VictorJuiz/thesis huggingface dataset:
Investigating the Roles of Anionic Phospholipids in Endocytic Trafficking in Mammalian and S. cerevisiae Cells
Keywords: Endocytic trafficking
Non-vesicular transport
Phosphatidylinositol
Phosphatidylserine
PIPKH
Retrograde transport

A fundamental feature of eukaryotic cells is their compartmentalization into organelles. This allows for the segregation of biochemical processes, such as protein translation, energy production, macromolecule catabolism, and the transcription of genetic materials. Organelles are delineated by membrane bilayers that are composed of transmembrane and peripheral proteins and lipids. For organelles to maintain their functionality, they must constantly refresh or receive new lipids and proteins. Additionally, organelles are not static structures found in the cytoplasm but are highly mobile and moved around the cell using microtubule-based motors. Two main mechanisms are responsible for the movement of material between organelles. This includes vesicular transport of proteins and lipids and non-vesicular movement of lipids. Non-vesicular transport is best characterized to occur at sites of contact between the ER and other organelles. However, other contacts have been described which do not rely on the ER. Importantly, not only are lipids essential components of the bilayer of organelles but they also contribute to the identity of the organelle, signal transduction, functionality, and vesicular transport. This thesis examines the roles of negatively charged lipids, specifically phosphatidylserine (PtdSer) and phosphorylated variants of phosphatidylinositol (PIPs) on organelle identity, vesicle budding and transport, and the relative roles for vesicular and non-vesicular transport in the subcellular distribution of PtdSer and cell polarity. Results from my studies reveal i) a redistribution of the phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) to endomembrane structures upon PIPKH (PIP5K homolog) overexpression that is accompanied by an accumulation of PIPs, which increases the negative surface charge of endomembrane that in turn leads to the relocalization of polycationic proteins. ii) PtdSer is not only a cargo of Snx4 and Retromer mediated retrograde transport pathways but is also essential to support the formation and recycling of cargo, and iii) Osh6 and Osh7, two proteins involved in the non-vesicular transport of PtdSer, are dispensable with regards to the polarization of PtdSer in the plasma membrane of yeast and not required to support robust cell polarity pathways. Together, my results highlight the importance of anionic phospholipids in organelle identity and endocytic trafficking.
Conceptualizing Life after Death. The Evolution of the Concept of Duat and Related Notions in Egyptian Funerary Literature
Keywords: Afterlife
Ancient Egyptian Language
Ancient Egyptian Religion
Archaeology
Egyptology
Funerary Texts

The aim of this dissertation is to trace the diachronic development of the notion of Duat, the ancient Egyptian realm of the dead. Despite being a key component of the afterlife beliefs, this notion has defied all scholarly attempts at a clear definition, as it underwent a process of evolution over thousands of years without ever designating just one place at a time, but always possessing both chthonic and celestial features at once. Furthermore, new images and ideas were constantly introduced, and new layers were added to the core ideological framework established in earlier times. This study is based on the analysis of royal and non-royal funerary texts from the end of the Old Kingdom to the end of the New Kingdom (Pyramid and Coffin Texts, Book of the Dead, Underworld Books, and Books of the Sky) and aims to outline what the term Duat encompassed, where it was thought to be located, and how its characterization evolved over time. Besides presenting the most significant passages mentioning and/or describing the Duat in the various funerary compositions, each chapter will also discuss any relevant theological, cosmological, geographical, and astronomical notions necessary to clarify the conceptual framework, of which the Duat formed but a part, and will try to relate its evolution to the concurrent changes in Egyptian culture, society, and ideology. Additionally, since patterns of distribution of texts and imagery played a significant role in both temples and tombs, an analysis of the correlation between the various funerary texts and their material support complements the study, with the purpose of highlighting what the Egyptians believed to be a magical synergy between the texts for the afterlife and their context. By bringing together all these aspects, significant insight will be gained not only into the conceptualization of the next, metaphysical world but also into the understanding of the physical reality in which the Egyptians lived every day, long before those funerary texts would be of any use to them.
Post-2003 Collective Forest Tenure Reform in Fujian, China: Institutional Diversity and Farmer’s Preferences
Keywords: collective forests
common-property resources
community forest management
farmer's preference
forest decentralization
forest tenure reform

