From the years 1946 to 1958, the Republic of the Marshall Islands (RMI), a sovereign nation in free association with the United States, endured the nuclear detonation of 67 atomic bombs conducted by US military. As a result of the nuclear testing, many Marshallese were gravely affected by the radiation exposure: suffering multi-generational health problems as well as being displaced from their homes. The unprecedented amounts of nuclear contamination have inevitably forced the Marshallese to abandon their lands, which has severely disrupted their cultural practices and lifestyle that has been passed down for years. The people have suffered countless traumas including birth defects and miscarriages, cancer, and autoimmune diseases. Through interviews, literature reviews, documentaries, and other modes of anthropological discourse, we will be demonstrating how the Marshallese have been affected by the US Government Nuclear Testing Program, and how this may parallel to the detrimental health effects of the people living near the Hanford Facility in Eastern Washington. Given the severity of health problems and involuntary migration in the RMI, we argue that the US government should take more responsibility and initiative to ensure that the Marshallese are granted proper restitution for the irreparable damages these nuclear test operations have caused to them and their culture. By implementing codes of ethics as well as more access to healthcare, we believe the health and wellbeing of the Marshallese will begin to thrive once again.

We present optical and infrared photometry of the T Tauri binary KH 15D acquired in the 2017/2018 observing season. The data were obtained from the A Novel Dual Imaging CAMera (ANDICAM) instrument on the 1.3m telescope operated by the Small Moderate Aperture Research Telescope System (SMARTS) at the Cerro-Tololo Inter-American Observatory (CTIO). KH 15D includes two young stars (A and B, with 0.72 and 0.74 solar masses, respectively) orbiting their common center of mass, surrounded by an inclined precessing circumbinary disk. The recent data reveals Star B gradually emerging from the trailing “fuzzy” edge of the disk and is now in a stage that is completely unocculted for the first time since the system’s discovery in 1995. We use time-series photometry, or light curves, to probe the composition of the disk, derive parameters of Star B, and demonstrate the overall mechanics of the system. Recent data also shows reddening during the egress of the last eclipse, proving that the trailing edge of the disk is transparent and consists of dust-sized particles. Additionally, the most recent data displays Star B at a brighter magnitude than ever than before, allowing us to calculate an apparent I magnitude of 14.079, which is 12% brighter than previously computed.

If you're tiling a circular room with square tiles, how many do you need? What if your tiles are parallelograms? As the circle gets larger, is there a pattern? Mathematically, this can be framed as counting integer points in a large circle. We're interested in how this count changes as you change the shape of the tiles, and to understand this better, we started by counting the number of integer vector pairs within a ball of radius R so that the parallelogram they make has a fixed area (determinant). We created a Python program that would generate all of the primitive points out to radius R, which we then extended to count the number of vector pairs with a certain determinant k. We were able to compute the limiting density of this count, extending known results for the case of determinant 1. We are now studying other discrete sets, such as ones generated by objects from hyperbolic geometry, known as Hecke triangle groups. In the future, we plan to use our research for counting pairs of vectors in different spaces and generalize it for counts of k-tuple vectors. Come for floor tilings, stay for beautiful pictures!

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.

The average number of coronary artery bypass surgeries performed annually in the United States is roughly half a million. Recently, extensive research has been conducted on the use of acellular tissue engineered vascular grafts which could be implanted into the body to replace the blood vessels that fail due to cardiovascular disease. The Ratner lab is working on creating a novel vascular graft based on a pro-healing porous material which is best suited to guide native blood vessels to heal into the material so that the vascular graft can transform into a living blood vessel. However, a paradox in this design is that right after the graft replaces the blood vessel, before the healing happens, the pores in the graft could give rise to bleeding if not monitored properly. This project addresses that problem by creating a hydrogel that seals the pores, preventing initial bleeding, while degrading at a rate in sync with the rate of healing and is ultimately replaced by vascular tissue. Initially, a series of hydrogels with varying crosslinker levels were made. Subsequentially, an in-vitro degradation assay was used to test each hydrogel in a cell culture medium. This assay showed that the higher the concentration of crosslinker, the slower the hydrogel degrades. In addition, the hydrogel was implanted under the skin of a mouse and the observed degradation of the hydrogel in vivo closely matched the in vitro data but was slightly slower. In the future, the hydrogel with the optimized crosslinking will be applied to a vascular graft for large animal experiments in sheep and pigs and the healing and degradation rates will be observed to measure the effectiveness of the hydrogel as a sealant.

