Mutations in phosphodiesterase 6 (PDE6) underlie photoreceptor degeneration through cyclic guanosine monophosphate (cGMP) accumulation, triggering a series of down-stream processes, which eventually kill photoreceptors. We hypothesize that knocking out inosine monophosphate dehydrogenase 1 (IMPDH1), the rate-limiting enzyme in de novo guanine synthesis, will rescue cell death caused by PDE6 mutations. Supporting evidence from a mouse mutant model (rd10) suggests that inhibiting IMPDH1 pharmacologically delays photoreceptor degeneration (Yang, 2020). Our procedure for this experiment is as follows. Fish heterozygous for impdh1a and pde6c mutations are mated to produce fish that are double homozygotes. Fish homozygous for mutations in both the cone-specific pde6c and the impdh1a genes are genotyped and embedded for histological analysis of the retina. Histology is examined on days 3,5, and 7 post-fertilization (dpf) for cone degeneration. To date, we have genotyped our two mutant lines. Normally, pde6c^-/- fish have severe cone photoreceptor degeneration at 5 dpf and impdh1a^-/- fish show no signs of photoreceptor degeneration even as adults. If degeneration is rescued, the double knockout larvae should retain similar photoreceptor nuclei counts to wildtype fish at all time points. Demonstrating that IMPDH1 inhibition rescues PDE6 deficiency would provide proof-of-concept for the therapeutic potential of IMPDH1 targeted inhibition for the treatment of photoreceptor degeneration due to cGMP imbalance.

Neuroscience research relies heavily on cell counting to assess brain injury and evaluate neuroprotective treatments. While manual methods (i.e. hand counting) have been used traditionally, automated programs offer the potential for standardized and error-free data analysis. In the context of studying hypoxic-ischemic encephalopathy (HIE), a prevalent brain injury in infants, we aimed to assess the accuracy of an automated cell counting program in an in vitro slice culture brain injury model of injury and treatment. Code templates from ImageJ/Fiji were taken and modified using ChatGPT, and other snippets were used and modified from online forums like GitHub. The program searches through folders/subfolders for images, converts them into a binary image based on fluorescence threshold data (used to stain cell nuclei), applies the ImageJ function “watershed” that breaks larger groups into smaller groups, runs the “analyze particles” function which outputs a total cell count based on the size and circularity of the cells, and then saves the final image. Fluorescence threshold, cellular size, and circularity values were determined before data collection by adjusting the values to best fit the final image of a random slice. The settings were then kept consistent within studies. Preliminary results show the program’s high accuracy and precision, with consistent results across caffeine and Azithromycin treatments in our in vitro injury model. Despite yielding higher counts than manual methods, the program remained consistent across models. Validating this automated method represents a significant advancement in research methodology. These programs offer standardized data collection, error elimination, and faster analysis compared to manual counting, potentially saving time and resources for labs. Current limitations in our research involve differentiating between healthy and dead or dying cells, which would be an important future step for automated cell counting.

Resilience in Alzheimer's Disease (AD) is defined by the difference between a person's expected and actual rate of cognitive decline given the severity of their disease. However, the mechanisms behind resilience are still unclear and I wanted to see if the anatomy of the brain over the course of AD could offer any clues. To accomplish this, cognitive tests and brain scans were obtained from patient data taken at Harborview Medical Center. Brain tissue atrophy in regions of interest were defined and combined into two measures. The first--biological subtypes--is whether the disease primarily affected the limbic regions or the cortical regions, while the second is left-right asymmetry. I found that resilience correlated with biological subtypes but not asymmetry. This suggests a way for us to predict resilience to better personalize treatment and eventually find ways to increase resilience.

This research project explores the relationship between community social capital and corporate gender diversity, focusing on female executives within S&P 1,500 firms. Previous studies have shown that it is important to have more women in top leadership roles in business organizations today because it provides different perspectives and facilitates various leadership styles, promoting innovation and driving performance. Unfortunately, during the sample period of 7 years between 2010 and 2017, only 8% of top executives in C-suit at S&P 1,500 firms were female. To understand why this is the case and suggest a way to improve this case of female underrepresentation in executive positions, I study the community social capital that fosters a culture of trust, cooperation, and mutual respect, which are foundational for creating inclusive work environments that value diversity. I hypothesize that substantial regional social capital promotes a higher representation of women in top management roles. I collected county-level social capital data from Penn State’s Northeast Regional Center of Rural Development (NRCRD) and gender diversity data from the WRDS ExecuComp database. To test my hypothesis, I conducted a regression analysis. Empirical results indicate that sample firms with greater exposure to higher community social capital are more likely to appoint women to top management positions, which allows them to make crucial decisions within the organization. This study highlights the impact of community dynamics on corporate policies and displays a new perspective on promoting gender diversity in leadership positions. This project intends to improve an individual learning experience by providing valuable insights into the interconnection between societal structures and corporate governance, concentrating on gender inclusivity.

Protists are single-celled eukaryotic plankton that are abundant and diverse in the surface ocean. Many of these protist species are motile often through the use of flagella or cilia. The gene expression of protists is closely synchronized with the daily cycle of light (diel), particularly through the activity of photosynthesis-related genes. However, there has been little investigation of which motility-related genes are expressed in open-ocean protists, among which species, and whether motility-related gene expression is also coupled with the diel cycle. This study aims to investigate the hypotheses that motility-related genes are highly expressed in protist communities, particularly among mixotrophs, and that their expression is synchronized with daytime light. To investigate motility-related gene expression of open-ocean protists throughout the diel cycle, triplicate eukaryotic metatranscriptomes, within the 0.2 – 100 μm size fraction, were collected from 15-m depth approximately every four hours for three days at 158 °W, 41.6 °N, located in the North Pacific Ocean. We annotated protein families (Pfams) present in the metatranscriptomes with Gene Ontology (GO) terms. Pfams were selected based on GO terms related to motility, such as flagella, motility, and cilia. This approach resulted in the examination of the expressions of 21 motility-related Pfams.

It is well established that formerly incarcerated individuals face stigma upon their return to society, negatively impacting reintegration efforts and life outcomes. Existing literature highlights the significance of stigma in influencing reentry outcomes, emphasizing gender-specific challenges faced by formerly incarcerated individuals, but fails to quantitatively study how these gender stereotypes impact public stigma. Although some research does address variations in the formerly incarcerated population and their influence on public opinion, these studies rarely focus on gender. My study directly explores how gender and stigma interact throughout reentry, by quantitatively investigating public perceptions of formerly incarcerated individuals in Washington State. I develop vignettes about hypothetical formerly incarcerated individuals that vary key facts between participants to examine the extent to which gender, offense type, and post-release behavior influence the public stigma of incarceration. Respondents are randomly assigned these vignettes to evaluate their varying perceptions, unveiling whether gender leads to differential perceptions and therefore, differential treatment in the daily lives of formerly incarcerated individuals. My preliminary expectations are that the public will value relationship-building (a traditionally feminine ideal) more for formerly incarcerated women than for formerly incarcerated men. Additionally, I hypothesize that respondents will exhibit a greater willingness to interact with formerly incarcerated women as compared to their male counterparts, due to negative stereotypes about male aggression and criminality. The implications of this research extend to a broader understanding of the obstacles faced by individuals with criminal records in achieving successful rehabilitation. My analysis will help create more targeted and effective reintegration support policies by uncovering how public stigma impacts the reentry outcomes for women differently than for men. Addressing these dynamics is crucial for fostering inclusivity and dismantling barriers that impede the social and economic participation of formerly incarcerated individuals.

Over the past few years, patients have been identified with debilitating phenotypes due to mutations in MSTO1, a nuclear gene. These patients often have distal muscle loss and weakness leaving patients incapable of walking but to date there is no known treatment. One barrier to progress is that virtually nothing is known about MSTO1 function, making the development of therapeutics for these patients extremely challenging. The goal of this project is to use an unbiased approach to discover functions of MSTO1. To do this, I will find genetic interactors utilizing yeast to perform an unbiased screen. Yeast DML1 is the homolog to MSTO1 and is required to keep the yeast cells alive. This screen will identify genes in the yeast genome that support survival of cells lacking DML1 when the gene is overexpressed. We utilize an auxin-degron system that targets DML1 for degradation when the yeast are grown with auxin. To find genes from the yeast genome that keep the cells alive when DML1 is degraded, I express random fragments of genomic DNA. Those genes must, therefore, be linked to DML1 function in some way, thus providing insight into what MSTO1 does, how it works, and how to help MSTO1 defective patients. I have obtained hundreds of yeast colonies that survive without DML1 when other genes are overexpressed. Currently, I am extracting these overexpressed DNAs to determine the gene(s). This work is an essential step toward fully understanding MSTO1 function in cells and we plan to characterize these connections in yeast and human cells.

Light sheet imaging differs from other forms of microscopy by illuminating the entire plane of an ex vivo extracted brain sample and computationally compiling these planes post-hoc into a 3-dimensional image. This technique allows users to preserve the structural integrity and map biological units such as cells, axons, and genes onto a standardized brain atlas. Using the SHIELD clearing, preservation, and staining protocol, we prepared fluorescently labelled ex vivo whole, intact brains for light sheet imaging and used the ClearMap open source pipeline on the Hyak cluster operated by University of Washington-IT to overcome computational limitations. While ClearMap registers images and identifies cell counts per brain region, it lacks quality assurance metrics as well as figures for visual confirmation of preprocessing performance. To overcome these deficits, we have built a quality assurance package for ClearMap that includes registration validation and group-level quantification figures. In testing this package we analyzed multiple mouse brain samples exhibiting Fos expression patterns under varied conditions. Using this dataset we found that registration performance between expected and actual slices measured in F1 score averaged 0.7 in medial sections of the brain and we were able to visually inspect the alignment of subregions identified in a standardized brain atlas. Additionally, we created an interactive script to visualize heatmaps that indicate expression patterns for user-defined brain regions on an animal level. This work will enable rapid validation of collected data and third-party package performance while streamlining the analysis, interpretation, and visualization of results. In the future we intend to include useful statistics (one-way ANOVA, classification models, etc.) to provide additional functionality and further increase the speed and quality of data analysis.

