Physical resilience is a measure of healthy aging, but current assessment methods are underdeveloped, relying on a frailty panel of subjective tests. A quantitative, reliable test for resilience using endpoints aligning with healthy aging is needed to provide a standardized measurement of resistance to age-associated decline. The chemotherapeutic drug cyclophosphamide (CYP) is an immunosuppressant used in clinical medicine for certain types of cancer and autoimmune diseases. Precursor neutrophils are especially sensitive to this chemical stressor, such that a single low-level dose stops cell cycling with a decrease in mature neutrophils, but neutrophils rebound as the drug is eliminated from the body. This study sought to characterize the neutrophil rebound response in aging mice as a biological sensor for how an organism might respond to physical stress with increasing age. One intraperitoneal dose of CYP at 100 mg/kg was given to groups of mice at various ages. White blood cell differential and total counts were enumerated to monitor cellular response over a 25-day period. A robust and predictable drop in neutrophils occurred across age groups five days after injection of CYP, followed by a robust increase in neutrophils beyond baseline measurements at day seven in an age-dependent manner. Strength of the neutrophil rebound had a moderate correlation with strength and stamina as measured by rod hanging time, a test that corresponds to hand grip assessment in humans as an indication of frailty. This observation suggests that the neutrophil rebound response to the chemical stressor CYP in young adult mice can predict resilience to aging in older adult mice. The clinical implications are that an in vitro bench test could be developed using CYP-induced rebound response of human precursor neutrophils to predict resistance to frailty and produce a more accurate assessment of resilient healthy aging in older adults.

The Arbuckle karst system consists of caves, microfractures, and hydrogeologic barriers. Isopods in the genus Caecidotea inhabit the pools of water within the groundwater system. Young Caecidoteas travel through microfractures, and small populations move from one cave system to the next. Over the time these fractures close, causing the populations of Caecidotea to be isolated and potentially drift genetically. The sampled distinct populations have become morphologically distinct, but it is yet to be determined if they also have become genetically distinct species. Genetic classification may also provide a more timely identification of fracture closing. DNA Barcoding using the Cytochrome Oxidase subunit 1 (COX1) gene will provide the percent of divergence in the samples obtained from different populations/locations; however, the chitin-heavy exoskeleton of isopoda could make it difficult to have DNA extractions that are “clean” (without protein) and decent yield. An extraction method was used proteinaseK (protK) and high salt to release the DNA followed by ethanol precipitation to concentrate the extract. For DNA Barcoding, the COX1 gene sequences need a PCR protocol with the robust primers is crucial. We plan to explore various primer sets for the optimal amplification.

Epilepsy is a neurological disorder in which abnormal brain activity causes spontaneous seizures, and behavioral comorbidities including anxiety, depression, and cognitive deficits. Epilepsy can result from many different inciting events, including infection, genetic background, or neurological damage. For example, status epilepticus (SE) is a clinical emergency defined as continuous seizures lasting longer than five minutes, which can increase susceptibility to developing epilepsy. Clinical studies in patients with epilepsy have shown that seizures of different severity can occur at discrete times of day or night, suggesting that there may be circadian patterns of seizure incidence in humans. In this study, a post-SE model of temporal lobe epilepsy (TLE) was used to first establish whether there are any notable circadian patterns of seizure activity in a preclinical rat model of epilepsy that is commonly used for antiseizure drug development. Male Sprague Dawley rats were implanted with cortical electrodes one week prior to the systemic administration of the chemoconvulsant, kainic acid, to induce SE insult. The rats recovered from the SE insult and then went on to develop spontaneous recurrent seizures days to week later. The onset and severity of spontaneous seizures were then continuously monitored for 6 weeks, with seizure segregated by time of day in which they occurred: light vs dark cycle. Preliminary data suggest that rats from this model more frequently experience seizures during the dark phase, i.e. the active period of this nocturnal animal. Results from this study will establish the circadian pattern of spontaneous seizures in the post-kainic acid SE model of temporal epilepsy in rats. Further, this study provides the basis on which to then determine if chronic administration of prototype antiseizure drugs can be optimally administered prior to periods of peak seizure incidence to more effectively reduce long-term seizure burden in this model.

Epilepsy is a neurological disorder that affects over 65 million people globally. The initial identification of antiseizure efficacy and tolerability of any investigational agent is routinely defined in mouse and rat models of epilepsy. C57BL/6 mice are a commonly used inbred strain for antiseizure drug discovery, while CF-1 mice are a commonly used outbred strain. Although there is established data on the median effective anticonvulsant doses (ED50) of common prototype antiseizure drugs (ASD) in mice, there is limited quantitative data pertaining to the acute impact of anticonvulsant doses of ASDs on locomotor activity in an open field, which may inform on the potential for adverse effects in a clinical setting. This study aimed to provide a quantitative evaluation of the impact of ASDs on locomotor behavior to provide an added way to compare investigational agents to ASD standards-of-care. Male C57BL/6 or CF-1 mice (n = 8/treatment group/strain) were habituated to an open field 24 hours prior to the testing day. On the day of testing, mice were administered prototype ASDs (valproic acid, carbamazepine, levetiracetam, lamotrigine, phenobarbital, diazepam, ethosuximide, phenytoin, gabapentin) or vehicle by the intraperitoneal route. Mice were then allowed to explore the open field for the 30 minute period encompassing the time of peak effect of each ASD. Endpoints of locomotor behavior in the open field included time spent in the center of the field, vertical rearing, fecal boli, and total distance traveled. In CF-1 mice, diazepam generally reduced all measures of exploratory behavior whereas gabapentin increased the total distance traveled. This study establishes a comparative pharmacological profile of the effect of prototype ASDs on exploratory locomotor behavior of male outbred CF-1 and inbred C57BL/6 mice.

Beat poetry and rhythm tap are two interests I have had for several years.  Through my separated exposure to and analysis of both, I noticed a similarity in their manifestations of improvisation and rhythmic complexities.  Initially, I assumed these resemblances were due to the heavy influence of jazz music both beat poetry and rhythm tap dance underwent in their formulations.  However, when examining the jazz music more closely, it became clear that the characteristics of the specific form of jazz beat poetry emulated (bebop jazz) purposefully opposed the characteristics of the form of jazz rhythm tap was danced to (big band swing).  This research henceforth sought to find how the rhythmic complexity and improvisation in rhythm tap and beat poetry could manifest themselves so similarly despite their rootedness in fundamentally contradicting forms of jazz music.  Through analyzing the historical shift from swing jazz to bebop jazz, it was found that the contrasts between the genre were actually essential, as they allowed for a different relationship with jazz music to develop per art form: rhythm tap integrated itself into swing music, while beat poetry emulated bebop. Because of this, rhythm tap had the autonomy to add improvisation and rhythmic complexity atop mainstream swing music’s lack of both, while beat poetry could echo the improvisation and rhythmic complexity of bebop without losing its individuality. This resulted in both having sonic similarities to bebop: the unintentional musical bridge between between beat poetry and rhythm tap which resulted in the two mirroring one another.

Is the neutrino its own anti-particle? This is a question physicists do not have the answer to, but if a process known as neutrinoless double-beta decay were observed then it could be said with certainty that the neutrino is indeed its own anti-particle. In an attempt to search for said process, researchers at UW have joined forces with researchers from a number of other institutions to form the group known as LEGEND (Large Enriched Germanium Experiment for Neutrinoless Double-Beta Decay). The source used for this experiment that undergoes double beta-decay is Germanium-76. This source is also used for the detector itself. When a beta decay happens in the detector a pulse proportional to the energy of the electrons emitted is produced. If these electrons have all the energy available from the decay, then it will be known that no neutrinos are present. What makes things tricky is that if this process occurs it does so with a half-life greater than 10²⁶ years. Thus, counting rates for this process will be very low, and very low backgrounds will be needed to effectively carry out the experiment. Currently at UW we are working on developing pulse rejection techniques that will allow us to get rid of unwanted background events that our detectors measure. The project I'm presenting on involves aiming a collimated alpha source at our detector, and the goal is to develop techniques that allow us to reject pulses resulting from alpha decays. A number of other collimated sources are also aimed at the detector in order to study rejecting the pulses that they give rise to. In order to help design this experiment I am running simulations in the Geant4 based application “g4simple” to determine collimator dimensions and materials that will work best for different radiation sources.

Throughout the United States, children and adults are forced to engage in sexual acts and use illicit drugs against their will, in what many would call modern day slavery, commercial sexual exploitation, or sex trafficking. Victims are controlled through coercion, force, fraud, physical and sexual violence and they endure many emotional and physical consequences. Approximately 80% of victims access healthcare during their time of exploitation for health reasons such as acute injuries, sexually transmitted infections, and mental illnesses, such as depression, anxiety, trauma, and suicidal ideation. The emergency department (ED) is the frontline to these patients. To date, little is known about nurses' confidence or competence in identifying or caring for this vulnerable population in Seattle, WA. The aim of this study is to examine what current practices exist at emergency departments in three, large referral hospitals in Seattle to identify victims, and to assess facility and nurse readiness for improved identification. Nine ED nurses in Seattle were interviewed to gain insight into how they currently identify trafficking victims, their opinion of the acceptability of existing screening questions (compiled from nationwide piloted studies) in their ED setting, and whether they felt such a standardized screening tool may be effective in identifying victims and improving subsequent care. Through transcription of audio interviews, nurses’ responses were analyzed and coded for common themes. Improved identification of trafficking victims by nurses and other frontline health workers in emergency settings may lead to more efficient and effective linking with vital support services and resources to assist them in safely exiting the sex trafficking industry. Results from this study will be shared with the participating hospitals, as well as public health officials and stakeholder organizations in order to improve awareness of sex trafficking, victims, and provision of necessary care and resources to support this vulnerable population.

Sixty percent of adults in the US have a chronic disease (e.g., heart disease, cancer, diabetes) and forty percent of adults have two or more chronic diseases. Risk for chronic disease is strongly influenced by a short list of health behaviors such as tobacco use, physical activity, diet, and alcohol use. College students, as they become independent from their families, start to establish lifelong habits through their time in school. Students who experience high stress are more likely to engage in less healthful behaviors which can increase their long-term risk of chronic disease. The purpose of this study is to understand how stress and lifestyle behaviors among low-income and international college students impact risk for chronic disease. This is a survey study in which 300 undergraduate international and native students at Portland State University will complete questionnaires about health behaviors, stress, socioeconomic status and demographics. International student participants are recruited from different clubs and programs that provide support for international students. We expect our results to indicate that international students and students from low-income families experience higher than average levels of stress, which may negatively impact their engagement in health behaviors and further increase their risk for chronic disease.

This is a rhetorical analysis of Hulu’s televised adaptation of the 1985 Margaret Atwood novel The Handmaid’s Tale as an episodic rhetorical act. This analysis merges feminist and ideological criticism to analyze the show’s twenty-three episodes and explores how the series is influenced by the veneration of feminist tropes within our current cultural milieu and how it influences social and political mobilization from its empirical audience. Within a context of historical gendered oppression, I analyze how The Handmaid’s Tale series furthers hegemonic ideologies regarding gendered behavior and reproduction by representing cisgender, heteronormative, nuclear families. I also examine how the repression inherent in each trope leads to the championing of biological essentialism from the show’s viewers. Finally, I examine how the series denotes personal agency as it relates to biological motherhood and any disruption to the state of biological motherhood as immoral, thus reasserting rhetoric inherent in modern, restrictive reproductive public policies. Drawing from scholarly sources and popular media such as news articles and protest images, this paper deconstructs the show’s narrative which positions reproductive tyranny at its center. This paper examines the cultural perspective on reproduction while contributing to the understanding of reproductive oppression in the United States; broadening the choice/anti-choice conversation to include other examples of gendered oppression, such as forced sterilizations and maternal mortality.

Tooth sensitivity is a common affliction that leads to discomfort or even pain when teeth come in contact with a variety of stimuli, such as cold drinks or brushing. The pain is a result of the tooth's natural protective enamel layers wearing down over time, exposing microscopic channels in the teeth known as dentin tubules. These dentin tubules transmit sensation from the tooth surface to the nerves, which is why exposing them leads to greater sensitivity in the tooth. The goal of this study was to evaluate the effectiveness with which a mineral dentin desensitizer could cover and seal the dentin tubules, thereby decreasing tooth sensitivity. Samples of human teeth were cut into disks to expose the dentin tubules and applied with the desensitizer. One treatment group was immediately processed for imaging using a scanning electron microscope, while the other was stored in simulated body fluid for four weeks before imaging. Cross sectional and surface images were taken of the dentin samples, at several magnifications. Both treatment groups showed effective coverage and mineralization not only over the open tubules, but also penetrating into the tubules. These results suggest such treatments may be an effective way to treat patients with tooth sensitivity caused by exposed dentin.

Small-angle neutron scattering (SANS) is a powerful tool that provides access to molecular-level structure in a variety of material, such as soft matter, colloids, and biomolecules. Currently, researchers must follow a manual and inefficient procedure to reduce and analyze data due to inconsistent meta-data storage and varying reduction processes. Thus, our project is aimed to improve the automated reduction of SANS data and streamline data flow at the experiment site by the use of machine learning (ML) and data science techniques. We propose a machine learning classification algorithm, trained on a historical SANS dataset, to automatically sort raw data into six categories of scattering profiles and relevant background measurements required for reduction. The first stage of our research project uses a feature reduction model to create a subset of most significant and relevant meta-data in the historical scattering data set. After pre-processing, we then explore different ML models (e.g. neural networks) to sort the data in a comprehensive, accessible, and maintainable form that can be easily applied to sorting data directly from experiment sites. In addition, we incorporate a Postgres database to improve data management as well as an interactive front-end to enable user interaction. Currently, we are building meaningful and useful data processing and management methods by starting with a small SANS dataset from the Pozzo Research Group at the University of Washington. In the future, these methods will be expanded to larger historical SANS datasets to train our machine learning models. By developing this machine learning algorithm that can utilize experimental information and scattering patterns for auto-labeling of raw data and relevant meta-data, we will enable more efficient storage, reduction, and analysis of SANS data for researchers in the future.

High rates of early dropout or premature termination in university psychology training clinics adversely affect both patients and clinicians. Prior research suggests that among clients seen at training clinics approximately 70% terminate prematurely and approximately 55% do not report reliable change at the conclusion of treatment. To help assess the generality of this issue, we are investigating the rate of premature termination in a university-based clinical psychology training clinic in the Northwest. Using the Reliable Change Index (RCI) as a marker of recovery, we calculated the RCI for 3 outcome measures: the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder 7 (GAD-7), and the Brief Adjustment Scale-6 (BASE-6). Additionally, the training clinic in this study practices Measurement-Based Care (MBC) which involves the systematic administration of symptom rating scales known to increase treatment efficiency and effectiveness by assisting with clinical decision-making and informing patient progress. The hypothesis was that there would be a higher rate of reliable improvement and lower rate of deterioration at the end of treatment. Our examination of the test-retest reliability within 2 weeks of these outcome measures found the total scores of all three scales to perform adequately. Within the training clinic, 18.18% reliably improved using the GAD-7, 21.51% reliably improved using the PHQ-9, and 27.27% reliably improved using the BASE-6. These results did not support the hypothesis and instead found a lower rate of reliable improvement than the published norms. Potential reasons for the discrepancy will be discussed. This study will benefit those suffering from ineffective treatment outcomes and those struggling with untreated debilitating mental disorders. It will also add to the growing literature on the benefits and obstacles of MBC which has been gaining increasing recognition recently. 

Over 30 years after the Vietnam War ended, Quang Tri province was still affected by explosive remnants of war (ERW), which killed and injured more than 8,000 people, about 1.4% of its total population 2011 since 1975. Peacetrees Vietnam is an international non-profit organization, collaborating with local partners in Quang Tri Province to clear dangerous explosives from Vietnamese land, and return healthy land, and building sustainable communities. My internship at Peacetrees Vietnam in Seattle provided a value resources to accessing the impact of Community-based Explosive Remnants of Wars program in Quang Tri Province. Methodologically, I had informal interviews with the staffs, collecting statistics through their annual reports, read intensively literature reviews about remanats, and developed a visual population profile. I chose a qualitative interview method by developing questionnaire to understand the Peacetrees Vietnam's project. I traveled to Vietnam, Quang Tri province to interview and observe staff, mine clearance teams in Peacetrees Vietnam, the residents in Quang Tri Province, and others sustainable projects such as kindergarten, libraries, black pepper projects. In addition, I developed communication strategies for the organization to reach broader donors, by researching representatives who participated in UXO Caucus, then matched with donor's Peace trees Vietnam. The purpose was asking those donors representative to support for demining humanitarian program in Vietnam, particularly Peace trees Vietnam organization. 

 I am an enrolled member of the Nor Rel Muk Wintu Nation located in Hayfork, California. My tribe has been fighting for federal recognition since 1986, leaving many of us in precarious situations without our sovereignty recognized by the federal government. Many tribes in California are seeking federal recognition due to the restrictions of services accessible, which hinders our access to beneficial federal policies such as the Indian Child Welfare Act of 1978 (ICWA). I understand the issues surrounding tribes that lack federal recognition and the problematic issues that arise without our sovereignty recognized, rendering our communities’ invisible. Due to this invisibility, my research focuses on the absence of knowledge pertaining to non-federally recognized tribes in California, such as the Nor Rel Muk Wintu, and our continued fight to utilize these policies, such as ICWA, while we remain sovereign with or without federal recognition. For my project, my methodology is a critical analysis of historical and contemporary policy; also examining the statistical data surrounding ICWA. Using statistical data gives me a framework to focus on the inclusivity of non-recognized tribal communities in California. Setting the foundation of settler-colonialism and Federal Indian Policy is essential to understand the precarious situations found in communities that lack federal recognition as these laws create barriers for tribal people. The ICWA as a federal law inhibits the help associated with non-federally recognized communities and leaves these children unprotected from historical known Indian child removal as an attempt to assimilate American Indian and Alaskan Native peoples into white society. As programs and research focus on the ICWA law, I have examined if they are inclusive of tribal communities that are not federally recognized. My preliminary results thus far have not included tribal Nations that lack federal recognition within their data.

Abstinence-based treatment has long been considered the standard of care for people with alcohol use disorders (AUD). However, abstinence-based treatment fails to engage severely affected populations (e.g., homeless people affected by AUD) because many are not yet ready, willing or able to stop drinking. A recent randomized controlled trial tested the efficacy of a lower-barrier harm-reduction treatment for alcohol (HaRT-A), in which participants could define their own harm-reduction and quality-of-life (QoL) goals. The aim of this present secondary study was to describe participants’ own harm-reduction and QoL goals and document their achievement of these goals over the course of HaRT-A. Participants were people currently experiencing homelessness and AUD (N = 86) who attended the 4-session HaRT-A, during which interventionists elicited participants’ own harm-reduction and QoL goals. The Safer-drinking and Harm Reduction Efforts (SHaRE) form was administered to elicit and record participant-generated harm reduction goals, which were entirely participant-driven with no suggestions from study interventionists for any specific drinking-related goals. Directed content analysis was performed to classify participant-generated treatment goals. Results indicated that goals fell into 7 primary categories, the top 3 being drinking-related goals, quality of life goals, and health-related goals. These findings suggest that a client-driven, goals-setting approach could inform accessible and appropriate treatment and QoL-enhancing interventions for people experiencing homelessness and AUD.

Worldwide, there are currently more than 50 million people living with dementia and this number is projected to exceed 135 million by 2050. Unfortunately, negative stereotypes and misconceptions about dementia continue to exist, which can result in harm, isolation, and stigma towards those living with dementia. Dementia Friends is an anti-stigma and educational campaign that trains volunteers called “champions” to host informational sessions out in the community. During these sessions, champions educate local community members about the impact of dementia and what they can do to help. These community members are known as a “dementia friend” and are encouraged to help those with dementia live welll. Although Washington state is the fourteenth state to adopt the Dementia Friends program from the United Kingdom, limited research is available about the effectiveness of the program. This study seeks to evaluate the effectiveness of the Dementia Friends program in training the champions in Seattle and Yakima by comparing pre-training and post-training questionnaires. Results from this study will guide the expansion of the Dementia Friends program in other cities. Online questionnaires were distributed to 15 champions before and after the training session via RedCap. In order to assess the champions’ attitudes, perceptions, and experiences about dementia, participants were given 20 subjective statements about dementia and a 7-point Likert scale to assess the degree to which participants agree or disagree with each statement. We anticipate that Dementia Friends will be effective in educating community members and reducing misconceptions regarding dementia. If efficacious, we recommend Dementia Friends to be adopted across Washington to de-stigmatize dementia by educating community members.

 Developmental epileptic encephalopathies (DEEs) are a group of severe neurological disorders that present with seizures in early infancy and developmental delays. A genetic cause can be identified in up to 50% of affected individuals and is most commonly a de novo genetic change. However, for some patients a genetic change is not evident through DNA sequencing. In this research project, we are using RNA sequencing to search for and identify abnormal splicing events that may be due to splice-altering variants in the genome of previously undiagnosed patients. Splicing occurs naturally in unaffected and affected individuals; it is the process of introns being removed from mRNA transcripts and exons being joined. The process of RNA sequencing allows us to discover abnormal splicing errors by looking at splice junctions, which are sites on the intron and exon border where splicing normally occurs. We search for abnormal splicing defects using RNA sequencing by comparing the splice-junctions from our patients to a reference database of healthy controls (Genotype-Tissue Expression Project), filtering out common splice junctions, allowing us to identify unique and abnormal splice junctions. If we identify abnormal splicing, we will also investigate the genome of the patient to determine whether there is an underlying DNA change. Using RNA sequencing, we hope to provide a genetic diagnosis for a subset of our undiagnosed patients and for more individuals affected by DEE in the future.

Traumatic fracture of the bone surrounding the eye (the orbit) can result in functional impairment of vision. Double vision, diplopia, is one such sequelae. The cause of diplopia in orbital fracture patients has most commonly been attributed to loss of orbital volume caused by an open fracture that allows the contents of the orbit to shift. However, in cases where the orbit is surgically repaired and orbital volume is restored, some continue to have diplopia. Our hypothesis in these cases is the anatomy of extraocular muscle pulleys is affected by the trauma. The aim of this study is to test this research question by analyzing computed tomography (CT) scans. Patients were selected from a previous study of orbital fracture patients in which all patients had CT scans available for review and consented to be part of a research study on orbital fractures. Locations of the extraocular muscle pulleys were measured relative to the center of the orbit in the lateral, anterior and superior directions. Pulley location was determined by a tangent plane drawn where the optic nerve meets the orbit and crosses the muscle. The measurements were input into Orbit, simulation software, to produce a prediction of visual changes in Lancaster plots. The Lancaster plots were compared to the data from the patient’s clinical visual testing to determine the accuracy of the prediction at each point in the visual field. Our results showed that the accuracy of our prediction varied, as the location of the pulleys is not the only factor that contributes to diplopia. Other factors that may contribute include weakened muscle, entrapment and damage that is not visible on CT. More research is needed to determine how the muscle pulley system is affected in orbital fracture, and to determine how clinical interventions including surgery may help improve diplopia.

At present, there is a disconnect between people’s awareness of environmental crises and their motivation to act on this knowledge. Novel ways of fostering a sense of connection with the environment are currently being explored to address this problem. Dance, among other artistic disciplines, has the potential to motivate pro-environmental actions because it appeals to people’s emotional centers through empathy-inducing experiences, community building, and non-traditional communication. Using members of the Seattle dance community as a case study for environmental dance, this research explores whether and how environmental activism through dance is manifested in Seattle, if barriers exist to engaging in environmental dance, and if current forms of environmental dance effectively motivate action. To execute this exploration, I will conduct several one-on-one semi-structured interviews with members of the local dance community; interviews will last between 0.5-2 hours. Interviewees will be selected to represent varying degrees of participation in environmental dance--from minimal to explicit environmental dance activities--and will include internationally recognized dance creatives to rising entrepreneurs. These discussions will inform a qualitative analysis of how dance has or has not been used as tool for promoting environmental action locally. Furthermore, they will provide the context for my own choreographic pursuits on environmental dance. Based on relevant research and my 10+ years of involvement in the Seattle dance community, I predict that environmental dance can be identified as choreographic productions, site-specific explorations, embodied knowledge, sustainable practices in the arts, and collaborations between scientists and dancers. The results will be communicated to a performing arts audience through creative demonstrations of key research findings and through excerpts of my choreography. I hope, by engaging with both the environmental science and dance communities, to promote a dialogue within and between these communities and to inspire further environmental dance endeavors beyond the scope of Seattle.

