In the age of the internet, literature is consumed in unprecedented ways. Modern social movements often call upon those of the past through key quotes and references to influential literary works. Quotes can go viral, seen outside of their context by thousands of people and become associated with these movements or rediscovered by new communities. For instance, key figures in post-WWII literature such as author and civil rights activist James Baldwin have had their words re-immortalized within the context of contemporary movements such as Black Lives Matter. Baldwin’s era of literature was one of marked social change and evolution within the literary world that parallels our society today, making it significant to understand how quotes from this period can reappear and spread across social media. To analyze the reception of post-war literature on Twitter, we utilized a dataset of over 40 million tweets quoting or referencing James Baldwin, as well as similar datasets quoting four other influential authors of the time including David Foster Wallace and Kurt Vonnegut. We focused on the patterns of text reuse (i.e., the repetition of known quotes) in tweets from 2006-2023, examining key moments of reception and exploring the context of virality for key quotes. During this context-finding process, we also developed a novel method for conducting self-identified user demographic analysis. We implemented clustering algorithms on both tweets and user bios, supplemented the resulting clusters with manual merging processes, and experimented with various visualization strategies. Our results yielded clear quote usage patterns for certain demographic groups, demonstrating the efficacy of the novel demographic extraction method. These methods can be expanded for further demographic-focused social media research and help us understand how cultural movements evolve today.

Post-Traumatic Stress Disorder (PTSD) is one of the most common mental disorders in the world. People with PTSD often have difficulty managing time or have witnessed a traumatic event in the past. PTSD is also associated with memory issues which are characterized by intrusive memories that can cause re-experience aspect of the traumatic event. Through the use of computational models, we aim to investigate the differences in memory retention in spaced vs massed practice presentations. We hypothesize that mass practice will lead to less accuracy in recognition and less intrusive thoughts during retention. Through recruiting healthy adult participants with no history of PTSD or other stress-related psychiatric disorders we get a base data avoiding discrepancies. Participants view visual stimuli as images, either neutral or triggering which are presented in pseudo-order and are asked to rate them based on their valence ranging from neutral to extremely negative. The images are presented under two conditions: mass and space presentation. For spaced presentation, different versions of the triggering image category are presented in no particular order with neutral and filler images in between. For massed presentation, all versions of the triggering image category are presented one after the other with no neutral or filler images in between. 24 hours after the initial presentation of the images, participants are tested on memory retention in the form of image recognition. Participants are asked about the difficulty of recalling the image and how often they think about the image. Having collected data during AUT 24, we were able to understand there is a correlation present between memory retention in mass and spaced recognition in terms of traumatic and non-traumatic events. By collecting data through WIN 25, we will have greater accuracy in terms of significant data.

Chiral molecule sensing has important biochemical applications for detection of disease, as well as cognitive and neurodegenerative disorders. Circular dichroism (CD) has emerged as a powerful spectroscopic tool for probing post-synthetic ligand exchanges of chiral molecules onto originally achiral quantum confined CdS morphologies, manifesting in chirality corresponding to the electronic transitions of the nanocrystals. In this work, we first describe making water soluble quantum dots (QDs) and nanorods (NRs) via ligand exchange with glycine. After this exchange, aqueous chiral thiol solutions are then titrated into glycine capped achiral CdS, and the optical properties are monitored via UV-vis, photo-luminescence (PL), and CD spectroscopies. Preliminary results show we can controllably produce measurable chirality equal to or exceeding previous literature values whilst using orders of magnitude less L-cysteine than previously reported. Moving forward, we intend to correlate growth in CD with changes in PL across a myriad of cysteine derivatives. Additionally, we plan to examine the impact of NR aspect ratio on normalized maximum CD absorption (g-factor).   

Human liver microsomes, or HLMs, play a key role in drug metabolism because they contain important cytochrome P450 (CYP) enzymes that are critical in oxidation and hydrolysis processes. We hypothesized that the variability in CYP enzyme concentration and activity among individuals will contribute to differences in metabolic capacity. In this study, my goal was to characterize HLMs from a bank of individual donors with different genetic backgrounds. I assessed their drug-metabolizing capabilities, with an emphasis on CYP-mediated pathways. I used bicinchoninic acid assays (BCA) to quantify protein content, carbon monoxide heme spectra (P450 spectra) to determine CYP enzyme concentrations, and a cytochrome c reduction assay to measure P450 reductase activity. For conducting these experiments, we used HLM samples from five different individuals from the UW Human Liver Bank. From the first subset of samples, I found that the ratio of CYP protein to total protein content varied across individuals with different clinical presentations. The differences among individuals in our findings emphasize the importance of HLM characterization in preclinical drug trials to understand the need for the personalization of pharmacological treatments. The implementation of such characterization can have a tremendous effect on predictions of drug responses and optimization of drug dosages, ultimately improving drug efficacy and safety.

King County’s population growth over the past two decades has significantly shifted area demographics. The influx of a large volume of highly-paid residents has led to a housing shortage, driven up housing costs and area median income, and displaced long-time residents and businesses — a process known as gentrification. Residential gentrification often coincides with commercial gentrification, where local, minority-owned businesses are replaced by high-priced specialty stores or chains. Commercial gentrification impacts residents of the surrounding neighborhood and people countywide who rely on local businesses for socialization and community building. Despite its impacts, business displacement is understudied compared to the residential effects of gentrification. The 2024 Population Health Initative’s Applied Research Fellowship project sought to close this gap and examine the scope of commercial gentrification in King County with an analysis of business-level data from Data Axle, a data analytics firm, to quantify business openings and closures by size and industry from 1997 to 2023. This research examines which of King County’s communities and industries appear to be most impacted by recent commercial gentrification. To better understand spatial trends in businesses, we used King County’s 61 Health Reporting Areas (HRAs) and also focused on unincorporated King County as a whole. For our industry-level analysis, we identified three essential services: grocery stores, pharmacies, child care providers, and four categories of third places: retail, entertainment, eating and drinking, and services establishments. Our research showed the limitations to using this data to calculate King County’s top employers by business size. Moreover, despite significant population growth in King County since 1997, grocery store and child care provider numbers remained relatively stable, with the number of pharmacies increasing; despite 8 of 61 HRAs having two or fewer pharmacies. Third place services, eating and drinking, and entertainment establishments increased since 1997, while retail establishments decreased

Autism spectrum disorder (ASD) is a neurodevelopmental disorder marked by repetitive behavioral patterns and challenges with social interaction. Gastrointestinal symptoms are a common comorbidity of ASD, and individuals with the disorder tend to have a distinct gut microbial community composition and circulating metabolomes. Elevated levels of gut-derived metabolite 4-ethylphenolsulfate (4-EPS) are associated with ASD mouse models and children with ASD. Administration of 4-EPS to conventional mice induced atypical myelination and anxiety-like behaviors. 4-Ethylphenol (4-EP), its precursor, is produced by gut microbiota before host-mediated sulfation; however, its microbial biosynthetic pathway remains unknown. We propose a pathway involving stepwise conversion of plant-derived complex polysaccharides to 4-EP. My project aims to identify a gut microbial enzyme that completes the first step of this proposed pathway: a hydroxycinnamoyl esterase. After extensive literature review and biochemical study, candidate enzymes from resident gut microbes were identified and selected using bioinformatic tools. In vitro and in vivo experiments will be used to assess their activity towards model and dietary substrates. Remaining substrate and product concentrations will reveal species and strain specific enzymatic activity and substrate uptake. If the results are negative, this bioinformatics to experimental analysis pipeline will be repeated on new candidate enzymes. This work complements ongoing lab investigations to demonstrate the complete enzymatic pathway in a single species. Elucidating the microbial biosynthetic pathway of 4-EPS will contribute to detangling the gut’s role in ASD, regardless of if it is causal to the disorder or simply a biomarker. More importantly, studying the biochemistry and metabolism of gut microbiota supports the efforts to fill fundamental gaps in understanding the gut-brain axis. 

Cancer Cachexia is a condition characterized by muscle wasting, functional impairment and decreased quality of life that leads to 30% of cancer-related deaths. Cytokines, proteins secreted by both the body and tumors that drive inflammatory response, are potential therapeutic targets and biomarkers for tracking disease progression. However, their role in cancer cachexia and relationship with physical function, patient-reported quality of life, and body composition have not been fully characterized. We hypothesized that in cancer patients, inflammatory cytokines would be elevated in patients with weight loss compared to weight-stable patients and inflammatory cytokines would be negatively correlated with muscle function, patient-reported outcomes and body composition. Body composition was assessed by Dual-energy X-ray absorptiometry (DEXA) and X-ray computed tomography (CT). Muscle function was assessed by stair climb power, hand grip strength and one-repetition maximum (1RM) muscle strength of different muscle groups. I assessed 55 cytokine plasma levels with Mesoscale Discovery Assay kits. Preliminary analyses show that in patients with cancer, interleukin (IL)-6 is negatively correlated with CT skeletal muscle mass (r=-0.36, p<0.05, n=53), IL-8 is negatively correlated with body weight (r=-0.40, p<0.01, n=53), body mass index (r=-0.41, p<0.01, n=53), CT skeletal muscle mass and subcutaneous adipose tissue (r=-0.49, p<0.05, n=53). Tumor Necrosis Factor-Alpha was negatively correlated with hand grip strength (r=-0.30, p<0.05, n=53). IL-5 was positively correlated with Anderson Symptom Assessment Scale (ASAS) fatigue (r = 0.40, N = 47, p = 0.005) and ASAS total (r = 0.45, n = 47, p = 0.002). Certain cytokines are linked to worse muscle mass and function, while others correlate with better patient-reported outcomes, suggesting inflammation’s role in cachexia is complex. More research is needed to distinguish these differences for targeted therapies treating specific attributes of cachexia.

For biomass derived molecules to serve as precursors for biofuel and other related energy sources, more stable and efficient catalysts are needed. Drawing inspiration from enzymes, our group has recently shown that a bifunctional acid–base metal–organic framework (MOF) with co-localized acid and base sites outperforms a MOF with randomly dispersed acid and base sites as a catalyst for the aldol condensation of biomass-derived carbonyls. These active acid–base sites are composed of a primary amine and carboxylic acid. However, to further improve catalytic activity a templated framework with secondary amine and carboxylic acid active sites can be developed. Relative to primary amines, secondary amines should favor the formation of the key enamine intermediate and increase catalytic rates. Framework synthesis and characterization show success of incorporation of the secondary amine, and preliminary catalysis results indicate how successful this secondary amine has been. Overall, this work expands on the previous introduction of metal-organic framework catalysts as an alternative to common industrial catalysts in the biomass upcycling process by exploring the utility of a new templated secondary amine acid–base MOF. 

Neuroethics explores the ethical paradigms surrounding neuroscience as it relates to new technologies, research and improved understanding of the brain and nervous system. A study within the Department of Neurosurgery includes human participants who have experienced a stroke. Participants get brain surgery to have intracranial electrodes implanted, have time for surgical recovery, then participate in follow up study sessions to gather neural and other data as they engage in rehabilitation therapy while being recorded and stimulated via the electrodes. From a neuroethics view, there is a limited understanding of why eligible people would choose to opt in or out of participating in this or similar studies. The neuroethics research group has done prior work to explore motivations for people who choose to participate in research and understand their experiences with implantable neural device research. However, few studies explore motivations surrounding a person’s decision to decline an invitation to participate in a research trial for which they are eligible. This project presents a literature review of potential  motivating factors in prospective participants’ decision to decline or participate in research. We will present how this literature review is used to construct a survey instrument to be administered to study decliners and a data analysis framework to interpret the survey results that we will gather. The results will have broad implications for understanding how people living with neurological conditions think about the potential risks and benefits of neurotechnologies that directly modify brain activity.

Microbial odors are essential for attracting mosquitoes to their hosts, but their role in attraction to other nutrient sources remains unknown. Sugar sources provide nutrients that lengthen the lifespan of both male and female mosquitoes and increase the vectorial capacity in host-seeking female mosquitoes. Microbial odors have been shown to act as proxy signals for the availability and composition of certain nutrients, such as amino acids and mineral ions, found in nectar and fruit sap. As microbes are abundant in flowers and fruits, we hypothesize that Microbial Volatile Organic Compounds (mVOCs) from these nutrient sources play an important role in the feeding behavior of mosquitos. To test this, we analyzed the microbial community of a known attractive fruit, Mangifera indica ‘Keitt.’ Microbial species were identified from our environmental samples through amplicon sequencing of the 16S and 26S regions. Isolates of the most abundant and relevant species were cultured for mVOC collection and chemical analysis via Gas Chromatography and Mass Spectroscopy (GC-MS). Behavioral assays were then performed with Aedes aegypti mosquitoes to observe the effect of microbial odors on the attractiveness of nutrient sources. Through the identification of behaviorally-relevant microbial compounds, we can gain a stronger understanding of the ecological dynamics of mosquito chemoreception and microbial community signaling, which can help inform future mosquito-control measures.

Orientation Patch Count (OPC) is a method of research used by biologists and paleontologists to analyze the complexity of an animal’s feeding surface while inferring their diets; diet and tooth complexity have evolved in concert with one another, which is why this method has been used on reptilian and mammalian (denticular) species. However, it has not been extensively tested on edentulous (toothless) clades. Therefore, my research examines the OPC of an edentulous species - specifically the endangered Madagascar big-headed turtle (Erymnochelys madagascariensis) using  three CT-scanned specimens. Three primary programs were used in order to analyze the quantitative morphometricsof the species: Slicer for processing and editing CT scans from the University of Washington’s Friday Harbor Lab, MeshLab for editing 3D models, and RStudio for data analysis. This research contributes to a broader study on turtle species led by paleontologist Brenlee Shipps, who will apply these findings to extinct beaked clades, specifically dicynodonts.

Increased mitochondrial oxidative stress causes fatigue and metabolic dysfunction in muscle tissue. It is unclear whether the oxidative stress is due to elevated production or impaired consumption of reactive oxygen species (ROS). The purpose of this study is to test whether the capacity of the antioxidant defense system is impaired or the mitochondrial ROS production rate is elevated in response to chronic changes in mitochondrial oxidative stress. To experimentally manipulate mitochondrial oxidative stress, we use an inducible mouse model to knockdown superoxide dismutase 2 (SOD2) in skeletal muscle and heart to increase oxidative stress, and exercise training to decrease oxidative stress. Knockdowns (KD) or littermate controls (CON) performed a six-week voluntary wheel running (EX) or sedentary control intervention (SED). Following completion of the intervention, I isolated heart and skeletal muscle mitochondria using differential centrifugation. I measured mitochondrial hydrogen peroxide (H₂O₂) production rate and tested the antioxidant capacity by treating isolated mitochondria with Auranofin (AFN) or 1-chloro-2,4-dintrobenzene (CDNB), which inhibit the thioredoxin and glutathione S-transferase components of the mitochondrial antioxidant defense system, respectively. KD heart and skeletal muscle had similar absolute H₂O₂ production rates compared to CON, but normalized to oxygen consumption the KD had significantly higher H₂O₂ production. Since absolute H₂O₂ production under vehicle conditions was not different, this suggests that the antioxidant capacity adapts to meet the changes in mitochondrial H₂O₂ production. We will collect data from the exercise-trained cohort next month. I expect to see an increase in H₂O₂ production rate and antioxidant capacity in both groups due to the increased mitochondrial biogenesis from exercise training. These results demonstrate that chronic increases in mitochondrial oxidative stress decrease mitochondrial H₂O₂ production capacity from skeletal muscle.

Soil-transmitted helminths impact over 1.5 billion people worldwide, disproportionately affecting school-aged children and pregnant women. Hosts issue a “weep and sweep” Type II immune response to expel helminth parasites from the intestines. Ruptured epithelial cells secrete the cytokine interleukin (IL)-33, which recruits innate lymphoid type 2 cells (ILCs)2 and CD4+ T-helper type 2 (Th2) cells. ILC2s release IL-13, encouraging stem cell differentiation into tuft and goblet cells to facilitate tissue repair and worm expulsion. Anemia is prevalent in helminth-rich environments because of elevated rates of malaria and malnutrition. Despite correlations between anemia and helminth infection, the impact of anemia on the Type II immune response in the small intestines remains unknown. Using N. brasiliensis (Nb), a bloodsucking hookworm-like parasite, I observed that one week post infection, iron-deficient (ID) mice were less capable of expelling worms compared to iron-sufficient (IS) mice. Through tuft cell immunofluorescence staining in the small intestine, I observed comparable hyperplasia in IS and ID-Nb infected mice but noticed differences in cell localization: ID-Nb infected mice had decreased numbers of tuft cells in the crypts compared to IS-Nb mice. This suggests that ID Nb-infected mice could be experiencing decreased migration/proliferation of tuft cells, compared to their IS-infected counterparts. Using EdU, a synthetic nucleotide tag that labels newly synthesized DNA, we can understand cellular proliferation patterns in IS vs. ID Nb mice. Co-staining for tuft cells permits us to merge events and track unique vs. universal trends in cell behavior, including cells’ migration patterns. I hypothesize that ID-Nb mice will have decreased cellular proliferation and migration compared to IS-Nb mice, ultimately impacting worm burden. These findings offer insights into the mechanism behind negative outcomes in anemic hosts, and could contribute to dietary intervention or therapies targeting the epithelium to alleviate burdens of helminth infection.

Circadian clocks have evolved as a powerful adaptation in response to daily environmental changes, allowing optimally timed sleep-wake cycles. The solar light-dark (LD) cycle is the dominant zeitgeber (time-giver) for entrainment (synchronization) of sleep and wake to external cues. While our lab has found that humans sleep less and later the days prior to the full moon phase where moonlight is available in the early night, moonlight was found to be an unreliable cue in determining lunar modulation of sleep for the light-polluted city population. Thus, my project investigates whether lunar cycling on activity patterns remains present without photic moonlight exposure using a diurnal non-human primate model: captive titi monkeys (Plecturocebus). The California National Primate Research Center collected titi monkey data (n=16) between 2022 to 2024 using AX3 from Axivity, a wearable data log that measures acceleration to monitor physical activity. I am using the statistical software R to derive activity onset and sleep onset/offset as phase markers of activity. Additionally, I am fitting different cosine models to a 30/15-day period, respectively lunar and semilunar, to analyze the periodic data for activity across the lunar month. We expect to see phase markers of activity oscillate with the monthly lunar phase, showing how the lunar cycle influences circadian rhythms in diurnal non-human primates, even in the absence of moonlight. This study may reveal a novel finding on lunar rhythms on activity patterns and could incur interest on how endogenous processes have adapted to the lunar cycle. Further molecular work could elucidate the neural mechanism behind lunar modulation of sleep and provide insights on improved treatment of dysregulated sleep.

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a fatty acid β-oxidation disease associated with severe hypoglycemia and sudden death. MCADD is caused by biallelic pathogenic variants in the ACADM gene, which codes for a dehydrogenase specific to carnitines C6 through C12. MCADD is included in newborn screening (NBS) and characterized by elevated medium-chain acylcarnitine fats, annotated as C6, C8, and C10:1. Diagnostic testing is performed in plasma. Acylcarnitine results in dried blood spots have been described to differentiate carriers from affected individuals to reduce false positive NBS. Disease sensitivity and specificity, particularly to differentiate carriers from true positive cases, has not been well described in plasma. We posit that MCADD diagnosis will be more accurate if additional ratios beyond the primary disease markers, C6, C8, and C10:1 acylcarnitines, are considered. This study is a retrospective data review of NBS cases that were positive for possible MCADD and diagnostic testing was performed at Seattle Children’s Hospital. Cases are sorted into four groups: MCADD with homozygous disease variants, compound heterozygous MCADD, carriers of MCADD, or true negative. In collaboration with the biostats core service, linear regression models and receiver operator characteristic curves will compare acylcarnitine species and ratios by group. Preliminary results demonstrate that the primary markers associated with MCADD, C10/C2, C10/C6, C8/C2, C8/C10, and C8/Free carnitine, clearly discriminate affected individuals from control cases in plasma. Analysis is in process to compare the different genotypes of affected MCADD from carriers. Uncovering the diagnostic accuracy of plasma acylcarnitine profiles may influence future testing plans and improve the cost-effectiveness of healthcare services. DNA testing remains costly and slow. Additional biomarkers that provide a conclusive diagnosis of MCADD without requiring genetic testing may lead to more equitable patient care.

Previous work has shown frequency-specific modulation of dorsal hippocampus (dHPC) neural activity during simple behavioral tasks, suggesting shifts in neural population activity during different task phases and animal behaviors. Relatively little is known about task-relevant orchestrated shifts in theta, beta, and gamma rhythms across multiple behavioral timescales during a complex task that requires repeatedly adapting behavioral strategies based on changing reward contingencies. To address this gap in knowledge, we used a spatial set-shifting task to determine whether dHPC plays a specific role in strategy switching. The task requires rats to use two spatial strategies on an elevated plus maze: 1) alternating between East and West reward locations or 2) always going to the same reward location (e.g., only East or only West). Across specific timescales (session based alignments, comparisons of trial types, within trial epochs), dHPC associates differentially with all three temporal categories. Across a session, we observe a decrease in theta and beta power before, and an increase in theta power after, the target strategy changes. Beta power is increased around the point at which rats learn the current rule. Comparing trial types, on trials before a rat has learned the correct strategy, beta power is increased. Within a single trial, after an incorrect (but not correct) choice, beta and gamma power increase while the rat returns to start a new trial. If gamma (but not beta) power was high during this return, the rat is more likely to make a correct choice on the next trial. On the other hand, low gamma power during the return is associated with incorrect trials. dHPC, therefore, appears to track task demands, with the strength of each rhythmic frequency differentially associating with specific behaviors across three distinct timescales.

Intimate partner violence (IPV) is a widespread problem across the U.S. that typically begins in adolescence which can cause severe struggles for the impacted individuals. IPV can be mitigated through some preventative factors, such as education and understanding of IPV. The purpose of this study is to evaluate rejection sensitivity (RS)-- the tendency to strongly react to rejection, including the dismissal or refusal of ideas, people, or offers-- as a mediator between comprehensive sexuality education (CSE) and IPV. I designed this study to use a cross-sectional online survey to measure levels of RS, themes of CSE from middle and high school education, and levels of IPV that individuals have experienced. It includes a representative sample based on Unites States census data of 340 participants who range from 18-25 years and have had a romantic relationship lasting at least two months. The data is analyzed through a mediation model, with RS as the mediator, as well as testing the direct effects of CSE on IPV using R Statistical Software. Analysis models the three pathways: path a-- CSE to RS, path b-- RS to IPV, path C-- direct effects of CSE on IPV (CSE to IPV). I anticipate that RS will act as a mediator between CSE and IPV such that higher levels of CSE will be associated with lower IPV levels through the mediation of RS. Additionally, I hypothesize there will be a direct effect of CSE on IPV. This study aims to improve the understanding of potential preventative factors of IPV as well as inform future interventions, such as CSE. Keywords: intimate partner violence, rejection sensitivity, comprehensive sexuality education

This project investigates the effects of Chile’s 2020-2021 pension withdrawals on household consumption across food, housing, transportation, healthcare, and education. I use existing socio-economic household survey data for my analysis. Chile’s Covid response allowed civilians to withdraw up to 30% of their pensions, impacting 11 million workers and reducing pension assets by an estimated 22% of GDP. This policy mirrors actions in 30 other countries globally, now facing similar challenges. This research aims to address the literature gap in consumption research, and provide a framework for policymakers in affected nations to understand how the pension funds were used in terms of consumption. My role encompasses everything, from design to analysis. First, I make sure the two groups being compared (Chilean households who withdrew funds and who did not) were on similar spending paths before the withdrawals happened, known as pre-trend analysis. I use statistical tools, such as t-tests, to check if those trends were similar—basically confirming that the two groups were spending similarly before the policy change. Second, I use a statistical model, called Difference-in-Differences (DiD), to isolate the specific effect of the withdrawals from other things that might have affected spending. Third, I look at how the pension withdrawals affected retirees and non-retirees as well as different income demographics, to see if the impact was the same or different for everyone, known as heterogeneity analysis. As this project is in-progress, I assume I would find a statistically significant, varied impact on household consumption. I anticipate increased spending on essential purchases since the Covid crisis led to many financial difficulties that affected households' spending. These findings can help inform younger generations around the world about their decisions regarding their own retirement planning decisions, as this global issue disrupted their retirement savings.

Acute Pancreatitis (AP) is a sudden inflammatory condition of the pancreas that can lead to significant mortality. Despite its rising prevalence and associated healthcare burden, treatment options remain limited to supportive care, with mortality rates in severe cases reaching 30%. Activin A is a key contributor to AP, interacting with the ACVR2A receptor to regulate various pathophysiological processes, including inflammation through immune cell recruitment. This study hypothesizes that activin A binds to ACVR2A to activate the ERK pathway, leading to increased NF-κB expression and elevated production of pro-inflammatory cytokines, including TNF-α and IL-1β. Experiments were designed using the 266-6 immortalized pancreatic acinar cell line and RAW 264.7 macrophages. These cells will be cultured for western blot analysis, ELISA assays, and transwell migration assays following activin A stimulation. Lower ERK phosphorylation and reduced NF-κB expression are expected when cells are treated with ACVR2A inhibitors in combination with activin A, compared to activin A treatment alone. ELISA assays are anticipated to confirm increased TNF-α and IL-1β production in 266-6 cells following activin A treatment. Macrophage migratory capacity is expected to increase when exposed to conditioned media from activin A-treated 266-6 cells. These findings will provide insights into the role of activin A in AP pathophysiology, potentially identifying new therapeutic targets for mitigating pancreatic inflammation and immune cell recruitment.

Advancements in antiretroviral therapy research are leading to longer life expectancy for people living with HIV (PLWH). Aging is a process that happens with every individual, involving changes in the physical and mental state. However, age-associated symptoms typically occur earlier in these individuals as the disease’s chronic inflammation accelerates the aging process, decrementing PLWH’s lifestyles. Some of the symptoms include fatigue, slower walking speeds, and balance problems. Previous studies prove that exercise is a non-pharmacological method used to improve physical function and wellbeing. Exercise performed at a higher intensity is known to enhance the overall health state of PLWH and generate positive effects on cardiovascular health. The aim of the study is to compare the effects of different exercise intensities on the symptom experience of PLWH. The HEALTH Study is an exercise trial conducted by the University of Washington and the University of Colorado for 120 PLWH aged 50 years or older who reports symptoms of aging and have a sedentary lifestyle. After enrollment, HEALTH Study participants are randomized to either a High-Intensity Interval Training or Continuous Moderate Exercise program lasting for 16 weeks. Participants exercise three times a week in a research center while supervised by trainers. During the study, participants complete many assessments to monitor their physical function and fatigue. The outcome for this study utilizes the HIV symptom index score, collected at baseline (week 0) and post-intervention (week 16). This index score is a 20-question survey that assesses the severity of HIV symptoms, categorized by presence and severity ratings. The end goal of the research is to explore how exercise training can change the symptoms occurring in people living and aging with HIV, creating a strategy for more individuals with HIV to live longer and healthier lifestyles.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that affects millions of people. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive stimulation typically used in psychiatric conditions such as depression and anxiety. rTMS works by using an electric current to generate a transient magnetic field, depolarizing neurons in a target region and creating lasting changes in brain connectivity via synaptic plasticity. Patients with AD show disruptions in the Default Mode Network (DMN), a network of brain regions typically active during rest and crucial for memory consolidation. We hypothesize that strengthening the DMN through rTMS targeted at the left Brodmann 8AV region, selected for being an easily accessible node of the DMN, will improve memory in AD patients. To test this hypothesis, we are conducting a single-blind, single-arm, randomized cross-over trial of rTMS on early-stage AD patients over a 12 week period with week 1 where we scan for the 8AV region via MRI, during week 3 and 8 being the placebo or treatment week. We measure our primary outcome of the participants’ speed of forgetting —a novel index of memory function—through an individualized, adaptive memory test. To eliminate potential confounding variables, we also measure depression and anxiety symptoms during the 1st, 8th and 12th week of the study. Additionally, functional MRI scans will be analyzed for potential structural or functional differences caused by treatment. Preliminary results from our initial participants have shown promising improvements, and we are hopeful that similar outcomes will be observed in the remaining participants. Successful results would provide a novel target for AD treatment using rTMS, and support further investigation of rTMS as a viable treatment option.

Malaria is one of the most prevalent diseases worldwide, with nearly half of the world residing in regions at risk of transmission. It is commonly spread to humans through the bite of a female Anopheles mosquito infected with Plasmodium spp. parasites. When feeding, mosquitoes ingest biogenic amines at concentrations found in the blood of the host. Adult patients with severe malaria have altered concentrations of serotonin and histamine in their blood compared to healthy individuals. Previous work showed the ingestion of serotonin and/or histamine concentrations associated with adult patients with severe malaria influenced key mosquito behaviors, such as the tendency to take a second blood meal, flight behavior, and visual object inspection—traits that are related to the transmission of malaria. However, the mechanisms by which serotonin and histamine modulate mosquito behavior remain unclear. Given the known involvement of these biogenic amines in physiological processes, we hypothesize that the ingestion of varying serotonin and histamine concentrations in Anopheles stephensi mosquitoes will alter their distribution across tissues. Mosquitoes are fed with deuterated serotonin and histamine at levels associated with patients with severe malaria versus healthy individuals. These deuterated compounds serve as tracers to distinguish endogenous (natural) from exogenous (ingested) serotonin and histamine in the tissue. The mosquitoes are dissected to retrieve the head as a proxy for the brain, the midgut, and sensory appendages including maxillary palps, antennae, legs, and proboscis. All tissue samples are extracted and analyzed via liquid chromatography-mass spectrometry (LC-MS) to distinguish and quantify deuterated and non-deuterated serotonin and histamine. By viewing all aforementioned tissue regions and comparing endogenous versus exogenous biogenic amine levels in the samples, we hope to understand the modulation of biogenic amine distribution in An. stephensi tissue and offer insights into possible connections between neuromodulators and behavior in the mosquitoes.

The tongue base is a key structure in respiration and swallowing and morphological and functional adaptations to its volumetric changes are largely unknown. Thus, addressing this gap could enhance the understanding of breathing and swallowing disorders in the enlarged and reduced tongue base. Twelve Yucatan minipigs 8-to-9-month-old (half each sex) were analyzed. Six minipigs received a high-caloric chow pellet to reach a BMI>50 (enlargement group), while the others underwent surgical partial tongue base ablation (reduction group). Five weeks after surgery all minipigs were scanned using magnetic resonance imaging (MRI) synchronized with respiratory cycle gating. Mid-sagittal cross-sectional areas of the velopharyngeal and oropharyngeal airways, and retroglossal space during inspiration and expiration were quantified using ITK-SNAP. The volumes were also calculated using segmentation techniques. These measurements were compared between the enlargement and reduction groups in the inspiratory and expiratory cross-sectional areas to determine differences. Extrapolating from one minipig from the enlarged group observed larger mid-sagittal cross-sectional areas of the interested regions compared to the reduction group. The enlarged minipig observed greater differences in range and larger averages and medians for each cross-sectional volume. The enlargement group also had slower inspiratory and expiratory rates than the reduced group. Observations from one minipig from the reduced group were observed to have smaller cross-sectional areas, medians, and averages for all interested regions. Additionally, the reduced minipig had more frequent respiratory rates. The current analysis of the sagittal views from the obese enlarged tongue base versus the reduced tongue base minipigs revealed larger volumes within the enlarged group. This pattern currently suggests enlarged tongue base minipigs with larger cross-sectional volumes, but less inspiratory and expiratory rates. However, the reduced tongue base minipigs are anticipated to have smaller cross-sectional volumes and more frequent respiratory rates compared to the enlarged group.

