DNA-Binding Proteins (DBPs) hold a strong affinity to interact with the major grooves of DNA for the purposes of transcription, translation, and repair. Although DBPs are found in nature, their specificity is difficult to predict and their production expends excessive resources. Therefore, our project’s goal is to efficiently generate DBPs that allow us to enable exact processes to occur. This is promising for future use in treating genetic diseases. In our research, we studied point mutations in the hexosaminidase subunit alpha (HEXA) gene and adenosine deaminase (ADA) gene, which can lead to Tay-Sachs disease (TSD) and Severe Combined Immunodeficiency (SCID), respectively. TSD is a rare genetic disease that affects infants and ultimately leads to brain damage, resulting in these children not making it to grade school age. Similarly, SCID is genetic, where children lack a strong immune system. This increases their susceptibility to infections, especially during their first year of life. Targeting the HEXA and ADA genes, we first developed designs utilizing computational software like RosettaFold, RFdiffusion, x3DNA, and LigandMPNN, followed by rigorous filtering via RosettaFold Nucleic Acid. Afterwards, we tested the final designs using yeast cultures and fluorescence-activated cell sorting (FACS) in the laboratory to determine which bind best to their generated DNA template sequences. Overall, we expect to find a few specific DBPs that bind effectively as predicted during the computational pipeline. These successful designs can be utilized as genome-editing proteins, correcting their target DNA sequences and restoring normal function.

Evidence-based changes to instruction can lead to better student outcomes and performance. For this reason, instructors are interested in collecting data about student experience and outcomes. However, the process of data collection and analysis can be time-intensive for instructors, making it challenging to gather data necessary to improve their classes. Moreover, when data collection does happen, it often centers quantitative data, but this systematically devalues students' experiences. Therefore, we sought to develop a tool that aids instructors in processing and analyzing qualitative data pertaining to students’ class experiences. As part of our research project, we have developed an R-shiny based data processing app that integrates Artificial Intelligence to summarize findings from open response questions on student surveys. This tool is intended to alleviate the time-intensive nature of analyzing student responses to open-ended survey questions. In order to validate the accuracy of AI-generated summaries, we compared them to manual summaries generated using in vivo qualitative coding methods. We find that our app generates responses that are comparable to the manually generated summaries. The summaries include prominent themes along with details about student experiences within those themes. With this tool, instructors can gather real-time data, even in large classes, eliminating the concern of the time-intensive process of manually reviewing responses. By developing this tool, we hope to empower instructors to explore diverse questions that provide them with valuable insights on how to optimize the structure of their classes to improve student experience and outcomes.

Ethnic/racial minorities often face challenges associated with adjusting to a dominant or new host country. These challenges, known as acculturative stress, include difficulties with behavioral, emotional, and social adaptations, and are linked to adverse outcomes. Understanding the degree to which, for whom, and in what contexts acculturative stress may affect mental health is important in designing culturally-informed interventions. Yet, there are several limitations in the current literature on acculturative stress. First, most studies focus on Latino or Asian ethnic groups or international students/cross-national migrants; it is unclear how acculturative stress is differentially associated with health across populations. Second, most studies have focused on mental health outcomes, whereas other important outcomes (academic, relationship) are neglected. Using records from a large-scale meta-analysis project, we conducted a scoping review of research on acculturative stress to characterize the heterogeneity across studies. We performed literature searches using keywords (e.g., “acculturative stress,” “bicultural stress”) in databases including PsycINFO, and identified 3746 relevant studies. Abstract and full-text screening yielded 681 published and unpublished articles eligible for quantitative analysis. Primary studies were included if they measured acculturation in the context of intercultural adaptation and migration, acculturative stress, and health, academic, and relationship outcomes. We coded and summarized sample characteristics of all articles (e.g., % immigrants, % female/woman, mean age). We will randomly select 50 articles that examine acculturative stress and its associations with mental health, academic, and/or relationship outcomes. We will review and present common outcome measures, instruments assessing acculturative stress, and conclusions. We expect the scoping review to indicate patterns, variability, and gaps in the acculturative stress literature. Results will inform future research on overlooked outcomes and understudied populations, and shed light on necessary basic scientific information (e.g., mediators, modifying conditions) that will support the development of culturally-informed interventions and policies.

Panãra, an Indigenous language native to Brazil, is currently the focus of Dr. Myriam Lapierre, Sunkulp Ananthanarayan, Ella De Falco, and Jessamine Jeter as some of the only linguists to document and conduct a comprehensive study on this language. Our research focuses on streamlining the process of organizing and analyzing field data – specifically in the context of Panãra, though generally applicable to other Indigenous and/or under-researched languages  – for use in future research by Dr. Lapierre and other scholars in the field of linguistics as it applies to Indigenous and minoritized languages. We have digitized the data from the field journals of Dr. Lapierre and the graduate students working with her, and our current focus is on the analysis of verb and sentence construction, via this digitized data, to organize grammatical paradigms into efficient and accessible indexes. We are also compiling and organizing PDF, image, sound, video, and experimental data for use on the California Language Archive (CLA) with a similar focus on efficiency and accessibility. The completion of this research entails the more complex understanding and organization of Panãra sentence and word structure for use in future research, both by Dr. Lapierre and by other scholars, as well as for usage in a Panãra dictionary. Our expected results also involve the creation and organization of the CLA page dedicated to Panãra, with a transparent structure making this data available to a wider audience of both linguists and non-linguists interested in learning more about the language.

 The aim of this project is to process and analyze fieldwork data on Triestin to help construct a JIPA (Journal of the International Phonetic Association) Illustration of the language’s main sound systems. Triestin (Glottocode: trie1242) is a dialect of Venetian, a language spoken by approximately 200,000 people in Trieste, Italy. Triestin is spoken at the unique intersection of the Germanic and Slavic language families, and as the number of native speakers of Venetian dialects continues to decrease each year, it becomes increasingly crucial to document the linguistic intricacies of such a vulnerable dialect (UNESCO). Four native Triestin speakers were recorded reading 100 words from a word list. These words elicited vowels in different environments (each vowel sound would be surrounded by other specific sounds), allowing us to record the variations in the pronunciations of each vowel. After evaluating the data from two speakers, Triestin was found to have a 5 vowel system, differing from Venetian and Italian’s 7 vowel systems. Triestin merges the mid-high and mid-low vowels (vowels made with the tongue in the middle of the mouth), a phenomenon not documented in any other Venetian dialect. We found that the two mid vowels vary significantly depending on their environment, raising to [e] and [o] in stressed syllables and lowing to [É›] and [É”] in all other environments. We anticipate finding a system of vowel harmony, whereby the mid-vowels lower in environments to match the height of surrounding vowels. Since Triestin is the only Venetian dialect known to have a 5 vowel system, our goal is to add to the growing body of research on unique vowel systems. In doing so, we investigate the complex relationships between language families and dialects, and provide valuable documentation of Triestin as a low-resource language.

Air pollution is a key component to understanding the Public Health of populations globally, with Diesel Exhaust Particles (DEP) being a significant contributor to traffic-related air pollution. Exposure to DEPs varies across populations and is therefore crucial to understanding the continual impacts of traffic-related air pollution on the public. Prior research has indicated that the formation of Amyloid-𝛽 (A-𝛽) plaques and activation of the  nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome is linked with the development of Alzheimer’s disease (AD) later in life. AD is a form of progressive disease that impairs memory and other cognitive functions and impacts the lives of tens of millions of people globally. This study aims to confirm the linkage between exposure to DEP and memory impairment through NLRP3 inflammasome activation, utilizing an animal model to investigate a potential increase in AD later in life. We exposed male and female low-density lipoprotein receptor knockout (LDLR KO) mice chronically to inhaled DEP or filtered air as a control for 18 weeks. We then utilized the Object Location Memory (OLM) and Object Recognition Memory (ORM) behavioral tests to investigate the immediate impact of multi-week DEP exposure on short-term memory, another indicator in AD progression. Afterward, we sacrificed the mice and harvested a variety of tissues, including the brain. I conducted Immunohistochemistry (IHC) on cryosections of the exposed and non-exposed brain to assess DEP-induced AD-like brain architectural changes and to quantify the impact of DEP exposure in activating the NLRP3 inflammasome, ultimately leading to neurotoxicity, and to the development and progression of AD. Confirming the association between diesel exhaust and the NLRP3 pathway provides a potential therapeutic target in populations at an elevated risk for AD.

There is currently a lack of tractable data on what was published in England in the early 20th century. However, this information exists in printed volumes of The English Catalogue of Books, which have been digitized through the HathiTrust digital library. The English Catalogue of Books, released in the UK by the trade publication Publishers’ Circular, provides a yearly record of books published from the mid-19th to the early 20th century. Each catalog has been converted to plain text automatically through optical character recognition (OCR). Our aim was to parse this plain text into user-friendly data on books published each year in the UK. However, the OCR-generated text often contained errors and inconsistencies that prevented the effective extraction of data on books listed in the catalogs. Thus, we aimed to gauge the accuracy of existing methods for parsing the catalogs and to tailor processes for gathering data from catalogs published between 1908 to 1922. By writing regular expressions to capture, split, and match the patterns of bibliographic entries, we were able to improve the accuracy of processes for extracting data. Our solutions increased the number of publications for which information was accurately being captured by on average 28%, and we were able to record information on over 21,500 books that previously had not been captured. We also created a summary dataset from the catalogs with information on the overall output of the publishing industry during these years. By analyzing and visualizing this publishing data, we were able to show that fiction was the most frequently published genre during the period. We anticipate this project to be the foundation of more work towards efficiently parsing The English Catalogue of Books in order to offer insights into the British publishing industry in the 19th and 20th centuries.

This essay dives into three key stories: the myth of Pygmalion and his statue from Ovid's Latin epic Metamorphoses, the story of Acis, Galatea, and Polyphemus also from Metamorphoses, and Madeline Miller's novella Galatea. The major factor that these stories have in common is the overlying theme of male desire, and the consequences of not being able to attain that desire, typically in the form of control or violence. I analyze the literary choices made by both Ovid and Miller, and how they characterize their male characters in juxtaposition with their female characters. I take these analyses and connect them to the modern phenomenon of the Internet "Incel", which is a colloquial term for "involuntary celibate"— an online community of avid misogynists. My main methodology is utilizing critical sources by feminist classicists such as Donna Zuckerberg in conjunction with research studies done on male-dominated online forums to understand how misogynistic rhetoric is formed out of male desire. My essay focuses on Pygmalion and Polyphemus as prototypical Incels, and how this sort of misogyny and desire for control over women has a long history in popular media, and emphasizes the role that the classics play in modern day sexism.

The causative agent of malaria, Plasmodium spp., generated 608,000 deaths worldwide in 2022 according to the World Health Organization and disproportionately threatens endemic areas of Africa. Plasmodium sporozoites infect the host by entering the bloodstream through the skin following bites by female Anopheles mosquitoes. From there, sporozoites migrate to the liver and infect hepatocytes. A single sporozoite-infected hepatocyte is capable of producing thousands of merozoites, which go on to enter the bloodstream. Complete elimination of infected hepatocytes is necessary to achieve sterile protection. In order to observe adaptive and innate immune cell localization towards infected hepatocytes, we applied fluorescence microscopy on livers in a BALB/c rodent model of malaria. Naïve unvaccinated mice were infected with sporozoites of Plasmodium yoelii, a rodent malaria parasite. Two important cell populations are recruited to infected hepatocytes. The first are tissue resident memory CD8+ T cells (Trm), which are crucial in pre-erythrocytic protection. The second are Kupffer cells, which are specialized liver macrophages. To measure these adaptive and innate cell populations, respectively, we applied fluorescently-labeled antibodies to mark the parasite as well as Trms and Kupffer cells. After staining the collected liver tissue and imaging with a widefield fluorescent microscope, we visualized recruitment and measured immune cell proximity quantitatively within a region of interest of the area surrounding infected hepatocytes using microscopy imaging analysis software. This method will be used to test the hypothesis that Trms and Kupffer cells are induced following sporozoite challenge in the rodent malaria model.

Neurons, the fundamental cellular units of the human brain and nervous system, are crucial to transmitting signals throughout the human body. In human anatomy, anything that obstructs the communication between neurons could lead to neurodegeneration, decline in function, disorders, and diseases. Alzheimer’s disease (AD), which affects more than 6 million people across the nation as of 2023, is one such disorder. An extensive array of research has been done investigating the underlying cause of the neurodegeneration that occurs in AD. One such theory of neuronal dysfunction, the amyloid hypothesis, points to an accumulation of a protein called beta-amyloid that is present in the brain but in some people accumulates in excess and disrupts neuronal signaling. This ultimately leads to neurodegeneration and cognitive decline. I take part in conducting the AHEAD study, a Phase 2 clinical trial, which is currently underway investigating this theory and a new drug called lecanemab. The drug is designed to remove beta-amyloid from the brain and prevent further neurodegeneration in individuals who have accumulations of amyloid and are at risk of developing AD. This is one of the first preventive clinical trials for Alzheimer's. In this review, I have explored findings from Phase 1 of the AHEAD study and described the screening process for participants for the Phase 2 trial. I have also explored the science behind beta-amyloid, Alzheimer’s disease, and treatment with lecanemab. I expected a large population to pass the screening process, but the statistics show otherwise. I dive into why this is in this project.

This project aims to document the phonology (sound systems) of Triestin, a Venetian dialect spoken by about 200,000 people in Trieste, Italy. Triestin lies at the intersection of the Germanic, Romance, and Slavic language families and thus exhibits many unique phonological phenomena. The documentation of these phenomena is increasingly important as the number of native speakers rapidly decreases. I recorded four native Triestin speakers reading over 300 words each to elicit a variety of words and sentences. In my illustration, I analyze two main phenomena: (i) the vowel system and (ii) intonation. To analyze the vowel system of Triestin, I took 100 words with vowels in different phonological environments (surrounding sounds) and analyzed patterns in their formant values (resonant frequencies that distinguish one vowel from another). I found the vowel system is unique in its reduced size, having only 5 distinct vowels as opposed to other Venetian dialects’ 7 vowels. My analysis describes how this reduced vowel system exhibits variations unique to the dialect, such as raising in stressed penultimate syllables. Triestin sentences also have a rich system of intonation that differs significantly from other Venetian dialects. In my research, I demonstrate how declarative sentences’ intonation is a function of the pragmatics (contextual meaning) of the conversation. The data also suggests that the intonation interacts with the stress of the final word in the sentences, resulting in greater rising intonation for sentences ending in a stressed syllable. The unofficial languages of Italy, including Venetian and its dialects, are extremely under-documented. Projects such as my illustration of Triestin phonology help with expanding the body of literature on the unique features of endangered dialects. This project is also the first step in a more holistic documentation of Triestin, with future projects aimed at studying the syntax and sociolinguistics of the language.

The inner ear is crucial for both hearing and balance and undergoes rapid changes during embryonic, fetal, and postnatal stages. Its complex structure poses challenges in studying auditory systems, especially the organ of Corti responsible for sound perception. Hair cells (HC’s) within the cochlea are essential for hearing, and their loss in mammals results in permanent deafness due to their inability to regenerate. We recently established Early B cell factor 1 (Ebf1) as an important factor for the development of the cochlea. Our lab’s work with conditional knockout (cKO) mouse models revealed that Ebf1 restricts sensory development within the cochlear duct. The Slc26a9-Cre Ebf1cKO model deletes on embryonic day (E) 9.5. We have seen over 2-fold increases in HC’s and their associated support cells (SCs). We have developed a tamoxifen-inducible Sox2Cre recombinase mice model for precise timing of genetic manipulation within the cochlea. Specific temporal activation of tamoxifen-inducible Sox2Cre recombinase in the cochlea will uncover critical regulatory time periods for the establishment of the sensory domain. Activation of tamoxifen-inducible Sox2Cre at embryonic day 11/12 only shows an increase in inner hair cells. These findings lead us to ask, what’s the critical window for Ebf1’s regulatory role in cochlear development? To determine the optimal window for Ebf1's regulatory role, I will activate the Cre expressed in Sox2 Ebf1-cKO mice with tamoxifen at different embryonic days (9-14) via oral gavage. Immunostaining experiments utilizing HC markers (Myo7a), inner HC markers (Vglut3), and SC markers (Sox2) will be conducted. I will quantify HC densities and cochlear length of Sox2 Ebf1-cKO and littermate control mice. Due to tamoxifen toxicity, samples will consist of embryonic day E18 specimens. Anticipated results include varying HC numbers, innervation and the presence of ectopic sensory patches. This study will offer valuable insight into the temporal dynamics of Ebf1's regulatory role.

Alcohol and other substance use are associated with a range of negative physical, mental, and social consequences including blackouts, unintended injuries, involvement in interpersonal violence, and other health problems. Young adults in college are particularly at risk for alcohol and other substance use. While existing research on reduction interventions often emphasized individual responsibilities of those that engage in alcohol and substance use, peer interventions remain an overlooked approach to harm reduction. Bystander interventions have been shown to be effective in preventing and reducing the harm of sexual assaults among college students. However, there is less empirical attention on applying bystander interventions to reduce the negative consequences of substance use. An important first step of understanding how to incorporate bystander interventions to address substance use is to have a reliable and valid measure assessing these behaviors. This study aims to develop and examine the psychometric properties of a new bystander behavior scale specific to substance use. Data came from a large multi-site survey study with 930 college students (Mage = 19.39, 69.6% female, 58.1% White). I will conduct exploratory factor analysis to extract underlying factors that best explain the observed correlations between the items. Next, I will examine convergent and discriminant validity of the scale scores by correlating them with established instruments such as Drinking Refusal Self-Efficacy Questionnaire and Personal Assessment of Responsible Drinker Identity. Individuals who score higher on the bystander behaviors measure are expected to score higher on self-efficacy in resisting alcohol and be more likely to identify as responsible drinkers. Results will provide initial validation data for the bystander behaviors measure and can be used in future research and intervention implementation that address substance use among college students.

Family businesses are some of the most important economic contributors in the United States, accounting for approximately 64% of the U.S. GDP. The family business model, which refers to any business with two or more family members on the board or in ownership, is a crucial and enduring part of business in the Seattle area and abroad. Historians have often pointed out that the family business model seems to be the base model for business and has thus been present since the beginning of organized business, often in the form of farms, merchant companies, banks, and other small businesses. Despite its prevalence, the family business model is far from perfect because of its numerous commonly encountered limitations. One of the limitations family businesses face is the challenge of succession, as only about 30% are able to succeed from the first generation to the second. Other limitations relate to growth, sustainability, and qualification problems. This study, conducted as a literature review, uses a combination of peer-reviewed articles and popular sources (chosen based on criteria of relevancy and prominence) as quantitative data to examine the consensus of family businesses in Seattle and the solutions that have been proposed to address these limitations. Interviews with family business owners in the Seattle area were also conducted to provide qualitative data and to highlight specific opinions. The economic and historical implications of Seattle family business are also discussed. This research aims to provide insight into otherwise costly financial, succession, and leadership difficulties in order to ensure that the family business model is an enduring contributor to the Seattle economy. Having the proper knowledge on how to approach these difficulties and reconcile with their seemingly conflicting nature can help family businesses in the Seattle area thrive while working through complicated business situations.

Rare Intracranial Tumors (RIT) are a heterogeneous group with unmet medical needs. Although infrequent in individuals, RIT affect millions of people who lack effective disease monitoring and treatment. Frequent chromosome gains and losses are common in cancer, leading to the upregulation of oncogenes and downregulation of tumor-suppressor genes, respectively. Somatic Copy Number Variations (CNVs) affect a greater fraction of the genome than single nucleotide polymorphisms (SNPs) and have been correlated to drug resistance and tumor progression, highlighting a potential prognostic value. Cell-free circulating tumor DNA (ctDNA), which are DNA fragments released by necrotic or apoptotic tumor cells can act as a noninvasive cancer biomarker, offering a potential alternative to invasive tissue biopsies. In the present work, we aim to establish the somatic CNV signature of tumor and matched ctDNA to identify non-invasive tumor-related CNVs that may serve as biomarkers for use in liquid biopsy. We performed Whole Exome Sequencing (WES) in gDNA isolated from tumor tissue and matching ctDNA of 15 patients with RITs (pituitary tumor (n=9), craniopharyngioma (n=2), and meningioma (n=4). Raw reads were assessed for quality (Trimmomatic, FastQC), following alignment against human reference genome GRCh38 (BWA). Aligned reads were sorted and subject to duplicate removal using Picard. CNV profiles will be generated using CNVkit tool. Data analysis and visualization will be performed using R and python. The most promising aspects of liquid biopsy in cancer applications are cancer screening and early diagnosis because they can lead to better survival results and less disease burden. At the end of this work, we hope to identify the CNV signatures shared between tumor tissue and ctDNA, provide novel insights into the pathophysiology of these RITs and ultimately, suggest promising biomarker candidates for liquid biopsy.

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

Alzheimer’s Disease (AD) is a progressive brain disorder that debilitates memory, learning, and decision-making. Early-stage AD represents the initial phase where individuals are still able to function independently, but with increasing age, their condition steadily progresses to dementia and loss of independence. Because a significant number of the aging population is affected by AD, understanding the neuroinflammatory processes would help develop more effective strategies for treatment. Examining markers such as MCP-1 and TNF-alpha, known to be associated with inflammatory response, will help identify the modulatory processes that lead to mild cognitive impairment associated with early-stage AD. Subsequently, higher levels of inflammation markers within the brain leads to mild cognitive impairment. This research study involved 40 C57BL/6 mice, 20 males and 20 females (21 months old), retro-orbitally infected with 80 µL of neurotrophic AAV-AD vector or AAV-Sham for a duration of 2 months before humane euthanasia. Brains were collected, and specific regions were examined by immunohistochemistry (IHC) and digital imaging to assess the expression levels and distribution of the inflammation markers. Preliminary observations showed that hippocampal regions of the brain from mice with early-stage AD had higher staining intensity for MCP-1and TNF-alpha compared to respective areas in Sham mice, suggesting increased inflammation is a very early lesion that develops in the presence of AD pathogenic components that might be controlled by anti-inflammatory drugs. The preliminary data suggests that the characteristics of AD manifest in part due to the neuroinflammatory response of brain factors that change with onset AD.

Family medicine requires effective dissemination of its growing research base to inform practice, education, and policy. The new Consensus Reporting Items for Studies in Primary Care (CRISP) guidelines may contribute to success. We will describe the pathways primary care (PC) research follows from presentation to publication and test if encouragement to use the CRISP guidelines is associated with increased acceptance and publication rates. We are conducting a confidential online survey in two phases of everyone who presented original research at the November 2023 meeting of NAPCRG (North American Primary Care Research Group), using the Qualtrics platform. Currently in progress, Phase 1 collects data on presenters, studies, research reports, author teams, submission processes, acceptance rates, and publication outcomes. Bivariate and multivariate analyses will identify factors associated with submission, acceptance, and publication. In Phase 2, a randomized controlled trial (RCT) will assign participants to either an observation-only control group or an intervention group receiving the CRISP guidelines. A follow-up survey at 6-9 months will assess presenters’ experiences with acceptance and publication of their written reports. The ongoing Phase 1 survey of 659 presenters worldwide includes diverse professions, specialties, scientific disciplines, and research roles. The presented studies include a broad range of research methods, study designs, problems, populations, and research questions. We will describe presenter experience with the submission, acceptance, and publication of these studies and examine associations with characteristics of the researchers, studies, and reports. The later Phase 2 RCT and follow-up survey will test for differences between the CRISP guideline group and the observation-only control group in success with acceptance and publication. Study results will describe the current practices and patterns of submitting and publishing reports of PC research to guide the dissemination and implementation of research findings to help improve patient care and population health.

Growing environmental stresses such as ocean warming have led to a rise in coral bleaching events. Where reef-building corals lose their symbiotic algae that usually supply most of their energy. Bleaching events have led to widespread coral starvation and death, damaging the structure of coral reefs. This study aims to identify if the sex of a coral colony will impact the colony’s ability to withstand growing environmental stresses. Although most coral species are hermaphroditic, we worked to gain insight into the responses of gonochoric corals (in which individuals are either male or female). We focused on a major reef-building species, Porites compressa, from Hawai'i, to better understand how reproductive development compares to bleaching events, and colonies’ ability to recover from bleaching. We hypothesized that female colonies would be better equipped to withstand environmental stress due to excess nutrients stored in their eggs, which can be re-absorbed during stress. While males grow faster at the cost of investing less nutrients in sperm leaving them vulnerable to heating events. Coral polyps from male and female colonies were collected at different points between 2021 and 2023. Using the polyps, I determined each colony’s sex and the developmental stage of each egg or spermary. With this data the varying developmental stages were compared, to present the expected differences between male and female gamete development. I also measured each colony’s annual growth through skeletal growth rings preserved in frozen colony fragments. We analyzed this data to determine if females grow more slowly to better survive bleaching due to earlier annual investment in nutrient-rich eggs, to keep available during bleaching events. Through this study, a better understanding of coral development and success based on the reef’s sex will allow greater predictions to be made in future research as ocean warming increases.
 

Plants utilize cell surface protein receptors to recognize insect herbivory through the detection of Herbivore Associated Molecular Patterns (HAMPs) Following the detection of HAMPs, plants initiate specific immune responses, often measured by the increased production of the hormone ethylene gas and by Reactive Oxygen Species (ROS). The Inceptin Receptor (INR), which is specific to legume plants, recognizes the HAMP Inceptin11 (In11). The binding of In11 to INR initiates a signaling cascade, leading to an immune response. However, the signaling mechanism activated by INR is unknown. The Receptor-Like Cytoplasmic Kinase (RLCK) gene Herbivore Induced Kinase 1 (HIK1) is upregulated by In11 treatment in the bean species Phaseolus vulgaris. The goal of this research is to determine if HIK1 and other RLCKs are downstream proteins required for INR signaling. Because of the genetic intractability of P. vulgaris, I transform Arabidopsis thaliana with RLCK genes using Agrobacterium tumefaciens infiltration. Isolated genetic lines are then used to analyze the effect each RLCK has on immune signaling. Transgenic plants are treated with bacterial associated molecular patterns to trigger an immune response, then tissue samples of the leaves are measured for ROS and ethylene gas production. Results are then compared with ROS and ethylene gas production of wildtype plants. If the studied RLCKs are involved in downstream INR signaling, the transgenic plants will have increased ROS and ethylene gas production. I anticipate HIK1 to have the strongest increase in ROS and ethylene gas production due to the upregulation of HIK1 after In11 treatment in P. vulgaris. Understanding the INR signaling pathway is vital for engineering of plants that are resistant to insect herbivory without the use of pesticides.