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. 

Small Heat Shock Proteins (sHSPs) play crucial roles in protein homeostasis, the state of maintaining steady internal cellular conditions, despite changes to the cellular environment. As the “molecular life rafts” of the cell, sHSPs target partially misfolded proteins during stress measured as chaperone activity, and without consuming energy, prevent toxic aggregation. Mutations or malfunctioning of the sHSP, HSPB5 (B5), in humans are associated with neurodegenerative diseases such as Alzheimer's and Alexander's disease, as well as cancers, myopathies, and cataracts. As one of the ten sHSPs encoded in the human genome, B5 contains structural elements (the building block) common to all sHSPs: a highly conserved alpha-crystallin domain (ACD), that is flanked by variable, less conserved, N- and C-terminal regions (NTR and CTR, respectively). Previous studies determined that interactions between building blocks occur between a three amino acid region known as the I-X-I motif (a “knob”) in the CTR, and a hydrophobic groove (“hole”) in the neighboring block, similar to how two pieces of Lego come together to build a larger structure. Interestingly, in B5, there is an additional I-X-I motif in the unfolded NTR, but its role and structure are unknown. I hypothesize that the CTR and NTR motifs compete for binding into the hydrophobic groove, indicating the “knob” into “hole” interaction is loose, where the other “knob” can bind the “hole” when one leaves. To test this hypothesis, I prepared mutants containing CTR, NTR, and double motif deletions. I aim to uncover the effects of these mutations on chaperone activity and oligomeric size, by optimizing protein purification and using a combination of in vitro biochemical assays, and native (non-denaturing) gel electrophoresis on purified B5 mutants. These results will assist in demystifying the role of the NTR, direct future sHSP studies, and provide important insight for development of future therapeutic strategies.

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.

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.

Altrenogest (ALT) is a potent synthetic steroidal progestin commonly used as a veterinary pharmaceutical to maintain pregnancy in females, match estrus periods for breeding, or postpone the estrus period. ALT usage was estimated as several thousand kg across ~3,600,000 horses and ~66,000,000 swine; it subsequently enters the aquatic environment through agricultural runoff. ALT can act as an environmental endocrine disruptor because it has progestogenic and androgenic activity, however, little is currently known on its environmental fate, persistence, and ecological risks. Our study focuses on characterizing the biodegradation kinetics and product identification for ALT and its primary photoproducts.To evaluate altrenogest fate, we build microcosms by mixing altrenogest, water and growth media for mixed microbial communities collected from representative agro-ecosystems and municipal waste waters. We then concentrate water samples through solid- phase extraction and then use liquid chromatography and triple quadrupole mass spectrometry to analyze remaining ALT concentrations over time, to understand transformation kinetics. To identify transformation products, sample extracts are analyzed using high resolution mass spectrometry. Study results will aid in the risk assessment of ALT by improving our understanding of its environmental fate and management.

Reported human tissue properties and behaviors vary significantly across studies based on the characterization protocols utilized. My undergraduate research at the Center for Research in Education and Simulation Technologies (CREST) aims to address the gap between practitioners in the hospital by developing high-fidelity materials for medical simulation through data analytics. This will allow more accurate research in the field as well as better access to material properties and data. Raw uniaxial and puncture human tissue data is analyzed through MATLAB scripts to quantify human tissue behaviors. The processed data is restructured and transferred into bulk storage databases using Azure SQL servers and SQL databases, enabling cloud access. By utilizing Azure SQL databases, Tableau is used to visualize and manipulate targeted data. The human tissue property database bridges the gap between engineering and medicine. This database will be used to create the next generation of finite element models of the human body to help build virtual reality simulators.

The geriatric population is the fastest growing population in the U.S. Mental health is crucial to the quality of life of geriatrics and the family members who take care of them. While mental illness is a common health concern in the geriatric population, under-diagnosed and under treatment of mental illness creates challenges for the health and well-being of both elderly patients and their families. Unfamiliarity with psychiatric health, such as recognizing signs, symptoms, and providing appropriate referrals and treatment, may result in myths, the stigma of mental illness, and appropriate and timely psychiatric care. The purpose of this meta-analysis research is two-fold. First, the research provides a summary of the current evidence regarding the cause of geriatric psychiatric issues in nursing-related settings. Second, it highlights the possible solutions to the shortage of psychiatric nurse practitioners. As healthcare practitioners, nurses must have proper training in order to be aware and recognize geriatric mental health illness and provide appropriate care for our patients and their families. Providing patient education to the geriatric population and family members will allow them to assist in identifying the signs and symptoms of potential mental health problems. Lastly, the meta-analysis will examine possible solutions provided by current geriatric researchers for the best way to identify and treat psychiatric problems in the geriatric population.