Currently, monitoring the heart's electrical activity to diagnose cardiovascular disease requires the patient to have electrodes placed on their chest. A novel approach was proposed to record ECG (electrocardiogram) signals from human fingertips, which could offer a more convenient alternative for in-home use. A prototype device was designed to capture and process the ECG heart signals for real-time health monitoring. The development process included schematic design, printed circuit board (PCB) layout creation, hardware assembly, troubleshooting, and data acquisition and analysis. The device has three rounded copper electrode plates for collecting ECG from 3 fingers, with one serving as a noise-canceling electrode. ECG signals were successfully recorded from volunteers using these fingertip copper electrodes mounted on a PCB with biomedical signal amplifiers. Additionally, basic signal-processing algorithms have been implemented in MATLAB to remove noise and enhance ECG signal quality for parameter extraction. With further research and refinement, this prototype could evolve into a portable, user-friendly device suitable for at-home monitoring or clinical use as an alternative method for tracking heart activity.

Rising atmospheric carbon dioxide levels have driven research into efficient gas separation materials. Polymers of intrinsic microporosity (PIMs) is one promising solution due to their rigid, porous structures and processability, allowing them to be turned into thin films for membrane-based gas separations. My research focuses on enhancing the carbon dioxide selectivity of helicene-based PIMs through post-synthetic modification of these polymers. I have synthesized a small molecule model of the PIM to screen for amine substitution conditions and ensure the viability of post-synthetic modification on the larger helicene-based PIM. Characterization techniques, multinuclear NMR and mass spectrometry, have verified the synthesis and amination of my model system. By incorporating nucleophilic amines into PIMs, these polymers can feature enhanced binding to electrophilic carbon dioxide, thereby increasing the interactions with carbon dioxide over other mixed gases, leading to separation. In my future studies, I will extend these modifications to the helicene-base PIM, fabricate films and evaluate their properties. Surface area measurements using N₂ gas sorption methods and CO₂ absorption isotherms will quantify gas-binding affinity and separation performance.

The external fertilization and transparent embryos of zebrafish make them an informative model of vertebrate embryonic development from the 1-cell stage. In this study, we examine the impact of de novo GTP synthesis on the formation of the embryonic somites, which are embryonic cells which develop into segmented blocks of muscle that run the length of the body. We hypothesize the de novo GTP synthesis is required for the correct patterning of somite borders in zebrafish embryos, and that this process facilitates the formation of a vertebrate body plan. Inosine monophosphate dehydrogenase 2 (IMPDH2) is the enzyme which catalyzes the conversion of inosine monophosphate (IMP) towards the de novo synthesis of GTP instead of ATP. To test the impact of de novo GTP synthesis on somite formation, we inhibited IMPDH2 function with mycophenolic acid (MPA) both before and after somite formation began. MPA caused stronger defects in the somite morphology and embryonic body shape when added to embryos before somite formation began, earlier in development. We performed in situ hybridization against xirp2a to assess the effect of inhibiting IMPDH2 function on the formation and patterning of the somite borders. MPA treatment decreased the definition of somite borders we could observe in the posterior tail. Inhibiting IMPDH2 with MPA produced somites with smooth, round borders instead of the chevron-shape typical of zebrafish. We next conducted immunohistochemistry against IMPDH2 to examine the expression and localization of this enzyme in embryonic cells when GTP conditions are low. In MPA-treated embryos, we observed increased expression of IMPDH2 across the entire embryo. We will next explore how GTP abundance affects activity of the clock, a mechanism which synchronizes gene expression of embryonic cells.

Large Language Models (LLMs) have demonstrated remarkable performance in code generation and problem-solving, but their effectiveness varies across problem domains and complexities. In this study, we assess the problem-solving capabilities of different LLMs on a subset of LeetCode problems, categorized by difficulty, topic, and computational complexity. Through a systematic analysis of LLM performance across question topics—such as dynamic programming, matrix, and binary search—we identify trends in their strengths and weaknesses. Our findings reveal that LLMs excel at problems likely included in their training data but struggle significantly with novel or unseen problems. By evaluating their performance across different algorithmic domains, we offer insights into the potential limitations in specific algorithmic domains and implications for AI-assisted coding, competitive programming, and software engineering education. 

This study examines whether female managers foster a more employee-oriented corporate culture. I hypothesize that firms led by female Chief Executive Officers (CEOs) exhibit stronger commitments to employee well-being and Diversity, Equity, and Inclusion (DEI) initiatives compared to those led by male CEOs. To test this hypothesis, we conduct Ordinary Least Squares (OLS) regression analyses. Analyzing S&P 1,500 firms from 2001 to 2013, I find that companies led by female CEOs demonstrate stronger commitments to employee relations, diversity, and inclusion, particularly in areas such as professional development, health and safety, retirement benefits, employee involvement, no-layoff policies, union relations, workforce diversity, child labor reduction, and work-life benefits. Notably, during economic downturns like the dot-com bubble in 2002 and the financial crisis in 2008, while most firms reduced their investments in DEI, those led by female managers maintained their commitments. These findings contribute to both academic discussions and practical strategies for advancing DEI in corporate leadership, highlighting the influence of female executives in shaping corporate policies. By offering fresh insights into the role of leadership diversity in corporate culture, this study underscores the importance of inclusive leadership in fostering a more equitable workplace. As an undergraduate researcher, I find this project both intellectually stimulating and profoundly educational, providing nuanced insights into the intersection of leadership and corporate responsibility. 

Depression is one of the most commonly co-occurring mental health conditions among individuals with autism spectrum disorder (ASD) for which there are not currently effective strategies to minimize onset. Given that early caregiver support in autism-specific and general areas of functioning predict the development of a range of adaptive social and behavioral patterns, leveraging caregiving processes in childhood and adolescence may represent one approach to decreasing the risk for psychological disorder. However, current research recognizes that the high levels of stress experienced by many families with an autistic child may undermine the quality of support caregivers are able to provide. As a result, there is limited understanding of caregiving strategies that will reliably confer resilience to depression and that will support the successful implementation of mental health-related interventions in autism. As such, this project assesses caregiver involvement in childhood and adolescence as a predictor of depressive symptomatology in autistic adults, and additionally to evaluate the family environment as a moderator of this relationship. It is hypothesized that there will be a negative association between caregiver involvement and severity of depression symptoms, and that the association will be stronger under conditions of high familial warmth but reversed in family environments characterized by high control or rejection. Taken together, family environment will account for appreciable variations in the effectiveness of parent involvement as protecting against the development of depression. This survey study will lay the groundwork for researchers and autism service providers to develop an informed approach to leveraging parent involvement as a preventative measure against depressive symptoms in adulthood.

Dynamic marine environments require long-term spatiotemporal datasets to successfully monitor and understand patterns in ecosystem composition on a decadal scale. High-resolution photography is often used to compensate for the field logistical constraints associated with marine sites, such as personnel availability or weather conditions, and works well to quickly capture data in the field. However, these photos require extensive manual analysis after the fact. As a research mentee, I asked the question: “Can image annotation with machine learning models provide enough clear data to inform community ecology studies of sessile organisms in subtidal habitats?” Using images collected through transect/quadrat sampling by the Sebens Lab’s Salish Sea Long-term Monitoring Project (University of Washington Biology and Friday Harbor Laboratories), a variation of an open-source model (CoralNet) was trained in the identification of relevant sessile flora and fauna. I then used CoralNet to continue the work of the lab by generating sessile assemblage metrics for a single site in the Friday Harbor Laboratories Biological Preserve. This site included images from transects at two different depths, with sampling from 2014 and 2024. After being uploaded, CoralNet identified 200 random points per image to the lowest possible taxon. I then reviewed all annotations for accuracy and corrected them whenever necessary. This technique greatly reduced the time spent per identification, without sacrificing accuracy. Next, I calculated species richness and Simpson’s Diversity for each quadrat and transect, comparing between depth and year. My analysis showed significant increases in both metrics from 2014 to 2024 and no significant differences between depths, demonstrating a successful report on the dynamics of a subtidal marine community. Application of this method to the entire existing dataset (7 sites, 63 transects per year), and others, provides opportunities to streamline analysis of sessile community composition.

The health risks of particulate matter measuring less than 2.5 micrometers (PM2.5)  include: respiratory disease, cardiovascular issues, and cognitive impairments. Its presence near schools and colleges remains underexplored. This study examines the relationship between PM2.5 exposure levels and academic outcomes in community colleges located in historically redlined neighborhoods across four major West Coast cities: Los Angeles and San Diego in California; Portland, Oregon; and the greater Seattle area in Washington. Using data from the PurpleAir Network, state air quality indices, and community college governing bodies, we analyzed and compared PM2.5 levels near institutions located within historically redlined neighborhoods and institutions located outside those neighborhoods. Leveraging the Python programming language and Google Colab, we examined correlations between an institution’s demographic makeup and transfer rates relative to PM2.5 exposure. Data sets obtained were filtered between the hours of 8 AM and 1 PM during the months of January 2024 through December 2024. Our findings indicate a correlation between higher PM2.5 exposure and lower academic performance for colleges serving predominantly racially marginalized communities located within historically redlined neighborhoods. This research reinforces the role of environmental inequities in shaping educational disparities and highlights the need for targeted policies to address air quality in affected communities.

Accurately describing a child’s language skills is difficult, but identifying children with atypical language development adds even more complexity. In an ordinary language assessment session, a Speech-Language Pathologist (SLP) will use both standardized, norm-referenced assessments and non-standardized assessments, like Language Sample Analysis (LSA). However, there is little research about how these different assessments relate to one another. To better understand this relationship, the language abilities of children (n=38) were assessed after turning 6-years-old and attending Kindergarten by SLPs using the following norm-referenced tests: a sound-in-words subtest from the Goldman-Fristoe Test of Articulation, 3rd Ed. (GFTA-3); core language subtests from the Clinical Evaluation of Language Fundamentals, 5th Ed. (CELF-5); and a nonverbal IQ subtest from the Kaufman Brief Intelligence Test, 2nd Ed. (KBIT-2). Then, a 10- to 20-minute language sample of the child’s spontaneous speech was collected for analysis. This project extends from previous research by including participants beyond clinical populations and using multiple sampling contexts to holistically capture the child’s naturalistic speech. I transcribed each language sample with Codes for Human Analysis of Transcripts (CHAT) and utilized Computerized Language Analysis (CLAN) software to automatically compute measures reflecting language skills from the language samples. I will conduct correlational analyses to inspect the associations between measures from norm-referenced tests and measures extracted from language samples. I expect to see significantly positive correlations between several CELF-5 measures and LSA measures of morphosyntactic development (i.e., grammar) that demonstrate a convergence between these two methods of assessment. Correlations between LSA measures and GFTA-3 measures are expected as well but to a lesser degree of association because they do not index identical elements of language. Overall, relationships discovered during this process will lend themselves to further understanding the information we gain from these common tools of language assessment.

Cervical spinal cord injuries (SCIs) often result in impaired locomotion and forelimb mobility. Assessed with a forelimb locomotor scale (FLS), previous research demonstrated improved forelimb locomotion with task-specific physical therapy (PT) training following a unilateral 150 kdyne C6 SCI in a rat model. Improvement in locomotion was calculated using a recovery ratio, which measures the difference in FLS scores normalized to the animal’s baseline score. There was a significant improvement in the recovery ratio (3dpi-14wpi) for animals that underwent task-specific PT training (p ≤ 0.0014). The underlying molecular mechanisms behind this improvement are still unclear. A potential explanation for these functional changes is the task-specific PT-induced increase in brain-derived neurotrophic factor (BDNF) targeted at the injury site. Task-specific PT stimulates neurons, microglia, and astrocytes to release BDNF, promoting neuron survival, growth, and synaptic plasticity. These processes are crucial for mediating the effects of cervical SCI trauma. This study investigates whether BDNF expression in the spinal cord varies in rats that underwent task-specific PT training following cervical SCI. PT-trained rats are hypothesized to have increased BDNF within the spinal cord, especially proximal to the injury site, which would help mitigate SCI trauma and enhance forelimb locomotion and mobility. To this end, we performed immunohistochemistry staining and quantification of BDNF in the spinal cord and compared it across three groups: PT + SCI, SCI-only, and Sham. The expression levels of BDNF in neuronal cells, astrocytes, and microglia were then correlated with their FLS scores to determine if there was a positive correlation between BDNF expression and forelimb locomotion. This would indicate that BDNF supports synaptic plasticity and recovery from SCI-induced trauma.

The identification of synergistic drug combinations remains a significant challenge in oncology due to the large amount of existing drugs and complex interactions between these drugs. In this work, we propose an active learning framework applied to the NCI ALMANAC dataset to efficiently uncover promising drug pairs that conventional screening methods might overlook due to lack of time and resources to handle these nearly countless combinations. Building on established greedy sampling strategies—such as GSx, which selects samples based on maximal minimum distance in the input space, and GSy, which focuses on output diversity—we introduce modifications to potentially enhance sample selection diversity and predictive performance. First, we explore replacing the traditional greatest minimum distance criterion with a greatest average distance metric, hypothesizing that this adjustment captures the overall variability in the data differently than the traditional method. Second, we redefine the improved greedy sampling (iGS) approach by standardizing the distance metrics from both the input (GSx) and output (GSy) spaces using Z-score normalization (or alternative standardization methods) prior to their aggregation, rather than combining them multiplicatively. We conduct a comprehensive comparative analysis against traditional methods to evaluate improvements in model convergence, prediction accuracy, and the ability to identify rare but potent drug combinations. We also explore other active learning strategies as Query By Committee (QBC) and others. Our preliminary findings suggest that these tailored active learning techniques offer a promising pathway toward more efficient and insightful exploration of high-dimensional drug interaction landscapes.

The stimulation of the genioglossus muscle may prevent upper airway collapse in breathing disorders such as obstructive sleep apnea (OSA). Thus, the present study was to analyze the 3D-changes of the tongue base by electric stimulation of genioglossal muscle in relation to volumetric alterations of the tongue base in minipigs. Twenty 8-to-9-month-old Yucatan minipigs were used. Of them, 8 were controls, and 12 were experimental. Each experimental same-sex sibling pair was randomly assigned: 1. Normal-weight having surgical tongue base volumetric reduction. 2. Enlargement having significant obesity, BMI>50. All minipigs received surgical implantation of eight 2mm ultrasonic crystals in a cubic-shaped array in the tongue base. The distance change between each crystal pair indicated dimensional deformations for lengths, widths, and thicknesses responding to the stimulation. Increased distances indicated elongations while decreased indicated shortenings. Stimulations to the left genioglossal muscle were ramping up in range of 10-40V to reach the maximal amplitudes (tetany). Stimulation of the genioglossus muscle in controls induced left lengthening, anterior thickening and overall widening along with posterior thinning and right shortening. In contrast, the reduction group showed thickening and widening with left lengthening and minor right shortening. Elongations in the reduction group were larger than those in the control group (p<0.05). The enlargement group showed decreased dorso-ventral lengths compared to those of the control and reduction groups (p<0.05), along with antero-posterior thickening and widening. Stimulation of the genioglossus muscle induces distinctive deformational patterns between the normal and volumetric-altered tongue bases. For instance, shortening in length in the enlarged tongue due to obesity may suggest retraction of the tongue base inducing narrowing of the oropharyngeal airway. These results may contribute to understanding kinematic adaptations in the respiratory dynamics in relation to the volumetric alterations of the tongue base, a current approach to treat moderate and severe OSA. 

Advances in antiretroviral therapy have increased life expectancy for people living with HIV (PLWH), but aging exacerbates symptoms such as frailty, neurocognitive disorders, and bone loss. Pharmacological treatments often present limitations, including side effects and drug interactions. Non-pharmacological approaches like physical activity and diet may offer holistic symptom management, yet remain understudied in PLWH. The aim of this study is to investigate the association between physical activity levels, diet quality, and symptom experiences in older PLWH. We will analyze data from the PROSPER-HIV study, a prospective observational study of 850 participants (over 50% aged ≥50 years) from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS) across four U.S. sites. Key measures include: (a) moderate-to-vigorous physical activity, assessed via accelerometry; (b) diet quality, measured by the Healthy Eating Index-2015 (HEI-2015) from 24-hour dietary recall; (c) symptom burden, evaluated using the 20-item HIV Symptom Index; (d) muscle strength, assessed via handgrip strength; and (e) physical function, measured using the Short Physical Performance Battery (timed walk, chair stands, and balance tests). Descriptive analyses will identify patterns in physical activity, diet quality, symptom burden, muscle strength, and physical function collected at baseline. Linear regression models will examine relationships between symptom burden, physical activity, and diet, adjusting for age, sex, muscle strength, and function. Findings will clarify the impact of lifestyle factors on symptoms, supporting the integration of non-pharmacological strategies into nursing care. The results will inform nursing practice and public health by highlighting the role of physical activity and dietary improvements in symptom relief.

Tuberculosis (TB) remains a major global health challenge, causing over a million deaths annually despite being a curable disease. A critical issue is treatment non-adherence, as many patients struggle to complete the required six-month regimen due to a lack of support and access to reliable medical guidance. Improving treatment adherence can significantly increase recovery rates and save lives. This project develops an AI-augmented chatbot powered by GPT-based models to assist Spanish-speaking TB patients. This is done by providing accurate medical guidance, fostering empathy, and enhancing communication between patients and healthcare providers. Integrated into a Human-System Interaction (HSI) interface, the system employs three AI models: a two-step pipeline that classifies messages as informational or emotional to tailor responses appropriately, a few-shot model that generates responses based on examples from prior patient interactions, and a Retrieval-Augmented Generation (RAG) + few-shot model that retrieves relevant medical information from guidelines while maintaining conversational fluency. These models leverage the same underlying technology as ChatGPT, optimizing responses for accuracy, linguistic fluency, and empathy. As part of the research team, I contributed to model development and implementation, ensuring alignment with medical guidelines and human-centered design principles. The chatbot is currently undergoing external evaluation by a multidisciplinary team, including healthcare professionals specializing in TB treatment and AI researchers. Evaluators interact with the chatbot using personas as TB patients, asking medical and support-related questions to assess response quality. They rate the system based on medical accuracy, linguistic fluency, empathy, and other key criteria relevant to patient-provider communication. Insights from this evaluation will guide future refinements, with the goal of improving AI-driven patient support systems in clinical settings.

Microglia are innate immune cells in the brain that play an important role in maintaining homeostasis, carrying out immune surveillance, and modulating synaptic plasticity. Through the secretion of cytokines, along with physical functions like synaptic pruning and network refinement via phagocytosis, microglia support the health of neurons and help establish a functional neuronal network. In previous experiments, our lab demonstrated that when cultured with microglia, neurons exhibit more robust morphology and greater synaptic activity. However, it remained unclear whether the beneficial effects of microglia on neurons occur during physical contact between the two cell types, or if the supportive factors secreted by microglia are sufficient to drive this change. To investigate this, I compared the morphology and function of neurons directly co-cultured with microglia, to neurons treated with media conditioned by microglia. In the microglia-conditioned media treatment, I conditioned the microglia media for 24, 48, and 72 hours prior to treating the neurons to determine the optimal conditions for establishing a healthy neuronal environment. To evaluate these results, I conducted immunofluorescence staining for microtubule-associated protein tau (MAPT) and microtubule-associated protein 2 (MAP2), both of which are indicators of neuronal health. I analyzed fluorescence intensity and neurite length to quantify morphological differences in neurons between conditions. To investigate differences in synaptic activity, I carried out micro-electrode array recordings of neurons in each condition. Using data from these recordings, I analyzed the coordinated and overall electrical activity to measure the functionality of the synaptic network in each condition. Given that microglia perform both secretory and physical functions, I expected that neurons directly co-cultured with microglia would exhibit more robust phenotypic and functional characteristics. These experiments provide insight into healthy neuron-microglia interactions and reveal possible avenues towards their dysregulation in Alzheimer’s disease (AD), potentially guiding the development of therapeutics targeting such interactions.

Mycobacterium abscessus is a non-tuberculous mycobacterial (NTM) species that causes severe pulmonary infections, particularly in immunocompromised patients and those with preexisting lung diseases such as cystic fibrosis. Treating M. abscessus infections is challenging due to its intrinsic antibiotic tolerance and capacity to develop multidrug resistance. To identify novel molecules that can target this pathogen and enhance current treatments, we screened a library of FDA-approved drugs (n = 2,400). Our data shows that Netupitant, a drug commonly used to prevent chemotherapy-induced nausea and vomiting, exhibits potent antibacterial activity against a broad range of M. abscessus clinical isolates, including multidrug-resistant strains, with a minimum inhibitory concentration (MIC) ranging from 4 to 16 µg/mL. Furthermore, in combination with amikacin, a standard treatment for M. abscessus infections, Netupitant demonstrated strong synergistic interactions, as confirmed by checkerboard microdilution and time-kill assays. These findings highlight Netupitant’s potential as a novel therapeutic option for M. abscessus, particularly in combination with existing antibiotics. Future studies exploring its mechanism of action and in vivo efficacy could further advance antibacterial drug discovery for difficult-to-treat NTM infections.

Surf smelt (Hypomesus pretiosus) are ecologically and culturally important forage fishes that rely on intertidal beach habitat for spawning. However, the combined effects of rising sea level and human modification (e.g. seawalls, bulkheads, riprap) have put this habitat at risk of coastal squeezing, which could reduce available spawning areas along Puget Sound. This research aims to assess the vulnerability of surf smelt spawning beaches to climate change by combining field data collection with quantitative analysis. We evaluated existing risk assessment methods, such as the Coastal Vulnerability Index (CVI) to determine its applicability to Puget Sound. Additionally, we conducted beach surveys at productive spawning beaches to characterize the beach morphology. Our morphodynamic analysis included measurements of beach slope, sediment composition, pH, and water table depth from the high tide line to the waterline. Our hypothesis suggests that spawning beaches with a lower slope, smaller sediments, and a shallow water table will be more resilient to climate change impacts. Findings from this study will improve our understanding of climate-driven and anthropogenic threats to intertidal ecosystems and provide insight into habitat resilience, supporting conservation efforts for surf smelt populations.

The aim of this study was to examine the respiratory 3D deformational changes in the tongue base with normal weight and obesity in a minipig model. This study included 6 same-sex sibling pairs (3 pairs each sex) of Yucatan minipigs 8-to-9 months old. Of each pair, one minipig was normal weight with a BMI<35 and the other was fed a special diet reaching a BMI>50 (obese,). While under sedation, eight 2mm ultrasonic piezoelectric crystals with an extended skin button attached to the back were surgically implanted at the base of the tongue in a cubic-shaped arrangement. These crystals represented dorsoventral lengths, anteroposterior widths, and thicknesses. The 3D deformational changes of the tongue base were recorded during respiration using a Sonometric system together with synchronized electromyography and airflow recordings to identify respiratory phases. The amplitudes and durations of each dimensional change within the crystal-defined region concerning inspiration were calculated for 5- consecutive respiratory cycles per minipig. The total respiratory cycle duration was 1.87±0.38s in the normal-weight group and 3.2±1.01s in the obese group (p<0.05).  Similarly, the durations of the inspiratory phase in the normal and obese groups were 0.62±0.36s and 1.19±0.77s respectively (p<0.05). Deformational changes in the normal-weighted group included dorsoventral lengthening, anteroposterior ventral widening with dorsal shortening, and thickening in all dimensions. In contrast, the obese group showed dorsal lengthening with ventral shortening, widening in all dimensions, and anterior thickening with posterior shortening. Overall, larger dynamics were observed in the normal-weighted group compared to the obese group (p<0.05). These results demonstrate that obesity affects tongue base respiratory kinematics, with longer respiratory cycles and decreased deformational changes mainly ventrally and posteriorly. These findings enhance understanding of obesity's impact on the oropharyngeal function, with implications for breathing disorders.

Societal industrialization and post-industrialization are associated with birth rate reduction. This decline coincides with the increase in accessibility to education, contraception, and employment for people with capacity for pregnancy. In a post-industrial society such as the United States, more people are electing to not parenting. However, an individual’s choice to remain childfree is still deviant from the expected social norms of female-presenting individuals. The mounting stresses of finances, political restrictions of bodily autonomy, and lifestyle lead many individuals to seek community and kinship outside the traditional understanding of family. We aim to describe the experiences and conceptualization of family of cisgender women, a demographic with presumed capacity for pregnancy, as well as a societal expectation of pregnancy and motherhood. Cisgender women of reproductive age, navigate the crux of societal expectation to reproduce while also experiencing factors that disincentivize traditional family-making and the increased accessibility to choose to remain childfree. Existing literature has looked into the reasoning of electing to not parent, however, there is a lack of research into understanding the individual’s schemas about family and their perceptions about their own autonomous decisions. The boundaries of societal expectations of kinship are evolving alongside the societal and political pressures that discourage people from having children. Therefore, we are conducting qualitative semi-structured interviews with cisgender women in Seattle to describe the conceptualization of kinship in a population with reduced barriers to remaining childfree and increased stresses that discourage people from having children. This research will illuminate how they understand and live the paradoxical pressures between the expectation of family-making and their decision not to parent and raise children.

We present BIOGEM, a fully biodegradable McKibben actuator with integrated sensing, made from gelatin-based composites. By tailoring the material compositions, we customize the mechanical and electrical properties of the biodegradable composites, creating an integrated biodegradable system that combines both actuation and sensing functionalities. BIOGEM integrates a McKibben actuating structure by using stiff gelatin as outer braiding and the stretchable gelatin as air chambers. It also integrates resistive strain sensing through ionic gelatin, allowing the actuator to monitor its own deformation without relying on conventional electronics. We characterize the actuator’s performance across key parameters including braid angle, wall thickness, and material stiffness, demonstrating reliable contraction and repeatable force output at low pressures. Biodegradation is validated through both enzyme-assisted and backyard soil studies, confirming the material’s sustainable end-of-life behavior under realistic conditions. We illustrate the potential of this platform through interactive, edible, and environmentally-degradable prototypes across human–computer interaction and soft robotics scenarios.

Neutrophils are a type of white blood cell in the human immune system that can migrate through tissues to respond to sites of injuries and infections. In the laboratory, we can recapitulate neutrophil migration under controlled experimental conditions by using a cell line, called HL-60, that was originally derived from a person with leukemia. These cells can be cultured to imitate the behavior of neutrophils, and specifically they are able to migrate while we watch them on the microscope. First, I determined how HL-60 cell migration depends on the physical nature of the substrate they are crawling on. I compared cell migration under three different conditions: 1) uncoated plastic, 2) plastic treated to make the surface stickier for cells, and 3) plastic coated with a protein, BSA, to make the surface less sticky. I found that cells moved faster and with straighter paths on the uncoated plastic. Next, I used a drug, CK666, which is known to inhibit a protein that is important in the assembly of the cell’s actin cytoskeleton, the mechanical driver of cell migration. As expected, I found that the cells moved more slowly in the presence of the drug. Also, I found that the drug made the cells move in less straight paths. Finally, I explored how the HL-60 cells responded when I exposed them to an electric field. Electric fields are thought to arise naturally at sites of skin wounds. I observed that the cells moved toward the cathode of the electric field. I am currently analyzing whether the cells also move faster or straighter when there is an electric field present. In future experiments, I plan to determine whether mutating specific proteins thought to be involved in cell motility can change the behavior of the HL-60 cells on the microscope.

In the paper "Planting Undetectable Backdoors in Machine Learning Models" by Goldwasser et al (arXiv:2204:06974), the authors establish the notion of "black-box undetectability" for machine learning models and prove it in many cases. This is a backdoor that is undetectable by merely looking at inputs and outputs of the model. The paper also introduces the concept of "white-box undetectability."  We aim to consider this stronger notion and outline how even with the knowledge of entire model weights, there may be undetectable backdoors in a model. More specifically, we establish an idea where one takes an innocuous model (say a Multi-Layer-Perceptron model) and enlarges it by adding "dummy" edges and using appropriate non-linear activation functions to effectively place a backdoor in the model. In our project, we establish a proof of concept by backdooring an MNIST classifier.

Relative Risk (RR) is a highly interpretable parameter in epidemiology and biostatistics, based on both binary input and outcome. It is frequently used in vaccine development to measure the relative efficacy between two treatment groups.
Researchers are often tempted to use generalized linear models (GLMs) to estimate the logarithmic RR with respect to a set of baseline covariates. However, this approach has inherent flaws, as GLMs do not account for variation dependence in Relative Risk on its nuisance parameters. Richardson et al. have developed an unconstrained and variation-independent doubly robust nuisance model using the log Odds Product (OP).
To expand on this work, we will explore alternative nuisance models—both those developed by us and those from other researchers—and compare their computational robustness to that of the log Odds Product (OP).
Additionally, using the brm R package (which streamlines the methods proposed by Richardson et al.), we will analyze a dataset where Relative Risk serves as the target of inference and compare these results to those obtained using regression methods.

Due to considerations such as dose reduction, or physical limitations of the scanner, computed tomography (CT) images must sometimes be reconstructed from sparse-view or limited-angle sinogram data, resulting in a loss of image quality. In recent years, there has been a great deal of interest in using neural networks to improve image quality in these scenarios. In this work, we implement three neural network architectures – denoising convolutional neural network (DnCNN), U-net, and transformer – and apply them to sparse-view and limited angle problems in both a post-processing and iterative, “plug-and-play” reconstruction context. In post-processing, the neural network is applied to the final image to remove artifacts, while in the plug-and-play approach, it is incorporated into the algorithm that reconstructs the image from the sparse-view or limited-angle data. Based on standard image quality metrics, the post-processing approach with the U-net is found to give the best image quality. The plug-and-play approach, while not always providing the best image quality, is able to ensure fidelity with the sinogram data.

Hemophilia A (HemA)—a severe genetic bleeding disorder affecting 1 in 10,000 people—is caused by mutations in the F8 gene. These mutations cause an inability to produce the coagulation factor eight protein (FVIII) necessary to stop bleeding after a wound. Current treatment- repeated FVIII replacement, is costly and frequently ineffective, as around 30% of patients develop inhibitor antibodies causing the immune system to reject the foreign protein. Alternatively, our lab hopes to utilize gene therapy to restore the functional gene and allow the body to continue producing the essential FVIII protein itself. 45% of human HemA cases are caused by a mutation of the human F8 gene where a large portion called Intron 22 (In22) is inverted. The In22 inversion halts translation of the rest of the gene, and the resulting FVIII protein is truncated and non-functional. To address the mutation, our lab aims to use a CRISPR-based knock-in approach to the DNA following In22, upstream of the mutation site. We expect that this strategy can restore endogenous production of missing FVIII and potentially provide curative treatment for affected patients. To test this treatment’s efficacy, this project utilizes a HemA mouse model (E16) in which a neo cassette insertion at the 3’ end of exon 16 disrupts FVIII expression. We propose using the same strategy to integrate the missing DNA upstream of the mutation and restore FVIII function in HemA mice. I use molecular cloning to construct and evaluate different versions of the CRISPR-Cas9 plasmid containing sgRNA, and a plasmid containing the donor DNA. This research allows us to determine the safety and efficacy of our gene therapy strategy, and evaluate how to maximize recovery of FVIII production. This project aims to eventually contribute to treatment of human HemA patients, without the expensive and unreliable replacement of the protein.

