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an Empire Of Liberty? Irish Immigrants, Native Americans, And American Imperialism In The Trans-Mississippi West Between 1840 And 1940
No full textThis dissertation examines the ways in which Indigenous peoples and Irish people combatted or contributed to U.S. imperialism in the American West during the nineteenth and early twentieth centuries. Between 1840 and 1940, the United States engaged in Westward expansion, displacing Native Americans in the name of imperialism, capitalism, and Anglo-Protestantism. Simultaneously, Anglo colonization in Ireland prompted millions of Irish people to flee to the United States. This dissertation follows the complex interactions between the Irish, Native Americans, and Anglo-Protestants in Ireland and North America.
In the American West, the Irish became the unwitting foot soldiers for U.S. expansion, engaging in bloody assaults on Indigenous people. They worked with Anglo-Protestants to undermine Native American nations in exchange for wealth and social mobility. Despite this, some Irish Catholics and Indigenous peoples found common ground in shared colonial experiences. They expressed political solidarity, used anti-Anglo language, cooperated to challenge Anglo-Protestantism, and promoted alternative visions of the world based on their traditional values. The mutual admiration and transatlantic solidarity led to intermarriage, joint political campaigns, innovations in the labor movement, and weapon exchanges.
The project draws on government reports, military records, newspapers, memoirs, diaries, letters, interviews, business records, and artwork. It also utilizes Indigenous letters and pictographs such as the Waníyetu iyáwapi, known as Winter Counts. Reading Anglo-Protestant sources against the grain in conjunction with Irish and Indigenous material helps provide insight into a neglected tale of transatlantic solidarity. In privileging the voices of Indigenous and Irish peoples, the dissertation offers valuable insights into alternatives to Anglo-Protestant hegemony, imperial expansion, and capitalist economic structures
Brain Metabolic Responses To Alzheimer Pathologies With Molecular Imaging And Machine Learning
No full textAlzheimer Disease (AD) is defined by amyloid (A) and tau (T) pathologies, with T better correlated to neurodegeneration (N) than is A. However, T and N have complex regional relationships in part related to non-AD factors that may influence N. Using machine learning, we assessed heterogeneity in 18F-Flortaucipir vs. 18F-Fluorodeoxyglucose positron emission tomography as markers of T and neuronal hypometabolism (NM) in 289 symptomatic patients from the Alzheimer Disease Neuroimaging Initiative (ADNI) and 115 cognitively normal older adults from the Harvard Aging Brain Study (HABS). Fromboth cohorts, we identified six T/NM clusters with differing limbic and cortical patterns. The canonical group was defined as the T/NM pattern with the lowest regression model residuals, while non-canonical groups reflected either resilience or susceptibility, with either less or greater hypometabolism than expected relative to T. Resilient groups displayed better cognition and less copathology-related factors than the canonical group. Susceptible groups exhibited worse cognitive decline and had imaging and clinical measures consistent with the presence of copathologies, including factors associated with vascular, α-synuclein and TDP-43 pathologies. Mismatch analyses were applied with a loglinear model and compared to a generative adversarial network with dual contrastive learning objectives. We performed theoretical and empirical investigations to optimize this contrastive learning model. Our proof-of-concept experiments demonstrate the advantage of multi-domain contrastive losses, the utility of training set and contrastive sampling diversity and the ability of image-to-image translation models to accurately map between T and NM domains. These findings provide the basis for further biological and statistical inquiries into the translation accuracy and reconstruction error of models that map between types of images in AD. Together, T/NM mismatch in AD reveals distinct imaging signatures with pathobiological and prognostic consequences that may improve clinical trial design, diagnosis and management of patients living with neurodegenerative diseases
Trust Fund Families: The Organization Of Elite Families And Persistence Of Wealth Inequality