Schistosomiasis is classified as a neglected tropical disease, ranking second only to malaria as the most common parasitic disease in the world. The two species of interest for this project are Schistosoma haematobium and Schistosoma mansoni, both of which can infect humans who come into contact with infested waters. The disease can manifest in urogenital (S. haematobium) or intestinal (S. mansoni) forms, leading to a variety of symptoms, including chronic pain, bladder and liver cancer, and – in extreme cases – death. Despite the extremely infective nature of schistosomiasis’ environmental stages and its complex transmission ecology, relatively little has been done to understand the effect of schistosome parasitism on the behaviors on its intermediate snail host. Expanding our understanding of snail behavior is necessary to explain the transmission dynamics of the disease and to reduce rates of human infection. In this research project, I examine snail choice behavior in infected and uninfected snails in a simulated lake habitat, and determine if schistosome infected and uninfected freshwater snails exhibit a difference in aggregation behavior, and where within a simulated pond environment infected and uninfected snails reside. I hypothesize that in a large population, both infected and uninfected snails will aggregate towards infected snails. I also hypothesize that infected snails will tend to linger closer to the surface of the water than uninfected snails and be less likely to quit the water, thus increasing the probability of transmission to a mammalian host. Understanding snail intermediate host behavior in the transmission of schistosomiasis gives us a way to control infection rates from an ecological perspective in addition to the traditional medical perspective.

Natural dermal armors are inspiring the development of advanced engineering materials and next generation flexible armors. Fish scales are an exemplary candidate and consist largely of laminated plies of unidirectional type I collagen fibrils. The mechanical properties of fish scales depend on the interpeptide bonds within the triple helix of the collagen fibrils. Adjusting the strength of these bonds to change the performance of the scales has applications to the design and functionality of bioinspired flexible armors. Here, elasmodine scales were exposed to polar solvents to adjust the extent of intermolecular bonding. Changes in the mechanical properties were evaluated in uniaxial tension and at two different strain rates. Results showed that the constitutive behavior was highly dependent on the intermolecular bonds. A significant increase was observed in elastic modulus (stiffness), strength and toughness as a result of increasing the extent of interpeptide bonding via solvents with low affinity for hydrogen bonding. A 300% increase was seen in the elastic modulus of scales soaked in acetone compared to HBSS at the highest strain rate. Furthermore, the importance of interfibril bonding was dependent on loading rate. Overall, results showed that the “protecto-flexibility” of fibrous armor materials can be improved by activating interfibril bonds and that this could spawn approaches for tuning armor performance.

Natural armors, like those found on animals, provide inspiration for the development of next-generation engineered materials. In this study, the microstructure and composition of the cuticle of the terrestrial isopod armadillidium vulgare was evaluated. The cuticle, composed of layers of mineral particles and chitin fibers, is multifunctional. It protects the animal from impacts, predation, and maintains internal moisture, while facilitating sensing of the environment. Prior literature has focused on mineralized portions or anatomical features, while this work integrates composition data with chitin fiber structure and orientation. Cuticles of the armadillidium vulgare were evaluated by scanning electron microscopy (SEM) and Raman spectroscopy. Cuticle cross sections were prepared by freezing individual tergites in liquid nitrogen, then sectioned by fast-fracture. SEM was used to image cross sections and view chitin fibers and ply orientations over the cuticle thickness. This data was used to understand fiber layer morphology and orientation throughout the cuticle thickness. Raman was used to evaluate the spatial dependence of composition across the layers. Results showed that the cuticle is actually a nanolaminate consisting of plys of chitin fibrils, and with ply thickness that varies through the cuticle. The stacking arrangement of the plies appears to follow a Bouligand structure, which is characteristic for other natural composites. Results of Raman indicate that the plies are mineralized chitin, however, it is unclear if there are changes in composition through thickness. This work is ongoing. An understanding of the ply arrangement and mineral distribution in this armor can be used to pursue new strategies for material design where resistance to impact and puncture are needed. Applying design principles found in this isopod, more efficient and effective materials can be designed for applications such as light-weight armors or protective coatings.

