VictorJuiz/thesis huggingface dataset:
Genetic and molecular features of placental abnormalities : preeclampsia, placenta accreta and mouse models
Keywords: Genetics.

Pregnancy is a complicated process were the maternal body dramatically adjusts to accommodate e developing embryo. The mediator of maternal-fetal interactions during pregnancy is the placenta, a transient organ that develops from extraembryonic cells in the blastocyst. Placental cells called trophoblasts promote remodeling of the uterine vasculature to ensure proper exchange of nutrients, gases and waste between the two organisms. In humans, these trophoblast cells in the maternal-fetal interface are highly invasive, and any misstep in regulating trophoblast invasion can bring about pregnancy complications that can be fatal to both mother and child. One of such complications is preeclampsia, where shallow placental invasion leads to limited perfusion to the placenta in the third trimester, causing organ damage and hypertension in the mom. If the placenta is not delivered, preeclampsia can develop into eclampsia, which leads to seizures and death. The rate of preeclampsia is about 5% worldwide, but incidence and death rates are much higher in non-European populations, where it has primarily been studied. In Chapter 2 of this thesis, I study indigenous families in the Andean highlands in Peru, where preeclampsia incidence is 16 20%, and find genomic regions associated to preeclampsia and its phenotypic features in the three organisms—mom, dad and child—involved in the disease. These regions include genes with both known and unknown roles in pregnancy that can be subject of functional studies to further understand healthy placentation and the root causes of preeclampsia. In Chapter 3, I and others perform the largest GWAS metanalysis on mothers of European descent and uncover four new regions of small effects in preeclampsia risk on the maternal side. Another placental disease is placenta accreta, in some ways opposite to preeclampsia, where trophoblast cells invade the uterus beyond the maternal-fetal interface because a proper barrier does not form. In Chapter 4, I describe some of the proteins that are overexpressed in these invasive trophoblasts, and then investigate the maternal plasma proteome to develop a biomarker-based diagnostic assay that can aid in early detection and intervention of accreta. Finally, in Chapter 5, I move into the mouse as a model organism to understand invasive trophoblast biology and describe the transcriptomic differences in two knockouts with altered trophoblast function related to the polyploid nature of these cells
The genetic basis of parallel and divergent evolution in threespine stickleback
Keywords: Developmental Biology.

A central goal of evolutionary biology is to understand the nature and extent of genetic patterns underlying adaptive phenotypes. For example, when faced with similar environmental challenges, does evolution use similar molecular solutions, and if so, how are they similar? And do diverse changes in common traits arise from modifying different genes, or particular genes in different ways? The threespine stickleback provides an excellent model system to study these questions due to its unique natural history and diverse ecological niches. In my thesis work, I utilize experimental and computational approaches to both the parallel and divergent aspects of stickleback evolution to address these key evolutionary issues from multiple perspectives. To examine recurrent patterns in parallel evolution, I identify a large set of genomic loci that change repeatedly during colonization of new freshwater habitats by marine stickleback. The same loci used in these extant populations also show rapid allele frequency changes when new freshwater populations are experimentally established from marine ancestors. Both the speed and location of changes can be predicted using empirical observations of recurrence in natural populations or fundamental genomic features like allelic age, recombination rates, density of divergent loci, and overlap with mapped traits. A composite model trained on these stickleback features can also predict the location of key evolutionary loci in Darwin's finches and cichlids, suggesting similar features are important for evolution across diverse taxa. To study patterns in divergent evolution, I analyze different wild populations of freshwater stickleback that have either increased or decreased the lengths of their prominent dorsal and pelvic spines and identify a new regulatory locus with a major morphological effect on spine length. Natural alleles at this locus are differentiated between marine and freshwater sticklebacks; however, alleles found among freshwater populations are also differentiated, with distinct alleles found in short- and long-spined freshwater populations with reciprocal regulatory effects on the bone growth inhibitor gene Stanniocalcin2a. Many other stickleback loci similarly show three or more major alleles, suggesting that diverse alleles at key loci may represent a common mechanism for producing diverse phenotypes from a smaller toolkit of genes
Geometric representations of W-algebras and applications to the quantum Langlands correspondence
Keywords: Mathematics.

