VictorJuiz/thesis huggingface dataset:
Essays on Urban Economics and International Trade

The three chapters of this dissertation explores different issues in urban economics and international trade. The first chapter shows that the reduction in travel time to China promotes the creation of firms in US cities, more in industries that use many different suppliers, employing a novel instrument for travel time constructed from the gradual deregulation of the US-China passenger flight market. To account for the heterogeneity in supplier presence within China, I estimate a quantitative spatial model featuring sourcing location choice, input-output structure, and a firm entry decision. The model illuminates that the 2004-2013 US-China aviation network expansion increases US firm creation by 1.7%. 42% of the increase comes from the supplier presence heterogeneity across Chinese prefectures because of assortative matching on the sparse US-China flight network. The second chapter uses a unique administrative dataset of the universe foreign firms in China to document that initial foreign direct investment was mainly driven by the Chinese diaspora; massive non-diaspora foreign direct investment did not materialize until a later stage. Leveraging the staggered opening up of Chinese prefectures during 1981-96 as an identification strategy, we find that following the opening up, diaspora direct investment is more likely to enter prefectures with stronger lineage connections. These prefectures also witness a greater number of non-diaspora foreign and domestic private entrants in the later period. The third chapter develops a spatial Ben-Porath model which introduces the endogenous life cycle forward-looking learning decision into a spatial setting. The model's novel predictions on the life cycle learning dynamics across cities, the dynamic agglomeration gain over life cycle by skill, and the spatial sorting of high skill workers into big cities over life cycle find supportive empirical facts. These facts are documented with a learning time measure constructed from time use surveys, and city size elasticities and sorting of high skill workers estimated using the US population census data.

Advisor: Baum-Snow, Nathaniel
An Ecological Systems Approach to Understanding Risk and Promoting Resilience Among Trans and Gender-Diverse Youth

The present research investigated the experiences of risk and resilience for trans and gender-diverse youth. Ecological systems theory emphasizes how one is impacted by both proximal (e.g., peer interactions) and more distal (e.g., societal attitudes) environmental factors. Factors impacting trans and gender-diverse youth’s risk and resilience were explored at multiple levels of influence to achieve a comprehensive understanding of how to improve these youth’s well-being. Study 1 examined the relationship between broad, environmental marginalization levels and access to gender-affirming healthcare for trans youth. Study 1 compared marginalization levels in the areas surrounding trans youth (N = 298) who accessed gender-affirming healthcare services in Toronto, Canada, relative to marginalization levels in background populations. Compared with background populations, there was some evidence that areas where trans youth patients came from were biased toward less marginalization (e.g., less ethnic diversity). Study 2 was a qualitative study focused on asking Black, Indigenous, and People of Colour (BIPOC) trans youth (N = 12) about their experiences of risk and resilience. Despite facing multiple forms of marginalization, BIPOC trans youth have received limited research attention. Through qualitative coding, I identified four superordinate themes: accessing community connection and fostering belonging; navigating the healthcare system; personal journey with and relationship to gender identity; and others’ reactions to gender identity. Participants commented on day-to-day social interactions, interactions with societal institutions, and prevailing societal attitudes. Study 3 explored the possibility of changing societal attitudes in order to improve the experiences of trans and gender-diverse youth. Specifically, I investigated whether an empathy-based intervention could improve children’s (N = 186) attitudes towards gender-diverse peers and reduce gender stereotyping. Although the intervention was not effective, girl participants who displayed higher levels of trait empathy also displayed more positive ratings of target children. Also, among all children, gender stereotyping was related to more positive appraisals of gender-conforming (relative to gender-diverse) targets, suggesting that reducing stereotyping is an important strategy for improving children’s gender-related attitudes. Overall, the present research highlights a variety of factors at multiple levels of the environment that could be targeted to improve the well-being of trans and gender-diverse youth.