Carpenter syndrome is a congenital disorder mainly characterized by craniosynostosis – soft spots of the skull fuse prematurely resulting in skull elongation. MEGF8, a protein in the MEGF8-MGRN1-MOSMO (MMM) regulatory complex involved in Hedgehog (Hh) signaling, has been previously linked to Carpenter syndrome. Hh signaling, a core developmental pathway, plays many roles in skull development, including functioning as a guidance cue for cranial neural crest cells (foundational cells for skull bones) and regulating bone ossification (bone hardening). Despite the previous research linking MEGF8 and anomalous skull development, the role of the MMM complex and Hh signaling in skull development and the mechanism behind this abnormal skull development is still widely unknown. I’m exploring the mechanism by which elevated Hh signaling influences cell fates during the development of skull structures. I investigated a whole-embryo knockout mouse model to identify regions where overexpression of Hh correlates to abnormal skull phenotypes. I explored and measured these phenotypes via imaging a genetic Hedgehog reporter mouse line and skeletal stained embryos of various ages. These knockout mice were embryonic lethal because of a congenital heart defect associated with loss of Hh. We introduced an inducible Cre to conditionally knockout the MMM complex at a later age, avoiding heart defects. My findings identified the interparietal and parietal regions of the skull as areas of interest, visualized by over-ossification and lack of defined structural boundaries- nasal and palatal development was normally observed. These findings suggest that elevated Hh signals result in abnormal development of skull structures, similar to craniosynostosis, and are involved in intramembranous ossification (skull structures) rather than endochondral ossification (nasal/palate). From these findings, I’m investigating how Hh signaling plays a role in skull development and intramembranous ossification.

Cytochrome P450 enzymes (CYPs) are a family of proteins that play an integral part in drug metabolism. An example is CYP3A4, a specialized protein within the CYP family, involved in the oxidation of small drugs and toxins, like cannabinoids, to allow for their removal from the body. Understanding this reaction is important in evaluating how different expression levels of CYP3A4 in different individuals affect the efficiency of drug metabolism. In this project, I studied drug binding to recombinant, purified, CYP3A4 protein. The binding assays of CYP3A4 allow evaluation of the quality of the purified protein. Ultraviolet-visible spectroscopy (UV-Vis) was used to quantify the protein, and spectral binding through drug titration was used to characterize the binding affinities of different substrates. Drug titration enables us to observe the amount of ligand bound to the protein at various concentrations, displayed as a binding curve from which we can determine the spectral binding constant (Ks). The CYP active site contains a heme group. Upon binding, the ligand replaces the water molecule that is originally docked in the active site. This transfer reaction shifts the heme spin state and appears on the UV-Vis spectra as an increasing absorbance at the 380 nm wavelength and a decreasing absorbance at 420 nm. Inhibitors would have the reverse spectrum. In vitro studies with purified protein have several benefits when investigating protein function, such as simplifying the experimental system and reducing the limitations of complicated sample preparations from living organisms. Having a well-defined assay to determine recombinant 3A4 protein quality will contribute to the value of further in vitro activity and pharmacokinetic studies with this protein. 

Indium phosphide (InP) quantum dots are a high-performing semiconductor material used in optoelectronic applications due to their tunable electronic properties and low toxicity compared to cadmium-based quantum dots. However, InP quantum dots are currently synthesized at or above 180°C because of the high energy input required for nucleation and growth of the covalent nanocrystals. This study explores the synthesis of small InP clusters at lower temperatures by investigating reaction conditions that can produce InP with reduced energy consumption. Using the precursors indium carboxylate and P(SiMe₃)₃ in a nonpolar solvent toluene, we systematically investigate the evolution of InP clusters at room temperature and 60°C via UV-Vis absorbance spectroscopy. The formation of atomically precise InP clusters was observed at room temperature after 23 days. To speed up the reaction, we investigate adding a polar aprotic solvent or amines to promote the formation of InP at low temperatures. Including 20% of N-Methylpyrrolidone in the solvent mixture with toluene allows InP to be formed in 2 hours. Amine additives interact with the indium cations to modulate their reactivity, therefore we investigate adding varying equivalents both to the pre-formed atomically precise cluster, and to the indium and phosphorous precursors in toluene. We found that adding up to 100 equivalents of benzylamine per cluster did not promote the growth of InP clusters. Our findings contribute to the understanding of how InP forms at low temperatures for scalable, environmentally friendly production.

Glaciers have long been used as the bellwethers of climate change, given their ability to store gases, dust, microbes, and other environmental materials in their layers; tracking their recession has also been an important visual indicator of climate change. In this research, I examine how anions in newly exposed vary with depth. To do this, I took samples from exposed vertical ice faces on the Coleman glacier, on the north face of Mount Baker. Samples were thawed and analyzed using ion chromatography.  Trace amounts of chloride, nitrate, sulfate, and phosphate were found in each sample. The ion concentrations showed no trend with depth, and the ice itself appeared uniform. This is in contrast from vertical cores taken from solid ice in numerous other surveys, which show distinct annual layers and variation. This suggests that the ice at vertical faces has different properties from that at the top layers, including in its ability to trap environmental markers. Further research is needed to confirm this difference and examine which of these markers is most affected. Increased understanding of these markers could give more insight into how glaciers change over time and interact with their environment.

As Cannabis use is becoming more widespread there is growing concern regarding the respiratory exposures of employees working in indoor cannabis processing facilities. Employees in these occupational settings are frequently exposed to volatile organic compounds (VOCs), particulate matter (PM), other respiratory irritants, and allergic sensitizers. These exposures are linked to work related illness and disease, such as occupational asthma. Notably, a fatality, in 2022, in a Cannabis worker due to occupational asthma highlights the urgent need for improved exposure controls. Cannabis processing workers experience prolonged and frequent exposure via inhalation with little knowledge on the respiratory hazards of this work. This study aims to evaluate the efficacy of a local exhaust ventilation (LEV) system to reduce exposure to airborne hazards during automated joint filling. Automated joint filling is a common process in Cannabis production facilities, using mechanized equipment pre-ground material is dispensed into pre-rolled cones. This method is preferred in the field as it increases both consistency and efficiency. Over a ~2-hour sampling period across eight batches of pre-rolled joints, we conducted gravimetric sampling for inhalable PM using two inhalable aerosol samplers (IOMs) positioned at the workbench and in the breathing zone. VOC exposure was assessed using thermal desorption tubes and photoionization detectors (PIDs), while continuous respirable PM concentrations were measured using a Nanozen DustCount monitor. Testing air concentration for PM and VOCs with and without the LEV mechanism is being conducted to determine its effectiveness at reducing exposure. We hypothesize that this may be an effective solution, as the LEV has controlled these agents significantly in other similar workplace settings. As this field grows due to recent state by state legalization of Cannabis, these findings hold great impact for workplace safety regulation and solutions. Additional research should be gathered on long-term exposure effects and preventive mechanisms.

The increasing concern over global warming has driven interest in clean energy solutions, with piezoelectricity emerging as a promising alternative. Piezoelectric materials generate electric voltage under external mechanical forces, offering an innovative method for energy harvesting. This work derives a system of partial differential equations (PDEs) and their accompanying boundary conditions that describe the coupled elastic-electric behavior of an Euler-Bernoulli piezoelectric beam. Under the quasi-static approximation for the electrical field, the assumptions of Euler-Bernoulli beam theory, and the constitutive relations for the 3-1 piezoelectric coupling mode (i.e., voltage is generated in a direction perpendicular to external mechanical force), we develop a Hamilton’s variational principle to derive the governing equations and boundary conditions for the piezoelectric Euler-Bernoulli beam. The obtained equations consist of Gauss’s law of electrostatics and the Euler-Bernoulli beam equation that are coupled due to the piezoelectric effect: apparent electric charges that depend on elastic deflection appear in Gauss’s law, while apparent mechanical forces and moments that depend on the electric potential appear in the Euler-Bernoulli beam equation and its boundary conditions. The derivation from first principles, as well as the study of the governing equations constitutes a fundamental framework for analyzing piezoelectric beam behavior, with implications to the improvement of design of piezoelectric energy harvesters.

Dense-core vesicles are membrane-bound structures that carry neuromodulators such as insulin, dopamine, and serotonin. The peptides within dense-core vesicles are initially larger precursor proteins that undergo enzymatic processing to achieve their functional forms. During the defecation motor program in Caenorhabditis elegans, dense-core vesicles released from the intestine harbor neuropeptides that trigger neurons which activate enteric muscles, promoting the act of defecation. Failure of certain proneuropeptides to mature into neuropeptides results in decreased frequency of defecations. CPD-1, a conserved transmembrane carboxypeptidase, is a poorly understood processing enzyme that affects the defecation motor program. I built on our knowledge of EGL-21, another carboxypeptidase known to process neuropeptides and peptide hormones, to better understand CPD-1’s function. I show here that these two carboxypeptidases, EGL-21 and CPD-1, process neuropeptides necessary for successful defecation patterns. Mutants lacking egl-21 had decreased defecation frequency while worms lacking both egl-21 and cpd-1 had an even lower defecation frequency. Additionally, my results show that CPD-1 is expressed in intestinal cells and can compensate for EGL-21’s function. Finally, I am conducting experiments to determine whether one of CPD-1’s targets is NLP-40, an important neuro-like peptide released from the intestine that regulates defecation. These results contribute to our broader knowledge of peptide processing in dense-core vesicles.

This project seeks to investigate the viability of a multi-channel grating coupler (GC) as an approach for individual ion addressing in ion-trap architectures. A multi-channel design is desirable because it allows for one GC to be used for controllable, individual addressing of many ions. Current approaches for ion addressing include bulky optical systems or single channel GCs which both have notable shortcomings. Optical arrays employing large lens and laser systems require complex, error-sensitive setups, challenging the scalability of those systems. Single channel GCs reduce the complexity and footprint of the optical setup, but they are unsuitable for individual addressing of ions within a chain. Single channel GCs provide the ability to globally address N ions using one integrated structure, or individually address N ions using N integrated structures. Both of these solutions are not optimal as global addressing lacks the specificity required for complex quantum operations, and using one grating structure per ion entails a massive footprint for large ion chains, much larger than the chain itself. A multi-channel GC allows many ions to be individually addressed by one compact integrated structure and, with optimization, multi-channel GCs can achieve high coupling efficiencies and low insertion losses, allowing for accurate and reliable addressing of ions. To design a multi-channel GC for this purpose, we first develop an idealized analytical model by deriving the relationship between the incident angle of guided light into a grating structure and the output angle of diffracted light into free space. Using this analytical model, a conceptual design for a multi-channel GC is formulated. Finally, the GC design is optimized using finite difference time domain (FDTD) simulation software. We will present the results of our idealized analytical model and results from optimization of a full FDTD simulation of our structure.

Liver fatty acid binding protein (FABP1) is highly expressed in the liver, kidney, and gut and is known for its role in binding endogenous lipids. FABP1 has also been shown to bind drugs and modulate metabolism in the liver. A high frequency single nucleotide polymorphism (SNP T94A) in FABP1 is shown to correlate with nonalcoholic fatty liver disease. We hypothesize that this SNP also affects drug binding. To evaluate drug-FABP1 binding, I measure equilibrium dissociation constants (K_ds) by fluorescent displacement assays for both FABP1 wild-type and T94A using two fluorescent probes, 11-(dansylamino)undecanoic acid (DAUDA) and 8-anilino-1-naphthalenesulfonic acid (ANS). FABP1 has a large binding pocket that can accommodate 2 ligands simultaneously in a ‘high affinity’ and ‘low affinity’ binding site. When DAUDA-FABP1 or ANS-FABP1 are titrated with a drug, a drug-FABP1-probe ternary complex is formed rather than the probe being fully displaced. This complicates data analysis and suggests that endogenous lipids may change the affinity of drugs for FABP1. Therefore, I use multiple fluorescent probes with different binding affinity to obtain drug K_d values. I use singular value decomposition (SVD) to isolate individual fluorescent components from the overall observed fluorescence spectra. I then estimate drug and probe K_ds for FABP1 T94A and T94T by fitting the fluorescent change due to binding to dynamic models in COPASI software. From forward and reverse titrations, DAUDA K_d for FABP1 wild-type was found to be 0.194 µM while ANS binds more weakly (K_d = 1.38 µM). From DAUDA displacement assays, diclofenac was found to have a K_d of 3.90 µM for wild-type FABP1 and 3.78 µM for T94A. I anticipate measurement of K_ds for 8 other drugs using both DAUDA and ANS in the coming months. The developed methods will enable evaluation of FABP1’s role in drug disposition.

Wildfires are capable of altering landscapes, devastating forests, and communities, and are increasing in frequency and intensity. However, the hazard extends well past the burn phase as burn scars are at high risk for the generation of debris flows and flooding in the days, weeks, and years after a fire. Conconully, WA, experienced severe post-fire debris flows and flooding in 2022 following the 2021 Muckamuck fire. Witnessing the effects of both the fire and the subsequent debris flow on my community motivated me to explore why these events occur, to investigate how they initiate, and help inform future warnings or mitigation strategies to increase resilience in the face of these hazards. Whether these floods and debris flows were initiated by shallow landslides, or storm runoff remains unknown, and could alter how post-fire hazard or evacuation warnings are issued. In this study, we employ geospatial analysis to identify areas affected by the fire and correlate these with the origins of the debris flows and flooding. Additionally, we use meteorological data and historical records of similar incidents over the past century, to identify thresholds for flooding initiation both before and after fires. By focusing on this topic, we hope to shed light on the long-term consequences of fires on communities and initiate a dialogue about the ongoing risks they face.

Erbium(III) doped cerium oxide nanocrystals are promising candidates for spin qubits in quantum computing and information science applications. Our goal is to tune the synthesis and composition of Er-doped CeO2 nanocrystals for monodispersity and desirable optical properties, particularly the intensity and lifetime of near-infrared emission features unique to Er3+. We optimized previously reported methods for making Er-doped CeO2 by altering the concentration of erbium, presence of water, and the amount of time allowed for the reaction to progress. These nanocrystals were then analyzed using several techniques, including transmission electron microscopy, X-ray diffraction, and photoluminescence spectroscopy. Our results indicated that by omitting water from the synthesis, the sizes of the nanoparticles decreased significantly. Additionally, smaller concentration of erbium(III) dopant in the nanoparticles correlated with a longer lifetime of photoluminescence intensity.

The electron transfer energy and the voltage of solar cells can be changed by tuning the energy band gap of photovoltaic materials. In lead perovskites, this is mainly controlled by the particular halides around lead atoms, with the best materials often having mixed halide compositions. Iodide substitution and identification in lead chloride APOSS perovskites to generate mixed-halide perovskites for control of light absorption in solar cells is creatively proposed in this project. In my previous work, I investigated new methods of bromide substitution and found that highly controlled substitution was achieved by heating copper chloride APOSS perovskites, (APOSS)[Cu₄Cl₁₆ ], in the presence of more stable organic bromides as normal methods, which includes highly reactive liquid bromine or trimethylsilyl bromide. Based on this preliminary research, proper experimental procedure and aims are put forward in this project as follows: lead chloride APOSS perovskite is first synthesized according to the synthesis method of copper chloride perovskite, which has already been published. After that, the iodide substitution is performed by exposing (APOSS) [Pb₄Cl₁₆ ] to a solution of relatively stable organic iodide reagents like carbon tetraiodide or diiodoethane at different temperature and concentration. In order to get more understanding about the substitution process on atom level, NMR and Gas Chromatography are performed to identify where the substituted chlorine atoms go.

The widespread use of makeup raises concerns about bacterial contamination, which can lead to acne, rashes, pink eye, and staph infections. Despite these risks, hygiene practices in cosmetic use, especially in public settings, are often overlooked. This study investigates bacterial contamination in both personal makeup products and in-store testers to assess potential health risks. Swab samples were collected from used personal cosmetics and store testers at popular beauty retailers, focusing on mascaras, foundation bottles, lipsticks, and sponges. Samples were transferred to nutrient-rich media plates, incubated at 37°C for 24–48 hours, and analyzed through colony-forming unit (CFU) counts and Gram staining for bacterial classification. Preliminary results suggest that store testers contain higher bacterial loads than personal products, emphasizing the need for improved hygiene practices in retail environments. These findings could encourage cosmetic brands and retailers to implement better sanitation protocols, such as stricter single-use applicator policies or improved packaging designs, to limit bacterial contamination and promote safer cosmetic use.

In their books Pihkal and Tihkal, Dr. Alexander and Ann Shulgin describe their experiences ingesting 234 psychoactive compounds, most of them newly synthesized by Dr. Shulgin. The goal of this project is to use natural language processing techniques to map the semantic space of the Shulgins’ qualitative comments and determine what commonalities, if any, exist between compounds of similar molecular structures. I first created a TF-IDF matrix to determine the importance of each word for each compound. I then applied three clustering techniques (k-means, DBSCAN, and affinity propagation) to group compounds based on their meaning and used UMAP after each technique to graph the clusters in two dimensions. Unfortunately, despite attempting different combinations of pre/post processing and hyperparameter tuning, each method resulted in only weakly associated clusters. My next analytical method is using Sentence-BERT modeling to compare the semantic meanings at the sentence level. Since sentences hold more meaning than single words, I anticipate that this technique will differentiate the compounds to a greater extent, therefore leading to more visibly divided clusters. I also have the compounds clustered by similarity in molecular structure and determined the most common words associated within each group. By quantifying the subjective experiences of these psychoactive compounds and mapping them to molecular structures, this knowledge could allow us to synthesize molecules to obtain a desired effect on a patient’s consciousness. This could in turn aid in synthesizing new medications to treat mental health disorders.

This investigation is based on the famous intermediate axis theorem, often called the tennis racket theorem. This theorem describes why objects with three distinct moments of inertia, around three different axes, have an unstable rotation around the intermediate axis (the axis with the intermediate moment of inertia) while the axes that have the largest and smallest moment of inertia have a stable rotation. This phenomenon can be observed in rotations of everyday objects like tennis rackets and phones. By videotaping rotations of different objects with three distinct moments of inertia around three axes, and visually examining the intermediate axis, one can notice the instability of the intermediate axis compared to the stability of rotations about the other two axes. We mathematically analyzed the motion around three axes using Euler’s equations of rotations, the equations governing the dynamics of a rigid body undergoing rotational motion. We solved the differential equations demonstrating the instability around the axis with the intermediate moment of inertia. This behavior was also simulated in MATLAB using Euler’s equations of rotations. Our graphs of velocity as a function of time for rotation around the three axes, demonstrated and justified the visual observations from the videos. These experimental and computational approaches can lead students to a comprehensive understanding of the intermediate axis theorem.

Formalization is the process of translating human-written mathematical proofs into a form that can be verified by a computer. A popular tool for this is Lean, a proof assistant that represents proofs as code. However, the process of formalizing proofs in Lean can be slow and time-consuming. Our research explores so-called "autoformalization" strategies, which aim to automate the generation of Lean proofs. We propose a tree-based search framework to formalize mathematical theorems in Lean using Language Models. This approach explores potential proof steps as branches in a tree, using AI models to suggest "tactics" at each node. This has the benefit of avoiding hallucinations by rigorously checking that AI suggestion represent valid Lean code. We employ both Large Language Models such as Claude Sonnet 3.5 and specialized fine-tuned Small Language Models such as Lean-Dojo. We use Pantograph to interact with Lean, leveraging its native support of Monte Carlo tree search. We assemble a small set of simple and medium-difficulty mathematical theorems to benchmark against, called nanoF2F. Additionally, we benchmark our system on the well-established miniF2F benchmark created by OpenAI.

Manduca sexta is a model lepidopteran insect organism which has been widely used in the field of chemical ecology due to its impressive olfactory senses. Odorant reception plays an important role in locating nectar sources, mating, and ovipositioning. Insects detect volatile chemical compounds (VOCs) present in their complex environment primarily through their sensory organ antenna. Each antenna is made up of thousands of olfactory receptor neurons (ORNs) and each neuron detects specific odor molecules with specific odorant receptor proteins. The whole genome sequencing of Manduca sexta has identified the major chemosensory receptor proteins: odorant (ORs), ionotropic (IRs) and gustatory (GR) but the role of each receptor is still unclear. In this project, we are investigating the role of female-biased odorant receptors OR5 and OR6, which might be involved in detecting VOCs present in their environment and play an important role in mating and oviposition. To investigate the role of these ORs, we have generated mutant strains by using a CRISPR/Cas9 approach and we are checking their effect on odor detection and oviposition behavior by comparing them with wild type strains. We are also performing an RNA-FISH experiment to visualize the ORs and locate the olfactory sensory neurons in the female antennae. In addition to this, we are also working on developing a neurogenetic tool which will allow us to measure the neuronal activity in response to different olfactory stimuli by generating a pan-neuronal BRP-GCaMP6s transgenic line.

Social expectations are constantly changing, and even subjects typically considered “taboo” are changing as well. Though sex is often seen as a private, maybe even secretive, discussion, this lack of public eye to the true nature of sex can lead to many difficulties in an individual's personal and intimate life through misunderstandings and social expectations. This literature review focuses on possible correlations between behavioral sex therapy treatment (such as guided open communication, and sensate focus) and aspects of unsustainable romantic relationships (such as stonewalling and criticism). Some sexual dysfunctions can arise from emotional difficulties, such as anxiety during or before sexual encounters, lack of enjoyment from one or both partners, or different perceived ideas of what is supposed to happen during sex. These difficulties can translate into daily life in the relationship outside of sex. By treating these dysfunctions there may be a domino effect which impacts the relationship outside of sexual relations, which can improve the relationship overall and lead to a relationship that is more sustainable for all parties involved. Through comparisons of articles on treatments typical in behavioral sex therapy and articles defining aspects of unsustainable relationships, like those published by John Gottman, initial findings support connections between the topics. These positive correlations indicate an innate connection between sexuality and relationships, which could lessen the social stigma that surrounds discussing sex or sexual topics

All mammals experience a slowdown of cardiac pacemaker rate with aging. The main mechanisms to explain that phenomenon are related to alterations in the ionic currents that underlie the diastolic depolarization phase of the action potential. We have previously reported that pacemaker cells from old mice have reduced L-type calcium currents. We further explore the mechanism underlying that reduction, testing cell hypertrophy and alteration in the scaffolding of L-type calcium channels as potential mechanisms. To test for cell hypertrophy, we combined immunostaining and high-resolution imaging to map the HCN4-positive pacemaker region of isolated upper heart explants from young and old mice. We compared cell length, width, and area between young and old cells. We also determined these morphological parameters in HCN4-positive enzymatically dissociated pacemaker cells. We found no significant difference in cell dimensions or area between ages, ruling out hypertrophy as a potential mechanism. We used mass spectrometry to identify expression changes in scaffolding proteins essential for calcium channel organization at the plasma membrane. Through this approach, we identified a large reduction of caveolin 3 as a possible mechanism. Caveolin is a protein essential to forming signaling microdomains between calcium channels and other proteins. Using western blotting, we confirmed a 50% reduction of caveolin 3 in isolated pacemaker tissues from old animals. Using proximity ligation assay and super-resolution microscopy, we showed altered recruitment of L-type calcium channels into caveolae. Our findings suggest that the age-associated decrease of L-type calcium current is caused by a reduced insertion of these channels in caveolae.

The heart's primary function is to pump blood to supply oxygen and nutrients to the body. The biomechanical principles of the heart are determined by specializations at the organ, tissue, cellular, and molecular levels. Little is known about how these specializations have adapted to sustain high heart rates in animals with extreme biology, as is the case of the hummingbird, whose heart rate above 1000 bpm makes it the endotherm with the highest heart rate observed in nature. We hypothesize that the hummingbird heart has evolved several adaptations at all the abovementioned levels to i) generate fast firing rates, ii) optimize electrical-contraction coupling, and iii) sustain fast contraction-relaxation cycles. Using different histological and imaging approaches, we have started to characterize the architecture of the hummingbird’s heart for the first time in a research lab. To describe the overall dimensions and structure of the hummingbird heart, we generated CT scans and 3D reconstructions of iodine-labeled Calypte anna hummingbird hearts. To characterize the organization of the tissue, we present data using hematoxylin-eosin and lectin stainings in fixed paraffin-embedded slices of the hummingbird heart. Our preliminary results showed that hummingbird ventricles have a cell density of 110 cells per 5000 µm2, around 7-fold larger than mouse ventricles. Ventricular cells in the hummingbird are 8-fold smaller with a cross-sectional area of 41 ± 4 µm2. Hummingbird hearts also have a higher capillary density with 18.0 ± 0.6 capillaries per 2500 µm2. Our results provide a foundation for structural and functional characterization of the hummingbird heart at an organ, tissue, and cellular level while opening avenues for further investigation of extreme cardiac physiology.

In vivo genome editing of hematopoietic stem cells (HSCs) offers a promising approach for treating hemoglobinopathies and HIV/AIDS. The Lieber Lab has developed helper-dependent adenoviral (HDAd) vectors that preferentially transduce primitive HSCs in mobilized CD46-transgenic mice, humanized mice, and rhesus macaques following intravenous injection. However, off-target transduction (including other blood cell lineages and various organs) remains a critical challenge, potentially compromising safety. Moreover, the comparison of PGK and the relatively strong Ef1α promoters revealed that the editor expression level influences editing outcomes, especially in multiplex editing approaches. To address these limitations, the project’s goal is to engineer a highly active HSC-specific promoter that maximizes on-target gene editing while minimizing off-target effects, improving both the safety and efficacy of HDAd-based therapies. I first generated GFP reporter plasmids containing roughly 2 kb of proximal promoter sequence from five genes highly expressed in HSCs: CD164, cKit, DSG2, PROM1, and PROCR. These constructs were introduced into human CD34⁺ cells via nucleofection, and the cKit and PROCR promoters showed the strongest GFP expression in the HSC-enriched (CD34⁺/CD45RA⁻/CD90⁺) subset. To further enhance promoter activity, we linked the top-performing promoters to distal HSC enhancers that, according to ENCODE/Hi-C analyses from Dr. David Hawkin’s Lab, regulate cKit (2 enhancers), CD164 (4 enhancers), and PROM1 (2 enhancers). Engineered promoter-enhancer constructs yielded 3- to 4-fold higher GFP expression than Ef1α in CD34⁺/CD45RA⁻/CD90⁺ cells, with the cKit promoter + CD164-3 and PROM1 enhancers showing the highest activity. Building on these findings, we have incorporated these HSC-specific promoter–enhancers into helper-dependent adenoviral (HDAd) vectors driving an ABE8e-base editor for γ-globin reactivation. Ongoing work is focused on evaluating the specificity and efficacy of these HDAd vectors in humanized mice and CD46/βYAC-transgenic mice, with the ultimate goal of achieving safer, more effective in vivo genome editing in HSCs.

Acetylcholine (ACh), a neurotransmitter known for its roles in neuromuscular function and cognition, has recently been implicated in immune regulation, particularly in the context of Type-2 immunity. The Type-2 response combats parasites at mucosal and cutaneous sites and plays a role in allergic diseases like asthma and food allergy. In the intestine, Type-2 inflammation involves a dramatic remodeling of the intestinal epithelium via the activation of intestinal epithelial stem cells (ISCs), which results in the hyperplasia of specialized effector-like secretory cells such as goblet and tuft cells. These epithelial cells then produce factors that talk back to the epithelium, such as Ach, and factors that promote Type 2 immune responses, such as the cytokine interleukin-25. Tuft cells are the only intestinal epithelial cells that express choline acetyltransferase, the enzyme for ACh synthesis. Recent work suggests that during helminth infection, tuft cells release ACh in response to IL-13 signaling, implying a role for ACh in regulating epithelial responses. However, its specific function in epithelial remodeling and Type-2 immunity remains unclear.This project aims to investigate ACh’s epithelial intrinsic role in Type-2 immune responses using an in-vitro enteroid model of the intestinal epithelium. Enteroids, 3-D cultures derived from stem cells, model the epithelium without immune cells, allowing for a focused examination of epithelial-intrinsic factors in immune responses. By culturing and treating enteroids from wild-type and tuft cell-deficient mice with ACh, we will assess its effects on goblet cell proliferation, inflammation, and stem cell renewal during injury regeneration responses. I hypothesize that ACh enhances the pro-Type-2 inflammatory response in enteroid epithelial cells, leading to heightened immune activity. This research will advance our understanding of the neuro-immune axis in the gut and may have implications for parasitic infections and allergic inflammation.

Stiffness measures derived from MR Elastography have shown value in guiding treatment decisions and monitoring effectiveness of therapies for liver disease but it requires extra hardware, longer scan duration and is susceptible to motion and breathing artifacts. Recent studies have revealed a strong linear correlation between water diffusion and tissue stiffness, demonstrating that Diffusion Weighted MRI (DWI) can be used to estimate stiffness values in liver tissue. DWI-derived stiffness values may help evaluate treatment-induced changes in breast cancer but to our knowledge, this has not yet been tested. The purpose of my ongoing study is to calibrate DWI estimates of tissue stiffness for the breast by optimizing DWI parameters (diffusion weightings, or ‘b-values’) and  calibration coefficients (a, b), evaluating the potential of stiffness measures for monitoring response to neoadjuvant chemotherapy (NAC) in breast cancer. We collected baseline and early treatment MRI exams from 25 patients undergoing NAC in this IRB approved study along with their treatment outcomes based on pathologic response post completion of NAC. I evaluated  the stiffness values obtained from different b-value pairs (low b-values: 100/200; high b-values: 800,1500,2000 s/mm²) and calibration coefficients(a,b=-9.7,13.9:-10.8,17.5:-8.8,21.2) and compared it to the invasive breast cancer stiffness values reported in literature. I also evaluated the performance of the optimized parameters to predict treatment response. The optimal b-value pairing (b=200,1500s/mm²) and coefficients a=-9.7,b=13.9 produced stiffness values consistent with literature. Using this approach, the performance for predicting treatment outcomes between responder and non-responder groups was AUC=0.84. These preliminary findings suggest that DWI based virtual elastography could serve as a non-invasive tool to assess tumor stiffness and track treatment efficacy, potentially improving breast cancer management.

Aquacultures are an environmentally responsible way of breeding and harvesting a variety of marine organisms. Challenges to aquacultures include the introduction of nonnative pathogens and parasites to wild fish as well as intense changes to the physical environment. Monitoring the environment for impacts of aquaculture is costly and time-consuming, so finding a cost-effective rapid monitoring solution is important. This project tests the feasibility of monitoring the diversity of meiofauna species present in the sediment via DNA sequencing. Meiofauna species are marine organisms between 0.06 mm and 1 mm in size that live in marine sediment. DNA sequencing is quicker and cheaper than current monitoring practices, and since changes to the physical environment affect meiofauna species diversity, observing the change in species diversity is a potential alternative to monitoring aquaculture health. Through samples taken before and after the introduction of a sablefish net pen aquaculture, analysis of both physical sediment samples and meiofauna samples will determine the feasibility of implementation. By looking at the total organic carbon content and grain size distribution of the sediment samples, we can determine the physical changes to the environment caused by aquaculture. Suppose the DNA sequencing results show shifts in species diversity that match the physical changes. In that case, we can confirm there is evidence supporting the feasibility of implementing monitoring via meiofauna DNA sequencing. 