Multiple studies have demonstrated an association between a long-term exposure to air pollutants and health outcomes in area of cardiovascular and respiratory diseases. However, there is suggestive, but insufficient, evidence linking the association between long-term exposure to air pollution and mental health outcomes, such as depression. In South Korea, a nationwide population-based, cross-sectional study investigated the relationship between long-term exposure to ambient air pollutants and mental health status. The study of 124,205 participants found a positive associations between Particulate Matter (PM10 and PM2.5 ), Nitrogen Dioxide (NO2), and Carbon Monoxide (CO) exposures and mental health status. The goal of this study is to determine whether the air pollution-depression relationship holds true in the ACT (Adult Changes in Thought) cohort by conducting a similar study to the cross-sectional study conducted in South Korea. In this study, I will consider air pollutants (PM2.5 and PM10) as exposure and depression as a measure of health outcome. The central working hypothesis of this study is that higher levels of PM2.5 and PM10 will be associated with an increase in CES-D (Center for Epidemiologic Studies Depression) score. Participants from the ACT cohort (members of the Kaiser Permanente in Seattle, Washington) who had an ACT study visit between 11/1/2000-4/1/2003 will be the study population. The primary analysis aims to evaluate the association between PM (PM2.5 and PM10) and CES-D scores using linear regression model after adjusting for age, sex, smoking, income, education, cardiovascular disease, and cerebrovascular disease. The secondary analysis aims to evaluate the effect modification of age, alcohol history and early vs. late onset of depression has on this association. It is hoped that the results from this study will expand our understanding of the relationship between air pollution and depression.

The receptor human protein kinase EphA2 has emerged as a therapeutic drug target for cancer and infectious diseases. However, the dearth of selective EphA2 inhibitors in the field is hampering EphA2-based research and therapies. Our lab recently developed a novel selective small molecule EphA2 inhibitor I268 using medicinal chemistry. Surprisingly, we observed the same inhibitory effects on cell proliferation paradoxically when inhibiting EphA2 with I268 or activating EphA2 with its agonist EphrinA1. We hypothesized that both I268 (inhibitor) and EphrinA1 (agonist) may lead to the same protein-protein interaction network of EphA2 that caused this paradoxical inhibition. We used a chemical proteomic method developed in our lab called “co-clickable precipitation (Co-CP)” to study the interaction network of EphA2 in colon cancer cell line HCT-116. We observed that the onset of inhibitory effect by I268 concurred with the association between EphA2 and a protein interactor called c-RAF, a key player in activating proliferation pathways in cancer cells containing Ras mutations such as HCT-116 cells. We are currently performing confirmatory experiments to characterize whether upon inhibition by I268 or activation by EphrinA1, EphA2 sequesters c-RAF in a form unable to transmit proliferative signals downstream. Our results may demonstrate a possible mechanism for inhibitory effects of EphA2 inhibition on cancer cell growth. These results validated EphA2 as a drug target and may provide novel ways for treating cancer cells by inhibiting cell proliferation pathways indirectly using EphA2 inhibitors.

Young adults are susceptible to a whole range of psychological disorders. Approximately 39.6% of young adults (ages: 18-25) in the United States have had a heavy drinking episode in the past year, and 9.6% of young adults have had a major depressive episode in the past year. Previous research has shown that young adult males tend to drink more alcohol, while females have higher rates of anxiety and depression. There is, however, limited research about the extent to which certain groups of young adults, based on living situation and college enrollment, may exhibit higher alcohol use and poorer mental health. The purpose of this research is to examine differences in alcohol use, alcohol-related consequences, and mental health by demographic characteristics (i.e. attending 4-year college or not, living with parents or not, biological sex) among a community sample of young adults (ages 18-23). Analyses use baseline data (N=764; 55.9% female, mean age 20.6 (SD = 1.72) from a larger longitudinal study on health behaviors. Outcomes will be alcohol use, alcohol consequences, depression, and anxiety. Separately for each outcome, an analysis of covariance (ANCOVA) will be conducted. The sample includes 352 4-year college students and 412 individuals not attending a 4-year college, 468 individuals not living with parents and 296 individuals living with parents, and 428 females and 336 males. We hypothesize that higher alcohol use and consequences will be found for males, individuals not living with parents, and individuals enrolled in a 4-year college. We also hypothesize poorer mental health for females, individuals not living with parents, and individuals enrolled in a 4-year college. Results from this study will provide a better understanding of which young adults are experiencing poorer mental health and higher alcohol use, thus providing valuable information to guide interventions.

Neutrinos (and their antimatter counterparts, antineutrinos) are some of the most mysterious particles in physics. Their masses are unknown; it is not even known which type is heaviest. Learning about neutrino mass might give clues about physics beyond the Standard Model. The Project 8 experiment is developing a new way to study neutrino mass called Cyclotron Radiation Emission Spectroscopy (CRES). Measuring the energy spectrum of the electrons emitted in nuclear beta decay can put an upper limit on the neutrino mass. In CRES, the electron’s energy is measured by observing the cyclotron radiation emitted by the electron as it accelerates in a magnetic field; because of a special relativistic effect, this cyclotron frequency depends on the electron’s kinetic energy. A radiofrequency detection system collects, measures, and digitizes information about the cyclotron radiation, and a Project 8 analysis software package called Katydid processes the data to distinguish electron signals from noise and extract the measured cyclotron frequencies. However, many electron signals are comparable in power to noise, which can lead to missed signals and errors in frequency reconstruction. This work aims to quantify the systematic effects of variations in signal properties on measured cyclotron frequencies. We use a Project 8 software package called Locust to create simulated electron signals and noise. We vary the signal-to noise ratio (SNR), and “slope,” which here is change in cyclotron frequency over time, of the simulated signals. We then measure how these variations affect Katydid’s efficiency in finding signals and its accuracy in determining their frequency. These calibrations will make it possible to quantify uncertainties in Project 8’s ongoing experimental observation of the spectrum of electrons emitted in the beta decay of tritium.

National calls have been made to strengthen our nation’s STEM workforce by improving preparation and increasing graduation rates. At Portland State University (PSU), Oregon’s largest urban university, over 60% of students transfer from community colleges and the large majority do not live on campus. Transfer students may perceive a loss of support and a drop in GPA during their first term post-transfer, elements of what is known as “transfer shock.” As part of a newly-awarded NSF S-STEM grant, we aim to measure if high-impact STEM support programs can mitigate factors related to transfer-shock and support student sense of belonging. Direct impacts of the S-STEM program are being assessed qualitatively (e.g. focus groups, reflections), and preliminary results for our first cohort of S-STEM Scholars indicate strong bonds among the cohort and feelings of success. To examine how students supported by the S-STEM and other high-impact STEM programs compare to other PSU STEM students, a survey measuring self-efficacy, scientific identity, scientific values, STEM involvement, and sense of belonging was broadly disseminated to students in Fall 2018 and will be repeated in Spring 2019. Initial survey results (n=933) allow us to compare student responses for students supported (n=93) or unsupported (n=840) by programs such as the S-STEM. We will also compare traditional four-year students (n=291), community college transfer students (n=398), and four-year college transfer, returning, and post-baccalaureate students (n=240). Preliminary results indicate that students supported by high-impact STEM programs such as the S-STEM report significantly higher sense of belonging, both at PSU and in STEM groups. Efforts implemented by the S-STEM program to improve STEM student experiences academically, financially, and socially, particularly to the most vulnerable populations, will ultimately improve and diversify the STEM workforce.

According to the NIH, 76.2 million Americans have suffered from pain lasting more than 24 hours, with millions more affected by chronic pain. With such a high prevalence and impact on health and quality of life, the understanding of pain is essential to effective treatment. Exploring the mechanism by which our neurons set the gain for what is perceived as painful stimuli is one way to further that knowledge. Different populations of neurons have different thresholds for activation, and oftentimes alterations to these thresholds can result in aberrant pain signaling. Phospholipase C (PLC) is a promising target to study, as it has been previously shown to potentiate the activation of pain neurons expressing Transient Receptor Potential cation channel subfamily A, member 1 (TRPA1). TRPA1 channels are responsive to noxious stimuli such as mustard oil (AITC). This study explores the effects of PLC using a PLC activator (m3m3FBS) and an inhibitor (U-71322) to examine its role in response to the noxious stimulus, AITC. We performed a locomotor assay of zebrafish larvae to explore behavioral effects, as well as neuronal imaging experiments using transgenic zebrafish with fluorescent calcium indicators in neural cells. We hypothesize that both behavioral responsiveness to pain and neuronal recruitment will likely increase with activation of PLC and decrease with deactivation of PLC because of PLC’s ability to modulate TRPA1 channel activity. With data collected thus far, the results look consistent with our hypothesis. We observed increased locomotion in response to activation of PLC with painful stimulus (AITC) compared to control and inhibitor groups. Likewise, zebrafish exposed to PLC activators exhibited greater numbers of AITC responsive neurons than zebrafish exposed to control or PLC inhibitors. Together, these results indicate that PLC is an important factor in modulating the sensitivity of TRPA1 expressing neurons.

In microbiology, matrix-assisted laser desorption/ionization time of flight (MALDI/TOF) is a method used for the identification of a wide variety of micro-organisms such as bacteria or fungi directly from the selective medium used to isolate them. The technique uses laser energy absorbing matrix to create ions from proteins with minimal fragmentation. It is a three-step process where first, the microbial sample is mixed with suitable matrix material and applied to a metal plate. Second, a pulsed laser irradiates the sample, triggering ablation and desorption of the sample and matrix material. Finally, the analyte molecules are ionized in the hot plume of ablated gases and accelerated into the mass spectrometer. The mass spectra generated are analyzed and compared to stored profile using a dedicated software. Species diagnosis by this procedure is much faster, more accurate and cheaper than other procedures based on immunological or biochemical tests. Consequently, MALDI/TOF is becoming a standard method for species identification in medical microbiological laboratories. Bacteroides fragilis and Escherichia coli are two bacterial species that MALDI/TOF can accurately identify directly from the media they are growing on. Certain strains of enteropathogenic B. fragilis and E. coli ETBF and EPEC respectively, cause severe enteric disease manifesting by watery diarrhea and colic. On the other hand, non enterogenic strains of B. fragilis and E. coli such as NTBF and DH5 alpha are completely benign. Using MALDI/TOF technology and virulent and non-virulent strains of B. fragilis (BFT and BFT) and E. coli (EPEC and DH5 alpha), we hypothesize that a correlation between peaks and virulence proteins can be made conferring to MALDI/TOF the potential to predict virulence of bacteria based on the expression of proteins mediating virulence.

ovine Leukemia Virus (BLV) is a disease that affects US beef herds and large-scale dairy herds. A recent studied found correlations to the presence of BLV particles and human breast cancers. Although no actual retroviral insertion (zoonosis) was found in tissue samples, this raises concerns about BLV consumption in from infected dairy samples. To investigate this phenomenon, the prevalence of BLV from raw dairy milk samples will be analyzed. Western blotting will be used to look for the major reactionary viral glycoproteins, gp51 and gp24. Controls were designed for blotting to subclone the coding region of gp51 or gp24 into bacterial expression vectors from a plasmid containing the entire bovine viral genome. Subcloning and quality assays were confirmed first by restriction digestions, PCR then also will be sent for sequencing. The expressed glycoproteins along with infected cell culture samples will then be used in blotting procedures as positive controls while analyzing raw milk samples collected from farms.

Plants take up silica over the course of their lives along with other essential nutrients in the water that they absorb through their roots. The silica becomes deposited within their tissues in the form of solid bodies (phytoliths); when the plant dies and decays, phytoliths are left in the soil where they can fossilize. Fossil phytoliths preserve the original morphology of plant cells and can be used to reconstruct past vegetation. The Middle Miocene Climatic Optimum (MMCO) was a major global warming event that happened ~17-14.5 million years ago. Researcher have reconstructed the climate of the Santa Cruz Formation in Patagonia, Argentina during this period as warmer and drier. While we would expect the vegetation to become more open (i.e., grassy or shrubby versus forested), phytoliths from the Santa Cruz Formation tell a different story; in particular grass phytoliths (and therefore grass abundance) seem to decrease through time, but also become smaller. Some researchers have noticed that grasses tend to respond to reduced water availability with reduced cell size. Therefore, we hypothesize that the reduced size of grass phytoliths observed in the Santa Cruz Formation during the MMCO is due to increasing aridity. However, because this trend of decreasing cell size was only noticed by qualitative observation, we need to quantitatively assess significant changes in cell size. To do so, I studied and imaged grass phytoliths under a microscope, categorized them by subfamily/tribe based on their shape, and measured their size. I then statistically compared the phytoliths from younger and older strata to test whether there was a change in size through time. This work will be used to predict how our current global warming event may impact plant life based on the trends of the past.

In Possession Sound, a salt wedge estuary in the Whidbey Basin in Northwest Washington State, interactions between the saltwater of Puget Sound and the freshwater of the Snohomish River create a dynamic environment. Students from the Ocean Research College Academy deployed two Sea-Bird Conductivity-Temperature-Depth (CTD) probes within the estuary to monitor water chemistry in this complex system. A grant from the National Science Foundation supported eleven students to analyze water chemistry data from summer 2018 to increase their understanding of biogeochemical processes in the estuary and communicate their knowledge to the general public. Data from the month of May were analyzed to investigate the river’s influence on the temperature and salinity. Lower levels of salinity correlated with peaks in freshwater input as indicated by river discharge data. Salinity also correlated with tide height. To further investigate the spatial influence of the Snohomish River on Possession Sound, this study endeavored to manufacture a Fast Oceanographic Automated Measurement (FOAM) sampler in collaboration with Gravity Consulting. This device uptakes surface water and pumps it over an EXO 2 Sonde to measure surface water chemistry while traveling on a research vessel, associating data with GPS points, to track the freshwater plume. Salinity was used to examine the relationship between the spatial extent of the plume, river discharge, and tidal patterns, and temperature and pH was analyzed to explore the influence of the river. Lower salinity levels were used as indicators of higher freshwater influence. During periods of high river discharge, average salinity values will be lower and the freshwater influence will cover a larger area. During high tides, higher average salinity values are expected and there will be smaller areas of freshwater influence. It is hypothesized that areas of higher river influence will be warmer and more acidic than areas of increased saltwater influence.

Methane reservoirs are commonly found throughout the world’s oceans and the release of methane from seafloor reservoirs is thought to make up 5 to 10% of the global atmospheric methane. In fact, the greatest deep-sea mass extinction in the last 97 Myr during the Paleocene-Eocene Thermal Maximum (PETM) may have been caused by methane release from seep sites along the upper continental slope margin. Recently, methane reservoirs along this margin have been gaining attention due to their potential to accelerate current global warming. Changes in seafloor pressure and temperature could destabilize these seafloor deposits and cause methane bubble plume release into the ocean. At SHR, an extensively studied active seep site located ~ 90 km offshore Oregon, discontinuity in methane plume release was observed, but still not well understood. Hence, using Acoustic Doppler Current Profiler (ADCP) and pressure data archived by the Ocean Observatories Initiative (OOI) Cabled Array, we are investigating the potential correlation between tides and the presence of methane plume at SHR. Our study detects methane plume structures based on the proxies of echo contrast caused by acoustic-bubble interaction. By analyzing the derived plume structures and their correlation with 226 tidal cycles, we expect a trend of plume release triggered by low tides. Our study provides the first high-temporal-resolution analysis on the methane plume release at SHR using OOI acoustic data. 

Located in the Whidbey Basin of the northern reaches of Puget Sound, Possession Sound contains the Snohomish River estuary, encompassing a river system that is the third largest contributor of freshwater to the Puget Sound. Myself, and several of my fellow students have had the opportunity to collaborate with the University of Washington, the Washington State Department of Ecology, and a local environmental consultant -- Gravity Marine. Utilizing data collected by permanently moored Sea-Bird CTD probes, during research cruises, and by the United States Geological Survey (USGS), my research partner and I have created a model to facilitate an investigation of how both tides and the discharge of freshwater from the Snohomish River influence the water quality of Possession Sound. To better understand the complex patterns of the water entering Possession Sound from the Snohomish River, we analyzed the relationship between a continuous stream of water quality data (temperature, salinity and turbidity) from a Sea-Bird CTD probe at the mouth of the Snohomish River and continuous discharge data gathered by the USGS at a station 12 miles up the river. The distance between these two sites results in a delay between when river discharge data is recorded up river and when it influences the water quality at the river mouth. From the analysis of these two locations and with guidance from ourcollaborators as well as outside professionals, we used the statistical analysis language R to create a model that predicts the travel time of water from the USGS stream gage to Possession Sound. This model can be applied when considering the effect on the estuary of important factors from the river, such as nutrient loading; influxes of cold water, which promotes upwelling; and the river’s contribution of heavy metals and other pollutants.

Recent studies have shown just how important microbiomes are for individual health, population health, and environmental health. Unfortunately, these studies are often limited by the costs of meta-Genomics. Furthermore, meta-Genomic data itself is limiting by only providing information on population characteristics, but not the functional contributions of members within the population. Single cell transcriptomic sequencing aims to lessen the latter issue by providing information on the gene expression of each individual cell within a sample. Even so, current single cell sequencing technologies are costly and require specialized equipment. SPLiT-seq is a single cell transcriptomic technology developed by the Seelig lab at the University of Washington that uses split-pool ligation to create uniquely barcoded cDNA for each cell using every-day laboratory bench tools and techniques and costs only one cent per cell. Currently, SPLiT-seq is well-optimized for mammalian cells. However, using this method on bacteria requires its own set of optimized procedures given the morphological and biochemical differences between eukaryotes and prokaryotes. The aims of this project are to deal with these biological differences to increase the information obtained from messenger RNA and decrease the amount received from ribosomal RNA, as well as reduce the amount of cells that get the same cDNA barcodes. By optimizing this single-cell transcriptomic technique for bacteria, future studies involving microbial communities will be able to obtain more robust information on the individuals within those populations.

Gull species in the genus Larus differ in breeding range, habitat use, size, and feeding behavior. During their post-breeding season, however, many species of gulls gather and temporarily occupy the same sites and habitats. Although there is evidence of niche partitioning by gulls in northeastern North America and northwestern Europe, the mechanisms by which gulls coexist in the San Juan Islands of Washington state are poorly studied. To investigate gull coexistence on San Juan Island, WA, we studied the intertidal feeding ecology of Mew Gulls (Larus canus), California Gulls (L. californicus) and Glaucous-winged Gulls (L. glaucescens). Patterns in abundance, behavior, substratum-use, and large prey type (identifiable through spotting scope) were investigated through observational methods at Jackson Beach. Pairwise chi-square tests revealed significant differences in large prey type and substratum use between California and Mew gulls and between California and Glaucous-winged gulls. Patterns in frequency of large prey captured illustrate differences in prey selection among species, with Mew gulls capturing primarily worms, California gulls capturing primarily fish, and Glaucous-winged gulls demonstrating generalist foraging behavior. These findings suggest that during foraging, the gull species use shared habitat differently by specializing in different large prey types. This supports previous evidence of niche partitioning among gulls, and suggests that niche partitioning reduces competition among gull species in the San Juan Islands.

Research has shown transgender children respond similarly to categorical measures of gender identity as their gender-matched cisgender peers, rather than those who share their sex assigned at birth. However, categorical measures may be limiting responses and not encompassing the diversity of gender identities. We presented a continuous measure to 223 transgender children (socially-transitioned children to live and present as a gender opposite the one assigned at birth), 71 gender nonconforming children (children who have not socially transitioned but show characteristics stereotypically associated with a gender other than the one assigned at birth), 281 cisgender control participants, and 181 cisgender siblings of transgender and gender nonconforming participants. Provided a line, participants were asked to mark their gender identity, with the left-most end indicating feeling completely like a boy, the right-most end indicating feeling completely like a girl, and in between representing varying degrees of a mixture of both. Each participant’s mark was converted to a percentage, with 100% indicating feeling completely like the gender they present as (for transgender/gender nonconforming children, opposite the gender assigned at birth). A univariate ANOVA examining the effect of participant group on identity showed a significant main effect, F(3,752)= 38.72, p < .001. Post-hoc Tukey comparisons showed, consistent with previous research, transgender children (M=0.81, SD= .189) did not differ significantly from the cisgender controls (M=0.87, SD= .181), nor cisgender siblings (M=0.87, SD=.206), in their identification with their current gender. However, gender nonconforming participants (M= 0.59, SD = .309) differed significantly in their scores from each of the other groups (ps < .001). These results are consistent with previous research conducted with categorical measures. Additionally, as none of the groups showed 100% binary identification, this study also demonstrates the importance of continuous measures of gender identity within gender development research.

Within the past decade, scholarly and media attention regarding the “homelessness crisis” across the country has increased. However, recent developments in the field have problematized much of the previous research done on homeless identity, due to the fact that “homelessness” has been treated as an unambiguous defining characteristic of the individual. Past research relied on the assumption that these individuals saw themselves as homeless upon entering a state wherein they were without stable housing. Contemporary research seeks to revisit the conceptualizations of homeless identity, and this project will investigate how individuals without shelter, or at risk of being without shelter, come to define their situation and identify themselves -- as “homeless” or otherwise -- in relation to that status. This study focuses primarily on homeless identity as self-acquired, rather than ascribed, by researching an understudied group: homeless young adults. Studying identity within the dynamic frame of emerging adulthood provides a suitable environment for understanding identity development and adoption. This project utilizes ethnographic interview techniques conducted with individuals aged 18-25 with a range of time spent homeless. Analysis of these interviews seeks to examine key mechanisms in negotiation between socially-ascribed identity and self-acquired identity among homeless individuals, and to shed light on the mental reasoning that informs such a process. By determining how and why people come to see themselves as homeless, this research project will inform modes of early-intervention social service outreach while simultaneously complicating traditional lenses of viewing and researching homelessness.

My research topic is on Black student-athletes’ classroom experience at predominantly White institutions. As a Black student-athlete myself, I have been in classes where not only am I the only Black student, but the only Black student-athlete. The research shows that Black students are primarily affected by their perceived ability to succeed in college by the lack of Black representation in amongst their peers and professors, in the classroom. In my thesis, I build upon aspects of UCLA scholar, Tyrone Howard’s view of the critical race theory. In particular, I explore the idea that rather than race being biologically grounded and natural, it is socially constructed and functions as a means to maintain the interests of the White population. My thesis argues that Predominantly White Institutions set the “lay of the land” in terms of what is socially acceptable and deemed okay, and which often excludes Black student-athletes. The methods I use are surveys, individual interviews, and a focus group,  with an equal number of of Black men and women study participants. This qualitative data will show that Black student-athletes’ experience in the classroom at predominantly White institutions is directly related to whether they grew up being around White individuals.

My proposed research examines how sexual racism is experienced by LGBTQ+ community members in the greater Seattle Area who use Tinder and Grindr and other mobile dating apps. Sexual racism can be defined as a specific form of racial prejudice enacted in the context of sex or romance. My primary research investigates a series of in-person interviews that qualitatively analyze and articulate the various experiences of Black individuals, as well as focus groups to help to understand different and diverse manifestations of sexual racism. I use information/narratives from the in-person, and one-on-one interviews to analyze the experiences and compile them into a data set that can be closely looked at for trends and overlapping experiences. My research analyzing the effects of the experience of sexual racism as shown through mobile dating apps helps readers understand one form of inequity in our modern digital society that often goes unspoken. In addition, my research helps to identify how microaggressions work by the microagressor’s dismissing their racialized/sexualized comments as simply an issue of personal preference. While my primary research focuses on sexual racism in local communities, my secondary research draws on literatures that examine sexual racism both nationally and internationally. By working closely with a variety of people in the local community as well as drawing on research from other scholars focusing on the ideas of white privilege, constructed racism, and intersectionality, this research helps me speak up for Black LGBTQ+ individuals who are often marginalized by sexual racism.