English sole Parophrys vetulus is a species of benthic flatfish that is commercially and tribally exploited off the coast of Washington State. The commercial value of English sole can decrease if the fish is infected with parasites, which degrade their appearance and health; in fact, widespread parasitic infection contributed to the closure of the commercial fishery in south Puget Sound in 1948. Clavinema mariae is a trophically transmitted nematode parasite that has increased in abundance by eight-fold since 1930 in Puget Sound. Since C. mariae is a nematode that infects hosts via ingestion, I used a diet analysis of English sole to: 1) assess the types of prey that sole consume, and 2) correlate the prey type abundance to C. mariae abundance. I evaluated the gut contents of contemporary sole collected in 2017 and historical sole collected over the past 80 years and held in the UW Fish Collection. I categorized gut contents to the lowest taxonomic family. Sole are hypothesized to primarily consume invertebrates, and C. mariae is transmitted by copepods, thus we expect copepods to represent a larger portion of the diet in more recently collected, more heavily infected sole. Knowing the type and number of organisms that English sole consume will improve our understanding of how sole interact with the Puget Sound food web; specifically, how they are initially infected with C. mariae, which would offer insight to their observed increase in abundance in sole over the past 80 years.

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.

With reduced operating hours and additional pressures, there is a rising importance in the development of an accurate surgical simulation. In order to improve the effectiveness of surgical simulations, there must be an accurate model of the human body that can be used for practice. Although cadaver and animal models are imperative to the training of future and current surgeons, there is a rising ethical interest paving the way towards alternative solutions. My undergraduate research at the Center for Research in Education and Simulation Technologies (CREST) aims to develop an accurate model for adipose tissue in the greater and lesser omentum. We have developed four prototype recipes for simulated adipose tissue using chemically-modified polydimethylsiloxane (PDMS) composites. In order to evaluate how the prototypes compare to in-vivo and in-situ adipose tissues, we have collected quantitative data through uniaxial tensile, coefficient of friction, and puncture testing in addition to qualitative data collected through conducting surveys of physicians. By utilizing this collection of both quantitative and qualitative data, we have developed an accurate synthetic adipose tissue model.

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.

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.

Botox (botulinum toxin) is commonly used to reduce facial wrinkles, but it is also injected into the masseter muscles, the main jaw closing muscles, for cosmetic reasons or pain reduction. Botox blocks neurotransmission, leading to partial muscle paralysis and atrophy. Although these effects are considered safe and temporary, we previously found that a single treatment of the rabbit masseter with Botox caused muscle atrophy persisting for at least 12 weeks. However, some muscle fibers were unaffected or even enlarged. The purpose of this study was to determine if the changes observed were more or less severe in specific regions of the masseter, and if differences in fiber size correlated with the regional electromyographic (EMG) response to nerve stimulation. Rabbit masseters were injected unilaterally. Regional EMG was recorded before euthanasia at either 4 (n=4) or 12 weeks (n=5) post-injection. The regions corresponded with the three sites of injection, anterior, middle and posterior in the inferior part of the muscle. Superior regions were also examined for the 12-week sample. Least fiber diameter was measured in histological sections (40-60 fibers/region). Linear regression was used to correlate EMG and fiber diameter. In general (6/9 treated muscles) the region with the largest fibers showed the highest EMG, but at 4 weeks there was no linear correlation; all regions showed both atrophied fibers and low EMG. At 12 weeks, all regions of treated muscles had larger average diameters and some also had increased EMG. Positive correlations between fiber size and EMG were seen anteriorly (r2=0.66) and posteriorly (r2=0.43) and in the muscle as a whole, both inferiorly (r2=0.36) and superiorly (r2=0.76). These results indicate that Botox injections have adverse effects long after the initial injection. Although no regions are consistently more affected than others, there is a general correlation between fiber recovery and signal strength.

One out of every two-hundred schoolchildren lives with type 1 diabetes. Type 1 diabetes is a chronic illness that requires monitoring blood glucose, calculating insulin needs, meal planning, and monitoring for and treating hypoglycemia and hyperglycemia. Effective coordination of care between school nurses, health care providers, parents, children, and school staff is critical to promote diabetes control and prevent adverse health outcomes. The purpose of our project is to describe parent and school nurse perceptions of care coordination in the care of children with type 1 diabetes. Our project is part of a larger project that aims to identify facilitators and barriers to effective care coordination in Washington state schools. Focus groups were conducted with parents of type 1 diabetics in urban and rural settings throughout the state that represent the diversity of resources and school nurses across the region. We recorded, transcribed, categorized, and analyzed verbal and written responses to identify themes. Our preliminary findings suggest that parents and nurses identify inadequate communication between school nurses, parents, and providers, and difficulties organizing care as a significant barrier to effective care coordination. Strong communication and involvement between all parties contributes to successful care coordination. Results from the larger project will be used to develop a care coordination model to inform interventions to improve the care of children with type 1 diabetes in schools.