Fluoride intake is essential for dental health, yet excessive consumption can lead to fluorosis, a condition negatively affecting teeth and bones. Tea, one of the most widely consumed beverages globally, naturally accumulates fluoride, making it a significant but often overlooked dietary source. Black tea is the most popular type of tea consumed in the U.S. In this study we compared fluoride levels across six brands of black tea and investigated how brewing conditions and water sources affect fluoride concentrations in tea. We brewed black tea from six locally popular brands (Lipton, Tazo, Fortnum & Mason, Twinings, Tetly, and Harney & Sons), using two water sources (distilled water and Seattle tap water), with four samples for each brand using both water sources. We brewed 50 mL of water at 100°C, then we let each sample of the tea sit for 5, 10, and 20 minutes. Ion chromatography was used to measure fluoride concentrations at each time interval. We compared these values to the U.S. Environmental Protection Agency's (EPA) recommended fluoride level of 4.0 mg/L. Our results help characterize the variation between brands and the influence of brewing duration on fluoride release. These findings contribute to a better understanding of fluoride exposure from tea consumption, helping consumers make informed choices about their dietary fluoride intake.

Beaver dams can function as natural filters helping decrease pollution in streams, creeks, and rivers. Beaver dams slow down the water flow in a creek or river, forming ponds that help trap excessive nutrients. An excess of nutrients such as phosphate and nitrate can cause eutrophication, leading to increased algal blooms that can produce toxins and ultimately deplete oxygen in the water. This study investigates the ion levels of chloride, fluoride, phosphate, nitrate, sulfate, and bromide upstream and downstream of the major beaver dam at Pipers Creek in North Seattle's Carkeek Park over the course of a year to better understand the long-term impacts of the dam. We collected three water samples at each of eleven sites along the creek, eight upstream from the dam, and three downstream. Ion chromatography was used to measure the concentrations of anions at each site. The results of this study help elucidate the role of beavers in moderating water quality and provide important baseline data documenting seasonal variations in the nutrient load at Pipers Creek. These findings can also be used to better understand the impact of new beaver dams in other freshwater systems.

Low-income communities are often disproportionately exposed to air pollution. High concentrations of pollutants such as particulate matter under 2.5 µm (PM2.5) and human aerosol emissions, including carbon dioxide (CO2), have been linked to various health and cognitive issues. Performance arts, including singing and playing instruments, produce human aerosol emissions and are considered high risk for airborne disease transmission. Our study evaluated the accumulation of CO2 and PM2.5 in high-risk environments (band classrooms) in low-income public schools in King County (WA), to determine whether there is a correlation between accumulation rates and Title 1 designation. Title 1 designation, which provides government funding for schools with a high percentage of students from low-income households, was used to represent low-income communities. We compared four middle schools that qualified for Title 1 designation to one school that did not qualify. Concentrations of CO2 and PM2.5 were measured using the Aranet4 Home CO2 sensor and a PurpleAir Classic sensor for PM2.5. We took a baseline measurement of both concentrations when the classroom was unoccupied. We then analyzed the change in concentration rates when classes were in session, taking into account classroom size and number of students. Our data showed concentrations above recommended levels at 1,370 ppm (parts per million) for CO2 in one of the Title 1 schools suggesting that Title 1 schools may be at greater risk of poor indoor air quality, though additional studies are needed. This additional exposure to pollutants and human aerosol emissions in already high-risk environments like band classrooms may lead to increased airborne disease transmission, highlighting the disparity in healthy learning environments. These classrooms require additional measures to maintain healthy concentrations of CO2 and PM2.5 to reduce the risk of airborne disease transmission particularly in low-income communities. 

Safe drinking water in schools is crucial for children's safety and academic performance. While Seattle Public Schools has tested for some contaminants, such as lead, the district's responsibility for ion-specific testing for anions such as phosphate, bromide, nitrite, nitrate, chloride, sulfate, and sulfite is less clear. High concentrations of anions pose potential health risks, including reduced oxygen in red blood cells, higher risks of tumors in children, and diarrhea. This research investigated the anion concentration in water fountains across seven high schools in the Seattle Public Schools. Twenty-one water samples were collected from seven public high schools and analyzed for anion concentration using ion chromatography. Results were compared to the Environmental Protection Agency's (EPA) maximum contaminant level (MCL). All test samples were below the EPA's MCL. These results suggest that the drinking water in these schools does not pose potential risks to students from anion contamination. While regular monitoring and management are still necessary to maintain safe drinking water, Seattle Public Schools have met the safety requirements for anion concentration in their drinking water. 

As individuals experiencing homelessness age, their healthcare needs become increasingly complex. People over age 50 are the fastest-growing group experiencing homelessness, yet there is little knowledge about specific subgroups, particularly older homeless veterans. The aim of our study was to explore the experiences of older veterans and non-veterans experiencing homelessness, with a focus on contextualizing the unique barriers to accessing healthcare and maintaining stable housing in each group to better understand how these factors impact healthy aging. Using a qualitative research design, we developed a semi-structured interview guide in collaboration with key informants from Compass Housing Alliance. We recruited participants aged over 50 who have recently exited homelessness and are living in Permanent Supportive Housing (PSH). We conducted forty-five-minute interviews with veterans (6-10 participants) and non-veterans (6-10 participants). The questions focused on daily living, work, healthcare, connection & community, access to structural support services, and perceived impact on aging well. We recorded and transcribed these semi-structured interviews, which we coded to identify key themes. Additionally, all participants completed a basic survey to capture demographics such as length of time homeless, age, and gender. After the initial thematic analysis, we had a second session with participants to check the accuracy of the identified themes. The qualitative approach of this study provides new data directly from those with lived experience. This study offers critical insights into the unique challenges faced by aging veterans in comparison to non-veterans in PSH, exploring gaps in healthcare access, limitations of healthcare services, and the role of housing stability for older adults. This research is significant to policymakers, healthcare providers, and housing organizations seeking to tailor support to the heterogeneous groups within the aging homeless population.

Antibiotic resistance is an increasingly critical concern for the treatment of bacterial infections, rendering new therapy options progressively more necessary. Gram positive bacteria are common infectious agents in skin and soft tissue infections, pneumonia, urinary tract infections, bacteremia, and more. A novel antibiotic candidate, MRS-2541 has been demonstrated to inhibit Gram positive methionyl-tRNA synthetase and decrease bacterial loads of both methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes in mouse thigh infections to the same degree as currently recommended therapy. This study aims to further characterize the activity of MRS-2541 against Gram positive bacteria including Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus lugdunensis, Staphylococcus saprophyticus, Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus salivarius. I conducted this study by first determining the preliminary minimum inhibitory concentration of MRS-2541 in growth media against each of the aforementioned organisms. I then use these results to guide time kill assays that characterize MRS-2541’s synergy with another antibiotic often used to treat Gram positive infections outside of the United States. Preliminary results demonstrate that MRS-2541 inhibits the above-mentioned organisms. Synergy experiments with MRS-2541 and existing antibiotics will be performed and results will be presented at the symposium. These results will further define the spectrum of activity as well as synergy of MRS-2541, allowing new insight into its candidacy for clinical trials. As a novel antibiotic candidate, the development of MRS-2541 will help address the increase in antibiotic resistance among Gram positive bacterial infections.

The angiopoietin-Tie2 signaling pathway is central to regulating vascular stability, remodeling, and permeability. Angiopoietin-1 (Ang1) promotes pAKT activation and vascular stability and regeneration, whereas Ang2 antagonizes these effects, leading to leaky vasculature. Although Tie2’s association with α5β1 integrin has been implicated in mediating these divergent outcomes, the requirement of direct F-domain ligand binding for integrin recruitment remains unclear. Here, we report the development and mechanistic evaluation of a de novo designed Tie2 mini binder (Tmb) that selectively targets the Tie2 receptor without engaging α5β1 integrin. Using an AI-based protein design pipeline, we designed Tmb with high affinity (KD ≈ 0.65 nM) for Tie2, as confirmed by CryoEM analysis, which demonstrated that Tmb accurately recapitulates its designed structure. When conjugated to multivalent scaffolds, Tmb effectively clusters Tie2 receptors, recapitulating the signaling profile of native Ang1. Notably, high valency Tmb constructs (e.g., H8T) robustly activated pAKT and induced nuclear FOXO1 exclusion, mirroring the pro-survival and vascular stabilizing effects of Ang1, despite lacking the capacity to bind α5β1 integrin directly. Detailed cellular assays revealed that Tie2 clustering leads to the formation of two distinct complexes: a Tie2–α5β1 integrin complex that facilitates focal adhesion assembly and cell migration via pCAS recruitment, and a Tie2–tight junction complex (comprising ZO1, claudin-5, and occludin) that underpins vascular barrier integrity. Importantly, competitive binding studies demonstrated that integrin recruitment to the Tie2 complex does not require direct F-domain engagement. In human iPSC-derived diabetic blood vessel organoids, treatment with Tmb-based Tie2 agonists ameliorated diabetic vasculopathy phenotypes by reducing pathogenic collagen IV deposition, restoring tight junction organization, and lowering nuclear FOXO1 levels. These findings provide novel insights into the mechanistic interplay between Tie2, integrin, and junctional proteins, and underscore the therapeutic potential of synthetic Tie2 agonists in vascular repair and diabetic vasculopathy.

Obesity is linked to reproductive dysfunction through defects in the hypothalamic-pituitary-gonadal (HPG) axis that arise by unknown mechanisms. Importantly, rodents fed a high-fat diet (HFD) develop similar hypogonadism and reduced ovulatory capacity. During HFD feeding, CNS immune cells (microglia) become activated in the hypothalamus, promoting inflammation, and altering neuronal function indirectly and via cell-cell contacts. Surprisingly, however, genetic ablation of this microglial inflammatory response exacerbates rather than improves HFD-induced HPG axis dysfunction including altering the activity of hypothalamic neurons that express the key reproductive neuropeptide GnRH. Therefore, we hypothesized that increased microglial inflammatory signaling during HFD feeding helps maintain GnRH neuron integrity. To test this hypothesis, we used immunohistochemistry (IHC) to assess microglia-GnRH cell-cell interactions in the hypothalamus of 15-week HFD-fed female mice with microglia-specific deletion of IKKβ (IKKβ-MGKO), a critical regulator of the inflammatory NF-κB pathway. IHC studies using GnRH and Iba1 (microglial marker) revealed fewer cell-cell contacts between GnRH neurons and microglia in the preoptic area of the hypothalamus (POA) of IKKβ-MGKO mice compared with controls. In addition, we found that IKKβ-MGKO mice have reduced levels of Iba1 and total numbers of microglia but no changes in microglial cell morphology as determined by Sholl analysis. These findings suggest that HFD-induced microglial inflammatory signaling promote cell-cell interactions with GnRH neurons that may contribute to maintenance of HPG axis integrity and female reproductive function during diet-induced obesity.

Despite the development of effective COVID-19 vaccines, countries with high rates of HIV infection still have limited vaccine access and inadequate access to antiretroviral medications essential for controlling HIV. Studying COVID-19 vaccination in people living with HIV (PLWH) is needed to improve vaccination strategies in immunosuppressed populations. Previously, in pigtail macaques (PTM) we showed that COVID-19 repRNA vaccination elicits durable and protective immunity against SARS-CoV-2 infection. Here we utilized the simian immunodeficiency virus (SIV)-infected PTM model of HIV/AIDS to test the hypothesis that COVID-19 repRNA vaccination is less durable during immunosuppression. Nine PTM were enrolled into the SIV naive (n=4) and experimental SIV-infected (n=5) cohorts. SIV-infected PTM were infected with 10,000 units of SIVmac293M seven weeks prior to the first vaccination. All PTM were given 2-4 COVID-19 repRNA immunizations, encoding the SARS-CoV-2 WA.1 Spike protein, to reach maximal immunogenicity and monitored for 26 weeks for vaccine durability. Vaccine recall was evaluated by administering a booster immunization after immunity responses waned. Blood and bronchoalveolar lavage samples were collected every 2-4 weeks. SIV-infected animals were monitored for SIV disease progression, including measuring CD4 counts in peripheral blood. Enzyme-linked immunosorbent assays (ELISAs) were used to quantify longitudinal Spike-specific binding IgG antibodies. Preliminary data shows that COVID-19 repRNA vaccination elicited robust anti-Spike IgG antibodies in both PTM groups, with diminished responses in some animals within the SIV-infected group.  Anti-SARS-CoV-2 neutralizing antibodies were also generated in both groups and interestingly, more durable in SIV-infected animals. Ongoing analysis includes evaluation of IgM and IgA binding antibodies. Collectively, this study suggests SIV-associated immunosuppression impacts vaccine-induced humoral memory, which could, in turn, impact long-term protection from COVID-19. These findings are crucial for improving vaccine regimens for PLWH and other immunosuppressed individuals.

Duchenne Muscular Dystrophy (DMD) is a severe neuromuscular disease caused by mutations in the dystrophin gene and characterized by progressive muscle wasting. Dystrophin protein is essential for the stabilization of muscle fibers; without it, continuous muscle damage eventually has devastating consequences in the skeletal, cardiac, and respiratory systems. While prior AAV-mediated editing strategies have been effective in targeting these mutations, there are significant immunological concerns from the uninterrupted expression of bacterial gene editing components. This project utilizes the mdx mouse model of DMD to address these concerns by developing methods to turn gene editing on and off using novel drug-responsive pA regulator vector constructs. I have been part of this project from the start, contributing to the assembly of the expression constructs using bacterial cultures and standard cloning techniques relying on restriction enzymes and high-fidelity cloning kits to piece together our editing constructs. Initial data was acquired from cell culture tests where I helped perform quantitative dual-luciferase reporter assay analyses. Subsequent in vivo experiments were performed by delivering adeno-associated viral vectors, carrying our constructs, into mdx mice via retro orbital injection. Activation of editing activity was achieved via three intraperitoneal injections of Tetracycline.  During analyses, I played a significant role in processing muscle tissues to extract proteins, DNA, and RNA for quantitative assays. Ultimately, our cell culture tests identified two lead pA regulator sequences exhibiting favorable activation levels at therapeutically relevant Tetracycline doses. Initial in vivo tests are promising, showing drug responsive editing and dystrophin expression in mice. We anticipate that our follow up tests will restore sufficient dystrophin expression and improve muscle function, without persistent editing activity. Overall, the outcomes of these studies could have significant implications for a multitude of genetic conditions amenable to genome editing and may help accelerate translation of effective methods towards clinical trials.

Viral evolution theory hypothesizes that specialist strategies increase fitness by reducing interspecific competition, while generalist viruses increase fitness by accessing multiple hosts. However, specialism may come at the cost of infecting few hosts, while generalism may reduce fitness in any single host. These tradeoffs have been demonstrated in Infectious hematopoietic necrosis virus (IHNV), an aquatic rhabdovirus infecting multiple salmonid species. High rates of viral replication have been observed for specialized subgroups in their respective hosts, while lower rates of replication across multiple hosts have been observed for the generalist subgroup. However, the host-virus mechanisms underlying these replicative differences are unknown. Here, I aim to characterize the early innate immune response of sockeye salmon, the ancestral host of IHNV, to specialist and generalist subgroups at target tissues. Specifically, I seek to test whether sockeye salmon display distinct transcriptomic responses to IHNV specialist and generalist subgroups in the kidney 2 days post-exposure (dpe). To accomplish this goal, RNA was extracted and sequenced from kidney tissue of individuals 2-dpe following exposure to specialist (n=9), generalist (n=9), or control (n=4) IHNV treatments. Overexpressed and underexpressed genes will be identified between each subgroup and control samples. These genes will then be used for pathway enrichment to compare differences in transcriptomic response. Replicative rates have shown a difference between specialist and generalist subgroups of IHNV 2-dpe in the kidney; therefore, we expect to observe differences in the number and magnitude of over- or underexpressed genes and enriched pathways between hosts exposed to specialist and generalist subgroups. Results from this study will aid in characterizing evolutionary mechanisms underlying viral specialism and generalism, understanding host innate immune response and evasion strategies, and identifying biological markers associated with response to viral exposure. This knowledge will be critical in predicting future disease outbreak and informing disease mitigation strategies.

Protein subunit vaccines are highly used today as an alternate vaccine platform to older vaccines such as live-attenuated viruses. They contain a protein antigen of the virus or bacterium that can be recognized and targeted by the immune system, and an adjuvant that amplifies the immune system response to this protein by widely putting the immune system on alert. The most commonly used adjuvants pose the risk of possible adverse reactions and are not created to target specific immune pathways, but rather stimulate general inflammation. To design a vaccine adjuvant that generates a more targeted immune response, we are using the self-assembling protein nanoparticle, I53-dn5, to display a CD40 binder that mimics the T Cell ligand, CD40L, by binding to B cell surface receptor CD40. We aim to create a particle that can replicate the binding interaction between B and T cells in the lymph node responsible for triggering antibody maturation, and B cell proliferation and differentiation. We hypothesize that this multivalent display of CD40 binder will generate potent B cell responses allowing us to respond to an antigen more effectively than current adjuvants. We are utilizing computational protein design methods like RFDiffusion, ProteinMPNN, and AlphaFold2 to optimize this display, and testing these designs in vitro for stability and ability to elicit downstream signaling effects of the CD40/CD40L interaction. This research holds two promising innovation potentials. The first is creating higher potency adjuvants by stimulating specific signaling pathways for use with protein subunit vaccines. Secondly, these materials can be used as a more stable and potent molecule in biochemical assays such as being an alternative to feeder cell lines in B cell support culture.

Over a hundred years after the Spanish Flu, the influenza A virus (IAV) remains a leading cause of respiratory infections and mortality worldwide. The proliferation of IAV causes many of the symptoms associated with IAV clinical disease. However, the severity of acute lung injury (ALI) from IAV is primarily driven by the host's immune response to infection. The mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated protein kinase (ERK) signaling cascade is a highly conserved pathway that is activated during lung injury and inflammation in both rodents and humans. Two MEK isoforms, MEK1 (Map2k1) and MEK2 (Map2k2), activate downstream effectors, ERK1 and ERK2, and control critical cellular processes, including the intensity and duration of inflammatory signaling. Our prior research revealed that MEK2-deficient mice exhibited improved weight recovery and overall fitness during IAV infection, suggesting that MEK2 is a host response exacerbating ALI during IAV infection. During IAV infection, excessive pro-inflammatory cytokine production drives immune cell recruitment into the lungs, leading to collateral tissue damage that impairs organ function and exacerbates disease. We hypothesize that MEK2 enhances immune cell recruitment to the lungs, enhancing inflammation, which may occur through exuberant chemokine signaling. To investigate this, we infected MEK2-deficient and wild-type mice with mouse-adapted IAV (H1N1, PR8) and collected cells from bronchoalveolar lavage (BAL) and lung homogenates. Using flow cytometry, we found reduced immune cell recruitment, including decreased numbers of monocytes, dendritic cells, monocyte-macrophages, CD4+ T-cells, CD8+ T-cells, and B-cells. Next, we assessed levels of key chemokines known to attract monocytes and lymphocytes by measuring their gene expression in the lungs and protein levels in the BAL. Investigating MEK2’s impact on chemokine signaling will elucidate the mechanism by which MEK2 perpetuates lung inflammation and injury during IAV infection and will guide the development of future host-directed therapies for IAV-induced lung damage.

The timing of flowering in Arabidopsis thaliana is tightly regulated by environmental cues that induce the expression of FLOWERING LOCUS T (FT), a mobile signal responsible for floral induction. Recent studies have identified FPF1-LIKE PROTEIN 1 (FLP1), a gene co-expressed with FT in phloem companion cells, as a potential regulator of flowering. Given FLP1’s genetic similarity to known flowering regulators, we hypothesize that it functions as a mobile flowering-promoting signal. Using predictive protein interaction modeling with AlphaFold 3, followed by Bimolecular Fluorescence Complementation (BiFC) and Yeast-Two Hybrid assays, we confirmed that FLP1 interacts with key proteins in the shoot apical meristem. Overexpression of FLP1 leads to early flowering in Arabidopsis, while loss-of-function mutants exhibit delayed flowering, supporting its role in floral induction. Interestingly, while FLP1 homologs generally promote flowering across species, a contrasting effect in Brachypodium distachyon has been observed, where overexpression of its homolog (BdFLP1/BdFLP7) delays flowering. This unexpected result raises critical questions about the molecular basis of functional divergence among FLP1 homologs. To investigate this, we are introducing BdFLP1 and BdFLP7 into Arabidopsis to assess their effects on flowering time and to determine whether structural differences or distinct protein interactions underlie their divergent functions. Through molecular cloning, transgenic expression analysis, and biochemical assays including western blotting, immunoprecipitation, and mass spectrometry, we aim to elucidate the role of FLP1 and its homologs in flowering regulation. Understanding these mechanisms will provide deeper insights into conserved and species-specific pathways controlling floral induction. This knowledge is essential for improving crop adaptation strategies in the face of climate change, highlighting the broader significance of our research in plant developmental biology.

Essentialist beliefs about gender modality, which conceptualize being transgender as an inherent and unchanging aspect of an individual, stand in contrast to perspectives that emphasize the social construction and fluidity of gender identity. These contrasting beliefs about the transgender identity are meaningful, as they shape the attitudes and behaviors among and towards trans individuals, who historically and currently face discrimination. To understand how trans people make sense of both cisgender and transgender individuals’ beliefs about the trans identity, I am conducting 12 semi-structured interviews with University of Washington students ages 18-25 who identify as transgender and/or non-binary. I analyze how specific assumptions, expectations, and cognitive worldview perspectives impact experiences and identity formation through a double consciousness perspective, a concept that has adapted from the writings of W.E.B. Du Bois about the impacts of racism. Double consciousness is an instinctive social awareness to uphold two identities, one that is “true” to oneself, and one that is constructed to conform in accordance to societal expectations in an act of self-protection. This can lead to feelings of inauthenticity and loneliness in a society that has rigid expectations for how gender should be represented. Therefore, certain assumptions and essentialist explanations about the social category of transgender, may motivate trans people to hold an additional social awareness to anticipate how cis people will react to their identities under the cis gaze. My data provides insight into the forces behind trans prejudice and offers transphobia mitigation recommendations, while centering transgender and non-binary voices in the research. Additionally, this research provides theoretical contributions, important for understanding the processes motivating essentialism and double consciousness. I conclude with directions and suggestions for future research.

According to the CDC report in 2022, Indigenous women experience 58% of intimate partner violence cases, which is one of the primary causes of homicide. The Reauthorization of the Violence Against Women Act (VAWA) has been credited for expanding protections for Indigenous women. This included increasing the provision of crimes under Tribal Jurisdiction and creating a pilot program for Alaskan Natives to prosecute non-Native offenders in villages. However, this policy reveals a gap between written law and people's experiences. This study examines the effectiveness of VAWA strategically, what demands were left out, and what those gaps represent in demanding changes through intersectional advocacy. In this qualitative research, I created a codebook to analyze the VAWA Congressional hearings from 2009 to 2022 to track the evolution of policy reforms from Indigenous activists. Applying a high-level textualized analysis by gathering a literature review, I utilized the framework of intersectional advocacy, which identifies the extent to which laws and interventions can create meaningful linkages across issues experienced by multiple marginalized people. VAWA remains to be a product of limitations in representation and holistic change to advance the needs of Indigenous people. Expected findings suggest that future policy reforms move beyond analyzing the issue through the lens of individuals to a community-based perspective. Intersectional frameworks will become a cornerstone of future policy work by propelling conversations centered around restorative well-being and healing. Creating bridges between people's lived experiences and legal institutions is foundational to creating critical correspondence. 

Injustice has permeated the criminal legal system and its punitive regime for as long as this society has existed. The rapidly expanding American carceral state arose from a myriad of retributive policies and legislation that became prevalent throughout the last quarter of the twentieth century. There is currently an abundance of research focused on the effects of incarceration on people of diverse racial, ethnic, and socioeconomic backgrounds. A crucial gap in prison reform research remains the effects of this system of punishment on LGBTQ+ people. My research endeavor aims to address that fact and reveal how individuals with queer sexual or gender identities have been impacted by this system within Washington State. The institutions that exact punishment in this state operate both on a heteronormative apparatus and a gender binary. My thesis involves placing formerly incarcerated LGBTQ+ people at the forefront of prison reform research to highlight their distinctive adversities and establish policy proposals to ameliorate them. I conducted interviews with people who fit this demographic to bring to light their lived experiences and discover what practices, policies, and changes they want to see implemented. The findings illustrate a need for reform in areas including programming opportunities, support systems, healthcare accessibility, gender-affirming care, therapeutic services, housing assignments, reentry assistance, and equitable treatment overall. Incarcerated LGBTQ+ individuals are subjected to exacerbated punishment from correctional staff and other incarcerated individuals, which leads to difficulties with interpersonal dynamics and an overall suppression of identity. Faced with heightened vulnerabilities while incarcerated, LGBTQ+ people maintain resilient attitudes as they reenter society and positively transform their lives. The voices of this community in this research illuminates the necessity of addressing LGBTQ+ rights within prison reform efforts.

Substance use disorder disproportionately affects sexual and gender minority (SGM) youth compared to their heterosexual and cisgender peers, a disparity which is driven by unique stressors and systemic inequities. This systematic review synthesizes 122 empirical studies to explore the factors contributing to elevated rates of substance use among SGM youth and to identify gaps in existing prevention and intervention efforts. Findings reveal significant disparities, with SGM youth experiencing heightened vulnerability due to stressors such as expectations of rejection, interpersonal and structural discrimination, familial rejection, and other challenges of navigating a heteronormative world. These challenges are compounded by individual-level covariates including race, ethnicity, and socioeconomic status, which are often overlooked in existing research. A key finding is the paradox of community. While SGM-affirming spaces provide essential support, they are often closely associated with substance use. Despite sparse availability of targeted interventions, existing studies underscore the necessity of culturally relevant affirming approaches that address the unique needs of this population. Recommendations for youth, schools, practitioners, and families are provided, emphasizing the importance of fostering inclusive environments, reducing stigma, and building pathways to resilience and mental health. This review highlights an urgent call to action to address these disparities through innovative and inclusive prevention and intervention strategies.  

In this project, we study the order polytopes of generalized snake posets, a particular family of polytopes (geometric shapes with flat sides) defined in recent work by von Bell and coauthors. We specifically investigate triangulations of these polytopes, which are subdivisions of the polytopes into simplicies (arbitrary-dimensional generalizations of the triangle). To do so we examine their secondary polytopes. The secondary polytope of a polytope is a related polytope in which each vertex corresponds to a triangulation of the original polytope and each edge corresponds to a bistellar flip (a specific type of transformation between triangulations), capturing the combinatorial relationships between different triangulations in a geometric object. Von Bell and coauthors conjecture that the secondary polytopes of order polytopes of snake posets have multiple unusually nice properties similar to those of the associahedra, a well-known family of polytopes that admit nice combinatorial descriptions and appear in many areas of mathematics. The overall goal of this project is to prove these conjectures. Collaborating with fellow undergraduates Molly Bradley (University of Pennsylvania), Mario Tomba (Dartmouth), and Katherine Tung (Harvard), I have written code to compute details of the smallest examples of these secondary polytopes, proved related theorems/results, proposed some new conjectures based on observed patterns in the examined examples, and made partial progress towards proving multiple of the von Bell conjectures. This project is ongoing, and we continue to explore multiple ways to approach the conjectures and more broadly understand the secondary polytopes.

Image processing using dithering finds important applications for data compression, data encryption, data security and cryptography. Dithering is used for the design of high-quality printers, computers and game consoles. Digitization and compression of images often involve reduction of color palette which gives rise to color bands due to quantization errors. Dithering involves the application of noise to randomize quantization errors which helps preserve key features of images when converted to black and white and other color reduced formats. We applied mathematical matrix-algebra based methods for image digitization, image recognition and image processing. We wrote Python programs to study image quality before and after application of different algorithms for dithering including thresholding, randomization, ordered methods like Bayer’s method, void and cluster methods, error diffusion methods like Floyd-Steinberg techniques, etc. This project offered excellent hands-on opportunities to integrate programming in python with matrix algebra methods for image processing and provides insights into how different dither algorithms enhance visual capabilities along with compressing image size. Dithering introduces some textural contours and color shifts but preserves most features in image data. We also find that in addition to enhancing image quality, dithering modulations offer powerful techniques for digital watermarking and image embedding indicating their key role in data security.

The Mars Rover Sojourner is an autonomous robotic vehicle that was used by NASA for space exploration on Mars. The Mars Sojourner landed in a location called Ares Vallis in 1997 where it explored and took several photos and collected data. Google Maps and network routing programs, often use the popular Dijkstra's algorithm used to find the shortest and most cost-effective routes between various nodes on a graph. Here, we used the free open Cyberbotics Webots code to simulate the Mars Sojourner which was designed to successfully navigate over the rocky terrains of Mars. Robotic simulation software like Webots offers an excellent testing platform to study the stability and routing of autonomous navigation vehicles on different terrains prior to their deployment in outer space. The robotic Mars Sojourner was equipped with a GPS sensor which kept provided measurements of position using geodetic coordinates involving latitude and longitude. We used the Haversine formula to calculate distances between various places it traversed on Mars. We used a python code to map the shortest optimized route to go from point A to point B on Mars using Dijkstra’s iterative algorithm. Such studies are important for future development of robot motion controller software that can be effectively used for cost effective autonomous navigation in outer space.

Autism is a neurodevelopmental condition characterized by social-communication differences and restricted, repetitive behaviors (American Psychological Association, 2013). While racial disparities in autism prevalence have been documented, not much research has examined how these differences appear in autism screening measures. This study investigates racial differences in Autism Spectrum Quotient (AQ) scores among non-autistic Asian and White adults to assess potential biases in autism screening. Using data from three NIH-funded studies (COBRA, BEAM, and The Korean Study), AQ scores from 166 participants (n=102 White, n=64 Asian) will be analyzed through t-tests and Repeated Measures Analysis of Variance (ANOVA) to compare total and subscale scores. Preliminary observation suggests that non-autistic Asian participants may be more likely to score higher on the AQ, raising concerns about false positives in autism screenings. Understanding these differences will help improve diagnostic accuracy, reduce disparities, and promote equitable access to neurodevelopmental resources.

Asian Americans are victims of anti-Asian racism, but recent studies have also shown that they have a different role in perpetuating anti-Blackness and White supremacy. Our research aimed to specifically examine whether White and Asian Americans perceive a difference between anti-Blackness and White supremacy. We ran a qualitative study where anti-Blackness and White supremacy were defined for Asian and White American participants, who were then asked to write about their racial group’s relationship with those phenomena. We defined anti-Blackness as the belief that Black people are inherently inferior to others, and the corresponding practice of them being given insufficient power. Similarly, we defined White supremacy as the belief that White people are inherently superior to others and the corresponding practice of them being given disproportionate power. A few research assistants and I rated the similarity between the responses on anti-Blackness and White supremacy on a Likert scale from 1 to 7, with 1 indicating “not similar at all,” and 7 indicating “very similar.” We then performed a two-sample t-test (a type of statistical data analysis in psychological research) on this data to compare the responses between the Asian and White American participants. As expected, we found that the Asian American participants rated anti-Blackness and White supremacy as being more distinct than the White Americans did. The p-value for this data analysis was a statistically significant 0.004. These findings establish a foundation for future studies on the Asian American role in anti-Blackness and White supremacy. I have also conducted data analysis and ran participants for two such studies, which examined whether reminders of anti-Blackness caused Asian Americans to take more responsibility for anti-Blackness and show more solidarity with African Americans more than reminders of White supremacy.

