VictorJuiz/thesis huggingface dataset:
Cardiovascular disease (CVD) in women: literature overview and medical database mining for reproductive risk factors and CVD in women aged 18 to 50
Keywords: Cardiovascular disease (CVD)
young women
pregnancy complications
female reproductive conditions
Thesis

The goal of this non-comprehensive literature review is to provide a structured high level summary of both the cardiovascular risks and the types of cardiovascular diseases (CVD) specific to women, as well as to raise key questions, such as whether there might be a link between the types of cardiovascular disease encountered in young women and risk factors related to pregnancy complications.
The key findings from the medical database analysis of women aged 18-50 are:
Women with reproductive and pregnancy related conditions have a comparable risk of early cardiovascular disease (CVD) to women with diabetes.
Preeclampsia or preterm labor, even in the absence of diabetes mellitus, are higher risk factors for early CVD than gestational diabetes followed by early diabetes.
In women with a history of preeclampsia but no prior risk factors, about 8.6% had a form of cardiovascular disease while still aged 18-50. Compared to all women aged 18-50, the preeclamptic women with no prior risk factors had a higher rate of all types of hypertension (4.70% essential hypertension), angina, ischemic heart disease and atherosclerosis.
The black and “other” race (mostly Latino) women aged 18-50 seem to be at higher risk of developing hypertension after preeclampsia; the proportion of black women with preeclampsia and subsequent hypertension almost quadruples, at 11% compared to the general proportion of blacks in women 18-50 in this data- base.
A sizable proportion of women aged 18-50 with a history of preeclampsia also had a history of gestational diabetes (at least 22%), preterm labor (at least 19%) or poor fetal growth (at least 14%).
Compared to preeclamptic women with no cardiovascular disease aged 18-50, preeclamptic women with subsequent cardiovascular disease aged 18-50 had significantly higher rates of the following reproductive/pregnancy conditions: ear- lier menopause, PCOS, teenage preeclamptic pregnancy, gestational diabetes, uterine fibroids, preterm labor, poor fetal growth.
The causal effects of online ratings on buyer and seller behavior
Keywords: Economics.

This dissertation explores how online ratings influence the actions of buyers and sellers. It begins by analyzing the causal effects of increases in star ratings on demand for products in an e-commerce market, and how those effects vary across different products, sellers, and customers. After finding significant responses from buyers to rating increases, it confirms that there is no pricing response from sellers in the same market to this demand shock. This dissertation concludes by finding that the relative pricing responses of high and low reputation sellers depends on the competition faced by the sellers
The causes and consequences of joint military exercises
Keywords: Political Science.

This dissertation presents three papers on joint military exercises. The first paper, The Joint Military Exercise Data Set, situates joint military exercises in the growing literature on peacetime military cooperation and signaling mechanisms. It presents a new data set of over 5,000 joint military exercises and shows that the use of joint military exercises has been increasing since 1980. The second paper, Expanding Missions, Multilateralism, and Flexibility: Explaining the Increase in Joint Military Exercise Activity Since the End of the Cold War, explains the reasons for one of the most unusual aspects of the growth of joint military exercises, that of exercises between states that do not share a formal defense alliance. I argue that the increase in non-aligned states conducting exercises is due to a combination of reasons. The end of the Cold War led military and defense bureaucracies to advocate for new missions and purposes for which joint military exercises are particularly well suited. An increase in using the military for sub-conventional conflict, such as for peacekeeping or responding to natural disasters, led to a need to establish relationships with new partners. Many of these missions are conducted multilaterally and exercises help establish the personal relationships that underpin their success. Exercises are also a flexible tool that allow countries caught between major powers to maintain relationships with both sides of geopolitical blocs. The third paper, coauthored with Lauren Sukin and titled Joint Military Exercises and Crisis Dynamics on the Korean Peninsula, examines the consequences of joint military exercises on military threats and signals, using the case of North Korean responses to South Korean joint military exercises. Rather than deterring North Korea, exercises are associated with more provocative rhetoric and actions, demonstrating that North Korea views joint military exercises as a serious threat to its security. Moreover, the intensity of North Korea's responses to joint military exercises is driven by the severity of the threat particular exercises pose, indicating that North Korea responds to exercises as serious security threats
Cell volume expansion regulates cell mechanotransduction in 3D microenvironments
Keywords: Mechanical Engineering.