The lithium isotopic composition of metasomatized rocks preserves a history of fluid movement that may be related to large subduction zone earthquakes. High pressure and temperature conditions within subduction zones cause the dehydration of hydrous minerals, and the resulting fluid can raise the pore pressure and trigger slip along the plate interface. The role of fluid movement in subduction zone processes can be better understood by constraining the duration of these events. These relatively fast and periodic fluid increases are recorded by chemical diffusion between the fluid and rock. Fluid containing lithium within a subduction zone can drive the diffusion of lithium into the surrounding rock. Lithium has two stable isotopes that diffuse at different rates, ⁶Li diffusing faster than ⁷Li, creating spatial heterogeneity in the isotopic composition of the reacted rock. Metamorphic rocks from the Western Alps have a reacted rind structure where fluid interaction occurred within an extinct subduction zone. The period of this interaction was examined using lithium isotopes. I prepared these samples for isotopic analysis, first weighing rock powders, then digesting them in acid, and finally separating the lithium with cation exchange columns. Lithium isotopes were measured on a multi-collector inductively coupled mass spectrometer. The spatial distribution of lithium isotopes along the profile from the reaction rind to the unreacted core, together with a thermodynamic model of Li diffusion through the rock, constrain the duration of the fluid interaction and provide insight into the role of fluid in catalyzing slip along the plate interface. I expect the duration of this fluid contact to be short, consistent with pulsed fluid movement within subduction zones. Modern subduction zones, including the Cascadia Subduction Zone that underlies Seattle, pose seismic hazards that can be better understood by examining the relationship between fluid movement and slip in extinct subduction zones.

Economic sanctions as a means of pressuring nations to improve human rights protections or end human rights abuses have become an increasingly common practice in recent years. Although the efficacy of sanctions for humanitarian ends remains under heavy scrutiny, the United States Department of State continues to both implement new sanctions and enforce existing policies of this kind. However, there is a notable discrepancy between regimes accused of human rights abuses by non-governmental organizations and those receiving these types of sanctions. This research aims to unveil potential factors that may explain this gap. I theorize that while investment and trade may protect a country from economic sanctions in an effort to keep certain markets open, past or present adherence to communist ideology increases the likelihood of receiving sanctions on the grounds that communism remains a perceived threat. To test my theories, I identify a set of countries that are currently verified by third party organizations as human rights violators. At this point, I conduct multivariate regression analysis to observe the relationship of both economic interest and conflicting ideology and the presence of sanctions citing human rights violations. While I expect to find that while both factors contribute to the presence of sanctions as outlined, I also theorize that economic interest will have a greater influence. This study serves to identify specific influences on sanctions that will enrich future discourse on their implementation.

The most prominent international organizations have emphasized their commitment in aiding the global transition to a carbon neutral world, which is estimated to cost hundreds of trillions of dollars. Despite these global efforts to mitigate climate change, countries, even when faced with similar levels of threat to climate disasters, prioritize the immediate issue differently. This study explores the relationship between economic security and state climate initiatives as a way to explain countries' varying commitment to climate change mitigation. While many scholars focus on the ability democracies have to combat climate change, I build upon and synthesize theories of economic opportunity, welfare programs, and class solidarity to hypothesize that both individual and state economic security impact states' prioritization of climate initiatives. I argue that economic security is a likely influence on the magnitude of effort which states put into climate initiatives, as it reflects both individual ability to safely fulfill essential needs and state ability to adapt capital. To test my hypothesis, I run a multivariate regression analysis to examine whether key indicators of economic security correlate to state carbon emissions per capita, controlling for regime type, institutional trust, political unrest, and median age of the population. I expect to find a negative relationship between economic security and state carbon emissions per capita. These findings would suggest that improving economic security is essential for the development and success of future climate initiatives. Understanding the underlying roadblocks of long term climate mitigation is crucial in guiding climate policy and optimizing climate aid.

Although oft-cited, the effects of campaign finance are neither well-understood nor well-evidenced; in particular, the supposed vote-buying motive --- contributions given with the expectation the recipient legislator will change their vote on specific bills --- lacks systematic evidence, and literature is mixed both in findings and in methodological quality. Nevertheless, since 2000 (before which much of the literature of “vote-buying” developed), gross campaign expenditures have exponentially increased; prima facie, this suggests that contributors expect returns to their campaign contributions and that (if their expectations are not systematically irrational) campaign finance does affect political outcomes. Building on the public choice theory of regulation, I theorize agents pay the cost of campaign contribution to produce political pressure on a recipient politician, who must then trade-off between the support of competing interest groups. Thus, it is expected that increased campaign finance contributions from interest groups that favor a bill’s passage are associated with a ceteris paribus increased likelihood of the recipient politician supporting the bill. Moreover, because interest groups are heterogeneous in their ability to generate pressure, the estimated treatment effect should systematically vary by contributor type. Previous literature has generally attempted to find statistical associations between contributions from a select few contributing groups and votes on a handful of selected bills (often selected because they are ex ante expected to give significant results), while also failing to incorporate adequate regression controls. Hence, this paper attempts to reconcile the literature’s differing results by using logistic regression to examine a large dataset of US House members’ legislative votes from 1980-2022 and concurrent campaign finance data. This paper's primary contribution is to extend current methods into a large-n analysis, the statistical strengths and methodological limitations of which are informative for future research into interactive mechanisms in economic theories of regulation.

Over 500 million adults worldwide have type II diabetes (T2D), which has caused 6.7 million deaths in 2021 alone. Yet, accessible and sustainable treatments remain limited and many address the symptoms of the disease rather than the root causes, one of which is insulin sensitivity. Recent research shows that therapies targeting glucose-regulating mechanisms in the brain that do not directly affect insulin secretion can enhance diabetes remissions in T2D rodent models. Such treatments may revolutionize diabetes treatment and public health. The Scarlett Lab’s previous studies show that exogenous intracerebroventricular administration of hypothalamic fibroblast growth factor 1 (FGF1) resulted in sustained hyperglycemic remission and increased insulin sensitivity in the mediobasal hypothalamus (MBH), suggesting that FGF1 signaling in the brain impacts glucose metabolism. FGF1 is also endogenously expressed in the MBH, but the functional role of endogenous FGF1 is still unknown. Thus, I hypothesize that endogenous FGF1 signaling in the MBH regulates glucose and energy homeostasis. To test this, I utilize adenosine-associated virus as a vector for gene editing therapy to knock out the Fgf1 gene from the MBH in adult male Fgf1-floxed mice. I then monitor food intake, body weight, and blood glucose levels; perform insulin and glucose tolerance tests; and measure insulin and glucagon levels using enzyme-linked immunosorbent assay. Finally, I use immunohistochemical analysis at the end of the experiment to validate Fgf1 knockout. Based on pilot studies, I expect to observe that MBH Fgf1 knockout significantly increases body weight and impairs glucose tolerance and insulin sensitivity. Follow-up work can elaborate on investigating the effect of a high-fat diet on FGF1 signaling and function. This project illuminates the functional role of endogenous FGF1 signaling in regulating glucose and energy homeostasis and contributes to the development of novel therapeutic strategies to treat diabetes and obesity.

The retina is a unique neuronal structure in the eye that facilitates vision. Many diseases cause the death of retinal cells and this can lead to blindness. Frogs and fish have retinal stem cells that can repair the retina after retinal cell death; these stem cells are concentrated in a region called the ciliary marginal zone (CMZ). It was thought that humans lack these cells; however, we have discovered a region of the retina that has some features of the CMZ. We call this the Late Proliferative Zone (LPZ). One of my research goals was to determine whether the LPZ in humans also contains retinal stem cells that could be harnessed to repair the injured retinae. To start, I measured the area of small cuttings of fetal retinal tissue grown in culture, called retinospheres (RSs), over time and identified a window from 250-325 days gestation in which the LPZ of the human retina continues to grow after the rest of the retina is quiescent. This result shows that the cells of the LPZ can make new retinal cells much later than we thought, supporting the idea that these are retinal stem cells. My second goal was to find factors that can stimulate the growth of these cells. I tested several factors known to be important for the stem cells in frogs and fish. I found the effects of these factors on the types of neurons made by the LPZ. In sum, investigating different ways to manipulate the LPZ provides the field with insight into what is needed to regenerate cell types lost in blinding diseases.

In response to acute genotoxic stress, such as chemoradiation therapy, stem cells undergo temporary cell cycle arrest at the G1/S phase transition. This state, called quiescence, is reversible once stress-free conditions allow reentry into the cell cycle. We have previously identified the underlying mechanism behind quiescence in Drosophila Germline Stem Cells (GSCs) and human-induced pluripotent stem cells (hiPSCs). Mitophagy, or autophagy of the mitochondria, is required to enter quiescence. Surprisingly, we have observed a reserve of cyclin E (CycE) associated with the outer mitochondrial membrane that’s present in normal GSCs and hiPSCs but is reduced in quiescent stem cells. The role of CycE in quiescence remains unclear. Previously we have shown that reduced levels of CycE via inhibition of mTOR have driven cells toward mitophagy-dependent quiescence. This reveals that mitophagy serves as an alternative mechanism of CycE inhibition in contrast to the typical p21-mediated inhibition. Additionally, Parkin, a ubiquitin ligase activated by a serine/threonine kinase PINK1, is a key protein involved in mitophagy required for quiescence, and it has been found that CycE is a degradation target of this protein complex. Our hypothesis is that CycE degradation is necessary for entry into quiescence. To test this we upregulated CycE with a deleted portion of its PEST domain, which is a target for ubiquitination, under UAS-GAL4 control and used the GSC spectrosome morphology to observe quiescence. We observed a six-fold reduction of quiescent GSCs with overexpressed CycE, and hence concluded that CycE degradation is necessary for entry into quiescence. Determining the mechanism of CycE in stem cell quiescence is critical to understanding how cancer stem cells can avoid chemoradiation therapy. This project allows us to characterize the role of CycE within mitophagy and strengthen our understanding of the mechanisms that govern the cell cycle and quiescence.

