presentation of Shakespeare’s ideas on music under the Boethian categories of musica mundana, musica humana, and musica instrumentalis. In Part Three, after tracing Shakespeare’s indebtedness to the Platonic tradition, an attempt to synthesize his ideas on music under major Neoplatonic themes is made. The present thesis comes to the conclusion that the wealth, extent, and use of musical allusions in the Shakespearean Corpus allow the definition of Shakespeare’s concept of music as predominantly Neo-Platonic, and centering on the notion of “harmony.” M.Phil. (by research) thesis, University of Liverpool, 1996.

Keywords: Shakespeare, William, 1564-1616
Neoplatonism in literature
English drama > Early modern and Elizabethan
Music imagery
Musicology > Philosophy
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Thesis
The Cost of Imperialism: Designing a Model of Reparations to Laos from the U.S. for the Secret War Bombing

During the Secret War concurrent with the Vietnam War era, the U.S. dropped over 270 million cluster bombs on Laos, making it the most bombed country per capita in the world. To this day, approximately 80 million unexploded ordinances remain in Laos. America’s Secret War on Laos continues to impact the livelihood and well-being of Laotian citizens today, yet there has been little conversation regarding what justice looks like for these people. In my thesis, I argue that the U.S. is culpable for wartime damage to Laos, that there is both legal and moral justification for transitional justice in the region and that reparations are the most appropriate transitional justice mechanism. My research seeks to answer the question: Based on the material needs of the Laotian people, what model of reparations is most appropriate and feasible? In other words, what form should these reparations take, to whom should they be directed, and how should they be administered? Through interviews with Laotian citizens, I hope to provide a snapshot of the war's continued impact on the Laotian people and their visions of justice and reparation for the Secret War. My interviews inform the design of a comprehensive model of reparations specifically tailored to address the needs of the Laotian people as they pertain to the lasting consequences of the war. I also evaluate the political feasibility of reparations through a comparative analysis of reparations implementation in other international case studies. Ultimately, I hope to establish a design precedent that encourages the pursuit of ambitious justice processes, especially for those peoples who continue to struggle against imperialism and its enduring impact.

Keywords: Reparations for historical injustices
Imperialism
Laos
Vietnam (Democratic Republic)
Cambodia
Secret War
Vietnam War (1961-1975)
Indochinese War (1946-1954)
Laotian Civil War
Laotian Americans
Laotian Americans > Cultural assimilation
Laotian Americans > Political activity
Laotians > Social conditions
Southeast Asia
Transitional justice
International Center for Transitional Justice
Decolonization
Solidarity
International Solidarity Movement
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Thesis
Advisor: Cohen David
The Economic Impact of Indigenous versus Colonial Languages as the Medium of Instruction in Africa: The Case of Tanzania

When African lands were colonized by European powers, not only were new systems of governance, boundaries, and economics usually imposed, their educational institutions were often designed to mimic the institutions of the relevant colonial power. For instance, in African areas colonized by the English, educational institutions were often made to adopt English-style curricula, English testing, and the English language as the medium of instruction (especially in upper grades). The same could be said for areas colonized by the French, Germans, Belgians, or Italians. On the one hand, teaching students in the colonial language might be negative because it may make instruction less comprehensible; it may encourage the development of curricula that are less accessible and relevant; and it discourage the development of institutions that are the best “match” with the people and their culture. On the other hand, teaching students in the colonial language may give them more opportunities to attend university in or emigrate to the colonizing country which, in practice, nearly always has a higher standard of living, more advanced educational institutions, and—possibly—more occupational opportunities. Note, however, that the extent of all these opportunities depends on the degree to which the relevant Africans are discriminated against in access to or treatment at these opportunities. In this paper, I analyze these two competing hypotheses by studying the economic and other effects of Tanzania’s 1995 switch of its language of instruction from a colonial language (English) to an indigenous language (Kiswahili).

Keywords: Educational attainment, economic growth, Africa, colonialization, indigenous language, native language, Kiswahili, English, French.
Text
Thesis
Advisor: Hoxby Caroline
The Effect of COVID-19 on Human Capital in a Team Setting: Evidence from the VA

At the start of the COVID-19 Pandemic, the healthcare industry faced unprecedented turnover and staff shortages caused in part by the difficulty of navigating a global pandemic. Registered Nurses (RN) in the United Sates were especially hard hit (Liss 2021). Research (Mark et al. 2004; Sales et al. 2008; Needleman et al. 2011; Bartel et al. 2014; Kelly et al. 2022) has shown RN staffing and specific human capital (proxied by tenure) strongly affect patient mortality and length of stay. If COVID-19 caused significant numbers of experienced RNs to retire or scale back their work hours, it may have adversely affected patient outcomes. Using unit level data from the Veterans Health Administration (VHA) I investigate how COVID-19 affected the specific human capital of RNs within the VHA.