 Individuals who have experienced armed conflict at some time in their life span up to the millions. Whether its domestic violence, PTSD or war. A small body of research has been conducted to understand self-image and the well-being of survivors of armed conflict. However little is known about the effects of armed conflict on social behaviors and the perception of social relationships. This research is based on interviews and ethnographic data from forty South Sudanese refugees living in Rhino camp, Uganda. Using interviews and qualitative methods this research addresses how armed conflict affects trust of others and social relationships. Key insights from this research will allow us to understand how armed conflict experiences impact one’s perception of social relations and how different genders view this same idea. This research addresses social behaviors and perceptions of social relationship which is an important aspect of health, well-being and survival.

High psychological resilience has been significantly linked to better medical recoveries, psychological recoveries, and resistance to psychological deterioration. Currently, many African American grandmothers are engaged in emergent childcare due to serious family trauma. I have identified key aspects of the lives of these women which are relevant to their resilience through a literature review, personal cultural experience, and focused interviews. This preliminary research informed my creation of a theoretical model relating resilience to faith, music, and justice. Utilizing thoroughly tested psychological measures which correspond to each aspect of my theoretical model, I am performing a pilot study to determine the strength of the relationships between all four of these constructs. More frequent, and deeply shared, music experience within a family is anticipated to covary with higher scores of resilience. This is due to shared emotional experiences fostering positive attachment amongst the family members. Also, stronger perceptions of injustice as well as doubt in one’s faith are both expected to negatively correlate to one’s resilience. If a person expects the world to unjustly not return their efforts or expects their personal coping techniques to fail, they will be less likely to utilize these avenues. Immediately, I am returning my findings to support groups for grandmothers and, under the guidance of a psychiatric professor, also sharing general information about resilience. Findings from this pilot study will guide future experiments to determine how best to support grandmothers, concerning resilience. Information yielded by larger scale research of this type will inform the development of fast, inexpensive, culturally appropriate, and non-invasive techniques for detecting individuals with low resilience.

This project aims to influence the next generation of flying robots by first studying how moths use multi-sensory information to increase their agility. These different types of multi-sensory information include visual- and touch-based feedback, which are influenced by forces such as those from flapping wings and changes in body posture (which affect a moth’s inertial distribution). In addition, flying insects are known to control orientation via torques arising from at least three distinct affordances: by varying aerodynamic center of pressure, by changing body posture to alter center of mass location, and by swinging body segments or limbs to harness inertial torques. We hypothesize that these sources of control are integrated in parallel to increase robustness and agility, are weighted according to behavioral context, and are tuned to body morphological parameters. To investigate this flight behavior, we first built a test apparatus to apply rapid pitch movements to a tethered flying moth, Manduca sexta, while having a minimal effect on a moth’s inertia and natural flight patterns. This system allows us to measure the torque exerted by the moth’s flight forces and body movement. Closing the loop between measured torque and applied movement enables control of the forces experienced by the moth. Projected video is used to simulate a changing environment and create a haptic-type interface for the moths. The video can provide a visual experience to either match the mechanosensory experience or provide sensory conflict (i.e. a mixed reality environment). The next engineering challenge is to design and build a system to electronically control and monitor the motion of the moth. After this, cameras and sensors will be used to record data that will contribute to a more realistic understanding of how the principles of animal flight can be used in robotics.

Myanmar has been enveloped in seemingly endless civil strife since their independence from British colonization in 1949. The country is comprised of a wide array of ethnic minorities, each with their respective language and culture. Myanmar’s government may publicly announce its pride at the country’s diversity, but within, human rights violations committed by the military abound. The peace process towards a federalist state is long and hard, and has seen many cycles of ceasefires and armed conflict. My time in Thailand during CHID’s Gender, Peacekeeping and Human Rights program addressed this conflict from a myriad of perspectives. As a result, I have learned about the silent heroes of Myanmar’s peacekeeping process: the community based organizations that are actively changing the power landscape of rural areas within the ethnic minority states. There are several community-based organizations operating from the Thailand-Myanmar border that are addressing and spreading awareness of the human rights violations inside ethnic states. Most importantly, they are addressing maternal and child health in high risk areas where maternal mortality rates are some of the highest in the world. Through meetings and interviews with various community-based organizations, I am exploring the relationship between family planning and maternal health programs on the ground and women’s participation in the peace process in the country overall. I am also using content analysis of reports done by the organizations, who have obtained valuable, on the ground data from remote areas within Myanmar. I am interested in whether investing in these programs and supporting this communtiy-based approach could be one possible solution to creating multilateral agreements that last in Myanmar because of the additional involvement of women in politics and leadership.

Here at the University of Washington we are characterizing one ton of NaI[Tl] crystal scintillator detectors for use in the COHERENT project. NaI[Tl] scintillating crystals detectors work by producing photons from the kinetic energy of charged particles passing through the scintillating material. COHERENT aims to detect coherent elastic neutrino-nucleus scattering, a novel interaction between neutrinos and matter that was first observed less than two years ago. It employs a large scale of scintillator detectors in order to record these events at an appreciable scale. Our characterization campaign allows us to group crystals with similar outputs by voltage which will determine the setup of our detectors once at ORNL. During this characterization, the crystals exhibited behaviors that correlated with the ambient temperature of the lab. The temperature dependence was first noticed during voltage gain characterization tests taken at different times of the day in the uncontrolled temperature environment of our lab. We expect the gain of our crystals to fit to a curve function, which breaks down if data is taken at different times of the day. The goal of this study is to understand the impact of temperature dependencies on our characterization campaign, and in particular to derive a relationship between voltage gain and temperature. I will present the data gathered toward this goal, and also our larger body of data on the relationship between light yield, voltage gain, peak resolution, and waveform rise time, as well as the techniques used to re-characterize previous crystals gain curve based on the derived relationship from this study.

High purity germanium (HPGe) detectors are an important technology in several leading experimental searches for dark matter and neutrinoless double beta decay. Understanding the interaction of various types of radiation on the different surfaces of HPGe detectors is essential to developing methods to reject unwanted signals from radioactive background sources. I have taken a leading role in the construction and use of the Collimated Alphas, Gammas, and Electrons (CAGE) test stand at the University of Washington, whose goal is to evaluate the response of an HPGe detector to different types of radiation on its various surfaces. CAGE is a vacuum cryostat with an internal system of motors that move a radiation source while keeping the detector active. It requires the operation of a liquid nitrogen cryostat, vacuum pump, temperature sensors, and various radioactive sources, all of which must be integrated into a single data acquisition (DAQ) system. We are currently constructing this system, fabricating and installing parts, and are planning to take initial data with the HPGe detector in the summer. In this talk I will present the current status of the CAGE detector, as well as preliminary data from radiation signals in the detector.

Mutation produces new variation in populations, and in each generation these variants are copied from parents to offspring. While almost all variants of genes are lost, they may remain in the population for many generations. We use branching process models to analyze counts of gene copies. In a population of constant size, on average, a gene copy produces one offspring copy at the next generation. An advantageous mutant will have a mean greater than 1, and a deleterious one will have a mean less than 1. It is thought that most mutations are slightly deleterious, and with high probability those variants become extinct rapidly. Nonetheless, the few deleterious mutants that are not yet extinct may achieve high numbers. Thus, we have a particular interest in those with a mean slightly less than 1. We use different probability models for the offspring distribution and consider the mutant’s survival about: the extinction probability over k generations, the expected copy count conditional on survival, and the probability of survival additional k generations conditional on surviving k already. We find that variances in addition to means of offspring distributions closely relate these statistics. By adjusting parameters of distributions, we let the mean and variance be approximately the same across distributions. Based on our simulations, when k is large and the mean and variance of offspring are the same, the mutant’s survival condition is uniform throughout. In other words, those statistics above can be estimated by the mean and variance exclusively, and the specific distribution does not affect much the conditional population dynamics. However, at the first few generations, these statistics are different for each distribution. Thus, if we know the mean and variance of a mutant, we can predict the long-term population behaviors conditional on survival without knowing the true distribution of the mutant.

Orbital fractures are one of the most common facial fractures and often result in functional deficits if not treated appropriately. No prior reports have assessed dynamic visual acuity (DVA) in these patients, which is critical in visually tracking objects during head movement. Our research seeks to determine the effect of orbital fractures on DVA and assess whether DVA will change over time in those who undergo surgical reconstruction of the orbit. We hypothesize that DVA is adversely affected in orbital fracture patients and improves after surgical reconstruction. We designed a prospective pilot study at a Level I trauma center. Adult patients who presented with an orbital fracture between November 2017-January 2019 without prior ocular history were eligible. All enrolled subjects underwent static visual acuity (SVA) and DVA testing twice: once within one month post-injury before surgery, and another at least ten days following surgery. SVA was assessed using a mobile Snellen eye chart. DVA was measured by having the subject rotate their head at a standard frequency while again reading a Snellen chart. DVA is defined as abnormal if acuity falls more than two lines on the Snellen chart compared to SVA. Eleven patients have been enrolled and tested. Four(36%) patients exhibited abnormal DVA prior to surgery, compared to two(18%) after surgery. For all patients, the mean change in visual acuity (DVA logMAR minus SVA logMAR per subject) before surgery was 0.17 (SD=0.09). Following surgery, the mean difference in visual acuity across all patients was 0.07 logMAR (SD=0.07). Our data shows that, surprisingly, the majority of orbital fractures patients tested did not have abnormal DVA. In patients that did demonstrate abnormal DVA, half improved after surgery. The mean difference in visual acuity of all patients also improved after surgery. A larger study is needed to determine the prevalence of abnormal DVA in this patient population.

It has shown that there are higher death rates with individuals with darker skin types due to lack of diagnosis based on wording of skin sensitivity surveys. In the realm of research and dermatology, the Fitzpatrick Skin Type (FST) scale has been the gold standard of measurement to classify sun sensitivity for human’s skin. More research of the subject is necessary but it is important not to underestimate the impact of UV exposure and exclude a portion of society. It is the scope of Study 3 to reword part of the survey for cultural awareness as well as introduce an objective source of measurement using photospectroscopy. It is important to include these groups that have been discounted in prior studies. Some of the language has been utilized in prior research and it was an attempt of this study to improve on the language used. Participants were asked to complete a brief self-report skin type survey prior to measurement of skin melanin using a reflectance photospectroscopy device. The areas measured were dorsal and ventral wrist area and ventral upper arm area. The results correlate well with the subjective and objective components. Improvement will be paramount to future research in this project as we aim to bring this group to understanding what might be necessary in the future design of this project and how a statistically significant correlation can bring us closer to asking the pertinent questions that help people determine their skin types. We hope to design a replicable and accurate way to categorize skin type which will be able to deliver the most accurate sun exposure behaviors.

Drinking water is essential in a person’s everyday life. However, not everyone has access to clean drinking water. This research explored the societal, economical, and environmental issues that are involved in helping a small system deliver clean and safe drinking water. The nearby community of Rollinsford, New Hampshire, was studied and worked with to help understand their issues and solve Rollinsford’s problems. As a small community that has approximately 2,600 people, Rollinsford wrestled with many challenges. Such as a need for optimization of their existing corrosion control due to recent lead and copper rule violations. This research explored the challenges faced by Rollinsford on an everyday basis. By expanding their website to include the latest information on lead and copper as well as answering their frequently asked questions, the community better understood the challenges it faced. To develop the best possible economic and environmental options for Rollinsford’s drinking water, we established a direct partnership with the town water facility operator and assisted him with laboratory research and water analyses. People in Rollinsford may not have the information they need about their water supply and might drink dirty water that could affect them for the rest of their lives. Therefore, this research helped inform a small town and provided the knowledge and experience that can then be applied to communities everywhere.

Pollution caused by large corporations is the primary reason for environmental degradation and the prison industrial complex is no exception. The purpose of this study is to contextualize the carceral system and its relationship to climate change from a critical ecofeminist perspective. Critical ecofeminism contends that the patriarchal nature of capitalism forces women to generate forms of resistance against essentialist systems--which attributes to their broader understanding of environmental degradation and the oppression of marginalized identities. Using the Fact Sheet Archive on Women in State Legislatures (1997-2016) which reports the percentage of women-identified legislators and governors in the US, this study will explore whether or not the independent effect of mass incarceration emissions decreases when more women are represented in legislative bodies. This work is meant to contribute to growing bodies of knowledge concerning critical environment justice studies, racial capitalism, and other intersectional frameworks.

Human T-Cell Leukemia Virus type 1 (HTLV-I), a retrovirus that currently 10 to 20 million people are infected with, has been shown to be associated with the Adult T-cell Leukemia (ATLL) and HTLV-associated myelopathy-tropical spastic paraparesis (HAM/TSP). 1 After an extended period of time, 3-5% of those infected with HTLV-1 will develop ATLL or HAM/TSP. The viral Tax protein is thought to have involvement in the development of these diseases. The Tax protein inhibits telomerase and topoisomerase-I which in turn inhibits the process of DNA repair. Tax prevents apoptosis and does not allow cells to enter the G0 phase of mitosis. The oncogenic properties of Tax are correlated to the interaction of Tax with host cellular proteins which are strongly influenced by the large amount of Tax protein made from the integrated provirus. We are using viral promoter magnetic pull-downs to investigate HTLV viral-host interactions involving minimal -306bp viral promoter containing vCRE enhancer sites and Tax-recruited host proteins. Experiments have used electrophoresis to determine whether or not the magnetic beads bind the promoter DNA. Absolute quantitation is necessary for consistency and reproducibility in analysis of proteins suspected of recruitment to the promoter.

Many genes are associated with microcephaly, a condition characterized by a small head size. Through exome-sequencing, we identified de novo missense mutations in an actin polymerization gene, ARPC4, in four individuals with microcephaly, mild developmental delay, and mild intellectual disability. ARPC4 is involved in actin filament formation. Actin is an essential component of the cell’s cytoskeleton that gives the cell its structure and aids in cell movement and division. The goal of this research project is to understand the molecular mechanisms that lead to the disease phenotype observed in these patients. I began by using CADD, a measurement used to predict the deleteriousness of single nucleotide variants. The mutations identified in the patients were located in highly conserved loci, indicating they might be pathogenic. To provide further evidence of the pathogenicity of the ARPC4 variants, we were interested in determining the functional effect these variants have on actin polymerization – specifically, the role of ARPC4 in this mechanism. I established fibroblast cell lines from two patients with the same ARPC4 mutation. I performed immunofluorescence staining for actin to quantify the amount of actin present in the patients and control cell lines. Preliminary data from this experiment suggests that there is greater abundance of actin filaments in the control sample compared to the patients’ cells. To observe the effect of decreased actin abundance on cell migration, I executed a scratch migration assay. The results from this study elucidate the impact of ARPC4 in actin polymerization, and establish actin deficiency as a clinically recognizable cause of microcephaly.

Over 350 million people are affected by major depression on a global scale according to the World Health Organization with an increasing economic impact of over $210 billion annually with a growth of 21.5% since 2005. The ability to switch behaviors or strategies when faced with chronic stress is an important determinant to the susceptibility and longevity of depression within people, also referred to as cognitive flexibility. The objective of this proposed study is to analyze the effects of the endogenous cannabinoid (ECB) system on cognitive flexibility through the lateral habenula. Cannula implant surgeries will be conducted on rats to input antagonist or agonist drugs into the brain. Behavioral tests will be conducted on rats to examine whether these manipulations will promote or deter cognitive flexibility.

The nucleus is the information center of the cell, acting as a hub for DNA storage, regulation, and replication. Therefore, transport of molecules into and out of the nucleus is vital for proper biological functioning. This transport is tightly regulated via the nuclear membrane, and a collection of proteins called nuclear pore proteins that interact with molecular signals. These signals allow molecules that cannot passively diffuse through the nuclear membrane (typically greater than 60 kD) to be shuttled into or out of the nucleus via a variety of pathways. Like all biological pathways, this process can be disrupted and lead to phenotypic abnormalities. Our lab identified two siblings with biallelic variants in NUP188, a known nuclear pore protein; we identified four additional cases in three families through collaborators. Clinical features include brain abnormalities with thin corpus callosum, progressive microcephaly, severely delayed myelination; congenital cataracts; mild dysmorphic features; and hypoventilation leading to death in infancy. In order to better understand our patients’ phenotype, we are investigating nuclear import pathways as a potential mechanism of disease. Using green fluorescent protein (GFP), we can directly visualize protein localization in living cells, without the use of additional stains such as immunohistochemistry. Based on size restriction of the nuclear pore, we used a vector construct with three repeats of GFP and our nuclear localization signal (NLS). Specifically, we are investigating four main NLS pathways: Importin α+β (SV40 NLS), Kap β2 (hnRNP NLS), Importin β (CREB NLS), and no NLS. We have been able to successfully create a viral vector for each NLS. Next steps include optimizing expression in patient cell lines. This approach will allow us to quantify and visualize discrepancies between patient and control localization patterns, leading to better understanding of causes of patient phenotype and potential novel therapies.

We introduce Project Sidewalk, a new web-based tool that enables online crowdworkers to remotely label pedestrian-related accessibility problems by virtually walking through city streets in Google Street View. To train, engage, and sustain users, we apply basic game design principles such as interactive onboarding, mission-based tasks, and progress dashboards. In an 18-month deployment study, 797 online users contributed 205,385 labels and audited 2,941 miles of Washington DC streets. We compare behavioral and labeling quality differences between paid crowdworkers and volunteers, investigate the effects of label type, label severity, and majority vote on accuracy, and analyze common labeling errors. To complement these findings, we report on an interview study with three key stakeholder groups (N=14) soliciting reactions to our tool and methods. Our findings demonstrate the potential of virtually auditing urban accessibility and highlight tradeoffs between scalability and quality compared to traditional approaches.

 Developmental and epileptic encephalopathies (DEEs) are an early-onset form of epilepsy characterized by intractable seizures and severe cognitive and developmental impairment. While most genetic variants that cause DEE reside in the coding regions of genes, splice-site variants can also be pathogenic. Splice-site variants are changes in the DNA close to, or on, the exon-intron boundary, which can cause aberrant splicing, resulting in exon exclusion or intron inclusion within spliced mRNA, generating a protein that is non-functional, partially functional, or aberrantly expressed. Aberrant splicing can have pathogenic consequences, but predicting which variants near splice-sites will have an effect on splicing is difficult. I am studying three potential splice-site variants in three genes associated with DEE: SYNGAP1, SCN1B, and WWOX. I used RNA extracted from fibroblasts from three DEE patients, each with one of these variants, to confirm whether the splice-site variants cause aberrant splicing and what the predicted consequences of this aberrant splicing is on the protein. I have been able to discover the effects of the variants on splicing in WWOX and SYNGAP1. In SYNGAP1, a synonymous variant at the exon-intron junction caused an exon 4 deletion, resulting in a severely truncated protein (SYNGAP1:p.Glu120Alafs*20). In WWOX, a duplication which included exon 5 resulted in a transcript with the inclusion of two copies of exon 5, leading to a frameshift mutation and predicted truncated protein (WWOX:p.His173Glyfs*13). We are still investigating the effects of the intronic variant in SCN1B, which appears to decrease expression of the gene. We are using nonsense-mediated decay inhibitors in order to better understand the mechanism through which this decreased expression occurs. This research could potentially improve the care of these patients by providing genetic evidence of the causes of DEE, which can be the basis for advancing better treatments.

The environment in which a molecule resides can drastically affect both its reactivity and its spectroscopic properties. These effects can be clearly seen in phenomena such as solvochromism or increased reactivity in a protein active site. The most accurate models that can capture these effects are purely quantum mechanical, but they also have a steep computational scaling cost that prohibits their use on large molecular systems. In order to circumvent this, less expensive models, such as molecular mechanics, can be used for the environment while maintaining the accurate model for the system of interest. In recent years, development of polarizable molecular mechanics has enhanced the accuracy of this technique for time-independent systems, but a gap still exists for time-dependent systems. In particular, the frequency dependence of polarizability has yet to be addressed. This research uses frequency dependent polarizabilities to parameterize a novel molecular mechanics scheme. Specifically, a machine learning model is trained to predict the best locations to place isotropic polarizabilities in order to recover the molecular, frequency-dependent polarizability.

Carbon dioxide concentrations have been on the rise since preindustrial times due to anthropogenic emissions. Understanding how past climates have responded to changes in the atmosphere is important to understand how our current climate will react to changes in our present-day atmosphere. Soil carbonates record the temperature at the time of their formation in their stable isotopic composition (called clumped isotope geochemistry). Ancient soil carbonates can record the temperature and allow us to better understand paleoclimates. Understanding what time of year soil carbonates form allows us to better interpret the temperature being recorded. The timing of changes in soil moisture is likely one of the most important environmental factors to consider. We test whether soil carbonates form during soil drying events using soil moisture and temperature data measured remotely by a satellite called Soil Moisture Active Passive (SMAP). This satellite has been gathering near-surface soil moisture data globally since 2015 at 35-65 km resolution. We compare the air temperature of the month with the greatest net negative soil moisture content month (determined from the satellite data) to the measured growth temperature of soil carbonates (estimated through geochemistry). We first compare the month of drying of three locales in North America, then extend the analysis globally to all locations for which soil carbonate clumped isotope data exist. Preliminary results suggest that the temperature of the month with the most drying agrees with formation temperature we estimated from clumped isotope geochemistry within one degree for a site in Nebraska and within seven degrees for a site in Wyoming. These results suggest that soil drying promotes soil carbonate formation in some environments. By using soil carbonates to explain past climates, we will improve temperature change estimates, which will help improve climate models for the future.

 Esophageal adenocarcinoma (EAC) has received considerable attention recently due to a three-fold increase in occurrence affecting 20,000 people each year in the US with <20% patients surviving 5 years past diagnosis. Thus, there is an urgent need to advance our understanding of EAC’s molecular pathology and to use this understanding in improving our ability to prevent and manage EAC. Gene mutations and epigenetic alterations drive the formation of a pre-malignant condition called Barretts’ esophagus (BE), which can then progress to EAC. Epigenetic modifications of numerous genes, in the form of DNA hypermethylation with subsequent gene silencing, have been demonstrated to occur frequently in BE and have been postulated as a driving force for EAC formation. In prior studies, we discovered a novel methylated gene, TUSC1, with silenced expression in primary EAC tissue samples and cancer cell lines (Yu et al., Gut 2018). This study aims to investigate the biological consequence of TUSC1 loss in EAC cell lines by utilizing CRISPR-Cas9 gene editing technology. We hypothesize that TUSC1 is a novel tumor suppressor gene in EAC. To test this hypothesis, we will be generating TUSC1 knock-out (KO) EAC cells by introducing TUSC1-silencing guide-RNA into EAC cell culture. We will be assessing the extent of TUSC1 KO at the gene expression and protein level by conducting quantitative real-time PCR and Western blotting, comparing the KO cells to the control cells. We will also use PCR-based sequencing to verify the DNA alteration introduced by CRISPR in single-cell colonies. Successful completion of these experiments will lead to the next stage of phenotypic assays, in which we will investigate whether loss of TUSC1 in EAC cells would promote oncogenic behaviors of cancer cells. The proposed studies would demonstrate the biological function of TUSC1 in EAC and illustrate the molecular mechanisms of DNA-methylation driving EAC tumorigenesis.

Methanol is a common pollutant in freshwater ecosystems due to its widespread use in industrial operations, fuel, antifreeze, paints, and insecticides, and being a result of the burning of garbage. As a bioindicator species, Daphnia magna health indicates changes in aquatic ecosystem health. They are an important part of the food web, eating algae, and as a food source to insects and fish. No previous studies have examined the effects of the pollutant methanol on Daphnia heart function and mortality. This experiment examined the effects of varying methanol concentrations on heart function and mortality of Daphnia magna. It was hypothesized that methanol significantly affects the heart and mortality rate of Daphnia. Fifteen experimental biospheres were used in each trial, with three jars for each of the five concentrations. The biospheres were filled with deionized water and methanol in concentrations of 0 ppm (control), 822.6 ppm, 1644.5 ppm, 3289.0 ppm, 7119 ppm. In a second trial, the concentrations were 0 ppm, 822.6 ppm, 1644.5 ppm, 205.7 ppm, and 411.3 ppm. Heart and mortality rates were observed and recorded for each trial over 4-8 days. For each jar, videos were recorded for 15 seconds each and heart rate was counted, and mortality counted every other day. Based on the survival and heart rate differences, it was concluded that as methanol concentrations increase, the heart rate of Daphnia varied but didn’t respond linearly to concentration levels. Additionally, higher concentrations of methanol negatively affect survivability, although the initial control groups had somewhat high death rates. This study highlights the negative impact of methanol pollution on Daphnia because a negative impact on Daphnia affects the whole freshwater ecosystem. Indeed, in Lake Washington, Daphnia represent a major source of nutrients for juvenile Sockeye Salmon, making Daphnia indispensable for their growth.