Advisor: VanderLaan, Doug P.
Essays on Evaluations and Inequality

Evaluations play a crucial role in determining resource allocation in markets. Through three empirical studies, this dissertation investigates this topic by focusing on how evaluations affect the outcomes of organizations and individuals and, furthermore, contribute to inequality among them. The first study examines the conditions under which a fall in rankings affects organizational outcomes. Using the Fortune 500 ranking as an empirical setting, the study finds that a fall in rankings is associated with negative stock market reactions but that this negative association is strengthened under three conditions: less alternative information, lower audience sophistication, and if the firm falls off the Fortune 500 list due to the fall in rank. Overall, this study develops an informational theory of rankings and illuminates their contingent effects on organizational outcomes. The second study examines bias and stereotypes that occur during evaluation processes within organizations. It asks why East Asian Americans are underrepresented in corporate leadership positions, despite their high socioeconomic status and stereotypes of being highly competent. The key argument is that a stereotype that East Asian Americans lack creativity is an important mechanism underlying their underrepresentation. Two experiments consistently showed that evaluators are less likely to select East Asian American candidates for corporate leadership positions because they perceive them to be less creative than White candidates. This study suggests that even socioeconomically successful demographic groups might face negative stereotypes that impede their status attainment in organizations. The third study examines the effects of certifications on racial discrimination and inequality on digital platforms. This study predicts that certifications on digital platforms tend to benefit White sellers more than Black sellers because they carry ambiguous meanings to buyers. Thus, reducing ambiguity in certifications can make it provide more equal benefits to Black and White sellers. Evidence for these arguments is provided using observational data from Airbnb listings and an experiment with Airbnb users. This study has implications for understanding racial inequality and the design of certifications. The final chapter discusses implications, limitations, and future research avenues.

Advisor: Tilcsik, András
Bowers, Anne
GATA4/5/6 Family Transcription Factors: An Ancient Guide for Cardiac and Pharyngeal Mesoderm Fate Decisions

GATA4/5/6 transcription factors play essential, conserved roles in heart development. To understand how GATA4/5/6 modulates the mesoderm-to-cardiac fate transition, we labeled, isolated, and performed single-cell gene expression analysis on cells that express gata5 at precardiac time points spanning zebrafish gastrulation to somitogenesis. We found that most mesendoderm-derived lineages had dynamic gata5/6 expression. In the absence of Gata5/6, the population structure of mesendoderm-derived cells was substantially altered. In addition to the expected absence of cardiac mesoderm, we confirmed a concomitant expansion of cranial-pharyngeal mesoderm. Moreover, Gata5/6 loss led to extensive changes in chromatin accessibility near cardiac and pharyngeal genes. Functional analyses in zebrafish and the tunicate Ciona, which has a single GATA4/5/6 homolog, revealed that GATA4/5/6 acts upstream of tbx1 to exert essential and cell-autonomous roles in promoting cardiac and inhibiting pharyngeal mesoderm identity. I further characterized the open chromatin landscape of the cardiac and pharyngeal mesoderm progenitors at single cell resolution and revealed a pro-cardiac role of gata5/6. Overall, cardiac and pharyngeal mesoderm fate choices are achieved through an evolutionarily conserved GATA4/5/6 regulatory network.

Advisor: Scott, Ian IS
Wilson, Michael MW
Genes and Neural Cell Types Influencing Reading and the Overlap with Neurodevelopmental Disorders

