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Exploring Nondual Awareness: Understanding the Experience and Factors Contributing to Its Development
No full textNondual awareness is a state of awareness focusing on a sense of unity and
oneness and free from subject-object fragmentation. Existing research on this type of
awareness reveals that it can be cultivated through various meditative, mindful or
psychedelic practices and can have significant effects on one’s mental wellbeing.
However, studies on this topic are still very limited. There is little understanding on the
direct experience of nondual awareness phenomenologically. Similarly, existing studies
lack exploration on nondual awareness’s effects on one’s sense of self.
In this study, I conducted a mixed method research study exploring the direct
experience and contributing factors of nondual awareness. Through analyzing
quantitative survey data, I discovered a significant positive correlation between one’s
level of nondual awareness and self-compassion. And through qualitative interviews, key
themes around the experience of nondual awareness are discovered such as initial
disorientation, peace and oneness, shedding control and agency, and improved mental
wellbeing. These study results help provide deeper clarity into the nature and experience
of nondual awareness and its potential effects on mental wellbeing. By understanding its
positive influence on self-compassion, peace and happiness and getting qualitative
insights on how it can be induced through meditation and various life experiences, we
can expand future studies and potentially develop new forms of mental health
treatment/meditation programs.Extension Studie
A Choroid Plexus Apocrine Secretion Mechanism Modulates Cerebrospinal Fluid Contents and Instructs Cortical Development
No full textThe choroid plexus (ChP) plays a crucial role in brain development by regulating the composition of cerebrospinal fluid (CSF) and releasing bioactive molecules that shape neural progenitor behavior. However, the full impact of ChP secretory activity on neurodevelopment, particularly during embryonic stages, remains poorly understood. This dissertation investigates a novel apocrine secretion mechanism in the ChP and explores how maternal drug exposure—specifically with serotonergic agents—can perturb ChP function and disrupt cortical development.
Our experiments first used the 5HT2C receptor agonist WAY-161503 to directly activate ChP secretion. Ex vivo imaging at embryonic day 14.5 revealed that WAY-161503 triggers robust calcium signaling in ChP epithelial cells, which induces a high-capacity release of proteins into the CSF. Proteomic analysis identified hundreds of proteins involved in essential neurodevelopmental pathways, including SHH, WNT, BMP, and IGF signaling, highlighting the ChP’s potential to influence multiple progenitor populations and cortical development simultaneously. Notably, we found that activating ChP secretion altered progenitor fate, leading to changes in the balance of cortical excitatory neuron populations and disrupting cortical architecture. These findings suggest that precise regulation of ChP secretion is critical for healthy brain development, and disruptions could have long-lasting consequences.
Building on these insights, we tested whether maternal exposure to LSD—a serotonergic hallucinogen that acts on 5HT2C and related receptors—would similarly affect ChP function and cortical development. Pregnant mice were administered either acute or repeated doses of LSD, and offspring cortical architecture was assessed postnatally. The LSD-exposed offspring exhibited significant reductions in Tbr1+ deep-layer neurons, altered Satb2+ excitatory neuron populations, and shifts in cortical organization that varied with both sex and exposure regimen. Although we did not perform proteomics after LSD exposure, the observed cortical disruptions align with the hypothesis that serotonergic compounds can alter ChP secretion and downstream neurodevelopmental processes. The behavioral consequences of these cortical changes were also evident, as mice exhibited hyperactivity, increased rotations in the open field test, and disrupted sensorimotor gating, particularly in male offspring.
