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Overview of Statistical Methods for T-Cell Receptor Sequencing Analysis
Get PDFThe human adaptive immune system is able to adjust cellular functions in the body to fend off pathogens and harmful cells. It does so through various methods, one of which involves the development of T-cells. These T-cells detect and respond to internal and external antigens with receptors on the surface of the cells. Receptors are made of two chains of amino acids — an -chain and a -chain, or less frequently a -chain and a -chain which bind to antigens, triggering a cascade of reactions to activate an immune response. The different combinations of amino acids and chain pairs allow the immune system to respond to a variety of pathogens.
As a result, one method of understanding the adaptive immune system and its health applications is through T-cell receptor (TCR) analysis. However, this field is still relatively nascent. Here, we provide an overview of the common tools and statistical packages that are used in TCR analysis. We discuss six different tools and packages — immunarch, alakazam, pyTCR, Platypus, Scirpy, scRepertoire — and their strengths and limitations. We run these packages on two data sets and show which packages are more memory and time-efficient, as well as which packages are best suited for which type of use case
THE ROLE OF OFF-GRID ENERGY IN 2050 IN DEVELOPING COUNTRIES
Get PDFThis paper explores the role off-grid energy may play decades into the future by exploring the correlation between rural grid electricity access and independent variables of gross domestic product (GDP) per capita, population density, and percent of the population living in rural areas. A strong positive correlation is found (particularly for less wealthy countries) between rural electricity access and GDP per capita, and further analysis is completed to predict rural electricity access into the future using predicted GDP per capita values from the Shared Socioeconomic Pathways (SSP) Scenario Database. It is found that for selected case study countries (Liberia and Rwanda), the model predicts that millions of people will remain off-grid in 2050. This demonstrates an enduring need for off-grid products and policies to support them as they are likely to be needed for decades
Building Bureaucratic Capacity: The Political Origins of Civil Service Reforms
No full textUnder what circumstances do democratic governments implement bureaucratic reforms? Professional bureaucracies are crucial for economic development, inequality reduction, and security provision. This dissertation explores the paths countries can take to professionalize their bureaucracies.
The study presents a novel theory where the success of bureaucratic reform is rooted in the type of patronage regime. Although all countries had some form of patronage, substantial differences in their firing practices can significantly impact the reform’s outcome. Patronage systems where rotation in office after party turnover is dominant, also known as a “spoils system,” provide two crucial institutional conditions for political entrepreneurs to emerge and advocate for bureaucratic reform: constituencies of grievances and an appealing campaign motto for reform. In these cases, bureaucratic reform succeeds. However, some patronage systems do not remove employees after party turnover. Instead, a “partisan layering” personnel management system is used, which features virtually no layoffs. In these cases, public employees are the only constituency for reform, and they view it primarily as a labor issue, resulting in a weaker mobilization campaign. Without external constituencies and a powerful campaign motto to rally different segments of the population around, entrepreneurial action does not emerge. Under these circumstances, bureaucratic reform fails.
The research method consists of a historical comparison of the U.S. and Argentina. It relies on original archival evidence—government reports and statistics, congressional debates, and records from civil society organizations— and secondary sources. The empirical chapters demonstrate similarities in crucial aspects of initial conditions between the two countries and highlight their divergence in administrative trajectories after the rise of mass politics. The study traces the self-reinforcing and self-eroding processes in each country.