Angiogenesis, or the formation of new blood vessels, is crucial for normal bodily function but is especially important in diseases that cause blood vessel breakdown such as diabetic vasculopathy. Angiogenesis is regulated by activation of the Tie2 receptors in endothelial cells, which have two main ligands: angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2). Ang1 binding has been shown to stabilize blood vessels and inhibit vascular leakage, while Ang2 antagonizes these effects. We have previously shown that a computationally designed Tie2 super-agonist which presents eight copies of the Ang1 F-domain strongly activates Ang1-like signaling in human umbilical vascular endothelial cells (HUVECs). In this project, we hope to assess the Tie2 super-agonist’s ability to rescue diabetes induced blood vessel defects in a diabetic blood vessel organoid (BVO) model. To model diabetic conditions, a three-dimensional blood vessel organoid model has been cultured in a high glucose media along with inflammatory cytokines associated with the diabetic phenotype. Western blotting and immunofluorescence staining will be used to assess the relative quantities and localization of proteins involved in vascular stability and inflammations upon treatment with the Tie2 super-agonist. Vascular degeneration is a very harmful condition associated with many prevalent diseases including diabetes, so the Tie2 super-agonist could potentially be a new therapeutic drug candidate for treating blood vessel dysfunction in patients with these conditions in the future.

Lizards in the family Tropiduridae have ventral epidermal gland organs that are involved in chemical signaling and whose secretory mechanism is entirely unknown. This is because, like other epidermal generation glands, 'alpha-glands' lack a pore through which their secretion can be exerted. Chemical signaling is a valuable aspect of tropidurid lizards' social and ecological interactions, and some have been observed territorially scraping their alpha-glands against the substrate. This process has been hypothesized to facilitate the release of chemical signals via abrasion. To investigate this abrasion hypothesis, we analyzed 74 skin samples from 27 tropidurid species, using light microscopy and scanning electron microscopy (SEM). The SEM revealed incredible surface variability in epidermal glands, providing morphological insight. We found that the exposed glandular mass of each gland scale rests atop the oberhautchen layer of the skin's subjacent generation, which indicates that the secretion of chemicals involves exposing a mostly solid glandular material on the outside of the scales. Histological sectioning of gland scales revealed morphological consistency, indicating that the same secretory mechanism is shared across the tropidurid phylogeny. Imaging of histology samples also revealed that the shedding process which exposes the glandular material may be facilitated by the clear layer, found directly above the glandular mass during development. Characterization of morphological patterns in the formatted SEM images and comparison with histological data should provide evidence for or against taxon-specific or ecology-specific alpha-gland structures, and further support the idea of chemical secretion requiring epidermal exposal of glandular material. Investigations of the morphology and functional mechanism of this unique organ provide insight into the behavior and evolution of tropidurid lizards and shed light on factors influencing the evolution of chemical signaling in terrestrial organisms. 

I am a cellist, improvisor and composer. I have experience performing diverse genres of music including electroacoustic, though I primarily I consider myself to be a classical cellist, composer and improviser.  I am interested in discovering new extended techniques on acoustic cello. I first discovered new bow harmonics and recorded compositions using them early in my career. My research into extended techniques on cello has continued recently and I discovered a new sound using a variation of an extended technique. This year I have been composing and improvising at UW and working with and learning from Huck Hodge. This Spring I will present the newly discovered sound via a performance of an aleatory composition for solo cello, including improvisatory elements, which will feature a new sound created by an extended technique I recently discovered on acoustic cello. The new sounds I have been discovering are akin to quantum particles: already present within the sound, yet normally hidden by standard classical technique. It is my intention to broaden the palette of colors for classical cello technique and repertoire.

Traumatic spinal cord injury (tSCI) is a devastating condition that causes sensory and motor dysfunction and permanently impairs normal life. Spasticity is one of the most common complications associated with tSCI that limits independent functional abilities. Spasticity is defined as a velocity-dependent increase in muscle tone, in response to passive movement and it is accompanied by pain and stiffness. Unfortunately, current treatments provide only transient and often incomplete relief of spasticity and individuals often experience long-term adverse effects. Through a collaborative project between three labs, we aim to develop a durable non-invasive electrical stimulation treatment to alleviate spasticity. I participated in preparing the model of spasticity by performing spinal surgeries on the cervical spine of rats. To evaluate spasticity, we studied the loss of Rate-Dependent Depression (RDD) of the H-reflex which is considered the electrophysiological hallmark of spasticity. To do so, I fabricated an electrode nerve cuff that was implanted on the median nerve of the rodent’s forearm to study the H-reflex of the affected muscle in the rat’s forelimb. I then recorded and analyzed the temporal development and change of spasticity. H-reflex results validated the spasticity model by showing RDD reduction in injured rats compared to the uninjured rats. The developed treatment shows promising modulation of the H-reflex and recovery of RDD in injured animals. Additionally, to measure velocity-dependent muscle tone, we developed a robotic device that passively moves the rodent’s forearm at different velocities. Employing this robotic behavioral assessment allows me to objectively assess the effect of stimulation on spasticity in the rodent forelimb. Obtained data reveals the muscle resistance to be three times higher in the injured rodent. This novel therapeutic stimulation protocol could potentially be used for clinical use as a non-invasive therapy, to help patients with spasticity in the hand after suffering from cervical tSCI.

Signaling of fibroblast growth factor receptors (FGFR) is critical for the development of vascular cell types. FGFR exists as two alternative splice variants: the b and c isoforms. Previous experiments have shown that activation of the c isoform leads to arterial endothelial cell development and inhibition of the c isoform is critical to perivascular development. These results were found using a c isoform-specific computationally designed protein. The goal of my project is to replicate these isoform specific results in an endogenous context. Our hypothesis is that induced pluripotent stem cells (IPSCs) overexpressing the b isoform will develop into pericytes and IPSCs overexpressing the c isoform will develop into arterial endothelial cells. I used the Gibson assembly method to create b/c isoform overexpression plasmids that can be inserted into the AAVS safe harbor site and used bacterial transformation to increase the amount of DNA. I am using stable transfection to create IPSC overexpression cell lines and adapting a previously verified 14-day protocol for creating endothelial cells from IPSCs to monitor each cell line’s differentiation. I am performing assays such as qPCRs, Western Blots, and immunofluorescence to quantify perivascular and endothelial markers in the cell lineages. Our findings should agree with our isoform specific hypothesis. In future experiments, we plan to engraft the overexpression cell lines into immunodeficient mice and assay how varying ratios of the two cell types affect their regenerative potential in vivo.

The Poolos Lab has made significant progress in elucidating the regulation of tau phosphorylation in the brain and its relationship to both Alzheimer’s disease (AD) and temporal lobe epilepsy (TLE). However, conflicting data exists in the field regarding whether patients with epilepsy exhibit increased or decreased tau phosphorylation and expression compared to health controls. From our preliminary findings using mass spectrometry, we hypothesize that tau undergoes dephosphorylation at several amino acid sites in TLE, as opposed to the hyperphosphorylation observed in AD. To validate this hypothesis, I conducted western blots to separate sample proteins based on their molecular weight via gel electrophoresis. Western blotting has increased sensitivity compared to mass spectrometry in measuring protein phosphorylation levels. I assessed changes in tau expression and phosphorylation using phospho specific antibodies that quantify site specific tau phosphorylation levels. These samples are derived from hippocampal tissues obtained from a chemo-convulsant rat model of TLE, which mimics the chronic seizures experienced by human patients, and compared to age-matched naive controls. Densitometry is employed to quantify the relative amount of phosphorylated tau, and a two-tailed t-test statistical analysis confirms significant changes in tau phosphorylation and expression between tissues from chronically epileptic animals and control subjects. Additionally, I plan to conduct western blots on human tissue from TLE patients to generalize our findings from animal models, deepening our understanding of tau dysregulation in epilepsy. Given the increased risk of premature death and adverse effects on physical and mental health experienced by epilepsy patients, our research holds significant implications for the well-being of epileptic patients and their loved ones. By identifying alterations in tau phosphorylation, we aim to develop a biomarker of epilepsy in cerebral spinal fluid and the blood, thereby advancing diagnostic tests and potential treatments for epilepsy.

Chemical communication is the oldest and most widespread form of communication across the tree of life, and markedly present among lizards. However, the drivers of chemical profile variations in this group remain for the most part uninvestigated. In South American lizards of the Tropiduridae family, semiochemicals are produced by epidermal gland organs called α-glands, exclusively found on the ventral side of male individuals of at least 40 species from four genera. The chemicals produced by these glands are hypothesized to interact with their environments in different ways since chemical species are naturally reactive and tend towards their lowest energetic state. Thus, the intrinsic properties of a semiochemical impact its survival and efficacy for communication. Given the diverse ecology and broad geographical distribution of tropidurids, we investigated whether variation in the chemical composition of α-gland secretions correlates with temperature, humidity, and habitat openness. We performed liquid chromatography-mass spectrometry (LCMS) to obtain the metabolomes of three different sample types. We sampled male skin containing the α-glands, undifferentiated male skin, and female skin. Environmental and chemical property data were extracted from online databases, literature, and field observations. Preliminary tests were done by making Venn diagrams comparing the metabolomes of each sample type. These revealed differences in metabolite compositions, notably between males and females as well as between glandular and undifferentiated skin. From the metabolomes of α-glands, we expect to see chemical species with properties that confer greater survival given the specificities of the environment. For example, given a lizard from a hot and humid environment, we expect the metabolome of the α-glands to contain higher molecular weight species with less functional group complexity. Understanding how environmental parameters drive the chemical composition of α-glands is expected to provide a deeper understanding of the evolutionary history of chemical signaling in terrestrial vertebrates.

Vaccines have successfully reduced global infectious disease burden, but there is room to improve vaccination technologies. Because many pathogens infect at mucosal sites, a goal of new vaccines is to promote strong mucosal and systemic antibody and T-cell responses. Integrated fiber microneedle devices (iFMN) are a novel oral vaccination method that may achieve this goal. These devices are patches with a polymer backfill matrix and multiple >1 mm pyramidal needles that penetrate immune cell-rich mucosal tissue in the mouth, inducing immune responses at draining lymph nodes. To test the hypothesis that priming with iFMN delivery of a DNA vaccine increases mucosal and systemic antibody responses after systemic booster immunization with the same vaccine, male rhesus macaques (n=6) were primed with an iFMN delivery of a DNA vaccine encoding Influenza A Virus (IAV) Nucleoprotein (NP) at weeks (0) and (6). The macaques then received a single boost of the same NP DNA vaccine at week (12) using the proven delivery modality of Gene Gun epidermal delivery (GG). Mucosal secretions (including bronchoalveolar lavage, saliva, and nasal/tracheal swabs) and serum were collected 2-4 weeks before and after each immunization. I conducted enzyme-linked immunosorbent assays (ELISAs) to quantify antigen-specific IgG and IgA binding antibody at each timepoint. To characterize the priming effect of iFMN oral delivery on systemic and mucosal antibody responses, I compared these animals’ responses to macaques (n=8) previously immunized with a single GG dose of the same NP DNA vaccine. The iFMN-primed animals had robust post-GG boost NP-specific IgG responses in serum but these responses were not significantly higher than for macaques boosted solely with GG DNA. These results demonstrate that iFMN delivery did not effectively prime for robust systemic and mucosal antibody responses. Additional experiments will be done to confirm these findings.