Overgeneral Autobiographical Memory (OGM) is a common symptom of depression and Post-Traumatic Stress Disorder (PTSD). Instead of remembering specific details, individuals with OGM can only describe past events from their lives in general terms. The "trauma hypothesis" suggests that OGM emerges because individuals suffering from PTSD tend to reduce the number of details they retrieve about their memories to avoid remembering their trauma. However, this hypothesis does not fully explain how this avoidance is learned, or why avoidance spreads from traumatic memories to all autobiographical memories. To this end, we propose a computational model of OGM that integrates theories of memory retrieval and trauma with reinforcement learning. In this model, multiple episodic memories are nodes in an interconnected network, and memories are retrieved when visiting that node in the network. The more nodes that are visited, the more detailed that autobiographical recall will be. On the other hand, visiting more nodes comes with an increased risk of encountering a traumatic memory, which comes with negative emotional valence. The decisions about whether to visit another node or terminate the retrieval process are made using reinforcement learning, which takes actions based on predicted outcomes. By obtaining a greater understanding of OGM through this model, we hope to improve treatments for PTSD that specifically targets its effects on memory. 

The King County Brightwater Treatment Plant includes a marine outfall pipe anchored to the seafloor that discharges highly treated effluent from the Seattle metropolitan area into Puget Sound, Washington. Since 2009, as part of an eelgrass survey study, King County biologists have collected annual video footage of the outfall pipes from which they witnessed the abundance of organisms colonizing the pipe at all depths. Consequently, in 2012, King County biologists launched a ten-year project assessing the effectiveness of the high-density polyethylene (HDPE) outfall pipe at providing habitat for marine organisms and the composition of organisms it houses. Using a  remotely operated vehicle (ROV), they placed thirty plates of HDPE material adjacent to the outfall pipe at 100ft, 300ft and 600ft depths. Sets of replicate plates were then retrieved after 2, 5, and 10 years of deployment, at which time King County staff immediately took photos of each plate for analytical assessment. In this study, we analyzed the photos for percent live cover and composition of marine organisms inhabiting the pipe material, all across depths and time intervals. We hypothesized that the wastewater outfall pipe can function as a habitat; and the extent to which different organisms, their identifications and abundance, likely vary by depths due to the environmental conditions at different levels of depths. We found that percent live cover increased over time but did not vary across depths, and that certain phyla consistently dominated cover on the plates but dominant groups varied across depths. These findings allow experts in the field to consider using outfall pipes to provide additional habitats for marine organisms, and to assess communities of organisms at depths that are less accessible. 

Harmful algal blooms (HABs) are threats to a number of species in marine environments. One hypothesis states that excess nutrients in water lead to accumulations of certain plankton species that produce toxins. This can explain some illnesses such as paralytic shellfish syndrome in humans who consume impacted shellfish. HABs can be identified directly, but given the delays involved in analyzing results, other indicators may be used to predict presence of HABs as well. Possession Sound is an inlet of the Puget Sound located between Whidbey Island and the coasts of Everett and Mukilteo, Washington, connecting to the Snohomish River, as well as Saratoga Passage and Port Susan to its North and the main Puget Sound basin to its South.  Since HABs can occur in freshwater and saltwater for different reasons, Possession Sound’s status as a salt-wedge estuary makes it notable as a study site. To investigate the nature of HABs in Possession Sound, I analyzed plankton density data, chlorophyll-a levels, and phosphorus concentration data I collected in 2024 as well as data collected by the Ocean Research College Academy from 2016-2024. Chlorophyll-a concentrations were measured with a YSI EXO Sonde. Phosphorus concentrations of water samples were collected using a Niskin bottle and measured by the University of Washington Marine Chemistry Lab. I analyzed the progression of each parameter temporally and spatially. I expect to see clear spikes in certain plankton species, especially dinoflagellates, that align with similar-timed chlorophyll-a and phosphorus spikes. However, I predict that trends will be the least prominent in phosphorus concentrations due to its greater prevalence in freshwater than in saltwater. Understanding which plankton species are most responsible for HABs and temporal alignment of potential drivers can allow for better prediction of HABs in Possession Sound.

Zostera marina (eelgrass) is one of the many important biological features of Possession Sound, acting as a substrate for many microorganisms, a filter of greenhouse gases, and as protection for many species. The Possession Sound has been marked as a Seagrass Sanctuary by the Department of Natural Resources, which protects and monitors nearshore eelgrasses within the basin. By looking at what kinds of species are found in a marine environment, researchers can assess an ecosystem's overall health. Environmental DNA (eDNA) is a data capture technique used by researchers that picks up DNA traces left behind by organisms, and shows their presence/absence in a given area. The study site, Mount Baker Terminal, lies inside the Possession Sound basin near Everett, Washington, and contains a large eelgrass bed. I collected 10 samples using passive filters submerged at various depths inside and outside the eelgrass bed in 2024 and processed at a WDFW lab. I analyzed these data and 40 additional samples collected by the Ocean Research College Academy from 2021-2024 using similar methods. I hypothesized that there would be more species such as crustaceans, fish, and other plants inside the eelgrass because of its ability to protect and maintain a nutrient-dense environment. These data will help shed light on species richness in each environment, which has potential implications for understanding the overall health of the ecosystem and the critical role eelgrass plays in the estuary.

Possession Sound, located between the city of Everett and Whidbey Island, is a part of both a key economic area and a bustling marine environment. Because of the marine activity, scientists study all sorts of parameters involving the water including noise. Numerous studies have assessed ambient noise in marine environments to investigate the influence of tidal forces on ambient noise. These reports found that tidal noise or “flow noise” is observed around the 0-100Hz range with the most significant impacts observed centered around 25hz. The Ocean Research College Academy operates a SoundTrap ST400 STD hydrophone mounted to Mount Baker Terminal that takes recordings daily for most of the year. Mount Baker Terminal is a small marine terminal operated by the Port of Everett, located just north of the town of Mukilteo. Using data collected from the hydrophone, I took measurements of ambient noise in root mean square amplitude centered around the 25hz range and compared that to NOAA tidal data at Everett, Washington. Using these data I investigated the potential presence of a relationship between the tides and ambient noise. When the initial measurements of root mean square amplitude were compared to tidal data from the area the results showed that tides had no significant impact on the ambient noise at Mount Baker Terminal. Investigating the effects of tides on ambient noise can be crucial to future acoustic research done by researchers in the area as results could be affected by noise created or affected by tides. Future analysis should investigate the impacts of other natural contributors to the soundscape such as rain and wind.

The Eastern North Pacific gray whales (Eschrichtius robustus) have a long migration from their breeding grounds in Mexico to their feeding grounds in Alaska. A subgroup of the Eastern North Pacific stock, nicknamed the Sounders, deviate from the migratory path most gray whales follow to feed in the Salish Sea, typically between the months of March and May. Other studies show that gray whales feed on benthic organisms such as ghost shrimp. Studies conducted in the Arctic area of the gray whale migration route have seen sea ice playing an important role in the gray whales being able to enter the areas where they feed. One working hypothesis is that gray whale shifts in migration patterns are the direct result of climate change; this could explain why some of the Eastern North Pacific gray whales enter and feed in Possession Sound. I analyzed sightings data, shared by the Whale Museum and recorded in Possession Sound, WA from 2000-2022. These data, most of which were compiled by the Orca Network, were filtered to identify the number of visitations each month over the study period. Early analysis shows a phenological shift in the time of the gray whale's arrival and departure from Possession Sound. The shift shows an increase in the number of months gray whales are present in Possession Sound, from a March to May visit to a year-round presence. Although these results cannot explain the reason for the phenological shift, future research must look into related shifts in the Arctic ice formation as well as ambient air and water temperature shifts. Future research calculating density of ghost shrimp in Possession Sound will also indicate why this location is favored.

Ocean acidification is the reduction of pH in seawater due to increased carbon dioxide from fossil fuels in the atmosphere and other anthropogenic factors. Ocean acidification causes shellfish such as oysters to experience difficulty building their shells. Acidification trends in the North Pacific Basin are well documented, yet pH trends in Possession Sound, a salt-wedge estuary located in the Salish Sea is less documented. Possession Sound receives discharge from the Snohomish River and has human activity along the shoreline. In this study, the average change of pH in the middle of the North Pacific Ocean was measured and compared to the average change of pH in Possession Sound since 2016. I analyzed data collected from ARGOS Floats located in the central North Pacific Ocean. For Possession Sound, I used data collected from a  YSI EXO Sonde in partnership with the Ocean Research College Academy (ORCA). I collected data on 12 research cruises in 2024. I expect to find a slightly greater decrease in pH within Possession Sound than the North Pacific Basin due to the additional anthropogenic factors present in the Sound. Preliminary analysis shows a slight seasonal change in pH in Possession Sound, but little to no change yearly. I expect the data to show a steady decrease in pH for Possession Sound and the North Pacific Ocean basin every year since 2016. Calculating acidification rates and learning how they differ in various geographical locations, with separate factors, will increase understanding of the impacts of ocean acidification, which may be used in conservation efforts. 

Initial work from our lab has demonstrated that decision-making in OCD patients varies along the approach-avoidance behavioral axis depending on their response to deep brain stimulation (DBS) treatment. Patients who do not respond to DBS exhibit heightened risk aversion and consistently make avoidant decisions, while responders balance risk and reward in their decision-making process. In contrast, patients who receive excessive stimulation display disinhibited behavior, making choices that maximize reward regardless of potential risk. While this 2D task has provided valuable insights into approach-avoidance behavior in OCD, it does not fully capture the naturalistic behavioral responses observed in daily life. To address this limitation, we are developing a virtual reality (VR) task designed to quantify approach-avoidance behavior in a dynamic 3D environment. Participants complete probabilistic decision-making trials while wearing a VR headset, allowing for precise tracking of eye movements, hand positioning, and body dynamics. This project aims to provide a naturalistic task to analyze movement velocity and behavioral trends to identify neural biomarkers associated with approach-avoidance tendencies. This work will act as a stepping stone, enabling deeper insights into how neuromodulation regulates these behaviors. We are currently finalizing the development of this VR task and will demonstrate the feasibility of using this task to collect unique behavioral data on approach-avoidance behaviors. In the future we hope to use this task to identify biomarkers of approach-avoidance behavior and use that information to further refine neuromodulation treatment for psychiatric disorders.

Dopaminergic signaling within the striatum plays a crucial role in modulating reward and aversion, shaping behaviors such as food-seeking and consumption. While striatal dopamine release has been implicated in reinforcement learning and decision-making, the spatial and temporal dynamics of dopaminergic activity along the anterior-posterior axis of the striatum during consummatory behavior remain poorly understood. We investigated the role of dopamine in the striatum during the consumption of multiple solutions by employing a trial-based multi-spout behavioral paradigm with head fixed mice. To record the dopamine activity in the ventral and dorsal striatum, we utilized multi-site fiber photometry to record the fluorescent biosensor GRAB-DA2m along the anterior-posterior axis. Food restricted mice were given varying concentrations of sucrose as rewarding stimuli, while water restricted mice were given varying concentrations of sodium chloride as aversive stimuli. Our results revealed that dopamine responses scaled more across concentrations in the anterior regions of the striatum compared to the posterior regions. Additionally, we found more distinction between dopamine responses for the various concentrations of the aversive solution compared to the rewarding solution. Lastly, posterior striatal dopamine responses had a more rapid onset upon stimulus consumption, whereas anterior regions exhibited delayed responses, highlighting region-specific temporal differences in dopaminergic encoding. These findings refine our understanding of dopaminergic circuitry within the striatum and how dopamine-mediated responses to rewarding and aversive stimuli regulate feeding behaviors. By exploring this pathway, we offer potential insights into the mechanisms underlying disorders characterized by dysregulated reward including eating disorders and obesity.    

The locus coeruleus (LC) is a major neuromodulator source with widespread projections to distinct functional targets that influence arousal, anxiety, learning, and other behavioral states. Our lab has previously shown LC excitation triggers the release of norepinephrine (NE) into the basolateral amygdala (BLA). Recent studies suggest LC terminal stimulation may release DA into the dorsal hippocampus (dCA1) enhancing novelty-associated spatial learning. Our recent data show LC stimulation evokes DA release. Previously, release across regions, paradigms, and behaviors typically associated with LC have not been characterized, due to difficulty in separating DA from NE using traditional sensing methods. Due to this, the relationship between the LC and other DA systems remains unclear. To understand the mechanisms by which the LC may release DA independently of the ventral tegmental area (VTA), a major DA source, we have employed optogenetic stimulation to evoke release from neuron terminals and quantify the release dynamics of NE and DA. We used fluorescent biosensors to detect NE and DA, captured by a fiber optic cable and amplified to observe the relative dynamics of DA release. These sensors have tuned affinity and selectivity for NE and DA and use fluorescence as a proxy for neuromodulator release. In this project, we aim to elucidate how and under what conditions the LC is releasing DA across regions with different functions during aversive and appetitive behaviors. These data will enhance our understanding of the LC neuromodulator signaling that can become maladaptive and afflict anxiety, addiction, and more, and also demonstrate that the release of DA from the LC is dependent on the behavior induced.

In mammals, the primary mechanism regulating circadian rhythms is the central circadian pacemaker in the suprachiasmatic nucleus (SCN). The 24-hour light-dark (LD) cycle is the primary environmental cue, or zeitgeber, that entrains the SCN and sets its phase by adjusting its timing via phase advancing or delaying. Our laboratory has demonstrated that when mice are foraging outside of their safe nest, cyclic fearful stimuli can act as a nonphotic zeitgeber, entraining circadian rhythms and shifting activity from nocturnal to diurnal. However, the mechanisms of this so-called “fear entrainment” and phase-specific properties of cyclic fear remain unclear. This study examined whether cyclic fear via footshocks differentially entrains activity depending on the circadian phase of exposure. Mice were housed under a 12h:12h LD cycle and divided into three groups based on shock timing: the first six hours of the dark phase, the last six hours of the dark phase, and the middle of the light phase. Both dark phase groups showed delayed activity, with only the early dark phase group exhibiting evidence of entrainment. The mid-light phase group remained nocturnal. To further investigate the interaction between light and nonphotic entrainment, we conducted a follow-up experiment in which mice were placed under constant laboratory conditions (constant darkness) before undergoing cyclic footshock exposure. We hypothesized that, in the absence of light cues, the phase shifts induced by fear would differ from those observed under LD conditions, potentially revealing a distinct mode of nonphotic entrainment. Our findings so far suggest that entrainment to cyclic fear may only be achieved through delays, and that circadian oscillators may use different mechanisms of entrainment in response to photic vs. nonphotic zeitgebers.

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 40 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 and PER2 protein quantification is currently underway in the SCN, basolateral amygdala, paraventricular nucleus of the thalamus, and dentate gyrus. We hypothesize that c-FOSs and PER2 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 and PER2 expression in response to time-specific fear. Results from this study may be useful for identifying putative brain regions containing fear-entrainable oscillator(s).

The ability to pattern three-dimensional microscale cultures opens new avenues for examining the effect of nonplanar mechanical environments on mammalian cells and tissues. Our lab has developed a method for generating suspended tissues with spatial control using open microfluidic principles called Suspended Tissue Open Microfluidic Patterning, or STOMP. STOMP utilizes spontaneous capillary flow and capillary pinning to pattern suspended, multi-region tissues. Using similar microfluidic principles as STOMP, we have developed a method to pattern large (cm-scale) models via semi-open microfluidic channels called Suspended Nonplanar and Planar, or SNaP, geometries. I design these devices with computer-aided design, fabricate components on stereolithography 3D printers, pattern devices with standard pipettes, and culture resulting tissues for short- and long-term time periods to model biological scenarios. With the broad statement that human tissue is generally nonplanar in mind, my research focuses on three different geometries of tissue, 1) a sinusoidal wave, 2) a transwell-like mogul, and 3) a multi-region dome, where each nonplanar geometry enables a different biomedical investigation. The sinusoidal wave construct allows us to ask if cells embedded in tissues with varying frequencies of undulation experience changes to cell morphology due to the topology of their environment; the transwell-like mogul enables investigation of cell proliferation of cells grown at or within an air-liquid interface; and the multi-region dome facilitates the study of tissue interfaces where a diseased region of cells meets a healthy region of cells, all within a single contiguous tissue. I am currently exploring these questions through multiple cultures where different device versions and/or multiple cell types are engaged to collect biological readouts which demonstrate SNaP as a translatable platform for the investigation of questions in biomechanics and regenerative medicine.

Electrochemical water splitting is an effective method for generating hydrogen gas (H2) and an attractive means for energy storage. During this process, hydrogen and oxygen bubbles form on the electrode surfaces often lower the efficiency of gas production. The overarching goal of this study is to probe and better understand the nucleation process of small H2 and O2 nanobubbles on the electrode. To do this, we use ultrasensitive fluorescence microscopy to monitor the transient adsorption and desorption of single fluorophore molecules, such as Rhodamine 6G (R6G), on the nanobubble surface. My project aims to study how different fluorophores interact differently with the bubble surface and how they may interact with each other when multiple fluorophores are co-adsorbed on the bubble surface. This research may help us better understand bubble-molecule and molecule-molecule interactions at confined spaces for enhanced chemical labeling of the nanobubble surface. Moreover, it may also help us better understand the chemical nature of the gas/water interface, which has direct implications for more efficient gas productions and energy conversion and storage.

The Molecular Case Network (MCN) connects biology and chemistry educators and fosters collaboration to create narratives that enhance interdisciplinary teaching and learning while providing support for their professional development. This research presents a case study of 10 MCN participants who were interviewed about their experiences creating interdisciplinary educational case studies to implement in their courses. These lessons aid the teaching of the content material and technology in a real-world context. These educators are considered expert participants and bring diverse perspectives and experience, allowing them to contribute unique ideas and create multifaceted case studies. Our objectives are to articulate the definition of molecular storytelling through the instructors’ perspective, gauge the instructors' confidence in the interdisciplinary teaching of biochemistry, and examine their self-efficacy in implementing the molecular case study with technology. We used a thematic analysis when looking at the interviews to identify common sentiments and refine them into themes to better understand the relationship between the participants' experiences. Through analysis of the interviews with the participants, we found major themes about the usefulness of technology and the importance of a strong leader in building confidence in both the technology and the writing of the case studies. We explore each unique narrative to find what motivates, excites, frustrates, and ultimately leads to the success of each instructor. By exploring these areas, we aim to provide insights that can help improve education in the relevant scientific disciplines. By understanding the factors that influence the success of these educators we hope to inform the MCN to help strengthen and expand their success long term.

Biodiesel, "an alkyl ester of fatty acid" and type of biofuel, can be used for fueling vehicles and can be produced via transesterification, the process of using the alcohol methanol along with a base catalyst (usually sodium hydroxide) to break down oils and fats that have many triglycerides into fatty acid methyl esters (FAMEs) and glycerol. The viscous triglycerides are broken down into ester bonds and free fatty acids (FFAs), which are not ideal for biodiesel synthesis because FFAs have high melting points, unlike FAMEs. Thus, biodiesel synthesis should be conducted in a manner that reduces the number of FFAs while having a high breakdown of triglycerides into ester bonds. Transesterification that involves alkali/alkyl (like the bases sodium hydroxide (NaOH) and potassium hydroxide (KOH)) as a catalyst can cause soap-FFA reactions, resulting in "emulsification" challenges (Cheng et al 2013) (Hasan et al 2017). KOH and NaOH both can cause soap formation if they interact with triglycerides and esters. Furthermore, KOH produces more soap that NaOH, but KOH also helped produce more biodiesel than that from NaOH at 0.2 mol concentration (Van Gerpen et al 2006). What are the effects of NaOH and KOH on the fuel value of the biodiesel produced over the course of eight weeks? If KOH is used to synthesize biodiesel, then the biodiesel's fuel value form KOH will be higher than that form NaOH. Although the research project is currently in progress, the anticipated result is that KOH better catalyzes transesterification (via causing more heat combustion of ethanol) than NaOH for producing biodiesel. The results' significance determines which catalysts are used to produce more biodiesel. This is because the amount of biodiesel produced can be used for daily life purposes like faster transportation without having to refuel automobiles as frequently.

Neuronal and endocrine cells store and secrete molecular cargos like neurotransmitters and metabolic hormones through the regulated secretory pathway. Dense-core vesicles (DCVs) originate from the trans-Golgi network and undergo a maturation process involving peptide processing and cargo sorting before being stimulated to release their cargos outside the cell. Dysregulation of this process leads to a wide range of neurological and metabolic disorders; yet the molecular mechanisms underpinning it remain poorly understood. Vesicular traffic are largely coordinated by the Rab family of GTPase proteins.  Previous work identified the conserved proteins TBC8 and RUND1 as regulators of DCV maturation in Caenorhabditis elegans; and both proteins bind active GTP-bound RAB2. TBC8 is the putative RAB2 GTPase activating protein (GAP) which promotes conversion of GTP-RAB2 into GDP-RAB2, thereby inactivating the Rab. RUND1 interacts with both active GTP-RAB2 and TBC8, yet its precise function remains unknown. This study aims to characterize the biochemical function of TBC8 and RUND1 in regulating RAB2 activity. Using purified proteins, we demonstrate that TBC8 greatly promotes RAB2 GTP hydrolysis, indicating it is the bona fide RAB2 GAP. Additionally, we show that RUND1 strongly inhibits TBC8-stimulated RAB2 GTP hydrolysis, suggesting RUND1 may compete with TBC8 for RAB2 binding. Given this interplay between RUND1 and TBC8 in binding RAB2, we hypothesize that RAB2 exhibits exclusively pairwise interactions with its partners. To test this, we will use mass photometry to study whether RUND1 and TBC8 can bind RAB2 simultaneously or if one complex is preferentially formed. Based on our current findings, we propose a model where TBC8 promotes RAB2 inactivation by stimulating GTP hydrolysis and RUND1 blocks RAB2 inactivation by TBC8, prolonging the activate state of RAB2.

Pulling apart DNA during replication induces DNA strands to wrap around each other, producing positive supercoils ahead of the replication fork. Positive supercoils hinder further DNA replication, and are removed by Type II Topoisomerases (Top2s), a group of essential enzymes that cleave positive supercoils to relax DNA for easy separation. Errors in supercoil resolution are linked to diseases like cancer and autoimmune disorders. A key question in the field is the mechanism by which Top2s locate positive supercoils. We recently discovered that GapR, an essential DNA binding protein conserved across α-proteobacteria, binds positive supercoils and stimulates the activity of bacterial Top2s DNA Gyrase and Topoisomerase IV. We hypothesized that GapR recruits Top2s to positive supercoils by direct interaction. We investigated this mechanism by using a Bacterial Two-Hybrid assay to screen for GapR interaction with Top2 subunit and identified an interaction between GapR and the A subunits of DNA Gyrase and Topoisomerase IV. Additionally, we discovered that GapR interacts with Top2 A subunits, and not with Top2 B subunits, in a gel shift assay. In collaboration with the David Baker lab, we generated predictions of the GapR-Top2 interaction which together support a model of interaction between GapR and the Top2 A subunit that is mutually exclusive to the Top2 B subunit. In our current work, we aim to identify the mechanism of direct interaction between GapR and Top2s aided by mass photometry and biochemical experiments to reveal a previously unknown mechanism of Top2 recruitment. Because GapR is conserved by alphaproteobacteria, our research could reveal a target for inhibition by antibiotics. If such Top2 recruiters are more broadly conserved, our work provides a novel pathway to target with anticancer therapeutics as human Top2 inhibitors are important chemotherapy drugs.

Hydrogen sulfide (H₂S), known for its distinct smell of rotten eggs, is recognized as the third endogenous gaseous signaling molecule, alongside nitric oxide and carbon monoxide. Often described as a double-edged sword, H₂S exhibits both cytoprotective and cytotoxic properties depending on the biological context. A 2018 study suggested that H₂S enhances the efficacy of doxorubicin (Dox), an anticancer drug, by promoting apoptosis and reducing colony formation in HepG2 cells, even restoring drug sensitivity in resistant cells. However, my preliminary experiments indicated a protective role of H₂S in HepG2 cells under stress, particularly when treated with NaSH (an H₂S donor). Rather than inducing apoptosis, H₂S appears to support cell proliferation and regulate reactive oxygen species (ROS) production. My research project aims to identify H₂S -dependent pathways in HepG2 cells under oxidative stress. Using Dox as a stress inducer, I conducted viability and cytotoxicity assays, demonstrating that supplementation with 250 µM NaSH at 0 and 12 hours significantly restored cell survival. To investigate the molecular mechanisms, RNA-seq analysis identified 2,996 differentially expressed genes in the H₂S + Dox group compared to Dox alone. Principal component analysis (PCA) revealed distinct transcriptomic profiles, while KEGG enrichment analysis highlighted significant alterations in genes within the PI3K-Akt pathway. To further validate these findings, I plan to perform flow cytometry and western blot analysis. While the role of H₂S continues to be debated, my data suggest a protective function in liver cells against Dox-induced stress via the PI3K-Akt pathway. Understanding these mechanisms could pave the way for new therapeutic strategies aimed at maintaining or increasing H₂S levels to support cell health in diseases characterized by oxidative stress, such as cancer and diabetes.

This study utilizes design research to explore how storytelling informs the design, usage, and knowledge production of a digital archive repository housing digitized memory objects. Ranging from ao dai to math booklets, these memory objects are grounded by narratives of Vietnamese diasporic identity and experiences shared by community researchers as part of Sarah Nguyen’s Sharing Stories, Sharing Trust (SSST) workshop series. To understand how story-driven approaches translate and transform digital archive design, I draw upon multiple methodologies such as case study analysis of existing community-based applications of digital archives and thematic analysis of SSST workshop discussions (formatted as observational memos). I also draw from user interviews with community researchers using a semi-structured, narrative-driven protocol. These analyses inform the design of a digital repository prototype that foregrounds story-driven design whilst exploring possibilities for the preservation and sharing of Vietnamese diasporic experiences.

I am currently assisting PhD student Jessica Luo in her research of the Sanmen Wu sound system, a language of the Wu family found in Southeast China. As Jessica writes an article that summarizes the sound structure of Sanmen Wu, I analyze utterances produced by speakers of the language. In my self-guided research, I focus on the sound quality of the consonants and their variations to determine underlying pronunciation. I also connect these variations to historical sound changes from Middle Chinese, its ancestor, into Sanmen Wu. I observe that Sanmen Wu speakers tend to freely alter pronunciations of certain consonants. For example, a speaker may say 部 [pu] or [bu] meaning ‘part,’ the latter only appearing after another spoken word. These two syllables contrast only in voicing, where [p] is voiceless and [b] is voiced. I use Praat, an industry-standard speech-analysis program, to read diagrams that depict the acoustics of these consonants to verify my findings. I am also creating a set of rules that predicts this alternation. One of the conditions is as follows: words with alternating voicing in their consonants change when pronounced within a sentence (‘medially’). Eventually, I will explain these rules, and I predict my explanation is related to the evolution of Sanmen Wu into its current stage. I reason that because the Wu language family stems from Middle Chinese, both of which require contrastive voicing to create distinct words, Sanmen Wu also contains the original underlying variation that exists in Middle Chinese. As such, I attribute this variation to an inherent part of the language rather than random circumstance. Ultimately, I intend to foster a thorough understanding of Sanmen Wu phonology and provide a foundation for further exploration of this topic.

The title of this project references Stuart Hall’s memoir, Familiar Strangers and encapsulates the experience many artists have when portraying family members they have never met but feel like they know through photographs. Drawing from Tina Campt’s definition of the haptic–how viewers touch or are touched by family photos–I look to Black artists’ uses of photos to express their relationship to themes of family, diaspora, memory, and history. How do Black artists use hapticity and embodiment to engage with family photos and produce alternative ways of conceptualizing identity? How do they view family photos as sites of memory activation? Why and when have these artists returned to family photos as source material?  This focus on hapticity reveals how Black visual artists recreate, re-enact, and revise family photos in their work to produce micro-histories that might otherwise be lost. I analyze artist statements, arts and culture literature, and academic articles to identify individual artists’ approaches to family archives. The featured 19 artists span the African diaspora, and I use Safia Elhillo’s home is not a country as a framework to situate the socio-political contexts of their work, which include the legacy of transatlantic slavery, transnational migration, diaspora, colonialism, racial apartheid. Many of the artists have gained significant attention as they portray family history and collective memory in their practice. This work can guide future exhibitions and continue the ongoing conversation on family photography in Black visual art.

Zanele Muholi is a queer, Black, nonbinary South African photographer who produces work depicting the lived emotional experiences of Black queer South Africans, specifically highlighting individuals who have lived through corrective sexual abuse. While corrective abuse against queer and Black people has been documented throughout the art historical canon, many depictions acknowledge only the physical pain, completely omitting the emotional toll this abuse causes. Acknowledgement of the range of emotion of queer and Black individuals in the art world is unfortunately extremely limited, especially when considering depiction of victimized forms; however, Zanele Muholi creates artwork that counters this inadequacy. Through the medium of black and white photography, captured with a “loving” lens, Muholi subverts the concept of corrective sexual abuse by emphasizing the true emotional impact it has through a focus on facial expression and body language, humanizing their subjects to decolonize and reclaim the long-exploited image of the black body from historical degradation under apartheid; they simultaneously challenge accepted gender presentation by depicting queer South Africans who fall outside of the accepted gender binary, making unavoidable the humanity of those who have endured this kind of abuse. Muholi’s work is intended for a wide audience; they want to provide an avenue for queer Black individuals to see themselves in the art world, however; they also want their work to be experienced by those who may be unaware of their communities’ struggles to humanize them to the world. By examining a selection of Muholi’s works alongside historical and contemporary examples of Black pain, and investigating responses to the artist, this paper proves that Muholi’s work questions how Black pain is depicted in media and pushes the boundaries of accepted gender presentation and sexual orientation in the museum space, ultimately creating a fuller picture of the queer Black lived experience.

Maintaining the integrity of genetic material and preventing changes over time is essential for normal cellular function. This genomic stability is directly affected by the DNA replication process. Replication must be both accurate and efficient; mutations that affect DNA replication can cause genomic instability and changes in the genetic makeup of the cell. Through a genomic instability screen in mice, researchers discovered a single base pair mutation in a highly conserved gene required for unwinding DNA during DNA replication. The presence of this single base pair substitution, called Chaos3, in both copies of the gene causes female mice to develop mammary tumors. We have found that in the yeast Saccharomyces cerevisiae, the corresponding Chaos3 mutation decreases activation or “firing” of some replication origins—the sites where DNA replication begins. Chaos3 does not affect all early firing origins in the genome; rather, origins near centromeres are specifically affected, thereby delaying replication of those centromeres, causing chromosome loss. We found that when an affected origin is replaced with an unaffected one, firing levels are restored to wild type function and that chromosome loss is rescued. To further understand what components are essential for timely DNA replication, and why only a subset of origin sequences are sensitive to the Chaos3 allele, I am focusing on the origin sequences directly. I am mutating the origin sequence itself and separately deleting different genes whose products have potential interactions with origin sequences. My research aims to advance the understanding of the role these genes play in the activation of origins for timely DNA replication and how the Chaos3 mutation may be interrupting normal function of these processes. This knowledge can help identify key molecular mechanisms that drive cancer development in higher eukaryotes.

