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Truncated ASXL1 in Myelodysplastic Syndromes (MDS): Using CRISPR Cas9 to mimic common mutations found in MDS to examine how cell behavior changes.
No full textMutations in the Additional Sex Combs-Like 1 (ASXL1) gene frequently occur in myelodysplastic syndromes (MDS) and correlate with poor patient prognosis. While ASXL1 mutations are known to create truncated proteins, their precise role in disease progression remains unclear. This study investigated whether truncating mutations in ASXL1 confer a competitive advantage in hematopoietic cells. Using CRISPR-Cas9 genome editing, we introduced multiple ASXL1 mutations, including the common G646Wfs variant and other truncating mutations (Y591X, E635fs, and R693X), into mouse 32D cells and primary bone marrow cells. Through competitive co-culture experiments and competitive methylcellulose assays, we demonstrated that cells harboring ASXL1 truncating mutations consistently outcompeted both wild-type cells and those with ASXL1 knockout mutations. Notably, the G646Wfs mutation showed particular dominance in competition assays, even when initially present at low frequencies. We also examined these mutations in the context of U2af1 Q157R, a splicing factor mutation commonly co-occurring with ASXL1 mutations in MDS patients. The competitive advantage of ASXL1 truncating mutations was maintained across different genetic backgrounds, suggesting a fundamental role in driving clonal expansion. These findings indicate that ASXL1 truncating mutations are not simply loss-of-function variants but likely confer novel properties that promote cellular fitness in hematopoietic cells, aligning with recent work by Köhnke et al. (2024) showing enhanced PR-DUB complex activity in ASXL1-mutant cells. This work provides new insights into how ASXL1 mutations may contribute to clonal dominance in myeloid malignancies and suggests potential therapeutic implications for targeting cells harboring these mutations, particularly through approaches that might normalize aberrant histone modification patterns
Cultivating Quality of Life: Assessing Diet, Physical Activity, and Mental Health Among Arab-American Breast Cancer Survivors - Uncovering Barriers and Facilitators for Holistic Well-Being
Get PDFThis dissertation examines the quality of life among Arab-American breast cancer survivors, with a particular emphasis on dietary practices, physical activity, and mental health. Despite increasing survivorship rates in this population, there remains a significant gap in the literature addressing their unique post-treatment experiences and needs. Employing a convergent parallel mixed-methods design, this study integrates quantitative survey data and qualitative narrative interviews to assess adherence to health behavior guidelines and to identify culturally specific barriers and facilitators to well-being. Quantitative findings indicated suboptimal adherence to recommended dietary and physical activity guidelines and highlighted prevalent psychological distress among participants. Thematic analysis of qualitative data revealed that enablers of healthy behaviors included fear of cancer recurrence, strong social support, and pre-existing cultural dietary patterns. Conversely, major barriers encompassed financial constraints, limited access to culturally appropriate resources, treatment-related physical limitations, and sociocultural stigma surrounding mental health. This research provides a nuanced understanding of the complex interplay between cultural, structural, and individual factors influencing survivorship among Arab-American women. The findings underscore the urgent need for culturally tailored, community-engaged public health interventions to improve survivorship outcomes and promote holistic well-being in this underserved population
DIM Theory Applied to Law: The Disintegration of American Law
Get PDFPlato, Aristotle, and Montesquieu each argued the importance of law to political regime and Constitution. The ancients emphasized the law as the rational component of the regime and Montesquieu applied some of the first political science to show how political regimes rely upon law. Still, the exact connection between law and politics, and law and philosophy more broadly has remained largely obscured. In my account, legal system ought to be understood as the institutional framework that supports and protect a particular kind of life accepted by the intellectuals and the people of a nation. Using DIM theory from The DIM Hypothesis by Leonard Peikoff, I examine American history to argue the connection between law and the philosophical mode of the dominant culture in American society. Separating out American history out into three different legal regimes, early, middle, and late, I discuss the progression of America’s legal systems. Each part of this dissertation discusses a period in terms of the philosophical context that led to the creation of the legal regime, the key cases that gave further definition to the regime, and a key justice for the period as well as the key attributes of the courtroom etiquette and structure. Together, the discussions of these aspects of a period’s