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.

Chronic pain is debilitating for millions of people worldwide and our understanding of how the central nervous system processes painful information is limited. If we are to create more effective therapeutics to treat chronic pain, it will be necessary to develop a better understanding of the circuitry and functionality of the somatosensory system. Our lab is interested in the calcitonin receptor-like (CALCRL) receptor, which is expressed throughout the central nervous system and is known to respond to pain-inducing neuropeptides. We aim to profile CALCRL receptor-expressing neurons within the dorsal horn to elucidate their functional roles in nociception and to determine how they process painful information. This was done by 1) utilizing an adeno-associated viral vector (AAV) to preferentially infect and fluorescently tag CALCRL-positive neurons in the dorsal horn, 2) utilizing a retrograde, monosynaptic rabies viral vector to infect neurons that are synaptically connected to CALCRL-positive neurons, and 3) immunohistochemical staining and analysis to detect a variety of neuronal markers of inhibitory and excitatory neurons, laminar markers, and several other known dorsal horn neuron subtypes. Thus far, CALCRL-positive neurons were successfully infected via direct injection using both AAV and rabies vectors into the dorsal horn. In addition, we have also been successful in costaining for multiple neuronal markers. We have begun to profile and classify these neurons according to known neuronal subtypes. Our next goal is to modulate the activity of this specific neuronal population followed by behavioral testing to better understand its functional role in the processing of painful stimulus. If we are able to create a clear profile of these neurons, then we may be able to identify future targets for specific therapeutics.

The narrative of nuclear patriotism was heavily promoted to justify the construction of plutonium production facilities like Hanford, as well as the use of plutonium-based atomic bombs against Japan. Nagasaki, bombed only days after Hiroshima, does not fit into this patriotic narrative and has subsequently been overlooked by the public. Just like the government minimizes the attention on Hanford in the United States, the bombing of Nagasaki is not as well known as the bombing of Hiroshima. As a result, Nagasaki victims have endured health disparities of equal magnitude in silence. We researched this topic further by conducting interview analysis, discourse analysis, critical film analysis, and literature review. We wish to connect Hanford and Nagasaki by focusing on downwinders and atomic bomb survivors. While Hiroshima has had more public exposure than the Nagasaki bombing, we want to bring to light the equally devastating impact of the bomb on the citizens of Nagasaki. Hanford and Nagasaki are tied together not only by association to nuclear weapons and radiation, but also by the silencing of their association to these weapons. These impacts are closer to home than one would expect, and it is essential to bring awareness to the unseen struggles within our international community. Cleanup of nuclear sites and nuclear regulation need to be regarded as national responsibilities to global safety, to ensure that history will not repeat itself.

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.

With only a handful of species known to the general public, many of the 4000 bees endemic to the United States go unnoticed. As crucial pollinators, bees are incredibly important to the environment. There is a notable lack of data regarding bees in the United States, thus data collection about bee species diversity and abundance is prudent. Citizen science, or the use of volunteers in ecological studies, is a relatively new concept, introduced only a century ago by ornithological and astronomical sciences. The invention of digital single-lens reflex (DSLR) cameras makes it easy for novice photographers to take quality pictures, and they have become more accessible to citizen scientists in recent years. Our research introduces methods using visual observation and digital photography to study bee species diversity and abundance. It is impossible to identify most bee species without a microscope so we have taken a morphogroup approach, adapted from Xerces Society monitoring protocols, to gather data about bee species without needing an identification expert. We group bees into eight categories according to key characteristics visible to the naked eye, as similar-looking species are often closely related. Using digital cameras we implement two timed survey protocols, one tallying abundance and one “capturing” as many species on camera as possible. Two years of preliminary data has yielded information regarding the abundance, diversity, and phenology of bee groups on the UW Bothell/Cascadia College campus. Our surveys revealed the presence of all eight morphogroups on campus, 23% representing honey bees and 77% other bee species; bumble bee species (Bombus sp.) dominated in abundance representing 55% of all bees seen in 2018. Research has thus far informed improvements to monitoring protocols, identified bloom gaps on campus, and has resulted in the creation of UW digital photo archive documenting the findings of the research.