Plants recognize herbivore-associated molecular patterns (HAMPs) during herbivory that activates signaling to induce immune defenses. Caterpillar oral secretions contain Inceptin 11 (In11) which is a HAMP recognized by legumes such cowpea via Inceptin Receptor (INR). Thus, In11 and INR are a model system to study proteins involved in HAMP induced defenses, including Kunitz trypsin inhibitors (KTIs). It is known that KTIs are serine protease inhibitors with anti-herbivore activity; however, the precise role of In11 induced KTIs and the effect of cysteine content variation in cowpea KTIs remains unknown. Here, we show that selective removal of cysteines has a negative effect on KTI function in cowpea experiencing herbivory from the fall armyworm (Spodoptera frugiperda). We found that cowpea KTIs act as antiherbivore proteins against the fall armyworm when expressed in Nicotiana benthamiana, as we saw reduced weight gain on larvae feeding on leaves expressing wildtype KTI. Furthermore, we found that KTI function was negatively affected by the removal of cysteines, and larvae fed leaves expressing any of the mutant gained more weight than those feeding on wildtype. We hypothesize that these findings are due to reduced protein stability because we did not detect mutant KTIs in frass samples by westernblot. Understanding KTI protein structure and how it influences protein function is important for designing and selecting antiherbivore proteins to be used for plant defense in agriculture.

In recent years, organizations have debated whether elements of “white supremacy culture”, including a sense of urgency, may create inequitable environments for people of color. We aimed to empirically investigate whether cultures of urgency in professional settings undermine the recruitment of racially minoritized groups. Undergraduate participants (N = 219) read job advertisements for two jobs: one where urgency culture is highly valued (e.g., “swiftly reset priorities at any given time”) and one with less sense of urgency (e.g., “adjust priorities based on capability”; order counterbalanced). Participants then reported how likely they would be to apply to each job. We hypothesized that individuals from racially minoritized groups will be more likely to apply to lower-urgency jobs over high-urgency jobs. The results show that most participants preferred lower-urgency jobs. However, countering our hypothesis, individuals from racially minoritized groups held more positive attitudes towards high-urgency jobs (e.g., how well they think they'd perform in the job) when compared to white participants. This finding casts doubt on the proposed elements of "white supremacy culture". It urges for more empirical research on how different racially minoritized groups may perceive these elements in work settings. Furthermore, our sample consists mainly of Asian Americans, which does not speak for the experiences of other racially minoritized groups. Our future research will focus on diversifying samples collected.

Religious nationalism is receiving growing attention because of its current influence in democracies, but it manifests itself differently across countries. Previous research has identified socio-historical characteristics that impact the salience of religion as a factor in an individual’s conception of national identity. However, scholars of these studies have mainly used International Social Survey Programme data to analyze European nations. My study uses World Values Survey (WVS) data from 1981 to 2022 to evaluate democracies from a global perspective. I conduct a multilevel analysis to determine the salience of contextual characteristics that prime religion to be used as a vector through which nationalism is mobilized among individuals. Accounting for individual-level factors, I identify which country-level factors influence the relationship between religion and support for nationalism among individuals surveyed. I determine an individual’s support for religious nationalism using the beliefs and groups they express to support in the WVS. I then compare these results to events of national stress to determine if a relationship can be identified. My results suggest that religions favored in church-state relations are more likely to be included in conceptions of national identity. Additionally, affiliates of favored religions are more likely to support nationalism during times of outgroup threat, such as increases in immigration, socio-economic turmoil, and political/cultural shifts. By completing a global analysis of these phenomena, I am able to identify a more comprehensive pattern, something less expansive studies struggle to achieve due to hyper-partisanship debates that can overshadow case studies and regional analyses. Furthermore, by determining which socio-historical characteristics have the greatest impact on conceptions of a religious national identity, I provide a framework to develop a predictive theory on the circumstances under which a religion is not only primed to mobilize nationalist movements, but then comes to be employed to mobilize these movements.

While environmental writing is nothing novel, environmental journalism as a beat and research area is relatively recent. The available literature on the field provides insight into the challenges environmental reporters face and what their environmental backgrounds in the field are, but little research details how they respond to challenges and why they originally chose the beat. This research examines how environmental journalists respond to the challenges they face, what values they attribute to the beat, and why they chose to write about the environment. My hypotheses are that these reporters have had influential experiences in nature; they see their work as a form of social activism; and they rely on their social connections as a form of support. For my sample, I first used random systematic sampling, followed by purposive sampling to reach targeted demographics, such as gender and race. I conduct semi-structured, in-depth interviews to collect my data, with a goal of at least 15 interviews or until saturation. So far, I have conducted five interviews that average around 45 to 60 minutes each. Most of them grew up as outdoorsy people, all of them see their work as important, and most find that talking to someone about challenges they encounter is helpful. Through more interviews, I hope to begin recognizing strong trends in responses to compare to my hypotheses. In addition to filling the gaps in the literature on environmental journalism, this research provides these reporters with a chance to talk about their experiences and challenges. Additionally, building on this beat as a research area could help provide data to create a meaningful support network for environmental reporters. As climate change intensifies and more people feel its effects, it’s imperative that these journalists feel supported enough to continue highlighting climate solutions and inequities to advocate for climate action.

In the US, our primary healthcare is mostly delivered via the fee-for-service model. Interactions between providers and patients under this model are mediated by insurance companies. In order to bypass health insurance companies, some primary care physicians have opened direct primary care clinics which charge a monthly fee for unlimited care. As part of my undergraduate thesis for the anthropology honors program, I investigated two clinics operating under this model in the Pacific Northwest using participant observation and semi-structured interviews with physicians. My aim was to determine how the direct primary care model affects the agency of physicians and influences the therapeutic process via the clinical encounter. I found that physicians in the US face a unique dilemma of role conflict between the competing identities of business owner and doctor. Additionally, I explored how the expectations of patients differ for male and female physicians and how direct primary care can play into this. My findings highlighted the inadequacies of our existing healthcare system in the United States. Further, I concluded that although direct primary care is a solution to this broken system for some patients and some physicians, systemic changes must be made in order to make primary care a more desirable field for physicians and to provide equitable and quality care for all patients.

In my research, I explore the role of children in Late Bronze Age Mycenaean society (ca. 1600-1100 BCE) by focusing on the relationships, socioeconomic and religious roles, gender dynamics, and burial practices of and for children, as well as ideas surrounding adolescence and the representation of children in Mycenaean art. Children hold a unique role in society, and it is important to understand the roles and perceptions of children. In doing so, we gain a better understanding of the experience of childhood as well as the culture as a whole. I begin by defining Mycenaean views on childhood, providing a framework to contextualize the discussion. This project is a synthesis of previously published data, incorporating the Linear B tablets, sites, excavations, and art from Late Bronze Age Mycenae, explored in this paper through comparative analysis. I utilize a similar approach when discussing the burial practices for children, focusing on burial architecture and style and archaeological reports on specific sites, such as Ayia Sotira and Mycenae. By studying the roles and lives of children, we gain insight into generational dynamics, family structure, gender roles, and domestic dynamics, which all contribute significantly to understanding the cultural structure of a society. Through the specifics of material culture, social spaces, and practices involving or surrounding children, I look to develop a larger picture of the experience and significance of children in Mycenaean society, in effort to give context and perspective for existing and future research surrounding Mycenaean culture.

Media coverage of the National Hockey League (NHL) has brought public attention to many accounts of physical and sexual violence, hazing, and illicit drug use by players and coaches over the past 20 years. My research investigates the institutional mechanisms the NHL, its teams, and the players union use in response to cases of criminal behavior by their athletes. I ask how consequences for player criminality vary by type of crime, status of player, and player network. I compiled a dataset of all incidents covered in the news or social media between 2009 and the present, and then identified the response type through qualitative coding and comparison. Given prior theorizations of men’s collegiate athletics as crime-facilitative environments based on low punishment risk and high temptation to participate in criminal deviance, I expect to find that fine-related punishments are levied more frequently against high-status NHL players and high level player networks than are playing-time related penalties, protecting their ability to continue contributing to a franchise’s game performance. I also predict violent crimes will more frequently include playing-time related penalties, with League Commissioner approval more consistently mandated. I anticipate the team sub-organization to most frequently levy punishments for player criminality. This research introduces a more comprehensive examination of NHL player criminality, extending beyond existing approaches of case-based analysis. Importantly, this allows for future comparison to leagues such as the National Football League and its handling of player criminality over time. More broadly, I clarify the consistency with which deterrence measures are employed by the organization, contributing to the body of literature analyzing private organizations and their governing power over employees.

University of Washington Food Pantry (referred to as "food pantry" in the rest of the article) has been providing free food and supplies to faculties and students for years. Visitors to the food pantry have been increasing since 2021, and even quadrupled from winter 2022 to winter 2023. I observed that the visitors to the food pantry are predominantly people of color since my start of volunteering at the food pantry in April 2022. Other observations include most visitors studying science or engineering majors. I designed a google form survey where visitors fill out during each visit which includes information including race, gender identity, major of study, age, and hometown. I conduct analysis to compare the demographic and academic profiles of food pantry visitors as collected through a Google Form survey during each visit, against the corresponding parameters of the entire student population at the University of Washington. I anticipate that there will be a higher percentage of STEM (Science, technology, engineering, and mathematics) majors visiting the food pantry, and a higher percentage of people of color visiting the food pantry compared to the entire student population at the University of Washington. Findings from this research aim to highlight the inequalities in higher education and provide evidence for underlying financial or social disparities in order to inform and raise awareness among university policies and support systems on resource distribution. The findings can also serve as the basis of long term future study on impact of food pantry use on academic performance, graduation rates, and post-graduation outcomes.

This paper examines several ancient sources for instances in which figures exhibit disconnection, aversion, or repulsion towards the erotic sphere that is so valued in societies. The paper will mainly focus on two myths: those of Narcissus (as illustrated in Ovid’s Metamorphoses) and Hippolytus (as shown in Euripides’s Hippolytus, Seneca’s Phaedra, Ovid’s Metamorphoses, and Ovid’s Heroides). In this essay, I argue that these figures can be read as asexual and that their untimely ends were brought about by their refusal to conform to the societal expectations placed on men–often characterized by vigorous sexual appetite, which would eventually lead to a man passing down his bloodline and fulfilling his duty to his oikos. Since myth often reflects real life, and works as a tool people can use to think about themselves, it can be argued that the inclusion of asexual-coded figures supports the contention that the asexual identity has always existed, even if the words to describe it are a more recent development.Therefore, the Narcissus and Hippolytus episodes are valuable pieces of evidence for both ancient and modern discourses of sexuality stepping outside the bounds of allonormativity. From a methodical standpoint, I first analyze the ancient texts, including secondary sources on them, then look at studies and papers on modern-day asexuality and examine the myths through this lens.

As the Anthropocene progresses, environmental stressors are becoming more noticeable in their impacts on aquatic ecosystems and the organisms that inhabit them. One such organism of environmental and ecological importance is the Pacific oyster, C. gigas. Under climate change, molluscan shells are likely to become weaker due to lowered calcium carbonate availability which may lead to increased mortalities. In Washington state, C. gigas provides 3200 jobs annually and lowers nitrogenous waste concentrations. Our focus in this work was to determine if temperature and pH would affect shell strength in C. gigas as climate change continues to affect their environment. We used C. gigas samples that grew in Puget Sound, Washington, over the summer months. Samples were tested for maximum load of pressure shells could withstand and correlating that to thickness to determine strength. We found that temperature and pH were not correlated to shell strength. We observed that the shell strength of C. gigas taken from Puget Sound did not depend on temperature or pH changes. Previous molluscan shell strength experiments in other settings and locations show contradictory results, but there is little evidence pertaining specifically to C. gigas. These experiments are typically conducted in laboratory settings as well, not in field settings like ours. Going forward, this concept should be reconsidered to confidently identify what the Anthropocene has in store for C. gigas.

This global change study examines the multiple-stressor impacts of heat and plastic leachates on a symbiotic clonal cnidarian, the aggregating anemone, Anthopleura elegantissima. Marine heatwaves and ocean plastics are two forms of anthropogenic pollution that are increasing and predicted to rise in future ocean conditions. In Puget Sound, intertidal marine organisms are most at risk of exposure to these combined stressors. In summer, low tides at noon leave intertidal organisms in stagnant warming water or fully exposed to desiccation. Marine heatwaves, like the one that occurred in June 2021, caused water temperatures to spike along Puget Sound coasts. Concurrently, road run-off and sewage likely expose intertidal organisms to higher concentrations of plastic leachates. Leachates are derived from machine-washed polyester clothing microplastics, polyvinyl chloride sewage pipes, and non-source point pollution that is swept through watersheds toward the coasts. Plastic pollution in the form of leachates is understudied in coastal ecosystems, compared to thermal stress. Plastic-derived leachates are the complex cocktail of chemicals that leach from plastics into the environment and are considered pollutants of emerging concern. We do not fully understand the impacts they have on the physiology of marine organisms, and even fewer studies address their impacts in the context of marine heatwaves. We will test physiological and photophysiological responses of aggregating anemones to thermal stress and plastic leachates, separately and combined. We will develop respirometry and light response curves for each of the treatment conditions and a control. We hypothesize that the cnidarian host will show increased metabolic activity indicating stress under both types of pollution, and that photosynthetic efficiency in the algal symbiont will increase with leachate exposure. We hope to use the results of this study to better understand how anemones and other cnidarians like corals are affected by the threats of plastic pollution and global warming.

Massive stars place powerful constraints on stellar evolution and exhibit a wide range of exotic evolutionary phases. They play a crucial role in regulating their environments, driving the chemical evolution of host galaxies, and establishing energy equilibrium through feedback processes. Stellar variability, notably, acts as a profound probe into the poorly-constrained physics of massive star evolution, illuminating intrinsic properties such as surface gravity. Drawing upon the collective insights from past literature on the dynamics of stellar rotation and surface gravity, this project delves into the correlation between variability metrics from the Zwicky Transient Facility (ZTF) and surface gravity measurements from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) data. By merging these datasets, our aim is to use modern statistical methods to decode the relationship between observed variability and surface gravity in massive stars, shedding light on their rotational behaviors and structural changes over time. This endeavor not only seeks to deepen our understanding of stellar mechanisms but also to improve the precision in classifying stellar masses by utilizing variability as a key diagnostic tool. We endeavor to connect empirical observations with theoretical frameworks, paving the way for future advancements in our comprehension of stellar dynamics and their cosmic significance. Our results will place key constraints on the study of massive stars.

Ocean acidification (OA), the lowering of the ocean’s pH due to human-driven increases in atmospheric CO2, threatens many coastal communities and industries, and is thus linked to high environmental, economic, and societal losses. Yet, OA and its local context remains under-discussed by educators, industry workers, and community members. To address this shortcoming, NOAA’s Ocean Acidification Program, the International Alliance to Combat Ocean Acidification, and the Aquarium Conservation Partnership collaboratively created the “Exploring Our Changing Ocean: Impacts and Response to Ocean Acidification in the U.S.” StoryMap collection. The six StoryMaps, which I researched for and storyboarded, support localized OA education, outreach, and calls to action by showcasing regional OA trends, impacts, and community responses taking place across each of NOAA’s six Coastal Acidification Network regions. The StoryMaps intend to 1) Increase understanding about impacts of carbon emissions on our oceans and contribute to aquariums' place-based storytelling efforts on addressing climate change in their communities, 2) Reach new audiences, specifically members of the public visiting U.S. aquariums and marine education centers, although traditional audiences, such as academics, government leaders, and seafood growers can engage as well, and 3) Accelerate calls to action by showcasing detailed personal calls to action which help move OA activities beyond science. Currently, I am working with the United Nations Foundation on effectively distributing the StoryMaps to partner aquariums and implementing the content into larger climate change narratives and outreach. The StoryMaps can be shared as interactive displays, virtual-learning materials, or hard-copy outreach materials in participating aquariums, as well as through networks like educators, non-profits, conservation organizations, or international climate leadership fora. Through regionalized storytelling, this project will increase awareness of local OA trends and responses, facilitating enhanced awareness and action in at-risk communities.

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

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

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

Tuberculosis remains a global public health threat due to the rising number of multi- and extensively drug resistant strains of the causative pathogen Mycobacterium tuberculosis. Development of novel drugs and an understanding of their resistance mechanisms is urgently needed. Aminothiazoles (AmT) are potent molecules with killing activity against M. tuberculosis; these compounds act as copper ionophores and target a key enzyme (enolase) by displacing its Mg²⁺ co-factor, a substance required for its activity, with Cu²⁺ imported by the compounds. Spontaneous mutations in an essential protein export system (the Esx 3 Type VII secretion system) confers resistance to AmTs. My research focuses on understanding how mutations in the secretion system cause AmT resistance. We hypothesize that copper imported by AmTs could disrupt other metallo-proteins including EccA3, a key ATPase of the of the Esx-3 secretion system that hydrolyzes ATP into ADP and inorganic phosphate, and that resistance mutations (e.g. E237K) reduce Mg²⁺ co-factor displacement by Cu²⁺. To test this hypothesis, I expressed wild-type (WT) EccA3 and mutant EccA3 [E237K] proteins in Escherichia coli BL21(DE3) expression strain and purified the proteins via Ni-NTA His-tag chromatography. Subsequently, I measured the activity of the purified EccA3 (WT) and EccA3 [E237K] proteins via an ATPase assay based on colorimetric detection of free inorganic phosphate released by ATP hydrolysis. I aim to understand whether copper inhibits EccA3 activity through this assay, anticipating that copper reduces EccA3 (WT) ATPase activity while EccA3 [E237K] ATPase activity is unaffected. Thus, my work will provide an avenue for understanding AmT resistance in M. tuberculosis.

Toll-like receptor 4 (TLR4) is an immune protein which binds lipopolysaccharide (LPS) present on the outer membrane of Gram-negative bacteria and activates the innate immune response. In mice, an mRNA splice variant composed of only the extracellular domain of TLR4 was shown to encode a soluble product (sTLR4) capable of inhibiting inflammatory response to LPS. sTLR4 has been recovered from human saliva and demonstrated to dampen the production of pro-inflammatory cytokines by macrophages. Prior work showed that TLR4 was also present in endometrial glands, uterine tube epithelia and endocervical glands. However, there are no published studies exploring the presence or role of sTLR4 in lower genital tract secretions. We tested primary female genital epithelial cells’ supernatants as well as human endocervical cytobrush and vaginal swab samples for the presence of sTLR4 by using a chemiluminescent immunoassay. We found sTLR4 in cervicovaginal secretions, with increased concentration of sTLR4 present in participants with endocervical ectopy and in those sampled during the proliferative phase of the menstrual cycle. Supernatants from endocervical cell lines possessed higher levels of sTLR4 than those derived from ectocervical or vaginal cells. sTLR4 concentration was not correlated with the presence of bacterial vaginosis, age, the concentration of common vaginal Gram-negative bacteria or with genetic variation in the TLR4 locus. By western blotting, we demonstrated that sTLR4 is composed of a ~100 kDa polypeptide, corresponding to the entire TLR4 ectodomain. In a reporter monocytic cell line, we showed dose-dependent inhibition of the LPS/Interferon-regulatory factor (IRF) pathway when LPS was preincubated with endocervical cells’ supernatants. These results point to an unappreciated form of innate immune regulation in the cervicovaginal niche, which could potentially open new avenues for understanding inflammatory disorders such as cervicitis and pelvic inflammatory disease.

Biofilm is a community of bacteria enclosed in an extracellular polymeric substance (EPS) attached to a surface. Inside the biofilm, bacteria can collaborate to increase their survival. The EPS also protects bacteria from drug penetration, leading to increased antibiotic resistance. Therefore, biofilm formation is often linked with chronic bacterial infections. Pseudomonas aeruginosa is an opportunistic pathogen that often causes chronic lung infections in cystic fibrosis patients. It is also a common model for studying biofilm formation. The initial step for biofilm formation is bacteria attaching to and sensing a surface. Upon surface contact, P. aeruginosa may produce cyclic adenosine monophosphate (cAMP), which is a universal second messenger that regulates cellular functions in both eukaryotes and prokaryotes. In P. aeruginosa, cAMP is synthesized by two adenylate cyclases, CyaA & CyaB, and degraded by a cAMP phosphodiesterase, CpdA. cAMP is a key regulator for P. aeruginosa virulence by upregulating the production of the type III secretion system, the type II secretion system, and the type IV pili. However, recent observations in our lab suggest that cAMP may also contribute to the homeostasis of the cell envelope. To investigate this phenomenon, I used microscopy to characterize the cell morphology of strains with different cAMP levels and found that increased cAMP levels lead to longer cells. I also found that high cAMP strains are more sensitive to êžµ-lactam antibiotics specifically, while low cAMP strains become more resistant. Ongoing work includes characterizing the genetic factors that connect cAMP and êžµ-lactam sensitivity, as well as using microscopy to determine changes in cell envelop induced by cAMP. Overall, this work reveals an important role of cAMP in bacterial physiology and provides insight into the complex relationship between virulence and antimicrobial resistance.

Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an opportunistic pathogen of wounds, cornea, and the Cystic Fibrosis lung. P. aeruginosa is also a model organism for the study of bacterial biofilm formation. Biofilms are multicellular communities that form from bacterial growth concomitant with the production of extracellular polymeric substances (EPS). EPS includes polymers such as polysaccharides, DNA, and proteins; these polymers provide structure and protection to the biofilm cells. Proteomics experiments by the Parsek Lab and others have demonstrated that a notable component of the biofilm matrix are the secreted proteases. Secreted proteases have defined roles in virulence and nutrient acquisition, but their role in the biofilm matrix of P. aeruginosa has not been explored. I hypothesize that these secreted proteases recycle nutrients, remove cell waste, and protect cells from host immunity. To test my hypothesis, I generated a mutant strain of P. aeruginosa that lacks the six major secreted proteases. While we see that loss of the proteases does not impact planktonic growth, preliminary data suggests that loss of proteolytic activity results in moderately increased biofilm formation. Using a general proteolysis assay relying on casein hydrolysis, I have determined the relative contribution of each of the six proteases to the total proteolytic capacity of P. aeruginosa in planktonic growth. I will further test the impact of the proteases on biofilm growth in different growth environments, including under flow conditions and in artificial sputum medium. I will also assess which proteases contribute the most to proteolysis during biofilm growth. My work fits into a growing body of literature that suggests that the biofilm matrix is not an inert scaffold, but is instead a dynamic and active network.

Mentoring is an effective way to improve diversity and retention in STEM fields. The UW Psychology Undergraduate Mentoring Program (PUMP) matches psychology students from underrepresented groups with mentors, including undergraduates, graduate students, faculty, and alumni. Matches are made based on a combination of career interests and personal identities. In this study, we aim to understand predictors of mentees’ success in the program, defined by feelings of belonging, academic preparedness, and satisfaction with the mentoring relationship. These predictors include meeting characteristics and match characteristics. We hypothesized that in-person meetings, more frequent meetings, and greater similarities between mentors and mentees would be linked with greater success. 32 out of 168 mentees completed our survey on Qualtrics in Spring 2023. We measured meeting frequency (“How often did you meet with your mentor during [quarter]?”), format (“In what modality did you meet with your mentor? In-person, video/phone calls, texting, email”), match characteristics (e.g., whether the mentor and mentee shared similar demographics such as BIPOC, first-generation, or gender; how far apart they were in their class levels), belonging (e.g., “I know other people in the psychology major”), preparedness (e.g., “I feel prepared to pursue the psychology major at UW”), and satisfaction (e.g., “My mentor and I have had a successful mentoring relationship”). We will conduct correlations and multiple regression analyses to test the prediction that in-person meetings, more frequent meetings, and greater similarity between mentors and mentees will be linked with higher feelings of belonging, preparedness for the major, and satisfaction with the mentoring relationship. We hope to demonstrate that controllable variables such as these can improve program outcomes. Identifying the most effective program strategies, like in-person meetings or demographics-based matching, can aid mentees in our program and may also guide the development of new mentoring programs in other departments.

Repetitive transcranial magnetic stimulation (rTMS) is a psychiatric treatment which has shown promise for experimental treatment of memory loss in Alzheimer’s Disease. rTMS uses a coil and electric current which is able to create a magnetic field that can depolarize neurons noninvasively and induce synchronized activity of large populations of neurons, ultimately inducing, lasting changes through synaptic plasticity. Alzheimer’s disease patients show disruptions in the Default Mode Network (DMN), a network of brain regions which is typically active at rest. The DMN has an important role in memory consolidation and is disrupted in Alzheimer's Disease. We hypothesize that strengthening the default mode network through rTMS applied to area left 8AV of the frontal cortex will create improvements in patient memory. To answer this question, we are performing a single-blind, single-arm, randomized cross-over trial of rTMS on early-stage Alzheimer's disease patients. Region 8AV is located by using MRI scans obtained before patients receive either the sham or experimental procedure. This region was chosen due to its connection to the default mode network and previous promising TMS research. Our primary outcome measure is the speed of forgetting, a new, reliable index of memory function obtained by fitting a computational model of episodic memory to behavioral data from an adaptive memory test. Due to the frequent use of rTMS in mood disorder treatment, we are using depression and anxiety scales to track possible mood improvements as a secondary outcome measure. MRI scans will also be analyzed to see if the experimental treatment caused any structural differences in patient brains. Should our hypothesis be correct, we expect to see improvements in memory or cessation of memory decline in patients. Successful treatment would provide a novel target for Alzheimer’s Disease treatment using rTMS, and additional evidence for the continued investigation of rTMS for Alzheimer’s Disease.

Methicillin resistant Staphylococcus aureus (MRSA) is an antibiotic resistant pathogen that causes severe illness and thousands of deaths each year in the US. It spreads within the community through improper hand hygiene and is often found in hospitals and on public transport surfaces. This poses a danger to the public, specifically to vulnerable populations such as the elderly and immunocompromised. This study in Seattle, Washington compares the prevalence of the antibiotic-resistant MRSA bacterium on public transport surfaces both proximate and distant to Harborview Hospital. Swabs from bus stops and pedestrian call buttons were collected outside of Harborview Hospital and urban areas of Capitol Hill, a Seattle neighborhood approximately one mile away from any major hospitals. The swabs were streaked onto Tryptic Soy Agar plates, gram stained, and streaked on Mannitol Salt agar plates;catalase and coagulase tests were run to help further confirm the presence of Staphylococcus aureus. The resulting colonies were then screened for antibiotic resistance using the Kirby Bauer Disk Diffusion method. One instance of potential MRSA was isolated from a crosswalk button in Capitol Hill. A higher MRSA prevalence on surfaces close to hospitals could establish a link between the spread of pathogenic bacteria from hospitals to Seattle's city surfaces but was not found in this study. These results suggest that the spread of MRSA in Seattle may have more to do with foot traffic and public transportation usage. However, the presence of MRSA on urban surfaces puts sensitive populations at risk regardless of its source. Practicing good hand hygiene can help curb the spread of MRSA in the community.