By their second birthday, toddlers help others. Moreover, infants as young as 9 months of age can detect others’ needs. Yet it is unclear if early helping behavior is based on and motivated by an underlying assessment of others’ needs, or motivated by other factors, like the desire to socially interact or affiliate with others. Here, we investigate whether toddlers utilize an experimenter’s needs when helping. We presented N=24, 24-month-old toddlers with two helping tasks: a puzzle and hunger-or-thirst task. In the puzzle task, toddlers watched an actor fail to complete a puzzle due to a missing puzzle-piece. Toddlers then had the opportunity to help the actor by either bringing her a puzzle-piece that fit the puzzle (need-fulfilling) or a puzzle-piece that did not fit the puzzle (not need fulfilling). Overall, toddlers were more likely to help with the puzzle-piece that fulfilled the actor’s need than the puzzle-piece that did not fulfill the actor’s need, p=.008. In the hunger-or-thirst task, the actor told toddlers that she was either hungry or thirsty. Toddlers could help the actor by giving her one of three different items: (a) cereal, (b) water, or (c) a shoe. Here, toddlers brought the needed item (e.g. cereal if she was hungry) at chance, p=.11. However, toddlers were more likely to bring the needed or the thematically related item (e.g. water if she was hungry) significantly more than chance, p<.001. Our findings provide initial evidence that 24-month-old toddlers are motivated to help based on others’ concrete needs: toddlers brought the needed puzzle-piece. However, toddlers have a harder time helping appropriately when the actor’s need is internal and therefore more abstract; hence, the equal likeliness to help with the needed and related item during the hunger-or-thirst task.

Despite possessing only one photopigment in its retina, a feature which should render an animal colorblind, the octopus, like other cephalopods, possesses an unrivaled capacity to camouflage itself with its surroundings. A recent theory suggests that cephalopods discriminate color in their environment through exaggerated chromatic aberrations, or the focusing of different wavelenths of light at different points behind a lens, caused by morphological changes in the eye. By monitoring the blurring of different wavelengths of light upon the retina from the visual field in response to the shape of the pupil, a cephalopod can still perceive color with only one photopigment. We test this theory using conditioning to a two-toned visual stimulus and its two differently-colored halves, to look at whether strobing between the two differently colored stimuli evokes the same response as that paired to the combined stimulus or one of its halves. Evoking the response of the combined stimulus would suggest that they can see the two differently colored halves simultaneously, and that a morphological change is not needed to see two different wavelengths of light. This would present a model for color perception with one photopigment that could be explored in various other vertebrates and invertebrates previously thought to be colorblind.

Despite their sophisticated visual system, convergent and comparable in complexity to that of vertebrates, Octopus rubescens is largely nocturnal and forages mostly at night. Without visual information, their primary means of gathering information from the environment is through the sophisticated chemotactile sensory system within their arms. Octopuses blinded from lesions to their optic nerves have been observed relying on chemotactile perception of their environment with their arms fully extended to maximize their sensory range. Such behavioral profiles optimizing the acquisition of one sensory modality in the absence of another would be critical for navigating and monitoring changes within their environment. Our intention is to characterize how Octopus rubescens modifies its chemotactile range after an acclimation period of either light or darkness, simulating a natural 24 hour light cycle, and then a rapid change to the opposite lighting condition. Using 3d tracking cameras we will be able to quantify the change in the range of arm extension and overall posture that accompanies locomotion during light and dark conditions.

Maternal exposure to persistent environmental toxicants polybrominated diphenyl ethers (PBDEs) is associated with many human diseases, notably hepatotoxicity, thyroid disorders, and reproductive toxicity. PBDEs, previously seeded into manufactured products as flame retardants in the United States, were phased out during the 2000s. A 2017 study of women in California showed modest average annual percent increases in serum concentrations of PBDEs. Accordingly, the gut microbiome is increasingly recognized as the “second genome”, impacting crucial health-related factors like host xenobiotic biotransformation and energy homeostasis. Persistent dysbiosis may contribute to altered susceptibility of disease in adulthood. My goal for this study was to test the hypothesis that perinatal exposure to BDE-47, a common PBDE congener that can cross the placenta and enrich in breast milk, modifies the developmental trajectory of gut microbiota. Pregnant Wistar rats were orally exposed to BDE-47 (0.2mg/kg) from gestational day 8 to postnatal day (PND) 21. Fecal samples were collected from mothers at PND21 and male pups at PND65 and 120. I isolated Microbial DNA using 16S rDNA sequencing (n=5~9/group) and analyzed my data through QIIME. Perinatal BDE-47 exposure had minimal effect on the richness of gut microbiota in PND65 pups and mothers, but profoundly increased richness of gut microbiota in PND120 pups. In PND65 pups, only 4 taxa were persistently regulated by perinatal BDE-47 exposure. Interestingly, the effect of perinatal BDE-47 exposure was evident in PND120 pups, with an increase in 3 taxa in the Lactobacillales order and 11 taxa in the Clostridiales order. Targeted metabolomics has confirmed alterations of distinct microbial metabolites (short-chain fatty acids and secondary bile acids) corresponding to BDE-47-induced dysbiosis. In summary, the present study showed that perinatal BDE-47 exposure modified the developmental trajectory of the offspring’s microbiota, possibly producing delayed onset of diseases in adulthood.
 

Cranial elaboration, in the form of domes, horns, and bony bosses, has evolved multiple times in vertebrate history, including in non-mammalian synapsids, the extinct ancestors of mammals. The lack of similarly thickened skulls in living animals has meant that very little can be inferred about how these features developed or why they evolved. Here we use comparative bone histology to describe the microanatomy of Oudenodon, a 255-million-year-old synapsid with distinctive nasal bosses. We compared thin-sections from the thickened portions of Oudenodon to the non-thickened skull of its relative, Diictodon, in order to better understand how cranial elaboration developed in synapsids. We took thin sections from the thick nasal bosses as well as non-thickened regions of Oudenodon to capture changes in tissue microstructure. Then, we compared these thin-sections to similar regions of the skull in Diictodon, which lacks cranial elaboration. In the bone tissue of both Oudenodon and Diictodon, we observed a cancellous, spongey interior sandwiched between two layers of compact cortical bone. This pattern of bone is typical in many modern skulls but the thickness of the cancellous region in Oudenodon is strikingly thicker, even in regions away from the boss. We hypothesize that increased cranial thickness in Oudenodon is due to this middle expansion of spongey, cancellous tissue. As a result of the increased bone thickness, sutures in Oudenodon are deep, wide, and convoluted when compared to the relatively simple interdigitated sutures in Diictodon. These and other histologic comparisons with distantly related taxa allow us to interpret the growth and construction of cranial elaboration in synapsids, adding to our understanding of how these thickened skulls evolved. Future work can also explore the possible soft tissue covering of these bosses and domes, which may have been used for intraspecific display or combat. 

Air pollution due to traffic causes many human health problems including neurological disorders. Recently, compelling evidence from the literature has demonstrated that gut microbiome is a newly discovered organ that critically regulates the neurodegenerative disorders including Alzheimer’s disease (AD) via remote-sensing mechanisms. One of the major classes of microbial metabolites are the secondary bile acids. My research focuses on the relationship between TRAP (Traffic-Related Air Pollution) and bacterial metabolism of bile acids that might have significant implications on human health. Male and female wild Type (WT) and transgenic (TG; over-expresses two human AD risk genes [mutant amyloid precursor protein and presenilin-1]) rats were exposed to TRAP or filtered air (FA) for different time points. I focused on rats up to 10 months old that were exposed to TRAP or FA for up to 9 months and from their intestinal contents I extracted bile acids, DNA and RNA to compare which factors might affect gene expression. Bacterial gene and taxa abundance were measured by quantitative PCR (qPCR) and statistically analyzed for significance. Two-way ANOVA analyses were conducted separately among male and female rats; only male rats showed significant changes by qPCR. Exposure to TRAP increased levels of Lactobacillus reuteri in WT males, but conversely decreased L. reuteri in TG males. By understanding different factors affecting bacterial metabolism of bile acids, we are exploring if this could possibly affect human health as well. This can potentially help clinicians and environmentalists to improve clinical outcomes and policies regarding traffic-related air pollution.

Electronic movement can be modeled using the Schrodinger equation. For many-electron systems, however, these equations are not algebraically solvable, which is why this research uses direct numerical integration of Schrodinger’s equation to model time dependent electronic characteristics of molecules. The choice of numerical integration scheme can drastically change the outcomes of the simulation – even causing qualitative changes in molecular behavior. First, an advanced numerical integration technique (4th order Magnus propagator) has been implemented in the ChronusQuantum software package. Next, the effects on molecular behavior of choosing this integration scheme over preexisting schemes are evaluated. The implemented integration algorithms can be used to model the elementary steps of chemical reactions, as well as analyzing the effects of light on electron movement. The research provides meaningful information about the impacts of different implementations of algorithms along with analyzing the simulated behavior of electrons.

Euphausiids (krill) are zooplankton that play a large role in Puget Sound’s marine ecosystem. They are widespread and numerous and have been suggested to play a large role in energy cycling and food web dynamics. Vertical layering of species is not uncommon, and patterns can persist between years, suggesting a significance to the layering. During the day, euphausiids form deep layers in the water column with a thickness in the tens of meters where ecosystem dynamics may differ between the top and bottom of the layer. These layers can be detected by acoustic systems, but characteristics of individuals cannot be resolved. In this study, we used net tows to sample euphausiids at different relative depths within a layer. We recorded the length, sex, and species for statistical analysis to assess the homogeneity of the layer. Comparisons against other locations in Puget Sound will allow us to see if vertical structures are consistent or if other factors such as the presence of predatory fish can explain for differences. This project will provide insight on ecosystem dynamics and carbon cycling.

Developing treatments for complex disease is hindered by a variety of obstacles including clearance by the reticuloendothelial system, degradative proteases of blood and tissue microenvironments, and overall limited tissue penetration. Nanoparticles hold potential as drug delivery platforms for overcoming these problems, where they can be used to encapsulate and protect enzyme therapeutics and improve delivery to specific organs of the body. Using poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles with a poly(ethylene glycol) (PEG) coating and catalase as a model enzyme, we compared two methods of nanoparticle formulations for enzyme encapsulation: nanoprecipitation and double emulsion. We tested the effects of F127 (Pluronic F127), P80 (polysorbate 80), and PVA (poly(vinyl alcohol)) surfactants on the size, polydispersity index (PdI), zeta potential, and enzymatic activity of nanoparticles formulated via nanoprecipitation. We determined PVA to be the ideal surfactant with the greatest enzyme loading for nanoprecipitation (~3.6%), similar to the activity obtained from double emulsion (~3.7%). For double emulsion, we determined similarly that PVA worked the best out of the surfactants tested. However, the nanoprecipitation method provided little to no enzyme protection in the presence of a protease with complete deactivation within 4 hours, while double emulsion nanoparticles extended activity through 24 hours (~6.6% of original activity). We further optimized the double emulsion method by altering the sonication times, determining that a sonication time of 15 seconds yielded particles with an activity of ~3.5% while maintaining similar size, zeta potential, and PdI. We also found that sonication conditions significantly affected enzyme deactivation. With a modified bicinchoninic acid assay, we measured total protein concentration within the particles, allowing us to calculate enzyme percent deactivation from formulation processes. Altogether, our work shows that enzyme-loaded nanoparticles made via the double emulsion method achieve high encapsulation and protection of enzymatic cargo for drug delivery.

Flow Cytometry is a quantitative data collection method which utilizes a laser and optics system to measure forward and side-scattering light from single cells in a heterogeneous solution, which when analyzed describe the structure and internal complexity of the cells in solution. Additionally, varying wavelengths of light emitted from the cytometer excite particular fluorescent dyes that can be conjugated to known antibodies, so that when cells contain the known antibody’s antigen, the dye color will be present. This allows for cell identification and/or protein expression to be determined and quantified within a heterogeneous mixture of cells. With the given technology, we optimized a flow cytometry panel for the use of analyzing immune responses to gene therapy treatments in canines. We stained extracellular and intracellular protein markers on canine peripheral blood mononuclear cells (PBMCs) with fluorescent dye conjugated antibodies thought to recognize canine antigens. This entailed staining the extracellular markers with conjugated antibodies, fixing and permeabilizing the cell, and doing the same to intracellular markers. Once this had been carried out, the cells were run through a flow cytometer to excite the dyes with varying wavelengths of light to highlight separate dye colors. Analysis of multicolored dye presence in cells post-excitement allowed for identification and quantification of cell types. We identified antibodies that recognize canine antigens and developed a multicolor panel identifying T helper cells, cytotoxic T cells, T regulatory cells, and B cells in canine samples. Once optimized, we used this panel to characterize immune responses in dogs following gene therapy. With a reliable canine cytometry panel, future canine immune responses, both broadly and in isolated muscular tissues, can be characterized.

Anatolia, in modern Turkey, is a complex assemblage of micro-continents that collided during the Late Cretaceous and the Paleogene, 80 to 25 million years ago. Despite the large volume of work on the numerous Anatolian terranes and collisions, basic questions regarding the timing of collision, style of post-collisional deformation and development of topography remain enigmatic. In western Anatolia, the timing and mechanisms of these successive collisions are poorly understood and do not conform with current continent-continent collision models. This project reconstructs the evolution of the collision zone in order to reconstruct the tectonic evolution of western Anatolia and refine models of collisional tectonics. Here, we present new data from the 160-40 million year old sedimentary archives preserved in the Central Sakarya Basin, a sedimentary basin that formed adjacent to the collision zone. Two methods for sedimentary analysis are employed in this research: detrital zircon dating and sandstone petrography. Detrital zircon ages attained through Uranium-Lead dating techniques are compared to known ages from surrounding mountain ranges to determine the source of sediment through time and apply age constraints to stratigraphic layers. Sandstone petrographic analysis examines the composition of samples to determine sedimentary provenance. The evolution of sediment sources through time provides a robust timeline of collision, post-collisional deformation and topographic development. The results from zircon dating and sandstone petrography show an evolution of sediment provenance where the oldest, pre-collisional sediments are derived from an adjacent volcanic chain. The onset of collision, around 60 million years ago, is marked by a change in sediment composition as collision creates topography and fault systems exhume older, buried rock. In constructing a progression of sediment source, this research determines a precise chronology for the collision and post-collisional evolution of western Anatolia and contributes to modifying current models on collisional margins.

Computer vision models are used to help analyze biomedical images for diagnosis and treatment through looking for differences between images by a comparison to a template image. For instance, optical coherence tomography (OCT) is used to diagnose and treat retinal issues. When looking at the brain, injury, cellular uptake and characteristic features vary across regions, therefore images are often segmented into established brain regions to determine how the brain is impacted in a particular study. Current models fail to work in segmenting brain regions because each brain has variation in local microstructure, making it difficult to compare one brain to another. Furthermore, when brains are sliced, the exact location within the brain can be difficult to pinpoint, particularly in regard to depth, because the regions vary slice to slice. Therefore, my research addresses the increasing need for a method of analysis to align and compare images from brain regions across slices from a single brain, and from brain to brain. Using scikit-image analysis tools, I extracted information from cell images and videos of nanoparticles obtained in brain slices and determined trends within various regions. My program extracted cell density, shape, and death, then analyzed the uptake of nanoparticles to determine where a small segment of an image is most likely located within the brain. Iterating over the entire image generated a rough map of the regions within the brain which is refined using mapping descriptions detailed in literature. This research resulted in a systematic program that uses image analysis tools to extract features of defined brain regions. This program allows for quick, accurate and consistent analysis of regional differences of cellular features, nanoparticle distribution, toxicity, and other important measures.

Depression is a neuropsychiatric disorder with a high rate of recurrence and increased mortality. One in six people experience depression at some point in their life, and the disease burden was over $200 billion in 2013. While little is known about the underlying neurobiological processes, the presence of inflammation in the central nervous system has been observed in those suffering from depression. This inflammation, mediated by microglial activation, astrocytosis, and pro-inflammatory cytokine production is involved in the progression of this disease. Past research has focused on the response of microglia in adults, but there are limited studies on the developmental features. Therefore, using a Sprague-Dawley rat model of lipopolysaccharide (LPS)-induced inflammation, this study aimed to understand the progression of the inflammatory response in the development of depressive-like behavior. We determined a suitable dosing scheme to induce inflammation while minimizing mortality to be an intraperitoneal injection (i.p.) of 0.05 mg/kg LPS on postnatal day (P) 7 and 0.1 mg/kg LPS on P9, P11, and P13. Control animals were injected with saline. The presence of inflammatory response was evaluated at P14, P21, and P35. This study showed that rats exposed perinatally to LPS had an increased number of microglia in the hippocampus as well as a hyper-ramified microglial phenotype in comparison to control animals. Similarly, rats treated with LPS showed decreased expression of anti-inflammatory TGF-β and increased expression of pro-inflammatory cytokines TNF-α and IL-6. LPS treated rats also tended to display more anxiety-related behavior including avoiding the open arms of an elevated-plus maze. These results support that LPS exposure in rats can be used as a model to study the effects of inflammation in the developing brain of rats displaying depressive behavior.

As the global burden of neurological diseases continues to grow each year, there exists a need for drug delivery vehicles that can overcome barriers specific to the brain. The heterogeneous brain extracellular matrix (ECM) is an understudied barrier to effective therapeutic delivery, particularly in the presence of disease states. We utilize a novel multiple particle tracking (MPT) approach to characterize microstructural changes in perineuronal nets (PNNs), a key structural mediator of plasticity, in the developing brain. Our overarching goal is to develop a combined approach of MPT, statistical analysis using Python-based software packages, immunohistochemistry (IHC), and mRNA expression profiles to monitor changes in PNN structure and function through development and in the presence of neuroinflammation and oxidative stress processes. For this, we cultured 300 μm-thick organotypic whole hemisphere (OWH) brain slices prepared from postnatal day 35 (P35) rats. We treated slices with 100 ng/mL lipopolysaccharide (LPS, induced-inflammation model) or 100mM glutamate (MSG, induced-excitotoxicity model) for 3 h, removed the toxin and fixed slices at 1 h, 6 h, and 24 h after toxin removal. Fixed slices were stained using Wisteria floribunda agglutinin (WFA) and PNN counts were quantified using the ImageJ software package. In LPS and MSG-treated slices, 100-nm particles were added to live slices stained with WFA and MPT was performed in WFA+ regions, followed by statistical analysis of individual nanoparticle trajectories. From the IHC imaging and PNN count quantification, we observed differences in the number and morphology of PNNs present in the MSG and LPS models when compared to healthy controls. Characterizing structural changes in PNNs in living tissue furthers our understanding of the impact of neuroinflammation and oxidative stress on neuronal plasticity, and the subsequent impact on progression of neuropsychiatric diseases.

It is an evitable instinct to develop snap judgements of people as we encounter them in passing; therefore, our experiment attempted to replicate this quick encounter and asked the question of whether one’s gender and race impacted how they perceive others’ friendliness. Our sample consisted of 35 males (27.1%) and 89 females (66.7%). 82 of our participants were Caucasian (63%), 25 Asian-American (19%), 4 African American (.03%), 1 Hawaiian (.007%), 20 Latino American (15%), 14 who identified as mixed race (10%); all an average age of 23 years (SD = 2.6). Participants were shown 8 photographs of White and Latino men and women smiling for 5 seconds each. They then had to rate the friendliness of each photo within 15 seconds of viewing. Our findings suggest that the intersectionality of race and gender play a role in how individuals perceive men and white men. Implications of these findings suggest that a holistic view of a person’s identity will give a better indication of how they might view those who do and do not look like them.

Drug addiction is a neuropsychiatric disease characterized by compulsive and uncontrolled drug use. Rodent self-administration models can represent certain aspects of substance abuse in humans. Studies have shown drug use and drug-associated cues increase dopamine transmission. Data from the Paul Phillip’s Lab demonstrated rats that escalated in their cocaine intake had a decrement in dopamine release to cues in the nucleus accumbens. Administration of Levodopa (L-DOPA), the molecular precursor to dopamine, decreased cocaine consumption to pre-escalated levels. However, we have not yet confirmed whether the impact of drug-associated stimuli and its dopamine-mediated aspects can be generalized to opioid use. Thus, the current study investigates if increased dopaminergic signaling via L-DOPA decreases consumption of fentanyl, a highly potent synthetic opioid. We tested L-DOPA’s effect in two separate behavioral assays. The first assay is a two-bottle choice paradigm in which the animal is given 3-hour access to liquid fentanyl (50μg/mL) and water. Additionally, animals were trained to self-administer fentanyl, in which rats were required to nose poke for liquid drug delivery. Preliminary data shows intraperitoneal injection of L-DOPA significantly decreases overall fentanyl consumption in both two-bottle choice (p<0.05) and in the instrumental task (p<0.05). These data imply that dopamine release is regulating opioid consumption. A second aim of the current work is to characterize drug-taking patterns in animals self-administering fentanyl orally. Permitting animals to extended access to drugs of abuse is known to induce escalation of drug intake. Utilizing this paradigm we provide six hours of liquid fentanyl access and examine intake patterns of individual animals across sessions. Future studies will utilize electrochemical detection techniques to examine subsecond changes in dopaminergic signaling during oral self-administration. Overall, this work provides evidence that dopaminergic signaling regulates fentanyl consumption and treatment with L-DOPA can stabilize and reduce drug intake.

Interferon-gamma Enzyme-Linked Immunosorbent Spot Assay (IFNγ ELISpot) is a laboratory technique that quantifies the number of cells producing interferon gamma (IFNγ) by utilizing antibodies that selectively bind to IFNγ molecules, resulting in spot formation corresponding to individual IFNγ-producing cells. Since cytotoxic T cells (CD8 T cells) and their helper Th1 cells (CD4 T cells) produce IFNγ to activate macrophages and inflammatory responses, quantifying IFNγ-producing cells allows for characterization of host immune responses. Our lab utilized a canine IFNγ ELISpot to test for immune responses against novel proteins expressed following gene therapy in dogs. Currently, we used a routinely given vaccine for canine flu, distemper, adenovirus, and parvovirus as a biological positive control. However, we tested our experimental proteins with peptides, making a whole-protein positive control, which required internal processing, flawed. Our goal was to optimize this ELISpot by identifying peptides from the vaccine that stimulates an IFNγ immune response in peripheral blood mononuclear cells (PBMCs) and splenocytes. Utilizing a commercially available canine IFNγ ELISpot, we stimulated PBMCs and splenocytes. These cells included lymphocytes (T cells) and macrophages, which acted as antigen presenting cells. We compared stimulation with the entire vaccine and various vaccine peptides in order to identify peptides that can be used as a biological positive control. These were compared to traditionally used mitogens that indiscriminately activated all lymphocytes. This optimization allows for greater confidence in the results obtained from our canine IFNγ ELISpot. The improved technique serves as a powerful tool to assist in preclinical trials of vaccine production and gene therapy. It is utilized in our lab to test for CD8 T cell-mediated immune responses against novel dystrophins following gene therapy in Duchenne muscular dystrophy dogs.

The most recent National Vital Statistics Report reports that approximately 9.85% of babies in the United States are born preterm, with 72% of those born late-preterm (at 34-36 weeks of gestation). Using neonatal ferrets at age 17 days old, the Juul lab in the Division of Neonatology at the University of Washington Medical Center has developed a preliminary model of brain injury to mimic late-preterm neonatal injuries. In this species-specific adaptation of the Vannucci Model, the left carotid artery is permanently ligated, along with a temporary (4h) occlusion of the right carotid artery. Ferrets are then exposed to periods of hypoxia and hyperoxia. By looking at data and outcomes from our surgeries, I aim to examine the effects of certain surgical parameters on ferret mortality. These parameters include: time the animal is exposed to isoflurane, the length of surgery, and the amount of time the animal is given to recover between surgery and hypoxia. Aside from mortality, I will also analyze the effects of these parameters on respiratory rate after surgery as well as gross brain injury and data from behavioral testing in an attempt to discern the level of injury in living animals and the most common predictors of death in those that died prior to their determined endpoint.