Copy number variation (CNV) is associated with genetic disorders in humans. One particular kind of CNV is a gene triplication in which the central copy is inverted. How such structures arise is poorly understood but is of great interest because of their association with cancer and other genetic disorders. We find similar amplified structures in budding yeast Saccharomyces cerevisiae, and therefore, we can use yeast to understand the mechanism that generates them. The Brewer and Dunham labs have proposed Origin Dependent Inverted Repeat Amplification (ODIRA) as a model that explains inverted CNVs. To understand which proteins/enzymes contribute to amplification, we are implementing gene deletions to observe the effect on the production of these ODIRA amplification events. ODIRA events are rare and thus large sample sizes are required to detect them. To streamline their identification, I am developing a system that uses color as a visual indicator of CNV. When a single copy of the bacterial gene, VioA, is expressed in yeast it produces light purple colonies; in multiple copies, the colonies are a darker shade of purple. I am inserting a single copy of the VioA gene into a region of the yeast genome that undergoes inverted triplication events. Simply scanning plates for dark purple colonies will enable me to screen for ODIRA events quickly and measure their frequency. Using this visual indicator will allow me to rapidly screen different yeast mutants and determine the role they play in the ODIRA amplification mechanism.

Preterm birth is a leading cause of neonatal morbidity and mortality, with intra-amniotic infection and inflammation being major contributors to early preterm labor (PTL). Despite ongoing research aimed at reducing inflammation in neonates, most studies have focused on post-delivery while few have been done prior to delivery. IL-1 is a central upstream mediator of inflammation in the amniotic cavity and the neonate. IL-1 is a key cytokine that is responsible for induction or propagation of the cytokine cascade responsible for PTL. Rytvela, an interleukin-1 receptor antagonist made up of seven D-amino acids, acts as a selective antagonist of IL-1 signaling, which could be used to act as a therapeutic approach to reduce inflammation and prevent PTL. The purpose of this experiment is to determine if interleukin-1 (IL-1) is a key molecular target for the development of antenatal therapeutics to prevent PTL and fetal injury. We hypothesize that Rytvela administered intravenously to the mother will cross the placenta and be detectable in the amniotic fluid and fetal plasma, suggesting that Rytvela could effectively block IL-1 signaling in the fetus and therefore reduce fetal inflammation. Maternal blood plasma samples were drawn at Day 1, 2, 6 and 10 post infusion. To confirm the transfer of Rytvela to the fetus, we used liquid chromatography-mass spectrometry (LC-MS) to detect the drug, looking at integration, peak identification, and backlog pressures to see if Rytvela is detectable in maternal plasma. Rytvela was detected and luminex plates were run to measure cytokine levels. After GBS infection, Il-1 beta and Il-23 concentrations increased. After Rytvela administration, the concentration of the pro-inflammatory cytokines decreased. Future directions will involve measuring cytokine levels at these time points and correlating them with Rytvela infusion to evaluate the drug’s impact on maternal-fetal inflammation

Bronchoscopy with bronchoalveolar lavage (BAL) is a common approach to assess the graft in lung transplant recipients. However, bronchoscopy is an invasive approach that carries procedural risks. Identifying plasma biomarkers levels which correlate with those measured in BAL fluid enables less invasive investigations. This study aims to determine the correlation between biomarkers measured from plasma and BAL fluid. We analyze paired plasma and BALF (BAL fluid) samples collected from lung transplant recipients undergoing for-cause bronchoscopy (n = 95 individuals and inclusive of 164 encounters). Researchers collect paired samples from each participant within a two-hour timeframe. Researchers measure a panel of 39 biomarkers in samples using electrochemiluminescence assays. We evaluate plasma/BAL correlation data using Pearson correlation coefficients on log-transformed concentrations. Among participants, the average age is 61 years, 74% are male, 93% are white, with Restrictive lung disease (60%) being the most common pre-transplant pulmonary disease. The median time from transplant to bronchoscopy is 412 days (IQR: 194-741). Results indicate that correlational data is highly variable. The two most highly correlated biomarkers are IL-12/IL-23p40 (r = 0.67) and CXCL10 (r = 0.64). There are no biomarkers that have significant inverse correlations. The levels of 11 out of the 39 measured biomarkers show moderate correlation, ranging from r = 0.20 to r = 0.45. Many of these biomarkers are chemokines related to immune cell migration to the lung (e.g., CCL2, CCL3, CCL4, and CCL22). A key implication of this finding is that researchers should exercise caution when extrapolating alveolar biology from circulating (plasma) samples. Future analyses will test whether the ratio between paired BALF and plasma biomarker levels provides biological or clinical insight beyond using these biomarkers measured in isolation.

Given a set of goods and a set of individuals, one might ask what the optimal way to divide the goods among the individuals is. This is known as a bargaining problem. Bargaining theory is a set of mathematical tools which can help us answer these sorts of questions. Assuming that the individuals’ preferences can be represented numerically, a bargaining solution concept tells us the optimal division of goods, called the solution to the bargaining problem, among the individuals. In some cases, solutions to bargaining problems involve randomly choosing how some or all of the goods are distributed. Of interest to us is the fact that the solutions to these bargaining problems may fail to be continuous, in a certain sense. If the strengths of the individuals’ preferences are changed even slightly, it may be the case that the optimal division of goods changes drastically. Broadly speaking, the goal of this project is to understand when and why this phenomenon occurs. I begin by formally defining what it means for the preferences of the individuals, as well as the sets of solutions to the associated bargaining problems, to be close to one another. I then prove that under certain conditions, small changes in individuals’ preferences cannot result in large changes in bargaining solutions. I am currently still working on proving that if these conditions fail to hold, then one can slightly modify the individuals’ preferences in such a way that the associated bargaining solutions change quite substantially. We hope that these results can be applied to justify randomization amongst options in collective decision making problems, particularly those related to experimental design.

Xylazine is a veterinary sedative that has become a common adulterant in fentanyl products due to its ability to prolong the euphoric effects of fentanyl. Adulterated drug mixtures containing xylazine have been linked to an increased risk for respiratory depression and fatal overdose. Existing treatments for overdose such as naloxone do not work against xylazine and there is currently no FDA approved reversal agent for xylazine toxicity. Monoclonal antibodies (mAbs) are a promising therapeutic option to reverse drug overdose and can be used to target small molecules by sequestering them in the bloodstream and preventing their passage into the brain. Previously, we made a series of xylazine haptens and formulated them into vaccines where they were found to induce strong antibody responses, reduce brain to serum ratio of xylazine, and mitigate respiratory depression in Sprague-Dawley rats. Based on the protective effects of our xylazine conjugate vaccines, we hypothesized that we can create an effective reversal agent by isolating xylazine specific mAbs. In this study, we immunized mice with xylazine conjugate vaccines to generate antibodies specific against xylazine. We then used the secondary lymphoid organs of the vaccinated mice to establish stable mAb producing cell lines using hybridoma technology. Hybridomas were screened with ELISA and lead candidates were selected and sequenced for further characterization. We will conduct in-vitro characterization assays to quantify binding affinity, functional activity, and thermostability of our lead mAbs. Furthermore, in-vivo studies will assess the efficacy of our mAb lead candidates in rodent models.

TBC domain containing kinase (TBCK) is an understudied protein with three domains: a pseudokinase; Tre-2, Bub2, and Cdc16; and rhodanese, and is highly expressed in the brain. Homozygous mutations in TBCK cause a rare neurodegenerative disorder in children, which clinically presents as syndrome infantile encephalopathy, brain atrophy, cerebellar hypoplasia, and muscle hypotonia. Two mutations in particular, Arg126Stop and Arg511His in the pseudokinase and TBC domains respectively, are commonly found among TBCK patients. The progression of the disease is characterized by a global regression in brain development, severe intellectual disability, and premature death in acute cases. The pathogenic mechanism underlying TBCK syndrome is unclear, but past studies show that TBCK patient neurons demonstrate aberrant metabolite buildup in the lysosome likely resulting from abnormal lysosomal activity. Immunoprecipitation mass spectrometry was performed for wild type TBCK in both N terminal and C terminal tags, revealing a preliminary list of both known and unknown interactors for TBCK. To further investigate the early developmental implications of mutant TBCK, CRISPR/Cas9 directed mutagenesis is being used to generate two induced pluripotent stem cell (iPSC) lines harboring the Arg126Stop and Arg511His mutants for subsequent differentiation into neural progenitor cells (NPC) and neurons. Immunofluorescent imaging of the mutant NPCs will confirm the recapitulation of growth and lysosomal defects present in patient cells. To analyze the effect of TBCK mutation on lysosomal function/content, we will immuno-isolate lysosomes through lysosome immunoprecipitation (Lyso-IP) and identify proteomic changes through mass spectrometry. While providing a crucial in vitro cell model of two common patient mutations, these experiments will offer critical insight into cellular dysfunctions that contribute to TBCK disease states.

Non-syndromic orofacial cleft (OFC), comprising cleft lip, cleft palate, or a combination of the two, is among the most common structural birth defects. OFC has both genetic and environmental underpinnings, though the genetic contribution is only partially understood. Members of the same gene regulatory networks associated with OFC are candidates to harbor the “missing heritability” for OFC. Van der Woude Syndrome (VWS) is an autosomal dominant condition characterized by cleft lip and/or palate, and lip pits. Mutations in IRF6, encoding the transcription factor Interferon Regulatory Factor-6, account for approximately 70% of VWS cases, mutations in GRHL3, a transcriptional target of IRF6, account for 5%, and it was recently found that mutations in PRKCi, encoding a kinase, account for 5% more. Published data support that IRF6 is phosphorylated and thereby activated by RIPK4. However, the kinases PRKCi and IKK1 are also required upstream of IRF6 activity. Regulatory interactions within this kinase cascade are unclear. The goal of this project is to shed light upon the kinase cascade encircling IRF6 to illustrate genetic causes of VWS and non-syndromic OFC and ultimately improve patient outcomes. I hypothesize that IRF6 phosphorylation is dependent upon RIPK4, which is activated by IKK1 and downstream of PRKCi activity, and all components are necessary for IRF6 activation. To test this hypothesis, I am conducting experiments injecting mRNA products from our genes of interest into zebrafish embryos and detecting phosphorylation activity within the harvested protein through immuno-precipitation and mass spectrometry analysis to determine protein-protein interactions. I anticipate that in the absence of RIPK4, the pool of Differentially Expressed Genes (DEGs) will align with the pool of DEGs in the absence of IKK1 and IRF6 respectively. Implications of these findings will ultimately give a stronger understanding of the molecular foundations of VWS and non syndromic OFC.

Copepods are an essential link between micro- and macroscopic trophic levels in Salish Sea food webs. The distribution of copepods across spatial and temporal scales is well-known and is partially attributed to physical oceanic processes. However, few studies have characterized copepod densities at different tidal heights in the San Juan Channel. This study investigates copepod densities at depths of 0-25m and 0-50m during high and low slack tides when tidal currents are at their lowest velocity. Higher overall copepod densities were expected during slack high tide due to the influx of oceanic water from the Strait of Juan de Fuca. Samples were collected over four days in the northern San Juan Channel during September 2024. Twelve vertical plankton tows were performed with six replicates for high and low tides respectively. Samples were diluted and randomized using a plankton splitter, creating 5ml aliquots to calculate copepod density. Copepod densities from 0-50m depth during slack high tide were significantly higher (p-value < 0.001) than all other samples. No difference in copepod density was found between 0-25m and 0-50m depths during slack low tide. Increased tidal height resulted in higher copepod densities for low and high slack tides. Our findings suggest the physical processes within the San Juan Channel, such as the influx of colder, saltier waters during slack high tides increase copepod densities in the top 50m of the water column. These shifts in copepod densities may impact the feeding behavior of higher trophic levels in the San Juan Channel food webs.

The first-in-class capsid (CA) binding antiretroviral, Lenacapavir (Len), inhibits viral spread at multiple steps in the viral life cycle. Structural studies show that Len interacts with an FG-binding pocket between the N-terminal and C-terminal domains of adjacent CA monomers resulting in destabilization of the CA core lattice. Three key binding functional groups within Len that interact with CA were identified. Subsequently, six Len analogues (Lenalogs) were designed and synthesized. These Lenalogs vary by the removal or replacement of one of the identified functional groups. My work investigates the impact of Len and Lenalog binding on CA assembly rate, as well as, the structure of the assembled protein. Using an IPTG  E. coli expression system and ion exchange chromatography, I have expressed and purified CA protein. I induced in vitro assembly of the purified CA protein by the addition of inositol hexakisphosphate (IP6) in both the presence and absence of Len or the Lenalogs. Relative to Len, LL-10.4 and LL-15 promoted assembly, LL-14 was similar, while LL-11, LL-19 and LL-20 promoted assembly to a lesser extent. Samples with LL-10.4 and LL-15 were chosen for cryo-EM analysis as these promoted assembly to a greatest extent. CA was assembled on lipid vesicles (templated CA-like particles or CLPs) by the Dick lab (Emory University, Atlanta, GA), and these were subjected to cryo-EM data collection and analysis. Both LL-10.4 and LL-15 bound to the FG-binding pocket like Len. Negative stain transmission electron microscopy and light scattering will be used to further assess the effect of Len and Lenalogs on assembly kinetics. My work will be used to inform the design of next generation CA-targeting antiretrovirals.

Neonatal hypoxic-ischemic encephalopathy (HIE) occurs when the brain receives insufficient oxygen and blood supply before or during childbirth. HIE is a leading cause of neonatal mortality and morbidity that may also affect later brain development, specifically gyrification - folding of the cerebral cortex creating gyri and sulci. The nonhuman primate (NHP) brain is gyrified, similar to humans, making NHPs a highly translatable model to examine brain development after injury, which has not been well-studied in HIE. In our nonhuman primate (NHP) model of neonatal HIE, we induced injury through in utero umbilical cord occlusion (UCO) for 20 minutes, mimicking the cause of HIE in humans. Twenty-two term-equivalent pigtailed macaques (Macaca nemestrina) underwent UCO and were randomized to no treatment (n = 11) or treatment with therapeutic hypothermia and erythropoietin (TH + Epo [5x1000 U/kg]; n = 11), while non-UCO animals served as controls (n = 7). All animals were delivered via cesarian section. Injury severity was determined by physiological parameters (Apgar score), lactate, and pH levels after resuscitation. To evaluate the impact of injury on gyrification, we will utilize magnetic resonance imaging (MRI) taken 6-months post-injury to measure the gyrification index (GI). GI will be calculated by taking brain’s inner-to-outer hemispheric ratio; the inner trace following the contours of the gyri and sulci, and the outer trace following the circumference of the cerebral cortex. We hypothesize that global and regional GI will be altered in animals exposed to UCO, corresponding with decreased brain volume and greater injury. We also hypothesize that treatment will mitigate some of these changes, leading to a GI closer to control. These results will help determine whether hypoxia-ischemia alters the trajectory of cortical development, as well as the association between injury severity, brain volume, and gyrification.

This study aims to understand users’ needs in designing a mobile application that assists Cardiopulmonary Resuscitation (CPR). This study is designed through a two-stage online interview, beginning with a screening survey that asks about participants’ occupations and experience with CPR, followed by the main interview that asks about their challenges when performing CPR and their opinions on the most efficient type of feedback. Eight participants who completed the survey included CPR instructors, paramedics, firefighters, and medical students with experience ranging from 3 to 20 years. The participants rated maintaining compression depth as more challenging (7.63 out of 10) compared to maintaining compression rate (5.25 out of 10) when performing CPR, with 10 representing the highest level of difficulty. Participants also reported that visual feedback would be more beneficial for compression depth and auditory feedback for compression rate. Therefore, these findings suggest that an effective assistive CPR device should have real-time visual feedback to aid in-depth consistency while auditory cues support rhythm accuracy similar to a metronome. By leveraging these findings, the proposed application has the potential to enhance CPR effectiveness, improve user confidence, and ultimately increase patient survival rates.

Pregnant women infected with influenza A virus (IAV) are at higher risk of morbidity, mortality, and poor fetal outcomes. However, the difference in the pathogenesis of IAV between pregnant women and non-pregnant women remains inadequately understood, primarily due to the lack of animal studies that use a translational model of infection. I hypothesized that higher IAV viral load and Type I interferon concentrations would be observed in the lungs and bronchoalveolar lavage of pregnant pig-tail macaques compared to non-pregnant macaques, and that correlating these metrics would yield different results across groups. We inoculated pregnant (n=11) and non-pregnant female (n=18) pig-tail macaques (Macaca nemestrina) with IAV H1N1 (A/California/07/2009) and euthanized them at 5 days post-inoculation, when we expected to observe peak lung pathology. We tested pulmonary function at baseline and study endpoint and conducted clinical assessments daily. I extracted RNA and performed quantitative polymerase chain reactions on the samples to calculate viral load. I also performed enzyme-linked immunosorbent assays to quantify concentrations of Type I interferons (IFN-α, IFN-β). Lastly, I analyzed pulmonary physiology data and clinical assessment scores as a reliable measure of disease severity. A bi-modal distribution of viral load was observed in the lungs of pregnant animals (high>9e5 copies/mg; low<2e4 copies/mg), which was not observed in non-pregnant animals.  When correlating viral load at 5 days post-inoculation with Type I IFN in the lung of the pregnant animals, I found a significant positive correlation between IFN-β and viral load in both the lungs (ρ=0.8, p=0.03) and BAL (ρ=0.9, p=0.02). These results suggest that despite a strong IFN-β response in the lung, a high viral load persisted in the pregnant animals. Next steps could explore whether the kinetics of the pulmonary innate immune response is delayed in pregnancy, which impairs viral clearance. 

Geographic Information Systems (GIS) are a powerful framework that enables the analysis of spatial data, or information connected to a location, that can be applied to a variety of fields, such as public health, policy, agriculture, and environmental management. With these frameworks, we can create maps to convey specific data or general information, make comparisons between data sets, and quantify spatial characteristics. In this study, I utilized a GIS framework together with Real-Time Kinematic Global Navigation Satellite Systems (GNSS RTK) methods to collect spatial data regarding hiking trails throughout Saint Edward State Park in Kenmore, Washington. I hypothesize that the positional accuracy of data collected via GNSS RTK is significantly better than positions collected via methods that do not incorporate differential correction. To test this hypothesis, I will collect differentially corrected positional data along trails in the park and compare them to uncorrected data gathered between 2013 and 2015 from the same trails. Comparisons will be made using a t-test to determine whether there is a statistically significant difference between the mean differences of each data set. Furthermore, I will use this spatial data to visualize more accurate trail locations, indicate areas requiring maintenance, and decommission unofficial trails that are harmful to the ecology in the park.

The Miocene Climatic Optimum (MCO) (17-14 Ma) represents the most recent significant global warming event and provides valuable insights into the future of our planet with higher CO2 levels and warmer temperatures. The Mascall Formation in central Oregon contains a fossil plant assemblage that reflects the vegetation present during the height of the MCO. Despite over 50 years of research in this formation, there is still much to learn about the ancient plant community. For instance, a fossil specimen, consisting of several leaves, that was collected recently exhibits similar trait to bamboo, which represents a new fossil finding in this formation. This project seeks to confidently assign this specimen to the bamboo subfamily Bambusoideae. By analyzing morphological and vein architectural features of the leaves using various microscopic techniques and digital photography. In addition to studying the specimen itself we explore the fossil plant silica bodies (phytoliths) also present in the surrounding substrate to provide independent evidence that bamboo was present in the region. The phytoliths can then be compared to those of current Native American bamboo to find evidence for relatedness or if it was part of some other lineage of bamboo, whether extinct or still present in South America or Eastern Asia. If the specimen turns out to be bamboo, it would have implications for the climate and ecology of eastern Oregon during the MCO as bamboo was not assumed to have previously been present.  

Cave formations, also called speleothems, are natural archives of past climate conditions. Analysis of these speleothems can provide information about environmental changes over thousands of years. Church Mountain Cave is in the Northeast Cascades and is distinctly characterized by its unusually predominant speleothems, which is relatively unusual for western Washington. This project explores the potential of Church Mountain and other caves as paleoclimate archives. I begin with a characterization of Church Mountain Cave, focusing on cave morphology, stratigraphic and structural position of the cave, and forming a hypothesis of cave formation and fault activity. This classification will allow for a detailed view on Church Mountain Cave and the factors impacting speleothem formation. We also characterize a range of speleothems from other caves using trace element and isotope analysis, with the eventual goal of using uranium-thorium dating to establish precise ages and stable isotope analysis with oxygen isotopes to infer past temperature, precipitation patterns, and other environmental factors. By refining regional paleoclimate reconstructions, we can improve predictions of future climate trends and extreme weather events. Additionally, this study underscores the importance of caves as climate archives and highlights the need for conservation efforts to protect these valuable and fragile environments for continued scientific research. 

Mycoplasma genitalium (MG) is a common sexually transmitted bacterium that causes serious health problems such as pelvic inflammatory disease, urethritis, and pregnancy complications. The efficacy of antibiotics has significantly decreased due to antibiotic resistance; about 50% of US strains are resistant to azithromycin, a common treatment path, and resistance reaches 100% in high-risk populations. Preliminary research done in our lab has shown that MG is susceptible to tinidazole (another antibiotic) in vitro. We hypothesize that tinidazole is effective against MG because it creates superoxide radicals that MG cannot detoxify. To test this, the sodA and katA genes, encoding enzymes that detoxify reactive oxygen species, were introduced into the MG genome. The insertion site was determined by whole genome sequencing, and we selected two mutants with insertions unlikely to affect other genes. These two strains were compared to the parent strain in time-kill experiments to measure susceptibility to tinidazole. Cultures of these strains were incubated for 10 days with two-fold dilutions of tinidazole, plating aliquots onto agar plates each day to quantify surviving MG. The individual colonies present on the plates are counted and graphed, allowing us to compare the efficacy of tinidazole on the separate strains. To confirm the enzymes are being expressed, we used a hydrogen peroxide assay to measure the levels of hydrogen peroxide, which is formed from the radicals released from the cells. In conclusion, we hypothesize that the radicals produced by tinidazole kill MG by inducing DNA damage. We, therefore, measured the susceptibility of 10 DNA repair mutants to tinidazole and found that deletion of MG_360 enhances susceptibility. Results from these experiments can be used to understand the mechanism by which tinidazole and other nitroimidazoles kill MG. This data is critical in the battle against antibiotic resistance and can improve treatment options globally. 

Overdose deaths in the United States have rapidly increased in the past few years accounting for over 107,000 deaths in 2022 with more than half being attributed to the co-usage of opioids and stimulants. Despite the prevalence of polysubstance use, research has predominantly focused on single substance use, leaving a gap in knowledge regarding its neurological effects. Addiction-associated behaviors such as drug-seeking, drug-taking, and relapse vulnerability has been attributed dysregulation of the striatum. We recently found that polysubstance exposure to methamphetamine and fentanyl leads to behavioral differences in methamphetamine-seeking but not fentanyl-seeking relative to single-substance rats, suggesting that polysubstance use causes distinct changes in striatal circuitry. Our overarching objective is to determine to what extent pursuit of methamphetamine and fentanyl involves shared neural pathways. How do distinct striatal neuron subpopulations responsive to either methamphetamine or fentanyl regulate drug-seeking in animals exposed to both substances? To investigate this, rats are placed into self-administration boxes and undergo two phases of daily intermittent access drug self-administration. In the first phase of self-administration, lasting 10 days, a novel targeted recombination in active population (TRAP) technology and recombinant viral vector is used to target inhibitory designer receptors exclusively activated by designer drugs (DREADDs) to striatal cells that are activated during fentanyl- or methamphetamine-seeking. For the second phase of the experiment, lasting 28 days, rats are then divided into groups for either self-administration of methamphetamine, fentanyl or a polysubstance model. Using chemogenetic manipulations in polysubstance rats, we will test the hypothesis that inhibition of the striatal neuron subpopulations active during fentanyl-seeking will decrease methamphetamine-seeking whereas inhibition of methamphetamine activated neurons will have no impact on fentanyl-seeking. These experiments will provide important insights and lay the groundwork for future studies into how striatal circuits regulate behavior during single and polysubstance use of opioids and stimulants.

Cancer immunotherapy, specifically Adoptive Cell Therapy (ACT), has revolutionized treatment approaches using genetically modified T cells to recognize and eliminate cancer cells. However, tumors combat this by creating an immunosuppressive tumor microenvironment (TME) blocking effective antitumor immune responses.  Dendritic cells (DCs) are innate immune cells that act as messengers between the innate and adaptive systems.   In the Oda lab we have designed Dual Costimulatory Receptor (DCRs) that combine a FLT3L or CD40L ectodomain with different costimulatory endodomains (e.g. CD40, 4-1BB, OX40), to provide both T cell-extrinsic and -intrinsic costimulatory signals.  These DCRs are expressed on the surface of antigen specific T cells, and the combination of these signals allows for enhanced tumor antigen presentation and dendritic cell activation, leading to an increase of the immune response to target and destroy cancer tumors. I will investigate how incorporating DCRs on T cells will enhance ACT effectiveness. I hypothesize these DCR signals on T cells will enhance dendritic cell function in the TME, allowing for increased T cell activation and antitumor immune responses. To test this, I will conduct in vitro coculture experiments to determine how DCR-T cells, dendritic cells, and pancreatic cancer cells interact together. I will study the interactions of these immune cells using live cell imaging technology such as the Incucyte. Additionally, I will analyze the phenotypes of our distinct cell populations via flow cytometry.  This research aims to enhance the development of immunotherapy for Pancreatic and all solid cancers by improving the recognition of cancer cells from the immune system. These results could help pave the way for improving solid tumor cancer treatment.

Serotonin serves a vital role in the regulation of stress responses, and variance in the release of serotonin was found to contribute to various mental illnesses such as anxiety and depression. Current mental health treatments heavily rely on Selective Serotonin Reuptake Inhibitors (SSRIs). While these medications are generally effective, there are patient populations for whom SSRIs show limited efficacy. Recent studies found that in response to stress, the expression of the FKBP5 gene also increases and modulates many neuronal pathways including serotonin. This experiment determined whether manipulating FKBP5 gene expression in the dorsal raphe (DRN) directly correlates with serotonin release in the basolateral amygdala (BLA), an established neural circuit for fear. To manipulate FKBP5 gene expression, an adeno-associated FKBP5-Cre virus was injected into the DRN of Pet1-Cre transgenic mice, causing up or downregulation of FKBP5 in the DRN. To gauge the effects of FKBP5, fiber photometry was used to measure the release of serotonin following optogenetic activation of the DRN-BLA pathway using a 5HT GRAB sensor injected into the BLA. We hypothesize that increased FKBP5 expression in the DRN will increase serotonin release to the BLA, and as FKBP5 expression is decreased, the release of serotonin to the BLA will decrease. Success in modulating serotonin release using FKBP5 gene expression will expand therapeutic targets in mental illness research, mitigating the gap in treatment efficacy for patients who have undergone ineffective SSRI therapy.

Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic gammaherpesvirus known to cause Kaposi sarcoma (KS), a cancer of the soft tissues, and several other diseases. KSHV has two distinct replication cycles: a latent and lytic cycle. During latent infection, only a small section of the viral genome, the KSHV latency-associated region (KLAR), is expressed. Spindle cells, the main proliferating cell type in KS tumors, are thought to be of endothelial origin and are primarily latently infected. Due to lowered viral gene expression during latency, these cells have few viral factors to target therapeutically. Cellular factors required for infected cell survival, like altered metabolic pathways, are potential therapeutic targets for latently infected cells. One metabolic pathway altered by latent infection is fatty acid synthesis (FAS). My research focuses on understanding how KSHV infection induces FAS in cells. Since previous research has shown that expression of KLAR is sufficient to increase lipid droplet formation, a measure of FAS induction, I hypothesize that expression of one of the four genes present in KLAR is likely what upregulates this metabolic pathway. To test this hypothesis, I infected telomerase-immortalized microvascular endothelial (TIME) cells with lentivirus containing a viral plasmid overexpressing one of the four KLAR genes. I then measured lipid droplet formation across each transduced cell population using a flow cytometer. This project is still in progress; however, if the increase in lipid droplet production in transduced cells is similar to the increase observed in cells latently infected with wild-type KSHV, then I will conclude that the over-expressed gene was sufficient to up-regulate FAS. Identifying which viral gene induces FAS in infected cells will provide a new direction for future mechanistic studies and aid in identifying potential therapeutic targets for KSHV-associated diseases.

Gene arrangements are observed in human diseases such as cancer and developmental disorders. In developmental disease, gene triplication with an inverted central copy is observed, while a hallmark of cancer are palindromes, or inverted repeats of DNA. Therefore, testing one mechanism of gene arrangement in an easily studied organism like the  budding yeast Saccharomyces cerevisiae may shed some light on the human genome and disease generation. Yeast cells grown for >200 generations in sulfate limiting media are enriched for triplication of the high affinity sulfate transporter SUL1 with the center copy inverted, as amplification confers a selective advantage. To explain how such a triplication occurs, the Brewer and Dunham Labs proposed a model called Origin Dependent Inverted-Repeat Amplification (ODIRA). The ODIRA mechanism requires a DNA origin of replication and short, inverted repeats flanking the SUL1 gene. During DNA replication, an error of the replication fork, or fork regression, causes annealing of leading and lagging strands to create a hairpin intermediate. The intermediate then replicates and recombines into the genome, forming interstitial triplications, with the middle copy inverted. While the proposed mechanism explains the observed triplication in yeast, the specific proteins involved are not yet known. The genes I've chosen to test are the DNA helicases MPH1 which prevents cross-over between ectopic sequences, and RRM3 which relieves replication fork pauses. Both are predicted to regulate necessary steps of the ODIRA mechanism, making them good candidates for genes that may be involved in these triplications. By deleting each gene, I can then measure the frequency of ODIRA events in those strains and compare them to wild-type strains. Increased ODIRA events in the knockout strains may implicate their role in the ODIRA mechanism and prompt further study of these genes and how they might affect copy number variation in humans.

This research aims to enhance the food literacy of volunteers at the University of Washington (UW) Food Pantry by providing foundational knowledge on food security, food policy, nutrition, dietary needs, and allergies. Many pantry volunteers lack a background in nutrition or public health, which limits their understanding of the complex issues surrounding food insecurity and food literacy. Through the Winter 2025 Food Systems, Nutrition, and Health Capstone project, my team and I will create a comprehensive brochure that will be incorporated into the pantry’s volunteer training materials. The brochure will include sections on the pantry’s background and goals, the scope of food insecurity among college students both at UW and across the nation, food policies that affect access to nutritious foods, and basic nutrition education. Our objective is to foster empathy and understanding among volunteers, encouraging a deeper connection to the shoppers they serve and the challenges faced by people who rely on the pantry. At the end of the quarter, my team will present the brochure along with other deliverables to community stakeholders. In Spring quarter, I will administer a pre-survey to pantry volunteers to assess their current food literacy and knowledge of food insecurity. Following the brochure’s distribution and review, volunteers will complete the same survey, allowing for an analysis of any changes in their understanding. The study will evaluate whether the brochure improves volunteers' knowledge of food insecurity, ultimately testing if this intervention leads to better food literacy outcomes. If the brochure proves effective in this regard we also hope it will foster increased empathy among pantry shoppers and volunteers.