In tissues, such as cartilage, marrow, and bone, cells are tightly surrounded by viscoelastic extracellular matrices (ECMs). These surrounding extracellular matrices may physically influence normal cellular behaviors such as matrix degradation, matrix deposition, differentiation, and migration, which are all critical to tissue regeneration and maintenance of health. However, little is known about the physical interactions between cells and ECMs that underlie the impact of ECM viscoelasticity on these cellular behaviors. Here, we showed the important role of volume expansion as a novel mechanism of how cells sense and respond to the viscoelasticity of the surrounding matrix. First, chondrocytes, sole cells generating cartilage matrix, were examined to understand the impact of volume expansion and matrix viscoelasticity on cellular function and disease progression. Restricted volume expansion of chondrocytes by the spatial confinement activated a pro-inflammatory phenotype of chondrocytes, consequently leading to osteoarthritic phenotypes. In contrast, viscoelastic matrix exhibiting fast stress relaxation allows the cells to form interconnected cartilage matrix and to expand their volume, leading to healthy chondrogenic phenotype. Mechanistically, we found that mechanical confinements of the surrounding matrix regulate volume expansion and intracellular calcium levels, consequently, control the chondrocytes phenotype through a TRPV4-GSK3β signaling axis. Also, we found that the TRPV4-GSK3β signaling axis is impaired in osteoarthritic chondrocytes, so that the OA cells cannot sense and respond matrix viscoelasticity. Next, we examined how cell volume regulates osteogenic differentiation of mesenchymal stem cells (MSCs) in 3D microenvironments. MSCs undergo volume expansion in fast relaxing matrices, and expansion in turn promotes MSC osteogenic differentiation. Osteogenic differentiation is reciprocally regulated by both volume expansion and activation of TRPV4 ion channels which increased nuclear translocation of RUNX2. Finally, the role of cell volume expansion for MSCs 3D migration was investigated. We found a physical mechanism that stem cells use to generate migration paths in 3D microenvironments that are confining and have no pre-existing migration paths. In these microenvironments, stem cells first extend protrusions, which subsequently expand due to movement of the nucleus into the protrusion and influx of ions into the protrusion, opening up a migration path for the cell to migrate through. Together, these findings highlight the remarkable role of volume expansion in essential physiological behaviors including such as cell function, disease progression, differentiation, and even migration in 3D microenvironments
Cell-cycle control in aging, cancer, and homeostasis
Keywords: Chemical and Systems Biology.

Mammalian development and homeostasis require precise control of cellular proliferation. Excess cellular proliferation causes cancer, while insufficient cellular proliferation is associated with aging. The work presented herein details specific mechanisms of cell-cycle regulation and how they contribute to homeostasis, aging, and cancer. The first study reveals how a lack of coordination between major proliferation signaling pathways contributes to cellular aging. In the second study, an unexpected mechanism of action is revealed for an important class of cancer therapeutics targeting the core cell-cycle machinery. The final study describes how cells navigate the inherently stressful process of genome duplication. Taken together, these studies contribute novel insights to our understanding of the mechanisms and importance of cell-cycle regulation
Cell-surface proteome and signaling in neural circuit wiring
Keywords: Biology.