The T3 Watershed Experiment Upland Silviculture Study explores innovative approaches to managing forests in the Olympic Experimental State Forest (OESF) managed by Washington state DNR. This model study is an addendum to the T3 study exploring different treatments to enhance ecological heterogeneity through the implementation of variable-density plantings in the context of marigold growth. Variable-density planting increases heterogeneity by adding a variety of clumped areas across a unit which has the potential to enhance biodiversity and habitat, improve ecological resiliency, increase carbon sequestration, and optimize tree growth. We chose marigolds to act as a model specie for conifers due to its short life cycle, ease of use, and ability to growth tall and straight. Our team planted marigolds using three treatment groupings including small clump, large hex clump, and regular spacing (control)— implemented in six boxes within a controlled greenhouse environment. In Autumn 2024, volunteers and I collected comprehensive data on various growth metrics. Later, I measured the biomass of leaves, stems, reproductive shoots, and total biomass to determine biomass variations. I analyzed the effects of treatment on the stem straightness/sway, mortality, biomass of different tissues, and social class proportions. This research contributes to the broader understanding of how variable-density plantings influence vegetation dynamics, providing valuable insights for silviculture practices. The findings aim to inform future land management strategies by providing data that supports the hypothesis that variable density planting may provide numerous benefits without decreasing timber harvests.

Vulcanized rubber, the main component of tires, is prized for its chemical durability and thermal stability. These properties, however, make disposal difficult and contribute to the increasing problem of polymer waste. To broaden the applications of end-of-life tires, we developed a method to chemically upcycle polybutadiene, a primary component of vulcanized rubber, via selenium-mediated allylic amination. We hypothesized that functionalizing the backbone of crosslinked polybutadiene with sulfonamide groups—without breaking their double bonds—would result in favorable thermal properties, creating a new life for the crosslinked polybutadiene. We used infrared spectroscopy and scanning electron microscopy with energy dispersive X-ray spectroscopy to confirm the aminated crosslinked polybutadiene’s molecular structure and differential scanning calorimetry and thermogravimetric analysis to measure its changes in thermal properties. Our research has future implications for the reduction of tire waste and reprocessing of other end-of-life crosslinked polymers.

The latest developments in health applications for large language models (LLMs) have shown promising prospects in providing preliminary diagnoses based on user symptoms, especially appealing to patients with mild conditions who prefer online consultation over in-person clinic visits. However, the accuracy of these symptom-based decisions remains uncertain. This gap is more pronounced in mental health applications, where there is a noticeable lack of research on the efficacy of LLMs in offering effective treatment advice. Our study addresses this issue by evaluating systems through a combined analysis of LDA topic modeling, word frequency analysis, and cosine similarity analysis, examining how chatbots based on LLMs utilize data from the American Psychological Association to provide diagnostic information and the accuracy of their treatment advice. We found that while these chatbots can provide highly accurate diagnoses and corresponding treatment recommendations for virtual patients, they typically offer less information about the prescribed treatment needed compared to human psychologists; moreover, chatbots based on LLMs tend to mention common relevant words across all topics, whereas responses from psychology experts are more likely to cover most relevant words within a topic. This raises discussions about the significance and limitations of LLMs in mental health diagnosis and treatment advice, calling for a highly academic approach.

The emergence of induced Pluripotent Stem Cells (iPSCs) have allowed researchers to better study the effects of various diseases and mutations on fetal development. One such way of accomplishing this is the breakthrough of the organoid: a complex, iPSC-derived, 3D structure, that provides biologically relevant models for human systems. Lung Organoids (LO) were developed through this technology. However, the current LO models utilize mature lung phenotypes, which do not consider progenitor stages that may be critical for fetal development and the understanding of diseases that may affect this development in utero. The goal of this project is to provide characterization to the early stages of iPSC LO development: the Embryoid Body (EB) and Anterior Foregut (AFE). Using a previously established protocol, the LOs were fixed with 4% paraformaldehyde (PFA) on day 4 (EB stage) and day 6 (AFE stage), then analyzed with immunofluorescence analysis of the corresponding fetal lung (FL) development markers. 135 day old FL tissue sections were used as a positive control. The markers used to establish characterization were SOX17, a marker for the early endoderm germ layer, OCT4, an iPSC marker for pluripotency, and ECAD, a marker for tissue layer separation and cell migration. We hypothesized that all markers would appear in the EB stage, and the AFE stage would experience an upregulation in SOX17 and downregulation in OCT4 and ECAD. My results confirmed an upregulation of 133% for SOX17 and a downregulation of OCT4 by 58% from the EB to AFE stages. Lastly, as hypothesized, ECAD was present in EBs, but not in AFE. In conclusion, the LO stages proved to be similar to developmental stages of in utero development. Further analysis could help with new disease and mutation models for early development in utero, helping prevent devastating outcomes.

According to some measures, the United States has the largest economy in the world. Despite its massive gross domestic product, US citizens still face high poverty rates across states and counties. Why are there persistent poverty rates and why do they vary across the nation? To answer this question, I hypothesize a negative relationship between welfare spending and poverty rates. Welfare spending is one of the most direct ways that the government can provide money to people experiencing poverty. When people have their most basic needs provided, through welfare programs, they are significantly more likely to get out of poverty. To explore this relationship I use a multivariate regression, controlling for other factors that can impact poverty rates. Through testing this data, I hope to illustrate the importance of adequately funding welfare programs to reduce poverty across the nation. By increasing welfare spending individuals can get out of poverty and communities can thrive, improving the lives of all citizens.

Current concentrations of carbon dioxide are 420 ppm, a 50% increase since the industrial revolution. Nitrous oxide (N₂O) concentration has increased by 18% since the industrial revolution and is currently 319 ppb. This slight increase may not appear alarming, but since nitrous oxide traps 300 times more heat than carbon dioxide, lowering emissions of this greenhouse gas will help stabilize the climate. One major source and sink of N₂O is production and reduction by microbes, respectively, which have been perturbed by anthropogenic increases of nitrogen. Novel microbes found in low pH (3-6) subsurface sites in Tennessee have been shown to respire N₂O, reducing it to N₂ using both Clade I or II nitrous oxide reductases. Microbes that can reduce N₂O at such low pHs (below 5) are rare but could be beneficial as a sink for nitrous oxide. One such strain is a novel Bacteroidetes that encodes a Clade II nitrous oxide reductase and was provisionally named strain S13. In my experiment, I aim to better understand the metabolic processes of this strain and identify the optimal temperature for growth, using xylose, a 5-carbon sugar, as the carbon source. S13 was then grown in an electron acceptor (N₂O) limiting environment, electron donor (xylose) limiting environment, and fermentative conditions. After the microbes completed their growth, the gas and metabolite concentrations were measured using Gas Chromatography and High-Performance Liquid Chromatography. When grown on xylose, the products produced were hydrogen gas, succinate, and acetate. Optical density of these tubes was measured over the course of their growth to determine growth rates and maximum yield (optical density). This was done at 6 temperatures: 15°C, 20°C, 25°C, 30°C, 35°C, and 40°C. These data indicated that S13’s optimal temperature for growth was 25°C. This information could be utilized in future bioremediation and nitrous oxide control efforts.

Current trends indicate that while adolescents and young adults are starting to engage in sexual activity later in life and less frequently, there is a notable shift towards experiences characterized by low commitment and higher risk. Despite numerous studies on sex-related attitudes and practices among young people in the United States, broader insights are necessary to achieve a holistic understanding of the newly emerging landscape of youth sexuality. Against this background, our research examines sexual attitudes and reported behaviors in a sample of 1,200 undergraduate students at the University of Washington. Our study employs a comprehensive survey to identify patterns in sexual attitudes and behaviors among a representative sample. Administering online questionnaires is crucial in ensuring increased reliability and validity of responses on sensitive topics. These include but are not limited to, pornography viewership, kink and fetish interests, sexual self-concept, and more. Preliminary findings indicate a complex interplay between cultural, educational, and social factors in shaping sexual norms and practices among young adults. This study contributes to the broader discourse on sexual health education and highlights the need for nuanced approaches in addressing the dynamic and multifaceted nature of young people's sexual relationships. The results of this investigation aim to inform the foundation of modern sex education in order to address the evolving challenges of today's sexual landscape.

From 2012 to 2022 violent crime in rural America has either increased or stayed above the national crime rate. At the same time, the amount of firearms in these counties rose dramatically while law enforcement expenditure and poverty reduction stagnated. I theorize that a combination of high poverty rates, increased firearm ownership, and fewer police has contributed to the increase in rural crime over the past decade. As the literature suggests, firearms make it easier to commit violent crimes, fewer police make crime harder to detect, and poverty pushes people into crime due to unstable living conditions. I will evaluate the effect of these three factors on rural crime rates by using FBI Uniform Crime Report, U.S Census Bureau, and RAND Corporation data to perform multivariate regression in order to determine causality. I expect to find a strong positive correlation between these three factors and the rural crime rate. I will use multivariate regression analysis to examine the influence of gun ownership, law enforcement spending and poverty on rural crime rates. By finding the causes of crime in rural communities, I will help identify the areas that local governments will need to address to solve problems of violence.

Historically, the field of healthcare and broadly STEM has been slow to match the diversity of our communities. This is in part due to attrition in college of key underrepresented groups (Flynn, 2016). One-time events that invite new students with every workshop, also known as touch-point events, allow for broader outreach and accessibility but it is unknown how impactful they can be on students’ self-efficacy. The aim of this study was to analyze how a touch-point event such as Anatomy for Change (AFC) workshops could impact a student’s learning abilities and academic confidence. We partnered with undergraduate student groups at the University of Washington (UW) from historically underrepresented backgrounds in medicine to host each workshop. Within our events, we invited UW School of Medicine students to guide undergraduates in completing various medical case studies. Our study measured the effects of our workshops with pre and post-event surveys given to undergraduate student attendees. These contained open-ended questions as well as scaled questions based on a 5-point Likert scale. For undergraduate students from a variety of racial, ethnic, and gender backgrounds we saw an increased confidence in their ability to learn anatomy, problem-solve in a medical context, and pursue a healthcare field. We also saw that the event increased their sense of belonging in the pre-health space. Our results are promising and indicate that a touch-point event can have a positive impact on a student’s educational journey. Furthermore, such programs can be done across a variety of disciplines and institutions throughout the academic spectrum to promote diversity and inclusivity in education.