No full textA historic peak of wealth inequality in the United States means that a small proportion of families have accumulated unprecedented wealth – these families must somehow manage this wealth. Scholars have tended to characterize elites as either powerful individuals or a homogenous ruling class. Meanwhile, research on managing money in intimate relations suggests that mixing the two can be a delicate process. In this dissertation I investigate how elite families organize their wealth as families using ethnographic methods. Specifically, over six months I observed a “family office” that manages the wealth of a handful of families with a minimum of $50 million per family. Additionally, I interviewed the office’s principal clients and a broader sample of 30 family offices from across the United States. I make three contributions to the literature on elites and the organization of economic relations: first, I argue that despite Weber’s definition of bureaucracy as oppositional to the family, elite families bureaucratize to hoard wealth across generations. Prior literature has pointed to the paramount role of entities like trusts in elites’ lives, but it has not exposed the practice of bureaucratization, which preserves capital while shifting relationships between family members. Second, as family bureaucratization hinges on expertise, I also investigate how wealthy families (and others) access new expertise through brokers’ behavior. Organizational literature points to the crucial role brokers play in networks, but it has not investigated how broker behavior, beyond broker characteristics, shapes the structure of networks. I show that brokers like family offices actively test brokerage opportunities, relying on contingent ties and brokerage uncertainty to expand the expertise accessible to their clients. Finally, I show that elite families do not all behave alike, and that different meanings they associate with death influence their inheritance plans. Elites use their wealth to bestow meaning onto their deaths, and by extension their lives. Thus, the meanings and practices elite families cultivate as families are crucial for how they manage their wealth and, consequently, broader patterns of wealth inequality and stratification
Evasion Of Innate Immunity By The Pathogen Coxiella Burnetii
No full textHost immune cells use multiple strategies to detect and protect against microbial infections. In turn, pathogens have evolved ways to evade these strategies to remain undetected. The elegant interplay between these host-pathogen interactions is displayed by studies on the innate immune system, which is on a constant evolutionary arms race with invading microbes. In this dissertation, we explore the innate immune response to the bacterial pathogen Coxiella burnetii. This intracellular pathogen has an intimate association with host cells and evades multiple host defense pathways, making it a unique model system in which to study pathogen countermeasures. C. burnetii infects alveolar macrophages and causes the emerging disease Q fever. It uses a type IV secretion system (T4SS) to inject over 100 bacterial effector proteins into the host cytoplasm, which modulate many host cellular processes to form a replicative niche for the bacteria inside the cell. We describe here the discovery of a bacterial effector that inhibits host signaling pathways and modulates the immune response. This effector interacts with the PAF1 Complex (PAF1C), a host factor that is highly involved in transcriptional processes and is a target of viral pathogens to counteract the antiviral response. We demonstrate that PAF1C promotes gene expression downstream of various innate immune receptors and describe for the first time a role for PAF1C in restricting a bacterial pathogen. Future studies will investigate whether the C. burnetii effector suppresses PAF1C function to inhibit the host immune response. Lastly, we investigate the interactions between C. burnetii and the inflammasome pathway. This host defense mechanism leads to the secretion of IL-1 cytokines and an inflammatory form of cell death, to simultaneously alert the body to the infection and eliminate the pathogen’s replicative niche. Our preliminary data show that C. burnetii suppresses various inflammasome responses and does not induce cell death in human macrophages. Collectively, our findings provide insight into how C. burnetii interacts with and evades the innate immune response, and further elucidate the host factors that contribute to defense against bacterial pathogens
Statistical Learning For System Identification, Estimation, And Control
Get PDFDespite the recent widespread success of machine learning, we still do not fully understand its fundamental limitations. Going forward, it is crucial to better understand learning complexity, especially in critical decision making applications, where a wrong decision can lead to catastrophic consequences. In this thesis, we focus on the statistical complexity of learning unknown linear dynamical systems, with focus on the tasks of system identification, prediction, and control. We are interested in sample complexity, i.e. the minimum number of samples required to achieve satisfactory learning performance. Our goal is to provide finite-sample learning guarantees, explicitly highlighting how the learning objective depends on the number of samples. A fundamental question we are trying to answer is how system theoretic properties of the underlying process can affect sample complexity.