In the evolutionary transition from unicellular to multicellular organisms, single cells assemble into highly organized tissues and cooperatively carry out physiological functions. To act as an integrated system, individual cells communicate with each other extensively through signaling at the cellular interface. Cell-surface signaling thus controls almost every aspect of the development and physiology of multicellular organisms. Taking the nervous system as an example, cell-surface wiring molecules dictate the precise assembly of the neural network during development, while neurotransmitter receptors and ion channels mediate synaptic transmission and plasticity in adults. Delineating the cell-surface signaling is therefore crucial for understanding the organizing principles and operating mechanisms of multicellular systems. My dissertation research integrates method development and mechanistic interrogation to investigate cell-surface signaling in neural circuit assembly. My collaborators and I developed, for the first time to my knowledge, a method for quantitatively profiling cell-surface proteomes in intact tissues with cell-type and spatiotemporal specificities. Applying this method to Drosophila olfactory projection neurons (PNs), I captured cell-surface proteomes of developing and mature PNs and observed globally coordinated dynamics of PN surface proteins corresponding to the wiring and functional stages of the olfactory circuit, providing the first systemic view on how neuronal surface evolves in development. A proteome-instructed in vivo screen identified 20 new cell-surface molecules regulating neural circuit assembly, many of which belong to evolutionarily conserved protein families not previously linked to neural development. These discoveries highlight the power of this new method in uncovering new regulators of brain wiring. Notably, this method should be readily applicable for profiling proteins on the surface of other cell types, tissues, and organisms, far beyond the fly olfactory circuit. In a complementary set of studies on the Plexin B receptor, I developed a generalizable protein tagging approach that reveals cell-type-specific endogenous protein distribution in vivo. Combining this tagging approach and genetic analyses, we found that the Plexin B receptor uses multiple molecular strategies: temporally-regulated protein distribution, level-dependent signaling, and divergent engagement of signaling motifs, to sequentially instruct several distinct steps of axon targeting. These include axon-axon interaction, axon guidance, and synaptic partner selection. Our findings illustrate how a single molecule achieves multi-functionality while preserving its signal specificity in brain wiring. In summary, this dissertation combines quantitative multi-omic profiling and in vivo mechanistic interrogation to elucidate the systemic properties and molecular bases of cell-surface signaling underlying the precise wiring of neural circuits
Cellular control of viscosity counters changes in temperature and energy availability
Keywords: Biology.

Cellular functioning requires the orchestration of thousands of molecular interactions in time and space. Yet most molecules in a cell move by diffusion, which is sensitive to external factors like temperature. How cells sustain complex, diffusion-based systems across wide temperature ranges is unknown. Here, we uncover a mechanism by which budding yeast modulate viscosity in response to temperature and energy availability. This "viscoadaptation" uses regulated synthesis of glycogen and trehalose to vary the viscosity of the cytosol. Viscoadaptation functions as a stress response and a homeostatic mechanism, allowing cells to maintain invariant diffusion across a 20°C temperature range. Perturbations to viscoadaptation affect solubility and phase separation, suggesting that viscoadaptation may have implications for multiple biophysical processes in the cell. Conditions that lower ATP trigger viscoadaptation, linking energy availability to rate regulation of diffusion-controlled processes. Viscoadaptation reveals viscosity to be a tunable property for regulating diffusion-controlled processes in a changing environment
Challenges for dark energy science : color gradients and blended objects
Keywords: Physics.

Some of the most exciting scientific challenges at present in cosmology are in understanding the nature of dark matter and dark energy. The billions of galaxies observed by Legacy Survey of Space and Time (LSST) will dramatically improve the statistical power of weak lensing observations and help probe the mass distribution in the universe more accurately. This increased statistical sensitivity means that potential systematic biases must be carefully identified, quantified, and minimized. My thesis will address two such systematic biases: galaxy color gradients and blending. In the first part of the thesis, I will describe how shape measurements of galaxies with varying spectral energy distribution across their profile -- called "color gradients" -- when seen by a chromatic point spread function can be biased. I estimate this bias expected for the LSST using simulations of parametric galaxies and realistic galaxy images. The second part of my thesis focuses on the blending challenge for the LSST where a significant fraction of the lensed galaxy images will overlap with images of other objects, affecting the accuracy of flux and shape measurements. I discuss two novel approaches to infer the presence of objects that go undetected because of blending and compare their performance to existing detection algorithms
Changes in the legal profession, changes in the law : slavery and legal culture in Illinois, 1818-1848
Keywords: History.