Astrocytes are a type of glial cells in the central nervous system, play a critical role in protecting neuronal signaling by regulating brain homeostasis, synaptic plasticity and transmission, and blood brain barrier functioning in central nervous system. Accumulating evidence has indicated that abnormal behaviors of astrocytic functions, including astrodegeneration and astrogliosis, are implicated as the primary factors contributing to a number of chronic neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Kir4.1 is an inwardly rectifying K+ channel expressed on the projections of astrocytes, which serve important roles in the neuroprotective function of astrocytes, such as maintaining K+ homeostasis and regulating extracellular glutamate. Abnormal expression of Kir4.1 has been reported in certain neurodegenerative diseases, including Amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD), suggesting a vital role in the development of pathophysiology. However, the association between the molecular mechanism and expression of Kir4.1 and the underlying pathogenesis of AD and PD has been largely uninvestigated. In this study, we have had the critical opportunity to access human post-mortem brain tissue, provided by the University of Washington Alzheimer’s Disease Research Center, and conducted confocal microscopy studies. Through a quantitative immunofluorescense staining approach, we expect to demonstrate a distinct expression pattern of Kir4.1 in various brain regions of AD and PD post-mortem tissues when compared to control subjects. Determining the role this protein has in neurodegeneration may provide new insight into the development of therapeutic targets to ameliorate the progression of AD and PD.

Chimeric antigen receptor (CAR) T-cell therapy is the latest treatment option available for those suffering from certain forms of cancer such as lymphoma and leukemia. These engineered cells are able to recognize specific proteins found in tumors, and subsequently induce CAR-T cell proliferation, cytokine secretion, and lysis of the cancerous cells. Despite its promise, a percentage of patients who receive this treatment develop a range of neurotoxic symptoms. My research project tests the hypothesis that endothelial activation of vascular tissue in the brain, which would allow for increased permeability of immune cells through the blood-brain barrier, is contributing to the development of these clinical symptoms. Using a technique called immunohistochemistry, I used the antibodies claudin-5 and cd31 to fluorescently label tight-junction proteins and adhesion molecules of endothelial cells from brain tissue harvested from a developed mouse model. This mouse model received CAR-T cell injections and underwent behavioral testing to confirm the presence of neurotoxicity symptoms. I then used microscopy skills to visualize the labeling of the endothelial cells and proteins. If my hypothesis is correct, I expect to see a quantifiable decrease in the number of cerebral tight-junction proteins connecting endothelial cells along the blood-brain barrier, as compared to negative control tissue that received no CAR-T cell injections. In order to make these comparisons, I will use a software program such as Image-Pro Premier software (Media Cybernetics) to help me quantify the positive fluorescence labeling of endothelial cell proteins and adhesion molecules in both the control and experimental tissue. Tissue with less tight-junction proteins and adhesion molecules would permit the influx of foreign particles into the CNS. Understanding the cause of CAR T-cell related neurotoxicity will be first step in promoting prevention and increasing the effectiveness of this new cancer immunotherapy.

Neonatal mammalian heart tissues possess regenerative capabilities after injuries like myocardial infarctions that are mostly lost in adult mammalian tissues but conserved through adulthood in other vertebrates like zebrafish. Previous studies have shown that regeneration in ventricular cardiomyocytes (CM) occurs through de-differentiation and proliferation, but the underlying mechanisms that cause cardiomyocytes to enter the primed cell-cycle are unknown. Here we show that amino acid and metabolite levels in injured cardiomyocytes result in a primed state for regenerating cells. In chemically ablated zebrafish, it is shown that the amino acid profile activates the mTOR pathway to drive regeneration. Amino acid activation of mTOR is a result of high glutamine and leucine levels post-injury and in early heart regeneration in adult zebrafish, which is lost in adut mammals. Inhibition of the Wnt/β-catenin signaling pathway upstream of mTOR shows down regulation of mTORC1, showing that mTOR is necessary for CM proliferation in regenerating heart tissue. How Wnt signaling gets activated upon injury is unknown, and this study aims to understand the pathways upstream of Wnt signaling for activation. It is known that scarring needs to occur before regeneration occurs in heart tissue. This study also investigates why macrophages are essential for scar formation in ablated heart tissue and its underlying mechanisms. Further, single cell RNA sequencing one-week post injury is used to determine cell fates of the heart tissue. Cardiac cell types like CMs, endocardial and epicardial cells, and bulbus arteriosus (BA) cells were activated post-injury, with epicaridal cells promoting CM regeneration and BA cells activating signaling pathways during heart regeneration. This study demonstrates the signaling and metabolic pathways that activate cardiomyocyte regeneration in zebrafish hearts.

Proteins are essential to life, but many structural methods fail to capture the dynamic nature of proteins. This means researchers are left with an incomplete view of how protein function and structure relate. The Stoll lab uses electron paramagnetic resonance (EPR) to study the dynamic structure of proteins. The project I am working on is investigating the way in which the measurement conditions in EPR affect the determined protein structure. We use maltose binding protein (MBP) as a model system, since its structure has been previously well-characterized. My primary role has been to create new mutants for site-directed spin labeling, in which a radical spin label is attached to the protein. This radical is measured by placing the sample in a magnetic field and results in a probability distribution of distances. Common spin labels used in EPR, however, have many rotatable bonds, andd can cause uncertainty in the extracted distance distribution. Our project is investigating the contribution of spin labels to the EPR experiment. I use polymerase chain reaction to create new mutants of MBP by swapping a native residue with a cysteine residue in the mutants. Each mutant has one or two amino acids replaced with a cysteine. After mutating the DNA, I then transform the mutant DNA into wild type cells to grow the mutant protein and purify the protein. The spin label forms a disulfide bond with the cysteine residue in the mutant, providing an unpaired electron for measurement. By using various commonly used spin labels on many different site pairs in MBP, we hope to develop a model in which the contribution of spin labels to the probability distribution of distances is accounted for. This will ensure more accurate results in determining protein structure and will aid in structural characterization of many proteins.

Hearing loss is often due to the absence or degeneration of hair cells in the cochlea, thus it is important to understand the transcriptional control mechanisms specifying the prosensory cells that generate hair cells and support cells. Early B-Cell Factor1 (Ebf1) is a transcription factor that was brought to our attention from motif enrichment in replicated ATAC-seq peaks detected in prosensory cells and non-prosensory cells. We observed that in the open chromatin regions and dynamic regions during the development of prosensory cells showed greater enrichment of Ebf motifs. This suggested that Ebf1 could be acting as a pioneer factor. To determine whether Ebf1 influences cochlear development, we generated a Sox2CreER: Ebf1 fl/fl allele by crossing Sox2-CreER mice and Ebf1-floxed mice. Administration of tamoxifen to mice orally leads to Cre-mediating deletion of Ebf1 DNA binding domain and formation of the recombinant Ebf1-GFP fusion protein. To determine whether the Ebf1 knockout is successful we will compare Ebf1 expression between the Ebf1 knockout and wildtype through qRT-PCR. We will also compare the localization of Ebf1-GFP fusion protein in the Ebf1 knockout and wildtype. To determine whether Ebf1 affects cochlear differentiation, we will immunolabel for Sox2, Egfp, and Myo7a, this allows us to determine the presence of support cells (anti-Sox2), hair cells (anti-Myo7a) and the Ebf1 reporter (anti-Egfp) and compare support cell and hair cell counts between the Ebf1 knockout and wildtype. If the comparison shows a decrease or increase in support cell and hair cell counts in the Ebf1 knockout compared to the wildtype or the lack of support cells or hair cells in the Ebf1 knockout, then it suggests that Ebf1 is necessary for cochlear differentiation.

Marine mammal strandings can serve as an indicator of marine ecosystem and mammal population health, providing an opportunity to learn about the life of individual animals prior to their deaths. Existing stranding networks are focused on response to opportunistic reports of stranded or beached marine mammals, which limits their usefulness in establishing baseline data. The Coastal Observation and Seabird Survey Team (COASST) engages volunteers along the western coast of the United States in collecting and reporting data for two effort-based programs, beached birds and marine debris. Looking to the future, COASST hopes to complement information gathered by marine mammal stranding networks by expanding their effort-based surveys to include marine mammals. COASST has already begun this process by asking volunteers to report sightings of marine mammals along with pictures of their beached bird or marine debris finds. These pictures can be used for species identification, and by looking at these photos in correspondence to other survey data such as region, beach, and survey date we can learn about species distribution along the western coast of the United States. We found at least 300 beached pinnipeds, through photo identification we were able to place them into at the least the families Otariidae or Phocidae. Using current literature on marine mammals, pinnipeds specifically, and their identifying characteristics, I aim to map pinniped species distribution and locate hotspots to ultimately test a pinniped species identification key that will be used by COASST volunteers. With this distribution and hotspot identification we will be able to idenify whether pinnipeds follow already established beaching patterns of beached birds or if they differ. These differentiations could lead to more information about the death of marine mammals and allow future research on the death of these animals in more focalized areas. 

Ovarian cancer is the deadliest gynecological malignancy: nearly 70% of patients are diagnosed at late stage and 70% relapse. Cytoreductive surgery and chemotherapy are the standard of care, yet fewer than 50% of patients live 5 years past diagnosis. Innovative therapies are desperately needed. Immunotherapy using T cells engineered to express a T cell receptor (TCR) targeting proteins overexpressed in tumors is a promising strategy that limits tumor growth and has minimal toxicity. Mesothelin (Msln) is overexpressed in over 75% of ovarian cancer patients and has been identified as a promising cancer antigen because it contributes to the malignancy and invasiveness. Our group has shown that targeting Msln with engineered T cells (TCRMsln) in the mouse ID8 ovarian tumor model, which recapitulates essential aspects of the human disease, can prolong survival of mice with advanced disease. However, our data also show that immunosuppressive features in the tumor cause T cells to become dysfunctional and/or die. Fas ligand (FasL) is a transmembrane death-inducing protein present in ovarian tumors, and may be used by tumor cells to escape the immune response by inducing cell death of beneficial lymphocytes expressing the Fas receptor (Fas). We hypothesized that we could overcome this T cell evasion mechanism using immunomodulatory fusion proteins (IFP). We generated IFPs that combine the Fas extracellular binding domain to a co-stimulatory domain, CD28 or 4-1BB, instead of the standard death domain, to trigger T cell activation. T cells expressing an IFP had enhanced proliferation and persistence in ID8 tumors relative T cells lacking an IFP. Further, ID8 mice treated with TCRMsln T cells expressing an IFP had prolonged survival compared to mice treated with the TCRMsln T cells alone. Many solid tumors overexpress FasL, thus our findings have the potential to enhance engineered T cell therapy against other malignancies.

Natural language generation (NLG) aims to generate meaningful and coherent natural language from a machine-representation system. There have been many approaches casting this task as a reinforcement learning (RL) problem. The NLG RL paradigm usually has a generative model to produce response for a given query, and a discriminator model to distinguish between human-generated dialogues and machine-generated ones, analogous to the human evaluator in Turing test. Previous research shows that such adversarial-trained generators can generate higher quality sentences than baseline supervised generators. However, the current state of the art focuses on how to fine-tune the generator using the discriminator, rarely incorporating the discriminator in the final language generation. Formally, we define the NLG as a planning problem. The agent (model) is trying to generate responses given prior query. Each action in the plan represents the intermediate state of generating a response. At each state, the agent decides which word to generate next. The main issue for that paradigm is the enormous number of possible actions at each step, equal to the total number of words in the vocabulary. To solve this issue, we incorporate an idea from AlphaGo, another great success in RL. AlphaGo uses the Monte Carlo Tree Search (MCTS) algorithm to reduce the searching space to avoid intractable computations from the enormous search space in Go. Inspired by current NLG RL paradigm and AlphaGo’s success, we propose to incorporate MCTS into NLG RL. The agent estimates initial word values using the generator probability distribution, and picks the next words through Upper Confidence Bounds for Trees (UCT), a widely used MCTS planning algorithm. Our results approach the current state of the art. My main responsibility was implementing the paradigm and seek ways to improve it. This work’s main contribution is presenting an effective way to incorporate discriminator into NLG.

Minimizing cognitive load is an integral part of human-centered design, where a more intuitive, easy to learn, and adaptive interface is desired. In this study, I implemented a program which was used to measure cognitive load using blink rates collected from pilots during takeoff and landing in a flight simulator. A GoPro camera was used to capture pilots’ blink rate. The program I wrote analyzed the GoPro video by first extracting the face of the pilot and then points on the face called facial landmarks. These facial landmarks are then rotated and scaled to standardize for analyses. The facial landmarks are fed into an Support Vector Machine (SVM), a type of machine learning model. To train the model I labeled around 60,000 frames that were sampled from the GoPro videos, as having pilot eyes “open” or “closed”. To predict blinks, the model is tasked with classifying each frame in a video as either eyes open or eyes closed. This data is then smoothed by a heuristic 20 frames. That is, if any two frames within a set of 20 frames is marked as closed, the entire series is marked as closed. The middle of each series of closed eye frames is then marked as the frame where the blink occurred. The output of the process is the video where each frame is marked as being the apex of a blink or not. I evaluated several machine learning models (random forests, gradient boosted decision trees, a multi-layered perceptron, and a support vector machine) and the support vector machine had the greatest precision and recall. This work is important because identifying peak workload tasks in aircraft cockpits contributes to the identification of areas that require better user interfaces and automation improvement to increase safety and efficiency of aircraft operations.

This project looks to understand the role of women in the second rise of the Ku Klux Klan in the 1920s to understand why this manifestation has been categorized as the largest right-wing movement in the history of the United States. I argue that the addition of women as active participants in Klan activity, unlike the first rise during Reconstruction which was a strictly fraternal society, transformed the movement from a domestic terrorist organization into a political club with immense social influence on the white Protestant population in America. Primary sources used to build this argument came from Klan documents such as pamphlets and newsletters as well as local and national newspapers from across the U.S between 1918-1927. Women in this time period were emboldened to participate in politics after their victory with the suffrage movement, and those who employed racist and nativist ideology easily transitioned into the white supremacy of the Klan, who desperately sought to recruit blocs of voters. Using coded language such as "100% American" to describe themselves, the Women's Ku Klux Klan (WKKK) utilized issues such as poor education, alcoholism, and immigration as a silk screen to vilify their ever-growing list of "enemies" (a tool used to recruit membership from a larger base) among them Catholics, Jews, Bolsheviks, blacks, labor unions in the North, and immigrants. The addition of women allowed the Klan to become an organization that supported nuclear family structure and encouraged all to be involved, including children, which served to develop “Klan culture” to recruit and retain members by building community. While Klanswomen were different from their male counterparts, they worked within social networks that maintained consistent growth, starting chapters in almost every state and amassing political and social influence on a local and national level.

Students of the Ocean Research College Academy (ORCA), an early college program through Everett Community College, have monitored bacteria data near Everett, Washington where the Snohomish River meets the Possession Sound since 2004. Used as an indicator of fecal contamination, Escherichia coli (E. coli) are found in the intestinal tract of humans and other homeothermic animals. This study investigates the spatial and temporal trends of E. coli levels at three sites within the Possession Sound between 2014-2019 in order to better elucidate the ecosystem’s health and potentially negative anthropogenic influences. Variation in coliform levels were analyzed with regard to physical and chemical factors such as tidal stage, depth, the Snohomish River discharge, salinity, temperature, dissolved oxygen, pH, and point sources  including combined sewer outflows and storm drains. Water samples were collected with a Niskin bottle while a YSI 650 CTD or a YSI EXO Sonde was utilized to measure salinity, temperature, dissolved oxygen, and pH for each of the samples. ORCA students followed the Coliscan® Easygel® Protocol for inoculation, incubation and quantification. Data were reported as colonies of E. coli per 100 mL of water. Preliminary results show that E. coli levels have a seasonal correlation with river discharge, increasing in the fall, winter, and spring months when river discharge spikes. Coliform levels are higher at the halocline than at the surface or near-deep. Further sampling at additional upriver sites will demonstrate more sources of E. coli data. The results of this study will provide a foundation for understanding the fluctuations in the spatial and temporal trends of E. coli levels within the Possession Sound in order to better assess threats to the ecosystem health.

The Snohomish River estuary serves as a conjoined and biodiverse body of water in Everett, WA, with influence from the freshwater Snohomish River and saltwater from the Pacific Ocean flowing through the Strait of Juan de Fuca into the Possession Sound. Factors of water chemistry and heavy metals, residing in sediment and influenced by surrounding anthropogenic activity, contribute to the estuary ecosystem and support various trophic levels of marine life. This study observes temperature, salinity, pH, and chlorophyll in the water column, and lead, copper, zinc, and mercury in sediment from 2009 to 2018 at three sites with differing proximity to the Snohomish River: MBT, Buoy, and Everett Marina. The parameters were analyzed through boat-based research and Sea-Bird CTD data collected by the Ocean Research College Academy (ORCA) with funding from the National Science Foundation and in partnership with the University of Washington, Gravity Marine Consulting, and the State Department of Ecology. Longitudinal research at ORCA allows students to monitor marine mammal abundance, including sightings of harbor seals, California sea lions, gray whales and harbor porpoise. This investigation is motivated by potential connections between water quality parameters and the abundance of marine mammals. Results indicate heavy metal levels at Buoy reached a maximum in 2011 with mercury, copper, lead and zinc metals averaging 0.05 mg/kg, 29.73 mg/kg, 7.03 mg/kg, and 54.33 mg/kg, respectively; however, average zinc levels were highest at approximately 55.60 mg/kg in 2016. Comparably, MBT heavy metal concentrations were lower and demonstrated greater variability. In 2018, Everett Marina salinity levels show more fluctuation than MBT, while chlorophyll had a max of approximately 46.4 ug/L at MBT. Gray whales that return to Possession Sound to feed on benthic organisms are potentially impacted by these conditions.

Eelgrass (Zostera marina) is an ecologically important species of marine angiosperm that inhabits sublittoral sediments in the northern hemisphere. Eelgrass beds provide critical food and habitat for many species of fish, invertebrates, and birds. Its root system has the capacity to interact with both the water column and sediment, making it uniquely poised to influence metal cycles within the ecosystem, including those affected by anthropogenic activity. Eelgrass, sediment, and water samples were collected from three sites in Possession Sound, a part of Puget Sound that borders the City of Everett and contains the Snohomish River Estuary. Samples were processed in the University of Washington Isotope Geochemistry Lab before being analyzed for trace metal concentrations using an ICP-MS. In addition, two-meter long sediment cores were taken from three sites in the Possession Sound and the bottom 5cm were analyzed, allowing the researcher to quantify the anthropogenic influence on metal concentrations within sediment. It was hypothesized that the roots, shoots and blades of the eelgrass would exhibit differing concentrations of heavy metals, and that sediment collected within eelgrass beds would contain higher concentrations of metals than sediment collected outside eelgrass beds. Additionally, samples from sites closer to human activity would contain higher concentrations of metals and a greater proportion of metals from anthropogenic sources. Preliminary results of the ongoing study show that concentrations of arsenic, copper, and zinc were higher in eelgrass blades than roots, and eelgrass tissue had higher metal concentrations than the surrounding sediment. These results suggest that eelgrass uptakes metals from its environment, accumulating as well as translocating them in its tissues. Additionally, study locations nearer to the mouth of the Snohomish River and human activity had higher concentrations of heavy metals overall in both sediment and eelgrass.

Dysregulation of the dopamine system is a central mechanism driving substance use disorders. Our laboratory has shown that chronic cocaine consumption decreases dopamine release in the nucleus accumbens of the rat, which is a brain area that is important in reinforcement learning. This study also found that restoring dopamine transmission through the administration of the dopaminergic drug, L-DOPA, decreased their cocaine consumption. Recently, we have also shown that acute administration of L-DOPA decreases ethanol (EtOH) intake. Thus, the present study sought to examine the effects of chronic L-DOPA on operant responding for EtOH in adult male rats. Rats were presented with a 2-bottle choice between an EtOH (20%) solution or water, daily for 21 days. Next, animals made nose poke responses (FR1) for 0.2 mLs of an EtOH (20%) solution over 1-h daily sessions for 35 days. On Days 26-35, rats consecutively received either vehicle or L-DOPA (30 mg/kg) for 5 days, counterbalanced across days, and L-DOPA decreased operant responding for EtOH compared to VEH. We are presently examining the effects of L-DOPA on dopamine release during operant responding for EtOH. Together, these data may suggest the efficacy of L-DOPA as a treatment for patients with alcoholism.

Dynamic coordination of animal motion depends on the interaction between the neuromuscular system and body mechanics. Changes in muscle length resulting from neuromuscular activation drive the control of locomotion. This project seeks to predict change in muscle length over time based on electrical activity in the complex physiological environment of a living organism. During energetically costly insect flight, the antagonistic shortening of the dorsal longitudinal muscles (DLMs) and dorsal ventral muscles (DVMs) deform the thorax to indirectly power wing flapping. Using electromyography (EMG), we recorded both DLM and DVM activity in vivo during tethered flight of the insect model Manduca sexta. Simultaneously, we captured high-speed video of thorax deformation to measure the change in length of the DLM muscles, which attach directly to the exoskeleton. Unlike other insects, in M. sexta there is a one-to-one relationship between muscle electrical activation and length-wise contraction, allowing direct comparison between these two temporal data sets. Using machine learning, we created a model to predict the amplitude and time course of changes in muscle length 𝓁(𝑡) based on characteristics of the EMG recording. Predicting downstream insect flight mechanics based on EMG data is an exciting application of machine learning which enables us both to better understand the factors influencing muscle length in vivo, and to connect multi-scale muscle structural data through the common link of EMG data. For example, we will predict organism-level changes in muscle length that would have occurred in existing data sets of sub-cellular muscle kinematics based on EMG data collected simultaneously.

Gut Microbiome is increasingly recognized as a pivotal player in toxicological responses, thus dysbiosis or microbial imbalance may worsen chemical-induced adverse outcomes such as inflammation, metabolic syndrome, and cancer. Early life exposure to environmental contaminants may produce long term toxicities in adulthood, and little is known to what extent early life exposure to environmental contaminants modulate the gut microbiome beyond adulthood. Therefore, this study tested the effects of perinatal exposure to 3 human health relevant environmental contaminants (BDE-47, TBBPA, and BPS), on the composition and functions of the gut microbiome of perinatally exposed adult male mice. CD-1 mouse dams were orally exposed to vehicle (corn-oil, 10ml/kg), BDE-47 (0.2mg/kg), TBBPA (0.2mg/kg), and BPS (0.2mg/kg) once daily from gestational day 8 to the end of lactation (postnatal day 21). Feces from male pups were collected at 12-weeks of age (n=14-23/group). Microbial DNA was isolated, subjected to 16rDNA sequencing, and analyzed using QIIME. Microbial biomarkers for each chemical exposure were predicted using LefSe. Microbial functions and key taxa that drive functional changes were predicted using PICRUSt and FishTaco, respectively. None of the 3 chemicals markedly altered the overall richness of the gut microbiome in adult male pups. However, principle coordinate analysis showed a distinct separation among different exposure groups, and especially between BPS and vehicle exposure groups. A total of 73 taxa were persistently altered by at least 1 chemical exposure, among which 12 taxa were commonly regulated by all 3 chemicals. The most representative microbial biomarkers for each exposure condition were Clostridiales for vehicle, S24-7 for BDE-47, Rikenellaceae for TBBPA, and Lactobacillus for BPS. Together, these observations suggest early life exposure to these human health relevant environmental contaminants produce persistent gut dysbiosis in adult male offspring, leading to functional shifts that may play important roles in regulating certain diseases of the host.