Alzheimer's Disease (AD) impacts over 6 million people in the U.S, but there are currently no fully effective treatments. Ageing is the biggest risk factor for AD and is associated with cellular changes called senescence. Cellular senescence describes a natural process in cells, leading to cell cycle arrest and metabolic changes due to insults from aging/disease processes. Factors contributing to senescence include DNA damage, and others. A risk factor in neurodegeneration is the ageing of microglia- our brain's immune cells that maintain a healthy brain. Senescent microglia express a senescence associated secretory phenotype- a combination of inflammatory proteins released into their environment- that enhances neurodegenerative processes. My project investigates the relationship between microglial senescence and AD by comparing the levels of senescence markers in AD brains, healthy young brains, and aged brains. I hypothesized that AD brains will contain the greatest amount of senescence markers, followed by aged brains, then healthy young brains. I performed immunohistochemistry for p16Ink4a and gammaH2AX (two robust senescence markers) on 10 human individuals (5 male/5 female per cohort) who donated their brain post-mortem. p16Ink4a is involved in cell cycle regulation and gammaH2AX signals DNA damage. The brain samples were also stained with Iba-1 to identify microglia. A confocal microscope imaged the samples and data was analyzed using the IMARIS software and ImageJ. Senescence markers were quantified in each cohort and localized in microglia or non-microglia cells. I expect to see the greatest amount of p16Ink4a and gammaH2AX in AD brains (specifically AD microglia), with the least amount in healthy young brains. I also expect co-localization of gammaH2AX and p16Ink4a in my samples. Understanding the relationship between microglial senescence and AD pathology could aid in finding methods to target cellular senescence. Slowing down this process could be a usefull tool in decreasing the progression of AD.

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

Pain is the number one reason why patients seek medical treatment, yet current pain therapeutics such as opioids have limited efficacy and produce harmful side effects. This has produced a critical need for the development of novel therapeutics for the treatment of acute and chronic pain. Cannabidiol (CBD) shows promise as an analgesic, but the mechanism of action is not well understood as it interacts with several receptors such as cannabinoid receptors CB1 and CB2 and noxious nociceptors TRPA1 and TRPV1. I am investigating how CBD acts on the nervous system to disrupt nociception (pain perception) utilizing the Danio rerio model system and human embryonic kidney cell line 293T (HEK 293T). I use behavioral assays with genetic knockout models to interrogate the molecular mechanism of CBD-mediated analgesia and ratiometric Fura-2 calcium imaging of HEK 293T cells that express TRPA1 or TRPV1 to further elucidate their responses to combinations of CBD, heat, and allyl isothiocynate (AITC, a TRPA1 agonist). My preliminary results indicate that CBD is pronociceptive at low concentrations (10uM) and analgesic at high concentrations (20uM). Recent experiments suggest that CBD’s pronociceptive properties occur via TRPA1 activation, and that this sensitization attenuates CBD-mediated analgesia. I anticipate each CBD receptor knockout will alter CBD-mediated analgesia, with CB1 and CB2 null animals experiencing deficits, while CBD-evoked analgesia may be potentiated in TRPA1 and TRPV1 null animals. I anticipate observing heightened intracellular calcium concentrations when HEK293T cells expressing TRPA1 are perfused with CBD, and increased responses to AITC when cells are perfused with CBD. Importantly, this project creates a platform for the investigation and characterization of minor cannabinoids and other potential therapeutics, using behavioral phenotype based screening to aid in the development of novel, non-opioid analgesics that can revolutionize pain treatment.

Many transgender and gender diverse (TGD) people desire gender-affirming hormone treatment (GAHT) to alleviate discomfort due to the misalignment of one’s gender identity with their secondary sex characteristics, though little is known about its effects on the body. One area of interest that may be affected by GAHT is the gut microbiota (GM). GM and the sex hormones (estrogen, testosterone, and progesterone) have been shown to interact bidirectionally, referred to as the “gut microsexome.” At puberty, the commensal microbiota of males and females diverge due to circulating sex hormones. This difference is hypothesized to contribute to sexual dimorphism of disease prevalence between cisgender males and females, although little research on the effect of GAHT in the TGD population exists. Alteration of the gut microbiota, or dysbiosis, also has many adverse effects that overlap those of testosterone GAHT (THT) such as acne, weight gain, and hypercholesterolemia. Dysbiosis has also been shown to lead to intestinal and systemic inflammation by disrupting immune function. More information on the effects of THT on the gut microbiota is necessary to counsel transmasculine clients effectively. In this study, we injected mice born of the female sex biweekly with testosterone enanthate dissolved in sesame oil versus sesame oil alone. We profiled GM of mice throughout treatment using 16S rRNA sequencing and measured markers of inflammation in serum to assess the effect of THT on both the population of GM and intestinal and systemic inflammation. We expect that the mice receiving THT will have differentially abundant gut microbiota and increased concentration of inflammatory markers compared to controls. The findings of this study will serve as a basis for further studies exploring additional analysis of the gut microbiota and inflammation in both transmasculine and transfeminine people receiving GAHT.

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

Following the COVID-19 pandemic in March 2020, mental health has become a prominent issue in the lives of many as reports of depression, anxiety, and other psychological distress increase. However, due to the sudden and drastic decline in collective mental health, resources including access to therapy and other treatments have been highly in demand. This has caused a shortage with facilities that offer psychiatric and psychological care being overbooked and unavailable. Using a dataset that observed mental health during the COVID-19 pandemic in US households, we utilized a hierarchical Bayesian model to analyze the reported rates of those who took prescription medication for their mental health within the last four weeks for 51 different locations (50 US states including Washington D.C.) across 12 time periods (from August 2020 to March 2021). We used the rstan package in R to implement this model using Markov Chain Monte Carlo (MCMC) methods. Our model applies a partial-pooled model that allows data from different US states to inform others in the case that there are not a sufficient amount of data points or high variance. In our analysis, we were able to conclude that Bayesian modeling is useful for removing noise from data, as when we analyzed the prescription usage rates per state for fewer time periods, our model was able to correct for uncertainty in the given data and give a more accurate reflection of the true rates. The model did not influence the results as significantly when using data across all given time periods. Despite these findings, our hierarchical Bayesian model did correct for the reported variation between the different average rates across the different US states by helping distinguish between signal and noise in the data. Our analysis provides an alternative approach to statistics that allows for analyses tonot only utilize current data, but also considers prior information to create a more informed posterior conclusion.

As global urbanization accelerates, wildlife habitats are increasingly lost and fragmented, exacerbating the ongoing biodiversity crisis. Within urban ecosystems, remaining wildlife face multifaceted challenges. The heterogeneity of urban environments arises not only from ecological characteristics but also from social factors. This study addresses these complexities by deploying transects of baited tracking tunnels and camera traps in Seattle parks to assess indices of abundance for squirrels, mice, rats, and rabbits—integral components of urban small mammal communities. This investigation centers on comprehensive identification of primary predictors of small mammal abundance citywide, encompassing habitat variables like canopy cover and social factors such as median household income and environmental health. Leveraging statistical analyses, we delineate the relationships between these predictors and small mammal abundance, offering insight into urban wildlife population dynamics. These findings provide guidance for urban planners, wildlife managers, and policymakers endeavoring to foster coexistence between humans and wildlife in shared landscapes.

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

Recently there has been interest in two possible sources of mass in the outer solar system. First, observations of recently discovered remote outer solar system objects have suggested the presence of a ninth planet. Different numerical simulations have suggested either a less massive (1.5-3 Earth masses) planet with a semimajor axis of 250-500 AU from the Sun (the Earth orbits at 1 AU), or a more massive (5-15 Earth masses) planet at 400-800 AU. Second, data from the New Horizons spacecraft has suggested that there may be an additional roughly circular belt of objects, similar to the Kuiper Belt, beyond 60 AU. This raises the question of whether this belt would be compatible with some or all of the proposed forms of planet 9. To answer this question, I ran a series of orbital dynamics simulations with randomly generated test particles representing the proposed second Kuiper Belt, and different masses and orbital parameters for planet 9. By looking at how planet 9 changed the orbits of the test particles over the period of the simulation, I concluded that although planet 9 would not significantly affect objects orbiting at 60-100 AU, in the most extreme cases, it would significantly broaden the distribution of orbital inclinations of objects beyond 100 AU. Astronomical deep and wide surveys conducted over the next few years have the potential to detect both planet 9, and objects beyond the Kuiper Belt. If second Kuiper Belt objects are discovered, these objects having a wider-than-expected range or orbital inclinations would point to gravitational disturbances, such as those caused by planet 9. Alternatively, if planet 9 is discovered, these simulations suggest that a second Kuiper Belt would need to be more inclined than has been so far assumed.

Sudden unexpected death in epilepsy (SUDEP) is the most severe consequence of uncontrolled epilepsy. SUDEP is a multifactorial disease associated with serotonin (5-HT) imbalance and exacerbated neuroinflammation. Unfortunately, current preclinical animal models do not adequately explain all underlying causes of these events or their subsequent effects. Seizures are a common comorbidity in Alzheimer’s disease (AD), especially in patients with genetic variants in amyloid precursor protein (APP) and presenilin 1 (PSEN1) and 2 (PSEN 2). Clinical evidence suggests that seizures in AD patients worsen their cognitive decline and increase mortality rate compared to AD patients without seizures. Our lab demonstrated that 2-month-old mice with an APP/PS1 variant subjected to chronic evoked seizures resulted in premature mortality, heightened neuroinflammation, and altered 5-HT system enzyme expression prior to AD onset. These findings reveal a novel preclinical platform to test potential preventative agents for SUDEP. Given the relationship between seizures and AD, I aim to prevent seizure-induced premature mortality, and define 5-HT and neuroinflammatory changes in APP/PS1 mice treated with 2 investigational agents: lorcaserin, a selective 5-HT receptor agonist, and cannabidiol (CBD), a broad-spectrum anti-inflammatory and 5-HT modulator. I hypothesize that targeting seizure-induced neuroinflammation and the dysregulated 5-HT system with these compounds will decrease premature seizure-induced mortality. To assess this, 2-month-old APP/PS1 mice underwent corneal kindling procedure to evoke investigator-controlled chronic seizures and received lorcaserin (10 mg/kg) or CBD (100 mg/kg) via the intraperitoneal route. Then, I tracked survival during the chronic seizure period and performed molecular analysis to quantify neuroinflammatory proteins and 5-HT system enzyme expression. Our preliminary results show that mice treated with lorcaserin or CBD had a mortality rate of 10% compared to 75% in the untreated APP/PS1 mice. Future directions include using these compounds in other preclinical SUDEP models to confirm the translational potential of these medications to clinical use.

VLA-4 is a surface protein of immune cells that plays an important role in their extravasation into tissues during an immune response. In multiple sclerosis (MS), pathogenic T cells enter the brain and attack nerve cells by using VLA-4 to bind VCAM-1, a cell adhesion molecule on endothelial cells that line blood vessels. Current MS treatments rely on antibodies that bind VLA-4 and block interaction with VCAM-1, preventing a pathogenic immune response. However, antibodies are expensive to manufacture, and their binding cannot be easily regulated to control drug-induced side effects. Aptamers are single-stranded DNA or RNA molecules that fold into sequence-defined structures capable of binding targets with affinities and specificities comparable to antibodies. Being chemically synthesized, they are much cheaper to manufacture and offer no batch-to-batch differences. Unlike antibodies, their binding in vivo is rapidly reversible, which could alleviate some side effects of disease treatments. However, aptamers have limitations in vivo – degradation by nucleases in serum, and rapid clearance into urine. This project designs and assesses modifications to a novel VLA-4 binding aptamer to improve in vivo function, with the goal of developing an alternative for MS treatment. We designed various modifications to the aptamer backbone to prevent nuclease degradation and conjugated the aptamer to a polymer to increase size and reduce clearance. To assess aptamer functionality, an in vitro model of T cell adhesion is used. VCAM-1 coated plates are used to simulate endothelial cells, and VLA-4+ T cells are incubated in the plates to allow adhesion in the presence of modified versions of the aptamer and serum. VLA-4 inhibition by our aptamer designs is assessed by characterizing the extent of cell adhesion inhibition. Successfully designing a modification that significantly improves the in vivo function of aptamers will have broad implications for their clinical translation to in vivo use.

Consumption of highly reinforcing drugs, such as cocaine, can result in an escalation of drug consumption. Escalation is related to the most severe consequences associated with substance use disorder (SUD), including overdose. Chronic substance use leads to neurobiological changes including the signaling of the stress-related peptide corticotropin-releasing factor (CRF). Previous work has implicated CRF dysregulation in alcohol, psychostimulant, nicotine, and opioid dependence. CRF release in extrahypothalamic regions contributes to anxiety-like symptoms of withdrawal that can motivate individuals to consume drugs. There is limited evidence addressing whether CRF receptor (CRFR) activation alters cocaine consumption in individuals who have escalated their cocaine consumption. Additionally, the majority of the previous work has primarily been conducted in male subjects. The present study examines the underlying neurobiology of escalated cocaine consumption in male and female rats. Wistar rats were trained on long access (6hr) cocaine self-administration paradigm in which a subset demonstrated an escalation in their cocaine consumption. At the end of this paradigm, rats were subject to systemic administration of one of two CRFR1 antagonists, antalarmin (25mg/kg, i.p.) or N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5a]pyrimidin-7-amine (MPZP; 10 and 27.5 mg/kg, s.c.). I hypothesize, following previous work, that antalarmin and MPZP will both significantly reduce escalated cocaine consumption in rats classified as escalators but not non-escalators. These results would indicate that CRFR1 activation mediates escalated cocaine consumption in both male and female rats and may be a valuable target of clinical investigation into the neurobiological underpinnings of this dangerous facet of SUDs.

The Field of Cultural Mediation, along with Linguistic Mediation, has gained popularity in Italy as the country is increasingly a destination for immigration. As EU migration policies have become more selective, solidifying dangerous paths for “irregular migration” such as the Mediterranean and Balkan routes, reception systems become more complicated, borders become more violent, and public opinion polarizes (Lo Bianco, personal communication, 2023). In this context, it is increasingly important to ensure migrants have someone to facilitate communication between them and the various actors they encounter in an increasingly complicated and dispersed reception system built to dispel them. Thus, the Cultural Mediator, often a former migrant themselves, is increasingly employed by public institutions and social cooperatives to facilitate communication, integration, and to inform newcomers of their rights (Cuiban, 2019). There is inherent precariousness in being placed between these two often conflicting sides, requiring a high degree of social, emotional, and institutional expertise in addition to mere linguistic and cultural knowledge. Due to a lack of national regulation and decentralization, Cultural Mediators in Italy face social and emotional difficulties as well a lack of respect, proper regulation, payment, and support in their jobs. In this paper, I investigate the struggles Cultural Mediators in Italy face, which I argue is a product of the broader decentralization of the “Migration Industry”. By conducting surveys and Interviews regarding the Struggles Cultural Mediators in Italy face in comparison to existing primary and secondary resources, I aim to identify these struggles as well as their contexts.

Atherosclerosis is characterized by the accumulation of lipids, inflammatory cells, and fibrous tissue in arterial walls, forming plaques. Plaque accumulation can lead to stenosis and potentially severe outcomes such as myocardial infarction or stroke. The gut microbiome, including Collinsella aerofaciens, is believed to play a role in the prevention or development of atherosclerosis. Gut bacteria can directly influence systemic inflammation, a factor correlated with the pathogenesis of atherosclerosis, and produce metabolites that alter the disease course. This study explores the potential link between C. aerofaciens and atherosclerosis by investigating the abundance of C. aerofaciens in the gut microbiome of individuals with and without atherosclerosis. We collected 179 stool samples from participants at the Kisumu District Hospital HIV Clinic in Kenya and conducted a comprehensive analysis of their gut microbiomes. 100 participants had carotid ultrasonography, categorized as showing atherosclerosis with visible plaque or intima medial thickness ≥ 0.7 mm. We employed bacterial 16S ribosomal RNA gene sequencing to characterize the stool microbial composition and noted that the relative abundance of C. aerofaciens was 2.6-fold less in participants with atherosclerosis (p=0.006). To validate these findings, I employed a Quantitative Polymerase Chain Reaction with a cloned plasmid control for targeted quantification of C. aerofaciens. We found 6.9-fold more C. aerofaciens copies per total 16S in Kenyan adults without atherosclerosis versus with (p=0.020). This suggests a potential protective or mitigating role for this bacterium in cardiovascular health. Future work could include assessing changes in C. aerofaciens abundance over time and its association with cardiovascular disease progression. Additionally, in vitro or preclinical studies could reveal the specific mechanisms by which C. aerofaciens influences atherosclerosis development and progression. This research contributes to our understanding of the intricate interplay between the gut microbiome and atherosclerosis, offering insights that may inform future therapeutic strategies and personalized interventions for cardiovascular diseases.

Substance use disorder (SUD) takes a tremendous toll on human life every year, which makes understanding the underlying neural circuitry behind SUD a very high priority. A key neurotransmitter in the discussion surrounding SUD is dopamine, which has been implicated in mediating reward-seeking and motivational behavior. More specifically, these behaviors are believed to be mediated by the dopaminergic projection from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). Using contemporary technologies like fiber photometry paired with dopamine biosensors, live dopamine dynamics can be viewed in real time and aligned to certain behavior events collected during tasks performed by animals to further understand dopamine dynamics relating to SUD. With this in mind, we injected a cohort of male and female Wistar rats with a viral vector containing the dopamine biosensor dLight, which fluoresces when bound to dopamine, into the NAc and implanted fiber optic cannulas directly above the injection site to monitor the transmission of dopamine in real time during drug consumption. From there, we ran the cohort through a drug self administration cycle consisting of a training period, short access sessions to establish baseline drug consumption (1hr), and finally long access sessions (6hr) which is known to produce escalation of drug consumption, an SUD-like phenotype. Dopamine dynamics were recorded during several time points across this task. We then performed data analysis to assess various relationships between the behavioral and photometry data, along with immunohistochemistry to confirm the injection. Understanding the dopamine dynamics underlying drug consumption and how they change across changing behavior, such as escalation of drug consumption, is essential to building our understanding of SUD, and our current research helps to illuminate the inner workings of that relationship.

Adoptive Cell Therapy (ACT) is a novel modality of cancer therapy, in which immune cells can be engineered with T cell receptors (TCRs) to aid in targeting specific antigens presented on the surface of cancer cells. ACT has already brought curative therapy to many previously treatment-refractory blood cancers. However, TCR-T cells often have limited persistence after transfer into patients, which has hampered the effectiveness of this therapy for solid tumors, which require a sustained anti-tumor response. I evaluated if functional improvements could be induced by a small molecule inhibitor of LSD1 (LSD1i), a histone lysine demethylase that modifies chromosome accessibility, as a strategy to improve long-term activity against tumor cells after infusion into patients. Previous research has also found that “helper” CD4+T cells enhance the functionality of cytotoxic CD8+ cells, and I am now seeking to assess broader activity and benefits of LSD1i on a combined population of CD4+ and CD8+ cells. I first treated CD8+ T cells with a small molecule drug, Bomedemstat (an inhibitor of LSD1) during the in vitro cell expansion process, and demonstrated enhanced function in a co-culture system that models chronic stimulation as would occur in a solid tumor. To assess activity of Bomedemstat on CD4+ T cells, I used lentiviral transduction to insert functional TCR constructs into both CD4+ and CD8+ T cells, and plan to expand these cells with the optimized concentration of Bomedemstat in a second coculture assay, this time with combined CD4+ and CD8+ populations. I expect Bomedemstat will prevent dysfunction similar to our previous results with a LSD1i in CD8+ T cells, as illustrated by improved tumor killing and changes in T cell phenotype and function. Demonstrating applicability of LSD1i pretreatment on combined T cell populations would establish a stronger foundation to advance this epigenetic perturbation to clinical applications.

Staphylococcus aureus is an important human pathogen that has increasingly developed resistance to antibiotics and antimicrobials. It is important to understand how genetic mutations influence antibiotic resistance to anticipate how the organism is able to evolve and combat emerging resistance. My project aims to fully characterize the impact of variants in the norA gene, which is associated with efflux-mediated resistance. The Salipante lab has developed a system for precision genome engineering in S. aureus by constructing a vector that is able to conduct recombineering while suppressing DNA repair, and a separate vector for killing unmodified bacteria using programmed CRISPR/Cas9. Using this system, I will construct a library of genetic mutations in the S. aureus genome that will encompass all possible single mutations in norA and to subsequently test the fitness costs of those mutations in the presence and absence of antibiotics.We will recombineer into S. aureus randomly mutagenized oligonucleotides that encode a silent mutation that renders transgenic bacteria immune to targeted CRISPR/Cas9 cutting. After killing off unmodified bacteria, the transformed population will be composed entirely of different mutants, so that with a large population size, we can statistically ensure that all possible random mutations are represented. We will analyze the gene sequence from the initial population, after the population has expanded in the absence of drugs, and after exposure to different concentrations of drugs, to compare the relative representation of each specific mutation. Changes that are detrimental under a condition will be underrepresented relative to the starting population, while those that are beneficial will be overrepresented. Mutations that are lethal will not be recovered in the first place. Our project has the potential to fully and comprehensively address clinically important questions regarding antibiotic resistance evolution in this gene.

This project evaluates the flight mechanics of a class of Autonomous Underwater Vehicles (AUVs) known as gliders using digital simulation via Python code. When used in the real world, these gliders perform vertical profiling of important marine quantities like temperature and salinity. These are then used by oceanographers and others to help them gain a deeper understanding of the ocean environment. The overall goal of the project is to optimize the trajectories of a fleet of vehicles to minimize energy consumption while maximizing uniformity of ocean coverage. Using specific engineering data on real world glider flight as well as public domain ocean environmental models, I have coded a custom Python application with guidance from my mentor at the Applied Physics Lab. We chose a computer simulation of glider flight so that multiple variables could be easily manipulated without the risk of losing a valuable glider if certain parameters are not favorable. This simulation produces data that describes the vehicles’ locations and energy states over time. The software is structured such that important parameters are specified in an easily-modified configuration file. The parameters I alter include geographic area, the number of gliders, the maximum flight depth, the vehicle’s available buoyancy range, and the glide angle. Then, using the data that the simulation produces, I analyze variations in energy consumption, uniformity of coverage, and the time required for each glider to reach their destination. The oceans, which cover about 70% of the planet’s surface, have a huge impact on the climate and health of the Earth as a whole. The result of this analysis is useful to real-world AUV operations by helping determine how to program them to fly more efficiently and maximize their utility as scientific instruments.

Snow is an essential resource, especially in the Pacific Northwest, where it provides clean drinking water, irrigation water, and helps prevent wildfires. Despite the importance of the snowpacks in the Pacific Northwest, the composition of snow is not well documented. The ion concentrations in snow can indicate where the snow came from. I have created a dataset of the concentrations of anions found in snow throughout Washington State. Snow samples were collected primarily throughout the Cascade Mountain Range by volunteers using sterilized plastic containers. Samples were melted and then analyzed using ion chromatography to quantify the anions in each sample. Samples were found to contain concentrations of fluoride, chloride, nitrate, bromide, phosphate, nitrite, and sulfate. These anions have previously been found to be present in glaciers, clouds, and freshly fallen snow. Cataloging these anions provides an important baseline from which to observe how human and natural impacts, including climate change, are affecting the snow in the Pacific Northwest.

When a landslide impacts a river, it may form a dam that blocks the flow of water and builds up a lake. These lakes are prone to sudden outbursts, where they rapidly drain and catastrophically flood downstream areas. Recent UW research has estimated how susceptible rivers in the Oregon Coast Range are to landslide dam formation. However, where these outburst floods would be most dangerous for humans remains unknown. In this project, we ask in which Oregon Coast Range drainage basins are the flood risk and vulnerability the highest. In other words, where would a landslide dam cause the most harm? To answer this, we follow a GIS based methodology for computing flood risk for the Oregon Coast Range. We assess the magnitude of the flood risk in the study area. We define risk as the amount of people (or building footprints) that may be exposed to future flooding hazards. We will also be assessing flood vulnerability, which we calculate using population demographic data. Using these results, we will analyze flood risk and vulnerability in concert with the probability of landslide dam flooding to determine which areas should be highlighted for further detailed study and possible mitigation planning.
 

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

The drug resistance in tuberculosis (TB) is a rising concern for the diagnosis and treatment of the disease. Being able to detect the presence of drug resistance accurately and rapidly in the patient strain is essential for improving individual treatment outcomes and reducing further transmission of resistant strains, which are more costly and difficult to treat than drug-susceptible strains. However, the current methods come in short in point-of-care (POC) settings, due to problems such as long processing time, high complexity, and necessity for specialized personnel/equipment. Oligonucleotide ligation assay (OLA) provides a high sensitivity and specificity against TB drug resistance, and here, I have developed a novel lateral flow test (LFT) device that incorporates OLA into it, which have shown comparable specificity and sensitivity against traditional protocol of OLA in lab setting followed by LFT. Moreover, the simplicity of the design enables further incorporation of other techniques such as isothermal DNA amplification, for a compact, one-step TB drug resistance diagnostic device for low-resource environment. 

The effective treatment of individuals with HIV relies on maintaining therapeutic drug concentrations, necessitating accurate measurement of antiretroviral (ARV) drug levels. Current methods, such as liquid chromatography tandem mass spectrometry (LC-MS/MS), are limited by cost and accessibility. Our research addresses this gap by developing the INTEGRase activITY (INTEGRITY) assay for measuring integrase strand transfer inhibitors (INSTIs), a leading class of ARV drugs. This 2-step assay quantifies INSTIs using a DNA strand transfer reaction and quantitative polymerase chain reaction (qPCR). The presence of INSTI drugs disrupts the strand transfer reaction, inhibiting full-length target DNA formation, which is then measured through real-time qPCR. My work focused on optimizing the limit of detection of INTEGRITY by altering the strand transfer reaction conditions and protocol. Specifically, I conducted experiments altering INSTI drug concentrations and optimizing pre-incubation times of integrase with the drug to enhance the LOD. I observed that preliminary incubation of integrase and INSTI drugs for 5 minutes at 37 degrees Celsius improved the LOD of INTEGRITY by an order of magnitude. The simplicity of the INTEGRITY assay, utilizing standard laboratory equipment, holds immense promise for broadening access to routine clinic-based ARV drug level monitoring. This advancement has the potential to significantly enhance HIV care on a global scale by offering a cost-effective and accessible solution for monitoring therapeutic drug concentrations.

The Allan Hill region of Antarctica has produced the oldest ice core samples ever recovered, which provide insights into Earth’s climate history prior to the existing 800,000 year ice core record. However, the highly disturbed nature of this ice complicates straightforward dating and interpretation. Understanding the scales of preserved climate records in this old ice will enable deeper insights into the variability of climate over the last 2 million years. Here I study a section of ice from ALHIC1901, an ice core recovered from the Allan Hills in 2019. This section has three parallel sets of water isotope measurements, and they all show a small but significant dip. However, the cause of this dip remains unclear. The goal of this study is to test whether this isotope change could be a glacial-interglacial transition preserved for 1.3 million years, or whether diffusion should have eliminated any climate signal. To investigate this question, I apply a simple water isotope diffusion model that takes as inputs temperature, an initial water isotope profile, and a thinning history, and provides as an output the resulting water isotope profile after a given number of years. I identify the range of possible temperature, thinning, and initial water isotope signals for this ice. I use these as inputs for the diffusion model, and compare the results to the ice core record to evaluate if the observed water isotope signal can be climatically driven. Constraining the cause of this water isotope signal will improve our understanding of fine scale paleoclimate proxy changes in the extremely old Allan Hills ice cores, enabling new insights into past climate variability.