legal system is meant to establish its identity properly categorized as based on one of the five DIM modes of in The DIM Hypothesis . The early American legal system is classified as of the integrative mode; the middle American legal system is classified as of the mixture of the integrative and disintegrative modes; and the late American legal system, yet to be, is classified by the disintegrative mode. The transformation of the American legal system has been from a philosophically integrative legal system, towards a disintegrative legal system. In the context of law, in Part Two, I argue that the early American legal system was the first objective legal system; in Part Three, I describe how the disintegrative pressures around the time of the Civil War led to the transformation of this objective legal system into a fundamentally administrative legal system; in Part Four I describe how the modal logic accepted by the pluralists in changing from an objective legal system led to the continued transformation of our legal system until today, toward egalitarianism. I argue this progression from integration to disintegration has yet to be completed, as the egalitarian legal system has not been fully formalized. The dominant philosophy of legal scholars today may be disintegrative, but until the American legal system sheds it integrative elements, the transformation of American law is not yet complete. This dissertation has two main conclusions. First, that law is a uniquely important subculture for DIM theory, as the law is the final step in crystalizing the dominance of a particular philosophy in the culture. Second, that American legal history should be understood as having three distinct legal periods and that it has progressively changed from a legal system based on the integrative mode to a legal system based on the disintegrative mode. The future of American law will depend on convincing the American people to accept a certain way of life
Integrating Play Into Work: Top-Down and Bottom-Up Approaches to Building Work Engagement Through Play
Get PDFEvolving expectations of what work should look like among employees have inspired companies to revisit working conditions and find a balance between driving organizational outcomes and creating a positive work environment. Work engagement is a positive outcome for organizations and individuals (Bakker et al., 2020). However, interventions centered around driving engagement often are isolated programs that remove individuals from their typical work experience. Integrating play into work offers a strategy to develop employee resources, assisting in actualizing organizational goals and cultivating a positive workplace culture through enhancing work engagement. In this mixed methods dissertation, which involves interviews with leaders (Study 1) and employee surveys (Study 2), I examine perceptions, benefits, and implementation strategies of integrating play into work from top-down and bottom-up perspectives. In Study 1, I interviewed organizational leaders (n = 16) to understand how play is perceived and implemented in a top-down manner at the leader and organizational levels. Using a thematic analysis, emerging themes of authenticity, managerial support, and work engagement added to the current understanding of play at work. In a bottom-up approach in Study 2, I surveyed 248 employees from Prolific to conduct a cross-sectional analysis testing the empirical relationship between an attitude of play with work engagement and two potential mediators, personal and social resources. Participants also responded to qualitative questions from the Study 1 leader interview protocol, which were compared through content analysis to determine differences between leaders\u27 and employees\u27 perceptions of play at work. Structural equation modeling indicated that a playful attitude significantly and positively predicts the level of engagement at work as well as personal and social resources. However, personal and social resources did not mediate the relationship between a playful attitude and work engagement when control variables were considered. Short answer responses from employees shared similarities to leader responses, particularly in identifying benefits of play at work and the prevalence of gamification as a form of play. Employees\u27 perception of detriments to play were overall more pronounced than leaders, indicating power differential may be a factor in perception of play at work. The combined results from Study 1 and Study 2 provides an overview of how play is perceived by leaders and organizations (top-down) and how play is experienced and perceived by employees (bottom-up). Findings contribute to the theoretical development of play at work by including Conservation of Resource Theory (COR) as an explanatory mechanism for how play can produce both positive and negative results. Play was also identified by both leaders and employees as positively contributing to a sense of engagement at work, providing triangulating evidence that play improves work engagement. From a practical implication’s perspective, findings offer suggestions for how to avoid detriments and maximize benefits through considering contextual factors at work, creating psychological safety prior to installing an intervention, and obtaining managerial support