Fix a reductive group G, and consider the affine W-algebra associated to a principal nilpotent element of the Lie algebra of G. We determine the block decomposition of its category of highest weight, i.e. positive energy, representations, and identify regular blocks with Whittaker sheaves on the affine flag variety of G. We also identify the latter category, under a mild hypothesis on the central charge, with Category O for the affinization of the Langlands dual Lie algebra at the dual central charge. The latter confirms a conjecture of Gaitsgory, and implies non-factorizably, a related conjecture of Gaitsgory and Lurie
Geophysical applications of sound : volcano infrasound and marine seismic sources
Keywords: Geophysics.

Acoustic waves are generated by a wide range of natural and artificial geophysical phenomena. By studying the acoustic signals, insight can be gained about the fundamental processes governing these phenomena. In this thesis I examine acoustic signals from two different sources; volcanic eruptions and pneumatic marine seismic sources. In Part I of this thesis I consider acoustic waves generated by volcanic activity. Volcanoes are prodigious sources of low frequency acoustic waves, which are termed infrasound as the signals are predominantly at frequencies below human hearing. Harmonic infrasound signals are observed at open-vent volcanoes and in Chapter 2 I develop a numerical model to demonstrate that these signals can be explained by acoustic resonance of the crater. In Chapter 3 I apply this model to the 2015 eruption of Villarrica (Chile) and show that the lava lake rose in the crater prior to the paroxysmal eruption. These two chapters illustrate the utility of monitoring infrasound resonant modes at open vent volcanoes and may aid in forecasting future eruptive activity. The majority of volcano infrasound studies assume linear wave propagation. However, volcanic eruptions are violent phenomena and there is increasing evidence of nonlinear wave phenomena, such as shock waves, during eruptive activity. In Chapter 4 I perform nonlinear computational aeroacoustic simulations of volcanic eruptions to explore the effect of nonlinear wave propagation and demonstrate that assuming linearity can result in overestimation of erupted fluxes for eruptions with high (supersonic) exit velocities. In Part II of this thesis I study pneumatic marine seismic sources, which are the predominant source used in marine seismic surveys. Pneumatic seismic sources are broadband sources that generate both geophysically useful low frequencies and high frequency noise that is harmful to marine life. In Chapter 5 I explore controls on the initial peak of a pneumatic seismic source signature. The initial peak is generated by the initial release of highly pressurized air into the water and is responsible for generating high frequency noise that can be environmentally damaging. In Chapter 6 I present numerical simulations of a novel pneumatic seismic source, called the Tuned Pulse Source, and demonstrate that this source will generate increased low frequency content. In Chapter 7 I digress slightly to compare marine seismic signals with the low frequency calls of fin whales and speculate on possible mechanisms of low frequency sound generation in whales
George Padmore's African Revolution: Reviving Marxism-Leninism in the 20th Century Pan-African Tradition
Keywords:  Department of History
George Padmore
Pan-Africanism
Black Britain
International African Service Bureau
Pan-African Congress
Black Marxism
Black Radical Tradition
International Trade Union Committee of Negro Workers
Stanford University History Department
Thesis

This thesis is an intellectual biography of the Trinidadian anti-colonialist George Padmore (1903-1959), focusing on his life between 1927 and 1945. Drawing upon archival research in London, Moscow, and New York, it traces how Padmore's early conversion to Marxism as a member of the Communist International influenced his thinking on how to achieve African independence. Throughout the 1930s and 40s, Padmore was a central figure of Pan-African organizing in the Anglophone world and worked alongside black revolutionaries such as C.L.R. James, Jomo Kenyatta, and Kwame Nkrumah.
Giant magnetoresistive nanosensor analysis of circulating tumor DNA for therapy response monitoring and early detection of cancer
Keywords: Chemistry.