Human Immunodeficiency Virus 1 (HIV-1) is a lentivirus and the causative agent of Acquired Immunodeficiency Syndrome (AIDS). HIV encodes a viral protease, the function of which is required for viral replication. The host innate immune sensor CARD8 detects HIV protease activity, leading to inflammasome activation during HIV infection. Inflammasomes are cytosolic innate immune complexes that recruit Caspase-1 and lead to secretion of pro-inflammatory cytokines and lytic cell death. Humans encode a single CARD8 gene; however Old World Monkeys (OWMs), the hosts of Simian Immunodeficiency Viruses (SIVs) encode two copies of CARD8. The function of the OWM CARD8 is unknown. To characterize the function of OWM CARD8s, I cloned CARD8 from representative OWMs and tested their responses to HIV and SIV protease in two ways. First, I determined if OWM CARD8s are capable of forming an inflammasome in response to HIV-1, a panel of SIVs, or the broad CARD8 activator VbP. I found that most, but not all, OWM CARD8s are functional but not responsive to HIV-1/SIVs. Human CARD8 senses HIV-1 through viral protease cleavage of its N-terminus. To determine if this lack of response of OWM CARD8s is due to the absence of viral protease cleavage, I will next perform western blots comparing human and OWM CARD8 proteolysis in the presence of absence of HIV/SIVs. My data suggests that the species-specific differences in CARD8 alters its capacity to detect viral proteases. We speculate that the absence of HIV-like pathogenesis in OWMs with endemic SIV may in part be due to the absence of CARD8 inflammasome activation to SIV protease.

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

Matrescence, the transformative journey into motherhood, encompasses profound physical, emotional, and psychological changes with lifelong implications. Postpartum mothers face various challenges including recovery from childbirth, sleep deprivation, hormonal and cognitive changes, insufficient support, and social isolation, often leading to depression and anxiety. While traditional medical interventions address some issues, alternative modalities of care such as horticultural therapy (HT) are gaining traction in postpartum care due to their holistic approach. This paper investigates the potential benefits of incorporating HT into postpartum care, aiming to explore its effectiveness in treating stress and related conditions, addressing psycho-social challenges, and integrating insights from other alternative therapies like occupational therapy (OT) to enhance postpartum wellness. Through an exploration of existing literature and a proposed pilot study, this research aims to fill the gap in understanding HT's efficacy specifically for postpartum mothers. The study proposes a comprehensive approach targeting physical and psycho-social aspects of maternal well-being through 12-week HT sessions with 24 postpartum mothers aged 18-35, incorporating health screenings, socialization, and horticultural activities. The study anticipates improvements in mental health, reduced postpartum depression symptoms, enhanced social support, and positive mother-infant interactions. Statistical analysis and qualitative assessments will evaluate intervention effectiveness, engagement, and feasibility. Understanding the transformative potential of HT for postpartum mothers advocates for a paradigm shift in maternal healthcare towards holistic and patient-centered approaches. Integration of HT into postpartum care models aligns with the evolving healthcare landscape and addresses the multifaceted challenges of matrescence, particularly in marginalized populations, emphasizing early intervention and culturally sensitive practices. This research underscores the importance of innovative interventions like HT in addressing the complex needs of postpartum mothers and calls for further exploration and integration into healthcare practices.

Translation seeks to convey meaning between one form of communication and another. The ways in which translation is completed can concentrate power and influence in ways that favor those whose languages and communication methods are dominant. This distribution of power and influence has important historical and modern consequences. This social science research project explores how translation has impacted nation to nation relationships between Indigenous people and colonial governments in North America. The treaty making history of the Blackfoot Confederacy will be considered as a case study, with a focus on the making of Treaty 7 between the British Crown in Canada and the Blackfoot Nations of Siksika, Kainai, and Piikani as well as other First Nations. Treaty 7 was signed in 1877 in a geographical, social, ecological, and cultural context that was heavily influenced by treaties, colonial westward expansion, and diminished bison populations. This case study on translation is being conducted through a review of firsthand accounts of the making and signing of Treaty 7 and a literature review of documented Indigenous oral histories of the event. These reviews will be conducted with consideration for the shifting power dynamics at play during that time. Finally, current academic work on language reclamation will be considered for its potential to support Truth and Reconciliation efforts, and a greater respect for Indigenous sovereignty. Language is a tool for carrying out translation, and carries significant elements of culture. Indigenous languages have a connection to the lands where they come from that are important for understanding current social and ecological challenges. Modern language reclamation efforts may have potential for restoring a more balanced distribution of power and offering solutions to these challenges.

Stimulator of Interferon Genes (STING) signaling contributes to tumor immunity. However, treatments targeting the STING pathway are limited by route of administration, insufficient STING activation, and off-target toxicity. We introduce poly-STING, a copolymerized, mannosylated variant of the diABZI STING agonist-3 known to activate the cGAS-STING signaling pathway, promoting the release of type-1 interferons and pro-inflammatory cytokines leading to tumor immunogenicity. The STING agonist-3 is a non-nucleotide molecule that activates the STING pathway, but it has poor solubility, which limits its usage in-vivo. The developed poly-STING platform improves the drug's solubility, is designed to target immune cells, and provides enzyme-triggered drug release upon delivery, which has been shown to induce improved therapeutic efficacy compared to the free drug. The Pun and Stayton labs seek to investigate modalities for optimization of the cGAS-STING pathway activation and characterize the mechanism of action. Specifically, my project will evaluate STING activation by observing macrophage repolarization from type M2, as the mannose from the poly-STING binds to the CD206 receptors on M2 macrophages. This activates the STING pathway, repolarizing the macrophage to pro-inflammatory type M1. To test effects in vitro, I will culture bone marrow-derived M2 macrophages with various formulations of poly-STING, and repolarization will be measured through flow cytometry and RT-qPCR to quantify expression of macrophage markers. We expect to find higher M1 activity in macrophages treated with poly-STING as opposed to the free drug. Next, I evaluate the therapeutic efficacy of the STING formulations through an in-vivo tumor reduction study using murine models of breast cancer and melanoma, expecting to find longer survival of mice treated with poly-STING. The culmination of this project will result in a polymer-based STING agonist delivery platform that solves the solubility and bioavailability issues associated with the STING-3 agonist, with enhanced efficacy and decreased toxicity after systemic administration.

Physics concepts dealing with charges, particles, and electricity are difficult to conceptualize, yet foundational for students' scientific understanding. As an undergraduate researcher at the Novel Observations in Mixed Reality (NOMR) lab, I work on developing virtual reality applications for introductory physics lab courses at UW. To develop tools and scenarios for the labs, we use C# in Unity. One of the tools that I worked on developing was the Charge Tool, a tool that allows students to change particle charges and experiment with the relationship between charge and force according to Coulomb's Law. We conducted usability testing by taking participants with different levels of familiarity with VR, using the “think aloud” method. Through this, we identified user pain points for ease of use and ensuring an easier learning curve for students who are new to using VR. Based on key insights, we improved the particle colors to being more intuitive and color-blind friendly, as well as redesigned the tool to make it more functional and easier to use. I also work on a decay particle project that focuses on the principle of conservation of charge, momentum, and mass-energy, and a tutorial project which allows students to access instructions and lab manuals inside the VR lab scene. Since virtual reality is still pretty new in the field of education, research in it becomes important as it allows students to interact with physics concepts in a way that they never have before.

The robotic exploration of Mars has found that the early atmosphere was similar to current day Earth, suggesting that life could have existed on Mars in its past. The former atmospheric conditions and potential ancient rivers and lakes are preserved in the sedimentary rocks found across the surface. Interpretation of the Martian sedimentary record in Gale Crater, a possible ancient lake, requires differentiating between a variety of processes that alter sediment chemistry. Our study will contribute to the reconstruction of source rock composition based on the sedimentary records in ancient river systems on Mars. Iceland is a useful analog to ancient Mars as it has a similar climate and geologic makeup as well as similar environmental features, such as glaciers, volcanoes, rivers, and lakes. Here we characterize the chemical composition of source rocks in a cold, basaltic Mars analog source-to-sink system in Iceland and compare them to adjacent sediments. If the source rocks are primarily composed of palagonite, a glassy product of hydrothermal alteration of volcanic glass that weathers easily, we hypothesize that palagonite is the dominant component of the sediments. We analyzed the samples using Micro X-ray Fluorescence (μXRF) to examine thin sections of rock for changes in the elemental composition, and X-ray Fluorescence (XRF) to measure the bulk chemical composition of rocks and sediments. We used thin section classification to quantify the percent proportion of altered rock (palagonite). In source rocks with relatively high amounts of palagonite (greater than 10%), there was no significant chemical difference. The sediment samples are higher in Al, Si, and Fe and have less Mg and Ca. The difference in sediment and source rock chemistry indicates that another process is occurring, such as chemical weathering, sediment sorting, or that palagonite is a major portion of the sediments.

While much has been done to understand rape as an act of genocide and as a war tactic, little scholarly work has focused on how the intentional wartime spread of HIV/AIDS in the Rwanda genocide led to a slow genocide of the Batutsi. This work argues that the spread of HIV/AIDS resulting from the rapes that occurred during the Rwandan Genocide has led to the continuation of the slow genocide against the Batutsi people. I analyzed seventeen semi structured interviews of rape survivors that were conducted between 2007 and 2008. These interviews were published in Sandra Chu et. al. The Men Who Killed Me Rwandan: Survivors of Sexual Violence. By using thematic coding, my analysis of the interviews concluded that Tutsi women were intentionally infected with HIV by the Interahamwe so that the women themselves would be turned into biological weapons of genocide that could be used to inflict a delayed death-sentence on another Tutsi. Roughly 80% of the women who survived the Rwanda Genocide were raped, and of those women, 70% contracted HIV. With the lack of medical treatment in Rwanda for HIV/AIDS, those who test positive for the disease have 7-15 years to live before they will die a slow death. The intentional viral spread of HIV and the subsequent deaths from AIDS is a direct result of sexual violence committed as a tactic in the 1994 genocide. Despite being purposefully killed due to their ethnicity, women who died of HIV-related illness in Rwanda are not calculated in the death toll for the genocide against the Batutsi in 1994. This work expands our conception of the long-term effects of the rape campaign led by Hutu militias that intended to inflict death upon survivors of the initial violence from April to July 1994 in Rwanda.

Exclusionary zoning laws — which limit population densities and land uses in specific neighborhoods — are a typical feature of American municipal land use regulation. An extensive body of evidence links traffic-related air pollutant (TRAP) exposure to adverse health effects. Using zoning data and a model of TRAP levels in cities across the Seattle metropolitan area, I hypothesize that TRAP exposure will be greater on average in zones where higher-density housing is an allowed use, and lower on average in zones reserved for lower-density housing. I used the software package QGIS to spatially join zoning and air pollution data and used the software package R to perform correlation analyses between zone types (classified by maximum population density) and three common TRAPs (NO₂, black carbon, and ultra-fine particles.) This research highlights the public health implications of normative policy regimes like exclusionary zoning. These results can assist elected officials and planners in pursuing a more geographically distributive approach to increasing housing supply in the Seattle area, in order to minimize the TRAP exposure burden – and associated adverse health effects – faced by residents.

As our relationship with public space continues to grow, pedestrianization remains an important tool for reclaiming our space for public social function. Pedestrianization of The Ave is both academically and statistically supported, yet there remains little movement in its favor. Through the lens of placemaking, this project examines the best practices for campaigning the pedestrianization of The Ave in a way that fosters community ownership. Incorporating insight from historical reviews and stakeholder surveys, this research identifies preferred engagement strategies for community stakeholders. Utilizing these findings this research conducts a pilot study and creative visioning that centers community culture. This will result in concepts of a pedestrianization that will best gain public support and feelings of community ownership. These strategies and materials will be compiled as a “campaign” that has the potential to be implemented in the near future. As community planning in the University District seems to be very disconnected from its stakeholders, this project is rooted in community empowerment, seeking to connect people to systems.

Cytomegalovirus (CMV) is a nuclear-replicating DNA herpesvirus that rearranges the nucleus to form a kidney bean shape during infection. CMV-induced cellular rearrangement is disrupted by knockout of a histone variant, macroH2A1. This disruption leads to significantly decreased infectious progeny for CMV. We examined how different transcriptional profiles during CMV infection of macroH2A1 knockout cells and found several host genes were misregulated in the absence of macroH2A1. One such gene is KIF1A, a kinesin-3 motor protein found in neurons. I previously found that KIF1A is induced in primary human foreskin fibroblasts (HFFs) during infection, which is unusual since KIF1A is not normally expressed in fibroblasts. Interestingly, KIF1A is not induced during CMV infection in the macroH2A1 knockout cell line. This led me to hypothesize that macroH2A1 is required for induction of KIF1A expression. To test this hypothesis, I overexpressed KIF1A in HFFs to establish if I can rescue the defect in infectious progeny. Wild-type and macroH2A1 knockout HFFs transduced with a plasmid containing the KIF1A gene are analyzed using Western blotting and plaque assays to determine KIF1A expression and viral titers. I anticipate that the defect is rescued by overexpressing KIF1A in macroH2A1 knockout cells. CMV is the leading infectious cause of birth defects in the United States, making its mechanisms of infection a key area of study for development of antiviral therapies.

Skin is a densely innervated sensory organ that protects us every day from environmental trauma. As a barrier organ, skin is susceptible to frequent damage that must be promptly and properly healed to prevent infection and restore sensory function. Our lab uses adult zebrafish as a model to study skin injury and repair. Adult zebrafish skin is similar in composition to human skin and transparent, lending itself to high-resolution microscopy. Previous experiments in our lab revealed that dynamic, skin-resident immune cells known as Langerhans cells (LCs) rapidly engulf cellular and axonal debris after injury in the zebrafish skin. Calcium signaling regulates phagocytosis and cell motility in other immune cells, but the role of calcium signaling in LCs is unstudied. Through skin explant assays, various injury paradigms, and confocal fluorescence microscopy, I have established a model for monitoring calcium signaling in LCs. I found that LCs exhibit rapid, transient calcium flashes under homeostatic conditions. However, upon engulfment of large cellular debris generated by precise laser-ablation of skin cells, LCs exhibit an atypical sustained calcium signal lasting an hour on average. To test the requirement of calcium during engulfment by LCs, I treated skin with the drug Thapsigargin to perturb calcium flux. I confirmed that Thapsigargin increases intracellular calcium in LCs and keeps intracellular calcium concentrations elevated for hours after drug addition. During Thapsigargin treatment, I showed that LCs formed phagocytic cups around cellular debris but engulfed fewer laser-ablated corpses compared to controls. Thapsigargin-treated LCs also experienced normal migration to a wound site. My results indicate that calcium flux regulates LC engulfment of large debris, but not through migration. Identifying the molecular mechanisms underlying LC motility and debris removal is ultimately relevant to understanding skin repair and disease states in which the wound healing response is attenuated, such as in chronic wounds.

Mitochondrial calcium is essential for energy metabolism and cell survival. Deranged mitochondrial calcium leads to pathological remodeling of the heart. Little is known regarding the regulation and roles of mitochondrial calcium in cardiomyocyte growth. Mitochondrial calcium uniporter (MCU) is a major channel for mitochondrial calcium uptake. Germline knockout of MCU on the inbred C57BL/6 background is lethal. However, αMHC-Cre-driven MCU deletion in the heart just before birth yields viable offspring with normal heart function. In this study, we will use human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) to study the regulation and roles of MCU in cardiomyocyte growth. First, the expression of MCU in iPSCs and iPSC-CMs at different stages of their differentiation and maturation process will be determined at mRNA and protein levels. Then, we will delete MCU gene in undifferentiated iPSCs and follow a protocol to differentiate them into beating cardiomyocytes. The iPSC-CMs will be monitored for their morphological changes, cardiac troponin T expression, and electric pacing-induced calcium transients and cell contraction. The proliferation of iPSC-CMs will also be evaluated by using BrdU staining and molecular markers. This study will demonstrate how MCU expression changes during the differentiation and maturation of iPSC-CMs and whether it plays a role in cardiomyocyte growth.

Cannabis use has dramatically increased in response to legalization in the U.S., with U.S. sales jumping 46% from 2019 to 2020. ᐃ9-tetrahydrocannabinol (THC) is the primary psychoactive compound in Cannabis, and it has been shown to modify learning and motivation amongst regular users. Learning and motivation are key central processes primarily organized by the prefrontal cortex (PFC) brain region. I sought to test effects of THC on PFC activity during appetitive Pavlovian conditioning in mice- a behavior in which a subject learns to pair two stimuli together over time. Doing so provided much needed insight into learning and motivation under the effect of THC. THC acts on the endocannabinoid CB1 receptor, a presynaptic signaling protein responsible for modulating neural activity throughout the brain, with robust expression in the PFC. To monitor neural activity during behavioral trials, we implanted optic fibers into the PFC and virally expressed biological sensors. We used VGLUT1-Cre mice with a Cre-dependent GCaMP6f sensor to selectively target pyramidal glutamatergic activity during conditioning. We also utilized machine learning tracking software, SLEAP, to analyze behavior through video recordings. In our conditioning paradigm, animals were presented with a houselight and a sucrose reward, which they consolidated an association between after many trials. The mice experienced 5 days of Pavlovian conditioning, and I injected a moderate i.p. dose of THC (5 mg/kg) to one cohort, while another was given a vehicle before undergoing further trials. Our preliminary results showed that glutamatergic activity correlated with learning and association to the cue over time. We expected and observed that THC decreased the signals across the animals and reduced motivation. We categorized THC-induced behavior using SLEAP, a program tracking the mouse’s body parts to capture real-time movement, and found that locomotion decreased and resting behaviors increased in the THC cohort.

A key neuromodulatory system involved in anxiety disorders is the locus coeruleus noradrenergic system (LC-NE), which projects broadly throughout the central nervous system. The LC is stress responsive and tonic activation of the LC and its projections to the BLA is anxiogenic. Previously, the Bruchas Lab has used two-photon calcium imaging to show that a powerful stressor (predator odor) increased synchronous activity of LC neurons. They also found that mimicking this predator odor evoked activity with optogenetics altered the activity of individual neurons downstream in the BLA in a β-adrenergic receptor (β-AR) dependent manner. Although these data support the LC's involvement in promoting aversion and increasing anxiety-like behavior, the specific neurotransmitter, neuronal cell types, and receptors responsible for these effects remain unidentified. Therefore in hopes of identifying these specific signaling molecules and neuronal cell types and receptors, I first used fiber photometry and a novel biosensor (GRABNE2m) to detect norepinephrine (NE) release in the BLA while mice were exposed to a predator odor. I found that predator odor produced robust increases in NE release in the BLA compared to control odor (n=5, 3 male, 2 female) Further, we found that optogenetic activation of terminals from the LC to the BLA produced very similar levels of NE release compared to what was evoked by predator odor. To determine the cell type and receptor that is sensing this stress-induced NE release, I used a CRISPR/SaCas9 virus, developed in collaboration with Dr. Larry Zweifel’s lab, to knock-down β2-adrenergic receptors (β2-ARs) in glutamatergic BLA neurons to test their causal role in stress-induced anxiety-like behavior. CRISPR knockdown of β2-ARs in the BLA blocked several stress-induced anxiety-like behaviors (n=4, 4 female). By understanding the circuit-based mechanisms of how stress-induced anxiety is regulated, researchers could identify potential targets for therapeutic treatments of anxiety disorders.

Cannabidiol (CBD), a non-psychoactive cannabinoid compound found in cannabis, has been reported to attenuate morphine tolerance and can potentially be used as an alternative to opioids in treating chronic pain. Previous work has established connections between morphine tolerance and Reactive Oxygen Species (ROS) production through JNK-mediated Peroxiredoxin 6 (PRDX6) activation. Excess ROS production promotes desensitization of opioid receptors, which in turn leads to opioid tolerance. CBD administration is associated with decreasing pain-related Reactive Oxygen Species (ROS) production, and it was hypothesized that CBD directly interacts with JNK, blocking JNK’s activities. This project aims to investigate the connections between CBD administration and ROS production to determine CBD’s effects on JNK-mediated ROS production. To quantify ROS production through fluorescence imaging, I will transfect wild-type HEK 293 cells with oROS, a genetically encoded sensor, which fluoresces proportionally to ROS production. Coverslips of HEK 293 cells expressing oROS are treated with buffer (control) and CBD before administration of Tumor Necrosis Factor alpha (TNFα), a known activator for JNK released during pain states. After imaging with oROS, I will quantify ROS production and compare this between groups with and without CBD pretreatment to determine CBD’s activity on inhibiting JNK-mediated pro-inflammatory pathways. I predict that relative to the control, cells treated with CBD will have significantly less ROS production. If the results are consistent with this prediction, CBD could be a potentially promising co-treatment with opioids in managing chronic pain as it can potentially attenuate opioids' side effects like tolerance. 

Marine cyanobacteria have developed many genetic defenses in response to viral infection. Similar defense genes have been found in diverse groups of cyanobacteria, suggesting different modes of evolution for defense genes. Berube et. al (2018) identified novel cyanobacterial clusters of orthologous genes (CyCOGs), families of genes with similar genetic sequences. However many of these CyCOGs remain uncharacterized. The goal of my study was to characterize an uncharacterized CyCOG called 60001830, which is expressed in the marine cyanobacteria Prochlorococcus and Synechococcus, and when expressed is correlated with the genes of viruses that infect cyanobacteria (cyanophages). This suggests CyCOG 60001830 has an adaptive response to the presence of cyanophages, which would make it a family of defense genes. Using phylogenetic analysis, I resolved the evolutionary history of CyCOG 60001830 by comparing it to the evolutionary history of a key gene in host genomes. I compared the phylogeny of CyCOG 60001830 to the phylogeny of RecA, a highly conserved and essential gene present in all Prochlorococcus and Synechococcus species because of its key role in DNA repair and/or maintenance. CyCOG 60001830 does not share the same evolutionary pattern as RecA, which suggests that it does not follow a pattern of vertical gene transfer but rather horizontal gene transfer, genes being exchanged between neighboring bacteria. Viral defense genes evolve rapidly in an evolutionary arms race between bacteria and phages, so CyCOG 60001830’s evolutionary pattern makes sense as horizontal gene transfer operates faster than vertical gene transfer.

The purpose of this study is to understand recent developments regarding curriculum standards for teaching Indigenous histories and contemporary matters, specifically within Michigan’s K-12 Public Schools(MPS). This presentation draws from interviews with a range of stakeholders, including: current and former students and educators within MPS; politicians and government officials involved in relevant legislation; university professors concentrating their work in Native Studies at universities in Michigan; and representatives of Tribal Nations located in Michigan. This project also integrates relational discussions with Washington-based educators involved in the teaching and implementation of Washington’s Since Time Immemorial (STI) Curriculum. This presentation will share research analyses of relevant pieces of legislation and academic sources pertaining to Indigenous-centered curriculum. The objective of this research is to inform a written piece addressing current efforts to expand education on Indigenous histories and contemporary matters in MPS including efforts made in the past, actions currently in progress, suggested plans for the future, and what Michigan may learn from Washington’s efforts to fully implement STI through examining shortcomings in the implementation of STI curriculum and how these failures may serve to inform Michigan’s protocol for introducing revised standards. Given that one of the major proposals to the expansion of Indigenous-related curriculum involves teaching Indian Boarding School histories, the long-term implications of this research contribute to ensuring youth are educated about the devastating consequences of residential schools, which in turn aims to assure similar policies are not introduced in the future. Discussion of these findings will emphasize institutions which allow(ed) destructive policies like that of boarding schools to be implemented, reframing the common narrative perpetuated in schooling systems that such policies are the result of a few “bad actors.” This research is interested in exploring how curricula contribute to the latter perspective, and whether newly implemented standards effectively convey the former viewpoint.

The US education system is a tool used to push the dominant Anglo-American cultures among immigrants and other minoritized cultures within the United States. With their proximity to the US border and historical events, Mexicans living in the United States have faced subjugation and discrimination from the Texas Revolution to the anti-immigrant policies and rhetoric; these educational practices have targeted Mexicans for almost two centuries. This causes a conflict of cultural identity for Mexican youths living in the United States, as they grow up within multiple social spheres that consider them too American to be Mexican yet too Mexican to be American. This conflict of identity has caused multigenerational trauma and is only made worse by the discrimination from the media and the bias of the schools, as these students are forced to look elsewhere to discover their history, such as family or the community. My research study examines the value of ethnic studies and bilingual education practices and how they not only empower these students but gives them the motivation to succeed within an academic setting. This research is based on interviews that I have conducted with Mexican Americans who have experienced the education system during different years, ranging from the 60’s to the early 2000’s. Furthermore, I examine the autobiography of a prominent Mexican American scholar as I draw scholarship on ethnic studies and bilingual education, criticizing the current education system while offering solutions to address those critiques. Through the interviews I conducted, I found that the people who were most connected to their heritage and the Spanish language, not only experienced more success academically, but were also happier, indicating the need for ethnic and bilingual studies within the K-12 curricula.

In the early 1990s as, feminist photography was gaining traction in contemporary Japan, young artists such as Rinko Kawauchi and Hiromix were emerging. As female photographers, their work was being labeled as, “onnanoko shashin,” or rather, “girl photography.” Twenty-year-old Yurie Nagashima had just returned from America and was completely astounded by this term; surprised to find out it had actually become a real photographic genre at all. Nagashima began to dominate the field (despite her dislike for the term) with her unique approach to photography.While her photographs vary in subject matter, themes of sexuality, body-image, and familial bonds remain consistent in her work. Her perspective as a woman allows her to capture emotions and experiences felt by not only her, but by all women thus allowing the viewer to reflect and recognize themselves in her pictures. Through self-portraiture, family portraiture, and photographic representation of the trials and tribulations of everyday life, Nagashima challenges the male gaze, and encapsulates the ever-changing roles that come with the experience of womanhood. A thorough visual analysis of her work will make clear the greater implications her photographs have on understanding the female experience, from a first-person perspective. Nagashima’s work is vital for not only “onnanoko shashin,” and contemporary Japanese art, but contemporary art internationally. Her personal connection to her work is vital to not only create meaning but to unite women in their shared experiences globally.

The Japanese animated film Kimi no Na wa (Your Name), directed by Makoto Shinkai, premiered in 2016 and quickly became positively revered and awarded as the second-highest-grossing anime film at the time of its release. The movie contains romantic and fantastical elements to tell the story of Mitsuha Miyamizu, a girl from the rural countryside, and Taki Tachibana, a boy from Tokyo, who somehow begin to swap bodies with each other and attempt to meet in person. However, things get more complicated when they discover Mitsuha is three years in the past, just before a natural disaster strikes her town. This study aims to understand how Kimi no Na wa expresses modern Japanese identity. This investigation will contain an analysis of the Kimi no Na wa's visual and narrative elements, including framing, lighting, color, score, and iconography, and their relation to Japanese culture as depicted in the film. The characters Mitsuha and Taki will act as case studies to showcase identity and allow us to focus on specific facets of Japanese society. These facets comprise of gender, Japanese historical traditions, geographical differences within Japan, and the effects of disaster on Japanese culture. The findings of this research will help us understand modern Japanese identity as a whole and how it appears in film. This study offers a platform for discourse on portrayals of identity in film as well as an understanding of modern Japanese identity as it is portrayed in film, with an emphasis on views on gender identity in Japan, historical traditions, regional differences within Japan, and how living in a disaster-prone area affects Japanese society.