Although a breadth of research has been conducted on Reading Disabilities (RD), the genes, molecular mechanisms, and cell types involved in its etiology remain to be elucidated. Understanding these processes is complicated by the frequent overlap between RD and other neurodevelopmental disorders. The purpose of this dissertation was to identify genes and neural cell types involved in the development of RD, while considering the genotypic/phenotypic overlap with comorbid disorders. To that end, genome-wide association studies (GWAS) and polygenic risk scores (PRS) were used to identify genes associated with word reading and examine shared genetic etiology with neurodevelopment/psychiatric disorders. We identified two novel loci for word reading, with top SNPs in or near ARHGAP23 (n=624) and the CCNT1/LINC00935 region (n=4430) (p~10-7) (significant by gene-based analysis (p~10-6)). We also identified significant genetic overlap for word reading and intelligence, word reading and educational attainment, and word reading and attention deficit hyperactivity disorder (ADHD) (threshold for significance=7.14x10−3) and observed shared genes between word reading and Autism Spectrum Disorder (ASD) and language. We observed genes involved in neuronal migration among top results. To increase power to identify genes for word reading, we performed Hypothesis-Driven GWAS in a larger sample. SNPs in DOCK7, CDH4 (n~26,000), and intergenic between BTG3-C21orf91 (n=4152) showed significant association. Top SNPs were eQTLs/sQTLs, providing hints to the molecular mechanism of risk for these genes. We also found that genes previously implicated in ASD cumulatively and significantly contributed to word reading (n=624). We hypothesized the link between RD-ASD was through deficits in language systems. To determine neural cell types, we used Linkage Disequilibrium Score Regression to look for cell enrichment in our GWAS results and correlated traits -- as determined by PRS. We demonstrated enrichment of adult excitatory neurons in word reading; adult excitatory neurons in ADHD; and adult and fetal excitatory neurons, inhibitory neurons, astrocytes, and oligodendrocytes in educational attainment and cognitive ability. This thesis contributed novel genes and neural cell types to RD, as well as an understanding of the shared overlap between its comorbid disorders. It can inform future functional studies examining the molecular mechanisms of reading.

Keywords: Attention Deficit Hyperactivity Disorder
Autism Spectrum Disorder
Dyslexia
Genome Wide Association Study
Reading Disabilities
RNA sequencing
Advisor: Barr, Cathy L
Inventing Texture: Food Science and Culinary Culture in Postwar America

In the second half of the twentieth century, food scientists in North America and eventually across the globe focused their attention on the human sense of texture. Largely ignored by scientists before them, and seemingly without cultural precedent, corporate and public research scientists set out to define texture as a measurable phenomenon, to ascertain what was generally desirable to chew, and to operate this knowledge in service of the ongoing global industrialization of food production and retailing. Above all, texture was staked as the solution to overlapping crises in the global food system, promising the Global South abundant meat prepared cheaply from plants and offering a palatable alternative to excessive dietary fat in the Global North. Through an examination of their research methods, published ideas, and the new products that resulted, this dissertation explores the messy entanglement between food science and culinary culture. As scientists drew upon cultural intermediaries like home economists, marketers, and vegetarians to direct their research, so too did increasing scientific control over the physical features of processed foods shape broader cultural understandings about normative taste. While the desired outcomes for texture research have thus far resulted in spectacular market failure, this dissertation suggests how the core concepts of modern food science have succeeded nevertheless in becoming part of culinary discourse, offering a terminology and indeed a terrain for navigating contemporary global cultural exchanges.

Keywords: cuisine
culture
food
industry
science
texture
Advisor: Pilcher, Jeffrey M
Systematic Investigations of the Regulation and Nuclear Organization of Alternative Splicing