Effortful Emotion Regulation Strategy Use and Cognition: An Individual Differences Approach
Get PDFAs we age, several cognitive abilities decline, yet the ability to regulate emotions remains stable (or improves) even when the emotion regulation strategy required is mentally effortful (i.e., requires cognitive resources for success). The primary aim of this dissertation was to examine how expressive suppression (i.e., the inhibition of emotional responses and behavior) impacts cognitive processing speed following a sadness induction procedure. Groups of younger (participants between 18 – 29 years of age) and older (participants over 60 years of age) adults completed three measures of processing speed, first following a no-regulation control condition. The control condition began with participants watching three film clips from BBC’s Planet Earth series. On a later day of testing, all participants completed the processing speed measures following an effortful emotion regulation experimental condition. The experimental condition began with participants watching three film clips meant to induce negative emotion, namely sadness. Prior to the experimental context of this study, all participants completed several individual difference measures of cognitive ability (e.g., crystallized intelligence, working memory, fluid reasoning, and rational thinking). It was predicted that younger adults would outperform older adults on processing speed tasks, and that effortful emotion regulation would generally impair subsequent cognitive ability (i.e., processing speed). Furthermore, it was predicted that younger adults would be impacted to a greater degree than older adults. Additionally, individual differences in cognitive ability were examined as potential moderators of the impact of effortful emotion regulation on processing speed. Main effects for both age group and emotion regulation, but no interaction effect, materialized in the project. First, younger adults outperformed older adults on the measures of processing speed, supporting the prediction made about this effect. However, regardless of age group, processing speed performance during expressive suppression was facilitated, not impaired. Additionally, these results persisted when statistically controlling for participants fluid reasoning and working memory abilities. This project supported previous findings regarding lifespan trends of cognitive development by demonstrating that, with age, processing speed performance and fluid reasoning ability declined, but crystallized intelligence ability increased. Following expressive suppression strategy use there was no cognitive impairment demonstrated regardless of age group. In fact, processing speed ability increased from the control to experimental test sessions implying that the degree of emotion regulation employed by participants led to facilitation. Additionally, the prediction that younger adults would require increased mental effort to use expressive suppression was not fully supported. However, the association did trend in the predicted direction. Furthermore, the requirement of increased mental effort during expressive suppression strategy use materialized for the entire sample of data and among older adult participants. These findings imply that effortful emotion regulation depletes cognitive resources regardless of the age of participants. In conclusion, self-regulation of negative emotions may function under a similar hyperbolic function like psychosocial stress. Additional lines of research with stronger methodological control are needed to determine these similarities. In conclusion, it is possible that small to moderate degrees of emotion regulation led to facilitation effects of concurrent cognitive ability due to increased focus and vigilance required during the regulation effort. However, larger degrees of regulation may lead to impairments expected by the predictions made in the study. This determination requires further testing under rigorous experimental control
Resource Allocation and Gender Equity in Intercollegiate Esports
No full textThe growth of esports has led to the rapid development of intercollegiate esports programs in the United States. This study explored the connection between resources allocated to intercollegiate esports programs and gender equity. Gender equity is a known issue in the esports community at all levels, including intercollegiate competitions. For higher education institutions, it is important to understand and address gender equity issues because colleges and universities must be able to prove compliance with Title IX, the federal requirement that individuals have equal access and opportunities to participate in activities, including sports, and are not discriminated against based on their gender. This study utilized an exploratory, descriptive survey to collect cross-sectional data from forty-nine higher education institutions. An analysis of these resource allocation and gender equity data revealed common themes among institutions that recruited women to participate in their