Traumatic brain injury (TBI) is caused by an external force to the head, resulting in brain injury and is a major cause of death, particularly in adults 75 years and older who are at increased risk of falls which can lead to disability. Humans have a natural response to impact and strain called the Valsalva maneuver, which leads to an increased pressure in the chest and abdomen, which can result in a neuroprotective increase in intracranial pressure (ICP). However, most people are unable to anticipate TBIs and cannot perform their own Valsalva maneuver. Using a ferret model of TBI, the neuroprotective effects of externally-stimulated Valsalva-like response will be assessed. Ferrets are used to model human TBIs because the cortical thickness and layer distribution of their brains are more akin to humans in the ferret compared to rodents. The ferrets will be randomized to one of the three groups: control, TBI+sham valsalva, and TBI+valsalva. To show that the intracranial pressure of ferrets can be transiently increased, an inflatable cuff will be utilized to exert pressure on the abdomen, resulting in a partial Valsalva maneuver. TBI will be induced in the ferrets using a closed-head impact, and the neuroprotective effects of increased ICP from the inflatable abdominal cuff will be assessed using a battery of motor and cognitive tests before and after the TBI event, additionally, brain injury and neuroprotection will be evaluated using histopathology. I hypothesize that the Valsalva maneuver induced by the inflatable abdominal cuff will reduce behavioral deficits resulting from impact. If the behavioral deficits are reduced, this study can work to inform future interventions for TBI, such as environment-sensing wearable devices for high risk populations.

Preterm birth is one of the leading causes of neurological deficits and mortality in neonates. Hypoxia-ischemia (HI), when the brain receives insufficient oxygen and blood supply, is a commonly observed condition among preterm infants. Preterm birth and HI affect the structure of the developing brain, particularly the formation of cortical folds (gyri) of the brain. This process is difficult to study in rodent models as they are lissencephalic and do not have gyrified brains. Ferrets, unlike rodents and more similar to humans, have gyrification – the folding of the cerebral cortex, creating gyri and sulci. Using the ferret as a model, examining changes in gyrification after injury can help us identify and further understand brain injuries like HI and its effects. Preterm-equivalent postnatal day (P) 17 ferrets received lipopolysaccharide intraperitoneally and underwent bilateral carotid artery ligation followed by hypoxia-ischemia plus hyperoxia (HIH). Animals were either non-HIH exposed (controls) or HIH-exposed and randomized to receive saline vehicle, erythropoietin, or therapeutic hypothermia. At P42, ex vivo (n=74) magnetic resonance images were collected. Using ImageJ software, the inner to outer hemispheric ratio was used to set the gyrification index (GI). We assessed the average GI across the whole brain and the peak GI of left and right hemispheres. Kruskal-Wallis test will be used to measure the differences in average and peak GI across treatment groups. We hypothesize that the average and peak GI of injured animals treated with Epo, TH, and saline will be lower compared to control animals. Gyrification can be an essential metric for researchers to analyze brain injuries like HI in preterm neonates. As preclinical and clinical studies for HI continue to improve, gyrification can inform the relationship of folding patterns in the cerebral cortex area, assisting us to examine the potential shared developmental processes between animals and neonates.

While recent advances in sequencing technology have increased the detection of missense variants in human genes, the functional impact of ~99% of these variants is unknown. Improving our understanding of variant effects will make precision medicine more effective, allowing us to define, test, diagnose, and treat genetic diseases better. One way to understand what variants do is to measure and read out each variant’s effect in cell-based assays. However, there are nearly 9 billion possible single nucleotide variants in the human genome. To measure variant effects in a comprehensive manner, scalable experiments are necessary. Previously, the Fowler lab developed landing pad (LP) vectors to conduct scalable cell-based assays over entire gene variant libraries. However, the current LP design suffers from rapid silencing in cell culture, a phenomenon in which cells deactivate the expression of transgenes, greatly limiting the scope of variant assays. Stem cells are known to rapidly silence most exogenous sequences during differentiation, but they are a target model as LPs embedded in stem cells would allow us to study the effect of gene variation in cells specific to the related disease. Through previous work at the Fowler lab and others, we have characterized a set of promoters, enhancers, insulator sequences and other elements that will provide stable and robust expression of transgenes over time. We hypothesize that combining the LP with this set of elements will allow us to stably express variant libraries regardless of cell context. To test this hypothesis, we have designed a nested LP delivery system that allows us to compare different LPs side-by-side in the same genomic context. By comparing expression levels of transgenes over time, we expect to find that LPs enhanced with a set of stabilizing elements will express stronger signals over longer periods of time compared to LPs that are not enhanced.

Hypoxia-ischemia (HI), or brain injury caused by a lack of blood flow and oxygen to the brain, is a leading cause of infant mortality and morbidity. Contrasting between ages, the effects of HI tend to be more severe in younger neonates. Curcumin, a dietary compound derived from turmeric, exhibits anti-inflammatory, antioxidant, and antiapoptotic properties, but is not bioavailable in molecular form, thus may serve as a neuroprotective treatment when loaded into synthetic nanoparticles to allow for effective absorption and crossing of the blood-brain barrier, forming the treatment NanoCurc. Gestational ages of 37 weeks through 42 weeks are all considered term neonates, yet their brain continues to develop and differ significantly in response to treatments against HI. Using the rat Vannucci model of unilateral hypoxic-ischemic brain injury, we studied the in vivo effects of NanoCurc in neuroprotection, in P7, P10, and P13 rats, equivalent to 34, 38, and 42 weeks’ gestation, respectively. Tissue is collected 72 hours after unilateral carotid artery ligation surgery, followed by tissue staining and analyzed by tracing the healthy tissue versus damaged tissue, to calculate the average percent area loss in treated and untreated rats. I hypothesize that in all ages, neonatal rats treated with NanoCurc will have lower injury in comparison to those treated with saline (vehicle), while the treatment will be more effective in younger rats in comparison to older ages. In the future, NanoCurc treatment may be used as a neuroprotective agent in reducing the effect of HI in preterm and term infants. If NanoCurc provides a stronger neuroprotective effect in the younger population, it may serve to target infants most severely affected by HI, potentially creating personalized treatment for gestational ages.

Perinatal asphyxia or hypoxia, where the infant brain does not receive enough oxygen or blood flow, commonly occurs in premature newborns and is one of the leading causes of neonatal mortality worldwide. Survivors often have altered white matter with cognitive impairments, motor deficits, and increased rates of cerebral palsy. There is currently no standard treatment for preterm brain injury, so there is a critical need to research neuroprotective strategies as well as ways to assess their impact. The ferret is a promising model species for studying preterm brain injury due to its gyrified brain and white-to-gray matter ratio, which are similar to that of the human brain. The gyrification index (GI) can be used to assess cortical development and is calculated using magnetic resonance imaging (MRI) images. These are analyzed using ImageJ software to perform hemispheric tracing by dividing an internal trace, including the gyri and sulci, by an external trace that excludes them. A higher GI is indicative of a larger cortical surface area. This project seeks to evaluate the effects of postnatal (P) age on post-hypoxic-ischemic (HI) gyrification in two ferret models. In both models, HI ferrets underwent bilateral carotid artery ligation and exposure to hypoxia, differing by date of surgery, with randomly assigned control animals not undergoing surgery. Model One ferrets underwent surgery at P10 (extremely preterm equivalent) and tissue collection at P70, and Model Two ferrets underwent surgery at P17 (late preterm equivalent) and tissue collection at P42. I hypothesize that GI will be affected by HI injury, with both age of injury and age of assessment altering GI relative to control animals. Contextualizing age differences in GI could help inform future therapy regimens to treat infants with premature brain injury.

Preterm neonates frequently undergo episodes of hypoxia, hypotension, and hyperoxia due to their underdeveloped cardiorespiratory system. As a result, preterm infants are particularly susceptible to brain injury from lack of sufficient oxygen or blood flow. In this study, we use a neonatal ferret model of hypoxic-ischemic-hyperoxic (HIH) brain injury to examine the neuroprotective efficacy of azithromycin (Az), a safe and accessible antibiotic with anti-inflammatory properties that crosses the blood-brain barrier in premature infants. Our HIH ferret surgery model produces global brain injury in Postnatal day (P)14 ferrets, which are developmentally equivalent to extremely preterm neonates. Ferret kits in the surgical group will receive a pro-inflammatory stimulus (E. coli lipopolysaccharide), followed by a bilateral carotid artery ligation and exposure to HIH. Then, surgical animals will be randomized to receive intraperitoneal injections of saline vehicle (Veh) or Az. Control animals will not receive LPS or undergo surgery. We will use a Kruskall-Wallis test to compare P21 ferret weights and brain measurements seven days after surgery to test whether Az is neuroprotective. We will assess pathology using quantitative immunohistochemistry with Iba-1 (microglia) and GFAP (astrocytes) stains. We have two main hypotheses. We hypothesize that 1) ferrets treated with Az will lose less body weight after exposure to inflammation-sensitized HIH than the Veh group, with Az-treated animals being similar in weight to non-injured controls, and 2) normalized brain measurements, corrected for body weight and sex, will show that Veh animals have smaller gyri and sulci measurements than controls, and Az-treated animals will have brain measurements that are more similar to controls. We are optimistic that our experiments will provide evidence that azithromycin is potentially neuroprotective and will offer a promising treatment option for preterm babies with brain injury.

Autism Spectrum Disorder (ASD) is a neurological and developmental disorder that affects around 1 in 6 children and 1 in 65 adults in the United States. Autistic individuals experience difficulties in social communication, interaction amongst peers, and language skills; any of the symptoms of ASD cause an influx of other problems that continue into adulthood; these differences may impact self-esteem and feelings of acceptance. Previous research has shown that a history of mental health concerns is related to worse Quality of Life (QoL) in individuals with autism as they transition into adulthood. This project aims to examine mental health comorbidities and self-reported QoL in adults with autism. 44 autistic adults from the NIH funded study on sex differences in autism were included. Participants completed a self history of current mental health diagnosis (anxiety, depression, OCD, ADHD etc.) and self reported QoL. Participants were grouped into 3 groups based on diagnosis: 1 (no diagnosis), 2 (1 diagnosis), and 3 (2+ diagnosis). QoL scores for each group will be calculated from the World Health Organization Quality-of-Life Scale (WHOQOL-BREF). I predict that individuals with more comorbid mental health diagnoses will have lower QoL scores. These data will inform us of how additional mental health struggles may impact quality of life in individuals with autism.