Alternative splicing is a key process by which precursor (pre)-mRNAs generate multiple mRNA isoforms and greatly expands transcriptomic and proteomic diversity. It is often precisely regulated by intricate RNA-protein interaction network, and tightly coordinated on a global level to modulate gene activities and interactions in diverse cellular, developmental, and pathological processes. Therefore, comprehensively dissecting the regulatory landscape of alternative splicing and its organization in the cell nucleus is of significant interest. During the course of my PhD thesis research, I co-led the development of a CRISPR-based strategy for the genome-wide elucidation of pathways that control alternative splicing, and applied this to alternative microexons with critical functions in nervous system development and that are commonly misregulated in autism. Approximately 200 genes associated with functionally diverse regulatory layers and enriched in genetic links to autism control neuronal microexons. Remarkably, the widely expressed RNA binding proteins Srsf11 and Rnps1 directly, preferentially, and frequently co-activate these microexons. These factors form critical interactions with the master neuronal splicing activator Srrm4 and bi-partite intronic splicing enhancer elements to promote the recognition and splicing of most neuronal microexons. Multiple steps of gene expression are highly compartmentalized in the cell nucleus. In particular, membraneless nuclear domains play an important role in the organization of gene expression and RNA processing. However, the composition and function of many of these structures are not well understood. I utilized APEX2-mediated proximity labeling and RNA sequencing to survey human transcripts associated with nuclear speckles, several additional domains, and the lamina. Remarkably, speckles and lamina are associated with distinct classes of retained introns enriched in genes that function in RNA processing, translation, and the cell cycle, among other processes. In contrast to the lamina-proximal introns, retained introns associated with speckles are relatively short, GC-rich, highly differentially regulated across diverse cellular contexts, and enriched for functional sites of RNA-binding proteins that are concentrated in these domains. Together, this thesis dissertation presents a versatile system for the comprehensive identification of splicing regulatory pathways impacting exons of interest, and further reveals speckles and lamina as hubs engaged in the splicing of distinct classes of retained introns.

Keywords: Alternative splicing
CRISPR screens
Exon definition
Nuclear organization
Nuclear speckles
Post-transcriptional gene regulation
Advisor: Blencowe, Benjamin J
Exploring the Body Language of Children with Autism Spectrum Disorder (ASD) during Physical Activity

Introduction: Children with autism spectrum disorder (ASD) participate in less physical activity (PA) than their peers. Research has shown that one reason is that some instructors lack awareness about ASD and how best to support these children. Differences with body language expression are a feature of ASD that limit social interactions and may compromise participation. This dissertation used mixed methods to explore how body language of children with ASD is demonstrated and perceived in PA settings and reports the first-stage validation and associated refinement of the Body Language Coding Scale (BLCS) to help instructors with body language identification and interpretation.Methods: Twelve parents of children with ASD (7-12 years) were interviewed to explore thoughts about their child’s body language and their impressions of its interpretation by PA instructors. Next, the BLCS was used to quantify body language during a motor assessment performed by 31 children with ASD (6-12 years). BLCS reliability and its association with motor proficiency and skill enjoyment were evaluated. A content validity evaluation was undertaken with three parents of children with ASD (8-12 years) to review cue valence. The BLCS scoring was revised and reliability was re-evaluated. Results: Misinterpretation of non-basic emotions expressed through body language was identified by parents as a knowledge gap. The BLCS showed excellent intra-rater and moderate inter-rater reliability. No significant associations were shown between body language, motor performance and enjoyment. Parents’ evaluation of cue meaning demonstrated concurrence with BLCS cue valence. Further refinement of the BLCS (including renaming of positive/negative categories to engaged/not engaged) resulted in the BLCS-v2-revised, which demonstrated excellent intra-rater and good inter-rater total score reliability, and excellent intra- and inter-rater category reliability. Discussion: The BLCS-v2-revised is a reliable and valid measure of body language of children with ASD. Further research is needed on the feasibility of using the BLCS-v2-revised in the community context. Conclusion: The BLCS is ready for introduction to PA instructors as a tool to help them communicate better with children with ASD. Bringing awareness of body language differences in children with ASD may help instructors create a more inclusive environment to support participation and enjoyment.