LGBTQ+ students face overwhelmingly negative statistics in and out of school, here and across the world. Supportive teachers and the educational efforts they are involved in like GSAs (Gay Straight Alliance), inclusive curriculum, and specifically inclusive policies make significant positive effects on LGBTQ+ students. The teachers that can understand these students the most though are LGBTQ+ themselves. This project explores the following questions. 1. How do teachers who identify as LGBTQ+ interact with their public education system? 2. Do teachers who identify as LGBTQ+ feel supported in the daily work life and in their professional goals as teachers? 3. What insights do teachers who identify as LGTBQ+ have for their LGBTQ+ students? Through collaboration with various equity and educational leaders, primarily from Washington State and the UW College of Education, a Google Forms survey was created and shared through various digital platforms. Qualitative data was taken from the survey responses of 20 LGBTQ+ identifying teachers in the United States and 2 in China. Responses were analyzed using coding techniques where I deep read responses and categorized them by relationships and on a scale of trust. A majority of teachers were open about their identity and stated feeling supported by their schools. However, analysis revealed that most long answer text responses showed varying levels of mistrust: between teacher and faculty; teacher, student and the school community; as a factor of race and ethnicity; and learned from their life history from student to teacher. The suggested solutions are to recreate and implement discrimination and protective policies, curriculum, and space and face reforms that are specifically inclusive to the entire range of identities that LGBTQ+ individuals inhabit. Additionally, more research needs to be done in how policies and LGBTQ+ issues affect the symbiotic relationships between students and educators.

Current methods of modeling tissues rely on two-dimensional (2D) cell cultures which fail to incorporate the three-dimensional (3D) aspect of native tissues in the body and therefore cannot mimic tissue-specific conditions in vivo. The inability to accurately mimic the native properties of tissues in vitro makes characterizing physiological cell behavior challenging and limits the applications of these models. As such, the lack of sufficient in vitro tissue models necessitates the need for a more advanced engineered tissue models that accurately recapitulates the native morphology and function of cells in vivo. Previously developed in vitro platforms that attempt to model human vasculature in vivo have been limited in their ability to imitate the circumferential architecture of smooth muscle cells which surround the veins and arteries. Through the production of a more advanced vascular tissue engineered platform that accurately recapitulates biomimetic conditions of native tissue, we could better study cardiovascular biology, disease modeling, and drug-response in a dish. We propose the fabrication of an architecturally-controlled multi-layered 3D smooth muscle cardiovascular model that mimics the tubular structure of blood vessels in vivo to study structure-function relationships. Utilizing a thermoresponsive nanopatterned film, we are able to direct cell alignment and layer sheets of cells to create a circumferentially aligned 3D smooth muscle tissue model that mimics the physiology of the vascular tunica media. Furthermore, we have designed a fibrin gel casting method to produce tubes with a hollow intraluminal space that has mechanical properties that are physiologically relevant to human tissue. We aim to determine how anisotropic alignment of smooth muscle affects vascular compliance. This model is highly versatile in nature and can be functionalized with a wide variety of cell types to accommodate different tubular tissue structure throughout the human body.

Many communities of color have been disenfranchised as a result of interactions with the criminal legal system. While many studies have shown that access to higher education reduces recidivism and encourages upward mobility, a very small percentage of this impacted population are actually able to access institutions of higher education. Therefore, the purpose of this research is to address the disparate representation of system-impacted individuals in higher education. This project aims to answer and begin to respond to the following questions: 1) What are the challenges and outright barriers for system-impacted students who wish to continue their education at UW? 2) What can UW do to make it a feasible destination for students who are system-impacted? This research project includes: the collection and analysis of existing data on system-impacted individuals and access to higher education; interviews with UW administrative offices that may play a role in the access to higher education for system-impacted individuals. Thereafter, a working group consisting of: system-impacted individuals; system-impacted students; students interested in criminal justice reform; and UW faculty interested in criminal justice reform; will form and implement strategies on how to lower institutional barriers and create clearer pathways to the UW for system impacted-individuals. By building partnering strategies with the UW community, the goal of the Pathways to UW project is to develop more clearer and transparent pathways for individuals who have been system-impacted to enroll on UW campuses. I want to ultimately build a community and a working network on campus that supports access and welcomes individuals impacted by the criminal and immigration system. Currently, there is no system in place on campus that supports such a marginalized population. To have such a system in place would address many racial and class disparities among the marginalized communities these impacted individuals traditionally come from.

Students who speak English as a foreign language (EFLs) are pushed within U.S. academic settings to strive for “standard” English—an academic English heralding grammar “correctness” and adherence to rules. EFL curriculum prioritizes for “standard” English, but ignores the ways that terms like “standard” are exclusive, and rarely addresses how an EFL writer may use language in more inventive ways. How do we re-imagine the teaching of writing in ways that can not only help EFL writers in formal high-stakes writing, but also open the door to other creative uses of writing which need not adhere to such strict and increasingly hackneyed standards? My research will draw from many of the conversations focused on second-language acquisition and bilingual education, including work from scholars such as David Freeman and Sara Alvarez, to understand the most recent and effective approaches to teaching English as a second language, as well as discover what approaches to teaching creative writing hold untapped potential for EFL students to acquire new language skills. I will use The Chicago Manual of Style as a contemporary example of a style guide which prescribes “standard” grammar convention. Using an assortment of the grammar topics selected from Chicago for comparison, I will discuss examples of deviations from grammar conventions by writers from various linguistic backgrounds, including Safiya Sinclair, Ocean Vuong, and Mohsin Hamid. By investigating who makes English “standards,” how EFLs best learn, and how these standards have been broken for the better, I aim to create a subversive style guide for EFL writers which is useful for both formal and creative writing.

Giardia lamblia, a microscopic flagellated parasite that causes giardiasis, is a highly divergent eukaryote in which conventional Golgi, endosomes, lysosomes, and mitochondria are absent. Similar to other parasites of medical importance, Giardia lamblia has two life cycle stages - proliferative trophozoite form and water-resistant, nonmotile, infectious cyst form. During encystation when Giardia trophozoites transform into infectious cysts, they secrete cyst wall proteins (CWP1-3) that are trafficked and processed in Encystation Specific Vesicles (ESVs). These vesicles are thought to be stage-induced Golgi in Giardia. Previous work in the lab has shown that the signaling activities of G. lamblia’s single Rho family GTPase, GIRac play an important role in regulating this encystation process. The aim is to characterize proteins in Giardia lamblia that potentially interact with GIRac, currently focusing on homologs of known players in membrane trafficking by examining their order of arrival using morphology of the ESVs based on CWP1 staining. Since this is subjective, there is a need for stage-specific molecular markers. In other eukaryotes, Rab GTPases have been established as markers of membrane identity and directionality of trafficking. Only two out of nine Giardia’s Rab GTPases have been localized and reportedly found at ESVs and based on published images, they appear to be recruited at different stages of ESV maturation. By tagging the N-terminus of all 9 Giardia Rab GTPases with fluorescent tags, we can screen them for their localization to ESVs and perform multi-color imaging to determine the order of arrival of these markers. Ultimately, this finding of stage-specific molecular markers could be a powerful tool to further suggests its potential as a novel target for drug development to treat giardiasis.

Extra chromosomal pieces of DNA, called plasmids, exist within bacterial populations. Many scientists believe that the relationship between plasmids and their bacterial hosts is mutually beneficial. Plasmids use replication machinery from their host to ensure their continued persistence. Meanwhile, the plasmid carries genes that can benefit the bacteria, such as genes that can provide resistance to antibiotics. In environments that contain antibiotics, bacteria that contain plasmids with antibiotic resistance genes would have a higher fitness and be able to survive and reproduce at a higher rate compared to bacteria that don’t carry plasmids. Contrary to popular belief, research by members in our group showed that different plasmids actually persisted in bacterial populations when they were not under selection. The purpose of this project is to see if the trend of plasmid persistence would continue in a nutrient limited environment. We performed a long term evolution experiment on three types of bacteria containing plasmids in a nutrient limited environment. Next, grew the evolved descendants in an environment containing antibiotic to see what portion of the population is still containing the plasmid. The results of this experiment will help scientists have a more holistic understanding of plasmid biology which could have implications on antibiotic treatments.

 As the number of American students who identify as mixed race or biracial continues to grow, the American education system still has yet to make the necessary changes that are responsive to the needs of this shifting demographic. While identifying students on their own terms is important for all students, for mixed-race students, the questions and potential disconnect between racial labelling and how one defines themselves is fundamental. This study examines the roles biracial categorization plays in today’s classrooms through lived experiences as remembered by college students. Many classrooms still struggle to incorporate the achievements of minorities, and, in some cases, the mixed identity of a historical figure is overlooked entirely. The inability to see themselves in the curriculum may be causing mixed-race students to feel invisible in the classroom and disconnected from their education (Joseph-Salisbury, 2017). Drawing on findings from survey results, focus groups, and individual interviews, this research project contributes to studies focusing on the schooling experiences of mixed-race students. Maria Root (1996) and Kristen Renn’s (2003) models of biracial categorization are used as a framework for the study, as the project re-assesses the inclusivity and adequacy of the biracial categories introduced. In the classroom, seemingly small interactions and events may be forcing students to choose one aspect of their identity, rather than celebrating both. Focusing on how the classroom setting impacts identity has the potential to make the classroom a more inclusive space that is responsive to the myriad of ways biracial students may or may not choose to identify.

Advanced oxidation treatment processes involve powerful and indiscriminate radical intermediates, including hydroxyl radicals (•OH) and sulfate radicals (SO4-•). Inefficiency in radical-driven treatment systems involves scavenging reactions where radicals react with non-target species in water and solids. Radical scavenging studies have been focused on soluble scavengers in the water and have not assessed radical scavenging by solids which are also present in oxidation treatment systems. The objective of this study was to quantify radical scavenging by solid surfaces. •OH were produced in iron (Fe)- and UV-activated hydrogen peroxide (Fe-AHP, UV-AHP) systems where the loss of rhodamine B (RhB) dye served as an indicator of •OH activity. The basis used to estimate the •OH surface scavenging rate constant (k≡S) were comparisons of treatment results between simple solids-free oxidation systems and more complex systems containing mineral solids. The solids-free system was based on Fe-AHP and UV-AHP reactions; the solids-amended systems were identical but contained different mineral species. Therefore, differences in the loss of RhB were attributed to •OH scavenging by the solid surfaces in the Fe-AHP and UV-AHP treatment systems. Alumina (Al₂O₃), silica (SiO₂), and montmorillonite (Al₂H₂O₁₂Si₄) (MMT) are solid minerals found in soil and aquifers. These minerals were used in this study to assess the solid surface scavenging rate constants. Preliminary results in the Fe-AHP system indicated that k≡S for silica (2.85×10⁶ 1/m²×s) was not statistically distinguishable from alumina (3.92×10⁶ 1/m²×s). k≡S values in the UV-AHP system for silica (4.50×10⁶ 1/m2×s) and alumina (7.45×106 1/m2×s) were greater than estimates in the Fe-AHP system and may be due to pH. k≡S,MMT (≤ 4.22×10⁵ 1/m²×s) was much less than k≡S for silica and alumina indicating k≡S is mineral-specific. A critical analysis suggests that radical scavenging by solid surfaces in aquifer systems is orders of magnitude greater than scavengers in the water.

The works of authors who blur the academic and the personal are often called genre-busting. Conferred that radical title, these authors occupy a liminal space in form and method. This is where I see a pivot to chart a course between recent discourses on queer affect and the potential of positionality in academic research. I will approach and put into dialogue Maggie Nelson’s Bluets and Samuel Delany’s Times Square Red, Times Square Blue to analyze the link between methodology and form, and attend to the places where scholarship oozes personhood. My own method will be partly autoethnographic, coupled with textual analysis that mobiliizes queer and ecofeminist discourses. I will explore how genre-busting writers navigate autographic and academic writing to package and represent experience, thinking nimbly about how they communicate interiority. What kind of vulnerability does this mode of writing perform? This dialogue will be extended to the cultivation of an environmental ethics, in which I propose that writers who write between genres have mapped modes of vulnerability and rupture that are vital to a sustainable discourse.

Immanuel Kant, in the Critique of the Power of Judgement, describes how we come to find objects beautiful through an aesthetic judgement. In particular, he claims that an object is beautiful in virtue of its property that we cannot find a concept to match it with. This explains our contemplation when looking at art whereas an object such as a hammer does not motivate us to contemplate it. He also notes that beauty does not rely on the idea of perfection, which is to have the most of certain qualities. In contrast to beauty, Kant puts forth the idea of purposiveness, which is a consideration towards an object's existence being a part of the causation of some end. This means for an object to have a purposiveness would be for it to fit as a means to an end goal. Kant then puts forth the idea of there being two types of beauty, being adherent and pure. Pure beauty follows Kant's general agreement that beauty should be free from concepts. However, Kant experiences certain tensions in terms of adherent beauty, in which an object is beautiful because of its utility. This appears contradictory to Kant's previous commitments to a lack of concepts. I explore these tensions and consider possible Kantian explanations for this. I’ve begun study on Robert Clewis’ “The Origins of Adherent Beauty” to inform this topic as well. Clewis elaborates on the different approaches during that time to reconcile utility and beauty, noting several position Kant takes before assuming his current ideas. If we are able to resolve answers relating to adherent beauty, we will be able to design possible criteria for secondary adherent beauty. Doing so will also allow us to possibly add a purpose to different types of art depending on what concept they are the perfection of.

The relationship between fertility and economic development can be modeled in many different ways. To microeconomists, fertility may determine the “quality” of children in one family, where quality is typically interpreted as a child’s level of education. These models of child quality are based on the classical quantity-quality tradeoff model by Becker, in which parents choose to substitute child quality for child quantity under some circumstances. The focus of this paper is to detect whether the quantity-quality tradeoff exists under the two-child policy in China, implemented in 2015. Since 2015, Chinese families have been permitted to have two children, and this change in the quantity of children in a family may affect child quality as well. However, the two-child policy was implemented only three years ago, so data is lacking. Thus, I chose Taiwan as my case study. I use data from Taiwan to find some the effect of fertility and apply those results to circumstances in China. By using linear regression, I find that the results from Taiwan are consistent with the classical model. Once the quantity-quality tradeoff under two-child policy is clear, scholars can further research on the short-term and long-term influence of two-child policy in China.

Crucial processes in clean energy research, such as the splitting of water into H₂ and O₂ and the reduction of CO₂, require multi-electron redox events throughout a catalytic cycle. Noble metals such as iridium and platinum prefer such events, while more abundant and consequently cheaper base metals prefer single-electron events. Redox-active ligands offer the potential of enabling noble metal behavior in base metals by combining a single-electron transformation at both the metal and the ligand to create an overall two-electron process. While redox non-innocent ligands are typically comprised of organic components, cobalt selenide clusters offer an attractive alternative given their wide variety of accessible oxidation states. Here, I present the synthesis of heteroleptic cobalt selenide clusters [cis-Co₆Se₈(PEt₃)₄(RNHP(C₆H₅)₂)₂ Et = ethyl, R = alkyl, aryl] containing ditopic aminophosphine ligands. The cluster was then metallated using copper(II) triflate and the product was fully characterized by multi-nuclear nuclear magnetic resonance, ultraviolet-visible, and infrared spectroscopies. Further analysis was performed using cyclic voltammetry and the solid-state structure has been solved via single-crystal X-ray crystallography. Upon spectroscopic analysis, it appears that copper(II) is reduced to copper(I) by the cluster. This result is encouraging, as using clusters as redox-active ligands would require facile electron transfer between the metal atom and the cluster core.

Black phosphorus, an allotrope of phosphorus with a unique layered structure, can be exfoliated to form a few layer variant called phosphorene.  Phosphorene has recently emerged in the field of 2D materials as a promising candidate for use in novel electronic and optical devices.  Phosphorene's Achilles' heel, however, is its air-sensitivity.  When exposed to air, phosphorene is rapidly oxidized, losing its valuable optoelectronic properties.  Herein, we propose Lewis acids such as GaCl3, AlCl3, and AlBr3 as effective reagents for protecting phosphorene.  This Lewis acid-based strategy has advantages over previous methods because it is reversible and leaves phosphorene optically and electronically accessible.  A Lewis acid can act as an electron acceptor for the lone electons pairs on the surface of black phosphorus.  By sterically blocking oxygen's access to these lone pairs, ambient degradation in phosphorene is drastically slowed.

Glioblastoma multiforme (GBM) is a highly aggressive variant of brain cancer that has been a focal point of chemotherapeutic development for years. However, initial drug screening using traditional in vitro culture of GBM cells frequently produces encouraging results that do not translate well to animal models and clinical application. To address this disparity, implementation of three-dimensional tumor modeling can better emulate the microenvironment that tumor cells experience in situ, improving accuracy of early in vitro screening. We developed two chitosan-based polymer blends to produce biocompatible, porous scaffolds that mimic the extracellular matrix and promote cell adhesion. Scaffold production was done in 96-well cell culture plates for high-throughput drug screening with a large sample size. These scaffolds were used to grow human GBM cell lines U-118 MG, U-87 MG and GBM6 for 14 days, confirming cell compatibility with the materials and promoting formation of tumor spheroids. The cultures were treated with the established chemotherapeutic agent temozolomide (TMZ) for 72 hours, and cells were then tested for metabolic activity using the Alamar Blue resazurin assay. We demonstrated increased resistance to chemotherapeutics in cells with this induced morphology relative to cells grown in two-dimensions for all cell lines and both scaffold compositions. Additionally, based on gene and protein expression analysis, GBM cell spheroids more strongly expressed cancer stem cell characteristics and greater malignancy. The presence of GBM resistance to chemotherapy and enhanced characteristics associated with in situ tumors indicates the potential of using chitosan-based tissue scaffolds for more accurate high-throughput screening of novel GBM treatments.

Primary care (PC) is the foundation of healthcare. Family physicians (FPs) are specialty trained and certified in PC and provide most PC services in the US. General practitioners (GPs), a separate group with no specialty training, are commonly confused with FPs despite differences in demographic, professional and service characteristics. Medical researchers commonly ignore this distinction and report the two groups together. Our study aims to document the rate that research in major medical journals separates or lumps GPs and FPs. We selected 23 journals on impact factor, US focus and relevance to primary care across MedLine categories of primary health care, general internal medicine, pediatrics, public health and health services. Using a MedLine search, we sought all papers published in these journals in 2017-18 that met inclusion criteria: original research, done in US, studying FPs and/or GPs and/or primary care physicians. Two researchers reviewed each article to determine inclusion, study characteristics and whether it lumped FPs with GPs or reported them separately in results. Literature search retrieved 440 total studies, with 104 (23.6%) meeting inclusion criteria. Among these, 42 (40.4%) included family physicians only, leaving 62 (59.6%) that also included GPs. Among studies including GPs, only 3 (2.9%) separated GPs from FPs. Another 23 (22.1%) lumped the GPs and FPs together. In 36 (34.6%) the reporting of GPs, FPs and others was unclear. We identified no studies on GPs only. Further analysis will examine FP-GP lumping vs. splitting by journal type, author specialty and source of specialty information.  In key medical journals, most studies lump together GPs and FPs, masking differences between these distinct groups of physicians. Most research reports fail to explain how they classify PC clinicians. Research reports need to accurately study FPs and primary care in the US.

The Puget Sound is an economically and culturally important marine ecosystem, and insects are a little understood part of this ecosystem. Research suggests that insects are an important food source for near shore juvenile salmon which has wider ecological and conservation implications, including at higher trophic levels; while some work has been done in coastal British Columbia, little work has been done on the insects themselves within the environment of the Puget Sound. To close this biodiversity knowledge gap, field and museum collection surveys were and are being conducted to gain a better understanding of the insects of Puget Sound. Various hand sampling techniques were utilized including net, aspirator and insect vacuum. So far, 15 individual species of 6 families of 2 different orders of insects were confirmed present in Puget Sound in this study. Additionally, 10 species of 2 families of 2 different orders of insects were reported in similar conditions in the literature, but were not observed in this survey or found in museum collections. The most abundant order was Diptera. In all, 14 beaches on the Puget Sound have assessed and some contained unique species. Further studies, in seasonality (and food availability), habitat substrate preference, insect behavior, insect population dynamics and a deeper look at predation of marine insects by juvenile salmon could be investigated based off the work done in this study.

The human adaptive immune system is composed of B and T cell lymphocytes. Of the latter, these cells are further differentiated and identified by the presence of CD (cluster of differentiation) molecules. CD molecules are expressed on the surface of the cell and can range from receptors essential to the cell’s functionality to glycoproteins marking distinct stages in their maturation. For example, CD45RA is expressed on naïve T cells while the presence of CCR7 marks the change to effector memory cells. Flow cytometry can be used as a tool to aid in detecting multiple types of T cells in a peripheral blood sample both rapidly and accurately. The use of 10-color flow cytometry in the clinical laboratory can provide simultaneous detection of ten cell markers to help differentiate the populations of T cells in a patient. Seattle Children’s Hospital utilizes this technology to monitor immune status in patients with auto-immune disorders, immunodeficiencies and post transplantation. Extended T-cell immunophenotyping by flow cytometry is not a mainstream clinical test. Since only a few laboratories offer this service, samples are often received from sites outside the hospital. With distance comes the issue of peripheral blood stability, especially regarding the loss of CD markers among the T-cell population over time. This study will compare the stability of T cell subsets through peripheral blood samples collected in EDTA vs sodium heparin collection tubes through four days of daily T cell immunophenotyping testing, as well as to determine the last day of stability for each T cell subset. The results will help form the guidelines regarding specimen stability for transport and the availability of offering this test to both adult and pediatric patients across the globe and help aid the diagnosis and treatment of various diseases and conditions that these patients face.

A positron emission tomography scan (PET scan) can be used to map areas of potential cancer in the body. Cancer cells multiply at an incredibly fast rate, and in doing so, use a greater amount of glucose to fuel their high-energy needs compared to normal tissues. PET scans use radiolabeled fluorodeoxyglucose to quantify cellular metabolic activity, producing visual hotspots that are usually overlayed on computed tomography (CT) images and correlate to cancer sites (“PET/CT”). PET/CTs are often used to follow patients with acute myeloid leukemia (AML) after hematopoetic cell transplantation (HCT). In the lab’s database of over 300 consecutive patients whose AML relapsed after HCT, we found 15 patients who were followed with PET/CT because of extramedullary disease. These patients received a variety of treatments for their AML relapses, including induction chemotherapy, radiation, and/or hypomethylating therapy. We sought to assess if a negative post-treatment PET was helpful in predicting a cure. Through detailed chart review, we found PET scan negativitity is hard to achieve, a negative PET is not reassuring (50% still relapsed) and even a low SUV-positive PET is prognostic of disease progression. Moreover, if any extramedullary disease is present, systemic therapy prolongs life more than local radiation alone, but no treatments are likely to be curative.

Becoming a mother can be an incredibly beautiful process, but it can also become overwhelming and extremely stressful, especially when lacking support and resources. The chronic and significant stress that low-income, pregnant women experience put them at greater risk for adverse health outcomes and their infant at risk for poor developmental outcomes. At the University of Washington’s Center for Child and Family Well-Being, our research team has developed mindfulness-based interventions to help new moms adjust to their new life. Our goal is to examine the effects of stress on the mother-infant dyad and to evaluate whether these programs are beneficial for moms and their babies. Expecting mothers are randomly assigned to attend one mindfulness-based program that focuses on preparing for childbirth, reducing postpartum stress, or developing parenting skills. Administration of extensive questionnaires to the mother and recordings of the mother and baby completing various tasks, before and after the program, measure the pair’s socioemotional development. We also collect cortisol, a stress hormone, and measure heart rate and breathing during a stress-reactivity paradigm to inform us of the physiological effects of stress. We hypothesize that mothers who exhibit high levels of mindfulness are more likely to engage in consistent, warm, and responsive parenting skills. As a result, these mothers' infants will display better self-regulation and focus. We also predict that mothers and babies who participate in these mindfulness interventions are more likely to show a decrease in cortisol production and have controlled cardiovascular reactivity. Recommendations for future research include establishing a systematic way of identifying mothers at risk so that we may prevent further harms caused by stress. Implications of the findings can be used to advocate for equitable, accessible mental health programs and implementation of public health policy centered around protecting and empowering vulnerable women and children in our community.