Using recent advances in statistical learning, high-dimensional statistics, and control theoretic tools, we provide finite-sample guarantees in the following settings. i) System Identification. We provide the first finite-sample guarantees for identifying a stochastic partially-observed system; this problem is also known as the stochastic system identification problem. ii) Prediction. We provide the first end-to-end guarantees for learning the Kalman Filter, i.e. for learning to predict, in an offline learning architecture. We also provide the first logarithmic regret guarantees for the problem of learning the Kalman Filter in an online learning architecture, where the data are revealed sequentially. iii) Difficulty of System Identification and Control. Focusing on fully-observed systems, we investigate when learning linear systems is statistically easy or hard, in the finite sample regime. Statistically easy to learn linear system classes have sample complexity that is polynomial with the system dimension. Statistically hard to learn linear system classes have worst-case sample complexity that is at least exponential with the system dimension. We show that there actually exist classes of linear systems, which are hard to learn. Such classes include indirectly excited systems with large degree of indirect excitation. Similar conclusions hold for both the problem of system identification and the problem of learning to control
Elucidating The Determinants Of Alveolar Epithelial Cell Fate From Lung Development To Regeneration
Get PDFThe alveolus is the functional unit of gas exchange in the lung and home to two major epithelial cell lineages: alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. Large, squamous AT1 cells cover the vast majority of the adult lung surface area, creating the gas diffusible interface between the external environment and the vasculature. Cuboidal AT2 cells secrete pulmonary surfactant to reduce surface tension at this air-liquid interface to prevent alveolar collapse. These cells are essential for lung function, and many are lost upon lung injury. Thus, understanding the signals required to generate and regenerate these cells is vital to develop interventions to support long term pulmonary health. In this dissertation, I use a combination of epigenetic and transcriptomic profiling, in vivo mouse genetic and injury models, ex vivo organoid assays, and human patient tissue to define essential mediators of the developmental emergence, lineage commitment, and plasticity of AT1 and AT2 cells. I demonstrate that Dnmt1 ensures the proper specification and compartmentalization of proximal and distal epithelial cell lineages during development. Developing a method to segment heterogeneously injured adult lung tissue into distinct zones by severity, I define specific injury niches and characterize the spatially restricted cellular responses to damage intensity in mice and humans. I determine that Fgfr2 maintains early AT2 cell identity and balances AT2 cell proliferation and differentiation during lung regeneration. Additionally, I demonstrate the extent of AT1 cell plasticity during neonatal and adult regeneration to generate AT2 cells. Finally, I show that Klf5 regulates AT1 cell lineage commitment during both lung development and regeneration. This work defines essential factors that determine alveolar epithelial cell fate and reveals how these choices impact both lung development and regeneration
Gsk3 Inhibition Rescues Growth And Telomere Dysfunction In Dyskeratosis Congenita Ipsc-Derived Type Ii Alveolar Epithelial Cells
Get PDFDyskeratosis congenita (DC) is a rare genetic disorder characterized by deficiencies in telomere maintenance leading to very short telomeres and the premature onset of certain age-related diseases, including pulmonary fibrosis (PF). PF is thought to derive from epithelial failure, particularly that of type II alveolar epithelial (AT2) cells, which are highly dependent on Wnt signaling during development and adult regeneration. We use human iPSC-derived AT2 (iAT2) cells to model how short telomeres affect AT2 cells. Cultured iAT2 cells with a mutation in DKC1, the most common cause of DC, accumulate shortened, uncapped telomeres and manifest defects in the growth of alveolospheres, hallmarks of senescence, and apparent defects in Wnt signaling. The GSK3 inhibitor, CHIR99021, which mimics the output of canonical Wnt signaling, enhances telomerase activity and rescues the defects. These findings support further investigation of Wnt agonists as potential therapies for DC related pathologies. Furthermore, this thesis describes the development of a transplantation of iAT2 cells into immunocompromised mice as well as the development of a novel iPS line with another DC mutation
Property And Distributive Justice: A Theory Of Moral Property Rights