The Hanford nuclear site is a 20th and 21st century example of America’s ongoing military industrial complex. Its ties with the aftermath of the Manhattan project shows that its harm was not unidirectional, but rather multidirectional since harm was done to the people of Nagasaki and to the communities within and around Hanford, Washington. Migrant workers have had ongoing misrepresentation regarding the nuclear site’s post-communal health impact; especially within oral and scholarly accounts. In this study, we explore what factors have had short-term and long-term impacts on the health, socioeconomic status, and autonomy of Hanford migrant workers. We use literature review and discourse analysis to understand these complexities affecting migrant health, and by developing these frameworks we reveal to the reader how such human and unalienable rights were undermined for the purpose of global control.

Current methods of drug delivery include the use of antibody drug conjugates (ADCs), lipid and polymeric nanoparticles, and top-down modified viruses. While successful in certain applications, these delivery platforms involve laborious production methods and have limited engineering opportunities. Synthetically designed proteins are viable drug delivery candidates that can be precisely modified to overcome the engineering challenges associated with other delivery platforms. Specifically, synthetic nucleocapsids (synNCs) are computationally designed icosahedral protein assemblies evolved to have virus-like genome packaging. The linkage between the encapsulated mRNA (genotype) and exterior proteins (phenotype) allows for directed evolution to be achieved through library selection. The synNC was evolved to increase the in vivo circulation half-life from less than 5 minutes to over 4.5 hours. The next step is to optimize the targeting ability of synNCs toward specific organs. We performed site-directed mutagenesis to introduce several mutations on the exterior of the synNC, performed two rounds of in vivo library selection, and identified several mutations that favored specific organs. Our current work involves producing five promising synNC mutants, biochemically characterizing the mutants, and examining their biodistribution in mice. The ability to target specific organs will be a successful step towards utilizing nucleocapsids in drug delivery and other biomedical applications.

Age-associated diseases, like neurodegenerative disease, cancer, heart disease, and metabolic dysregulation limit healthy human lifespan. In recent years, biologists researching aging and longevity have turned their attention towards maximizing healthspan, the healthy portion of one’s life before the onset of age-related disease. By delaying age-associated diseases, we can fundamentally improve quality of life globally. Natural products and other pharmacological interventions hold particular promise as interventions to extend healthspan and lifespan. We seek to identify novel compounds that extend lifespan using the invertebrate model system Drosophila melanogaster (fruit fly). We have tested an extract made from Pterocarpus marsupium (PME), a tree native to India and Sri Lanka with uses in Ayurvedic medicine. PME extends cellular lifespan in budding yeast, another invertebrate model system. We also tested pterostilbene, a compound found in Pterocarpus marsupium extract. As a positive control for lifespan extension, we are treating other cohorts of flies with rapamycin. Rapamycin is a specific inhibitor of the nutrient sensing mechanistic Target Of Rapamycin (mTOR) pathway, a known longevity regulating cellular pathway. Using multiple fly genetic backgrounds, performed a dose response to identify concentrations of PME and pterostilbene that extend Drosophila lifespan. Through pharmacological methods, we seek to delay aging and minimize human vulnerability to age-induced diseases. Discovery of specific compounds that prolong lifespan is a first step in developing therapeutic methods to delay human aging and health decline.

Visual art is one of the compelling factors in changing society and culture, and many visual artists--from primitive to modern times—have left their impact on the world. Art is thought of as a system or method of communication that goes beyond language and has the capacity to fully capture a moment in time or an individual’s experiences, emotions, desires, and more (Schellekens 44). For the artists themselves, discovering their reasonings, motives, and influences becomes a critical component in creating more meaningful artwork and understanding themselves. The purpose of this research is to investigate, learn, and predict the factors that are influencing my own personal body of artwork. The methodology of this research is divided into three steps: 1. Research and Identify, 2. Narrow Down & Categorize, and 3. Analyze & Conclude. Through an immersive, month long, experience at the New York Academy’s Summer Residency Program, data was collected and recorded. A list of the potential factors was created before attending the residency that consisted of a list of contemporary artists, old masters, techniques, and many more. After the residency, a comparison was drawn between the data. In order to have more tangible and quantifiable data to analyze from, each factor will follow a system of ranking. The results of this research is critical to developing a new artistic perspective and direction for my body of work.