Together, these findings demonstrate the importance of ChP-CSF signaling in neurodevelopment and highlight the risks posed by maternal drug exposure. The disruptions observed with both WAY-161503 and LSD raise concerns about the use of 5HT2C agonists in pregnant populations, especially as several such compounds are currently in clinical development. This work opens new avenues for investigating the broader pharmacological impact of ChP secretion and calls for further research into how the ChP-CSF axis shapes brain development and behavior. Understanding these mechanisms will be essential for identifying potential therapeutic risks and safeguarding healthy brain development.Medical Science
Statins and PDGFRA Inhibition: A Synergistic Strategy Against Diffuse Midline Glioma
No full textDiffuse midline glioma (DMG) is a fatal pediatric brain tumor with limited treatment options. While PDGFRA inhibitors, like avapritinib, have shown some promise in the clinic, DMGs have been shown to develop resistance to treatment through metabolic adaptations, including increased fatty acid synthesis and oxidative phosphorylation (OXPHOS). This study explores the metabolic basis of DMG treatment resistance to avapritinib and seeks to identify novel drugs that could synergize with avapritinib to provide a durable treatment effect. We demonstrate that atorvastatin synergizes with avapritinib, enhancing cytotoxicity in DMG cells by disrupting lipid metabolism, subsequently leading to increased apoptosis. Furthermore, we reveal that DMG cells treated with long-term avapritinib, called avapritinib-persister cells, exhibit a heightened dependency on OXPHOS and are subsequently more susceptible to statin therapy. Our findings highlight that metabolic reprogramming is a key driver of DMG treatment escape and supports the further consideration of statins as potential metabolic inhibitors when treating DMG with PDGFRA-targeted therapy. Given their established safety and widespread usage, repurposing statins in combination therapy for DMG warrants further preclinical investigation to determine if this approach improves outcomes for DMG patients.Graduate Educatio
Closing Gaps or Holding Steady? The Affordable Care Act, Medicaid Expansion, and Racial Disparities in Coverage, 2010-2021
No full textContext: The Affordable Care Act’s (ACA) Medicaid expansion produced major gains in coverage. However, findings on racial and ethnic disparities are mixed and may depend on how disparities are measured. This study examines both absolute and relative changes in uninsurance from 2010-2021 by race and ethnicity, stratified by Medicaid expansion status.
Methods: The sample contained all respondents under age 65 (N=30,339,104) from the American Community Survey, 2010-2021. Absolute and relative differences in uninsurance, compared to White Non-Hispanic individuals, were calculated for Hispanic; Black; Asian-American, Pacific Islander and Native Hawaiian (AANHPI); American Indian and Alaska Native (AIAN); and multiracial individuals. States were stratified into ever-expanded vs. non-expansion status.
Findings: After the ACA, three patterns of coverage disparities emerge. For Hispanic and Black individuals, relative to White individuals, absolute disparities in uninsurance declined but relative disparities were largely unchanged, in both expansion and non-expansion states. For AANHPI individuals, disparities were eliminated entirely in both expansion and non-expansion states. For AIAN individuals, disparities declined in absolute terms but grew in relative terms, particularly in expansion states.
Conclusions: All groups experienced coverage gains post-ACA, but with heterogeneity in changes in disparities. Focused interventions are needed to improve coverage rates for Black, Hispanic, and AIAN individualsAccepted Manuscrip
The Challenge of Indigenous Worldviews in Environmental Activism
No full textThis work of qualitative, phenomenological anthropological research investigates
the challenges that environmental activists (both Native and Mestizo, which is defined in
this study as a continuum, not a dichotomy), who are operating from nature-centric,
Indigenous worldviews have experienced in communicating those worldviews to those
who grew up within a Western worldview. How are Indigenous and Mestizo
environmental activists attempting to engage the political, corporate and institutional
decision makers in productive dialog during this period of climate crisis and species
extinction?
While Indigenous worldviews are simple to verbalize (i.e., "animals are our
relatives", "we must protect our Earth Mother", and so on), these worldviews have proven
very difficult for many non-Indigenous people to grasp and take to heart.
This profound cognitive disconnect has been identified by others (Deloria Jr.
2006, xxv), but I realized during the research that the truly fundamental question is: what
is the precise source of this disconnect? My interviews with environmental activists
indicate that the disconnect is real, but is not merely based on linguistic, textual, cultural,
conceptual, ideological, or prevailing received bodies of knowledge propagated via
Western economic, political and educational systems. It is deeper than that.
For this paper, I interviewed 18 Indigenous and Mestizo environmental activists
in the U.S. Southwest (northern New Mexico and the Rio Grande Valley of Texas), and
British Columbia, Canada. All operate from a nature-centric worldview and have
received pushback, from people "politely turning away", to being labeled in the media by
politicians as an "extremist" or "ecoterrorist". This reception to the worldviews they are
trying to convey can be baffling and discouraging for them, despite years of working to
communicate effectively and developing thick skins. While some activists continue to
reach out, others will no longer waste their time. Some are educators, some write, speak,
engage in public policy, practice law or engage in protests, some simply do their personal
life work, (particularly agriculture), while sharing their knowledge according to their
personal values of respect for the land and life. All have expressed different levels of
frustration at being held back by the barriers they have encountered in communicating
their views—which, to them, are reasonable, rational, and based in empirical
observation—to those in the dominant Western culture who find these viewpoints to be
totally alien, and in some cases, threatening. All describe progress in their environmental
work as "slow".