Although Illinois was considered a "free" state when it attained statehood in 1818, slavery was not extinguished under Illinois law until the Supreme Court of Illinois decided the case of Jarrot v. Jarrot in 1845. The interpretation Illinois adhered to in construing its foundational documents, although contrary to the plain meaning of those texts and federal policy, survived for nearly thirty years, favored by some Illinoisans and acquiesced in by others until the Supreme Court of Illinois declared it invalid. This project follows the changing status of slavery and the culture of law and the legal profession in Illinois from 1818 to 1848 to elucidate connections between legal culture and the expression of law in Illinois during the period. In the years between Illinois' first and second constitutions, the legal profession in the United States underwent a dramatic transformation in culture and practices. In the absence of standards of professional competency, early-nineteenth-century legal practitioners ranged broadly in general education and specialized training. But whether one was a classically trained attorney or a relatively unschooled country lawyer, in the earliest decades of the nineteenth century legal practice was characterized by generalism. Lawyers positioned themselves as knowledgeable public men by drawing on wide-ranging information and embodying leadership through public performance and community involvement. In the years when legal practice was characterized by generalism, law embraced localism. In Illinois during its early statehood, as elsewhere in the United States at that time, localism sanctioned policies and practices seemingly incongruent with the formal requirements of law. As early as the 1820s, however, changes were underway within the legal profession that would affect the conceptualization of law itself. As legal practitioners shared an increasing amount of specialized information across wide expanses and as an ideal of scientific jurisprudence spread among elite lawyers, localism gave way to formalism in law. Because slavery in Illinois was inextricably linked to localism in law, changes within the practice of law, unconnected with particular policy preferences, resulted in the ultimate extinction of legally sanctioned slavery in Illinois. Examining the changes in legal culture that resulted in the elimination of slavery in Illinois reveals how ideas and practices within the legal profession, typically seen as separate from the content of law, informed jurisprudence such that law itself changed, somewhat independently of the intentions or desires of lawyers or the communities in which they practiced
Characterising the Orosirian earth system
Keywords: Geology.

The Orosirian Period (2.05 to 1.8 billion years ago; Ga) is bookended by two remarkably contrasting intervals in Earth history. The preceding Great Oxidation Event (GOE) spanned ca. 2.5 to 2.05 Ga, and marks the first sustained oxygenation of Earth's atmosphere. The end of the GOE has been hypothesised as a so-called 'oxygen overshoot', with oxygen levels declining across the termination of the event. Closely associated with the GOE is the Lomagundi-Jatuli Excursion (LJE), Earth's longest-duration, largest-magnitude positive carbon isotope excursion, canonically interpreted to represent a period of elevated organic carbon burial. Following the Orosirian Period is an interval informally referred to as the 'mid-Proterozoic' or 'boring billion', spanning ca. 1.8 to 0.8 Ga. This interval has been broadly characterised by geologists and geochemists as recording stasis in the Earth system, with relatively stable levels of atmospheric oxygen and gross primary productivity, a mild, non-glacial climate, and ecosystem stability. While these two intervals have been subject to considerable study, the intervening Orosirian Period has been largely overlooked, in spite of potentially recording a transition between these two extremes. To better understand the Orosirian Period, field work and a suite of geochemical techniques were conducted on sedimentary rocks collected from northern Canada and Europe. Chapter One applies carbon isotope chemostratigraphy and U-Pb geochronology of volcanic zircons to establish a time-calibrated, high-resolution carbon isotope curve through the Orosirian. Chapter Two applies barium and multiple sulphur isotope ratios, as well as triple oxygen isotope anomalies, to diagenetic barite crystals in the Belcher Group to constrain gross primary productivity across the end-GOE transition. Chapter Three is a study of carbon isotope ratios in the Labrador Trough to better constrain the conclusion of the LJE within the succession. Chapter Four applies iron speciation to shale samples collected from the Belcher Group to constrain oxygenation of the local water column during deposition of the Belcher Group. Finally, Chapter Five uses molybdenum isotope ratios and rare earth elements (plus yttrium) of carbonate sedimentary rocks to constrain changes in ocean oxygenation across the end-GOE, both on a global and local scale. Overall, this thesis demonstrates that the Orosirian Period was a dynamic interval that is critical for understanding the transition out of the GOE/LJE and the onset of stable conditions that persisted through much of the Proterozoic
Characterization and Efficacy Analysis of a Novel Immunotherapy
Keywords: Cochran, Jennifer
cancer
immunology
immunotherapy
antibody
bioengineering
engineering
Thesis