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.

Springsnails are a broad group of highly diverse North American gastropods, with the most speciose genus being Pyrgulopsis (139 species). These tiny aquatic gastropods are often found in thermally-influenced freshwater springs, where endemism is common. Restricted occurrence and narrow habitat requirements of many species has generated conservation concern because of anthropogenic threats to spring systems and associated aquafers. The Blue Point Pyrg is endemic to Blue Point Spring in Lake Mead National Recreation Area within the eastern Mojave Desert. Two other springsnail species also occupy this unique spring. Little is known, however, about the distribution, abundance, and habitat associations of these springsnails. As a first step in a larger study investigating these parameters, we addressed methodological questions associated with the use of artificial tile samplers for long-term monitoring of springsnail abundance. We determined that the area of our tile samplers was adequate for sampling these springsnails and that our multiple, replicate tiles did not produce significantly different measures of abundance within our one meter sampling areas. These results indicate that monitoring could be accomplished with fewer tile replicates. We identified all three springsnail species within our samples and determined that identification of adult springsnails by shell morphology under magnification appears possible; we are currently developing genetic markers to confirm the morphological assessment. The relative abundance of springsnails peaked at approximately four meters below the springhead, and then dropped precipitously further downstream. Limited numbers of springsnails downstream may be related to the presence of nonnative, predatory fishes. We are currently investigating this hypothesis, and the findings of our methodological assessment have allowed us to use half of our sampler replicates in a fish exclusion experiment to assess the impact of predation.

Photoperiod is utilized in plants to control seasonal responses such as flowering. Flowering of Arabidopsis is promoted in long day conditions (LD), late spring to summer, but not in short day conditions. Arabidopsis thaliana is our model organism because of its short generation time and simple genome which allows us to apply our findings to other species. One of the major factors that determines flowering time response to the different lengths of photoperiods is a gene, FLOWERING LOCUS T (FT). FT is induced around dusk in laboratory LD conditions. In natural LD conditions, there is an additional induction of FT in the morning. Although the molecular mechanism behind flowering regulation is the most characterized in Arabidopsis, the mechanism behind the expression of FT in the morning under natural LD conditions is not fully understood. Investigating these mechanisms will help us to understand how Arabidopsis plants flower in spring in nature and ultimately better the accuracy of experiments that are run indoors. The regulation of expression levels of transcription factors may be important for this FT induction. Through RNA sequencing analysis, we found eleven transcription factors within genes that were found to be differentially expressed between laboratory LD conditions and natural LD conditions. Analysis through quantitative polymerase chain reactions (qPCR) will hopefully yield results pointing toward a transcription factor that is important for the regulation of FT expression. 

As climate change progresses, increasing temperature is expected to have community and population-level consequences. The temperature-size rule predicts shifts in both community and population structure to favor smaller bodied organisms over larger bodied organisms as temperatures increases. We investigated this hypothesis in the context of rocky intertidal invertebrate communities on San Juan Island, and examined changes in community and population structure over the past 45 years. We replicated historical ecology studies on the abundance of six intertidal species; three of which body size data was also collected. These species included grazing and predatory molluscs (Katharina tunicata, Nucella lamellosa), anemones (Anthopleura elegantissima), and crabs (Hemigrapsus nudus, Pugettia gracilis, Pagurus sp). Additional abundance data was collected on smaller molluscs (limpets, littorine snails). Predicted decreases in body size were not apparent in populations of K. tunicata., N. lamellosa, and A. elegantissima. However, when comparing abundances, shifts in community structure towards smaller-bodied organisms were apparent. We observed an increased abundance of smaller-bodied gastropods and crustaceans (limpets and Pagurus sp), but a decrease in K. tunicata abundance, one of the largest grazers in this system. This research highlights the potential for a variety of community and population responses including both stability and variability in the face of climate change.

Forage fish such as Pacific herring, Clupea pallasii, are a valuable economic and ecological resource in marine food webs. Forage fish are integral species as they can drive both top-down and bottom-up effects in pelagic marine communities. Understanding population dynamics of herring and other forage fish species is essential to management. Although poorly studied, parasites of forage fish are of particular interest due to their potential effects on population dynamics and ability to predict the presence of anthropogenic contaminants in the environment. The goal of this study is to determine if parasite communities differ in composition and diversity between year-zero herring collected in offshore and nearshore (marina) environments in the Puget Sound. I am performing necropsies on 180 herring collected from 6 Puget Sound sites. I expect to find a greater abundance of parasites that use direct transmission in nearshore herring due to decreased stock mixing, as well as a greater prevalence of certain parasites due to closer proximity to anthropogenic contaminants. Parasites remain understudied in important forage fish like herring; and, this research can be used to understand population dynamics of herring in local marine environments as well as aid in fisheries management.