China’s post-2003 collective forest tenure reform has drawn substantial attention. Based on the evidence from Fujian Province, this research focuses on three topics that pertain to this reform but have not been sufficiently studied in the literature. Chapter 3 focuses on the diversified approaches that villages developed to change their forest tenure systems. Based on the reform implementation archives of 41 villages, I identify various tenure change approaches and categorize them into two types: tenure form changes and tenure security enhancements. I find that the majority of commercial forests experienced tenure security enhancements instead of tenure form changes in the reform, and the possibilities of experiencing these two types of tenure changes vary across bamboo forests, economic forests and timber forests. Chapter 4 discusses how community commercial timber production is affected by the restructuring of devolving forests from the villagers’ committee to villagers’ groups, which is the major approach to changing forest tenure forms in Fujian. The comparative study based on two cases reveals the mixed effects of this restructuring. By decreasing groups size and decentralizing forest management powers, this restructuring increases the equity of allocating timber revenues and enhances the accountability of forest managers to ordinary farmers. However, this restructuring threatens the long-run efficiency of timber production because villagers’ groups often have weaker organizational capacities than the villagers’ committee. Chapter 5 focuses on the controversy regarding reallocating timber revenues according to demographic changes and discusses the trade-off between equal access and individual rights in the reallocation problem. I find that farmers support reallocating timber revenues to achieve equal access, and such preference pertains to social preferences including altruism and aversion to inequality. However, farmers’ preference for reallocation may be lower if they feel reallocation is difficult to implement. 中国2003年之后的集体林产权改革在学界已经引起诸多关注。基于福建省的经验证据，本研究考察了与本改革相关、但既有文献鲜有关注的三个问题。第三章聚焦于村庄层面上多种多样的林权变革方式。基于41个村庄的林权改革实施档案，笔者识别了各类林权变革方式并将其分为两类：产权形式变化和产权稳定性增加。笔者发现在改革中，多数商品林经历的是产权稳定性增加而非产权形式变革。而且，经历这两种产权变革类型的概率，在竹林、经济林、用材林这三种森林类型之间并不相同。第四章讨论把林权从村委会下放到村民小组这一产权变革方式的影响。对两个村庄的比较案例研究表明，这一制度变革既有正面也有负面影响。通过降低组织规模和下放森林管理权利，这一变革增加了木材收入分配的公平性，并且提高了森林管理者对普通村民的问责性。但是，由于村民小组通常比村委会的组织能力更弱，这一变革危及了木材生产的长期效率。第五章聚焦于集体木材生产中根据人口变化调整木材收入分配的争议，并且讨论了在林权制度设计中如何权衡平等受益与个体权利这两项目标。笔者发现多数农民支持根据人口变化来调整木材收入分配，从而实现平等受益的目标。这种偏好与利他、不平等厌恶等亲社会偏好相关；但是，如果追求平等受益的实施成本较高，农民对平等受益的偏好会降低。
Systemic and Local Modulation of the Immune Response to Allogeneic Cell Transplants
Keywords: Differentiation
Immune tolerance
Stem cells
T cells
Transplantation

Immune rejection is a critical barrier to successful organ transplantation and stem cell therapies. In this project, I investigated the targeted modulation of the immune system to induce immune tolerance and alter the immune response to allogeneic grafts: 1) The first part of my Ph.D. project aimed to develop a mouse model that had functional human T cells for studying patient-specific allogeneic graft rejection. In the thymus, thymic epithelial cells can “educate” developing T lymphocytes and induce a specific tolerance for T cells to recognize self and non-self. Here, human pluripotent stem cells (PSCs) were in-vitro differentiated into thymic epithelial cell progenitors (TEPs) by mimicking a series of signal pathways important for embryonic thymus development. The upregulation of appropriate cell markers was detected at each differentiation stage; however, the expression of TEP markers FOXN1 and Cytokeratin (CK) 5 was not robust in the differentiated cells. The following in vivo functional assay indicated the TEP-like cell graft in a humanized mouse model was not functional and could not attract the lymphoid progenitors and could not further support T cell development. More optimization of TEP differentiation protocol is needed for future research and the clinical applications. 2) Learning from the immune regulation, I expressed a combination of immunomodulators (IMs) in allogeneic cells in order to induce local immune tolerance and prevent allogeneic immune rejection. The in-vitro cell interaction between human immune cells and IM-expressing cells (H1-FS-8IMs) derivatives showed suppressed immune proliferation and proinflammatory cytokine production. Immune profiling results also demonstrated the dynamic changes in human immune cells in the IM-expressing group. We observed the shift in the immune cell homeostasis, the weakened homing ability of naïve T cells and dendritic cells, indicating the expressed immunomodulators induced immune suppression. The in vivo evaluation is still in progress. A more robust immune response to the allogeneic teratoma tissue derived from human ESC without IMs expression was observed in the hu-PBL-NSG humanized mouse model. Further in vivo analysis is needed to assess the immune response and immune tolerance induced by H1-FS-8IMs-derived allogeneic cell grafts in a humanized mouse model.
Probing the Religion-health Connection: Integrating Insights from the Life Course Perspective and Social Networks
Keywords: health
life course
religion
social networks