Westfield Southcenter Mall, located in Tukwila, Washington, is one of the largest malls in the nation, and like many malls, its aging retail spaces and surrounding strip malls are becoming less viable. With rising housing costs and a growing regional population, it is clear that spaces like Southcenter must be transformed into affordable, mixed-use districts that can provide housing, vibrant community spaces, and accessible transportation options. This project explores how Southcenter Mall can be redesigned using New Urbanist principles to foster a thriving community. Using site visits and global case studies of recent successful mall redevelopments, it analyzes the current shortcomings of Southcenter Mall and proposes a more successful mixed-use alternative. The final deliverables include a 3D model mock-up of a revitalized Southcenter that includes affordable housing, ground-level retail, and an overhauled transportation framework prioritizing pedestrians and cyclists.

Previous research has determined that nanoparticle systems require a wide parameter space to effectively conduct synthesis and characterization. As a result, the development of high-throughput techniques is essential for efficiently analyzing the large datasets produced in colloidal particle experiments. These methods enable the rapid assessment of particle properties, such as size, shape, and charge, which are critical for modifying nanoparticles for specific applications. In order to do this, advancements in automated synthesis platforms, such as the Jubilee automated multi-tool system, offer the potential to streamline the fabrication of magic sized clusters. This approach has the potential to accelerate the discovery of novel nanoparticles but also allows for real-time adjustment of synthesis parameters to achieve desired properties with high precision, throughput, and reproducibility. As a result of the optimized synthesis process, characterization using techniques such as small angle X-ray scattering (SAXS) and UV-vis spectroscopy can be done at an accelerated rate. Efforts to enhance the durability and performance of the Jubilee automated multi-tool platform are focused on integrating advanced materials to improve system lifespan. This work will incorporate glass syringes and resin-printed components which offer improved chemical resistance and precision compared to traditional plastic components, extending the utility of the platform to be able to work with solvents and chemicals that are corrosive, volatile, or strong solvating agents for typical plastics. These improvements aim to reduce wear and tear, extend the lifespan of critical components, and ultimately ensure the platform's reliability for long-term use in high-throughput nanoparticle synthesis.

Rhabdomyosarcoma (RMS) is a rare pediatric cancer that begins growing within soft tissue and becomes deadly with rapid tumor growth, eventually leading to therapy resistance and metastasis. Today, drug therapy options remain scarce in relapsed patients, resulting in significantly lower 5-year survival rates compared to patients with localized disease. Recent research in other cancers has implicated the hyperexpression of an oncogene, YBX1, and an immune checkpoint marker, PD-L1 in driving therapy resistance and immune response evasion of cancer cells. YBX1 is an RNA-binding protein that improves the survival of stem-like cells in RMS. Additionally, PD-L1 is a protein expressed on the surface of tumor cells that binds to PD-1 on T lymphoid cells and aids in the evasion of T-cell-induced cell death. We hypothesize that the combination drug therapy with atezolizumab, a PD-L1 inhibitor, and SU056, a YBX1 inhibitor, will synergistically inhibit tumor growth by increasing immune cell activity. I performed intraperitoneal (IP) transplantation of RMS tumor cells derived from a zebrafish RMS tumor line (‘3.2T’) using a syngeneic line of zebrafish, ‘CG1’. The drug treatment study consists of 4 experimental groups (SUO56 or atezolizumab only, two-drug combination, and vehicle control) receiving two drug injections via IP route over 7 days. I quantified tumor growth over 7 days via ImageJ/Fiji software. Additionally, we use RNAscope (RNA-targeted in situ hybridization) to determine mRNA expression levels of various tumor-associated immune cell markers, including CD4 and CD8 for T lymphocytes and PAX5 for B lymphocytes. Based on our knowledge of YBX1 and PD-L1, we expect to see a greater reduction in tumor growth and an improved immune response with combination therapy compared to single-drug treatments. Completing this research will address the current lack of effective therapies in treating relapsed RMS patients and possible combination therapies for improving RMS patients’ survival.

Individuals with Stage II/III severe periodontal disease were recruited from the Graduate Periodontics Clinic at the University of Washington School of Dentistry using an approved IRB (STUDY00016871). Subgingival plaque samples were collected from four tooth sites: an active inflamed site, two adjacent tooth sites, and a distant healthy tooth site. Sterile paper points were inserted into the gingival sulcus for 30 seconds. DNA was isolated and extracted using the Qiagen AllPrep DNA/RNA Mini kit (Cat. #80204), then purified and concentrated using the Zymo Clean & Concentrator (Cat. #D4014) kit. 16S rRNA libraries were generated and sequencing was performed on the MiSeq platform (Illumina, San Deigo, CA, USA) using 300bp paired-end chemistry. Raw reads were processed and analyzed using Qiime2 and the DADA2 algorithm to generate amplicon sequence variants (ASVs), which were then classified using the expanded Human Oral Microbiome Database (eHOMD). Differences between tooth sites were assessed within and across individuals. Correlation between taxonomic levels and clinical data was also assessed. Data analysis is still being performed at this time. Based on previous literature (Pawolski et al, 2005, Kerns et al. 2023), we expect that a subgingival community gradient radiates from tooth sites affected with periodontal disease toward distant healthy sites. We aim to resolve this within individuals using ASVs for the first time. Additionally, we anticipate an increase in disease-associated bacteria within actively inflamed tooth sites, such species within Porphyromonas, Tannerella, and Treponema genera. Furthermore, we anticipate a gradient of perio-pathic disease-associated bacteria will decrease in relative abundance the further away from active diseased sites. We expect that results from our study will highlight the presence of a subgingival microbiome composition and enrichment of specific gram negative perio-pathic disease-associated species within clinically healthy tooth sites in patients with active periodontal disease despite the absence of clinically observed inflammation.

The activation of inflammasomes is a crucial component of the early immune response to pathogens and initiates a form of inflammatory programmed cell death called pyroptosis. During infection, a cytosolic inflammasome-forming protein sensor detects a pathogen to assemble the inflammasome complex, which subsequently activates the protease Caspase-1 (CASP1). CASP1 processes Gasdermin D (GSDMD), inducing pyroptosis through pore formation in the plasma membrane, while also facilitating the release of proinflammatory cytokines, such as IL-1β and IL-18. Adenovirus (AdV) is a common pathogen that causes inflammatory symptoms by infecting multiple mucosal epithelial tissues in the respiratory tract and intestinal tract such as the nose, mouth, and eyes. We wanted to test whether AdV infection could activate one of the main inflammasome sensors in human conjunctival epithelial cells (hCjE cells), which is NLRP1. However, we found that upon AdV infection, NLRP1-mediated cytokine release is absent, suggesting that CASP1 signaling is suppressed. Interestingly, despite the loss of IL-1β and IL-18, pyroptosis remains unaffected. Recent studies indicate that in the absence of CASP1, inflammasomes can activate Caspase-8 (CASP8), leading to the cleavage of Caspase-3 (CASP3) and Gasdermin E (GSDME), resulting in an alternative, incomplete form of pyroptosis. Thus, I hypothesize that during AdV infection, host cells are still able to induce pyroptosis by activating the alternative CASP8-GSDME pathway. To test this hypothesis, we generated and validated genetic knockouts of CASP8, GSDMD, GSDME, and CASP3 in hCjE cells to assess their roles in pyroptosis during AdV infection. These findings will provide new insights into viral immune evasion strategies and inflammasome regulation in epithelial cells.

Traumatic brain injury (TBI) results from a blow to the skull that causes shearing forces in the brain. Elevating intracranial pressure (ICP) at the moment of impact may protect the brain from TBI by stiffening the brain tissue and decreasing shearing. When they expect an impact, humans naturally brace and perform a Valsalva maneuver (exhaling against a closed airway), which momentarily elevates ICP. In a ferret TBI model, we conducted abdominal compression using a blood pressure cuff to induce a Valsalva-like response (VLR) and determine whether VLR resulted in neuroprotection. The ferret model was chosen for its gyrified brain structure and white to grey matter ratio that closely resembles the human. TBI was induced using a CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration) device, which is designed to deliver high-energy, controlled skull impacts. Initial work showed that the abdominal compression procedures increased ICP. The TBI study involved a total of 36 adult ferrets of both sexes randomized into three groups: (1) a sham control group exposed to isoflurane with a cuff but no compression, (2) a TBI group with a cuff but no compression, and (3) a TBI group with a cuff and abdominal compression. Baseline behavioral assessments (CatWalk, Novel Object Recognition, Swim Test, and Open Field) were conducted one week prior to injury. Post-injury behavioral testing, using the same assessments, was performed at 24–48 hours and 8 days post-TBI to evaluate functional outcomes. On day 8, ferrets were euthanized, and their brain tissue was collected and assessed for neuropathological outcomes. We hypothesize that abdominal compression will mitigate deleterious TBI outcomes. If these findings are supported, this intervention could improve the lives of those at risk of TBI and contribute to ongoing research in the field.

Tau protein is highly expressed in neurons and other neural cells, including astrocytes. The accumulation of hyperphosphorylated tau aggregates, known as neurofibrillary tangles (NFTs), is a hallmark of neurodegenerative diseases, particularly Alzheimer’s disease (AD). While tau aggregation is thought to advance AD through toxic gain of function, the loss of tau physiological function may also contribute to the adverse progression of the disease. However, how the lack of tau physiological functions in neurons contributes to AD progression remains understudied.  Studies have shown that tau depletion results in minimal phenotypic differences and may even mitigate cognitive decline in AD mouse models. Here, we investigate the molecular consequences of tau loss in both neurons and astrocytes. Using CRISPR/Cas9 gene editing, we generated tau knockout (Tau KO) human induced pluripotent stem cell (hiPSC) lines, which were subsequently differentiated into neurons and astrocytes. We first focused on assessing how Tau depletion affects the hiPSC-derived neurons. Our findings indicate that tau depletion does not impair neuronal differentiation or increase cytotoxicity and cellular stress. However, preliminary data suggest that Tau KO neuronal cultures—composed of 95% neurons and 5% other neural cells—exhibit reduced synaptic firing activity and network burst frequency. These results suggest that tau loss in neurons and glial cells negatively impacts neuronal activity, providing new insights into the functional consequences of tau depletion in AD pathology. To gain deeper insight into how tau depletion negatively impacts neuronal activity, we performed transcriptomic analysis on Tau KO hiPSC-derived neurons using RNA sequencing (RNA-seq). We are currently analyzing and validating the results, which may further elucidate the molecular mechanisms underlying tau loss-of-function in neuronal regulation and AD pathology. In the second phase of this investigation, we will also differentiate the Tau KO hiPSC into astrocytes and assess how tau depletion impacts astrocytic viability and functions.

Cortical tracking, a method that examines how neural activity encodes the dynamic features of the incoming speech stimuli, allows for the study of naturally produced continuous speech. Successful encoding of acoustic features is fundamental for language processing and comprehension. Studies show that cortical tracking of at least some acoustic speech features is already robust in the first year of life. However, it is unclear whether bilingual infants exhibit enhanced cortical tracking of non-native languages compared to monolingual infants, consistent with the idea of having a "bilingual advantage" as suggested in prior research. To investigate this, we recorded neural responses from 11-month-old English learning monolinguals, English-Mandarin learning bilinguals, and two mature comparison groups of English monolingual and English-Mandarin bilingual adults, while they listen to naturally produced, continuous, infant directed speech using electroencephalography (EEG) in three conditions: English, Mandarin, and Vietnamese. Stimuli were presented at an overall level of 70 dB SPL in a sound-attenuated booth. Using a combination of machine learning and linear modeling (i.e., Multivariate Temporal Response Function approach), we analyze the EEG signals using a multivariate encoding model consisting of acoustic features including envelope, envelope derivative, word onset, and phoneme onset. We hypothesize that both bilingual adults and infants will exhibit enhanced encoding of acoustic features in Vietnamese compared to monolingual adults and infants, indicating bilingual advantage in processing a third language. Additionally, we anticipate the bilingual advantage to be more prominent in infants than adults. These findings will contribute to the understanding of how bilingualism influences neural encoding across different languages and provide neural evidence of bilingual advantage in processing and acquiring a third language. I participated in study design, recruitment, data acquisition and analysis.

Capillary microfluidics capitalize on surface tension effects encoded in microchannel geometry and chemistry to transfer liquids without external instruments - making them a user-friendly technology for point-of-care tests. For most applications, hydrophilic surfaces (contact angle < 90˚) are necessary to induce surface tension driven flow. Currently, vacuum plasma chambers that alter surface chemistry achieve this. Unfortunately, hydrophilic properties made with plasma processing are temporary, costly, and unstable. An inherently stable hydrophilic 3D-printing resin containing polyethylene glycol diacrylate (PEGDA) and acrylic acid (AA) was developed for capillary microfluidics [1]. Similarly, our group has also optimized printing parameters for resins containing PEGDA and Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) that are inherently porous, hydrophilic, and have applications for development of engineered living materials (ELMs) [2]. Our objective was to optimize and validate 3D printing parameters and geometries for both resins using a range of liquid crystal display (LCD) printers. Our proof-of-concept prints for the PEGDA-AA resin had average contact angle measurements of 42.8 ± 8.77°. Percent differences between designed and printed channel lengths, widths, and depths were 31.5 ± 0.23%, 28.9 ± 3.41%, and 2.40 ± 13.9% respectively. Additionally, we have demonstrated the feasibility of autonomous flow of fluids in the PEGDA-LAP resin with coefficients of variations (CVs) of <5% for microchannels of widths ≥ 137.6 µm. By exploring innovative resins, we increase accessibility and capability for rapid and inexpensive prototyping of microfluidics to be applied to diagnostic tests. These methods reduce costs and carbon footprints relative to traditional additive manufacturing methods.

The Kodiak Archipelago in southern Alaska has a rich archaeological heritage that has fascinated archaeologists and local communities for decades. Despite the presence of many archaeological research projects, archaeobotanical remains found during excavation have yet to be analyzed. The archaeobotanical remains recovered from the Kodiak Archipelago have often gone overlooked by archaeologists who considered preservation too poor in the wet climate and focused instead on fauna from shell-midden sites or other cultural artifacts. The Tanginak Spring site on Sitkalidak Island in southeast Kodiak was excavated by University of Washington field schools between 1994 and 2003. It is considered one of the oldest identified sites on the archipelago, dating to 7500-6000 cal BP. Sediment samples taken during these excavations were retrieved, floated, sorted, and identified by the archaeobotany class at the University of Washington. This poster presents the initial results of the analysis of wood charcoal and other preserved plant remains from the site, providing evidence to develop new insights into plant use by Kodiak’s earliest settlers.

Silica nanoparticles have diverse applications in catalysis, imaging, and drug delivery. Tailoring these nanoparticles for specific applications requires precise control over their size, surface chemistry, porosity, and polydispersity. These properties are controlled by a wide range of factors such as reactant type and concentration, pH, reaction temperature, and other synthesis parameters. Due to the large parameter space, determining the optimal reaction conditions for synthesizing silica nanoparticles with the desired size and morphology is time-consuming and challenging. An accelerated experimentation platform integrating automation and artificial intelligence can streamline the selection of reaction parameters for synthesizing silica nanoparticles with targeted size and morphology using machine learning-based iterative design of experiments to optimize material properties. This system uses the Science Jubilee flexible laboratory automation platform to carry out sol-gel synthesis. Small-angle X-ray scattering is used to characterize the sample. The data collected is used to optimize the reaction condition for synthesizing the targeted nanoparticle. We have successfully carried out sol-gel processes and synthesized silica nanoparticles with various sizes and polydispersity using the platform. Currently, we are working on optimizing the selection of sample synthesis conditions.

Parents play a significant role in shaping adolescent alcohol use. The specific role of adolescent decisional freedom—the extent to which adolescents independently make decisions— has yet to be examined. I conducted a brief literature review on adolescent decisional freedom, and this study explores its links with alcohol use within distinct developmental periods. Data from baseline to year 6 follow-up of the National Consortium on Alcohol and NeuroDevelopment in Adolescence study (N=831) were tested for cross-sectional associations between decisional freedom and alcohol use phenomenology (i.e., drinking days per average month, past month alcohol consumption, quantity of drinks during average drinking period, and binge drinking days in the past year and month). Separate models were tested for early adolescence (ages 12-14), middle adolescence (ages 15-17), late adolescence (ages 19-20), and emerging adulthood (ages 21-24). Adolescent decisional freedom was measured using a self-report 5-point Likert scale across distinct domains (e.g., spending money, drinking alcohol, time spent with friends). Gender and age of first drink were covariates, and each model examined associations between decisional freedom and gender. Regression results consistently linked lower decisional freedom to lower alcohol use across all phenomenology in early adolescence (bs ≤ −.41, ps < .01). For middle adolescence, the protective effect of limiting decisional freedom only emerged for drinking days per average month (b = −.29, p < .01) and quantity of drinks during average drinking period (b = −.46, p = .001). In early and late adolescence, the association between lower decisional freedom and fewer past month binge drinking days was stronger for boys (bs ≥ 0.43, ps < .05). These findings suggest that increasing control over early adolescents’ decisional freedom, particularly for boys, and flexibly granting greater decisional freedom over time may protect adolescents from harmful decisions associated with alcohol use.

Understanding the ecology of vegetation systems in Earth’s past in response to past warming events helps contextualize how they might respond to current climate events. Ecological succession is an ecosystem dynamic in which plant species with different life strategies replace each other as plants colonize a disturbed habitat. Reconstructing which successional stage a fossil plant represents is an important step in reconstructing this process in the past. However, fossil plants preserve a limited number of traits. Leaf vein density (LVD) is a trait that relates to maximum photosynthetic rates and can be measured from fossil leaves, but there is limited empirical evidence for how it varies across succession in temperate deciduous forests. To address this knowledge gap, our study measures LVD of modern plant communities across a successional gradient in western North Carolina. We hypothesize that plants in younger forests have greater access to sunlight due to a less established canopy and will therefore have higher LVD to support a higher photosynthetic rate. As succession progresses and the canopy closes, we hypothesize that LVD will decrease with reduced light availability. Samples were taken from five sites in western North Carolina that vary in how long forest re-growth occurred following clear-cut timber harvesting, 4, 21, 44, 94, and roughly 200 years. At each site, leaves were collected and sampled at a community scale and were chemically treated to create images that highlight the veins. We then used ImageJ to measure LVD. The community mean and variance of LVD across succession will be analyzed, using both unweighted and weighted approaches, to test our proposed hypothesis of decreasing LVD through succession. Preliminary results suggest a potential LVD decrease as hypothesized but driven more by understory species rather than dominant tree species. Future work will refine interpretations and consider implications for the fossil record.

Human gastrulation is the period of embryonic development during which a single-layered blastula develops the three germ layers, which give rise to all of the specialized cell types in our bodies. Differentiation of these layers is controlled by epigenetic factors, which chemically modify the DNA, therefore activating or repressing a gene’s activity. Very little is known about the role of epigenetic factors in human gastrulation, as it’s difficult to obtain samples at the proper time for study; samples from IVF are too early to study, and fetal samples are too developed. Despite these complications, it’s important to study gastrulation because it’s during this time that developmental disorders and loss of pregnancy can occur. My goal is to delete seven epigenetic factors and determine their role in human embryogenesis using a human pluripotent stem cell derived embryoid model (retinoic acid treated gastruloids). Using CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 technology, I plan to perform individual gene knockouts on our genes of interest in human embryonic stem cells. Next, we will generate mutant gastruloids from these knockout cell lines, and phenotype using single-cell RNA sequencing and fluorescent microscopy. From there, we can see how knocking out this gene affects gastruloid cell type composition and morphology. Using this strategy, our lab has successfully knocked out 60 genes. Given the strong phenotypes observed in null mutant mouse embryos for these genes, we expect to observe strong phenotypes from these seven epigenetic factors. With these findings, we can further understand the role of these epigenetic factors in development and disease. These findings can advance the progress of therapies and better understand our knowledge of human embryonic development as a whole.

Behavioral flexibility is the ability of an animal to adapt to environmental changes, crucial decision making and goal directed behaviors. Impaired behavioral flexibility has been linked to psychiatric disorders such as depression, anxiety, and substance use disorders. Emerging research suggests that psilocybin, a psychedelic drug that acts on serotonin receptors, may improve behavioral flexibility by promoting adaptability in responses to new information. Given the growing literature exploring the impact of psilocybin as a therapeutic treatment for psychiatric disorders, this study aims to explore the effects of psilocybin on the use of behavioral strategies on a complex spatial set-shifting task. Long-Evans rats were trained on an elevated plus maze with two start arms, north and south, and two reward arms, west and east. The task requires rats to alternate between two strategies: alternation and place. The alternation phase required rats to switch between reward arms (go West, then go East), and the place strategy required choosing the same arm (e.g. go West) continuously. Rats must determine the correct strategy and implement it; once 12 out of 15 trials are accurately completed, an uncued switch in the correct strategy will occur, requiring adaptation to a new strategy. Once animals were well-trained on the task, a single dose of psilocybin (1mg/kg) or saline was administered 10 minutes prior to a session and their behavior was analyzed. Metrics such as performance, and flexibility scores were assessed to determine the impact of psilocybin on behavior. Preliminary findings suggest psilocybin improves behavioral flexibility compared to the saline group, though overall performance remains relatively stable. These results provide insight into the potential of psilocybin as a therapeutic tool for conditions characterized by behavioral rigidity; even in wild-type animals, psilocybin improves flexibility, indicating the possibility for mitigating more severe impairments in flexibility seen in psychiatric disorders.

Adaptive algorithms used in brain-computer interfaces (BCIs) adjust to user strategies by dynamically adjusting how BCIs decode neural data throughout an experiment. Current adaptive algorithms continuously update the decoder using all available data during training. However, if users are unfocused or inattentive, it is likely that some of the training data is unhelpful towards decoder training and could lead to poor decoder performance. Unfortunately, determining attentiveness in a subject is difficult. Non-human animals cannot self-report attention levels, and even in human trials, self-reporting often leads to subjective data that varies between subjects. A non-invasive estimate of subject attentiveness could improve data selection for decoder training. Pupil size is correlated with a participant’s perception of task difficulty, and participants involved in attention-grabbing tasks display blinking rate-inhibition (Kucewicz et al., 2018; Maffei et al., 2019). I hypothesize that these eye data could be used to estimate a subject’s task engagement. I explored data from a novel task where both human and non-human primate subjects controlled a cursor on a 2D screen with 3D hand motions through some unknown mapping. Due to the unknown 3D-to-2D mapping, this task required constant cognitive attention in order for subjects to succeed. I looked at the subjects’ data to identify trends in pupil size and blink frequency across multiple days of task performance. In the future, I aim to build engagement classification models to better select training data for adaptive algorithms and apply these algorithms to realtime BCI experiments.

Neonatal tracheal intubation (TI) is a high-risk procedure requiring careful coordination to minimize complications and improve outcomes. The Personalized Intubation Neonate Safety (PINS) Bundle was developed to enhance team communication and optimize intubation practices for neonates at risk. The bundle incorporates five key domains: patient risk assessment, treatment threshold for intubation, premedication plan, equipment specification, and provider selection with escalation strategies. At the University of Washington Neonatal Intensive Care Unit, eligibility criteria for the PINS bundle include neonates requiring non-invasive respiratory support with >30% FiO₂, those meeting surfactant administration criteria (≥30% FiO₂ and PEEP 6 on NCPAP), already intubated and mechanically ventilated infants, those with difficult airway diagnoses (e.g., craniofacial anomalies, large tongue, micro/retrognathia), and extremely preterm infants (<1000g or <4 weeks old). We will evaluate the impact of PINS implementation by comparing intubation attempts and adverse events before (January – June 2024) and after (July – December 2024) the bundle’s introduction. Data was adjusted to exclude ineligible patients, ensuring comparable cohorts. Primary outcomes include the number of intubation attempts before success and the incidence of tracheal intubation adverse events (TIAEs). We hypothesize that PINS implementation will be associated with a reduction in intubation attempts and TIAEs, reflecting improved preparation and procedural success by the healthcare team. By standardizing an individualized pre-intubation plan, the PINS bundle aims to enhance neonatal safety and streamline team response during intubation. Findings from this study will inform future clinical protocols and may support the broader adoption of personalized intubation strategies in the NICU. Further assessment of long-term outcomes for infants will strengthen the bundle’s clinical utility.

South Thurston County's car-dependent and low-density built environment can affect the health and economic wellness of its residents. This research investigates the barriers that residents face in getting to work, their daily needs, and things-to-do. What are the best strategies to improve the built environment that provides access to employment, necessities, and entertainment for people in south Thurston County’s SR 507 and Old Highway 99 corridors? A process of observations, community surveys and interviews with government and other agency officials will allow for an understanding of current conditions in the study area, personal viewpoints of community members, and constraints that the government agencies and other organizations might face in making improvements. This project will include investigation into design, policy and economic practices. A free or low-cost guide that would allow rural governments to make economically smart design and planning changes, and help make towns more self-sustainable, will be created after understanding this research. As innovation in planning and re-urbanization occurs increasingly in the United States’ larger metropolitan areas, rural and tribal communities, too, deserve an opportunity at urban core making, simplifying the daily lives of its residents, and maintaining health and wellness for all.

The Campanian stage of the Late Cretaceous (~84–72 million years [Ma]) was a dynamic interval for North American ecosystems including the evolution of angiosperm plants and the regression and transgression of the Western Interior Seaway (WIS). These dynamics likely impacted terrestrial fauna across the continent. Most studies investigating biodiversity in western North America during the Campanian focus on a single group (e.g., dinosaurs or herpetofauna), whereas few investigate diversity patterns of multiple taxa. This approach is imperative because comparing diversity patterns among taxa can provide rare insight into the synecology of animal communities. Vertebrate microfossil sites are ideal for such a study because they preserve large sample sizes, multiple taxonomic groups that likely coexisted, information about environmental conditions, and they sample multiple stratigraphic intervals. The Judith River Formation (JRF) of north central Montana preserves ~4 Ma of the Campanian (~79–74 Ma) and large regressive and transgressive cycles of the WIS. This formation, which is contemporaneous with the Dinosaur Park and Two Medicine formations, is also rich in vertebrate microfossil sites. To examine vertebrate diversity patterns through this critical interval, we compared taxonomic richness and relative abundances of Dinosauria, Squamata, and Lissamphibia from the JRF from three temporally distinct microfossil sites: Makela-French 1 (~77.5 Ma), Milkshake (~76.5 Ma), and Clamfetti (~75.2 Ma). Over four years, we collected and screenwashed fossiliferous, bulk-sediment samples from these sites. Thus far, we have recovered 998 and aim to recover 1,200 specimens total. We use our data and knowledge from the literature to evaluate the extrinsic factors (e.g., seaway regressions) that drove diversity changes in the JRF fauna.  Our preliminary results suggest a connection between diversity patterns and WIS cycles. We observe shifts in relative abundances and richness near the onset of the WIS transgressive cycle. 

Prostate cancer has a significant heritable component. It is estimated that 10-15% of patients with advanced prostate cancer carry an inherited predisposing genetic mutation, and these patients generally present with a younger age of onset and a strong family history of cancer. The standard in the field of oncology is to conduct short-read DNA sequencing on such patients to find predisposing mutations. While short-read sequencing does well to identify simple mutations that cause disease in many families, our lab concluded that short-read sequencing misses critical mutations in many prostate cancer susceptibility genes. We hypothesized that prostate cancer in many families is due to complex inherited mutations such as genomic deletions, inversions, and mobile element insertions that are not detectable by conventional genomic technologies such as short-read sequencing. To test this hypothesis, our lab specifically recruited prostate cancer patients who, despite having family histories of cancer, did not have any mutations detected via conventional genetic sequencing methods. This project utilizes Nanopore long-read DNA sequencing, which reads DNA in longer fragments and can reliably detect complex mutations. My role is to conduct long-read sequencing on DNA samples from these patients, then analyze the DNA sequence for mutations. I have sequenced 32 patients so far and identified 4 complex mutations through long-read sequencing which were missed by other approaches. These complex mutations include insertions of repeat sequences and duplications which disrupt gene function in BRCA1 and BRCA2. This suggests that, consistent with our hypothesis, some patients who do not have mutations found via conventional sequencing methods do indeed carry causative mutations in well-established prostate cancer risk genes. By finding these mutations, patients can receive more targeted and effective cancer treatment, and undiagnosed family members stand a better chance of catching cancers at earlier stages.

This project aims to compare and contrast Little Free Pantries (LFPs) and Community Fridges (CFs) as models of micro pantries for those facing food insecurity. The primary focus is on the ability of each to safely provide nutrient-dense food. There is extensive research on what a nutrient-dense diet is and its importance on a person's health as well as budding research detailing the quality of food provided by food pantry organizations. However, this research is limited in the scope of donation programs being researched. Furthermore, there is a lack of understanding how different donation programs differ in their ability to provide nutritional food to those utilizing their services. This project compares five CFs to five geographically matched LFPs within the City of Seattle. To assess the nutrient-density of food donated to CFs and LFPs two dimensions of food nutrition are analyzed utilizing the FAST score and NOVA categorization methodologies. Each micro pantry is briefly assessed on its food safety standards as well. CFs are expected to provide food with higher nutritional quality than LFPs, and in a safer manner. This is due to their ability to be temperature controlled, allowing for a wider variety of foods to be collected and stored safely. This research will be presented in a final paper and poster detailing the findings of the project as well as any recommendations drawn for the City of Seattle. This project is significant because it addresses the nutrition of food made available to those facing food insecurity. Understanding the difference in quality of food offered between the CFs and LFPs will allow for an assessment regarding how accessibility to nutrient dense food for all residents of Seattle falters and how it can be improved.

The Campanian stage of the Late Cretaceous (84–72 million years [Ma]) was a dynamic interval for North American ecosystems and included the zenith of dinosaur diversity and the regression and transgression of the Western Interior Seaway (WIS). Most studies that investigate vertebrate biodiversity during this interval focus on dinosaurs, whereas few focus on changes in herpetofauna (lizards, frogs, and salamanders). Herpetofauna are important indicator species of ecosystem dynamics, because they are fragile to ecosystem change. Vertebrate microfossil sites are ideal for studying herpetofauna diversity dynamics through time because they can produce large sample sizes, sample aquatic environments, and are plentiful through stratigraphic intervals. The Judith River Formation (JRF) of north central Montana is rich in vertebrate microfossil sites, preserving ~4 Ma of the Campanian (~79–74 Ma). Here we aim to document patterns of herpetofauna diversity change in the JRF by quantifying herptile taxonomic richness and relative abundances using specimens from three temporally separated microfossil sites: Makela-French 1 (~77.5 Ma), Milkshake (76.5 Ma), and Clamfetti (~75.2 Ma). We collected sediment samples from these sites over four years and processed them via underwater screen-washing techniques. Presently we have studied 470 herptile microfossils (600 planned). Our preliminary results show changes in the taxonomic diversity across the sampled sites. Taxonomic richness of herptiles varies through the formation, first increasing and then decreasing. Salamanders have the highest relative abundance, lizards decrease in relative abundance, and frogs fluctuate. We hypothesize that taxonomic patterns are influenced by the impact of WIS cycles on water supply in ecosystems: amphibians thrive in wetter environments, whereas lizards are more terrestrial. These preliminary results reflect a connection between diversity patterns and extrinsic drivers not observable through the analysis of dinosaur fossils. Our continued analysis will provide more fine-scale resolution of herptile diversity during the Campanian.