Archaeologists are increasingly concerned with the long-term preservation and accessibility of research data. However, few have explored the challenges and opportunities of data management in the context of community-based research with Native communities. This project focuses on the data management practices of Field Methods of Indigenous Archaeology (FMIA), a community-based research partnership between UW and the Confederated Tribes of Grand Ronde Historic Preservation Office. It examines how these practices take on special importance when working with Native communities, including how they help bridge gaps between archaeologists’ interpretations of Grand Ronde history and those maintained by the tribal community. To explore this question, I photographed artifacts, digitized field and lab data, and assessed FMIA’s approach to data curation and accessibility. This archive of photographs and digital data ensures that project data remain usable to future researchers and the Grand Ronde community in investigations of tribal history. Thinking through archaeological data management thus facilitates better organization of research data and fosters increased community collaboration.

The recent large number of world-wide disasters has catapulted disaster research to a highly important endeavor. 2017 was the most expensive on record with 16 U.S. climate events’ losses totaling $306 billion. Research suggests the costliest effects may result from emotional and psychosocial health. Those who are: seniors, distressed, and/or experience early-life vulnerabilities are at increased risk for negative health responses. This study addresses the need to reduce vulnerability and increase preparedness by evaluating how older adults perceive/prepare for disasters, including psychological factors that may influence their motivation to prepare. Literature review results from 26 references indicate older adults are: (1) among our most vulnerable populations for natural disasters, (2) underprepared, though resources are available, and (3) preparing close friends/family before themselves. The Socioemotional Selectivity Theory (SST) posits that as we age, our time perceptions become constrained, motivations shift, and we prefer positive over negative information. Therefore, I asked: (1) if older adults are intuitively resistant to negative information, such as impending disasters, how might we reframe it to be congruent with their desire for positive information? (2) If we approach older adults through more positive experiences, will they be receptive and motivated to prepare? I employed a model, namely: disaster preparedness behavior (PB) is a function of vulnerability (V) and resilience (R). To test this, a survey was developed to assess how factors of V and R would interact and influence PB. I will pilot test this survey through the evaluation of community-living older adults. PB is expected to be negatively related to V, positively related to R. This study extends disaster research by using psychological variables to predict preparedness and evaluating motivation to prepare using SST as a guiding framework. Results should increase knowledge about older adults’ perceptions of disaster preparedness and factors to mitigate increased preparedness.

As anthropogenic climate change progresses and alters our marine ecosystems, it is important to monitor the changes it creates in order to inform plans for mitigation or management. This project, completed as part of the Puget Sound Foraminifera Research Project at The Burke Museum, uses sediment samples collected by the Washington State Department of Ecology and extracts benthic foraminifera from those samples to learn vital information about the health of the Puget Sound. Benthic foraminifera are single-celled organisms that live on or in marine sediment and form shells of calcium carbonate or agglutinated sand grains. This research looks at the dissolution of shells of a species of calcareous foraminifera called Elphidiella hannai in order to establish whether different populations across Puget Sound are affected differently and if dissolution primarily happens before or after the death of individuals. For this research, samples collected from a variety of Puget Sound embayments over four years starting in 2015 were processed and stained with Rose Bengal to ascertain whether the foraminifera were alive at the time they were collected. Following this, foraminifera were sorted and species were grouped. Finally Elphidiella hannai were assessed for dissolution on a 0-3 scale, 0 meaning pristine and 3 heavily damaged. Preliminary results show higher levels of damage in stained individuals and vastly differing amounts of damage in different Puget Sound embayments, suggesting most damage happened while foraminifera were still alive and that changes in acidity of water are impacting populations at different rates.

In the central nervous system, insulin acts as an anorexigenic hormone, regulating the desire for fatty and sugary foods. It also plays an important role in learning and memory. Thus, a malfunctioning insulin transport system across the blood-brain barrier (BBB) could be linked to obesity, the development of type 2 diabetes, and cognitive impairments as occur in Alzheimer’s disease. Studies have shown that insulin binds to insulin receptors (IR) located on the endothelial cells which make up the BBB; the activated insulin-IR complex is then taken up into the cell, where it sets off a signal cascade. Additionally, insulin binds a protein responsible for transport from the luminal to abluminal side of the brain endothelial cell. However, the mechanism by which this occurs is still not understood. Thus, we set out to elucidate the difference between insulin receptor uptake and insulin transcytosis in vivo, focusing on clathrin and caveolin, the two proteins primarily responsible for mediating endocytosis. To do this, we use radiolabeled insulin, the IR antagonist S961 (which binds to IR but is not taken up into the cell), and three pharmacological agents: phorbol 12-myristate 13-actetate (PMA) to promote endocytosis, monensin to disrupt clathrin-mediated endocytosis, and filipin to disrupt caveolin. To eliminate serum factors, cardiac perfusion in male CD-1 mice will be performed. One group will be the vehicle control group, and the other will receive radiolabeled insulin, S961, in addition to one of the three pharmacological agents. Perfusions will last from 1-10 minutes, in which brains are collected and dissected into brain regions. Radioactivity is measured in the hypothalamus and hippocampus as well as whole brain. The data collected will help us better understand the differences between insulin transcytosis versus endocytosis and how insulin transport may go awry in Alzheimer’s disease, diabetes, and obesity conditions.

Noncommunicable diseases (NCDs) are responsible for the majority of all global deaths. They reduce quality of life on a mass scale and threatening the United Nation's 2030 Agenda for Sustainable Development while creating massive financial burden in the Global South and developed countries alike. However, in 2017, NCDs received only 2% of total development assistance for health (DAH) in 2017 despite causing 67% of global deaths. This is a signficant lack of alignment between disease burden and funding. Researchers state that donor groups divert DAH to other causes because they are unaware of the impact of NCDs in low and middle income countries. In addition, curbing NCDs on a mass scale requires highly complex responses in comparison to the more cost-effective and evidence-based approaches for many infectious diseases. However, these claims are based on primarily anecdotal studies and there is limited quantitative research on how donor groups allocate foreign aid for NCDs. This report aims to understand how donor groups prioritize economic, political, social, and epidemiological determinants when deciding the level of DAH to provide to countries for NCDs. The master dataset is provided by RTI International and consists of grants for NCDs from 2010 to 2015. It is merged with demographic, economic, geographic, and epidemiological data extracted from publicly available sources. I model correlations between these factors and DAH received using a multiple linear regression. As foundations and NGOs provide the majority of global funding for NCDs, I concentrate on this donor group. I hypothesize that NGOs and foundations concentrate on health indicators and level of corruption when allocating aid for NCDs versus economic indicators, such as level of trade openness. Further research of donor behavior and development assistance for health will contribute to greater transparency in funding processes to better address the emerging NCD pandemic.

Marine terraces are geomorphic features created by wave erosion of the land, which is modulated by crustal uplift or past sea level changes. In this study, I consider possible driving mechanisms that could have generated the marine terraces on the archipelago of Haida Gwaii, Canada. Southwest of the island, there is a young subduction zone that was only initiated ~6 Ma. This subduction has generated a M_w 7.8 earthquake in 2012. From this study, we can find out more information about the plate boundary, including uplift and deformation histories. The island has also experienced ice coverage during the last glacial maximum. Since then, the ice has melted. As a result, the island may have uplifted in response to the ice melting during the Holocene. To obtain the data needed, I am using newly released LIDAR data which contain high resolution elevation topography to map the landforms digitally. The purpose of this project is to provide a resource for locations of the terraces and also to find patterns in distribution and in elevation of marine terraces in Haida Gwaii.

The identification and characterization of natural and artificial protein-protein interactions are fundamental to science and engineering. Although many technologies have been established to expedite research in this area, all can hardly meet the need to analyze vastly diverse protein-interactome networks, dynamics, evolution, and druggability. To develop a high-throughput quantitative interaction profiling technology, multimeric protein interaction sequencing (mPI-seq), we performed a 20×20-plex binding assay in a single aqueous solution using a set of de novo designed heterodimeric pairs. First, we barcoded the proteins with DNAs by ribosome and mRNA display. Then, barcoded proteins were assayed en masse in aqueous solution and immobilized into an ultrathin polyacrylamide gel layer attached to glass surface for in situ sequencing. DNA barcodes were amplified into discrete DNA clusters (polymerase colonies or polonies) and then sequenced using sequencing by synthesis. Finally, the protein-protein interactions were measured on the basis of the statistics of colocalized polonies arising from barcoding DNAs of interacting proteins. Through this project, we aim to establish a robust quantitative method to measure protein binding affinity massively in parallel and to use the large-scale functional data set to guide computational protein design.

Chemically induced dimerization (CID), in which two proteins dimerize only in the presence of a small molecule, has been widely used to control cell signaling, regulatory, and metabolic pathways, and used as logic gates for biological computation in living mammalian cells. However, few naturally occuring CID systems and their derivatives are currently available. Creating a CID system with desired affinity and specificity for any given small molecule remains an unsolved problem for computational design and other protein engineering approaches. To address this challenge, we have used a novel strategy to select CID binders from a vastly diverse combinatorial nanobody library. We have created new CID systems that can sense cholecalciferol and artemisinin. We are validating CID biosensors by a yeast three-hybrid system and built structural models to understand the small molecule-induced dimerization. Our work is a proof-of-concept that can be generalized to create CID systems for many applications.

Many of the world’s most important countries are experiencing large increases in their populations of older adults (e.g. Japan, China, Italy, Germany). Such longevity is requiring a greater need for long term care. However, societies can not afford to pay for formal care, so informal (unpaid family) caregivers (CGs) are becoming increasingly important. Unfortunately, many CGs are at high-risk for psychosocial/health problems. Moreover, caregivers with pre-existing health problems are particular risk. Our goal is to examine factors that may make cancer caregivers vulnerable. We used a vulnerability (have a cancer history or not) by exposure (being a caregiver or not) model, and stratified our participants into four groups: Cancer Caregivers, Non-Cancer Caregivers, Cancer Non-Caregivers, and Non-Cancer Non-Caregivers. At baseline and 15-18 months later, we measured indicators of life quality and caregiver demands: satisfaction with support, well-being, perceived support, loneliness, and hours spent caregiving. Cancer Caregivers reported poorer social supports and more time caregiving. This is important because previous work has shown that Cancer Caregivers have more negative and fewer positive life experiences and that these are related to the ability to fight tumor growth. Despite innovations, this study only included white Americans. Also, to increase participation among persons with cancer, we only included those who were not treated for at least one year and who had not suffered from serious forms of cancer. Our results would probably have been stronger had we included persons with more serious cancers, but such individuals might not have participated or been able to be caregivers. Given the rapid rise of cancer in China, we suggest that research examine cancer and caregiving in China and that cross-cultural research be done in the U.S. and China. To understand the dynamics of caregiving, health and well-being, one needs to study these processes cross-culturally.

Obstructive sleep apnea (OSA) is the condition of repetitive stops of breathing during sleep due to complete or partial occlusion of the upper airway. OSA affects around 34% in men aged 30–70 years and is associated with significant cardiovascular mobility. Studies have indicated that retro-palatal region is the most common site of upper airway collapse leading to OSA. However, few studies have addressed the respiratory dynamics of soft palate, tongue base, and epiglottis during sleep. The purpose of this study is to analyze the respiratory motions of soft palate and its relation to oropharyngeal structures during drug-induced sleep in verified obese/OSA and non-obese/non-OSA minipigs. The hypotheses is that obese/OSA minipigs would have larger variance of soft palate motions and altered motion pattern as compared to non-obese/non-OSA controls, which may contribute to OSA. Four obese and two non-obese minipigs were first revived live sleep monitoring using wireless BioRadio system to verify OSA, and all 4 obese showed different degrees of OSA by apnea/hyponea index (AHI) while 2 non-obese did not. Sleep videofluoroscopy was performed under sedation when subjects were places in the prone and lateral positions. The ImageJ was used to trace the movements of soft palate tip in inhaling and exhaling phases. The static reference was defined to be the intersection of mesial surface and occlusal plane of upper second molar. The purpose of reference is to compare relative location of soft palate tip and its relation to other oropharyngeal structures. Dynamic movement of soft palatal tip presented significantly larger variance in obese/OSA than non-obese minipigs. Going forward, I will further map the dynamic shape changes of the soft palate and to define how spatial relationships between soft palate, tongue base and epiglottis lead to oropharyngeal airway patent or collapse during respiration.

A patient’s performance status (PS) is a key determinant of eligibility for enrollment in acute myeloid leukemia (AML) clinical trials, as PS is regarded as a crucial predictor of death as a result of treatment on the trial. PS values range from 0 (minimally symptomatic) to 4 (bed-ridden). It is crucial to account for possible differences in PS when comparing results of different trials. However, the degree of concordance between observers in assessing PS remains unknown. Because of this uncertainty and the clinical significance of PS, my research studies inter-observer concordance in assessing PS. Specifically, I compare PS as assigned in electronic medical records by medical providers, as abstracted by myself given history of present illness and physical exam findings, and the patient’s own evaluation via a health questionnaire. Data was collected from 300 randomly selected patients arriving to Seattle Cancer Care Alliance from January 2015 to December 2017 with newly diagnosed AML. The results of this study may inform similar research within other treatment centers, and development of increasingly precise guidelines for evaluation of PS to improve reliability.

Alzheimer's disease has been labeled the disease of the 21st Century. Societies around the world have not properly prepared for the expected massive increase in cases projected for the next 30 years. It is unclear who will care for the increase in numbers of people who will not be able to care for themselves.  At present, the vast majority of care is provided in the home by family members. Spouses represent a sizable percent of these family members. Research on spouse caregivers (CGs) has focused mostly on Whites, with relatively little research on minorities.  Research that has examined minorities has mostly examined self-rated measures, with little work on biological indices. The current study compares four groups of spouses: Black CGs (n = 7), Black Non-Caregivers (NCGs) (n = 8), White CGs (n = 115) and White NCGs (n = 108).  We observe differences in perceived stress, coping, burden/distress and physiological measures. The outcome of our research recommends interventions that could be used to mitigate health problems in caregivers that may allow them and their care-recipients to remain in their homes and live independently.

The Irrawaddy River is Myanmar’s biggest river system and the world’s third largest river in terms of sediment load. It drains the eastern edge of the Himalayas and flows through the Central Myanmar Basin into the Andaman Sea. Its geological history remains yet poorly documented, and when its modern drainage basin was established is unknown. For my research, I reconstructed the history of the Irrawaddy drainage system by using sedimentary provenance methods. Sediments in the Central Myanmar Basin can be traced back to their source rock by using different geochemical and petrographic proxies; by using these proxies on dated sedimentary rocks in the basin, I aimed at determining when the modern sediment sources were established. My research focused on two proxies: zircon geochronology and petrographic analysis of sandstones. Zircon geochronology is a method of dating zircon minerals from sandstones. The zircon age distribution obtained from a particular sediment sample is a direct insight into the age of the sediment source rock. Sandstone petrographic analysis involves analyzing at least 300 individual sediment grains and classifying them according to their mineralogy to compare them with the known rock characteristics in the potential sediment source areas. Both proxies were applied on sedimentary rocks of different ages previously collected in the field. I compared the results from both analyses with the modern sediments collected from the Irrawaddy river mouth and modern sediment source areas. I looked for consistency in the zircon age distributions and petrography signatures between the modern and older deposits to deduce the maximum age of the river. My preliminary results suggest that the Irrawaddy River was established around Middle Eocene (40Ma), which would make the Irrawaddy one of the oldest drainage systems of Asia.

The mental health of transgender children, children who have socially transitioned to live as the gender “opposite” their assigned sex at birth, have not been researched extensively, although the occurrence of childhood social transitions have increased in recent history. Instances of bullying and discrimination are reported in the LGBTQ community in high rates, which has been known to lead to higher rates of internalized symptoms. Previous studies have looked at the stress buffering hypothesis, which postulates that social support protects against the negative effects of victimization experiences, but the results from those studies are mixed. In the present study, we examine whether social support moderates the association between bullying and discrimination with internalizing symptoms in transgender youth. To test our hypothesis, we had the parents of 265 socially transitioned children, from ages 3-15 (mean age 9.41), answer questions regarding a child’s support structure (family, peer, school) and whether their child has been bullied and/or discriminated against specifically because of their gender. Our results show that the relationship between victimization experiences and internalizing symptoms was moderated by peer support, but not by family support or school support. We found that when participants had less peer support, being victimized more was associated with more internalizing symptoms, while higher levels of peer support do not yield significant results between the two variables, indicating that peer support may act as a buffer between victimization experiences and internalizing symptoms in transgender youth.

The Olympic Mountains on the west coast of Washington State are an impressive topographic feature, the emergence timing of which remains poorly documented. The Olympic Peninsula comprises 52 million year old (52 Ma) igneous rocks, and marine sedimentary rocks deposited from 52Ma to present. Here, we use a proxy to model sourcing of sediment called detrital zircon provenance (DZP). We use DZP of sedimentary rocks from the Olympic peninsula and from the Seattle Basin further east to model ancient drainage systems in order to place age constraints on the uplift of the Olympic Mountains. Our data from both areas show that 52 Ma through 23 Ma sandstones display DZP patterns and sediment type in agreement with a direct supply from central Washington. Samples of 13 to 11 Ma sandstones and modern river sands from the west of the Olympic Peninsula display a youngest zircon age population at 17 Ma. These data indicate that this area was still fed by central Washington at that time. 11 Ma sandstones from the eastern part of the Seattle Basin display DZP patterns still in agreement with supply from central Washington. By contrast, contemporary river sandstones from the western part of the basin mostly consist of reworked older sediment. This change in sediment source shows that by 11 Ma, the Olympics had already emerged and reached sufficient topographic prominence to support eastward draining rivers that deposited the 11 Ma river sandstone units of the Seattle Basin. These data allow us to constrain the initial uplift of the Olympic Mountains sometime after 17 Ma but before 11 Ma. The data are in close agreement with previously published ages that establish the exhumation of the Olympic Mountains beginning at 18 Ma, and show that the Olympic Peninsula became an emerged topographic high in less than 6 million years.

Major Depressive Disorder (MDD) has the largest life time prevalence (17%) of mood and anxiety-related disease. The prevalence of MDD is also 1.7 times greater in women than men. Chronic stress and anhedonia are the primary symptoms of depression, and decisions are affected. Our laboratory has shown that corticotropin releasing factor (CRF), the stress hormone, potentiates dopamine release in the core of the nucleus accumbens (NAc), suggesting a relationship between stress and reward processing. While it is known that an individual’s decision making is altered in a depressed state, the precise neurological pathway between stress and reward processing in the brain is unclear. To characterize this “stress-reward” pathway, I used a novel decision-making framework where a cohort of male and female mice performed an operant concurrent-choice task choosing between 0.1M sucrose solution or water. Mice were injected intracranially with α-CRF, a non-selective CRF antagonist, or vehicle in the NAc prior to performing the task. I measured task performance. I hypothesize that mice injected with α-CRF demonstrate less appetitive and reward-seeking behavior compared to the vehicle group, implicating a lower sucrose nosepoke percentage, sucrose choice percentage, and higher sucrose latency during the decision-making task. I also hypothesize that females have a greater reward sensitivity system than males, resulting in an augmented decline in appetitive and reward-seeking behavior compared to males. If these results indicate a significance in further elucidating the “stress-reward pathway” through the decision-making task, this can pave way for potential new treatments targeting this pathway for depression.

Grasslands cover approximately 20% of Earth’s land today and spread gradually worldwide in subtropical areas during the last 40 million years. Pollen data from sedimentary rocks in Myanmar suggest that grasslands might have existed there as early as 25 million years ago but did not spread to other Asian regions until much later, 10-6 million years ago. To fully understand the ecology of these early Asian grasslands, I reconstructed the paleoenvironments of Myanmar during the late Oligocene and early Miocene, 25 to 18 million years ago. I used two paleoenvironmental proxies on paleosol samples from Burmese sedimentary rocks: carbon isotopic composition of bulk sediment and phytolith analysis. The bulk carbon isotopic composition in paleosol is an indirect insight into the local aridity and can help reconstructing soil productivity; phytoliths–silica bodies deposited inside living plant tissue that remain in the soil after the tissue decays, forming fossils—when extracted, can help identify the grass types and their relative abundance in the ecosystem. Documenting the characteristics and paleoenvironmental setting of these early grasslands will help us understanding why they did not spread until millions of years later in Asia –and if this timing of ecological expansion is linked to the regional evolution of monsoonal intensity.

Studying zebrafish embryos allows us to understand features of vertebrate embryonic development. Neuro-mesodermal progenitor cells at the very posterior end, or tailbud, of an embryo are bipotential. This is because the presence or absence of Wnt signaling commits them to either neural or mesodermal fate. Directed by environmental cues, mesodermal cells exit the tailbud, migrate anteriorward, and become somites, structural segments from which muscles differentiate. The Kimelman lab has found that Tbx16/Spadetail, a major driver of mesodermal morphogenesis, downregulates Arhgap29 and Arhgap35, members of Rho family GTPase activating proteins. This suggests Arhgap29 and Arhgap35 may be involved in mesodermal cell movement. My work in the lab is focused on finding out what roles these two genes play. I used heat shock promoter hsp70 to overexpress Arhgap29 and Arhgap35 in transgenic fish lines. Previously, our lab showed that sustained Arhgap35 affected somite morphology, and that sustained Arhgap29 also decreased the number of somites. In my experiments, I carried out in-situ hybridization in wild-type, Arhgap29- and Arhgap35-expressing embryos to examine genes regulating specification/differentiation of muscle cells and genes involved in transmembrane cell adhesion. I will present data on cell tracking and cell protrusions collected from Arhgap29- and Arhgap35-expressing embryos. These results will help me compare cell migration between Arhgap-expressing and wild-type embryos. The purpose of these analyses is to understand how these two proteins control cell movement in the embryo. In the future, I will continue to investigate cellular mechanisms underlying vertebrate posterior elongation.

My pieces are an exploration of how characters form manga and comics intersect with my own identity. The first piece is called the “Power of Uchiha Snake”. I am the character Uchiha Sasuke from Naruto who possesses the Uchiha bloodline special visual power Sharingans. The second piece is called “Death to Wayne(Wei)”. Adapted from the Deadpool movie poster. Wayne, and “Wei” is the last character of my Chinese name. Deadpool has super power of infinite regeneration. Although he runs his mouth, no matter how mad he gets his enemies, they won’t be able to destroy him. For these two pieces, I used the techniques and visual patterns of capturing the geometric shapes of human figures, and the rules of composing art works, and analyzing the shading to get how the light hits on the figures as well as the perspective analysis. Figure study is when human figures exist visually as geometric shape, proportions of figures are supposed to be treated as lines, lines of geometric shapes. In terms of the study of art history, European art is directly derived from the Christianity trinity. The triangle pattern is the central balance of human figure, as human figures are derived from the God himself. The lines form the geometric balance and then the balance itself forms human figures into perfect combination. The light determines the perspective significantly for the dimensions closer to the viewer are thicker while the further side of the dimension are relatively vague in visual. It creates the perspectives of human figures on the drawing. In the photographic term, it’s called “depth of field”. This enables the figures on paper to be dimensional and closer to real human figures. My conclusion of the drawings as present, is that human eyes is an interesting tool, that gifted the mankind.

Hypoxic-ischemic encephalopathy (HIE) and inflammatory responses are commonly seen in premature infants which can lead to cognitive delay and behavioral problems. A novel rodent preterm brain injury model is being developed to simulate histological and behavioral changes seen in preterm brain injury. It was hypothesized that injured pups [(in-utero hypoxia-ischemia followed by post-natal inflammation with lipopolysaccharide (LPS) + hypoxia + hyperoxia] will have a significant late behavioral deficit compared to controls. The rodent model of preterm brain injury includes: intrauterine hypoxia at embryological day 18, with LPS administration on Postnatal (P) day 2 followed by hypoxia (8% oxygen) and hyperoxia (80% oxygen). In order to assess late behavioral effect of early neonatal injury, I conducted motor tests on rats. The motor testing included: gait analysis via CatWalk XT and Rotarod analysis. For the Rotarod analysis, I performed testing on both, the injured rats and controls, on P28 to test their locomotor ability. Gait analysis was performed on P35. The results will be tested for significant differences between the groups. Future research will be conducted by repeating this experiment to verify these results and clarify what aspects of late behavior are impacted most by this injury model.