While the balance of existing evidence suggests that religion is positively related to health and mental health, the nature of this relationship is complex, with religiosity found to have positive, negative, and null associations with various forms of health. While much progress has been made in revealing this complexity, there are several promising directions that can illuminate currently understudied aspects of this relationship. This dissertation further probes the religion and health connection by integrating the life course perspective and the religious dimensions of people’s close social networks. I argue that the premise that earlier life conditions affect later life outcomes contains an underlying logic generalizable to the domain of religion. Using longitudinal data, Chapter 2 explores the potential long-term health effects of religiosity in the childhood home, and finds that children brought up in highly religious households have a higher risk of mortality than those socialized in more moderately religious households. Extending the findings of Chapter 2, Chapter 3 uses over 35 years of prospective panel data and expands on the life course perspective by considering religious accumulation—the consequences of remaining (ir)religious—as opposed to increasing or decreasing religious attendance, what I term religious mobility. Taken together, results suggest an enduring influence of childhood religiosity on health and mortality, and a beneficial impact of continuity of frequent religious practice over the life course. Health behaviors, particularly smoking, largely mediate the relationship between childhood religiosity and health. Finally, Chapter 4 examines why network religiosity may promote or detract from well-being. Social connection is often offered as the reason for why religion (broadly defined) is beneficial for health. Using nationally representative egocentric network data, this chapter indicates that various dimensions of network members’ religiosity—shared religious tradition, discussion of religious matters, and exchange of prayer support—have different implications for mental health. These associations, moreover, are contingent on respondents’ own religiosity. Considered as a whole, this dissertation broadens the vast body of work assessing the complex relationship between religion and health by offering insight into when and why religion may shape health, in both positive and negative ways.
Marriage, Work, and the Construction of the Family in Nineteenth-century English Law and Legal Thought
Keywords: Domestic Relations
Employment Law
Family Law
Legal History

This thesis is concerned with the dissolution of the household and the construction of the family in English law and legal thought in the long nineteenth century. It examines (intersecting) intellectual and institutional dimensions of this process, focusing on shifting legal concepts of work and family, and some of the specific legal-institutional moves (statutory, judicial, administrative) that contributed to the creation of the family’s categorical status in the social and legal order and a distinct and exceptional body of rules – Family Law – for its governance. Drawing on recent scholarship on Family Law Exceptionalism, it is concerned to show how a confluence of laws and ideas helped to shape the modern disaggregation of work and family, and adherence within Anglophone legal systems to regulatory models premised on divisions between realms of production and reproduction. This excavation of law and legal thought is designed to shed light on the historical processes that contributed to the emergence of English Family Law; and, in so doing, reveal the constructed, contingent nature of the legal family and its exceptional domain of regulation. Using the Blackstonian household as a launching pad, the story told in the thesis follows two mutually reinforcing narratives. One movement involved the staged extrusion of productive work relations (in the narrow sense of work for pay) from the household, and their re-characterization as market-based activities exterior to the family and governed by a legal regime that blended contract and coercion. Certain household-based forms of work, notably domestic service and apprenticeship, were treated in a different manner because of their ongoing connection to the family, but eventually they too were deemed non-familial (but also subject to differing schemes of regulation). The other movement involved a new legal emphasis on marriage as the core relation within the non-productive private family, which involved the conceptualization and treatment of marriage as a site of legitimate public concern and intervention. That process relied in part on a set of scholarly, judicial and (to a lesser extent) legislative moves that distinguished marriage from contract on the basis of the English state’s perceived interest in regulating conjugal practices.
Cellular Systems Biology of Trophoblast Heterogeneity in Human Early Placenta Development
Keywords: Data Science
Genomics
Placenta
Proteomics