A critical feature of autonomous cars is the ability to follow a road or predefined path. Classical methods often rely on extensive prior mapping with precise GPS positioning. These methods are labor intensive and struggle with changing, unstructured environments. Instead, machine learning (ML) models are trained to recognize paths and follow directions. In this work, we combine simulated and real-world data to train a neural network policy that controls an autonomous ground vehicle down a hallway, avoiding collisions. Training a ML road-following model consists of three steps: data collection and preprocessing, model training, and model evaluation. While all three steps pose challenges, collecting high-quality, real-world data can be expensive and dangerous in road environments. Because of this, simulator data is useful as it allows for data to be collected safely and inexpensively. Thus, we study how much the required amount of real-world data can be reduced to successfully train a road-following robot with the use of simulator data. So, we collected simulator data using AirSim to train a convolutional neural network that follows a path in simulation through live environment images. We then fine-tuned the model using real-world data collected from MuSHR cars through hallways of a building. Next, we test the fine-tuned model on the simulator to ensure limited degradation to the model solely trained from AirSim data. Finally, we deploy the model on a robotic car in a real-world environment and evaluate the model’s performance compared to the baseline model trained on real-world data. We demonstrate that we can successfully train a model in simulation (MSE <= 0.01radians), and we expect to show a comparable performance in reducing the number of collisions and minimizing trajectory differences between expert and learned controller from a model trained on simulator + less real-world data and a model trained solely on real-world data.

Hypoxic-Ischemic Encephalopathy (HIE) resulting from a lack of blood and oxygen to the brain is the leading cause of mortality in term newborns. Extracellular vesicles (EVs) serve as critical transporters of biomolecules between cells, with evidence of alleviating inflammation in models after hypoxic ischemia (HI) injury. Therapeutic efficacy of EVs has only been evaluated in males because males are more susceptible to worse outcomes following HIE injury, yet knowledge about EVs and their behavior when administered to females is still needed. In this study, I aimed to address this knowledge gap by systematically comparing the efficacy of male and female neonatal brain-derived EVs (mEVs, fEVs, respectively) applied on male and female neonatal rat ex vivo brain slices. I first confirmed the purity of isolated EVs with protein assays and immunoblots, and utilized an ex vivo oxygen-glucose deprivation (OGD) model of HI injury, applying fEVs and mEVs to sex-matched OGD-exposed brain slices. I evaluated cell viability after 24h of EV exposure, and my results show that fEVs decrease inflammation and cytotoxicity in OGD models. When compared to previous results using mEV treatment, my results suggest that females have a more robust anti-inflammatory response system to injury. Ongoing work to better understand the therapeutic effect of EVs involves further observing morphological shifts in microglia through confocal imaging, as fEV application will likely result in microglia shifting towards anti-inflammatory phenotypes, similar to what was previously observed after mEV application. I am also quantifying expression levels of various inflammatory and reparative genes through reverse transcription quantitative polymerase chain reactions (RT-qPCR). Overall, I have demonstrated in these pilot studies that fEVs have a different therapeutic effect in OGD injury compared to mEVs. This research is intended to open up pathways for more personalized sex-based treatments for various injuries and therapeutics in the future. 

Heart disease takes an estimated 17.9 million lives each year, highlighting the pressing demand for cost-effective treatments. Melusin, a chaperone protein in the heart, holds potential as a target for heart failure therapeutics. Previous studies done in wild-type (WT) and melusin knockout (MelKO) mice discovered the absence of melusin was associated with a hypertrophic response indicative of heart failure. I plan to investigate the biomechanical role of melusin in humans using human-engineered heart tissues (EHTs) created from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that lack melusin and their isogenic controls. EHTs are a 3D in vitro model of the human heart, ideal for studying the role of melusin in humans. I hypothesize that WT EHTs subjected to mechanical stress will outperform the MelKO EHTs. The EHTs are suspended between one flexible and one rigid silicone post. The EHT displaces the flexible post as it contracts, from which the displacement can be measured to calculate various auxotonic properties of the tissue. To induce mechanical stress on the tissues, I use a brace to restrict the movement of the flexible post. I am using histology to determine if there are any morphological differences between tissue types resulting from the brace. Thus far, I have cast WT and MelKO EHTs and completed twitch force measurements two and three weeks post-casting. Overall, I found the MelKO EHTs demonstrated lower contractile force than the WT EHTs. I plan to cast and collect more EHT data with and without braces in order to provide insight into the role of melusin in humans. Furthering our understanding of the heart’s mechanotransduction properties using EHTs is important in expanding our knowledge about the various pathologies of the heart. Ultimately, studying the pressure overload pathways involving melusin can lead to the development of future therapies for cardiovascular disease.

International students are an essential part of the UW community as they are able to bring in a unique set of lenses and perspectives to perceive, approach, and solve problems. The UW International Student Service (ISS) is a place that provides information and guidance for the international students to legally live and study in the U.S. After encountering difficulties using the ISS system as an international student and a design researcher, I started to wonder how the ISS might improve to create a better user experience of their website and services. I began exploring this question in HCDE 417 in Autumn 2023. This application supports the continuation of that work, motivated by the following two research questions: 1) How well does the UW ISS website navigation work in terms of guiding international students to complete the correct tasks? 2) How might we improve the ISS system to better support the needs of the international students? My research is a usability study focused on understanding three attributes of usability for the UW ISS system: the usefulness, discoverability, and satisfaction. By carrying out initial usability testing sessions in HCDE 417 with international students and analyzing the transcript data using open coding and axial coding methods, I was able to take a deep dive into the problems with virtual advising services. My initial research surfaced several insights including the inconvenient drop-in only advising services, unreasonable student-to-advisor ratio, and less discoverable content. The impact of this study is that I took my initial research findings to ISS UX intern to discuss potential changes that could be made to the ISS to improve students' experience. As part of the community, I would like to use my design background to advocate for international students to be receiving more attention and resources from the UW ISS.

Prominent author and civil rights activist James Baldwin (1924-1987) has found new life on social media in the context of the Black Lives Matter (BLM) movement. BLM is a social and political movement of protests, advocacy, and online activism spanning the past decade. Following incidents of violence and racial discrimination against the Black community, Twitter has been a platform for facilitating societal change, and a significant portion of BLM unfolded on this active forum. Through a comprehensive text analysis of relevant tweets during BLM, our team uncovered notable activity connecting James Baldwin to BLM, current and historical events, and other cultural phenomena that influenced this online discourse. We organized large datasets of various Tweets and dissected their timelines from 2013-2023 to reveal keyword frequencies, engagement, and the prevalence of Baldwin references and quotes, connecting them with ongoing cultural and political contexts. By examining Twitter activity surrounding James Baldwin in the past decade, we wanted to understand how Baldwin’s work contributed to shifts in engagement and public sentiment during this time. Our hypotheses included increased discussions of the author’s work during times of political events and incidents of violence against the Black community. By creating timeline visualizations in Python, we uncovered spikes in engagement and public sentiment of historical events during crucial incidents of the movement, demonstrating how historical literary figures play a role in contemporary digital spaces. We used different language processing techniques for categorizing tweets and extracting patterns. We specifically measured retweet frequencies, hashtag usage, documented valuable keywords, and direct quotes and excerpts from Baldwin’s writing. Our findings provide valuable insights into social media and serve as a resource to understand online perspectives of literature, trends, politics, and social justice.

Orofacial cleft (OFC) is a relatively common birth defect that has major impacts on affected individuals and their families. Underlying causes of OFC include genetics and environmental influences. Genome-wide association studies (GWAS) and linkage analyses have revealed genes in which DNA variants are enriched in OFC cases relative to in unaffected individuals in the same ethnic group. Only a portion of the genetic causes have been identified. Here we focus on ARHGAP29, which was identified in several GWAS of OFC. To uncover the role of this gene in craniofacial morphogenesis, and to identify other members of its regulatory pathway, we are working on deleting a paralog of this gene, arhgap29b, in zebrafish embryos. To this end, we have designed four CRISPR guide RNAs that target specific exons in the arhgap29b gene and injected them into zebrafish embryos. We predict that such embryos will a) harbor mutations in the arhgap29b gene, which we plan to test with PCR and sequencing, and b) display abnormal morphogenesis of the face, which we plan to test by microscopy. Alternatively, we may observe a) but not b). In this event we would simultaneously disrupt the other paralog, arhgap29a. These findings will advance our understanding of genes associated with orofacial cleft, hopefully leading to improved diagnosis and underpinning the design of therapies for this disorder.

Inhalation toxicology is a rising field of study as respirable toxicants become increasingly prevalent in our environment. Our research focuses on commonly inhaled toxicants: diesel exhaust (DE) and electronic cigarette aerosols (e-cig). Exposure to traffic-related air pollution and the use of e-cigs has rapidly increased, yet molecular pathways and health effects, and innate factors that impact health outcomes, remain largely unexplored. To assess cardiometabolic and neurodegenerative effects of DE, we exposed male and female mice (low-density lipoprotein receptor knockout, Ldlr KO) to filtered air or freshly generated DE for 18 weeks while fed a high-fat or Chow diet. We then conducted Object-Recognition and Object-Location Memory neurobehavioral tests to assess cognition, specifically hippocampus-independent recognition memory and hippocampus-dependent spatial memory and discrimination, respectively. We sacrificed mice and harvested brain, liver, and lung tissue for histopathological staining and biochemical measurements, including 3-nitrotyrosine, a biomarker of oxidative stress, via Western blot. To assess cardiopulmonary effects of e-cig aerosols, we exposed different mouse strains to acute (5 days) and chronic (3 months) e-cig aerosols with and without nicotine. We then harvested lung tissue and quantified glutathione (reduced and oxidized), an antioxidant and essential nucleophilic scavenger of electrophiles, via high-pressure liquid chromatography; and protein 3-nitrotyrosine. Statistical analyses of all the results obtained were carried out using R. Initial results revealed sex differences in biomarker levels between control and exposed mice. We plan to expand analyses by measuring an additional biomarker of oxidative stress, 8-oxo-dG. Additionally, we will quantify heavy metal accumulation in liver and brain in DE-exposed mice, along with metabolites of carcinogens such as acrolein in e-cig exposed mice. Forthcoming measurements will provide a more comprehensive understanding of biological responses to exposures and elucidate potential health implications. Our research in inhaled toxicants helps reveal critical insights for emerging public health challenges.

Birth asphyxia is the inability of a newborn to begin and maintain breathing. Twenty-three percent of neonatal deaths globally are caused by birth asphyxia. Birth asphyxia results in a neurological injury called hypoxic ischemic encephalopathy (HIE). Rapid HIE screening within six hours after birth is crucial to identify neonates at risk. Unfortunately, the diagnostic equipment is impractical for low resource settings because it is costly ($20/test and $5,000 for equipment) and requires technical staff, that are in short supply, to operate. We hypothesize that a cost-effective device can be developed for HIE analysis. pHast Cam quickly screens for birth asphyxia and HIE in infants via a paper-based blood pH sensor. The device combines an inexpensive pH sensitive dye, a smartphone camera, and a fixture that controls the imaging environment to quickly identify acidosis from samples. A low-cost paper-based strip is made with a water-soluble resin doped with a pH-sensitive dye, bromothymol blue (BTB), and a membrane to filter out red blood cells. The fixture removes lighting variation. The smartphone camera records the pH indicator image, and an algorithm captures, reduces noise, and accesses color change. pHast Cam incorporates four features: 1) accurate assessment of acidity within 0.05 pH units, 2) require only a few microliters of sample, 3) use electrical hardware and software only from the smartphone, and 4) affordability. At this stage, we have achieved a regressive linear model that predicts buffered solution acidity (y=-589.32x+4684.05 R2=0.9857), with 95% confidence interval of 0.04 pH units. In the future, we will transition from measuring buffered solutions to blood-plasma. Ultimately, we expect pHastCam to screen for birth asphyxia, and other acid-base disorders, by quantifying plasma pH in neonates so that timely therapeutic interventions and plans to address long-term complications may occur.

Genome-wide association studies demonstrate an association between the single nucleotide polymorphism (SNP) rs3184504 and many autoimmune diseases, including Type 1 Diabetes (T1D). The rs3184504*C allele encoding for arginine is mutated to encode for tryptophan in the rs3184504*T risk allele, resulting in a loss-of-function of the adaptor protein SH2B3, a negative regulator of various tyrosine kinases and cytokine receptors. The SNP is uniquely enriched in humans of European descent. Isolation of the SNP rs3184504 is challenging due to its presence in a linkage disequilibrium region. To normalize this donor variability we used a CRISPR/Cas9 system in human peripheral blood mononuclear cells (PBMCs). CRISPR guides target exon 4 of the SH2B3 gene to be cut by the Cas9 enzyme. This cut is then repaired by a green fluorescent (GFP) repair template cassette delivered by an adeno-associated virus (AAV) containing homology arms for the flanking SH2B3 sequence. The insertion of GFP permits the identification of the SH2B3 KO cells. Our previous experiments on SH2B3 KO mouse lines demonstrated heightened signaling response after IL-2 stimulation in T cells, particularly in CD8+ naive and effector cells and CD4+ effector cells. To test this in primary human T cells, we will stimulate our edited SH2B3 KO cells with IL-2 and use flow cytometry to compare differential responses between edited and unedited T-cell populations. We expect to see similar results in our edited cells. Successful gene editing of PBMCs to model the human SH2B3 disease haplotype enables us to more accurately study the biological underpinnings of T1D, ultimately providing new avenues for which to treat T1D.

Invasive species have spread around the world, purposefully or inadvertently. Many species do not survive in new environments, but of the ones that do they can thrive. These thriving invasives may crowd out native plants, creating ecosystems of a single plant type, which causes the system to lose ecological functions. Despite the issues caused by invasives, not much is known about the causes of their spread. This project aims to determine which parameters influence the spread of invasive English Holly (Ilex Aquifolium), Cherry Laurel (Prunus Laurocerasus), and Portuguese Laurel (Prunus Laurocerasus). I plotted species locations in Saint Edward State Park which is comprised of a mixed decidous and coniferous forest. As I plotted their locations, I also measured the diameters and height. Using the size data, I will be able to determine the age of the plants which will provide more information into time frames that the plants took root. Additionally, I gathered light and temperature data over a year which I will use to find average lux and temperature in each month as well as each season to create predictive temperature maps of the entire study area. Furthermore, I took soil samples, near the invasive plants and in areas where the plants were absent which I will analyze to see if there is a correlation between soil nutrient loads and locations of the invader’s growth. Finally, using a drone I took pictures that will be used to determine tree species, tree heights, and hillslopes in the area. I will then create maps that use all the gathered data to predict environments that the plants will grow in. The information from this project can be used Park wide to determine areas that these invasive species grow so that park managers can find and remove invasive plants quickly and efficiently.

While discussing as a group what types of experimentation we could potentially do, we had a variety of different ideas. We thought that with the DC plasma source available to us, it would be interesting to compare how the cleanliness of the vacuum chamber impacted when breakdown would occur. For our research, we are using a DC Plasma Discharge device, which creates a plasma between two electrodes inside of a vacuum chamber. A high DC (direct current) voltage is applied across the two electrodes and a current flows between them. Plasma, the 4th state of matter, is a gas where electrons have been stripped from atoms or molecules in a gas. What results is an electrically charged gas consisting of negative electrons and positive ions. The point at which a gas becomes a plasma is called breakdown. Breakdown depends on the pressure in the vacuum vessel, the distance between the electrodes, the type of gas and the voltage applied. A Paschen curve relates the breakdown voltage to the product of the distance between the electrodes and the pressure in the vacuum vessel. Our goal was to see how a dirty vacuum chamber would impact the Paschen curve. We expected that breakdown would happen at lower voltages with the clean vacuum chamber. We obtained data for creating the curve by running the plasma tube and measuring the pressure as the voltage increased while the vacuum chamber was contaminated with oil. We recorded pressure and voltage values for when breakdown occured and repeated this process with different distances. We then gathered the same data after the vacuum was cleaned. The implication of our research is that it will add to information on how the cleanliness of a vacuum chamber determines when breakdown happens in a plasma tube. In the future, more trials could be run and different gases could be tested. 

The purpose of this experiment was to visualize and record the different rates of expansion for multiple gases as they are launched into the higher parts of Earth’s atmosphere with a High-Altitude Balloon (HAB). The ideal gas law models the behavior of a gas that of which its molecules occupy no volume and have no intermolecular forces (IMF). It is a simple equation; however, it cannot model gases accurately. On the other hand, Van der Waals equation for non-ideal gases better resembles the behavior of a real gas as it includes what the ideal gas law lacks. To test this, we filled three syringes with three different gases to the same volume. We chose to test argon, helium, and nitrogen. We secured the syringes to a container, which served as the payload for the HAB. We also placed an altimeter, thermometer, and a barometric pressure sensor inside the container. Then, we connected the sensors to an Arduino to record each piece of data synced to a stopwatch that is displayed in the container on a screen. Finally, we secured a camera to the container facing the stopwatch and syringes to record the gasses’ volume. Because helium has the weakest IMFs out of the three gases, we believed helium would expand at a higher rate as atmospheric pressure decreases compared to the other gases. The results from our experiment serve as a good example of how far the behavior of real gases deviate from ideal gases modeled by the ideal gas law. Depending on how close our measured values reach the calculated values from the ideal gas law, we can predict which situations the ideal gas law can model the behavior of a particular gas relatively accurately.

We collected and compared the spectra of air plasma and argon plasma in a dirty and clean direct current (DC) plasma discharge device. After cleaning the plasma tube we hypothesize the measured plasma spectrum will have fewer lines because it wont have as many impurities. The fourth state of matter, plasma, is matter that has been superheated, causing the electrons to be ripped from the atoms. This forms an electrically charged gas that consists of negative electrons and positive ions. Our plasma was created using a DC plasma discharge device. This device creates a plasma between two electrodes inside of a vacuum chamber. A high DC voltage is applied across the two electrodes and a current flows between them. DC plasmas can be utilized as sputter sources to deposit thin films for solar panels and the purity of the plasma can affect performance. Our vacuum vessel was accidentally contaminated with oil and dirt. To evaluate the effectiveness of our cleaning practices, spectra was measured for plasmas in the vessel contaminated with oil and other dirt and then again after the vessel was cleaned. Spectra, the range of wavelength produced when light is dispersed, emitted by air plasma and argon plasma were measured between 645 nm and 1050 nm with an Ocean Optics ST-NIR spectrometer. Spectra before and after cleaning were compared to measure the effectiveness of the cleaning. Our research provides evidence for the best way to clean DC plasma discharge devices in order to remove impurities. The conclusion of this analysis is imperative for efficient thin film plating using DC plasma.

The placenta is a crucial fetal organ providing oxygen and nutrients to the developing infant. Placental cell models, which are derived from immortalized or placental cancer cells, are typically used to study the organ. The use of placental cell models is important because human samples are difficult to obtain, and placental physiology is highly species-specific. However, our understanding of these models and how they compare to placental tissue samples is limited. This project aims to determine which placental cell model most directly reflects the gene expression of the human placenta. We obtained twenty-eight RNA sequencing datasets from the HTR-8/SVneo, JEG-3, JAR and BeWo placental cell models as well as human placental villous explants and primary trophoblast cells using the Gene Expression Omnibus database. Fetal sex was determined by quantifying expression of the Y-chromosome for each of the models. From this analysis we identified that HTR-8/Svneo was of female origin, while JEG-3, JAR and BeWo was of male origin. A clustering analysis was also conducted which identified groups of genes that showed similar expression profiles across the groups of cell lines and placenta tissue. This was subsequently used within a pathway analysis to identify which biological pathway defined the cluster. Pathways are chains of reactions leading to products or changes in a cell. The analysis showed at 22 of the 53 clusters were enriched for 1 or more pathways, which helps provide insight into the biological functions of these clusters and indicates biological processes that may be different between these models. With this information we have created an interactive web application. This site allows users to search a given gene and identify the expression data across all the models. This tool aims to provide a resource to the placental biology research community in further investigations of the placenta.

Understanding how DNA folds in three dimensions is crucial for deciphering cellular function. Chromosomal contacts are interactions between different DNA regions. These contacts hold key information about tissue-specific characteristics, such as gene expression and regulation. However, current predictive models for genome folding primarily focus on within-chromosome interactions, largely ignoring variations across tissues and the role of interactions between chromosomes (trans-contacts). To address these issues, we developed TwinC, a machine learning model that predicts trans-contact maps from pairs of nucleotide sequences. To build TwinC, we used a convolutional decoder coupled with an encoder architecture that can be configured to employ transformers, convolutional networks, or a hybrid approach. Preliminary results suggest that the convolutional architecture achieves performance comparable to Orca, the current state-of-the-art in sequence-to-contact predictions. TwinC is trained and evaluated on contacts measured in two human tissues and one mouse tissue. We are experimenting further with other encoder architectures, fine-tuning the model, and investigating how it generates its predictions. This research will provide valuable insights into the underlying biological mechanisms responsible for chromosomal contacts and lead to an improved, high-performance model for predicting trans-contacts.

This video essay focuses on the use of scientific-based meteorological information as a means of shaping political unity in Taiwan as a turbulent state. After providing a brief overview of the history of informed weather announcements through electronic media-based reports from the 20th century - with an emphasis on East Asian regions - and their evolution in relation to ideals of nationality, I contend that governments strategize the publication of weather events such as smog to form public consensus during seasons of political turmoils and antagonize border nations. In addition, they utilize isolated weather satellite imagery during online weather castings to strengthen ideas of nationality by consciously selecting regions and borders to present on screen. For smaller governments that lack the technology, the representational choices of what and how to display their territory in weather segments indicate the mood of how the government wants to be perceived by its own people. Techniques of producing and circulating weather information morphs alongside instruments, networks, and political climates. For example, commercialized television stations and other forms of media enhance the spread of ideals by the spectacular influence of severe weather events. Therefore, information promoted by national weather services is used for sustaining political orders rather than a service for public welfare.

Group B Streptococcus (GBS) is a gram-positive bacterium that during pregnancy, can cause invasive disease including preterm-births, stillbirths, pneumonia, sepsis, and meningitis in newborns. Although GBS commensally resides in the vaginal tract, as a pathogen the bacterium can employ numerous virulence factors, including the serine rich repeat glycoprotein (SRRs) adhesins. GBS expresses one of two SRR’s (Srr1/Srr2) in a strain-dependent manner, and both can bind fibrinogen to increase GBS adherence to vaginal epithelial cells, increasing pathogenicity. Both proteins are heavily glycosylated, yet the role of glycosylation on protein function and GBS virulence remains unknown. Previously, our lab has conducted in vivo studies infecting pregnant mice with mutant GBS strains that do not express SRR or express an altered SRR glycoform. Data from these studies show that a decrease in vaginal colonization and ascending infection is seen for the SRR deletion mutant, while SRR glycomutants exhibited increased virulence compared to the wild-type strain. To further explore these findings in a more mechanistic manner, I will conduct a series of in vitro experiments to examine the host-pathogen interactions and immunological mechanisms of these mutants. Specifically, I plan to examine the role of neutrophil killing as an immune modulator of GBS pathogenesis and how susceptibility to killing changes when SRR glycosylation is altered. In addition, these GBS mutants will be used to explore whether the SRR adhesin and its glycosylation is important in inducing vaginal epithelial-mesenchymal transition – an important cellular pathway that predisposes vaginally infected mice to uterine infection and will test the susceptibility of the GBS SRR mutants to entrapment via fibrin clots. By examining how the SRR adhesin and its glycosylation impacts vaginal colonization and downstream disease-associated events, we aim to elucidate the role of SRR glycosylation in GBS virulence and identify new antimicrobial targets that can decrease GBS pathogenicity.

Oxygen deficient zones (ODZs) are large, naturally-occurring regions of the world's oceans where dissolved oxygen concentrations drop to low levels—less than 10 nM. These regions are important to the biogeochemical cycling of carbon, nitrogen, methane, and sulfur and are expected to expand as ocean temperatures rise due to anthropogenic climate change. Located above and below the anoxic ODZ core are oxyclines where dissolved oxygen concentrations change rapidly with depth. The deep oxycline extends into the deep ocean supporting an understudied microbial community adapted to these low-oxygen conditions. In this study, I examine a metagenomic library previously generated from a water sample collected at 1000 meters on the RR1804 POMZ cruise to determine both the diversity and genetic potential of microbes in the deep oxycline. I found that three groups of prokaryotes dominate in the deep oxycline: the cosmopolitan alphaproteobacteria, Pelagibacter ubique (20%); the uncultured candidate phylum SAR324 (16%); and archaea of the phylum Thaumarchaea (12%). I generated metagenome-assembled genomes (MAGs) from this sample to determine the genetic potential of this microbial assemblage. By examining these MAGs, I expect to find genes encoding for processes such as low-oxygen stress responses, alternate terminal electron acceptors, and carbon-fixation pathways. By better understanding the contributions of the deep oxycline microbial community to biogeochemical cycles, we can more accurately predict how nutrients will be consumed and regenerated in ODZs as they expand.