 Alcohol use disorder (AUD) is associated with both acute and chronic alcohol-related harm. Marginalized populations, such as those experiencing homelessness, are both less inclined to successfully achieve abstinence and at higher risk of experiencing alcohol-related harm. Identifying strategies for safer use are thus particularly important for this population. To this end, we analyzed interview data collected from 86 adults experiencing homelessness and AUD who received harm reduction treatment (HaRT-A) during the parent randomized controlled trial. Participants were administered the demographic and alcohol measures at baseline (week 0) and were provided with HaRT-A, at which point interventionists introduced a list of safer-drinking strategies. Participants’ endorsement of safer-drinking strategies was assessed at HaRT-A appointments at weeks 0, 1, 2, and 6. For the current analysis, we conducted a mixed methods approach to characterize and evaluate endorsement and implementation of safer-drinking strategies at week 0 and week 6. Findings indicated use of strategies to buffer the effects of alcohol (e.g., eating while drinking), change the manner in which one drinks (e.g., counting drinks), and reduce alcohol use. Quantitative analysis indicated all participants were able to successfully endorse and implement safer-drinking strategies over the course of the study. These findings support that people experiencing homelessness and AUD adopt strategies that minimize alcohol-related harm, including ways that change the amount and manner of drinking and buffering the effects of alcohol. This extends the findings from our parent study among chronically homeless individuals to people experiencing transitional or episodic homelessness.

I have always wanted to see someone that looks like me in a museum. This desire to be represented in society is something people fight for. I want to create work that empowers cultures and features that are not represented. I want to depict those that have been colonized in the same way their colonizers have been historically celebrated, through paintings. This series of paintings will go beyond just my culture but others that share similar wounds and scars from colonization. Addressing problems that come with colonization such as assimilation, patriarchy, cultural disconnect. The process of my paintings is finding a model that inspires me to paint. The model will most likely have features that don’t follow these western idealizations. Then I look into the model’s heritage and find clothing, embellishments, weaponry from their culture with the use of the Burke museum’s data base. I begin to draw the model adorned with these objects. Hours of preliminary work goes into composing these objects with the model. I will have set up the model in a pose that was popular in western paintings depicting royalty or power. I want to flip these preconceived notions of these colonized nations on its head. I invite the discussion of cultural identity and colonized beauty. The goal is to preserve these cultural aesthetics that were pre-colonial. I want to come out of this project with a deeper knowledge of who I am. I also want to have a body of work that provides the viewer insight into my culture and many other cultures that lack representation.

As climate change progresses, predictions of long lasting and severe droughts are projected to affect many communities. These communities are encouraged to utilize food resources that produce high yields for sustainability. Learning the key physiological differences between drought tolerant and sensitive plants may help communities like this adapt. A key difference between tolerant and sensitive plants is the efficiency of sugar mobilization. Drought sensitive plants tend to hinder mobilization of sugars while drought tolerant plants maintain this sugar flow. Here, our objective is to locate and understand where the mobilization of sugars is bottle-necked in the sensitive plants, and how that differs for tolerant plants. We hypothesize that more drought-tolerant plants display an increase in sugar mobilization resulting in higher fruit yield, faster rate of seed filling/fruit formation, and an overall greater rate of plant growth as compared to drought-sensitive plants. Our experimental protocol consists of eight different genetic lines ranging in sensitivity to drought. By reducing soil moisture content to 50%, we will induce drought and start measuring growth rates of the middle leaflet of the third trifoliate, pod elongation, seed length, and biomass of different plant tissues to determine the bottleneck of carbon and sugar movement in all lines. By contrasting this net movement of sugars across lines, we hope to observe differences indicating physiological mechanisms distinguishing tolerant from sensitive lines. Understanding these differences would help educate and improve communities who are affected by drought due to increasing climate change and overall help improve sustainability of crop production.

Many psychiatric disorders, including substance abuse, have been linked to risky decision-making, but the mechanisms underlying these pathologies remain unclear. Cortical intratelencephalic and pyramidal tract (PT) neurons have distinct projections, morphology, and firing properties, but their role in behavioral regulation remains unknown. PT neurons have been identified in the orbitofrontal cortex (OFC), which is known to be heavily involved in the cognitive process of decision making. Based on previous studies in our lab demonstrating that inactivation of PT neurons increases reward preference, we hypothesized that PT neuron inhibition would increase risky decision-making. To test this hypothesis, rats were trained on a risky-decision task (RDT) in which they were trained to lever press for a food pellet reward. In order to target PT neurons in the OFC, CAV2-CRE virus was bilaterally injected into the pontine reticular nucleus (PnC), and an inhibitory Designer Receptor Exclusively-Activated by Designer Drugs (DREADD; DIO-hM4Di) was injected bilaterally into the OFC; this strategy allows selective expression of DREADDs in PT neurons. In the RDT, two options were presented: a “risky” choice associated with descending probability of administration (100%, 50%, 25%, and 12.5%) for delivery of four food pellets, or a “safe” lever that always delivers one food pellet. To evaluate response flexibility, rats underwent a reversal task whereby five consecutive responses on the active lever switched the “active” lever to the previously inactive one. In both tasks, rats underwent two sessions: in the test session, animals received an injection clozapine-N-oxide (CNO) to activate DREADDs, and in the control session, animals received an injection of vehicle (DMSO). Interestingly, we found that inhibiting PT neurons did not significantly alter decision-making or reversal-learning. Future studies will monitor activity of PT neurons using in vivo calcium imaging to determine the contribution of this cell population to decision-making tasks.

Risk taking is strongly associated with many disordered behaviors. Many studies implicate the orbitofrontal cortex (OFC) in such behaviors, though its modulation yields inconsistent results. This could be due to possible contrasting effects of intratelencephalic (IT) and pyramidal tract (PT) neurons, which have distinct morphologies and projections. Despite this, specific functionality differences are unknown. Given that 5-HT2A and D1 receptors have predominant expression in IT neurons over PT neurons, and antagonism of these receptors decreases risk-seeking, it was hypothesized that inhibition of all IT neuron activity in the OFC would also result in risk aversion. IT neurons in rats were inhibited during a risky-decision making task (RDT). To modulate IT neurons, an inhibitory designer receptor exclusively activated by designer drugs (DREADD) was injected into lateral OFC bilaterally, conjugated to CRE and FLP drivers injected into contralateral nucleus accumbens. In the full RDT, animals were presented with two levers: The “safe” lever delivered one pellet reward per press, while the “risky” lever delivered four pellets, with descending probability of reward administration (100%, 50%, 25%, 12.5%). Two test sessions were conducted whereby animals received intraperitoneal injections of clozapine-N-oxide (CNO) or a vehicle (DMSO) 30 minutes prior to task onset. Animals receiving CNO the first time received vehicle the second time. To determine if IT neurons were involved in perseverative responding, animals underwent a reversal task. They were presented with an active lever -which administered a food pellet per press -, and an inactive lever. Five consecutive responses on the active lever switched the inactive lever to the “active” lever. Results showed no significant changes in decision-making or reversal learning upon receiving CNO or vehicle. IT neuron modulation may need to be more temporally specific; future studies will focus on monitoring IT activity during decision-making paradigms to further elucidate their contributions within OFC.

About eighty percent of the learning in young children happens through use of vision; therefore, any form of impairment may have a significant impact on a child’s ability to grasp information. The goal of the Educating Young Eyes (EYE) research project is to improve our ability to properly identify and assess a variety of potential near-vision problems that may hinder a child’s ability to learn. Once identified, we can then refer the child for a more detailed assessment by a vision specialist (i.e., an optometrist or ophthalmologist). Our research focuses on developing new, cost-effective and accurate diagnostics that will help identify vision problems – and also help provide for effective therapies. The mission of our research project is to work alongside optometrists and other health professional to build a wide range of applications and provide access to children’s near vision assessment and therapy using the latest technologies available. A series of software tools/applications that we are building include: 1) Red Flags – a mobile app that conducts a series of tests to help quickly discover children who suffer from convergence insufficiency, an anomaly of the visual system; 2) Vision Quick Check, a mobile app that provides school nurses with a convenient and efficient way to test near vision and distance acuity for children as well as testing for stereopsis; and 3) the EYE Web Portal which displays student credentials and testing history from the mobile apps – allowing nurses and administrators to communicate with the database and manage the student credentials records. In summary, we aim to increase awareness and provide access for all children to receive effective vision screening and help people better understand the importance of functional vision in children’s learning.

Armadillidium vulgare are terrestrial isopods characterized by their ability to conglobate (roll into a ball) as a mechanism of defense from predation. It is theorized that conglobation functions as both a defense mechanism against predation and a means to avoid desiccation in arid environments. This project tests conglobation as a mechanism of water conservation. Water-loss in A. vulgare, was investigated in the free and conglobated states. In experiment one, 40 specimens of A. vulgare were suspended in their conglobated state using dental rubber bands and kept at 30.5°C and 30% relative humidity for 22 minutes along with a control group of additional 40 specimens of A. vulgare in their free state. Water-loss rate decreased by 16.5% when specimens were in their conglobated form. In experiment two, we first varied the humidity and then temperature to test whether different conditions triggered voluntary conglobation. Four groups of 15 specimens of A. vulgare were kept at 25°C in environments of varying humidity: 18%, 30%, 46%, and 99% respectively for one hour. No voluntary conglobation was observed in response to humidity change. Finally, we observed that high temperature triggered conglobation beginning with 6% conglobating at 31.5°C and 100% at 50°C. Our findings suggest that while conglobation behavior may help to conserve water, A. vulgare conglobate primarily as a defense mechanism. Further research is needed to clarify the function and purpose of the conglobation response in A. vulgare.

We have built an air quality sensor to track smoke from wildfires at UW’s Manastash Ridge Observatory (MRO). The increasing number of wildfires over the last few years has raised concern that smoke may contaminate the telescope optics at MRO. Our goal is to measure the amount of smoke in the air at the site in real time. Our design consists of an Adafruit micro-controller connected to two dust sensors that connect to Wi-fi. We interviewed Edmund Seto, a professor at UW, since he has much more experience with building sensors. He suggested that we use multiple of the same device so that we could average the data or have a backup sensor if one were to stop working. Using Arduino code and Adafruit.io, we were able to code the micro-controller and connect the data to a Wifi-interface so we could watch the data come in. We are currently field testing the sensor in Seattle, but we expect to permanently install at the MRO this summer.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by clinically recognized deficits in social communication, repetitive behaviors, and restricted interests. While the etiological underpinnings of ASD have yet to be determined, biological indicators of the disorder (e.g. biomarkers) hold promise as valuable diagnostic methods. Neurological biomarker initiatives are particularly essential in their potential to pinpoint the neural activity that gives rise to the disorder’s hallmarks. Resting state electroencephalography (EEG) studies suggest altered default signaling associated with ASD, with particular deviations in the power of the alpha frequency band. However, previous work has produced contradictory findings regarding the directionality of these abnormal power patterns, which motivate the need to better understand the implications of certain methodological decisions. In this study, we acquired EEG recordings during resting state paradigms in individuals with ASD and a neurotypical control group. We hypothesized that individuals with ASD would display reduced alpha activity, in comparison. We suspect that activity will be reduced, both when analyzed by peak power and average power over the entire frequency band.

This project aims to better understand the effects of removing global topography on atmospheric and oceanic circulation in numerical climate model simulations. The Community Earth System Model (CESM) was run for a hundred years under three different scenarios: the removal of all mountain ranges, the removal of the Rockies, and the removal of the Tibetan and Mongolian Plateaus. When mountains are removed it results in changes to ocean and atmospheric circulation. This begins with warmer surface temperatures where the mountains were removed (without the elevation-induced cooling) and changes in both vertical and horizontal air motion in the vicinity of the mountains (as the topographic-induced circulations are disrupted). Consequently, rainfall is altered due to changes in temperature and air motion. Our research aims to better understand how mountain ranges affect rainfall, particularly in the tropics. and how this in turn affects local climatology in tropical regions.

 The Diabetes Community Care Ambassador (DCCA) Program represents a promising intervention for improving glycemic control in youth with type 1 diabetes (T1D) struggling with diabetes management. In this novel program, lay health workers called DCCAs supported youth with T1D with poor glycemic control (HbA1 >8.5%) and their caregivers through home visits, school visits, and phone support, and connected participants with legal support. Given the findings that youth with T1D in the DCCA Program demonstrated improved glycemic control, we carried out a follow up qualitative study to understand the salient components of the DCCA program that promoted improved diabetes self-management from the youth and caregiver participant perspectives. We conducted semi-structured exit interviews with a subset of DCCA Program participants (18 caregivers, 14 youth). Participants reported on how the DCCA was helpful in supporting the youth’s diabetes management and how DCCA support compared to care provided by the multidisciplinary diabetes care team. A qualitative content analysis was carried out and emergent themes were identified. We found that within the home environment, participants felt the DCCAs helped youth address underlying weaknesses in their diabetes management routine and provided accountability for self-care goals between visits with their diabetes provider. DCCAs also provided psychosocial support that youth and caregivers believed they did not sufficiently receive from their usual multidisciplinary diabetes care team. At school, caregivers, in particular, felt that DCCAs successfully advocated on behalf of the student’s interests to facilitate diabetes management at school and also provided diabetes education to school staff. Finally in the community setting, caregivers shared that DCCAs helped to connect them to legal and support resources and better navigate the healthcare system. Our study results highlight the value of using lay health workers in providing individualized assistance for youth with T1D in supporting diabetes management outside of the ambulatory care setting.

Platelets seal wounds in blood vessels in order to prevent blood loss. When there is an exposed vascular matrix, platelets bind at the wound site through the glycoprotein (GP) Ib-IX-V complex. Glycoprotein receptors allow platelets to initiate homeostasis by forming attachments to the damaged tissue. Platelets use their glycoprotein receptors to form bridges between other platelets and the surrounding proteins that form the clot within the blood vessel. Aspirin, a common household medication, produces its effects through inhibition of thromboxane production which prevents the formation of these blood clots by meddling with platelet aggregation. Standard doses of aspirin for an adult are 81mg, 325mg, and 500mg. However, there could be differences between male and female platelets, indicating that there may be different amounts of glycoprotein receptors between males and females. Here, we evaluated the force of single platelets without aspirin in males and females and single platelets with aspirin in males and females by using a reference-free traction force microscopy (TFM) platform. This TFM platform contained a grid of a fluorescent protein at known locations and was coated with von Willebrand Factor (VWF) to mediate platelet binding. Immunofluorescent staining and fluorescent imaging was conducted to visualize to platelet f-actin, a cytoskeletal component, and GPIb. Platelet binding, spreading, and contraction is observed on these substrates. By placing the platelets on the substrate, we are able to measure the deflection of the grid and determine the force a single platelet generates. In the future, we hope to measure the force of platelets at 0mg, 81mg, 325mg, and 500mg between men and women and hope to elucidate how GPIb expression, platelet mechanics, and response to aspirin varies in males and females.

Indoleacetic acid(IAA) is a common and well understood auxin class phytohormone that promotes plant growth by increasing cell division and elongation. IAA has also been shown to increase infectious adhesion and filamentation in certain strains of Saccharomyces cerevisiae. Increased IAA production by the plant’s microbiome has been demonstrated to stimulate host and symbiont growth. The IAA production in multiple strains of S. cerevisiae from the USDA ARS library was quantified using the Salkowski colorimetric technique, then the highest IAA producing strains were treated onto corn to examine the effect on biomass growth. Preliminary results have shown greatly increased root mass and moderately increased shoot mass in treated corn. This symbiotic yeast treatment could have agricultural applications, increasing crop yields without increased application of fertilizer, pesticides, or other products that could have a negative ecologial impact or detrimental effects on the crop.

In human-robot interaction, virtual reality (VR) provides strong potential to aid in the design of social robots. In order to understand teens' perceptions of, and interactions with social robots, we utilized a human-centered design methodology to develop a collaborative VR game for teens. The design process involved interaction studies with a local high school in three phases: (1) Brainstorming and Sketching environments on Paper, (2) Card sort game play for exploring robot design options (3) Developing and usability testing the low-fidelity VR game play. The design goals were to create an inviting game context for teens to engage in collaboration and to elicit and capture the details of teen-teen and teen-robot interactions within VR. From the design process, we found that (1) the human-centered design process engaged teens in the design process (2) teens expressed positive emotions during collaboration and (3) the asymmetric design of the VR game allowed for not only strong engagement, but also unexpected role play as teens identified themselves as the robot during gameplay. Through the design and development of this VR game, we recognized the effectiveness of a VR platform as not only a design tool, but also as an engaging collaborative platform for gathering interaction data from teens. Given this potenial, we anticipate several future applications for the study of teen-teen interaction through VR collaboration.

Self-disclosing personal stress is an effective way of managing stress. Previous research has shown that high school students disclose more when prompted by robot that discloses vulnerability. Thus, disclosure reciprocity in human-robot interaction (HRI) provides a promising way of offering stress intervention. The current study examines how different types of disclosure from a social robot affect reciprocal human disclosure and other user outcomes through a stress-disclosing activity. Using a between-subject design, 36 young adults were randomly assigned to converse and engage in a stress-disclosing activity with a robot that shared technical facts (technical condition), feelings from other users (by-proxy condition), or feelings from itself (emotional condition). We hypothesize that emotional robot disclosure will elicit longer and deeper participant disclosure, and higher robot attributional ratings (such as likeability, perceived safety, user satisfaction, and intention for future use) than technical disclosure or by-proxy disclosure. Participant self-disclosure was measured by word count and depth of response during the robot interaction. User satisfaction, intention for future use, robot likeability, and perceived safety were captured using 5-point Likert scales. Our multivariate generalized linear model revealed that participants who experienced the technical robot disclosure condition gave the robot significantly higher rating for perceived safety, but no significant differences in other variables, such as length and depth of participant disclosure among robot disclosure conditions. Surprisingly, we found that people with higher perceived stress significantly disclosed less in both breadth and depth, and rated the robot as less likeable, had lower future intention to use and user satisfaction. This study demonstrates the complexity of designing robot for stress-intervention and the importance of capturing perceived stress as a predictor for stress intervention in HRI. Future research will examine how high stress and low stress group might perceive and interact with a social robot differently in long-term repeated interactions.

T-cell immunotherapy is a treatment utilising the body’s own immune system to target cancer cells. Dr. Marie Bleakley’s immunology lab at Fred Hutchinson Cancer Research Center uses T-cell immunotherapies to treat hematologic malignancies — blood cancers which include acute myeloid leukemia and myelodysplastic syndrome (MDS). These treatments rely on the identification of neoantigens (cancer-specific gene mutations) which are potentially highly cancer-specific and are promising as targets for new immunotherapies. My project will be in the identification of these neoantigens, under the supervision and mentorship of Dr. Melinda Biernacki, a research associate in Dr. Bleakley’s lab. My project will focus on generating in silico and preliminary in vitro data for candidate neoantigens in high-risk MDS.
The project will have two parts. First, the identification of candidate MDS neoantigens using human leukocyte antigen (HLA)-binding prediction algorithms to identify mutated amino acid sequences (peptides) that have a high probability of binding HLA molecules. Because T-cell antigens consist of a peptide-HLA molecule complex, this step will filter out mutant peptides that are unlikely to be recognized by T cells. Second, in vitro assays will determine which candidate neoantigens are immunogenic (can actually be recognized by the body’s T-cells). HLA-binding predictions do not reliably predict immunogenicity of candidate neoantigens, so in vitro testing is needed to assess T-cell recognition. The end product will be the identification of potential T-cell targets from mutations in various genes that are shared in subgroups of MDS patients that could be used to develop immunotherapies for MDS.

Infection of the central nervous system (CNS) greatly contributes to and increases the risk of developing epilepsy. Individuals who present with seizure during a CNS infection are 22 times more likely to develop epilepsy in their lifetime than individuals who do not present with a seizure. Infection of mice with the Theiler’s murine encephalomyelitis virus (TMEV) is a preclinical model that is useful to understand the mechanisms underlying acute seizures and the development of epilepsy following CNS infection. In the present study, we aimed to determine how diet sterilization (autoclaved versus irradiated) impacts the development of acute seizures and chronic behavioral comorbidities. We infected C57BL/6J mice with an intracerebral (i.c.) injection of TMEV or sterile saline, and then fed the mice either an autoclaved or irradiated diet. Next, we monitored the mice for the incidence of acute handling-induced seizures 3-7 days post-infection. Under both dietary conditions, mice developed handling-induced seizures in the acute infection phase. There were 8/13 (61%) irradiated diet fed mice that developed acute seizures whereas 9/13 (69%) autoclaved diet fed mice developed acute seizures during this period (p >0.05). We then assessed behavioral comorbidities associated with chronic epilepsy 4-5 weeks post-infection by evaluating anxiety-like behaviors in an open field test, working memory in a novel object recognition test, and electroconvulsive seizure thresholds. Mice fed an irradiated diet demonstrated preserved working memory function compared to mice fed the autoclaved diet, who demonstrated significant reductions in working memory and increased anxiety-like behavior, suggestive of worsened disease severity. At the conclusion of in-life testing, animals were euthanized, and tissues collected for histopathology and immunohistochemistry to assess the extent of TMEV-induced neurodegeneration and neuroinflammation. Our findings highlight the potential for the sterility of diet to modify disease severity in the TMEV model.

There has been growing concern regarding rising carbon dioxide concentration in the atmosphere because CO₂ traps excessive heat and warms the planet through the greenhouse effect. One strategy to mitigate this problem is through the capture and conversion of CO₂ via hydrogenation to fuels and chemical feedstocks that are currently produced from fossil fuels. Given the complexity of these multi-electron, multi-proton transformations and the multitude of products that can result, catalysts are required to lower the energy barrier and direct the selectivity of CO₂ conversion reactions. One catalyst currently under development is a Ru(II) bis-(protic N-heterocyclic carbene) phosphine catalyst, which incorporates protic N-H wingtips adjacent to the metal center. The N-H wingtips are an interesting feature due to their ability to activate CO₂ through metal-ligand cooperation, their accessibility as a proton source near a metal active center, and the likelihood that they aid in splitting H₂ between the metal center and the nitrogen. Preliminary results have shown moderate turnover numbers (TONs) for both formate (130) and methanol (7), the latter of which is a rare transformation in a single catalyst system. In order to improve catalytic TONs and understand the role of protic N-H wingtips, a library of catalysts with varying ancillary ligands, including 2,2’-bipyridine, 4,4’-dimethoxy-2,2’-bipyridine (electron donating), 4,4’-dibromo-2,2’-bipyridine (electron withdrawing), and 1,2 bis(diphenylphosphino)ethane (sterics), is synthesized and screened under high pressure and temperature conditions using THF solvent and varying additives (e.g. Li₃PO, K₃PO₄, KPF₆) and additive concentration. It is expected that the ancillary ligands, bound trans to the bis-carbenes, will influence the proton donor ability of the N-H wingtips and catalytic turnover.

About 3.1 million adolescents are diagnosed yearly with depression. Adolescent onset of depression is associated with acute or chronic difficulties in physical, mental, and psychosocial functioning. However, over 60% of adolescents with depression do not receive mental health care, and, among those who do, treatment engagement is low. Behavioral Activation (BA) is an evidence-based psychosocial intervention for individuals with depression. While BA holds promise as an effective treatment, researchers have found that adolescents may be better reached and engaged through social and mobile technologies. In addition, BA requires frequent interaction from patients over time, which can be difficult and costly to administer in-person. There is an opportunity to improve the usability of and engagement with EBPIs via online technologies. Asynchronous Remote Communities (ARC) is a promising technology-based approach for engaging adolescents that leverages technology’s reach while providing support, social interactions, and motivation. ARCs are private online groups on which researchers can deliver weekly research tasks to participants and gather information about their perceptions in a format that is lightweight, accessible, usable, and low burden. We have used ARC to both discover design requirements and to design/build a platform for administering BA, which we have tested with clinicians and adolescents. We used ARC with 10 mental health clinicians specializing in treating teens with depression to discover their needs. Specifically, we worked with mental health clinicians to better understand their needs and to identify facilitators and barriers to adapting BA to ARC. We used the Slack online platform to create an accessible, anonymous environment where we posted 20-minute long design activities each week for 10 weeks to be completed asynchronously. We were then able to recruit teenagers to understand their needs. Based on the results, we are adapting BA to ARC settings and then testing out the feasibility.