The dissertation contributes to debates in political science by reconceptualizing patronage based on hiring and firing practices, offering new insights into its resilience and erosion. It explores the impact of patronage on bureaucratic reform, specifying the traditional “state first” and “democracy first” trajectories by introducing two contrasting outcomes—success and failure— in the latter. Methodologically, it innovates by comparing the U.S. and Latin America, reframing American exceptionalism and contributing to recent efforts to de-center Eurocentric state development theories
EXPLORING THE INTERNATIONAL STUDENT EXPERIENCE IN CANADIAN UNIVERSITIES
Get PDFDespite Canada being a major global recipient of international students, research on the international student experience in Canada is limited. A complex interplay of factors influences international students’ academic and experiential outcomes. Although international students pay, on average, more than four and a half times the tuition of domestic students, wage gaps exist upon graduation, and there is evidence to suggest inequitable academic and experiential outcomes for international students studying in Canada. Through a mixed-methods convergent parallel design, this study explored both faculty and student perceptions of the international student experience at one host institution in Canada. The challenges the students reported were similar to those in the literature. This study was unique in that it explored faculty and student perceptions alike. Based on the study’s results, a second literature review was completed and culminated in the recommendation of a new evaluation study using first-year learning communities to better meet the needs of international students in the context under investigation. The proposed study recommends that first-year learning communities support new international students adjusting to a different education system and host country. Learning communities have long supported first-year students’ transition to university studies. However, there is a paucity of literature on their use in supporting international students
Protein Kinase G-Mediated Phosphorylation of CHIP: A Protective Mechanism against Myocardial Infarction in Female Mice
No full textMyocardial infarction (MI) and subsequent oxidative stress damages intracellular proteins that, if not removed, will accumulate within the cardiomyocytes. Proteotoxicity results from insufficient clearance of misfolded or damaged proteins, which further reduces cardiac function following a MI. Estrogen is known for its cardioprotective properties, one of which is an enhancer of protein degradation capabilities, although the precise mechanism remains elusive. Notably, estrogen has been shown to increase the activity of protein kinase G (PKG) in the heart following injury. PKG is also known for its cardioprotective properties, including the stimulation of protein degradation to abrogate cardiac proteotoxicity. We recently uncovered a novel signaling nexus whereby PKG phosphorylates the carboxyl terminus of Hsc-70 interacting protein (CHIP), a ubiquitin ligase/co-chaperone, at serine 20, to increase the stability and the functionality of the CHIP protein complex. This study was conducted in male mice, and it remains to be determined if female mice are cardio-protected by PKG-CHIP activation. In this study, we aim to investigate the role of CHIP in female mice following a MI. To specifically probe the role of the CHIP S20 site, we employed mice harboring CHIP S20 phospho-mimetic (SE) and phospho-null (SA) mutations. We subjected these female mouse models to MI surgeries (or sham surgery as a control). We find CHIP SE mice have decreased fibrosis and protein aggregation following a MI compared to CHIP SA mice. These findings suggest that increased CHIP S20 phosphorylation may maintain proteostasis to protect the myocardium of female patients following an adverse cardiac event such as a MI
THE RESILIENCY OF A BORDER TOWN SCHOOL’S SUPPORT STAFF
Get PDFThe shortage of school social workers and counselors in the United States (Whitaker et al., 2019) is likely to impact school communities and the students being served. The need for social workers and counselors in schools is substantiated by the alarmingly increased levels of anxiety and depression experienced by children (ages 5–11) and youth (ages 12–17) in recent years (American Academy of Child & Adolescent Psychiatry, n.d.; American Academy of Pediatrics, 2021; White House, 2022). The present study was conducted in a border town context where 21.7% of the population falls below the poverty line and 82% of the population is Hispanic (Census Reporter, 2022). Minority children are at a greater risk of experiencing adverse childhood experiences than their White counterparts (Ho et al., 2007; Loria & Caughy, 2018). Yet, ambiguity in the role of school counselors and social workers and high student caseloads with uneven ratios of serving professionals to students (DiSchiano, 2019; Graham and Price, 2020) may be the leading cause of the shortage. A mixed-method approach led the present study’s efforts where a six-session curriculum was designed per the needs of staff from the Southwest Texas District. Variables studied included levels of compassion fatigue, secondary traumatic stress, burnout, compassion satisfaction, trauma-informed perspectives, and adoption of self-care activities from nine participants. Participants completed pre- and post-surveys and answered feedback surveys at the end of each session. Five of the nine participants were interviewed. Results pointed to a significant change, with reduced levels of secondary traumatic stress, increased levels of compassion satisfaction, a shift in perspectives toward a trauma-informed perspective, and an increase in self-care activities. The findings support the literature in that psychoeducational content, a sense of belonging among staff, and dialogue in professional development sessions can have positive impacts on the variables studied. Further research is encouraged to understand the factors that can contribute to a significant impact on burnout among serving professionals in communities and the ways in which professional development can be delivered to all members of the school community
COVALENT ORGANIC FRAMEWORK AS ARTIFICIAL SOLID ELECTROLYTE INTERFACE FOR LITHIUM METAL ANODE
Get PDFTo combat global climate change and to reduce anthropogenic carbon-emissions, there has been a dire need to transition away from internal combustion engine vehicles. Li-ion batteries, which are used in most electric vehicles, lack the specific energy capacity to deliver desirable driving distances that current internal combustion engine vehicles deliver. Lithium metal battery is a promising next-generation battery with significantly higher theoretical capacity, but it suffers capacity loss and safety issues due to dendrite growth at the lithium metal anode. Covalent Organic Framework (COF) is a porous organic material that has been gaining huge attention in energy storage applications due to its durable structure and versatile structure/function modification strategies.