In the era of precision medicine, molecular subtyping of non--small cell lung cancer (NSCLC) has revolutionized therapeutics tailored to individual actionable mutations, particularly the use of tyro- sine kinase inhibitors (TKIs) for Epidermal Growth Factor Receptor (EGFR) mutations. However, efficient therapy selection remains challenging for some patients, and it is estimated that 20% of lung cancer patients begin therapy prior to EGFR testing. Common reasons for lack of molecular testing include insufficient tissue biopsy or inability to biopsy certain patients, and long turnaround times to results. Clearly, new technologies that are rapid, cost--effective, and highly sensitive are needed for effective companion diagnostics. This thesis outlines the development and clinical translation of a blood--based circulating tumor (ct) DNA EGFR genotyping assay using giant magnetoresistive (GMR) nanosensors as an alternative for therapy selection and response monitoring. This GMR as- say achieved analytical sensitivities of 0.01% mutant allelic fraction for 3 common "hot spot" EGFR mutations, equivalent to detecting 1 mutant allele in a background of 10,000 wild--type alleles. In a clinical study of therapy selection and response monitoring of metastatic NSCLC patients, the assay achieved high sensitivity and specificity (AUC > 0.95) and was able to accurately predict therapy response after just 2 weeks. This represents a vast improvement compared to the current clinical standard of radiographic (CT) assessment after 2--3 months, which can be a harmful delay for patients who do not respond to targeted therapy and need immediate changes in therapeutic regimen. GMR sensors were also utilized for the early detection of colorectal cancer (CRC). While CRC diagnosis in Stage I is associated with a 90% 5--year survival rate, common screening methods such as colonoscopy or fecal testing are underutilized, resulting in a majority of CRC patients diagnosed at later stages. A non--invasive blood--based ctDNA test with GMR sensors could aid in screening efforts, with methylation biomarkers indicated for improved early cancer detection compared to mu- tations. This thesis also details the technology development of integrating methylation--specific PCR with high resolution melt (HRM) analysis on GMR sensors for quantifying methylation density. The technology was first optimized in a melanoma cell line model, and then extended to a multiplexed panel of 4 putative biomarkers of early CRC. This assay achieved analytical sensitivities of 0.01% methylated allelic fraction for 3 of 4 markers, and was validated in 2 late stage CRC patient samples
Glial Priming in Neocortical Circuit Maturation
Keywords:  Department of Biology
Biology
Neurobiology
Neuroscience
Astrocyte
Glia
Neural Circuit
Neurodevelopment
Neuroinflammation
Neuroimmunity
Thesis

The combinatorial effects of sequential neuroimmune insults have been implicated in the pathogenesis of many neurological disorders. To explore how prenatal and early postnatal innate immune activation impacts the developmental establishment of neural networks, we developed a neuron-astrocyte coculture model of virus-like neuroinflammatory challenges and used calcium imaging with the GCaMP reporter to document cell- and ensemble-level activity patterns over time. Neurons co-cultured on naïve astrocytes provided baseline measures of activity and synchrony within neuronal ensembles. Interferon gamma (IFNγ) exposure measurably accelerated the acquisition of synchrony within ensembles co-cultured with serum-preactivated, but not naïve, astrocytes. Machine learning analyses of neuronal synchrony data identified distinct, immune exposure-dependent patterns of maturation which are sufficient to predict the immune exposure history of cells based on their signaling properties with over 90% accuracy. Combined exposure to IFNγ and primed astrocytes was also correlated with increases in the ratio of protein expression levels of chloride symporters KCC2 and NKCC1, suggestive of accelerated neuronal maturation in dual hit-challenged cells. Collectively, these findings suggest that early-life inflammatory exposures can prime astrocytes to respond differently to later immune events than naïve astrocytes and identify one potential mechanism through which immune challenges can alter key neural network milestones in perinatal development.
Global changes in the structural dimensions of national education systems : high stakes exams, tracking, and national assessments, 1960-2010
Keywords: Sociology.