Keywords: Nursing, Labor Market, Healthcare, Human Capital, COVID-19, Shortage
Text
Thesis
Advisor: Duggan Mark
Phibbs Ciaran
The Effects of Occupational Licensing on Wages and Employment, 2014-2019

This study updates and replicates the findings of Gittleman, Kleiner, and Klee (2017) that those with occupational licenses have higher wages and lower unemployment rates. The update is motivated by the changes that have occurred in licensing policy and the American economy between Gittleman et al.'s primary reference year of 2012 and this study's final reference year of 2019. This study also includes an original time series analysis of the effects of occupational licensure on wages and employment between 2014 and 2019. I consistently replicate Gittleman
et al.'s results on the impact of licensure on wages and find that the wage premium associated with licensure decreased by 6.6% between December 2016 and December 2019. I do not find a significant impact of licensure on the likelihood of employment beyond the simplest model and do not identify a time trend across these results.

Keywords: Licensure
Certification
Credentials
Labor economics
Low-income occupations
Barriers to entry
Interstate compacts
Reciprocity agreements
Universal license recognition
Text
Thesis
Advisor: Boskin Michael
THE IMPACT OF DE FACTO REFOULEMENT ON THE HEALTH SYSTEM AND THE MOST VULNERABLE IN LIBYA

The ongoing migrant crisis in Libya is a multifaceted international security issue as well as a major humanitarian crisis. The Mediterranean has been the locus of migrant deaths for over a decade. This thesis examines the relationship between the European Union’s adherence to international refugee law and the Libyan health care system. Incorporating evidence from non-governmental organizations, individual reports, social media, and a number of other sources this thesis seeks to demonstrate that the European Union is engaged in de facto refoulement using the Libyan Coast Guard as a proxy force. Using a mixed-methods survey tool, this thesis attempts to show the effect of de facto refoulement on the Libyan health system. This thesis makes two main contributions. First, detailing the impact of de facto refoulement on health care provision, this thesis argues that the European Union’s de facto refoulement policies have led to an overburdening of Libya’s public health system, with associated negative implications for migrant medical care. I will argue that if the European Union fulfilled its obligations under the non-refoulement principle of international refugee law, the Libyan health care system would be better able to provide health access for migrants seeking refugee status in Europe and Libyans alike.

Keywords: Health
Libya
Refoulement
Libyan Health System
Migrant Health Access
European Union
Frontex
European Border and Coast Guard Agency
Libyan Coast Guard
Text
Thesis
Advisor: Sallam Hesham
Blaydes Lisa
Crews Robert
The Impact of Mindfulness-Based Interventions (MBIs) on Chinese Adolescent Mental Health: A Systematic Review and Meta-analysis

This systematic review and meta-analysis examines the impact of mindfulness-based interventions (MBIs) on adolescent mental health outcomes in China. Through a comprehensive search of seven international and three Chinese electronic databases, a total of fifteen (15) eligible studies were included in the analysis. The pooled effect size of the included studies reveals a substantial reduction in depression and anxiety levels among adolescents who underwent MBIs (standardized mean difference = -1.00, 95% CI [-1.34, -0.66]). The strongest evidence of effectiveness exists for MBIs implemented in clinical settings (standardized mean difference = -1.50, 95% CI [-2.09, -0.91]) and among adolescents with pre-existing mental health disorders (standardized mean difference = -1.37, 95% CI [-1.82, -0.92]). Across different types of MBIs, Mindfulness-Based Stress Reduction (MBSR), mindfulness-based yoga or Tai Chi Chuan, and Mindfulness-Based Cognitive Therapy (MBCT) demonstrate significant effects on improving adolescent mental wellbeing. While the field of MBIs in China is still emerging, these findings make a significant contribution and provide valuable insights for the future design and implementation of mindfulness interventions for adolescents.

Keywords:  Stanford Global Studies
mindfulness-based interventions
mental health outcomes
Depression in adolescence
Anxiety in adolescence
China
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Thesis
Advisor: Rozelle Scott
The Junctional Epithelium Organoid: A Novel System for Periodontitis Research

Periodontitis is an ultra-prevalent oral disease affecting more than half of the US population. The disease is characterized by the breakdown of the Junctional Epithelium (JE), an oral tissue with important barrier and antimicrobial functions in the mouth. The vast majority of research on JE dysfunction is conducted using animal models. However, these animal models have deficiencies replicating all the aspects of the disease.  In this work we describe the process of differentiating murine stem cells toward a JE organoid aimed to replicate the regional identity of the JE particularly the proliferative and anti-microbial functions of the organ. This project draws on the recent finding that the JE is maintained by its own stem cell population. This project aimed to develop a JE organoid from stem cells harvested from a murine model. Within the last 5 years the number of researchers that commonly use the organoid culture model has increased rapidly. Organoids have been grown mimicking brain, kidney, lung, intestine, stomach, and liver tissue. Organoids derived from patient biopsies faithfully replicate critical aspects of human disease; consequently, organoids can be used for drug screening. Similar to other organoid models, a validated JE organoid model could also be used to carry out a deep, unbiased interrogation of other unknown signaling pathways that participate in JE homeostasis. The development of a validated JE organoid system would represent a significant advance in the study of periodontal diseases.

Keywords:  Department of Biology
Junctional Epithelium
Oral Epithelium
Stem Cells
Periodontitis
Organoid
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Thesis
Advisor: Helms Jill
Feldman Jessica