Here, we demonstrate a simple same-phase interfacial synthesis method to synthesize a free-standing TpPa-SO3H COF membrane at room temperature and pressure. By taking advantage of the anionic sulfonyl functional groups in the pores of the TpPa-SO3H COF membrane, we utilized the TpPa-SO3H membrane as an artificial solid-electrolyte interface as a lithium protective layer to suppress dendrite growth and facilitate uniform lithium deposition. By applying TpPa-SO3H membrane as an aSEI, we demonstrate higher coulombic efficiency and enhanced stability in the Li | Cu half-cell. Furthermore, the simple synthesis method and free-standing nature of the COF membrane synthesized in this work sheds further insight to developing robust yet scalable COF membranes which can be applied to many more applications
A Tendon-Driven Anthropomorphic Prosthesis: Where Biology and Engineering Go Hand in Hand
No full textProstheses aim to aid individuals within the limb loss community in effectively interacting with their environment. This manuscript details the development of a custom tendon-driven anthropomorphic prosthetic hand that was created to more accurately test the use of haptics in providing feedback that improves sensorimotor control. This novel design improves on previous prosthetic hands by implementing human-like movement, even force distribution, lower friction, and multiple grasp types. The hand was validated through benchtop evaluation and an activities of daily living study with six individuals without limb loss. The validation test results are presented and compared to the previous design, which demonstrate its superiority in task performance, thereby allowing the prosthesis to conduct more effective research in the future
Essays on Applied Microeconomics
No full textMy dissertation is composed of three essays on Applied Microeconomics. I apply various methods, such as structural modeling and causal inference, to topics in Labor Economics and Political Economy.
In Chapter 1, I build a structural model of location choices and marriage market matching. With this model, we can open the black box of intrahousehold decisions and better understand the gender welfare gap beyond the gender wage gap. I find that the marriage market reduces the dispersion of the spatial distribution of highly skilled workers and can increase some workers’ responsiveness to local wage shocks. Counterfactual analyses show that childcare subsidies encourage people to move to locations that pay higher for their skills and increase the marriage rate and labor supply. Childcare subsidy increases aggregate social welfare and decreases the welfare gap by gender but increases the welfare gap by education.
In Chapter 2, I investigate the effect of Paid Family Leave (PFL) on marriage decisions. Through event study and synthetic difference-in-difference methods, I find that PFL programs have a positive effect (1-2 percentage points depending on specification) on marriage decisions. By building a simple marriage matching model following Choo and Siow (2006), I find that PFL has a positive effect on gains from marriage if both the husband and wife come from the same education level. For mechanisms, I find that PFL enlarges the gender wage gap, which affects marriage decisions through specialization and bargaining power within the household.
In Chapter 3, we study how Fox News viewership affects xenophobic actions through racial animus and perceived social unacceptance. Using the multiple proxy variables collected in Deng and Hwang (2023), we estimate Fox News viewership’s effects on the distributions of racial animus and perceived social unacceptance correcting for measurement errors in dependent variables following Hausman et al. (2021). We find that Fox News viewership significantly increases racial animus and decreases perceived social unacceptance at each quantile. Then we borrow the model from Deng and Hwang (2023) to predict the effects of Fox News viewership on xenophobic actions. We find that Fox News viewership increases xenophobic actions in the partial equilibrium but shows different magnitudes in the general equilibrium
Defining lipid synthesis requirements for pancreatic cancer development
No full textOrganisms must be able to adapt to changes in nutrient availability in order to maintain normal physiology. The mechanisms involved in these homeostatic pathways are of relevance in many disease contexts, including cardiovascular disease, diabetes, and cancer. In the Espenshade lab, we are interested in studying the mechanisms that control lipid homeostasis. Specifically, we aim to investigate lipid metabolic genes that are required for tumor growth and progression of pancreatic ductal adenocarcinoma (PDAC). PDAC is historically one of the deadliest forms of cancer and is predicted to increase in incidence over the next several years, making new therapeutic strategies essential for combating this disease.
In this dissertation, I utilize PDAC patient-derived cell lines to examine the mechanism behind the requirement of the sterol regulatory element-binding protein (SREBP) pathway in PDAC tumor growth. SREBPs are a family of transcription factors that are essential for maintaining lipid homeostasis and regulate the expression of genes required for fatty acid and cholesterol synthesis. Previous work from the Espenshade lab established that the SREBP pathway is essential for PDAC progression in mice. Using stable knockout cell lines and small molecule inhibitors, I defined the nutrient requirement of cells deficient in SREBP pathway activity and showed that oleic acid is a requirement for cell growth in vitro. This followed with my review of stearoyl-CoA desaturase (SCD), which is the SREBP target gene required for the synthesis of oleic acid. Finally, I designed a custom CRISPR knockout screen of SREBP target genes to broadly survey these genes’ requirement for PDAC cell growth in vitro and in vivo. Using genetic and pharmacological approaches, I demonstrated that the mevalonate pathway is essential for PDAC tumor growth in mice, and specifically that the isoprenoid geranylgeranyl diphosphate is an essential product of this pathway. These data validate a method for genetic screening in mice and identify SREBP target genes required for tumor growth in PDAC