This project examines how industries' return-to-work policies influence public transit ridership patterns across various business sectors in the Puget Sound area. By analyzing ORCA card data from local transit agencies and reviewing company policies, the research tracks the impact of policy on industry ridership trends from January 2018 to January 2025, spanning the pre-pandemic, pandemic, and post-pandemic periods. The findings provide insight into industry-specific ridership changes, revealing which industries in the Puget Sound area have experienced the most significant shifts in public transit ridership post-COVID-19, and how return-to-work policies may have influenced these changes. The results of this research can be used by public transit agencies to focus and adapt their strategies to engage low-ridership sectors. This work can also help advance equitable, sustainable, and resilient public transit systems, particularly in the context of evolving remote work policies.

Individuals with Stage II/III severe periodontal disease were recruited from the Graduate Periodontics Clinic at the University of Washington School of Dentistry using an approved IRB (STUDY00016871). Subgingival plaque samples were collected from four tooth sites: an active inflamed site, two adjacent tooth sites, and a distant healthy tooth site. Sterile paper points were inserted into the gingival sulcus for 30 seconds. DNA was isolated and extracted using the Qiagen AllPrep DNA/RNA Mini kit (Cat. #80204), then purified and concentrated using the Zymo Clean & Concentrator (Cat. #D4014) kit. Whole genome libraries were generated and whole genome sequencing was performed on a NovaSeq X (Illumina, San Diego, CA, USA). Relative abundance of species-level assignments represented by clusters were determined, and best matched genomes were then used to generate species pangenomes for comprehensive multi-genome wide read mapping and gene-level analysis. Taxonomic and gene level functional analysis was also performed. Data analysis is still being performed at this time. Based on previous literature (Basic and Dahlén, 2023), we anticipate that the activity of certain microbial metabolic pathways associated with oral disease and their functions will be heightened in the active disease site and lower on the non-affected site within strain-level disease-associated bacteria, such as those of the Porphyromonas, Tannerella, and Treponema genera. Specifically, we expect amino acid fermentation and lipid metabolism activity to be increased in the active disease site. We expect that results from this study will highlight the presence of heightened activity of bacterial metabolic pathways and functions at the strain level associated with specific gram negative perio-pathic disease-associated species within clinically healthy tooth sites in patients with active periodontal disease despite the absence of clinical observed inflammation.

Hypertrophic Cardiomyopathy is the most common form of hereditary heart disease affecting ~1:500 individuals, characterized by progressive thickening of the left ventricular wall. The first mutation linked to this disease was the heterozygous R403Q mutation in human beta-myosin heavy chain (β-MHC). Conflicting reports of contractile kinetics between human myectomy samples vs transgenic mouse and rabbit models motivated us to study the molecular mechanisms of altered contraction in a CRISPR/Cas9 gene edited human inducible pluripotent stem cell line. Following differentiation to cardiomyocytes (hiPSC-CMs) and maturation in culture, we isolated sub-cellular contractile organelles called myofibrils. Myofibril contractile kinetics from this line had slowed force development and cross-bridge detachment, with reduced maximal force compared to the WT line. hiPSC-CMs were cast into fibrin matrices to form three-dimensional, engineered heart tissue (EHT) for measures of twitch force and contractile kinetics. At 1Hz stimulation, heterozygous mutation EHT’s exhibited a hypercontractile phenotype compared to WT EHTs, with slowed relaxation kinetics. Since the penetrance of our heterozygous R403Q hiPSC-CMs is unknown, we are now studying a homozygous iPSC-CM line where 100% of the β-MHC is mutated. This will allow us to assess the direct contribution of the mutation to the disease contractile phenotype. We will repeat the myofibril and EHT measures of contractile properties and perform stopped flow kinetics analysis on isolated myosin to determine ATP turnover and ATP hydrolysis product release rates. This will provide molecular mechanistic insight of the contractile abnormalities, allowing development of therapeutic interventions that specifically target the mechanisms that alter contractile function. 

During embryonic development, gene expression is temporally and spatially coordinated to control organogenesis and fetal growth. We previously identified a subset of 140 genes that conferred lethal and sub-viable phenotypes in mice and are likely to be haploinsufficient in humans. These genes presumptively play essential roles in fetal development, but their function is unknown. I aim to uncover the role of these genes in mouse embryonic development using Weighted Gene Co-Expression Analysis (WGCNA). Co-expression analysis will be conducted on mouse embryonic stem cell RNA sequencing data obtained at three different stages of in vitro differentiation and across two different genetic backgrounds, creating a subset of nine samples encompassing 12555 genes. Choosing three different time points allows us to see how expression of our genes of interest changes over time, and choosing two different genotypes (wild type and knock-in) allows us to investigate if expression changes due to a single point mutation. We performed dynamic clustering on this RNA sequencing data to identify co-expressed gene clusters. I will map these gene clusters to biological pathways to make inferences about which cellular processes, metabolic functions, or structural components the genes of interest are involved in. This may indicate the role of these genes in fetal development and help reveal why fetal viability is compromised. In future studies, the functional characterization of these genes will generate new ideas and hypotheses about the basis of genetic disease.

Acetaminophen (APAP) is a widely used over-the-counter drug known for its analgesic and antipyretic properties. Several clinical factors can influence how APAP is absorbed, distributed, metabolized and excreted from the body (i.e., its pharmacokinetics (PK)). APAP is metabolized into several metabolites, including APAP-glucuronide, APAP-sulfate, APAP-cysteine, and APAP-N-acetylcysteine. Therefore, accurately determining plasma concentrations of APAP and its metabolites is crucial for understanding how individuals metabolize APAP and environmental influences on APAP PK. To address this, I am reproducing a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay to determine concentrations of APAP and its metabolites in plasma. I analyzed plasma samples collected from seven healthy volunteers following oral administration of 500 mg of APAP. To prepare the samples, I added 70 μL of diluted internal standard mix into the tubes containing 30 μL of plasma. Samples were centrifuged and the supernatants were transferred clean tubes and dried down with nitrogen gas. Samples were reconstituted in mobile phase for analysis using LC-MS/MS. I analyzed the LC-MS/MS data to calculate the plasma concentration vs. time curves for each analyte. I used Phoenix WinNonlin to estimate key PK parameters, including peak concentration (Cmax), time of peak concentration (Tmax), clearance, half-life, volume of distribution, and area under the curve (AUC). This LC-MS/MS assay provides a platform for precise quantification of APAP and its metabolites, and will be essential for our lab’s future studies on the impact of the gut microbiome on APAP’s PK.

Duchenne Muscular Dystrophy (DMD) is the most common lethal genetic muscular disorder of children and is caused by mutations in the 2.2 MB DMD gene. Absence of the dystrophin protein from the dystrophin-glycoprotein complex, leads to myofibers being highly susceptible to contraction injury, leading to progressive rounds of degeneration and regeneration. There is no cure, and most DMD patients eventually experience cardiorespiratory failure. Utrophin (Utr) is a dystrophin paralog that has long been suggested to be a potential therapeutic for DMD. Here we evaluated 4 novel micro-utrophins (µUtr), with the original micro-utrophin (µUtr1) and micro-dystrophin (µDys5) as controls. Two-week-old mdx^4cv mice were intravenously administered vector genomes of recombinant adeno-associated viral vector (rAAV2/9myo1) with human codon-optimized micro-transgenes, driven by the creatine kinase regulatory cassette (CK8e). At ~8 months of age, we assayed lower limb muscles for contractile performance. After functional testing, I processed heart and gastrocnemius muscle tissues to enable purification of proteins and nucleic acids. I then conducted molecular assays, followed by metabolomics via mass spectroscopy to compare wildtype, mdx^4cv, and treated mdx^4cv mice. These results revealed a leading 6-R µUtr variant (µUtr2) that showed physiological improvements in resistance to contraction-induced injury. We also performed univariate and pathway analysis of ~200 targeted metabolites, revealing fold-changes in tricarboxylic acid (TCA) cycle intermediates along with several genes controlling glucose metabolism. The µUtr2 variant resulted in metabolic and physiological improvements towards alleviating symptoms associated with disease progression in the mdx^4cv mouse model, and may hold promise as a treatment for DMD. Gene delivery of functional utrophin-centric proteins could avoid the adverse immune response events that recently occurred in human clinical trials against dystrophin sequences, potentially providing an alternative therapy for some patients.

Alzheimer’s disease (AD) is a neurodegenerative disease that impacts millions of people and costs billions of dollars annually, with both estimates increasing as our aging population grows. Women are diagnosed with AD at a 2:1 higher rate than men, although the biological drivers of this difference remain elusive. Previous studies have demonstrated that changes to the function of microglia – the brain’s immune cells – observed during AD may be driving disease progression. Furthermore, microglia morphology is related to its function. Thus, we seek to characterize differences in microglia morphology between men and women with and without AD. We hypothesize that microglia from women have, on average, a more disease-associated morphology than those of men, and that differences are exacerbated in individuals with AD. We obtained tissue from the dorsolateral prefrontal cortex of 48 individuals who donated their brains to AD research at UW. We conducted immunohistochemistry (IHC) to stain for microglia markers (IBA1) and two markers of AD pathology (AT8 to stain for phosphorylated Tau and a pan-amyloid β stain). I imaged the samples on a Leica SP8 confocal microscope at multiple depths, which allowed us to compose a 3D rendering of the tissue through an image analysis software called IMARIS. Using IMARIS, I quantitatively measured key aspects of each microglia, such as volume and branching details. Using the data from 12-20 microglia per person, we used multiple regression to test for differences between men and women in both healthy and AD cohorts. We anticipate there are differences in the various measurements of microglial morphology between men and women with AD, which may partially explain the discrepancy in AD rates between sexes. This research is important to better understand the role of sex in AD pathology and help contextualize molecular differences observed in the larger project to which it belongs.

My project intends to discover a DNA aptamer, a single stranded DNA oligonucleotide, that binds selectively to the protein Interleukin-6 (IL-6). IL-6 has an important role in the immune system response and in excess it is known to cause inflammation. Aptamers exhibit binding affinities like that of antibodies but are ~50 times cheaper to produce. The method of aptamer discovery is through SELEX (Systematic Evolution of Ligands by Exponential Enrichment) which involves the selection from an aptamer library that contains 52N random nucleotide region and constant 5’ and 3’ 18 base pair regions for PCR amplification. Positive and negative selection are completed by incubating aptamer libraries with IL-6 or random protein immobilized on magnetic beads respectively. After each round selected aptamer sequences are amplified with a polymerase chain reaction (PCR) with primers that anneal to the constant regions. Reverse primer has biotin on 5’ end that is used later for strand separation with streptavidin agarose. After each round aptamer pool is going to be sequenced using nanopore sequencing platform till the enrichment of IL-6 specific sequences is observed. Binding will be tested through an enzyme-linked immunosorbent assay (ELISA) using the fam on 3’ end. The end goal of this project is to design a cost-effective method of IL-6 depletion from patients blood, allowing for cost-effective method of treatment for overactive immune system inflammation in sepsis patients.

During neonatal transport, specialized pediatric transport teams closely monitor the status of critically ill newborns. Hyperspectral imaging, a method of manipulating light for medical imaging, can be used for remote monitoring using video of the patient’s physical appearance and to measure vital signs. Appropriate light intensity is critical for clear visibility of the newborn and hyperspectral imaging accuracy, but this must be balanced with safety for sensitive eyes. My previous studies have determined the minimum range of light needed to accurately view the neonate in a transport incubator. My current research is focused on developing a novel method for vital sign analysis by using hyperspectral imaging. A smartphone camera will be used to take RGB photos of a calibration chart and a short video of the wrist of study participants. After taking the RGB photographs, custom MATLAB code will be used to extract physiological data such as hemoglobin and bilirubin content from the skin. Data analysis will compare the vital sign data collected using hyperspectral imaging and using a pulse oximeter to understand the feasibility of hyperspectral imaging for vital sign extraction. The expected result of this study is that the heart rate and blood oxygen levels measured using light and a pulse oximeter will be highly correlated. In conclusion, this research will demonstrate the potential application of hyperspectral imaging to pediatric transport.

The ability to manipulate and ligate proteins has been a driving force in advancing our understanding of the complex regulation of biological processes in space and time. Protein ligation, in which two or more polypeptides are covalently linked, is a powerful strategy in biomacromolecular engineering, enabling precise control over protein modifications, stability, and functionality. This is particularly useful in understanding protein function and interactions, as well as modulating protein activity, including immobilization of protein-based signals within materials triggered by cytocompatible light. One proven system known for its specificity and ease of use is SpyTag/SpyCatcher, a peptide-protein pair capable of irreversible ligation via isopeptide bond formation. Recent work has demonstrated the ability to control SpyTag/Catcher ligation using cytocompatible light due to its non-invasive nature and spatiotemporal (i.e., 4D control) manipulation of protein signals on a biologically relevant timescale. However, the application of this reported photoligation strategy is hindered by the use of genetic code expansion which limits protein yield, entails additional orthogonal protein machinery, and involves translational incorporation of a non-canonical amino acid. To address these challenges, we aim to develop a photocontrolled protein ligation strategy using native protein activity while maintaining spatial and temporal control. We predict this strategy will enable dose-dependent reconstitution of ligation by varying light exposure duration and intensity in native protein systems while sidestepping challenges associated with genetic code expansion. We intend to use this strategy to further assess our capability to control split protein reconstitution and for future applications in directing complex cell fate, which has significant utility in stem cell biology and regenerative medicine.

Heart attack survivors experience elevated risk of subsequent events and death, as such there is a clinical need for regenerative techniques to rebuild damaged myocardium and reduce risk. Transplantation of human-induced stem cell-derived cardiomyocytes (hiPSC-CMs) into non-human primate hearts has been shown to significantly improve contractile function after heart attack, however, transplanted hearts were also shown to be at elevated risk for developing potentially lethal arrhythmias. Researchers developed a line of hiPSC-CMs to correct this arrhythmia-promoting behavior by inducing a series of four gene edits to prevent the hiPSC-CM spontaneous beating behavior known as "automaticity", these gene edits spawned the cardiomyocyte cell line dubbed MEDUSA (Modification of Electrophysiological DNA to Understand and Suppress Arrhythmia). I have conducted an in-vitro study of the electrophysiological effects of the MEDUSA edits, knockouts of the sodium-calcium exchanger NCX1, the hyperpolarization-activated pacemaker current channel HCN4, the low voltage Calcium ion channel Cav 3.2, as well as overexpression of the potassium channel Kir 2.1. I have employed immunofluorescence microscopy to analyze sarcomere structures, used lentiviral transduction of calcium-sensitive green fluorescent protein to quantify calcium handling, and constructed engineered heart tissue casts to measure contractile force, to compare the electrical and physiological characteristics of MEDUSA CMs and their wild-type counterparts. Characterizing the MEDUSA cell line is essential for identifying issues that could compromise the cells' ability to function in grafts while uncovering its potential for use in regenerative treatments. Here I show that the MEDUSA gene edits create arrhythmia-resistant cardiomyocytes without compromising the integrity of their structure or function, supporting the development of a regenerative therapy future for the field of cardiology.

Robots must be able to pick objects from densely packed shelves in order to automate industrial warehouses. Dense packing gives rise to challenges in grabbing targeted objects efficiently as the shelves can be clustered, objects can be stacked, and the target object can be obstructed from direct reach. The goal of this research project is to create a new gripper combined with reinforcement learning to manipulate objects within a shelf without multiple attempts or repositioning of the robot arm. The new gripper design includes four fingers that are linear actuators with vacuum units and suction cups attached to the ends of each finger. Additionally, each finger contains a time-of-flight sensor at the tips which provide spatial information for different objects within the shelf. I integrated time-of-flight sensors into the multi-fingered gripper and filtering algorithms for the sensor’s data. I modified the previous vacuum ejector unit which only provided support for one unit to four vacuum ejector units. I also conducted a series of experiments that provided cases where the new gripper design proved to be better than the previous design. We also collected suction cup vacuum data and trained a neural network to predict the success rate of suction cup attachment. The results of this project will inspire new designs for increasing the success rate of robotic grasps within densely packed environments.

We are developing a RNA scaffold-based CRISPR activation and inhibition system to controllably tune gene expression in  primary immune cells, which will allow us to manipulate and increase production and function of immune cells, vastly increasing their efficacy in fighting diseases such as cancer. Here we target Bcl11b, a key T cell transcription factor necessary for progenitor cell commitment to the T cell lineage. CRISPR activation and CRISPR interference (CRISPRai) enable activation or repression of targeted genes. Due to the large size of dCas9 activator and reperessor fusions, it is not possible to express the necessary machinery in primary mouse T cells. Thus, we are developing a CRISPRai system where the gRNA (guide RNA) contains an additional RNA hairpin to recruit RNA binding protein-effectors, enabling activation and repression in the same cell. To optimize the efficiency of CRISPRi in T cells, we are 1) cloning and testing a repressor domain for its ability to drive gene silencing and 2) testing alternative RNA base pairs (BP) and hairpin pairs. We are testing these optimizations in a T cell progenitor cell line which has turned on Bcl11b with a downstream YFP (fluorescent) reporter. Here, YFP expression, which we measure using flow cytometry, is directly correlated to Bcl11b expression levels. We hypothesize that an alternative validated RNA hairpin BP in conjunction with a novel compact transcriptional effector will result in decreased levels of YFP expression compared to the existing system.

Cells in the human body contain the same DNA, and yet encompass an incredible range of structures and functions. This is possible due to genetic regulatory circuits that precisely control gene expression in response to external factors. While this is a central aspect of human biology, we lack a mechanistic understanding of how the majority of these regulatory circuits work. In this study, we investigate how the expression of Bcl11b, a gene that plays a large role in T cell development, is controlled by nearby noncoding DNA (referred to as a cis-regulatory element or CRE). We conduct a CRISPR interference (CRISPRi) screen in which a culture of P2C2 cells modified to express Bcl11b coupled to a fluorescent reporter protein is transfected with a guide RNA (gRNA) library that targets locations on the Bcl11b enhancer/promoter, and recruits repressive proteins to these sites. Cells transfected with gRNAs that bind to crucial regulatory locations experience a drop in Bcl11b expression that is measured via flow cytometry. These cells are analyzed using next generation sequencing techniques to determine which gRNA sequences are present, and thus which CRE sequences are the most essential for Bcl11b expression. In preliminary experiments, we have found that cis-regulatory elements at a distal Bcl11b enhancer, containing binding site locations of transcription factors controlling T cell specification, including T cell factor 1 (TCF-1), that play roles in controlling Bcl11b expression. The knowledge obtained from this experiment allows us to conduct future CRISPR gene expression studies in primary immune cells, where by precisely altering Bcl11b expression we can gain a mechanistic understanding of its effect on T cell development. This will drastically improve our ability to program human immune cells, resulting in medical advances such as far easier production of specialized T cells for cutting edge immunotherapies.

Cyberbullying is repeated, intentional harm inflicted through digital platforms, including social media, messaging apps, and online forums. Most researchers focus on cyberbullying in adolescence, but it continues into adulthood. Young adults (ages 18–25) undergo major life changes and use social media frequently, which increases their risk of experiencing cyberbullying. LGBTQ+ individuals, especially transgender and non-binary people, face higher rates of online harassment. Cyberbullying can lead to severe mental health issues, including depression, anxiety, and social isolation. While existing research focuses on cyberbullying among LGBTQ+ individuals as a broad group, few studies examine its specific impact on transgender and non-binary people. This study employs a mixed-methods approach to investigate cyberbullying in transgender and/or non-binary emerging adults. A survey of transgender and/or non-binary participants aged 18–25 will be conducted using a modified Cyberbullying Victimization Scale to measure three types of victimization: Verbal/Written, Visual/Sexual, Social Exclusion/In-Person Bullying. Participants will report experiences in public online spaces and private online spaces. The study will collect demographic data such as gender identity, racial or ethnic background, level of outness, and social media usage to examine correlations between these factors and cyberbullying experiences. By integrating statistical trends and personal narratives, this research will provide a deeper understanding of cyberbullying in transgender and non-binary communities. The findings will inform social media policies, platform safety measures, and mental health support efforts for LGBTQ+ individuals navigating online harassment.

Carpels are invaluable floral organs that have undergone myriad innovations in flowering plant evolution, providing fruits and seeds. Carpels consist of a pollination site (stigma), pollen growth area (style), and a region containing ovules (ovary) which become the fruit after fertilization. Understanding carpel development and evolution is fundamental for efforts to increase food production. A decreased abundance of insect pollinators due to anthropogenic climate change has made this pursuit all the more urgent. The plant genus Thalictrum comprises perennial herbs in temperate regions that have repeatedly transitioned from insect to wind-pollination in their evolutionary history. Hence, they are ideal to investigate the adaptations and genetics that decrease reliance on insects for reproduction. A key feature of wind pollination is a longer stigmatic surface that increases pollen capture. I am taking a candidate gene approach, examining homologs of the stigma development gene families STYLISH (STY) and NGATHA (NGA). I am characterizing the role of NGA and two STYLISH gene copies in our model species, Thalictrum thalictroides. Previous work has found that silencing one of the STY gene copies results in the loss of stigma development, while the function of the other copy remains unknown. In other genera, altered NGA expression has been shown to alter stigma development. To characterize the function of both NGA and STY, I am implementing Virus-Induced gene Overexpression (VOX) by infiltrating tubers with Agrobacterium transformed with Tobacco Rattle Virus (TRV) carrying an overexpression construct. STY genes will be overexpressed, and NGA will be both overexpressed and silenced using Virus-Induced Gene Silencing (VIGS). I will characterize the phenotypes resulting from these treatments to determine the functionalization of STY and NGA. By dissecting the genetic basis of floral adaptations to wind-pollination in this system, I hope to contribute solutions to enhance crop production in the face of pollinator decline. 

There are a vast number of pathogens that impact global public health, necessitating an accessible assay capable of detecting multiple targets simultaneously. Lateral flow assays (LFAs) have the potential to fill this role as a cost-effective, rapid, and simple technology instrumental in the detection of many analytes. However, multiplexed detection using nucleic acid LFAs is difficult due to the increased chance of non-specific binding as more targets are added to the assay. In this work, we aim to increase specificity and multiplexing potential in LFAs. We first showcase the process of developing a nucleic acid LFA by evaluating both fluorophores and gold nanoparticles to generate a visible signal. As fluorophores require a fluorescent light source, we moved forward with gold nanoparticles, which have a readout visible to the naked eye. Additionally, we automated the LFA fabrication process using an Echo Liquid Handler. Finally, we assessed methods to convert double-stranded to single-stranded DNA, required for compatibility with LFAs. In the future, we look to optimize signal visibility while increasing multiplexability. This work highlights the potential of multiplexed LFAs as a robust technology capable of significantly improving public health responses and outcomes.

Tuberculosis (TB) remains the world’s deadliest infectious disease, claiming over 1.25 million lives annually—surpassing malaria and HIV in mortality. TB’s causative pathogen, Mycobacterium tuberculosis (MTB), continues to spread rapidly due to inadequate access to accurate molecular diagnostic tests. The most commonly used tests include sputum-based and tuberculin skin tests, which require follow-up visits and have suboptimal sensitivity, particularly within certain patient populations. Moreover, these assays cannot identify emerging drug-resistant strains (DR-TB) that have reduced susceptibility to first-line antibiotics. Our aim is to design a diagnostic tool to detect cell-free DNA (cfDNA) in urine and identify the infecting strain to ensure patients receive appropriate antibiotics. To achieve this, we are developing a probe-ligation assay with single-nucleotide specificity. Current implementations are limited by the low specificity of ligase, leading to false positives and an inability to differentiate between mutated MTB strains. We hypothesized that Flap Endonuclease-1 (FEN1) could confer a specificity advantage by integrating a second enzymatic “check” into the process. The protocol involves a ligation reaction with MTB genome-derived targets and two probes, each containing a DNA flap with additional nucleotides. To detect the ligated product, FEN1 must cleave these flaps before the ligase catalyzes the repair of the nick between probes. To experimentally observe this, we carried out several ligation reactions containing FEN1 and ligase with wild-type and mutant targets, followed by PCR or gel electrophoresis to measure ligated product formation. We evaluated the efficiency and precision by analyzing the amplification profiles of WT targets and mutants containing SNPs neighboring the ligation site. Our data about whether FEN1 confers a significant specificity advantage remains inconclusive, but the double enzyme reaction is functional and could be further exploited in future experiments with additional optimization or modifications to enzymes or DNA probes.

Grasses (family Poaceae) are highly diverse (~11,800 species), cover nearly 40% of Earth’s ice-free land surface, and play critical ecological and economic roles. Grasses have evolved a variety of unique traits, including an exceptionally high accumulation of silicon in the form of biological silica bodies (phytoliths) in some lineages. Silicon accumulation confers resistance to both abiotic and biotic stresses, including drought and salinity resistance, herbivore defense, and structural support. Despite the role of silicon in the enormous success of grasses, a clear picture of the exact drivers of silicon accumulation in grasses across species and environments has not yet emerged. I hypothesize that elevated silicon concentrations are primarily driven by environmental stress, most notably high temperatures and low precipitation. To test this hypothesis, I used X-ray fluorescence to analyze the leaf silicon concentration of 482 grass leaf samples, encompassing approximately 200 species across all 12 grass subfamilies. Using occurrence records from online databases, I identified the realized climate niche and its environmental conditions (e.g., temperature, precipitation) for each sampled species. The next step is to collect geolocation data from each individual sample, which will be combined with the climate niche data of its species. By comparing the relationship between a plant’s climate niche, its individual growing conditions, and its silicon concentration, a better understanding of environmental drivers of silicon will begin to emerge. Preliminary results taking into account only climate niche and silicon concentration showed no relevant correlations, illustrating the need for individual growing condition data. Because many of the stresses that silicon helps to alleviate are also those that will worsen under climate change (high temperature, drought, insect herbivory), an improved understanding of the environmental drivers of silicon accumulation will allow us to better prepare for the impacts of climate change on our agricultural and ecological systems.

Plastic is a prevalent and useful material, experiencing a 230-fold increase in production from 1950 to 2019. However, problems revolving around plastic production and disposal are becoming increasingly clear. In 2015 virgin plastic production was responsible for 4.5% of global greenhouse emissions, with the United states collecting only 9% of plastic waste for recycling. For polystyrene, a common plastic in food storage containers, less than 1% was recycled. The decomposition of polystyrene can also release dangerous chemicals, such as additives Bisphenol A (BPA) and polystyrene oligomers, directly linked to human health hazards such as diabetes, breast cancer, reproductive harm, thyroid regulation issues, heart diseases, and liver problems. To prevent both the need for new plastic and decrease plastic decomposition products from harming both humans and the environment, it is critical to develop a circular plastic economy, where plastic waste is broken down back into the chemical building blocks, or monomers, which can be re-manufactured into new high-quality plastics. The use of basic heterogeneous catalysts, such as zinc oxide (ZnO) can improve the yields of polystyrene deconstruction back into monomers compared to other chemical recycling techniques such as pyrolysis and acid-catalysis. To further improve yields, it is critical to understand the impact of relative basicity of ZnO on styrene yield. To examine base strength effects, the relative basicity of ZnO will be systematically varied through alterations in pretreatment methods. Reactions were tested in a mini-batch reactor at 623K over three hours using a 10:1 substrate to catalyst ratio, with product distribution examined using Gas chromatography-mass spectrometry (GC-MS) and a flame ionization detector (FID). 

With the increasing prevalence of large wildfire events, especially near urban areas, the identification and quantification of combustion-derived air pollutants is critical. The collection, quantification, and identification of particulate air pollutants, also known as aerosols, provide important insights into air pollution sources, evolution, and health effects. To improve capabilities in this area, with funding and support from the Beckman Foundation, we have designed and developed an aerosol collector that uses high-voltage Dielectric Barrier Discharge plasma and Electrostatic Precipitation (DBD-ESP) to collect and desorb target nanosized aerosols (30 nm – 800 nm) containing components typical of woodsmoke, such as levoglucosan and phenolic compounds, among others. The DBD-ESP is integrated with an Ultra-Portable Time-of-Flight (TOF) Mass Spectrometer (UP-ToFMS) to produce online, near real-time analysis of the chemical composition, mass, and size of target aerosols. Based on preliminary collection and desorption testing, we expect to have a 75% collection and desorption efficiency of submicron aerosol particles within 5 minutes. The DBD-ESP has an internal volume of less than 2 cm3 and an overall external volume of around 1 L. Once coupled with the UP-ToFMS, the overall ultra-portable system will be no larger than 0.095 m3 and weigh around 35 kg, enabling the remote sampling of aerosols from wildfire events while still yielding high-quality mass spectral data.

It is estimated that ~15% of all cancers are caused by oncogenic virus infections. Two of the top seven cancer-causing human viruses are members of the gammaherpesvirus family: Epstein Barr Virus (EBV) and Kaposi’s Sarcoma Herpesvirus (KSHV). Our lab uses Murine Herpesvirus 68 (MHV-68), a mouse gammaherpesvirus with shares significant genetic homology to KSHV and EBV, as a model system to understand how gammaherpesviruses alter the metabolism of their host during lytic infection to promote their replication. We recently metabolically profiled MHV-68 infected host cells at various time points during the lytic infectious cycle. Our data showed nucleotide metabolism is significantly induced in MHV-68 infected NIH/3T3 cells, revealing a potential antiviral target. This study investigates the antiviral efficacy of Methotrexate (MTX), an FDA-approved nucleotide biosynthesis inhibitor currently used to treat cancer, rheumatoid arthritis, and psoriasis. MTX inhibits dihydrofolate reductase (DHFR), an enzyme crucial for producing thymidylate and purine nucleotides, which are essential for de novo nucleotide synthesis. We hypothesized that MTX can block MHV-68 production and be repurposed as an antiviral drug. To test our hypothesis, we first determined a safe concentration of MTX in NIH/3T3 cells using both qualitative (microscopy) and quantitative (trypan blue exclusion) cell viability assays. Next, we infected NIH/3T3 cells with MHV-68 and treated them with a safe level of MTX or solvent control. After 48 hours, we assessed viral production in control vs MTX treated cellular supernatants via viral plaque assays. Our results revealed that MTX significantly suppressed MHV-68 virion production by ~50-fold. These findings suggest that targeting host metabolic pathways could be an effective antiviral strategy against gammaherpesviruses in humans. Further research is needed to explore the use of MTX as a broad viral therapy against other viruses.

Driven by the growing commitment to environmental stewardship and climate action, the aviation sector is adopting more creative technologies to move towards cleaner and more eco-friendly propulsion systems. The substantial CO2 emissions from current jet engines make creative solutions for environmentally friendly air travel a necessity, such as electrifying said engines. However, there are several obstacles that prevent current electric motors from being used in aircraft. Overheating is a serious problem that jeopardizes dependability, efficiency, and safety. Because of these drawbacks, existing electric motor technologies are not a viable substitute for many aircraft propulsion systems. To overcome these obstacles, this study optimizes electric motor designs using cutting-edge temperature control and energy-saving techniques. The suggested method makes use of thermoelectric modules (TEM) and high-temperature superconductors (HTS) to efficiently control thermal energy, lessen overheating, and improve motor performance. By integrating these innovative materials, this work aims to create reliable, efficient, and scalable electric propulsion systems that meet the rigorous demands of the aviation industry.