It is my intention to contribute to a deeper understanding of the communication
challenges that environmental activists who operate from an Indigenous worldview face
in their work and to explore potential avenues to reach those who are deeply disconnected
from nature. Time is short for those attempting to convey an Indigenous longue durée
value system to non-native political, corporate and institutional decision makers who do
not value Indigenous land-based histories, knowledge or points of view. This gap is
seemingly intractable. Can this problem be improved upon or solved? Is this
communication breakdown conceptual, based in cognition and cultural norms, or is it a
manifestation of something else? Can this disconnect be bridged to avert climate
catastrophe and collectively build a better future for all life on earth?Extension Studie
An Unplugged Curriculum: Empowering All Middle Schoolers with Computational Thinking
No full textComputational thinking is a newly popularized concept, and many have argued for its place in the K-12 curricula. The pedagogical approach is one that creates discussion and debate on how to effectively educate the current and future generations. This thesis presents a novel way of teaching computational thinking skills, specifically to middle school students. The approach links computational thinking concepts to everyday life occurrences and utilizes a teaching strategy that combines aspects of Montessori, peer learning, and unplugged instruction. This method enhances students’ comprehension of computational thinking concepts, cultivates their long-term interest, and encourages their engagement with the material at a deeper level. It helps bridge the unfamiliarity gap many students have with computer science and computational thinking and introduces a new way of thinking about problems in this heavily computational world. A curriculum framework is provided along with sample units that can be used, edited, or iterated upon. With hopes to continuously equip students for the ubiquitous technological world around them, this work serves as a first step in a new direction.Computer Scienc
Deficiency of Sensory Afferents Impairs Dental Pulp Stem Cells (DPSCs) in a Mouse Model of Pulpitis
No full textVital pulp therapy has recently gained traction within the endodontic community as a more conservative and biologically driven alternative to traditional root canal treatment. While sensory nerves are primarily known for their role in pain perception, emerging evidence suggests they also contribute significantly to tissue repair by regulating dental pulp stem cells. However, the precise mechanisms underlying the interaction between sensory nerves and dental pulp stem cells during injury repair remain poorly understood. This study investigates whether sensory nerve deafferentation affects DPSC-mediated homeostasis and the injury repair process in pulpitis. Using a Gli1-CreER/Rosa26-tdTomato mouse model, we performed inferior alveolar nerve deafferentation followed by a dental pulp capping procedure. Single-cell RNA sequencing post-deafferentation revealed a phenotypic shift in Schwann cell clusters, transitioning from a non-myelinated to a myelinated state. Additionally, a significant increase in immune cell populations was observed, indicative of heightened pulpal inflammation following sensory nerve loss. Importantly, sensory nerve deafferentation led to a marked reduction in Gli1⁺ cell aggregation and impaired tertiary dentin formation at the site of pulp capping. These findings suggest that sensory nerves play a pivotal regulatory role in guiding the migration and differentiation of Gli1⁺ cells into odontoblast-like cells, which are essential for effective tertiary dentinogenesis. This study illuminates a previously underexplored dimension of vital pulp therapy, emphasizing the potential role of sensory afferents and their associated molecular mediators in orchestrating mesenchymal stem cell behavior—particularly their migration and transdifferentiation—during the reparative response to pulpal injury.Endodontic
A New Algorithm to Efficiently Match U.S. Census Records and Balance Representativity with Match Quality
No full textWe introduce a record linkage algorithm that allows one to (1) efficiently match hundreds of millions of records based not just on demographic characteristics but also name similarity, (2) make statistical choices regarding the trade-off between match quality and representativity and (3) automatically generate a ground truth of true and false matches, suitable for training purposes, based on networked family relationships. Given the recent availability of hundreds of millions of digitized census records, this algorithm significantly reduces computational costs to researchers while allowing them to tailor their matching design towards their research question at hand (e.g. prioritizing external validity over match quality). Applied to U.S Census Records from 1850 to 1940, the algorithm produces two sets of matches, one designed for representativity and one designed to maximize the number of matched individuals. At the same level of accuracy as commonly used methods, the algorithm tends to have a higher level of representativity and a larger pool of matches. The algorithm also allows one to match harder-to-match groups with less bias (e.g. women whose names tend to change over time due to marriage).Version of Recor