Autism Spectrum Disorder (ASD) is a developmental disorder that is characterized by difficulty in social cognition, communication, and behavior. Social cognition refers to mental processes related to how individuals perceive, process, and respond to social information. Elpers and Coyle (2021) found that there is a correlation between social cognition and general intelligence for adults with ASD. However, there is limited research on this relationship in younger age groups and for individuals without ASD. The goal of this study is to replicate the findings from Elpers and Coyle (2021) examining the relationship between social cognition and the intelligence quotient (IQ) in adolescents and young adults with and without autism. 193 participants (ASD = 96) from the NIH funded study on sex differences in autism were included in the sample. To measure social cognition, participants completed the Reading the Mind in the Eyes Test (RMET), a 36-item assessment measuring Theory of Mind or the individual's ability to recognize that others may have different mental states. Participants also completed the differential ability scale (DAS-2) as a measure of verbal IQ. We expect positive correlations for RMET scores and verbal score, in that as RMET scores increase, verbal IQ scores will also increase for adolescents and young adults with and without ASD. We will also explore how age impacts the scores, as we expect older children and young adults to have more verbal skills, hence performing better on the RMET measure. The results of this study will contribute to our understanding of the relationship between social cognition and intelligence from adolescents and young adults to the existing data that has been previously gathered. 

Sensory processing is a process in which the nervous system receives, processes, and integrates incoming sensory input from the environment to allow individuals to perceive and respond to their surroundings. Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social and behavioral skills. Many individuals with ASD experience hypersensitivity to sensory stimuli, thus individuals with ASD may experience more difficulty when navigating the world around us. These sensory challenges may result in increased anxiety symptoms. The purpose of this study was to explore the relationship between sensory processing and anxiety in autistic and typically developing (TD) adults. 256 participants (ASD = 149) ages 18-35 from a NIH funded study on sex differences in autism were included. Participants completed two self-report questionnaires: “Sensory Processing 3-Dimensions Scale” (SP3D) measuring sensory processing difficulties in auditory, visual, and tactile domains, and the “Screen for Adult Anxiety Related Disorders'' (SCAARED), measuring the intensity or frequency of anxiety symptoms and assessing four factors of anxiety (panic disorder, generalized anxiety disorder, separation anxiety disorder, and social phobis disorder). Correlations will be used to compare SP3D scores and SCAARED scores. Given the hypersensitivity to sensory stimuli in ASD, we hypothesize the effects of anxiety symptoms will be increased in the ASD group who experience more domains of hypersensitivity. The results of this study will contribute to a greater understanding of the effect sensory sensitivity has on anxiety in adults with ASD.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social communication and interaction, and restricted or repetitive patterns of behavior or interests. ASD is associated with features beyond its core characteristics, including alexithymia and anxiety. Alexithymia is characterized by difficulty recognizing and describing one’s own emotions, it influences physical and mental health, and it is associated with symptoms of anxiety. Despite current research demonstrating the correlation between alexithymia and anxiety in both ASD and the general population, there remains a significant research gap in how alexithymia and autism traits individually and collectively influence anxiety levels among the participants. This study has two aims: 1) To explore the relationship between alexithymia and anxiety in participants with ASD and TD. 2) To analyze the role of alexithymia as a mediator of the relationship between autism traits and anxiety in adolescents and young adults. This sample includes 149 participants (93 ASD) ages 15-34, from the NIH funded study on sex differences in autism. Measures included alexithymia via the 20-Item Toronto Alexithymia Scale (TAS-20), anxiety via the Screen for Adult Anxiety Related Disorders (SCAARED), and autism traits via the Social Responsiveness Scale (SRS-2). We will first conduct regression analyses to examine the relationships between alexithymia, anxiety, and autism traits. Then, we will employ Preacher and Hayes’ INDIRECT Method to investigate the mediating role of alexithymia in the relationship between autism traits and anxiety. We expect to see a significant relationship between alexithymia and anxiety in both groups and the relationship between alexithymia and anxiety in the ASD group to be significantly different than TD group. Understanding the relationship between anxiety and alexithymia could aid in the development or improvement of interventions for anxiety in people with ASD.

Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects social and behavioral development. Although autism is most associated with social difficulties, it is also correlated with issues such as sleep disturbances. Previous literature suggests that 50-80% of autistic individuals experience sleep difficulties. One common feature of autism is differences in sensory processing compared to typically developing (TD) individuals. These differences may result in behaviors that are detrimental to sleep habits. This project aims to identify the relationship between sensory processing and sleep quality in autistic and TD adults and to identify a type of sensory concern that correlates to increased sleep disturbance. 150 participants (ASD = 94) ages 18-25 from the (National Institutes of Health) NIH funded multisite study on sex differences in autism were used in the analysis. Participants completed self-reports on sensory systems using the Sensory Profile, and on sleep quality using the Pittsburg Sleep Quality Index (PSQI). The Sensory Profile scores participants among 4 quadrants: low registration, sensation seeking, sensory sensitivity, and sensation avoiding. The scores reflect the participants sensory systems compared to their age range separated into five groups. The PSQI takes participant responses and assigns a score with “0” being no difficulty and “3” being severe difficulty across 7 components of sleep. Component scores are then summed for a global score. A t-test will be performed to compare the mean global PSQI score for the five groups across each quadrant on the Sensory Profile and for autistic and non-autistic populations. We expect to see higher mean global PSQI scores for those with autism and for those with higher Sensory profile scores within the ASD population. Increased differences in sensory processing in autistic individuals is important to investigate because studies have shown that filtering out sensory input is key to falling and remaining asleep which leads to improved quality of life.

Children diagnosed with Autism Spectrum Disorder (ASD), often experience co-occurring language impairments, including grammatical and lexical difficulties. Word segmentation, or the ability to identify word boundaries in continuous speech, is done through statistical learning and identification of speech cues. Recent studies in typically developing infants have shown a linear relationship between the ability to recognize words from continuous speech and the size of an individual's lexicon. The neural activity of the cerebral cortex, specifically the delta frequency band (1-4 Hz), contains the time scale of words and phrases. The delta band was found to track speech rhythm, along with semantic dissimilarity between successive words. Extracting acoustic features from sound signals and their linguistic representations (syllables, words, and phrases) is essential for speech comprehension. This study aims to look at the relationship between delta power recorded via scalp electroencephalogram (EEG) and communication skills in children with and without ASD. 193 participants (ASD = 96) from the NIH study on sex differences in autism were included in the sample. EEG recordings were collected while participants listened to phonemes that were statistically presented to result in 4 learned nonsense words. Parents completed a semi-structured interview on their child’s communication skills. EEG delta power was calculated over frontal, central and posterior regions of interest (ROIs). We expect children with ASD (compared to typically developing children) to have decreased delta power during nonsense word perception and lower delta power will be related to lower communication ability. This study will provide insight into the relation between neural perception of language and verbal communication in children with ASD.

My research explores why conflict breaks out in some contexts but not others. Specifically, I question whether bilateral security agreements and democracy reduce the likelihood of conflict between states in volatile regions. First, I hypothesize that security measures reduce the likelihood of armed conflict because they prevent or reduce dangerous misperceptions, fear, and insecurity, which international relations and political psychology literature identify as catalysts of conflict. Second, I hypothesize that as the democratic health of states improve, the likelihood that they will engage in conflict decreases. This is because democracies share values and norms, institutional and public opinion restraints, and other entanglements that render conflict too costly to be in either’s interest. To test these hypotheses, I will compare bilateral relations between each state dyad in five historically volatile regions: the Middle East, Eastern Europe, the Balkans, Central Asia, and South Asia between 1990 and 2010. For each dyad, I will measure the number and severity of conflicts, the number and type of bilateral security agreements, and the democratic quality of each country. I will test my hypotheses by running statistical analyses including a multivariate regression, controlling for other confounding variables that may influence the likelihood of conflict. From my quantitative analysis, I expect to find that security agreements and democracy decrease the likelihood of conflict. This research is important because we have observed an increased prioritization of forming security agreements in western diplomatic relations during the 20th century as well as foreign policy guided by an understanding that democratic states are less likely to fight each other, especially during the Bush administration. If the US and West prioritize forming security agreements and promoting the spread of democracy, we should understand whether these truly increase security.

In this study, I investigated distinctive electroencephalogram (EEG) patterns associated with processing social and nonsocial information in both typically developing individuals and those with Autism Spectrum Disorder (ASD). A total of 139 youth and young adults aged 10-24 years participated, including 63 individuals with ASD (23 females, 40 males, mean age = 17.57) and 76 typically developing youth (35 females, 41 males, mean age = 17.47). Data collection occurred across four sites as part of the multisite ACE Network GENDAAR Wave 2 study (R01 MH10028, Pelphrey). EEG data were collected using a 128-channel Geodesic sensor net, concurrently capturing live social and nonsocial attention responses. During the social condition, participants viewed videos featuring social stimuli (vignettes of women telling or singing nursery rhymes), while during the nonsocial condition, they viewed videos of objects (dynamic toys). Additionally, all participants underwent assessment using the Vineland Adaptive Behavior Scales-2 (VABS-2). I calculated power spectral density (PSD) values for 8 channels based on the 10-20 system across various frequency bands, and performed analysis using this data. The results indicated a main effect of condition (social vs. nonsocial) at several frequency bands and electrodes. Furthermore, a main effect of the group revealed higher alpha power in typically developing individuals compared to those with ASD. Notably, no significant relationships were observed between Vineland Adaptive Behavior Scales-2 (VABS-2) subscores and neural responses. This study highlights a difference in neural activity during attention to social vs. nonsocial information in both groups of participants and underscores the importance of understanding these neural correlates in individuals with ASD.