My dissertation examines global changes in several fundamental structural dimensions of national education systems that shape social stratification and the quality of a country's education: national high stakes examinations, tracking, and assessment tests. To analyze these changes, I draw on a newly constructed global panel dataset of 140 countries from 1960 to 2010. Using panel data and event history models, I argue that worldwide shifts in conceptions of education after World War II, toward universal and egalitarian norms of educational access, led to a decline in the use of high stakes exams and tracking at lower levels of the educational process; they also contributed to the dramatic expansion of national assessment testing in countries around the world. These changes have been shaped by the globalization of democratic norms, the rise of global social movements like "Education for All, " and international non-governmental organizations that shape and disseminate world societal discourse on education. My findings have broader implications for understanding: (a) the role of macro-level cultural/institutional processes in shaping educational stratification, (b) how competing conceptions of education, as a mechanism for both spreading equality and allocating individuals to unequal roles, create tensions in the way that nation-states construct their education systems, and (c) theoretical tensions between cultural processes of rationalization and expanding notions of individual personhood
Gluca-gone : an examination of glucagon secretion from human islets and stem cell-derived alpha-like cells transplanted in a novel glucagon-null mouse
Keywords: Developmental Biology.

Glucose homeostasis is a common process throughout the animal kingdom. The importance of glucose control is made apparent by the mortality of diseases that affect energy management tissues, like diabetes, if left untreated. The cause of diabetes is largely rooted in the dysfunction of hormone signaling axes between endocrine micro-organs, called the islets of Langerhans, and the tissue targets of their hormones. Islets of Langerhans are clusters of heterogeneous endocrine cells dispersed throughout the pancreas. Islets maintain glucose homeostasis via hormone regulation of glucose metabolism and glucose uptake in target tissues. Islet endocrine cells are glucose-sensing, and hormone release from islet cells is tightly coupled to circulating glucose levels. Islet α cells secrete glucagon under low glucose conditions, which drives hepatic glucose output through glycogenolysis and gluconeogenesis. In contrast, increases in blood glucose trigger islet β cell insulin secretion, which promotes glucose uptake in target organs. Diabetes is characterized by insufficient or dysregulated hormone output by α and β cells. While both glucagon and insulin secretion are dysregulated in diabetes, compared to β cell insulin secretion, little is known about mechanisms regulating α cell glucagon secretion. Our lack of knowledge about glucagon regulation may be partly due to the lack of tools to study human α cells in a physiological setting, like after transplantation into immunocompromised mice. Distinct mouse and human insulin peptides permit studies of human β cells after xenotransplantation into immunocompromised mice. However, evolutionary conservation of the glucagon peptide sequence amongst placental mammals prevents accurate measurements of glucagon release from transplanted human tissue after xenotransplantation, where variations in endogenous rodent-derived glucagon can obscure measurements. In this thesis, I present a novel immunocompromised transplantation mouse model that lacks endogenous glucagon and thus permits studies of regulated glucagon secretion from human islets. Using this mouse model, we provide evidence that hyperglucagonemia exhibited by patients with type 2 diabetes (T2D) is an islet intrinsic defect that partly contributes to T2D fasting hyperglycemia. Additionally, I present evidence that this glucagon-null mouse model provides a physiological setting to allow longitudinal maturation studies of human embryonic stem cell-derived α-like cells. Along with these in vivo studies, I present a preliminary in vitro study of lentivirus-mediated genetic screens in primary human islets to identify genes that play a role in regulating human α cell function. Overall, the data presented in this thesis underscores the importance of tightly regulated glucagon secretion, provides a new tool to study human α cells in vivo, and will aid in the identification of genes that impact glucagon secretion
Governance under Xi: Party Leadership and Centralized Decision-Making in the Xi Jinping Era
Keywords:  Stanford Global Studies
East Asian Studies
Stanford Global Studies
Asia
Politics
Xi Jinping
Centralization
Party
Thesis