Benzalkonium Chlorides (BACs) are widely used as an antimicrobial disinfectant in a variety of food and consumer goods processing. Exposure to BACs has increased significantly due to the COVID-19 pandemic. BACs have been reported in common foods like fruits, milk, and other dairy products, raising concerns about the impact of BACs on human health via oral exposure. Recent work in our lab has reported that BACs are metabolized by cytochrome P450 (CYPs) 4Fs and 2D6 in the liver. However, there is a gap in knowledge regarding how BACs and BAC metabolites are distributed throughout the body, post-oral exposure. We hypothesize that insight into BAC disposition and distribution following an oral exposure route could lead to valuable knowledge of BAC accumulation and subsequent toxicity. In this study, we exposed male and female C57BL/6 mice to deuterated C12- and C16-BACs at 120 μg/g/day for one week via a gel food diet. We harvested liver, lung, heart, spleen, and intestinal section tissues at the end of the study, as well as fecal samples at two time points, and a singular urine time point. Through a targeted BAC and BAC metabolite quantitation analysis using liquid chromatography-mass spectrometry, we found omega-oxidation of the alkyl chain to carboxylic acid followed by beta-oxidation to be a major route of metabolism. Additionally, we found that the liver and big intestine had a higher metabolizing capacity than other tissues and the C16 BACs were preferentially metabolized compared to the C12 BACs. This work provided a deeper look into the disposition and metabolism of BACs and revealed organs that are susceptible to BAC exposure for future studies

Asthma exacerbations often begin and increase in severity at night. Though animal models have shown molecular circadian rhythm involvement in immune and inflammatory responses, little is known about how circadian rhythms impact responses in humans or diseases such as asthma. BMAL1/ARNTL, CRY1, NR1D1, and PER2 are the genes that form the “cellular clock” by which cells tell time. Our hypothesis is that core circadian gene expression is maintained in an expected, rhythmic manner in epithelial cells from donors with asthma. We use an ex vivo model with human airway epithelial cells cultured at an air-liquid interface in a temperature cycled incubator to mimic the epithelia of the human airway. After temperature cycling to synchronize cellular circadian cycles, RNA collection occurs every four hours over a 48-hour period. After RNA isolation, I perform reverse-transcriptase quantitative polymerase chain (RT-qPCR) on a planned eight donor lines (4 healthy/4 asthmatic) to measure the gene expression of the four clock forming genes. In three asthmatic donor lines, I have found that core circadian rhythmicity is maintained in asthmatic epithelial cells and resembles the circadian rhythm expression in eight healthy donor lines previously analyzed. Shown through a preliminary study conducted by the lab, genes linked to asthma in the IL-17 signaling pathway have altered circadian rhythms of gene expression. In the future, I will use qPCR to study immune and inflammatory genes to confirm the altered rhythmicity across a wider scope of donor lines. In addition, I will analyze gene expression in different subsets of asthma to investigate whether altered circadian regulation contributes to asthma subtypes, such as T2-low which has been linked to IL-17 signaling pathway dysregulation. Investigating the differences in asthma-related circadian gene expression is essential to the development of chronotherapeutics – therapies that take into account time of day.

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

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

El Niño is an atmospheric-oceanic phenomenon characterized by the periodic warming of the sea surface in the eastern equatorial Pacific. Profiling data from Argo floats in the eastern equatorial Pacific is used for this research. An Argo float is an underwater profiling technology that can record and transmit real-time data of various ocean parameters at different depths. This technology supports the analysis of temperature, salinity anomalies, and other nutrients. In addition, a numerical model will be developed to simulate the progression of El Niño and evaluate its regional oceanic impacts. With both observational data and modeling output, this research aims to enhance the understanding of the dynamics of El Niño-induced impacts on oceanic parameters at a broader global scale. Based on the current data, I have discovered a clear variation in temperature and salinity according to the annual average. The El Niño Southern Oscillation (ENSO) indicator also suggests that the 2023-2024 El Niño is very strong and still in its development phase.
 

Although physical activity benefits children's health and development, most children do not meet the recommended 60 minutes of physical activity per day. Additionally, barriers to physical activity, such as lack of access to staffing or equipment at low-resource schools, can exacerbate population-level health disparities. With the goals of promoting physical activity in children and tackling health inequities, 13 schools across WA state were recruited for participation in this study with support from the Office of Superintendent of Schools (OSPI). Schools were randomized to either receiving a Physical Activity Coordinator (PAC) (n=4) or being an Active Control school (n=9). The purpose of this study is to investigate the PAC program's impact on children's physical activity at school and how children feel about physical activity. Data was collected via student surveys and observations before school, during lunch, and after school using the System for Observing Play and Leisure Activity in Youth (SOPLAY) method. Metrics collected via SOPLAY include area conditions, the number of children engaged in physical activity, the type of their physical activity, and the type of social interactions. Using our collected data, we are now working to analyze the impact of the PAC program and anticipate finding increases in some of our collected metrics. As part of the team, I worked on data collection through school observations, data verification, and data analysis. These findings are important because investing in building healthy habits in our children will pay dividends for their current and future health. Hopefully, the lessons learned through this study can be applied on a broader scale to help promote physical activity and tackle systemic health inequities.

Inflammatory Bowel Disease (IBD) is comprised of Crohn's disease and ulcerative colitis, which are autoimmune chronic inflammatory conditions affecting the gastrointestinal tract. IBD symptoms include abdominal pain, diarrhea, weight loss, and fatigue, which significantly impact patients’ quality of life. Hence, recognizing and researching these symptoms is critical to creating and implementing targeted interventions that can enhance the wellbeing of individuals with IBD. This project’s aim is to analyze the baseline symptoms and quality of life of individuals with IBD who are enrolled in a comprehensive self-management intervention program. For the study, we utilized a randomized controlled trial where 23 participants with IBD, recruited from March to December 2023, completed an electronic survey through REDCap. The mean age of the participants within the sample was 39.39 years, and 78.26% of participants in the sample had Crohn’s disease. In the survey, the participants rated the severity of symptoms (abdominal pain, bloating, fatigue, joint pain, nausea, gas, and urgency) over one week on a scale of 0-10, with larger numbers corresponding to greater severity. Additionally, participants completed a 10-question short inflammatory bowel disease questionnaire (SIBDQ) on a scale of 10-70, in which a score less than 50 indicates poor health-related quality of life. Among all patients, fatigue was the symptom with the highest severity (M: 6.70, SD: 2.51). The following most severe symptoms were bloating (M: 4.22, SD: 2.49), abdominal pain (M: 3.87, SD: 2.16), joint pain (M: 3.83, SD: 3.49), and nausea (M: 3.57, SD: 3.01). The total mean SIBDQ score for the sample was 44.17 (SD: 11.12), indicating low health-related quality of life (<50) among our sample. Our study’s results suggest that future IBD research should aim to create interventions that not only improve quality of life, but also improve extraintestinal symptoms, such as fatigue and bloating, in patients with IBD.

Per- and poly-fluoroalkyl substances (PFAS) are colloquially known as “forever chemicals” due to their long-lasting chemical characteristics that allow them to persist in nature. Specifically, their man-made carbon-fluorine bonds are extremely durable which makes them valuable in coating non-stick cookware and waterproof materials. These compounds are so indestructible that they accumulate in waterways and are eventually found in animal tissue. Firefighting foam is the most prominent source of PFAS pollution in waterways, which can accumulate in shellfish such as mussels, which humans often consume and can potentially lead to cancer formation. However, it remains unclear how much PFAS are actually in shellfish in Washington State. Using liquid chromatography tandem mass spectrometry (LCMSMS), we will analyze the amount of PFAS in homogenized mussel tissue samples collected from many different sites within the Puget Sound and surrounding waterways. PFAS levels have not been significantly monitored in shellfish in Washington State, this novel research which will provide valuable insight on the potential bioaccumulation of these compounds in various marine organisms and potentially find associations between the proximity to centers of high population density and PFAS concentration.

Learning management systems (LMS) are used for facilitating communication between instructors and students, disseminating lecture materials, and grading assignments. They collect large amounts of student data, necessary or otherwise, with or without explicit consent from students. Furthermore, they make the data visible to instructors, which could have significant implications for students’ grades and experience in the classroom. My project aims to understand the unique nature of student privacy issues on LMS to inform design solutions. I consider how we can design features on LMS to protect students’ privacy and improve students’ educational experiences. We hypothesize that student privacy controls will improve education and student experiences, creating a more equitable learning environment. Using transcripts from 31 interviews with students who use the Canvas LMS at UW, my mentor and I used inductive thematic content analysis methods to understand themes in students’ attitudes toward these solutions. So far, our research suggests that students are concerned about the lack of transparency and control on LMS and would feel more comfortable with the implementation of a privacy dashboard that would allow customizable, context-appropriate data sharing. According to our findings, key factors influencing student comfort include transparency in data collection and sharing with instructors, concerns about instructor bias resulting from irrelevant data sharing, feelings of surveillance arising from lack of data protections and transparency on LMS, and the level of meaningful control students have over their data on LMS. Our findings indicate that this research could guide the design of student privacy dashboards in LMS, improve instruction by helping instructors facilitate better experiences online, and inform policy impacting the way LMS are used around the world.

Individuals differ in how easily they perceive and internally represent visual and verbal information. However, these differences in information processing style are not all or nothing; individuals vary not only in the direction of attentional bias, but also its strength. Prior research found that when forced to choose between competing visual and verbal stimuli, people exhibit different degrees of bias when selecting what information to attend to. The present study examines whether individuals with greater visual or verbal attentional biases, relative to neutral attenders, show different levels of sensitivity to conflict between visual and verbal information during a categorization task. Data will be analyzed from 185 participants who completed a card sorting task in which they were asked to sort stimuli into one of three card suits. Each trial contained visual (shape) and verbal (word) representations of the card suit. On 75% of trials, the word and shape matched (congruent) and the other 25% of trials contained inconsistent information (incongruent). Our analysis will compare response times on incongruent and congruent trials (incongruency effect) in high- and low-biased individuals, to measure conflict experienced. We hypothesize that individuals showing a greater attentional bias towards either task modality will ignore information that is misaligned with their preferred information processing style, resulting in a smaller incongruency effect. These results would suggest that biased attenders have quicker access to the information that aligns with their processing style, while neutral attenders notice both information types and experience conflict when they are incongruent. Alternatively, if attentional bias is unrelated to incongruency effect magnitude, this suggests that people process information similarly, and experience biases only at the decision phase. This study has important implications for understanding how individual differences in information processing style affect how much information individuals process in situations with attentional competition.

This study presents a design research project to create high-fidelity prototypes for culturally inclusive and responsible Indigenous e-publications, specifically targeting the Cherokee community. The initiative addresses the issue of knowledge transmission, which has traditionally relied on oral traditions, by leveraging digital platforms to record and organize traditional ecological knowledge. Using Cherokee Earth Dwellers (Teuton & Shade Family, UW Press, 2023), a comprehensive book on Cherokee culture, as a primary source, the project integrates audio and video with text from the print book to craft a multimodal educational resource. The methodology is grounded in 10 usability heuristics and participatory design principles, involving members from the Cherokee community in the design process to ensure the final e-publication meets their needs and expectations. Drawing on previous research in Indigenous studies, co-design workshops, participatory sciences, and human-computer interaction, the project aims to produce an interactive e-publication as a vital resource for Cherokee educators and youth, enhancing access to Cherokee culture for educational purposes through digital mediums, thus fostering language revitalization and cultural education. Anticipated outcomes include design guidelines for research towards Culturally-inclusive, Relational and Responsible web design.

Inflammatory bowel disease (IBD) is a chronic autoimmune disease of the gastrointestinal tract, impacting an estimated 3-million people in the United States. IBD can significantly hinder quality of life and is related to increased rates of depression and anxiety.  Treatments focused on medications often do not consider the social determinants of health. Through a holistic approach, the Comprehensive Self-Management (CSM) IBD study at the University of Washington sought to empower patients in their symptom management. Those randomized into the intervention group participated in an 8-week intervention that considered external factors, like exercise, diet, sleep, life stressors, and relaxation, which could contribute to IBD symptoms. Participants were adults over 18-years old. Patients in the treatment and control group completed an end of study interview about their study and intervention experience. This project's aims were 1) to describe the process of interviewing participants; and 2) to examine the major themes associated with participant experience with the intervention based on the end of study interviews. I conducted interviews over the phone, asking patients about their experience with stool samples, satisfaction with the study, food diaries, intervention modules, and most positive or negative aspects of study participation. Both quantitative findings on participant demographics and qualitative findings from the interview surveys are presented. Thematic analysis was used to identify key themes. Some positive themes from the intervention included accessibility, lifestyle changes, and feeling supported. Some challenges included symptom overlap between IBD and irritable bowel syndrome, recalling daily diet, and implementing study skills when disease was inactive. 90% of participants would recommend this study to a friend, and 70% considered study participation to be easy or very easy. These findings will allow for future improvements and/or revisions to the CSM intervention and the interview process. This will help increase the resources available for IBD patients.  

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

Upconversion (UC) is a non-linear optical process where a material absorbs two lower energy photons and subsequently emits one of higher energy. Currently, inorganic UC materials used in lasers and photovoltaics are primarily lanthanide-based. However, a few transition metals also exhibit UC, such as Re4+ , Os4+, Ti2+, Ni2+, and Mo3+, and due to their high oscillator strengths, d-d transitions, and a strong ligand field dependency, offer the potential for greater tunability and efficiency in upconverting optoelectronics than their than their lanthanide counterparts. The goal of this work is to increase Re4+’s PLQY by isovalently doping low-phonon vacancy-ordered double perovskites (A2BX6 : A = Cs+, NH4+; B = Ti4+, Zr4+; X = Cl-, Br-) with rhenium to minimize non-radiative decay that can occur through defects and lattice vibrations. This has been attempted via schlenck line synthesis of the host lattice and coprecipation and ion-exchange doping procedures. While [ReX6]2- has previously demonstrated near-IR to visible upconversion in the bulk, this work aims to characterize its upconversion mechanism on the nanoscale with variable temperature and time-resolved photoluminescence. If made successfully, the colloidal stability of Re4+:Cs2TiBr6 nanocrystals would allow for new post-synthetic processing avenues including electrohydrodynamic inkjet printing and core-shelling, and new applications in flexible electronics.

Inflammatory bowel disease (IBD), a chronic autoimmune condition encompassing ulcerative colitis and Crohn’s disease, significantly affects individuals' health and quality of life. This study centers on patient activation and self-efficacy, which are critical concepts in the management of IBD. Patient activation—encompassing an individual’s understanding, abilities, and confidence in managing their health—is measured using the Patient Activation Measure. Similarly, self-efficacy, which relates to one's confidence in carrying out behaviors necessary to achieve specific performance goals, is assessed by the Self-Efficacy for Managing Chronic Disease Scale. These factors are essential as they enable patients to actively participate in their healthcare, potentially improving outcomes. This study aims to explore patient activation and self-efficacy among individuals with IBD enrolled in a Comprehensive Self-Management Intervention. Participants in a randomized controlled trial completed baseline measures and follow-ups at 3 and 6 months. By assessing change in baseline to 3 months in patient activation and self-efficacy, the study seeks to understand how this comprehensive intervention influences the self-management behaviors of individuals living with IBD. We expect that patients receiving the intervention will exhibit enhanced self-efficacy, indicating a positive direction in IBD self-management practices.

Serratia marcescens is an opportunistic pathogen that can infect multiple human organs and is responsible for many healthcare-associated infections. It has a mortality risk of up to 58% and early diagnosis is crucial for timely treatment. S. marcescens secretes a unique restriction endonuclease, which has been recognized as a virulent factor and thus can be used as a diagnostic biomarker. To detect this restriction enzyme biomarker, I have designed and investigated a model system using novel restriction endonuclease mediated DNA strand displacement (resDSD), adapted from the enzyme-free DNA strand displacement (DSD) reaction. In a typical DSD circuit, a DNA input “invading” strand invades a duplex DNA substrate, replacing the previous incumbent strand through branch migration to reveal a fluorescence molecule. In contrast, my resDSD circuit employs a restriction endonuclease enzyme input. In my design, the toehold region is concealed and blocked by a strand that the restriction enzyme can cleave. Once cleaved, the toehold region is exposed, allowing an invading strand to hybridize and initiate the DSD cascade. This study represents the first demonstration of the resDSD system. To validate the concept, I used commercially-available restriction endonuclease BamHi instead of S marcescens’ endonuclease. I will also modify E. coli 5-alpha competent strain (c2987h) to secrete BamHi in place of S. marcescens. By investigating this innovative resDSD approach, I aim to establish a reliable method for detecting bacterium such as S. marcescens based on its secretion of the restriction endonuclease. Such a diagnostic tool could contribute to early detection and prompt treatment of infection caused by this opportunistic pathogen or similar pathogens in healthcare settings.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect, requiring patients to undergo multiple invasive cardiac procedures, including pulmonary valve replacement (PVR). However, with recent clinical advances, new tools are needed to optimize PVR timing. We believe noninvasively collected cardiopulmonary exercise testing (CPET) data can provide insight into a patient’s need for PVR. Specifically, we hypothesize that patients with a more severe stage of pulmonary valve dysfunction have a limited ability to increase their stroke volume during exercise, an abnormal response that can be assessed by analyzing the behavior of the oxygen pulse (O2-pulse) curve during CPET. A ‘flattening’ of this curve suggests impaired augmentation of stroke volume and potentially a more urgent need for PVR. This research aims to identify metrics that can characterize patterns in O2-pulse. Data were collected from 44 participants with TOF undergoing CPET PVR evaluation and 10 healthy individuals. To find a maximum O2-pulse, we fit a penalized bilinear regression model to this curve. We extracted 8 parameters to mathematically describe the O2-pulse curve, as well as 20 traditional CPET performance metrics. One important parameter that was calculated is the ‘lost area under the curve’ (LAUC), defined as the area under the two calculated regression lines over time subtracted from the area under the curve as determined if the first regression line were to continue on the same slope as is typically expected during a maximal CPET. This value captures both the change in slope and when participants transitioned from a steep increase in O2-pulse to a relatively flattened O2-pulse. The LAUC, among our other identified metrics, can potentially provide insight into the optimal timing of PVR in patients with TOF. Unsupervised machine learning may be a useful tool to characterize patterns in these metrics and search for clinically relevant patient phenotypes.

Marine microbes produce over half of the world’s oxygen and are major greenhouse gas processors. These tiny organisms are vital to life on Earth as they cycle nutrients through marine microbial communities via metabolic pathways that are not yet fully characterized. We gain insight into how key compounds are cycled throughout different environments and microbial communities by studying transporter proteins as they mediate nutrient uptake and export in microbes. We aim to compare the abundance of transporters between marine microbial communities by translating and processing sequence data obtained from sequencing the RNA in water samples from multiple locations, capturing a diverse range of organism's genetic information. Currently, there is no standard methodology for identifying genes of transporter proteins from environmental sequence data. We developed a bioinformatic pipeline that identifies transporter genes and allows them to be characterized according to a standardized transporter classification system. This pipeline annotates amino acid sequences from oceanic samples with mathematical models to identify transporters and then annotates these results with taxonomic information. The pipeline enables us to compare transporter abundances between different marine microbial communities, which can be used to infer and map nutrient flow through marine microbial communities.

In a recent breakthrough, bullvalene, renowned for its “shape-shifting” molecular nature with over 1.2 million degenerate isomers, has been successfully integrated into polymer backbones. This integration addresses challenges in solubility and thermal properties crucial for tailoring polymers used in manufacturing diverse products ranging from phone screens to organic solar cells. This project aims to deepen our understanding of the interplay between fluxionality and thermal properties by examining the thermal stability of small molecule bullvalene models. Through extrapolating insights for bullvalene-substituted polymers, our research seeks to contribute to the advancement of the development of advanced materials suited for varying thermal conditions. We synthesized small molecule bullvalenes to mimic polymer chains, subjecting them to diimide reduction to suppress fluxionality before comparison with their fluxional counterparts. Their thermal properties were characterized using Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC). Key findings reveal a decrease in glass transition temperature upon reduction of bullvalene, highlighting the impact of fluxionality on thermal stability. Future work will delve deeper into exploring the thermal properties of small molecule models, providing insights into polymer behavior. We anticipate bullvalene as an internal plasticizer capable of modulating rigidity, solubility, and thermal properties within different classes of polymers, thus enabling a more efficient and cost-effective large-scale industrial production of a wide array of polymeric materials.

Western U.S. wildfires are a growing threat to human lives, societal infrastructure, and global climate. While it is well known that meteorological factors impact wildfire intensity and growth rate, quantitative relationships between meteorology and wildfire are scale-dependent. For example, a recent study evaluating all recently observed California wildfires found that explosive fire growth was strongly related to short periods of strong winds and dryness. However, that study used data from a global atmospheric reanalysis (which cannot resolve local winds). As such, even the strong relationships found between meteorology and wildfire growth may have been underestimated. Given the potential consequences involved in predicting and mitigating future wildfires, it is important to understand the real-world accuracy of previously determined fire-environment relationships. To do so, this project compares how local meteorological observations from Remote Automated Weather Stations (RAWS) differ from reanalysis observations during known wildfires. The seasonal and spatial variation in the different relationships is also evaluated. Analysis has shown that the RAWS network is dense enough to adequately represent conditions at each fire being examined. Early results indicate that RAWS and reanalyses have similarly timed wind events during the max growth period. These results are promising, as they indicate that global atmospheric reanalyses can be used as a proxy for ground observations in remote terrain when analyzing periods of extreme wildfire growth.

Sulfate aerosols cause pollution and affect climate by influencing cloud properties and incoming solar radiation. Emissions and abundances of sulfur-containing aerosols are one of the largest sources of uncertainties in global climate modeling. The largest biogenic and most uncertain emission source of sulfur aerosols is from phytoplankton in the form of dimethyl sulfide (DMS). In the atmosphere, DMS is oxidized to methanesulfonic acid (MSA), sulfur dioxide, and hydroperoxymethyl thioformate (HPMTF), all of which can form sulfate. Historical emissions of DMS are studied by measuring MSA concentrations in ice cores as a proxy for DMS oxidation. Declining levels of MSA have been found in ice core records, implying that production of DMS has also been decreasing; however, anthropogenically driven changes in atmospheric chemistry have altered the ratio of MSA to sulfate produced from DMS over time. To better understand DMS oxidation mechanisms and its relationship to the production of MSA and sulfate aerosols, we need more recent ice core records of MSA and sulfur isotopes of sulfate (δ³⁴S(SO₄^2–)) at higher temporal resolution. To measure δ³⁴S(SO₄^2–) at monthly resolution in an ice core, the measurement size is smaller than previously measured by an order of magnitude, at about 1 µg S per sample. We will develop a method to isolate 1 µg of sulfur from an ice core sample by concentrating the sulfur using an anion-retaining resin, precipitating with barium chloride, and drying in an oven. We will quantify the efficacy of our method using a stable isotope mass spectrometer compared to laboratory-prepared standards. We expect that we will reduce our sample size by an order of magnitude (to 0.1 μg sulfur) and improve the accuracy by 50%. Quantifying sulfur isotopes at this resolution will provide information about the seasonality and change in phytoplankton sulfate production.

A direct current (DC) discharge is one method for producing plasma. Plasma, the 4th state of matter, is defined as the separation of positive ions and electrons in a gas. A gas transforms into a plasma in an isolated low-pressure area between two electrodes, a cathode and an anode. The DC discharge, particularly the DC glow discharge, has historically been significant for both investigating plasma characteristics and providing a weakly ionized plasma for various uses. This project explores the utilization of Faraday’s Law as a fundamental principle for quantifying plasma currents. A fundamental principle of electromagnetism that I have been exploring on this project is Faraday’s Law, this law is especially useful in plasma physics when figuring out the current flowing through a plasma column or confinement device. The device I am building is called a B-dot probe which will be used to measure the current when the discharge turns on. The B-dot probe is essentially a coil made of conducting wire with a “tail” (twisted pair). Through a series of tests, I have procured the average magnetic field produced by the plasma current. From this average magnetic field and geometric measurements the average plasma current is deduced. Plasma is used everywhere now a days like in your TV and neon lights as well as in nature like the aurora borealis. With this research I hope to make the understanding behind the physics of plasma as well as it's magnetic fields easier to comprehend.

Lck is a lymphocyte specific tyrosine kinase involved in T cell activation in response to T cell receptor (TCR) mediated signaling. T cell activation is essential for the adaptive immune response, as it results in the proliferation of T cells after the detection of a peptide presented on a Major Histocompatibility Complex (MHC) and the production of cytokines necessary for immune response coordination. Lck activity is dependent on its global conformation, which is dynamically regulated via phosphorylation on its activation loop and C-terminus tail. Upon TCR engagement, active Lck phosphorylates the CD3ζ chains of the TCR complex, transducing the intracellular signaling events that activates T cells. Because Lck activity is dependent on its global conformation, we sought to map the conformational changes in Lck upon TCR simulation, as well as identify cysteine-reactive fragments that target and stabilize Lck in its conformational extremes. Lck has few endogenous cysteines, so we performed a yeast-growth-based deep mutational scan (DMS) of Lck–in which we utilized Lck’s toxicity to yeast to calculate the activity scores of ~5,000 Lck mutants–and identified 109 solvent-exposed, wild-type-like cysteine mutants of Lck. Expressing these wild-type-like cysteine mutants in T cells, and utilizing competition-based mass spectrometry, we can quantify changes in electrophilic reactivity of the cysteine side chains in the wild-type-like cysteine mutants upon T cell receptor (TCR) stimulation. Thus far, I have identified six wild-type-like cysteine mutants of Lck that are quantifiable using mass spectrometry and exhibit reactivity to our set of cysteine-reactive fragments, some of which show differential reactivity upon TCR simulation and fragment selectivity. Currently, I am using these mutants to map the dynamics of a hyperactive mutant of Lck. These quantifications provide insight into changes in the conformational flexibility of Lck, accessibility of the mutated residue sites, and intramolecular protein-protein interactions of Lck upon TCR stimulation.
 

The northeastern quadrant of Washington State is an area of vast public lands. It includes 2-3 National Forests, three State Forests, three Indian Reservations, five Wildlife Areas, and 28 Sno-Parks that contain a wide variety of recreational amenities, including kayaking, rafting, horseback riding, snowshoeing, skiing, camping, and backpacking, among others. This area is also part of the Okanogan Dry Forest and Canadian Rockies Mountains ecoregions, which are characterized by dense coniferous forests that are easily ignitable. As a result, the region is regularly impacted by devastating wildfires, which are accompanied by heavy smoke and pose significant threats to local air quality, small town economies, and natural resources. The purpose of this project is to understand how smoke and fire impact two important resources serving tourists in the area: outdoor recreational amenities, and the production of apples and wine. To investigate these impacts, I reviewed data on recent fires that caused damage to orchard and vineyard land, tribal land, recreational land, and private real estate, looking at the cost of this damage in terms of lives and property lost and the particular impacts of smoke hazards. This data was augmented with interviews of local real estate agents, business owners, and members of the Washington State Department of Natural Resources. The final results I'm expecting from this research is on how recreational amenties are impacted by mega-fires that causes devestating damage towards the forest, recreation amenties, local tribes, people lives,property, public health and the community. By doing this reserch it help me get better understanding how we should managed fire on recreational areas in the Okanogan Highlands area by following proper fire suppression tactics and resources. The results of this project help us better understand the growing effects of fire and smoke on this region in general, and on recreational and tourist activity in particular.

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

The immune system and inflammatory responses to viral infections are regulated by molecular circadian rhythms in mouse models. Mice infected with influenza just prior to their active phase have a mortality rate four times higher than mice infected just prior to their rest phase. As a result, circadian rhythms are hypothesized to regulate viral replication and early immune responses in airway epithelia during viral infections. Prior work has shown circadian cycles regulate gene expression in human epithelial cells. However, the influence of time of infection on viral replication in human airway epithelia has not yet been explored. We hypothesized that circadian-synchronized human airway epithelial cells would demonstrate differential viral replication and immune responses when infected at two different times of day. To address this gap, we differentiated primary epithelial cells from healthy children at an air-liquid interface to create an ex vivo cellular model of the human airway. Airway epithelial cells underwent circadian synchronization using temperature cycled incubators and were exposed on the apical surface to human rhinovirus-16 at time 0 and 12 hours during a circadian cycle. The RNA from seven total cell lines was sequenced and viral genome copy number was quantified at hour 96 following infection using GeneSig qPCR. Infection at hour 12 led to two-fold higher viral genome copy number 96 hours after infection as compared to hour 0. Infection late in the circadian phase (time 12) leads to increased viral replication at the airway epithelium and may explain the difference in mortality in mouse models of viral infection. Ongoing work is investigating immune responses based on time of infection. In the future, we will investigate changes in circadian regulation of viral infection in airway epithelia from healthy children and children with airway diseases such as asthma.