While Tropical Storm Harold struck off the coast of Corpus Cristi, the Texas State Legislature ratified a bill effectively making their state a fossil fuel sanctuary. Scientists agree that the Deep South is one of the most vulnerable regions in the United States to climate change and the rise in climate-caused disasters. Why is it that despite being the most vulnerable region, the Deep South continues to offer pushback against climate mitigation? This research project attempts to understand the psychological components that induce preferences to policy. In the past, researchers have primarily focused on the economic lobbying power of Big Oil and Coal industries within jurisdictions. Utilizing rational choice theory, this project evaluates this puzzle from the perspective of voter preferences in response to economic reliance on the fossil fuel industry. The fossil fuel industry proves vitally important to local communities, providing jobs and resources. Using multivariate regression, I examine the effect of employment in the fossil fuel industry and reliance on nonrenewable energy within 467 different counties across the Deep South and other states. I weigh these results against possible other factors including partisanship, age, race, and vulnerability to observe if economic reliance accurately characterizes the misalignment observed within the Deep South. Based on previous literature and rational choice theory, I hypothesize that in counties economically dependent on the fossil fuel industry there will be less support for climate change legislation. Policy implications of this research include securing resources for communities threatened by a transition to renewable energy sources.

The human genome is associated with numerous variations, some of which can be pathogenic. Any variations larger than 50 base pairs (bp) are considered structural variants (SVs), and SVs impacting copy number of the genome are termed copy number variants (CNVs). By studying CNVs, we can understand the underlying mechanisms of damage and repair within DNA, which can help work towards prevention and cure in other fields, such as cancer genomics. My project investigates a CNV on chromosome 2 of a pediatric patient, who presents with tetralogy of Fallot, global development delay, and multiple other congenital anomalies. Using array comparative genomics hybridization (aCGH), we identified a 3.2 megabase (Mb) complex genomic rearrangement (CGR) spanning the 2q31 region of the proband’s chromosome 2. Detailed analysis of the short-read whole genome sequencing (WGS) allowed us to locate the exact coordinates of each junction, or the beginning and end points of each extra copy. PacBio long-read genome sequencing and optical genome mapping detected the same junctions and facilitated confirmation of the overall structure. The CGR can be characterized as a duplication-triplication-duplication-triplication-duplication (DUP-TRP-DUP-TRP-DUP), meaning this segment of the genome contains a segment of alternating 1 and 2 extra copies of this region. The CGR is de novo, or not inherited from the proband’s parents. Due to the nature of this variant, it is likely to be impacting the phenotype of our patient. To establish a genotype-phenotype correlation, I did a literature review of patients with overlapping CGRs, comparing their phenotypes to our proband, as well as reviewing any known disease-associated genes in the region using the online catalog of human genes and genetic disorders (OMIM). Patient and disease comparison revealed the extreme rarity of our patient’s CGR, leading us to believe the phenotype of the proband results from impact of multiple genes in the affected region.

This research investigates the impact of ethnic diversity on corporate boards in relation to the frequency of security class actions faced by firms. Security class action lawsuits hold significant concern for today's corporations and society at large due to their implications for accountability, investor protection, and the reinforcement of ethical standards. In this study, our team focuses on ethnic diversity as a vital contributor to enhanced monitoring and ethical practices by integrating varied cultural insights and ethical standards, thereby strengthening corporate governance and ethical oversight. We hypothesize that firms with greater ethnic diversity among their board members are less likely to encounter security class action lawsuits. To test this hypothesis, we sourced data on security class action lawsuits from the Stanford Securities Class Action Clearinghouse, and derived information regarding the ethnicity of board members from the Wharton Research Data Services Institutional Shareholders Services (WRDS ISS) database supplemented by various web sources. Employing a linear regression model to analyze the data, the empirical results substantiate the hypothesis, revealing that S&P1,500 firms with at least one director of minority ethnicity during the sample period of 2009 to 2015 are significantly less likely to face security class action lawsuits. This finding suggests that ethnic diversity on corporate boards is not only a marker of inclusivity but also serves as a protective measure against legal challenges. The study's implication is clear: promoting ethnic diversity within corporate boards is a strategic move for firms and shareholders, potentially reducing litigation risks and associated costs. This research contributes to the broader discourse on corporate governance, emphasizing the practical benefits of ethnic diversity in high-level decision-making bodies.

The Great Recession was one of the most devastating economic downturns experienced in the United States since the Great Depression. However, the rate at which states recovered from the crisis varied drastically across the country, with some states recovering in less than a year while others languished for over five years. While many previous scholars have explored the structural, demographic, fiscal, and other conditions of states leading into the Great Recession and their impact on recovery, this paper explores the impact of a variety of state fiscal policy decisions while actively in the recession and their impact on economic recovery. To conduct this study, I examine the relationship between the change in several state fiscal policy indicators – including tax, expenditure, and budget indicators – from the start of the recession to the trough, and the rate of recovery measured in the number of months for the state to recover fully from the recession. I conduct a multivariate regression analysis to determine the relationship between my selected indicators and the rate of recovery while controlling for various factors that previous scholars have identified as having a potential impact on recovery, including state economic composition, relative federal stimulus, and more. I expect to find a positive relationship between general increases in tax revenue, increases in expenditures on welfare, and a more equal ratio of revenue to spending and a faster recovery (a lower number of months to recovery). The findings of this study will contribute to informing improved strategies for state policymakers as they navigate fiscal policy decisions during future recessions.

In mammals, circadian rhythms are regulated by a hierarchy of oscillators governed by a central circadian pacemaker in the suprachiasmatic nucleus (SCN), which is principally entrained by the light-dark (LD) cycle. Recent experiments in our lab have revealed that cyclic 24-h fearful stimuli can act as a potent nonphotic zeitgeber, entraining circadian rhythms of behavior in mice and rats. This discovery utilized a naturalistic rodent cage with a safe nesting area separated from a foraging area where feeding and drinking occur. While foraging behaviors naturally occur at night, when the foraging area is rendered dangerous by nocturnal aversive stimuli (footshocks), animals entrain behaviors to the shock schedule by shifting activity to the daytime. Under conditions of fear-entrainment, SCN clock gene expression remains loyal to the LD cycle and the SCN is necessary but not sufficient for sustaining diurnal activity. Therefore, we propose the existence of extra-SCN fear-entrained oscillators capable of overriding SCN output and influencing behavioral timing. Here, we subjected 16 mice to either diurnal shocks (DS; control) or nocturnal shocks (NS) under a 12:12 LD cycle. Following confirmation of fear-entrainment, animals were released into constant conditions and sacrificed between 24-36h after the last presentation of footshocks, either CT 1 or CT13. Brains were dissected, sliced, prepared for immunohistochemistry processing, and c-Fos protein quantification is currently underway in the SCN, basolateral amygdala, paraventricular nucleus of the thalamus, and dentate gyrus. We hypothesize that c-Fos expression within the SCN will align with the LD cycle, while centers involved in fear processing and memory will exhibit altered levels of c-Fos expression in response to time-specific fear. Results from this study may be useful for identifying putative brain regions containing fear-entrainable oscillator(s).

Collision avoidance studies find important applications for motion planning of mobile robots for deployment in outer space, nuclear waste management, mobiles used for process automation, etc. Here, we integrate mobile robot simulations with mathematical modeling using Python to understand collision avoidance for mobile robotics. We used the open-source Pioneer code on the Webots platform for simulations of mobile robots which employ Kinect-based optical and IR sensors and cameras for live-tracking of objects in the environment variable and have motion controller Matlab software that provides the kinematic variables like position, velocity, and acceleration of various objects in real-time. We wrote a Python code to digitize the image matrices obtained from simulations and identified the pixels having objects that the mobile robot must avoid for collision avoidance. We calculated the instantaneous distances between the mobile robot and various objects to interpret and analyze the simulated trajectories. We used jump collision avoidance models to estimate the mobile robot trajectories in the vicinity of objects. The calculated object avoidance jump trajectory of the robot was smoothened using Gaussian data convolution methods to obtain smooth trajectories. The simulations provide attractive visualization and are useful for machine learning and testing algorithms for collision avoidance and motion planning.

Falls are a leading cause of injury, disability, and death in older adults. One common but understudied risk factor for falls includes knee instability (KI), defined as the loss of postural support across the knee during weight bearing, which is more common in older adults with knee osteoarthritis (KOA). The goals of our project are to (1) evaluate the feasibility of using a new thigh worn accelerometer device called Move4 to measure movement-evoked pain and (2) explore the association between movement-evoked pain and KI in older adults with KOA. Move4 uses sensing technology to trigger a brief survey (called an Ecological Momentary Assessment [EMA]) on a participant’s study phone asking them to rate their pain after a bout of physical activity (e.g., 15 minutes of walking) or inactivity (e.g., 30 minutes of sitting). EMAs are also collected at random times in the day (morning, early and late afternoon, and evening) over a 1-week period to assess pain level, mood, and incidence of KI. Feasibility is established if >80% of participants wear the Move4 device for 6-7 days and complete >70% of the triggered EMAs over a 1-week period. Multilevel statistical modeling is used to examine movement-evoked pain and KI occurrence and examine physical activity patterns before and after KI. The findings of this study may establish a novel method to measure movement-evoked pain in daily life that can overcome challenges of recall bias and improve estimates of KI incidence through real-time data capture. This research has the potential to improve our understanding of a prevalent symptom that increases risk of falling and limits physical functioning in a rapidly growing population of older adults with KOA.

This study explores how experiences with mental health issues affect stigma and outlook on life. An experience with mental health issues can have an enormous impact on a person's functioning and wellbeing. Stigma and bias against mental health can hinder help-seeking behaviors and increase distrust in professional treatment. One's attitude toward life, such as how optimistic a person is, can significantly mediate a mental health experience. I explored the following questions: (1) How do experiences with mental health issues relate to a person's stigma against mental health topics? (2) How do experiences with mental health issues relate to a person's outlook on life? (3) Is there a difference in the significance in the different forms of or lack of an experience relate to stigma and outlook? Surveys were collected digitally through an undergraduate campus, poster on the same campus, and multiple social media campaigns. 242 participants (M_AGE = 27.4, SD_AGE = 16.6) completed the Satisfaction with Life Scale, Revised Life Orientation Test, Stigma Scale for Receiving Psychological Help, Self-Stigma of Seeking Help Scale - Revised, and investigator written assessment of mental health experiences. All measures were reliable. There were significant correlations between experience, stigma, and outlook. Multiple linear regression analysis revealed experience significantly predicted the variance in stigma (R² = .03, R²_ADJUSTED = .02, F (2, 239) = 3.67, p < .05) and the variance in outlook (R² = .11, R²_ADJUSTED = .098, F (2, 239) = 14.04, p < .001). Experience of someone close with mental health issues significantly predicted outlook (Beta = .14, p = .05). These findings suggest that sharing experience and promoting optimism would improve wellbeing and foster positive attitudes. 