No full textProperty rights are central to debates over distributive justice. In this dissertation, I defend three interrelated claims about the nature of property rights and distributive justice. First, I argue that different types of property have different moral standing in social and political philosophy. Some property rights constitute basic moral (or natural) rights and therefore come with strong presumptions against state interference for redistribution. Other property rights are social conventions and as such do not enjoy any special moral status. There is no presumption against redistributing this latter type of property rights. Second, I offer a justification for private property rights as a basic moral right. Here I argue that the same considerations that generate the basic moral rights in Rawls’s Theory of Justice also generate a limited basic moral right to property. The justification for property as a basic moral right is that certain property rights are necessary for realizing our fundamental conception of personhood through the development and exercise of the moral powers. This justification also supplies the criterion for distinguishing the set of morally special property rights from the set of merely conventional ones. Only those property rights necessary for the development and exercise of the moral powers belong to the morally special set. Third, I defend a Hohfeldian conception of property and argue against Blackstonianism. Blackstonians conceive of property rights as despotic dominion. By contrast, Hohfeldians conceive of property rights as a bundle of rights, powers, duties and liabilities that can be specified in many different ways. Here I argue that property is a normative concept that must be tied and tailored to its justification. I conclude that only the Hohfeldian conception of property is capable of tailoring the incidents of property to its underlying justification. After developing and defending these three claims about the nature of property rights, I consider several consequences of the theory for property law and policy
Electrifying the Vehicle Fleet Within the United States, a Feasibilitiy Analysis of Environmental Impact and Technical Deployment
Get PDFIn November 2021, the Infrastructure Investment and Jobs Act was passed and signed into law, which along with many other funding initiatives, will provide $7.5 billion to begin the infrastructure expansion of electric vehicle charging stations within the United States. This specific funding from the federal government is a crucial step towards the current administration’s carbon neutral goals and the building of a national connected network of 500,000 electric vehicle charging stations and having 50% of light duty vehicles sales being electric by 2030. However, achieving these goals is complicated and the beneficial environmental effect of further electric vehicle integration is often debated. This is due to the concerning total carbon footprint produced from the manufacturing of electric vehicles, usage, and growth of power demand from charging station infrastructure. To counter that common viewpoint and through a feasibility analysis of environmental impact and technical deployment, this study has been able to highlight the beneficial and adverse effects of increased usage of electric vehicles and found many solutions and initiatives that are available to alleviate the negative effects. Long term environmental impact comparisons to existing internal combustion engine vehicles do demonstrate the positive environmental advantages of increased electric vehicle usage, although as highlighted, the scale of those advantages vary depending on contributing infrastructure factors. Effective and measurable ways to increase feasibility and mitigate the total carbon footprint from electric vehicle usage and charging station infrastructure include further development and grid inclusion of renewable power sources, utilization of alternative critical material extraction technologies, policy changes to tax benefits or infrastructure construction incentives, and proper societal planning of charging station infrastructure. Committing to more sustainable technologies such as electric vehicles is always promising, however, many factors contribute to the total carbon footprint and utilizing mitigation strategies must be done to make the transition efforts environmentally meaningful. With electric vehicle ownership continuously rising in the United States and government funding becoming available for the construction of more electric vehicle charging station infrastructure, assessing the feasibility of increased electric vehicle usage and renewable based solutions is important to efficiently meet the ever-growing demand
Penn Library\u27s LJS 424 - Non[us] Alma[n]sor[is] cu[m] an[n]otatio[n]ib[us] ... (Video Orientation)
No full texthttps://repository.upenn.edu/sims_video/1171/thumbnail.jp