teams. Using the analytic tool of pattern matching, the study then compared these findings to a literature-derived best-practice model of resource allocation and to Title IX’s Three-Part Test for gender equity. The former comparison identified opportunities for universities to further promote gender equity in esports via changes in resource allocation. The latter comparison indicated how institutions may risk noncompliance with Title IX. In short, the study illustrated how lack of institutional governance, data transparency, and efforts to provide multiple paths to participate in intercollegiate esports make colleges and universities vulnerable to noncompliance with Title IX. It further illustrated how compliance with Title IX may be enhanced by utilizing different patterns of resource allocation
The US Unconventional Monetary Policy and International Capital Flows to Emerging Market Economies
Get PDFThis dissertation investigates the spillover effects of US monetary policy on international capital inflows to emerging market economies (EMEs) from 2003Q1 to 2019Q4, with a focus on quantitative easing (QE) and its normalization phases, including both tapering and quantitative tightening (QT). Using a panel data model with fixed effects, this dissertation finds that the spillover effects of US monetary policy during the QE period have a more pronounced effect on EME capital inflows than do those during the normalization period, where the effects are relatively muted. Second, decomposing the normalization phase into tapering and QT periods reveals that the impact on EME capital inflows during the tapering period is significantly lower than that during the QT period. Although the Fed’s 2013 tapering communication affected EME financial markets in terms of exchange rates and interest rates, there is no evidence that the actual tapering process led to a significant reduction in EME capital inflows. In contrast, during the subsequent QT period, US monetary policy had statistically and economically significant effects on EME capital inflows, specifically for portfolio and FDI inflows. Finally, this dissertation highlights several important determinants influencing EME capital inflows, particularly global risk aversion, domestic political stability, and expected investment returns driven by EME macroeconomic fundamentals
Three Essays on Behavioral Economics : Bribery Solicitation, Pity System and Information Avoidance
No full textThis paper include three parts analyzing the effect of bribery solicitation, the effect of pity System and the effect of meat consumption on information avoidance. The first chapter is the analysis of the effect of bribery solicitation on behavior change. Bribe solicitation is a critical but overlooked part of corruption. This paper uses a one-shot online experiment between citizens and government staff (n = 550) to examine how the opportunity to send no, ambiguous, or clear solicitation messages affects bribery behavior. I find that bribe solicitation opportunity increases corruption by affecting behavior on both sides, depending on message content. The findings indicate that the bribe solicitation opportunity affects the behavior of government staff by reducing its moral cost. These results highlight the importance of recognizing solicitation behavior in the design of anti-corruption policies. The second chapter is the analysis of the effect of pity-system on buying behavior of loot box. The pity-system is a guaranteed reward mechanism commonly used by electronic game companies to bypass gambling regulations. This paper tests the effect of the pity-system in an online experiment (n = 200) where subjects choose to buy the loot-boxes-like lottery with or without the pity-system. The pity-system only increases the number of rounds played, leading to a mild increase in the total number of purchases. These findings challenge the assumption underlying certain regulation policies that pity-system mitigates excessive gambling engagement. This study contributes the first experimental evidence to the literature on digital gambling, risk preferences, and consumer behavior. The third chapter is the analysis of the meat consumption on information avoidance. Animal welfare in meat production is concerning for ethical reasons. Research in psychology has shown that contemporaneous consumption of meat causes people to have less moral concern for farmed animals. Following this research, we run a laboratory experiment to test whether near contemporaneous meat consumption can affect behavior directly through information choice about animal welfare, contributions to an animal charity, and a proxy measure for political behavior. We also test for the indirect effects of meat consumption on our charity outcome and political outcome by way of its effect on information preferences. Though we find that meat consumption changes attitudes towards animals, and information changes charitable contributions, we find that meat consumption does not affect our behavior outcomes. The null result casts doubt on the extent to which shifts in attitudes translate to shifts in behavior. An online hypothetical experiment finds that information preferences are consistent with expected-utility theory, and we again find no evidence of motivated thinking on behavior