Keywords: Autism
Body language
Engagement
Physical activity
Advisor: Wright, Virginia
Supporting Kindergarten Student’s Development of Knowledge, Skills and Understanding about Truth and Reconciliation

In Kindergarten, educators and students are called to action to engage in learning related to truth and reconciliation. The purpose of this study is to explore how educators can engage Kindergarten students in learning about truth and reconciliation within three Kindergarten classrooms. Using a qualitative case study approach, this study investigates the question: What practices support Kindergarten student’s development of knowledge, skills and understanding about truth and reconciliation? This study will extend our understanding of how to respond to the Calls to Action in the early years theoretically and pedagogically and contribute to the literature.The results from this study indicate that there are practices that educators can engage in as they move through a continual process of teaching and learning about truth and reconciliation and adopt a ‘reconciliatory stance’ to support Kindergarten students’ knowledge, skills and understanding of truth and reconciliation. Challenges related to teaching and learning about truth and reconciliation in Kindergarten include encountering resistance or pushback from others regarding the appropriateness of this work and the lack of capacity building for educators. The seven major findings from this study include: 1) there is a continual process that educators must engage in throughout the school year to develop knowledge, skills and understanding about truth and reconciliation; 2) there are practices that educators can use to support the development of knowledge, skills and understanding about truth and reconciliation; 3) educators need to have a strong understanding of how to connect teaching and learning about truth and reconciliation to the Ontario Kindergarten Program document and other guiding documents; 4) educators must continue to engage in professional learning to have the knowledge and understanding of how to bring this work into their practice; 5) more Kindergarten-specific resources need to be developed; 6) adopting a ‘reconciliatory stance’ allows educators to respond to teachable moments within the classroom related to teaching and learning about truth and reconciliation; and 7) this work needs to be done in relation and in community. Implications of this study suggest that there are powerful possibilities for developing a strong foundation for truth and reconciliation with students in Kindergarten.

Keywords: Kindergarten
Truth and Reconciliation
Advisor: McDougall, Doug
Validating the WD Repeat Protein CDC40 as a Potential Therapeutic Target for Lung Cancer

Lung cancer is the second most diagnosed and most lethal cancer globally. Presently, there is a need for novel targets for the development of improved therapeutics. Data mining of whole genome genetic dependency screens suggested that the pre-mRNA splicing factor Cell Division Cycle 40 (CDC40) is essential for lung cancer cell survival. In this study, I characterized the effects of CDC40 knockdown in a panel of lung cancer cells. I show that CDC40 knockdown induced cell cycle defects resulting in strong growth inhibition and activation of late-stage apoptotic markers in all lung cancer cells tested. To further understand the cellular consequences of CDC40 suppression, I investigated global transcriptional and splicing changes and found that CDC40 knockdown resulted in a perturbation of splicing and translation-related genes in addition to a higher number of transcripts with intron retention. I explored one specific intron retention event in the mRNA transcript of the cell cycle regulatory protein CDCA5, a potential prognostic marker for cancer, and showed that CDC40 knockdown induced retention of its first intron leading to an increase in the unspliced CDCA5 transcript, and subsequent decrease in CDCA5 protein expression. Finally, I explored the direct protein interactions of CDC40 in lung cancer lines and found spliceosome components as the predominant binding partners for CDC40, further highlighting the major role of CDC40 in splicing. CDC40-CDC5 interaction, identified in the current thesis, was investigated using peptide displacement assay for drug development purpose. So far, no hits have been confirmed from screens. In addition, no disruption was observed even with quadruple mutations within the putative binding pocket on CDC40. This implies that it may be difficult to disrupt key protein-protein interactions using small molecules within this very large complex. In summary, I was able to demonstrate that CDC40 is important for lung cancer cell survival and has potential as a novel therapeutic target for lung cancer treatment. I confirmed that CDC40 is involved in the human pre-mRNA splicing process as it is an important component of the spliceosome like its yeast counterpart. Furthermore, I characterized several CDC40 interactors to look for pockets for future therapeutic intervention.

Keywords: CDC40
Drug discovery
Protein-protein interaction
shRNA knockdown
Splicing
WD Repeat protein
Advisor: Al-awar, Rima RA
Vedadi, Masoud MV