Chorionic villi, the functional units of the human placenta, form the only inter- face between fetal and maternal systems facilitating exchange of nutrients, metabolic waste, and signaling factors. Complex and branched villi structures composed of cy- totrophoblast, extravillous trophoblasts, syncytiotrophoblasts, and stromal cells arise from a single epithelial layer of a blastocyst. How a single cell monolayer specifies and differentiates into the three trophoblast lineages during early development re- mains uncharacterized. Additionally, heterogeneity within each trophoblast lineage has described on the basis of varying cell morphologies but a wide scale investigation to characterize functional differences has not been conducted. In this thesis, I inves- tigate the cellular composition of the human placenta in order to characterize hetero- geneity within trophoblast lineages and how population dynamics change during the first trimester. Firstly, I identified dynamic trophoblast subpopulations through cell surface proteomics and single cell transcriptomics. A novel EpCAM positive popula- tion identified with greater expression before gestational week 6 is further explored as candidate progenitor marker. This population is more mitotically active than the respective negative population and does not express markers of terminally differentiated trophoblasts. Temporal information is required to investigate the role of these cell populations in the development of a placenta. This motivated me to create a cell atlas of first trimester development by integrating four individual single cell sequencing datasets. Single cell transcriptomics of over 65 000 cells covering placenta develop- ment from gestational week 2 to 12 suggests the existence of a transient bipotential progenitor during early first trimester compared to two separate developmental cen- ters for EVT and STB lineages in late first trimester. Work in this thesis highlights first trimester trophoblasts are much more heterogeneous than perviously believed and due to their rapidly dynamic nature, gestational age is an important consideration for future studies.
CRISPR-cas9 and TALEN Mediated Gene Editing for Treating Cystic Fibrosis
Keywords: CFTR
CRISPR-cas9
Gene Editing
Gene Therapy
Genetic Disease
TALEN

Cystic Fibrosis (CF) is an inherited monogenic autosomal recessive genetic disease that is most commonly seen in the Caucasian population. CF is caused by mutations along the Cystic Fibrosis Transmembrane Regulator (CFTR) gene which is a channel protein that regulates chloride- secretion. Conventional treatments such as physical therapy, antibiotics, and nutritional care only alleviates symptoms but does not provide a cure. New emerging channel potentiators and correctors slowed disease progression for 90% of patients. Gene therapy is an attractive strategy for treating CF as it treats all mutation classes along the CFTR gene. Targeting the airway stem cells for permanent integration of CFTR gene may provide a long-term cure for CF. In this study, we utilized a helper-depended Adenoviral (HD-Ad) vector system to package both gene editing tools and donor genes into a single vector for delivery, owing to its large carrying capacity (36 kb). TALEN and CRISPR-cas9 were utilized as gene editing tools. We first utilized a LacZ donor system to evaluate integration efficiency before integrating CFTR. We demonstrated 5% integration efficiency at the AAVS1 locus using TALEN and 10% using CRISPR-cas9. In addition, the level of TALEN/CRIPSR-cas9 and vector genome diminishes rapidly following delivery, suggesting expression of these components are transient. We showed CRISPR-cas9 mediated gene editing efficiency can be enhanced by supplying cells with key factors involved in cellular repair pathways, SCR7 (DNA ligase inhibitor), CtIP, and Exo1. Integration of CFTR using both TALEN and CRISPR-cas9 lead to long-term stable CFTR mRNA and protein expression; functional analysis showed 50% CFTR channel function restoration without enhancement and close to 100% channel function rescue with enhancement. Collectively, these data showed feasibility of permanent CFTR integration for future in vivo applications.
Studio of Nature: The Transformation of Artists' Studios, 1845–1910
Keywords: Landscape
Modern Art
Nature
Nineteenth Century
Studios

"Studio of Nature: The Transformation of Artists' Studios, 1845–1910" examines artists' studios in Britain, France, and the United States from the advent of Realism to the Arts and Crafts movement at the turn of the twentieth century. I consider in particular how changing conceptions of the natural environment in the nineteenth century contributed to the emergence of new studio paradigms. The nineteenth century witnessed a dramatic rise in the number of artists who left the studio to paint outdoors. Artists associated with movements as diverse as the Barbizon School, the Hudson River School, Realism, Pre-Raphaelitism, Naturalism, and Impressionism all engaged in plein-air practice to varying degrees. A close engagement not only with physical nature but also with the ideals it represented guided artists working across a variety of artistic genres. In addition to the continued rise of landscape painting in the nineteenth century, the emergence of Realism challenged inherited notions of the studio as a place of retreat that had prevailed since the Renaissance. The positivism that informed artistic movements around midcentury encouraged a direct engagement with reality. While fragments of the natural world could be brought into the studio for study, by and large the studio separated artists from physical nature. This epistemological shift catalyzed numerous studio innovations that unfolded in the decades that followed: the studio was variously transformed into an optical instrument, a mobile apparatus, a transparent prism, and an agent of social reform. As the identity of the modern artist emerged in the nineteenth century, the studio was reimagined to meet the needs of a new generation of artists. "Studio of Nature: The Transformation of Artists' Studios, 1845–1910" foregrounds the significance of the studio as both a contributor to as well as an index of changing artistic standards in the context of modernity.