 âˆ†9-Tetrahydrocannabinol (THC), the primary psychoactive compound in Cannabis, is responsible for the experience known colloquially as “being high.” Considering its alarmingly high rates of usage, THC’s effects on movement behavior are insufficiently studied. My project addresses this crucial gap in our knowledge by investigating the dose-dependent effects of THC on movement behavior using mouse models in tandem with novel behavioral neuroscience techniques. My research aims to establish a preclinical model for THC-induced impairment, focusing on studying its impact on locomotor control. My main experimental tool is a behavioral linear track, which is a clear glass corridor with a 45 degree-angled mirror placed beneath it. The linear track allows us to create a standardized multi-dimensional environment in which mice are recorded after they are treated with either a control or variable doses of THC. The videos taken of the mice are then analyzed using SLEAP. SLEAP is a machine-learning, pose-estimation algorithm that I helped train to track individual points of interest on the mice, such as the nose, paws, and tail. Behaviors of interest, such as walking, rearing, and grooming, are classified by a random forest algorithm that analyzes SLEAP label data to output identified behaviors. This data is then tabulated and graphed to reflect the dose-dependent changes in behavior elicited by THC. These classifications are also used to further analyze metrics during a represented behavior. For instance, for a walk event, we can utilize positional data from SLEAP to calculate and measure kinematic features such as stride length and limb speed, allowing us to distinguish between an unimpaired and an impaired walk. This computerized analysis approach minimizes human bias, reduces error, and produces exhaustive data that can characterize subtle differences in behavior, like when comparing mice exposed to low THC doses of 0.1mg/kg and 0.3 mg/kg.

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

Merkel cell carcinoma (MCC) is a rare and aggressive cancer of the skin with a mortality rate of ~30%. In the US, most MCC tumors arise from integration of the Merkel cell polyomavirus (MCPyV) DNA into a host chromosome, leading to expression of viral T-Antigen (T-Ag) oncoproteins that drive tumorigenesis. Though current treatment options have significantly improved MCC prognosis, new therapies are needed to address recurrent/resistant disease. While T-Ag-specific antibodies are usually detected in the blood of patients with virus-driven MCC, the role of these antibodies in tumor immunity remains unclear. Here, we analyzed blood samples from 100 MCC patients prior to definitive treatment, 51 of whom had high titers of antibodies recognizing the T-Ags. These 51 high titer samples were assessed for binding across two domains of the T-Ag. Suprisingly, we found that patients who had high titers of antibodies binding both regions of the T-Ag had worse MCC control than patients whose antibodies predominantly bound one region (median PFS 5.5 vs. 14.2 months, p=0.003). These data suggest that careful mapping of circulating antibody reactivity to different regions of T-Ag can serve as a biomarker to identify high-risk patients for which a more aggressive treatment regimen is needed. Future work is also focused on understanding the immune response resulting in differential response to T-Ag domains.

Merkel cell carcinoma (MCC), a rare and aggressive skin cancer, shows approximately 60% response to immune-checkpoint inhibitors (ICIs) in immunocompetent patients. The efficacy of ICIs in immunosuppressed patients, who generally have poorer MCC prognoses, is less clear. This retrospective study assesses ICI outcomes in both immunocompetent and immunosuppressed MCC patients, and across various immunosuppression types. In this project, I determined the cohort of 183 patients with advanced MCC who were treated with first-line ICIs from a Seattle-based data registry. I collected the following data from analyzing patients’ medical records: treatment response, immunosuppressive status, disease-specific and overall survival. I coordinated with the statisticians for Kaplan-Meier analyses of the data, and am now working on the manuscript. The results show that initial response rates to ICIs were comparable between immunosuppressed (50%) and immunocompetent (61.5%) patients (p=0.17). After starting ICI treatment, immunosuppressed patients experienced a 65% increased rate of disease progression compared to immunocompetent patients (Hazard Ratio [HR]=1.65, p=0.04), with their median time to disease progression being 11.2 months, versus 32.9 months in the immunocompetent group. Outcomes also varied by immunosuppression subtype, with chronic lymphocytic leukemia patients having the lowest chance of response (20%, 2/10) and highest progression risk. In our cohort, immunotherapy often elicited an initial response in immunosuppressed MCC patients; however, the duration of this response was significantly shorter. Despite limited duration in immunosuppressed patients, ICIs still offer a high response rate for patients with advanced MCC, regardless of immunosuppression type. It is crucial to have a comprehensive prognosis discussion with patients before initiating treatment.

Merkel cell carcinoma (MCC) is rare and aggressive skin cancer with high risk of metastasis. Developments of PD-1/PD-L1 immunotherapy has significantly improved treatment outcomes of metastatic MCC. Unfortunately, only 50% of patients demonstrate long-term responses. Previous studies by our lab have demonstrated that infiltration of CD8+ T cells in MCC tumors correlates to long-term responses. However, the impact of other innate immune cells and lymphocytes remains unclear. I hypothesize that the spatial interaction of pro-inflammatory cells (primarily T and B cells) associate with better outcomes in the absence of suppressive macrophages that disrupt this immunological crosstalk. To investigate this, I have been using QuPath, a spatial analysis software, to examine the microenvironments of 75 MCC tumors. These tumors have been stained with 18-marker antibody panel to identify subsets of B, T, and innate immune cells. Using QuPath, I have been quantifying different immune cell populations, as well as investigating their spatial relationship to each other. Using this data, I have been working with a PhD student and Dr. Paul Nghiem, to correlate this immunological data to clinical outcomes. Our preliminary data demonstrates that high B-cell infiltration may correlate with better clinical outcomes. While this is promising, I plan to expand my studies, investigating the impact of other innate immune cells on immunotherapy outcomes. I will then work to validate my studies by investigating a different cohort of 35 MCC tumors taken from a recent immunotherapy clinical trial. By investigating the tumor microenvironment, my goal is to help identify which population of cells associate with better responses. This in turn may lead to a diagnostic assay that may help assess cancer aggressiveness, which physicians can use to tailor treatment course. In addition, this information can help guide future drug development, showcasing which cells are the most important to target and/or enhance.

The COVID-19 pandemic has brought to our attention the lack of fast, affordable, and sensitive diagnostic tests available on the market. The majority of commercial diagnostic tools are expensive, despite being quick and sensitive. This conundrum has brought attention to the necessity for developing high-quality tests at an affordable cost, emphasizing the importance of accessible diagnostics that are both rapid and sensitive. The Yager lab has been developing detection tools for infectious diseases, mainly based on isothermal nucleic acid amplification tests, using loop-mediated isothermal amplification (LAMP). The LAMP assay includes a DNA polymerase known as Bst. It was found that assay sensitivity improved when the samples were pretreated with HUDSON, which consists of TCEP (a reducing agent) and EDTA. I am investigating the improvement of Bst DNA polymerase activity with TCEP, using a commercial enzyme kinetics kit (EvaEZ) to quantify the Bst polymerase activity. The EvaEZ assay allows quantitative comparison between conditions by measuring fluorescence intensity indicative of DNA amplification. This was achieved by assessing primer binding, enzymatic extension, and EvaGreen dye intercalation, enabling comparison of the rates of fluorescence generation to evaluate amplification efficiency across positive, negative, and experimental control conditions. This project is still ongoing, and preliminary findings suggest promising results. This study demonstrates the potential for using reducing agents to optimize enzyme efficiency and improve detection sensitivity. This technique can readily improve detection speed and sensitivity both simply and affordably. We are able to be better prepared for the next pandemic.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects various cognitive functions. Progressive neurodegeneration and disruption of normal brain function can arise due to accumulation of neurofibrillary tangles (tau) in neurons within the entorhinal cortex and hippocampus, driven by a burden, or buildup of amyloid beta (ABeta) plaques. Motivating the present work, those who have experienced traumatic brain injury (TBI) have an elevated risk of developing AD. Our previous study found that low-intensity focused ultrasound (LIFU) reduced the ABeta burden, in a mouse model of AD. Additionally, studies have shown that enhanced activation of cholinergic pathways (therapeutically, by the drug Idazoxan) may be required for improved ABeta clearance and, subsequently, reduce tau accumulation. We therefore sought to test that LIFU (alone or with Idazoxan) can improve brain function after TBI, using a 3XTG AD mouse model expressing both ABeta and tau. After induction of a controlled cortical impact (CCI), we applied treatment to four cohorts of 3XTG AD mice while testing their visual-spatial working memory via a weekly T-maze alternation test. Treatment conditions consisted of: LIFU alone; Idazoxan alone; LIFU + Idazoxan; and CCI only (sham) for four weeks post-injury, whereafter the animals’ brain tissue was collected for protein quantification. I specifically carried out a number of the aseptic (minimal contamination), survival surgeries to create a mouse model of TBI, administered LIFU and Idazoxan treatment, and performed computational analysis of protein burden and behavioral testing results. We observed that AD mice treated with LIFU performed significantly better in the T-maze alternation test at 4 weeks post-injury, despite no change in their ABeta burden as well as significant increase in the phosphorylated-tau/total tau burden. The finding of this study challenges prevailing theories of Alzheimer’s intervention, which largely focus on reducing ABeta burden as a means of reducing tau burden.

Music box, invented in the 18th century, has been reimagined by the design industry as an interactive and assembly-friendly toy product. This innovation serves as a seamless integration of a nostalgic object with the demands of contemporary life experience. However, such "packaged in box" products face significant customization limitations from the user's perspective, including fixed music options and predetermined model parts. Given the burgeoning resources in digital modeling and rapid prototyping, the product design process is poised to advance into the computational fabrication era. Our interdisciplinary student team has been re-envisioning the structure and functionality of our music box through programming, Computer-Aided Design, and 3D printing. Specifically, our team developed the three parts to construct the music box: a digitally constructed spinner, where its 3D model was transformed from MIDI file, allowing for a wide range of musical expression; an adaptable mechanical connection structure for spinners of various sizes; and an innovative mechanism that triggers keyboard notes without direct spinner contact, maintaining sound quality and reducing wear out plastic parts. These designs enable customizable features, easy part replacement, and solve sound and durability issues associated with plastic components. With the goal of creating a customizable product in mind, each member of our team contributed to and took responsibility for the components in which they specialized. The purpose that our music box serves does not stagnate as a mere music playback machine; rather, its functionality expands across various aspects. Our innovation is not only ideal for those who wish to integrate artistic perspectives with functional machine prototyping and customize their songs , but also boosts creativity for individuals and institutions, enabling further projects that could benefit early education and future engineering workshops.

Eutrophication fuels toxic algal blooms that can harm biodiversity and human health. Phosphate is often the limiting nutrient in freshwater ecosystems and, when in excess, causes eutrophication. Our study compares urban lakes prone to algal blooms to rural lakes with fewer anthropogenic sources of pollution to better correlate nutrient dynamics of pacific northwest lakes to population density. We collected sediment and water samples from two lakes in the Seattle area and two lakes in a more remote setting, then measured phosphate uptake and release over time using ion chromatography. To determine the potential for the sediments to uptake phosphate, we placed air-dried sediment samples into a phosphate solution and measured the concentration over time. We also put the sediment in distilled water and measured the phosphate released from the sediment over a 24 hour time period. These two data sets allow us to quantify the capacity of sediment to store and release phosphate into the surrounding environment. Our research shows sediments from urban lakes release more phosphate and have a reduced ability to uptake nutrients from the water. This suggests that the lake will continue to eutrophy whereas the lakes more removed from human activity have a better ability to mitigate excess phosphates. This model for assessing the ability of sediment to store phosphate allows prediction of future eutrophication events.

Plant root signaling is a complex process. An important growth hormone that is hypothesized to regulate this complexity is Auxin; this hormone is known to oscillate in a region of the root that initiates lateral root development. Auxin oscillations are established by auxin exporters called PIN proteins. However, the regulatory mechanism that determines PIN expression and distribution is unknown. In this project, we built an agent-based model in order to characterize expected auxin dynamics and investigate hypothesized PIN regulatory signaling cascades. In the model, each cell is an individual agent that follows a given rule set. Cells independently calculate their growth and the amount their circulatory components change as the root develops. I analyzed previous models and extracted parameters to determine the necessary spatial and circulatory conditions that initiate our model. I constructed the circulation module to calculate the concentration of circulating components and updates information stored in circulation data structures to track how the values have changed after each round simulation. I also implemented the input and output modules for initialization and results export respectively. The model is implemented in Python and was built following test-driven development to ensure all class functions and modules are tested using pre-defined conditions. Preliminary simulation results revealed an oscillatory change in auxin concentration. This agent-based model provides a means to explore the auxin circulation dynamics and interrogate the viability of hypothesized mechanisms that regulate the lateral root development by applying different rule sets.

Heschl’s gyrus (HG) is a region of the brain containing the primary auditory cortex. The extent of folding within the HG shows high morphological variability across individuals. Interestingly, increased HG folding is more likely to be found in expert than amateur musicians, suggesting a possible role of auditory experience in shaping HG gyrification. In my research, I examined HG folding in blind individuals—another population with extensive auditory experience. I hypothesized that, if experience alters HG structure, then individuals with early-onset blindness might have increased HG gyrification compared to those with late-onset blindness or those who are sighted. I analyzed T1-weighted images collected from previous MRI studies at the University of Washington, University of Pennsylvania, and Oxford University. The combined dataset included 6 anophthalmia (individuals born without eyes), 48 early blind, 18 late blind, and 28 sighted control participants. I created hand-drawn HG regions of interest for each participant in both hemispheres and measured HG gyrification in two ways: 1) by visually categorizing the extent of HG folding (single, partial, or complete duplication), and 2) by obtaining continuous metrics (gyrification index and curvedness index) using FreeSurfer. A chi-squared test revealed that the degree of HG folding was not different across the four groups. A linear mixed-effects model (controlling for the effects of age, hemisphere, and scan location), similarly showed no effects of group on the gyrification index or the curvedness index. To conclude, my findings show that blindness does not affect HG gyrification. The results challenge the idea that auditory experience alters HG structure and offer important insights into previous findings in professional musicians. Our results suggest that the prevalence of duplicated HG in musicians may be the result of individuals with larger processing capacity within the auditory cortex being more likely to take up music as a profession.

Alzheimer's disease (AD), the most common form of dementia, is characterized by the improper cleavage of amyloid precursor protein by a complex containing presenilin 1 (PSEN1) or presenilin 2 (PSEN2). Notably, PSEN1 and PSEN2 are strong genetic risk factors for heritable AD. However, 95% of AD cases currently have no known genetic cause. Recent work from the Valdmanis lab found PSEN2 isoform variations at the RNA level in sporadic AD. One such variation was the detection of differential 3'UTR lengths on the PSEN2 transcript. The 3'UTR is an important regulatory region that controls transcript maturation, stability, and abundance and is subject to environmental regulation. The length of this regulatory region is determined by RNA processing machinery during polyadenylation, and differences in this post-transcriptional process lead to differences in the 3'UTR length known as alternative polyadenylation (APA). APA may represent a functional mechanism by which PSEN2 regulation differs in AD. The goal of these studies is to understand the impact of PSEN2 APA on neuronal function. We hypothesize that the length of the 3'UTR on PSEN2 transcript aligns with phenotypic changes associated with AD. To test this hypothesis, we are cloning PSEN2 with short and long 3'UTRs to test the functional differences of PSEN2 APA in vitro. Our goal is to introduce the short and long PSEN2 3'UTR constructs in the cells, specifically, microglia, the brain's immune cells, which are heavily implicated in AD pathology. Then, we will visualize the subcellular location of these transcripts and test for altered amyloid beta processing, which is a pathological hallmark of AD. We anticipate detecting differences in regulation and subcellular localization between the short and long PSEN2 3'UTR transcripts. Elucidating the functional relevance of the short and long 3'UTR of the PSEN2 transcript will further our understanding of APA in AD.

While research on burnout has focused specifically on service-oriented roles (e.g., healthcare), recent trends indicate a growing prevalence of burnout in academic settings. Burnout syndrome (BS) is a set of psychological symptoms arising from interplay of chronic occupational stress and individual factors. These symptoms often manifest as emotional exhaustion, depersonalization, and diminished professional satisfaction. Academic burnout has become a concern due to its association with poor academic performance, dropout rates and mental health symptoms (e.g., depression & anxiety). This study employed a pre-and post-design, assessing burnout before and after a burnout management workshop. An online survey via Qualtrics gathered data from community college students in the Pacific Northwest (N = 28, primarily women (78%), aged 16-20 (63%), including dual enrolled high school students. The survey employed a revised Purdue Burnout Questionnaire and collected demographic information. The burnout management workshop, facilitated by two psychology faculty members, addressed burnout facets and various management techniques. We hypothesized that participating students would show improvement after attending the workshop. Initial analysis revealed a reduction in total burnout scores before and after the workshop. Despite a noteworthy decrease, the change did not reach statistical significance. This nonsignificant trend suggests a positive direction, and further qualitative data, scheduled for collection in Spring 2024. Understanding and addressing academic burnout is crucial as it directly correlates with students' academic performance and mental health. By examining burnout in the college setting, we hope to contribute valuable insights that can inform policies and interventions to create a more supportive academic environment. 

Cervical spinal cord injury (SCI) can severely limit motor functions of the arms and hands. With very few available and effective therapy options, SCI results in reduced independence and quality of life. Electrical stimulation of the spinal cord is a promising therapeutic method that improves motor function in individuals with a spinal cord injury beyond what can be achieved by spontaneous recovery. However, this improvement has primarily been measured by manually scoring motor-based tasks and it remains unclear how these functional improvements are represented in the control of muscle activity. In this study, we conducted differential, intramuscular electromyography (EMG) recordings in rats while they performed a forelimb reach and grasp task. These recordings targeted the tricep brachii, wrist extensors and digit flexors. Trials highlighted the initial, intermediate, and final stages of an eight-week therapeutic window during which the rats received targeted, activity-dependent spinal stimulation (TADSS). TADSS is based on the principles of spike-timing dependent plasticity to enhance the electrical activity of spared motor pathways. The stimulation protocol delivers intraspinal microstimulation in synchronization with functionally related motor movements. I hypothesized that rats with a unilateral, cervical contusion of the spinal cord receiving TADSS will exhibit changes in EMG patterns throughout therapy with improved muscle strength and coordination of activity across muscles. This would suggest that TADSS can improve the strength of signals traveling through the injured spinal cord to the muscles. Results also measure functional recovery using an objective method rather than subjective behavioral scoring addressing a methodology problem in the field. Future directions will be directed towards differentiating the precise mechanisms of motor improvement as an objective method of recovery analysis.

Are we happier when we experience more comfortable weather, or do we prefer seasons that provide increased social opportunities? Current studies have shown improvement in mood due to warmer, more tolerable climates or spending more quality time with loved ones. There is a gap in the relation of these two factors combined towards an individual's mood. We hypothesized change in relationship between mood and social activity throughout fall and winter. After our second survey period, we will review and organize data points based on temperatures and climates, time in and out of school sessions for students, levels of socialness, and those who changed their answers after reflecting on the social aspects of the questions. In this study, we surveyed 260 Washington State residents aged 18-64 (M = 24.46, SD = 10.03), 56% from Eastern Washington and 44% from Western in the fall prior to the holiday season (September-November 2023) and again in winter (January-February 2024) to measure changes in mood changes. Both surveys, administered through Qualtrics, asked participants about weather types experienced during each season, followed by a Brief Mood Introspection Scale (BMIS) regarding their last two weeks and the Self-Assessment Manikin (SAM) scale of weather tolerance (0°F-104°F). Participants then were asked about socialness during each season and potential seasonal affective diagnoses. We had two target populations: participants under 23 and those who are students and those who are not students or are 23 or older. We expect students to favor periods not in school regardless of socialness, as opposed to those who are not students, who we expect to favor the times they spend with those they care about over periods of isolation as they tend to have more defined schedules.

Spinal cord injury (SCI) causes physical disability and chronic pain, but there can also be psychological issues like depression and/or anxiety. Clinically, the estimated rates of depression among the SCI population are from 11% to 37%, according to UW Medicine. In rodents, after SCI, both males and females demonstrated anxiety-like behavior, and female mice became more anxious while male rats became more hypersensitive to thermal stimuli. These findings highlight the complexity of the systematic changes after SCI, all of which may impact the quality of life and limit functional recovery. We have found a sex difference in the effectiveness of electrical stimulation in promoting functional recovery after cervical SCI. In our experiment, females show robust functional improvements with activity-dependent spinal stimulation. The current study aims to investigate the role of affective behaviors (depression and anxiety) and pain after SCI on functional recovery in male and female rats. Before injury, all rats will undergo baseline assessments to establish behavioral norms, which involve training and evaluations designed to measure motor ability, emotional state, and sensitivity to various stimulations. Three weeks after SCI, rats will be assessed with the same battery of tests and then start daily treatment of drugs that can modulate emotional states and relieve pain, including a mixed serotonin and norepinephrine reuptake inhibitor, duloxetine (or no drug control), for five weeks. Behavioral assays will be repeated at the end of the treatment period, and tissue will be collected for histological analysis. I will primarily be responsible for conducting and analyzing an assay of anxiety-like behaviors, the open field test, and the assay of depression-like behaviors, the sucrose splash test. We expect to understand better the relationship between affective responses and motor function post-SCI, and the potential therapeutic benefits of antidepressant treatments, and particularly identify sex differences that may limit recovery.

Various anti-cancer therapeutics, known as microtubule targeting agents (MTAs), target the microtubule, a tube-like structure that is a major component of cell mechanisms including mitosis and maintenance of the cell shape. MTAs selectively bind to tubulin — the building block of microtubule —, disrupting microtubule dynamics and inducing cell death. Despite their known impact on antitumor activity, the precise mechanism by which MTAs promote cell death remains unclear. To understand the efficacy of ST-401 (an MTA drug) as a tumor suppressor, I conduct various assays including drug treatment and Western blot to compare the expression of specific proteins in response to the drug treatments. These assays contribute to understanding cellular processes, molecular interactions, and the effects of various treatments or conditions on cells. Currently, I am being trained to conduct an experiment called XFe Seahorse analyzer. I’m carrying out this experiment to assess how the laboratory-discovered drug affects the mitochondrial function in various cancer cell lines. This experiment aims to determine whether the compound down-regulates mitochondrial function, leading to cell death. I’m leading a project to test a specific fission (cell splitting) protein, DRP1, and how its protein level responds to treatment with ST-401 in two GBM cell lines (resistant and sensitive) and one Colon cancer cell line. DRP1 regulates mitochondrial fission to maintain healthy mitochondrial function. Recently, I found an increase in mitochondrial fission 24 hours after ST-401 treatment in the sensitive GBM cell line, so I’ll further examine DRP1 expression by drug treatment and Western blot to understand these results and see whether ST-401 recruits DRP1, resulting in promotion of mitochondrial division. After DRP1 project, I will expand the project to asses the combination drugtreatment where we combine FDA-approved cancer drug and ST-401 to reflect real-world scenarios, aiming to ensure clinical relevance and safety by studying potential drug interactions.

Bacteria face a variety of threats, including antagonistic killing by other bacteria in competition for space and resources. In response to this antagonism, many bacteria have evolved specific defense systems. One pertinent example is the Pseudomonas aeruginosa Response to Antagonism (PARA) in P. aeruginosa, which provides defense against various antagonists by activating a suite of genes, mediated by two-component pathway Gac/Rsm, in response to kin cell lysis. The Gac/Rsm machinery is conserved across the Pseudomonas genus, but its function in defense has not been studied outside of P. aeruginosa. Here, we investigate whether two divergent Pseudomonas species, P. putida (KT2440) and P. protegens (Pf-5), similarly use Gac/Rsm in defense. To do this, we performed competitive growth assays against an antagonistic competitor, Enterobacter cloacae, comparing Gac/Rsm deletion mutants against wild-type, and quantified relative survival as an indicator of competitive fitness. Preliminary data indicate that the deletion of the core Gac/Rsm gene gacS results in dramatically decreased competitive fitness for Pf-5, but not for KT2440. This indicates that Pf-5 uses the Gac/Rsm system in a similar manner to P. aeruginosa and that, while Gac/Rsm is conserved, it may differ in function between species. To identify additional specific genes involved in defense systems, we set up a genome-wide screen. The screen indicated that genes related to the flagellum and lipopolysaccharide biosynthesis may be involved in defense against antagonism, which was surprising because these well-characterized structures have never before been implicated in defense. Work is currently underway to validate these genes as true defense factors and determine the mechanism by which they confer survival. Our findings advance the understanding of defense systems among Pseudomonas species by shedding light on their conservation and complexity, thus providing a foundation for future work on defense systems across bacterial phyla.

The use of pesticides in the Pacific Northwest is essential in the process of safeguarding public health, most notably by mitigating pests, protecting our food supply, and aiding in distribution to supermarkets, restaurants, and our homes. However, long-term exposure to pesticides can result in illness for those handling the substances as well as their families. Prior research has shown that current pesticide application methods play a role in accelerating illness. Newer methods, such as aerial drone spraying and “smart” sprayers, involve the use of emerging technologies that are poised to change the landscape of the agricultural industry and health outcomes of farmworkers. Under the supervision of the Pacific Northwest Agricultural Health and Safety (PNASH) Center, my project will be assessing thoughts regarding adoption of these technologies. Through the creation of an electronic REDCap survey, I will be obtaining a variety of responses from agricultural workers, farm decisionmakers, and others involved in the application of pesticides on farms. Once the survey is deployed, I will analyze responses both quantitatively and qualitatively using Dedoose and R statistical methods, respectively. From these responses, I will work with the PNASH team to evaluate the adoption of current and emerging pesticide technologies among Northwest fruit growers, as well as their impacts on occupational health and safety. Through this project, I hope to collect a wide range of perspectives and thoughts regarding the implementation of new pesticide application technologies, particularly unique opinion points (positive and negative) I did not otherwise consider in my initial research with the PNASH Center. The main objective of my research project is to capture the attitudes of the pesticide application technologies to inform policy, regulations, and decision-making regarding their uses.

