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Single Cell Mass Spectrometry Metabolomics Study of Drug-resistant Cells
Get PDFSingle cell analysis is an emerging area to reveal the heterogeneity of individual cells among all populations. Understanding the cell-to-cell variation can greatly promote the development of drug discovery, disease diagnostics and prognostics. Metabolites, the end products of cellular metabolism, directly reflect the phenotype, status, and microenvironment of cells. Single-cell metabolomics is the study of complete metabolites’ profiles in individual cells under certain conditions, illustrating the biological heterogeneity among different cells. Numerous studies of single cell metabolomics have been achieved, and the pioneering work is benefited from technology development in this field. The analytical techniques utilized for single cell metabolomics primarily include fluorescence, electrochemical analysis, and mass spectrometry, whereas the integration of different analytical tools can provide additional molecular information of single cells. My Ph.D. studies mainly focus on single cell mass spectrometry (SCMS) metabolomics studies of drug-resistant cancer cells. This thesis consists of four chapters. Chapter 1 introduces the background information covering the current MS-based techniques for SCMS studies to date. In Chapter 2, I summarized the major projects that I accomplished. Studies in Chapter 3 are focused on elucidating the influence of combinational drug treatment. The Single-probe SCMS technique was utilized to study the metabolomic changes of Irinotecan-resistant cells upon metformin treatment and metformin-Irinotecan co-treatment. Combinational index values calculated by Chow-Talalay method verified the synergistic effect between metformin and irinotecan in our cell models, enzymatic activity assay of fatty-acid synthase was further performed to the possible mechanism of synergistic interaction. In Chapter 4, a workflow was designed to combine the Single-probe SCMS technique with fluorescence microscopy to study cell-cell interactions in co-culture systems involving cells with different levels of anticancer drug resistance
Nosology, Urban Infrastructure, and Public Health Discourse in 18th-century Philadelphia: An In-Depth Look at Fever Debates During the 1793 Yellow Fever Epidemic
Get PDFBy the 1790s, Philadelphia was a thriving port city that saw numerous ships arriving daily from foreign ports throughout the Atlantic world. In 1793, many of these in-bound ships were not carrying the typical goods to be sold in the local market, but were instead carrying displaced Saint Domingans fleeing the bloody turmoil of the Haitian Revolution. Their arrival set off one of the biggest outbreaks of yellow fever Philadelphia had seen in over three decades. What resulted from this outbreak was a high number of victims and a fearful public demanding answers from their medical community. This paper takes an in-depth look at the state of Philadelphia just prior to the outbreak, the arguments of the nature of fever coming from prominent members of the medical community while they struggled to treat their patients, and the attempts made to slow the transmission of yellow fever both during and after the 1793 epidemic. The urban infrastructure of Philadelphia and quality of the city’s atmosphere were now being considered as potential contributors to the transmission of yellow fever throughout the city. These considerations changed how Philadelphia physicians understood the nature of yellow fever, as well as their recommendations to prevent its return in future years
Modeling the Effects of Disinformation Spread on Multi-Commodity Networks
Get PDFDisinformation has become a more common weapon amidst growing social media platforms and users, targeting consumer behavior to affect physical infrastructure. Understanding how disinformation could attack a multi-commodity network and how to minimize its spread will help alleviate stress on systems during attacks. This research integrates an epidemiological model (SIR) with a mixed integer programming (MIP) model to minimize weighted shortage across commodities, evaluating the change over time dependent on disinformation spread β and recovery γ. It is then applied to a multi-commodity Swedish railway network carrying 14 goods over 200 nodes. Results demonstrated how different spread and recovery rates change the degree and timing of shortage
The Masculine Dilemma: Entanglement of Violence and Maleness in "The Only Good Indians"
No full textThis thesis examines the four Blackfeet male protagonists within Stephen Graham Jones’s "The Only Good Indians" in order to investigate stereotypes often applied to masculinity, specifically Indigenous masculinity. Examining portrayals of characters that demonstrate these stereotypes, this thesis is written to spark conversations about the why behind these social expectations, to recognize where stereotypes are rooted, and to build discussion about how to overthrow these conventions. Borrowing from—and entering into conversation with—Indigenous Gender Studies scholars such as Sam McKegney, Daniel Heath Justice, and others, this thesis relies upon real life experiences and realities in order to frame the conversation regarding portrayals of hypermasculine behaviors and internalized expectations. This thesis hopes to create discussions of how and why men act in certain manners, live in certain ways, or even make certain decisions by recognizing ourselves within Jones’s portrayals of his protagonists
Living well with worries, humility, and other people: learning to reflect on life with the Analects
Get PDFIn this dissertation, I present three distinct papers connected through the theme of control.
The Analects suggests a view of control or human efficacy that we have a great deal of control over events related to us. But our control is often partial, limited, and indeterminate. It suggests, in other words, a continuum of control that goes from having (relatively) full control over certain things to having (relatively) no control over certain things, with a middle section where we exert partial and indeterminate amount of control. Operating under this model of control, I develop and argue for three theses regarding 1) the emotion of worry when our control and concern over things should go beyond a small set; 2) humility when we are humbled by the challenge of self-cultivation and others’ contributions; and 3) relational virtue when we give up a certain control and let others partially determine not just what we do, but who we are.
In the first paper, I argue that in the Analects, learning to worry well is part and parcel of the Confucian cultivation program, and it includes learning to worry broadly about non-related others, and deeply about intimate others.