In recent decades, cancer immunotherapy has emerged as a potent strategy to promote immune clearance of tumors. Checkpoint blockade, a specific form of cancer immunotherapy that aims to block inhibitory immune checkpoint proteins, has proven to be therapeutic for certain cancers. V-domain Ig Suppressor of T Cell Activation (VISTA) is an immune checkpoint protein that inhibits the T cell response against cancer. Similar to blockade of checkpoint proteins like PD-1 and CTLA-4, VISTA blockade promotes anti-tumor immunity. However, unlike PD-1 and CTLA-4, VISTA is highly expressed as a ligand on antigen-presenting cells (APCs) and other myeloid cells, including myeloid-derived suppressor cells (MDSCs), which are often found in the immunosuppressive tumor microenvironment. While other groups have engineered antibodies against the human VISTA protein, an antibody that can bind tightly to both human and mouse VISTA is not available. An antibody developed by Hummingbird Biosciences, binds to mouse VISTA, but with significantly weaker affinity as compared to human VISTA. Having an antibody that can inhibit both mouse and human VISTA allows for improved clinical translation with fewer unanticipated toxicities when transitioning from preclinical animal models to human clinical testing. Here we characterize the ability of a new species cross-reactive anti-VISTA antibody to inhibit VISTA function. We also compared the molecular interactions of this antibody to other clinically relevant, human-specific anti-VISTA antibodies. Confirmation of our antibody’s ability to inhibit VISTA function was confirmed via in vitro analysis of T cell interaction with VISTA. Furthermore, we show that our anti-VISTA antibody blocks interaction between VISTA and the protein PSGL-1, which is expressed on T cells and thought to mediate VISTA inhibitory signaling. Finally, we demonstrate that our antibody shows therapeutic efficacy in in vivo tumor studies. Thus, we show this species cross-reactive anti-VISTA antibody has therapeutic promise while providing a framework for the development of next-generation cross-reactive anti-VISTA therapies for cancer.
Characterization of failure and energy dissipation mechanisms in MEMS resonators
Keywords: Mechanical Engineering.

Silicon microelectromechanical systems (MEMS) resonators are used in many applications, such as inertial sensors and clocks. The performance and sensitivity of these devices are limited by mechanisms that cause failure and energy dissipation. This thesis first characterizes fatigue failure in epitaxially deposited polysilicon and demonstrates ways in which it is accelerated at high temperatures. The second section of this thesis demonstrates ways to manipulate thermoelastic energy dissipation (TED) in MEMS resonators. Different schemes of shape and parameter optimization of the device geometry are explored to show how they reduce the TED and increase performance. Finally the last section of this thesis, demonstrates how a high amplitude driving scheme induces nonlinear energy dissipation, proportional to the squared vibrational amplitude, in MEMS resonators. The source of the nonlinearity is explored to understand how pressure losses and TED could be involved