Polycystic Ovary Syndrome (PCOS) is the most prevalent reproductive condition in pre-menopausal women, impacting around 5-10% of women in the U.S., despite being underdiagnosed. Previous research has linked a higher free androgen index with cardiovascular risk factors in women with various forms of ovarian dysfunction. Given that elevated androgen levels are a criterion for PCOS diagnosis, understanding the potential association between total testosterone and cardiometabolic risk factors in women with PCOS, specifically, is crucial. This cross-sectional study investigates the relationship between total testosterone levels and cardiometabolic risk factors among women diagnosed with PCOS. Limited research exists on endocrine and cardiometabolic health in PCOS patients, prompting our inquiry. Data for this study was extracted from women with PCOS who attended the University of Washington Endocrinology Clinical and Diabetes Institute. Blood samples underwent analysis for biomarkers including total testosterone, glucose metabolism, and lipid levels. Linear models, both adjusted and unadjusted, were applied to assess correlations between total testosterone levels and the aforementioned biomarkers. Insights into the impact of total testosterone on insulin resistance and lipid levels could offer better insights into how women with PCOS can better manage their health. Preliminary findings indicate a limited correlation between total testosterone and cardiometabolic risk factors, contradicting previous studies. Further analysis, including controlling for factors such as oral contraceptive use, will be done to bring greater clarity to these results. This study aims to bridge gaps in our understanding of the mechanisms by which PCOS can affect the health of women. It also seeks to address the underfunding and underrecognition of research in diseases that primarily affect women. Future research in this domain must be done to investigate biomolecular pathways on how testosterone could potentially affect cardiometabolic health.

Many individuals living in refugee camps have limited access to soap. Ready access to soap gives refugees the ability to maintain their own hygiene. Proper hygiene helps to reduce the spread of diseases through proper sanitation, thereby increasing life expectancy–especially among young children and mothers. The goal of this research is to empower individuals living in refugee camps by giving them the ability to make their own soap. To achieve this goal, I first, identified methods for making soap with resources accessible to refugees, such as oils, sodium hydroxide, and protective gear like gloves to ensure their safety during the process. Second, I created and led two workshops to teach leaders within refugee camps how to make soap with these resources. I conducted pre- and post-workshop focus group questioning with 30 refugees to assess their beliefs, attitudes, and experiences with using soap and making their own soap. The results of the pre-workshop focus group with women living in refugee camps revealed that soap is important for their daily lives, particularly for those working in the farming field. They reported that having more access to soap would significantly contribute to an enhanced sense of self and promote a healthier community. Post-workshop focus group responses revealed that participants expressed positive feelings about learning to make their soap, and many expressed interest in experimenting with ingredients like milk or rose flowers for added fragrance. Participants also reported that they plan to test their handmade soap, and if satisfied with its quality and feel, intend to sell it in the local market. Empowering refugees to make their own soap has the potential to provide them with greater agency over their health, dignity, and self-sufficiency. It could also potentially create opportunities for income generation, which could significantly improve their lives.

B-cell lymphoma-extra large (Bcl-xl) is a mitochondrial transmembrane protein that acts as an anti-apoptotic protein by sequestering the apoptosis-inducing proteins Bim, Bak, and Bad. This prevents the release of cytochrome c from the mitochondria, preventing activation of apoptosis pathways. Higher levels of Bcl-xl expression are commonly found in cancer cells. This contributes to the prevention of apoptosis in cancer cells, allowing them to proliferate uncontrollably. Bcl-xl is an incredibly important target for cancer therapeutics. A Bcl-xl binder would inhibit the interaction between Bcl-xl and apoptosis inducing proteins, allowing cancer cells to undergo apoptosis. In my research, I am using deep learning methods to design cyclic peptides that bind to Bcl-xl. To design the binders, I used RFDiffusion - a generative diffusion model - to produce thousands of cyclic peptide binder scaffolds bound to Bcl-xl. I then used a sequence-based deep learning tool to generate multiple sequences for each backbone design. The resulting binders were computationally validated with the highly accurate, machine-learning-based structure prediction tools AlphaFold and RoseTTAFold. Of the 40000 generated cyclic peptides, 2052 were predicted to bind to Bcl-xl based on standard metrics. Along with their excellent metrics, these designs show a high structural similarity and binding location to the known Bcl-xl binders Bim, Bak, and Bad. The designs were clustered by backbone into 350 unique clusters. We synthesized the top designs and identified which peptides display binding to Bcl-xl through a Homogeneous Time-Resolved Fluorescence (HTRF) assay. A successful Bcl-xl binder has the potential to serve as the basis for an effective and affordable cancer therapy.

Gastrointestinal symptoms are a common comorbidity of autism spectrum disorder (ASD), and individuals with the disorder tend to have a distinct gut microbial community composition and circulating metabolomes. My work in the Rajakovich Group focuses on a gut-derived metabolite, 4-ethylphenolsulfate (4-EPS), found in higher abundance in ASD mouse models and children with ASD. 4-Ethylphenol (4-EP), its precursor, is produced by gut microbiota before host-mediated sulfation, but the microbial biosynthetic pathway is unknown. A proposed metabolic pathway suggests the microbial stepwise conversion of plant-derived complex polysaccharides to 4-EP. My project goal is to identify a gut microbial enzyme responsible for the first step of this proposed pathway: a hydroxycinnamoyl esterase. I used literature searches and bioinformatics tools to identify characterized bacterial cinnamoyl esterases and candidate enzymes. I designed plasmids for two candidate enzymes (both from E. faecium, known to colonize the gut) and one characterized esterase (from L. plantarum). Currently, I am working on expressing the proteins in E. coli cells and purifying them by affinity chromatography. Once purified, I will assess the enzymes for their anticipated cinnamoyl esterase activity by incubating them with dietary hydroxycinnamic acid esters and detecting products with high-performance liquid chromatography (HPLC) and UV/Vis spectroscopy. Since the candidate enzymes are homologs of confirmed esterases and have conserved catalytic motifs, I hypothesize that they will have hydrolytic activity. If correct, I will see consumption of the substrate (no detection) and detect the anticipated products. Positive results from these assays would complement ongoing work by the lab to identify other E. faecium enzymes in this proposed pathway. Though it is debated if 4-EPS is causal to the disorder or simply a biomarker, elucidating its biosynthetic pathway and studying the biochemistry of gut microbes will contribute to detangling the gut’s role in ASD.

In the 20th century, the discovery and widespread use of antibiotics became humanity's primary weapon against pathogenic bacteria. Overuse of antibiotics has unfortunately given rise to antimicrobial resistance, weakening us in this evolutionary arms race. Proteolysis-targeting chimeras (PROTACs) have been proposed as a strategy for development of novel therapeutics. By tagging target proteins with ubiquitin, targeted protein degradation (TPD) can occur via a eukaryote's own molecular machinery. Due to prokaryotes lack of ubiquitin, research has shifted to the development of PROTAC-like molecules to achieve proteolysis and cell death in bacteria, called BacPROTACs. However, to eventually experiment with these small molecules and see their mechanism of TPD, off-target effects, and changes in host and bacterial proteomes, we must be able to profile the degradation of proteins in an unbiased manner. Proteomics and mass spectrometry can identify and measure thousands of proteins simultaneously, enabling systems-level and mechanistic understanding of these novel therapeutics. In order to ensure reliability, reproducibility, and overall accuracy in analyzing a cell’s proteome, an optimized proteomics workflow is imperative. Our lab sought to understand the downstream impacts of different sample preparation protocols, differing in the material used to capture precipitated protein. Here, I present an evaluation of three proteomic sample preparation methods used on triplicates of reduced and alkylated aliquots of human cell lysate: "SP3" (single-pot solid-phase sample preparation), uses magnetic carboxylate beads as a substrate for protein aggregation; "SP4", omits a capture substrate in favor of centrifugation; and "S-Trap/S-Tip," captures protein on a borosilicate glass fibers filters. Following a Trypsin and LysC digest and desalting, samples will be run on an Orbitrap Eclipse mass spectrometer. Analysis and subsequent optimization with more complex human samples will ensure the selection of a protocol providing the highest proteomic coverage for further research.

Adipose tissue, also known as body fat, is vital in storing energy. It is composed of adipocytes and present in different depots. In this study we focused on omental (OM) adipose tissue, which is found between organs near the stomach, and subcutaneous (SC) adipose tissue, which is found under the skin. Functional differences have been observed among adipose depots. SC adipose tissue is responsible for insulation while OM adipose tissue has endocrine functions. OM adipocytes have been observed to be smaller and more variable in size compared to SC adipocytes in individuals with obesity. I hypothesized that the size of both OM and SC adipocytes is associated with increasing BMI. I tested this hypothesis using SC and OM adipose tissue biopsies collected during elective surgeries from metabolically healthy participants (20 females, 11 males) with a range of ages (25-65 years) and BMIs (21-56). Afterwards, the tissues were fixed and stained with H&E. I drew 2-5 squares per slide and counted the number of adipocytes within each square. The size difference between OM and SC adipocytes was tested using a Wilcoxon signed-rank test and a significant difference (p=0.004) was observed. A correlation between BMI and the size of OM (p = 0.008) or SC (p = 0.009) adipocytes was detected with weighted linear regressions. Sex was not observed to be a significant covariate. These findings expand on prior data by including lean individuals, and patients with obesity who are otherwise metabolically healthy. The results show there is a clear difference in the size of adipocytes. The adipocyte size in both depots correlated with BMI. This data shows that progressive obesity and adipose tissue enlargement is due to the enlargement of the adipocytes rather than an increase in the number of adipocytes in both OM and SC depots.

Global Positioning Systems (GPS) technology plays a pivotal role in ensuring the safe and efficient navigation of drones by providing near real-time tracking of location and speed. The precision and reliability of GPS receivers are crucial for effective planning, sensing, and control applications in various domains. As Unmanned Aerial Vehicles (UAVs) continue to rise in demand and predominantly rely on GPS, minimizing the uncertainty in GPS performance becomes imperative. UAVs utilize the cost-effective nature of Micro-electromechanical Systems (MEMS) GPS receivers. This study identifies and analyzes GPS errors, specifically within consumer-grade MEMS receivers. The MEMS receivers are preferred for their low cost, low power, and low weight, making them ideal for integration into UAVs. Our methods include a series of controlled experiments in urban and semi-urban environments, encompassing varying weather conditions such as sunny and cloudy days. Static experiments evaluate GPS signal accuracy under stationary conditions, while dynamic experiments monitor GPS performance during drone flights. Our preliminary findings have shown a range of inaccuracies in GPS signal measurements. Horizontal signal accuracy varied from +/-1 to +/-14 meters, while vertical signal accuracy ranged from +/-3 to +/-12 meters. These results underscore the significance of further investigation to enhance GPS reliability, particularly in scenarios critical for UAV operations. In ongoing research, we are conducting more testing in other geographical locations and weather conditions to ensure the robustness of our conclusion. Additionally, we are developing environment-specific error detection algorithms utilizing the sensor fusion approach. Merging data from multiple sensors can reduce the uncertainty of an object's location, helping us when the GPS technology is not fully reliable. Our research contributes to advancing GPS technology capabilities, particularly for UAVs where accurate localization is important.

The cerebellum, which accounts for 10% of human brain volume, contains approximately 80% of all brain neurons and has long been understudied relative to the cerebral cortex. During development, the cerebellar ventricular zone (VZ) is a transient progenitor zone which generates all cerebellar GABAergic (inhibitory) neurons. This includes Purkinje cells (PCs) and PAX2+ interneuronal progenitors (PIPs). While the mouse cerebellar VZ has been relatively well characterized, there is limited knowledge about its human counterpart. In this study, we investigated organization of progenitors and birth of neurons derived from the human cerebellar VZ, uncovering several notable features. Specifically, I conducted image analysis in conjunction with immunohistology (IHC) assays to (1) identify different cell types and marker gene expression across developmental stages and (2) quantify proliferative cells at different stages of development. We found that a substantial number of PCs are generated during embryonic development, particularly within the first 50 post-conception days, within a compact two-week timeframe. This occurs well before the onset of cerebral neurogenesis, with interneuronal differentiation commencing during early fetal development. Neuronal differentiation predominantly occurs from the inner and outer subventricular zones (SVZ), zones which are completely absent in the mouse developing cerebellum, with the initial wave of differentiation occurring from the outer SVZ. Significantly, relative to mice, we observed variations in migratory patterns and the quantity of PC plates, including a subset of PCs that retain the expression of cell cycle genes several weeks after these cells leave progenitor zones. This work extends our knowledge of human-specific birth and organization of progenitors and neurons originating from the ventricular zone and cellular and molecular differences in ventricular zone progenitors, Purkinje cells, and PIPs across different developmental ages.
 

As the climate changes, we are beginning to see the impacts on a global scale. In order to understand how our landscapes will change with future warming, we can look back to see how landscapes were impacted by past warm, variable climates. This project looks to understand how climate variability in the Middle Miocene is expressed in terrestrial sedimentary records. Using X-ray fluorescence (XRF) analysis, we created a high-resolution elemental geochemical profile of sediment samples from Clarkia, ID (~16 Ma). From XRF, elemental concentrations for a host of elements, including Ca, Fe, K, Mn, Sr, Ti, Zn, and Zr, were calculated. Some elements, notably Ca, showed long-term trends but also sections of shorter-term cyclic variability. It is possible that this variability reflects changes in basin weathering rates of Ca-bearing minerals as a function of climate change occurring on timescales of tens to hundreds of thousands of years. Alternatively, Ca concentrations may reflect changes to precipitation of Ca-bearing minerals within the ancient lake, responding to algal productivity. These hypotheses are tested using X-ray diffraction (XRD) to identify minerals and their crystalline structures as well as characterizing the elemental trends from an additional site, Clarkia’s P-40. Understanding the depositional history of the Clarkia lakebeds aids our understanding in how climate impacts Miocene landscapes.

African immigrants are highly disproportionately affected by Human Immunodeficiency Virus (HIV) compared to US-born individuals in the U.S.. In King County, HIV stigma is a significant barrier to HIV testing among African immigrant communities. Our study aims to partner with communities to confront the HIV epidemic among the African immigrant population in King County by decreasing HIV stigma that prevents individuals from utilizing HIV testing. In this formative study, we have partnered with three African community organizations, Ethiopian Health Board, Eritrean Health Board, and the Congolese United Foundation, to deliver community-based HIV testing via health fairs at faith-based organizations and adapt and pilot an existing HIV stigma reduction intervention (Project FAITHH). We are working with faith-based organizations to address religious/moral beliefs that may foster negative social labels towards and further stigmatize people living with HIV. Data collected at health fairs hosted in churches serving each of these communities include HIV stigma scales, perceived barriers faced by individuals and community members that impact HIV testing, and demographics including country of origin, gender, religious affiliation, and primary language(s). Additionally, we have adapted an 8-module, faith-based stigma reduction intervention for these communities, aimed to address inequities in HIV testing perpetuated through HIV stigma, misinformation, and lack of awareness among intersecting, religious identities. The intervention includes activities to explore and address the sources of stigma around HIV in African immigrant communities, as well as information about HIV, including HIV epidemiology in King County. Anticipated findings regarding HIV stigma of participants before and after the intervention will inform our implementation of Project FAITHH among a more diverse group of African immigrant communities in King County. This work furthers the impact of community-based interventions designed to address the disparities in HIV in King County.

Spasticity is an increase in muscle tone (hypertonus) and abnormal muscle stiffness that impedes functional activity. Oftentimes observed among individuals with chronic neurological conditions such as traumatic brain or spinal cord injury (SCI), spasticity develops as a result of damage to the central nervous system (CNS). This damage disrupts the balance of supraspinal inhibitory and excitatory inputs to the spinal cord, which can lead to the loss of inhibitory inputs and hyperexcitation of the spinal reflex arc. The aim of this project is to develop an electrical stimulation protocol that regulates imbalances of supraspinal input and the spinal reflex in order to potentially alleviate spasticity caused by traumatic neural injury in patients. The hyperexcitation associated with spasticity is measured using the Hoffman-reflex (H-reflex). Previous studies have revealed that electrical stimulation of the rat motor cortex can modulate long-term spinal excitability. In this study, behaving noninjured Long Evans rats are implanted with cortical implants to induce stimulation to the motor cortex, grounding electrodes to filter environmental noise, cuff electrodes to evoke the H-reflex, and EMG electrodes to record the H-reflex response. The H-reflex is assessed by stimulating a cuff electrode surrounding the median nerve and measuring the consequent activity of EMG electrodes that are implanted into the flexor, extensor, and tricep muscles before and after electrical stimulation of the motor cortex. Our preliminary results indicate that different frequencies of cortical stimulation can modulate the H-reflex, suggesting that our novel cortical stimulation protocol may reduce spasticity and promote restoration of motor function. In future studies, I plan to assess the efficacy of cortical stimulation for improving spinal excitability in spastic animals following chronic SCI.

This poster describes a qualitative study highlighting the intersection of ethnic identity and Christian faith in shaping South Asian college students’ perceptions of LGBTQ+ individuals. Current sociopolitical climates toward LGBTQ+ individuals in South Asian countries tend to be hostile, and even South Asian communities within the United States can reflect similar beliefs. Zaidi (2014) found that shame in the South Asian community was in conflict with a desire to express one’s queer identity among South Asian youths (Zaidi, 2014). Moreover, environmental factors such as the religious setting might contribute to varying perspectives regarding LGBTQ+ individuals; in the current study, we highlight faith-based higher education institutions (i.e., Christian university) as an institution that can shape views regarding LBTBQ+ folks and their experiences. We conducted 6 semi-structured interviews with South Asian college students enrolled in a Christian university located in the Pacific Northwest region of the U.S. Our three-member research team transcribed the interviews, coded the transcriptions, and placed the codes in themes according to Braun and Clarke’s (2006) guidelines for Thematic Analysis. The four themes that we identified include support for LGBTQ+ people on campus, Christian messaging around LGBTQ+ identity, South Asian communities, and participant’s own attitudes. These major themes also included subthemes, some of which are campus advocacy and protests influenced participant’s beliefs, feelings of an internal struggle, attitudes of South Asian communities, and individual affirming attitudes. Broadly, we found that the participants viewed their own South Asian communities as generally silent or passive in LGBTQ+ dialogues, and that their Christian campus promoted both helpful and unhelpful conversations about the topic. We will present some implications for practice in higher education around fostering an inclusive space for LGTBQ+ individuals, especially as they pertain to intentional integration of culture-specific (e.g., South Asian) and religious (e.g., Christian) perspectives.

Alzheimer's Disease (AD) is clinically characterized as a predominantly amnestic (memory impairment) syndrome at presentation that progresses to affect other cognitive domains. AD is pathologically defined by the presence of amyloid plaques and neurofibrillary tangles of hyperphosphorylated tau (pTau) in stereotypical brain regions. AD shows clinical and pathological diversity, including non-amnestic subtypes, severity of tau pathology across brain regions, and co-pathologies such as aggregates of hyper-phosphorylated transactive response DNA-binding protein 43 (pTDP-43). This study aims to examine the association between pTau and pTDP-43 using new highly quantitative approaches. By examining the combined pathology, we hope to identify patterns of pTau related to pTDP-43 across the different clinical and pathologic subtypes. The University of Washington Alzheimer's Disease Research Center clinical core autopsy cohort was characterized and subdivided into amnestic and non-amnestic syndrome subtypes. The subjects were analyzed to identify the prevalence of pTDP-43 and its correlation to the subject's cognitive data and patterns of progression. This analysis was used to select a subset of 29 cases with non-amnestic dementia and a matched subset with an amnestic subtype for more in-depth neuropathological and molecular profiling of several brain regions. Using the HALO platform, I generated quantitative measures of pTau in the frontal, temporal, and parietal cortex, as well as the hippocampus. The integration of these findings aims to understand how pTDP-43 pathology influences tau distribution based on clinical presentation These results will allow us to select a small set of cases for further work that will include using NanoString GeoMx Digital Spatial Profiling to identify potential pathways relevant to the association between pTDP-43 and pTau severity concerning mechanisms of clinical and pathologic heterogeneity in AD. These insights will allow for further research of these pathways to determine their biological relevance and ways to mitigate their effects.

Sound symbolism is a phenomenon wherein the phonetic forms of certain words iconically represent attributes of the objects, qualities, or events they describe. This study focuses on the sound-meaning link in Panãra animal names, using vocabulary from field notes collected in the Panãra community by Dr. Lapierre the summers of 2015-19 and by Dr. Lapierre and PhD students Ananthanarayan, De Falco, and Jeter the summer of 2023. The Panãra vowel system has a combination of features not present in some more widely studied languages such as English, namely, a back, unrounded series, contrastive length, and contrastive nasality. Using this extensive inventory, I assess strength of size sound symbolism created by nasality, height, vowel length, and backness, as well as the interactions between multiple features. I organize Panãra names for different animals and find the average weight of that species. I calculate the percentage of vowels that have a certain feature in a word and assess the correlation between this percentage and the weight of the species denoted using a regression model. Previous research has shown that front and high vowels are associated with smaller sizes and back and low vowels with larger sizes. I predict that the phonetically central and mid series will be associated with sizes intermediate to the peripheral series. Alongside providing observations from an under-documented language regarding its sound symbolism, findings from this study will help guide the continued lexicographic and field research inquiries into the Panãra language.

The interplay between physical environments, particularly indoor spaces, and psychological well-being is an emergent research area with significant practical implications. Despite acknowledging the positive effects of clean and luminous spaces, robust methodologies to evaluate such environments objectively are scarce. This study addresses the challenge by proposing to estimate an environment's influence on well-being from a single photograph. Support Vector Machines, a type of machine learning algorithm particularly effective for pattern recognition tasks by finding the optimal hyperplane that best separates data points of different classes, are employed to analyze specific features like messiness and brightness, which have been empirically linked to comfort and mood. This analysis is part of a broader set of variables our comprehensive model assesses, aiming to provide a nuanced environmental quality assessment tool. The aim is to quantify this analysis into a suitability score that reflects an indoor space's potential to enhance well-being, based on the model’s confidence. Our model is trained on a diverse and ethically sourced dataset, including anonymized student contributions and internet images, preparing it to offer refined classifications. The ultimate objective is to inform non-clinical, preliminary evaluations of environmental quality and suggest enhancements for spaces used in daily life.

Plainfin midshipman (Porichthys notatus) are seasonally reproducing teleost fish found along the Pacific Coast of North America. During the non-reproductive months (December-February), midshipman live offshore in deep waters. Between March and July, they migrate to the intertidal zone to reproduce. During the reproductive period, dominant (type I) males build and defend nests and hum to attract female mates. Unlike most vertebrates, courtship (humming to attract mates) and parental care (egg cleaning, nest defense) are both conducted only by type I males. These males therefore face energetic and temporal trade-offs between courtship to parental care within a single reproductive season. Our research investigates the neural mechanisms underlying the transition from courtship to paternal care in type I males during the reproductive period. We propose that this behavioral shift is regulated by steroid hormones (i.e. testosterone and estrogen) and neuropeptides (i.e. galanin). We are measuring hormone levels in blood and brain of midshipman fish across various conditions of courtship and parental care. We show the relationship between changes in steroid and neuropeptide levels in both blood and brain and changes in courtship and parental care behavior in type I males. Understanding these mechanisms in midshipman fish is crucial, as the steroid and neuropeptide pathways that regulate social behaviors share similar pathways across vertebrates. Therefore, studying this in teleost fish can provide valuable insights into the broader regulatory mechanisms of reproductive life-stage transitions in vertebrates.

Trapped ion quantum computing (TIQC), with its large decoherence times and small operation times relative to other physical quantum computing architectures, has garnered significant attention in the public and private sectors. Planar Paul traps, which simultaneously utilize radio frequency and static voltages in a two-dimensional electrode array to spatially confine ions, are the primary candidates for trapping ions for TIQC due to their manufacturability and ability to shuttle ions between multiple trapping zones for quantum logic gates and memory storage. The growing relevance of this technology necessitates educating students about the advanced electrodynamics of ion trapping and ion shuttling. Therefore, I developed a macroscopic planar Paul trap which utilizes 50µm diameter proxy-ions along with high voltage (HV) alternating currents (AC) at 60 Hz and HV direct currents (DC). These are applied to a 5-rail electrode geometry to demonstrate ion shuttling and ion-group splitting along a linear trapping axis. The goal is to educate students on the electrodynamics of ion traps by allowing them to experiment with the tunable trapping parameters, such as AC voltage amplitudes, DC voltage magnitudes, and applied shuttling waveforms and observe the changes in the dynamics of the proxy-ions relative to theoretical predictions. I designed the trap by implementing the recommended relative electrode dimensions into COMSOL Multiphysics and optimizing the geometry by maximizing the pseudopotential confinement while simultaneously minimizing electrode surface area. Afterwards, I utilized an analytic model of a 5-rail planar Paul trap, along with the method of Lagrange multipliers, to optimize the voltage magnitude and waveform of the segmented electrodes for smooth, effective shuttling and ion-group splitting. I then integrated an HV relay circuit and the 5-rail electrode geometry onto printed circuit boards to allow for student-controlled ion shuttling via an Arduino microcontroller.

Smartphone use among adolescents has dramatically increased in the past decade, with adolescents allocating more time inside on their screens and less time outside in nature. Given these shifts in behaviors, there has been a rise in concerns about the impact of smartphones on adolescents’ mental health. Studies on nature exposure have found that spending time in nature promotes human well-being; however, a limited body of research exists exploring how smartphone use impacts our ability to experience these physical and psychological benefits of nature exposure. To address this gap in the literature, we conducted a between-subjects experiment with college students at the University of Washington (N ~ 40) randomly allocated to one of two conditions to spend 20 minutes in nature: a smartphone condition and a no-smartphone condition. Participants self-reported on positive and negative affect and rumination before and after their experience in nature. After completing these scales, participants reported on their experience of Presence, a state of being in which the mind is highly aware but without active thought, by self-reporting on a recently validated 14-point scale and writing about it for further analysis using an interaction pattern approach. I anticipated that participants who feel more attached to their smartphones spend more time using them in nature and, in turn, are less likely to experience the emotional benefits of nature. If the findings reflect this, future research should explore how smartphones impact adolescents’ mental health and the extent to which smartphone-free time spent outside in nature can improve their well-being.

In quantum computing, computer engineers require a method to control the logical state of a quantum bit (qubit). Unlike its classical counterpart, a qubit’s logical state is not defined by a binary and discrete voltage. The QT3 lab is developing a quantum testbed with a defect in diamond known as the nitrogen-vacancy (NV) center. We present an on-diamond antenna that is optimized to manipulate the electron spin state of an NV center, which defines the qubit. Applying a radiofrequency magnetic field equal to the energy difference between the two spin states of our qubit, also known as resonant excitation, enables control of this state. The strength of this field directly correlates to the frequency at which this manipulation may occur. That frequency is known as the Rabi frequency. This is important as we want this frequency to be faster than the state can undergo decoherence, where state information is lost to the environment of the qubit. We have designed and simulated an antenna using finite element analysis software, which will supply our field and be fabricated on the diamond surface. For its geometry we realized a coplanar waveguide with a shorted end shaped around the NV center, which optimizes the field strength at the NV center, power reflections, and area consumption. Preliminary fabricated samples have been mounted, wirebonded, and characterized using a vector network analyzer, and have shown behavior that aligns with simulated results. We expect to have the antenna fabricated on our single NV center testbed sample and achieve a Rabi frequency on the order of 10’s of MHz. Once this sample is fully integrated into our cryogenic system, it will enable us to expand control to multiple nuclear spin qubits from a single NV center, as a quantum register. The testbed will be accessible to researchers and educators.