In the second paper, I argue that in the Analects, humility is about ritually expressed vigilance developed from a strong desire for cultivating oneself and devotion to responsibilities that honor forerunners and check against misanthropy.
In the third paper, I argue that relational virtues that characterize being a good friend, spouse, sibling, or child require more than the agent’s disposition, but also acknowledgement from intimate others, and in unfortunate situations, public acknowledgement and evaluation. To be relationally virtuous, the agent does not fully determine whether she is virtuous or not
Engaging with Stakeholders to Produce Actionable Science: Moving from Theory to Practice
Get PDFOver time, the idea of the public value of federally funded science has slowly transitioned from basic science that helps fight disease and maintain national security (Bush 1945) to use-inspired science that directly informs decisions about the most urgent issues facing society, such as climate change (Lubchenco 1998, 2017). Natural and cultural resources across the world are already experiencing demonstrable impacts due to changes in our climate system, and stewards of these resources are turning to the scientific community for actionable science – information and tools that can be directly applied to decisions about how best to adapt to these future conditions (IPCC 2022). Such societal impact is more likely to be met when decision makers are engaged in the process of knowledge production (Ferguson et al. 2022). In response, public funders of climate science are changing how they design solicitations, review proposals, and make other programmatic decisions to encourage research to meet decision making needs (Arnott et al. 2020a). However, when the knowledge created does not fit decision contexts or is not used appropriately, vulnerability or contributions to climate change can instead increase and maladaptation can occur (Barnett and O’Neill 2010). Ensuring that engagement of decision makers in actionable science is carried out in a thoughtful and reflexive way is critical to achieving the desired societal impact.
In this dissertation, I examine three key questions regarding the engagement of stakeholders in the production of actionable climate adaptation science. First, how should researchers align their stakeholder engagement processes with their desired goals for societal impact and actionability? In Chapter 2, I propose a framework of engagement approaches that describes the wide variety of tools that are available for including stakeholders in the creation of actionable science, and I provide guidance on how researchers might consider tradeoffs among those approaches and tools. Second, how should researchers conduct engagement for societal impact in a way that maximizes benefits and minimizes harms to stakeholders? In Chapter 3, I analyze interviews (n=15) with stakeholders who were highly engaged in actionable climate adaptation science projects to examine their perspectives on the benefits and harms that they experienced, and I argue that researchers must proactively consider the ethical implications of engagement when developing their project idea. Third, how should researchers define successful societal impact and evaluate against such standards? In Chapter 4, I draw on the discipline of evaluation to develop a survey tool to examine the process, outputs, and outcomes of actionable science based on the perspectives of stakeholders engaged in those projects, and I analyze survey responses (n=49) in a case-study deployment of the tool.
In Chapter 5, I synthesize the findings from Chapters 2-4 and summarize key takeaways. Overall, I recommend that researchers thoughtfully consider stakeholder engagement goals and benefits as early as possible to best meet expectations of societal impact and actionability, ideally at or prior to the proposal development stage. Doing so in a robust manner often involves skills in which many biological and physical researchers may not be trained, requiring additional resources and expertise to be included in project plans
Palynology of the Upper Flowerpot Formation, Mangum Area, Southwestern Oklahoma
Get PDFMy study examines the plant palynomorphs recovered from a new section of the uppermost Flowerpot Formation of middle Permian age in southwestern Oklahoma. My goal is to document the species diversity and abundance of plant taxa using palynology—dispersed pollen and spores—and to compare observations with prior studies from leaves and palynomorphs, during an interval of time near the end of the Late Paleozoic Ice Age. Based on correlative megafossils in adjacent areas, this interval marks a profound expansion of seed plants and of a seasonally dry/arid climate in the region. My results are in agreement with these general patterns. Although showing relatively equivalent diversity of pollen (e.g., from seed plants) and spores (e.g., from ferns), my samples illustrate an overwhelming abundance of striate bisaccate pollen, in particular of the genus Lueckisporites, indicative of dry climate, and low abundance of free-sporing plants (e.g., mosses, ferns). In my sampled section, a conspicuous layer of copper bearing minerals was observed. Three samples were tested using x-ray fluorescence and registered markedly high concentrations of copper. The prevalence of palynomorphs in the upper Flowerpot Formation in southwestern Oklahoma, widely noted by previous investigators, might be related to the stratigraphic and diagenetic conditions that also foster copper deposition, but this requires further investigation
Optimal selection of short- and long-term mitigation strategies for flooding hazard
Get PDFEvery year, flood hazards cause significant economic losses in different locations worldwide with devastating impacts on the buildings and the physical infrastructure. Therefore, investing in flood mitigation is crucial for communities to protect their physical and socio-economic systems. While there are multiple mitigation options for communities to implement in the floodplain at the building-level, an optimization method is developed to determine the optimal strategy for the buildings to implement for minimizing.
In this research, I propose a mathematical model to study the effects and trade-offs associated with pre-event short-term and long-term mitigation strategies to minimize the expected economic loss associated with flooding hazards in a community. I illustrate the capabilities of the proposed model with a case study on Lumberton, NC, which is a small, socially diverse inland community with around 20,000 buildings. Over the last several decades, Lumberton has been affected by severe flooding events with significant recurring economic loss of more than hundred million dollars. The model uses the cost from a portfolio of mitigation strategies, each representative of a different mitigation level, and the resulting flood-induced monetary losses corresponding to each mitigation strategy/level. Finally, the mathematically optimal building level flood mitigation plan is provided based on available budget level to reduce the total direct economic loss of the community