 COVID-19 is an infectious viral disease that is caused by the SARS-CoV-2 virus entering host cells through surface spike proteins that bind to surface ACE-2 receptors. Some anti-SARS-CoV-2 antibodies allow SARS-CoV-2 to also have antibody-mediated entry (AME) into immune cells, independent of the ACE-2 receptor. Instead, they often enter via Fcγ receptors. This phenomenon has been correlated with cytokine release syndrome, which occurs when the immune system has a highly inflammatory response to infection and is implicated in severe COVD-19 cases. It has also been shown that other antibodies have demonstrated inhibition of SARS-CoV-2 entry. During binding and viral fusion, all three receptor binding domains (RBD) of the spike protein fold to an upward conformation, which is necessary for binding. Inhibitory anti-SARS-CoV-2 antibodies can impede this process through competitive binding as well as mechanisms such as premature cleavage of the RBD or stabilizing a three-down conformation. We hypothesize that inhibitory antibodies can stop AME from occurring to varying degrees of effectiveness based on inhibitory mechanisms and avidity to the spike protein. To understand the dynamic between AME and inhibitory antibodies, we tested the infection levels of monocytes by SARS-CoV-2 pseudo-virus in the presence of antibodies shown to induce AME combined with varying concentrations of inhibitory anti-SARS-CoV-2 antibodies that have different mechanisms of affecting the spike RBD conformation. ELISA-based assays were also run to quantify antibody avidity to the spike protein. Analysis suggests that high concentrations of multiple neutralizing antibodies inhibit AME and that conformationally inhibiting antibodies are more effective at inhibiting AME than strongly activating ones. Studies of this type can aid in continued development of safe vaccines and therapeutics, as well as help understand how antibodies affect SARS-CoV-2 spike conformational regulation and therefore viral entry.

Preterm birth is one of the leading causes of infant morbidity and mortality worldwide, with a strong association between the degree of prematurity and the likelihood of death or neurodevelopmental impairment. Intracranial hemorrhage (ICH) is one of the most common neurological injuries for extremely preterm infants (born less than 28 weeks’ gestation). During the last trimester of pregnancy, neurons and glial cells develop in the germinal matrix requiring vast amounts of vascular support. In preterm infants, disturbances to blood and hydrostatic pressure are thought to rupture the immature vessels of the germinal matrix, leading to the bleeding in and around the ventricles. ICH is rated on a scale of I to IV, with severe ICH being grade III-IV. Mortality associated with ICH ranges from 30-60 percent, increasing with ICH severity, and survivors have an increased risk of cerebral palsy, seizures, and neurodevelopmental delay. From 2018-2020 the University of Washington (UW) neonatal intensive care unit (NICU) implemented an ICH Prevention Bundle, which focused on minimizing blood pressure disturbances during the first 72 hours after birth in infants born extremely premature, and appeared to result in a decrease in severe ICH. This study will evaluate the incidence rate of ICH at the UW NICU over a ten-year period. In a retrospective analysis of the UW NICU’s admissions, we will investigate extremely preterm infants born during the time periods of December 2013-September 2016 versus January 2017-December 2023 and record the incidence of ICH. Our primary outcomes will be ICH, by grades I-IV, as well as ICH complications such as posthemorrhagic ventricular dilatation with and without need for intervention, and death before discharge. We hypothesize that with improved prevention methods, such as the implementation of the ICH Prevention Bundle, we will see an associated long-term decrease in the incidence rate of ICH.

Down syndrome (DS, trisomy 21) is the most common chromosomal condition, affecting 1 in 700 live births. In addition to neurodevelopmental issues, people with DS also have an increased susceptibility to infections such as influenza and COVID. Altered immune function is one likely driver. Additionally, non-immune factors may also contribute. For example, upregulation of TMPRSS2, an enzyme that promotes cellular entry of SARS-COV2 encoded on chromosome 21, may predispose people with DS to severe SARS-CoV2 infection. This project builds on recent data from the Khor lab that suggests a link between DS and susceptibility to malarial infection. P. vivax is a parasite that causes malaria and is endemic across wide regions, from South America to South Asia. P. vivax enters cells through a protein called Duffy which is a chemokine receptor on the surface of red blood cells (RBCs). Recent profiling of whole blood from patients with DS showed dysregulation of many genes. Geneset enrichment analyses identified heme metabolism as the second most affected pathway. Within these heme metabolism genes, ACKR1, the gene encoding Duffy, was particularly and disproportionately upregulated. This suggests that people with DS may express higher levels of the Duffy protein on their RBCs, which in turn may predispose to P. vivax infection. This project seeks to better understand and validate how Duffy expression is dysregulated in people with DS. The goal of the project is to quantify the level of Duffy present in the RBC’s of patients with and without DS. If validated, the next step will be to test the susceptibility of these cells to malaria. This may point to a need for altered clinical management of malaria in people with DS and inform further studies looking at the mechanistic differences in RBC biology in people with DS.

Most eukaryotes use histones to package the genome. However, many animals package their sperm genomes using specialized DNA-binding proteins called protamines, which package DNA in sperm more tightly to fit inside the sperm head. Based on the transcriptional silencing role of protamines, we hypothesize that protamines can suppress meiotic drivers, which kill other sperm to bias their own transmission. Previously, we found that one protamine gene, Mst77F, is required to suppress meiotic drivers on the Y-chromosome in Drosophila melanogaster. Since drive is generally deleterious for the transmission of autosomal alleles (due to lower male fertility for example) theory predicts that multiple suppressors of drive will arise in populations; Mst77F may represent just one such suppressor. We hypothesized that multiple natural variants in distinct genetic loci interact with and impact meiotic drive in Drosophila melanogaster. To identify these natural variants, I crossed wildtype flies to knock out flies and generate hemizygous Mst77F flies carrying genetic backgrounds from four different populations. I measured the fertility and drive strength by crossing a single hemizygous male from each cross to five wild type females. In all cases, I found that the sex ratio was skewed to favor male offspring, indicating they all carry X-linked targets. However, I did not identify any dominant genetic variation associated with the drive strength, indicating Mst77F might be the major suppressor of this drive. I am conducting reciprocal crosses to determine whether Y chromosomes from different populations carry the same strength of drive. In the future, I will extend my analyses to other genetic backgrounds. My study contributes to a better understanding of the pervasive effects of meiotic drive in natural populations and unexpected functions of protamines.

The poster highlights our study of shared pantry operators in Washington State. Shared pantries are generally small, unattended, open-access food-sharing areas that operate on a "take what you need, leave what you can" concept, supplied by donations from members of the local community. Professor Emily Hovis and I developed and deployed an operator survey to examine the differences between pantry operational structures. This research was prompted by a pattern we noticed during previous fieldwork: many pantries located at private residences were no longer active. I was involved in developing the survey, analyzing the data, and creating the poster. Over 300 current or former share pantry operators were contacted to participate in an online survey focused on operator demographics and operations. We received 62 survey responses in Autumn 2023. The majority of survey respondents (95.2%) identified their pantry is located outdoors, open 24/7, and accepts community drop-off food donations. More than half of the pantries are operated by individuals. Most of the organizations or groups operating the pantries were churches, schools, university groups, neighbors, and advocacy services. The majority (87%) of the pantries do not have a fridge/freezer section. More than half of the operators visit the pantry site more than four times a week. Only half of the respondents indicated that they provided guidelines on appropriate/safe donations. This study not only emphasizes the critical role of shared pantries in community solidarity but also raises an important future research question: How could the development and implementation of standardized guidelines and support systems impact the sustainability and effectiveness of shared pantries, particularly in enhancing community participation, donation quality, and pantry longevity?

Tissues like the meniscus, a wedge-shaped pad of connective tissue found in the knee, are fibrous and have complex architecture that regenerates poorly and undergoes active mechanical stimulation which modifies cell signaling and tissue health. In vitro models are beneficial for characterizing these interactions as they create a controlled environment where single variables can be altered. We previously used the J1 Mechanoculture bioreactor to apply strain on a fibrous polymer scaffold laden with primary meniscal cells and observed nonsignificant variances between testing groups with mock injury vs. no injury. Applied strain was modeled after physiological strain levels, ~10%. Based on the minimal changes in cell behavior observed in mock injury samples, it is likely that the mock injuries in conjunction with the applied strain did not induce comparable plastic deformation to that experienced post injury within the native meniscus. We hypothesize that increasing strain and applied force to achieve plastic deformation within the electrospun samples will create a fibrotic and apoptotic response like that in vivo. Ongoing work is analyzing how the bioreactor will interact with unaligned electrospun polymer samples with no cells present. This will demonstrate the optimal parameters to instigate a significant material response. By inducing significant changes to scaffold material properties and underlying structure, it is more likely cells with demonstrate fibrotic and apoptotic responses in vitro mimicking immediate cell reactions to meniscal injuries in vivo. This response will be assessed by assaying for fibrosis through αSMA activation and apoptosis by caspase-3 activation. On the conclusion of this study, we expect that greater applied stress and associated strain will cause more plastic deformation within the polymer scaffold. This can be applied to an in vitro meniscus injury model to better understand the response of primary meniscal cells to stress in an environment with disrupted mechanics.

Seattle is known to be infested with invasive rodents such as the Norway rat or the roof rat; both of which are considered public health nuisances, causing damage to the built environment, carrying zoonotic diseases, and causing overall mental unrest as a communal species. This project collected community-level data using two urban rodent survey (URS) methodologies: The Centers for Disease Control (CDC) URS methodology, which focuses on identifying causative conditions for rodents, and a newer method, Indexing, which focuses on active rodent surveillance. We surveyed census tracts spanning the University of Washington Seattle campus, UDistrict, and Ravenna neighborhoods using both URS methodologies. We then assessed the effectiveness and efficiency of both methods in determining the severity of rodent infestation within these communities. The data collected was used to inform a URS classroom model for ENVH 442, Zoonotic Diseases and their Control, offered by the Department of Environmental and Occupational Health and Safety at the University of Washington Seattle. In addition, this project was shared with the Public Health Seattle & King County Rodent Control Program, to help inform their work on active rodent surveillance in the city of Seattle.