VDDM: A Value-Driven Decision Model to Augment Value-Focused Thinking Methodology
No full textDecision-making is a fundamental human behavior. Most scientific research on Decision-making focuses on alternatives: their evaluation, the psychological mechanisms framing the evaluation, and the dynamics of human interaction around alternatives. Value-Focused Thinking (VFT) offers a paradigm shift by emphasizing the primacy of values in framing decision problems prior to evaluating alternatives. This approach is critical as it shapes the decision-making process and outcomes from the outset. Despite the theoretical and practical benefits of VFT, its integration into mainstream Decision-Making research has been minimal. A thorough review of VFT literature reveals its promise as a problem-solving approach but also uncovers seven key areas where it is deficient for practical, real-world decision-making applications. These deficiencies include challenges in the identification of stakeholders, the articulation and elicitation of values, the development and structuring of objectives, and the creation and evaluation of alternatives. This dissertation introduces the Value-Driven Decision Model (VDDM) to address these shortcomings. The VDDM refines VFT with a comprehensive set of definitions, protocols, and best practices that address the seven areas of improvement and include: (1) a classification method for identifying stakeholders; (2) a definition of value’s three dimensions and a standardized protocol for value elicitation; (3) a structured approach for crafting high-quality objectives; (4) detailed guidelines for constructing and quantifying an Objective Network; (5) a framework for generating and evaluating alternatives; and (6) an empirical evaluation to assess the model’s effectiveness in enhancing decision-making processes. The model is operationalized through a prototype and tested within a real-world decision-making scenario. The evaluation of the model validated its effectiveness and informed further refinement of the VDDM and its applications. While developing the VDDM, a novel design approach emerged within the realm of Design Science Research (DSR). This approach is characterized by its three-dimensional focus on theoretical development, practical application, and usability. The theoretical dimension ensures that the VDDM is rooted in a deep understanding of decision-making principles and contributes to academic discourse. The practical dimension addresses the real-world applicability of the model, ensuring that it solves tangible problems and improves decision-making efficacy. The usability dimension emphasizes the user experience, ensuring the model is accessible, intuitive, and adaptable to various decision-making contexts. The dissertation advances the theoretical decision-making methodology by critically examining the limitations within VFT and introducing the VDDM as a comprehensive enhancement. The VDDM not only enriches the theoretical understanding of decision-making processes but also offers empirical evidence supporting the optimization of decision outcomes, demonstrating the practical benefits of a value-driven approach. The VDDM\u27s practical implications are far-reaching. It provides a prescriptive model that supports decision-makers in a wide range of fields, including decision science, information systems, operations, and management. The model\u27s utility is showcased through its application in a real-world scenario, which highlights its effectiveness and adaptability. The VDDM facilitates a more strategic and value-aligned decision-making process, crucial in today\u27s complex and fast-paced environment. Methodologically, the VDDM represents an innovative approach within Design Science Research (DSR), integrating theoretical rigor, practical relevance, and usability into a cohesive framework. This tripartite design framework ensures that the artifacts developed through the VDDM are not only theoretically sound but also practically viable and user-friendly. The VDDM stands as a testament to the potential of integrating values into the decision-making process, offering a new lens through which to view and navigate the complex decision landscapes of the modern world. The VDDM\u27s development and evaluation serve as a blueprint for future research and practice, paving the way for more informed, value-aligned, and impactful decisions across various domains
A Practical Rule of Divisibility By 7 in Uqlīdisī’s Kitāb al-Fuṣūl fī al-Ḥisāb al-Hindī
Get PDFThere are many known examples of divisibility rules in modern mathematics. However, some of these rules are far from being practical, such as the current divisibility rule by 7. A far more useful method can be found in the work of the tenth-century Islamic mathematician Abū al-Ḥasan al-Uqlīdisī (d. 980), who proposed a divisibility rule for 7 in his treatise Kitāb al-Fuṣūl fī al-Ḥisāb al-Hindī. Compared to modern techniques, Uqlīdisī’s rule is both simpler and more practical. This article (re)introduces this rule, and provides an exposition of the mathematical reasoning that underpins it