Under Xi Jinping, China saw the increased prominence of the role of the Party in governance as well as a trend towards greater centralization of power. How we interpret these two phenomenon has implications on our reading of China's trajectory going forward. This thesis seeks to explore these two themes from the lens of the CCP, providing an analysis on the larger drivers behind the changes.
Grasping the Heavenly Vault and the Vessel in Raku Kichizaemon XV's Chawanya
Keywords:  Stanford Global Studies
Raku
Raku ware
Raku-yaki
Raku Jikinyu XV
Raku Jikinyu
Raku Kichizaemon XV
Raku Museum
Sagawa Art Museum
Kuta
Tenmon
Tianwen
Chojiro
tea bowls
chawan
youth
coming of age
tea ceremony
chanoyu
chawanya
Stanford Global Studies
Center for East Asian Studies
Thesis

Should I stage a coup d’etat, or be more je ne sais quoi? Am I just a pendulum swinging from frictionless pivots, and like earth to the firmament and the Chawanya, Raku Kichizaemon XV, to the flames, where do I fix my limits?
Ground-satellite optical two-way time and frequency transfer through atmospheric turbulence
Keywords: Electrical Engineering.

Ground-satellite optical time and frequency transfer links will be an essential part of future global clock networks. New time transfer links are needed to support the comparison of state-of-the-art optical lattice clocks in space, and at intercontinental distances across the Earth. New satellite optical links, leveraging optical communications technology, can enable applications in global timekeeping, precision navigation, tests of General Relativity, mapping of terrestrial coordinate frames, and more. This dissertation applies the theory of optical propagation through atmospheric turbulence to the ground-satellite link geometry, for the purpose of analyzing the timing and frequency instability of two-way ground-satellite optical links
Guns, Germs, And Alleles: Analyzing Lone Insider Bioweapons Threats
Keywords:  Center for International Security and Cooperation
Center for International Security and Cooperation
bioterrorism
lone insider threats
Thesis

Prior to the 21st century, biological weapons were considered largely the purview of state bioweapons programs. As the life sciences quickly advanced into the 2000s, including an exponential drop in the cost of DNA sequencing and synthesis, there was increasing concern that weaponizing pathogens may become within reach for non-state actors. The ability to synthesize whole viruses, first demonstrated in 2002, stoked concern that scientists could synthesize agents with pandemic potential that could be used in a mass-casualty attack. Lone insiders in biological laboratories, who have technical training and access to laboratory equipment, were considered a particular threat. Despite these concerns, why have no mass-casualty attacks using pathogens been perpetrated by lone insiders? This thesis considers two factors: the historical capabilities of lone insiders to acquire pandemic potential viruses, and their motivations to perpetrate mass-casualty attacks. First, I show that the malicious acts historically perpetrated by lone insiders are bio-crimes rather than bioterrorist acts, and therefore largely not intent on inflicting mass casualties. Conversely, transnational groups that may have this intent have not sought to recruit insiders in biological laboratories. However, professional and financial gain can be powerful motivators for lone insiders and may still lead to event that can incur large-scale harm. Second, drawing on bibliometric data from synthetic virology papers, I argue that the historical threshold for capability required to synthesize viruses has been prohibitory to those who were not early adopters or innovators in the field synthetic virology, and so there is a small pool of concerning actors that make such attacks less likely, although this is changing as capabilities rapidly diffuse. By more fully understanding the threat of mass-casualty attacks posed by lone insiders and developing better indicators of rapidly changing capabilities, policy makers and research institutions can work to assess this threat and position themselves to prevent and prepare for biological threats.