 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.

Advancements in fabrication of manufacturing and medical systems is focusing on using computer-aided fabrication methods, also called additive manufacturing or 3D printing. In civil engineering, we still rely on traditional methods of construction. Although there are researchers and companies investigating 3D printing of concrete, most focus on form, not on engineering properties. This research project has begun to remedy that by investigating mix design methodologies, new extrusion techniques and use of large-capacity testing equipment to advance engineering of 3D printed concrete structures. The first phase has investigated extrudable and stable (in its fresh state) mix design(s); a new protocol is being developed to test the engineering properties, including stiffness, strength of the extruded material, as well as multi-layer adhesion and deformation. The second phase will investigate the hardened properties. The research is funded by Pactrans, with the ultimate goal of printing components for multi-modal concrete structures, such as pedestrian and bicycle bridges.

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.

 During development in most animals, tubes form as precursors to complex organs such as the neural tube, digestive system, and vasculature. To create a tube, cells within a sheet, or epithelium, must coordinate specific shape changes and movements. This coordination requires each cell to establish and maintain directional identity, thereby distinguishing the ‘top’ of the sheet from the ‘bottom’. While extensive research on a group of proteins, called ‘polarity proteins’, has elucidated how cells establish directional identity, little is known about how they maintain that orientation during the shape changes and rearrangements that occur during tube formation. To address this gap in our understanding, I am studying how these polarity proteins contribute to proper tube morphogenesis during the formation of specialized structures on Drosophila melanogaster eggshells called dorsal appendages (DAs). These appendages, which provide the developing embryo with oxygen, are formed from an epithelium that wraps into a tube, elongates, and then fills with eggshell protein. The epithelium sloughs off when the egg is laid, leaving the appendages as a visualization of the earlier tube formation. I used RNA interference (RNAi) to assess the role of 24 candidate proteins in DA formation. My initial results led me to hypothesize that one protein, Crumbs (crb), regulates the tube’s directional elongation. To explore this role, I am studying crb protein localization during tube elongation, assaying DA defects after knocking down expression using RNAi in subsets of cells, and analyzing the distribution of adhesion, motor, and other polarity proteins when crb is completely absent in null clones. These analyses will add to our understanding of the role of polarity proteins in the conserved development of epithelial sheets into tubes.

Stress-related disorders impact over 18% of the United States population. Further definition of the mechanisms behind stress responses in the brain is necessary for understanding and treating stress related disorders, such as anxiety and depression. Specifically, the lateral habenula (LHb) is a brain region known to modulate stress and anxiety responses, but the ways in which it modulates these responses is relatively unknown. In order to investigate potential mechanisms for this modulation, we examined differential gene expression in the pathways from the LHb to three brain regions: the ventral tegmental area (VTA), the dorsal raphe nucleus (DRN) and rostromedial tegmental nucleus (RMTg). Rats were stressed using a forced swim protocol and tissue from the LHb was homogenized in order to extract RNA using RiboTag. Using a combination of transgenic mice and a RiboTag viral vector we were able to extract highly specific RNA from complext brain tissue. We used a portion of our collected RNA to perform RNAseq, a molecular tool used to identify differential gene expression in certain pathways. Using the results from our RNAseq analysis, we used extracted RNA to perform quantitative PCR to verify the pathway specific genes found in the LHb. By determining the pathway specific patterns of differential gene expression, we propose a molecular mechanism for neuronal response to stress in the LHb.

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.

Widespread distribution of dissolved uranium (U) from natural and anthropogenic sources poses a challenge to both environmental and human health. Some bacteria are known to reduce highly soluble U(VI) into more insoluble U(IV), limiting the rate it may leach into subsurface environments. Therefore, understanding how this metabolism functions in situ is vital for predicting subsurface U transport. Any thorough understanding of microbial metabolisms must compare different means of energy production (i.e. catabolic reactions). This means the metabolic processes involved in U(VI) reduction must be compared to those where an alternative terminal electron acceptor (TEA) is used. The facultative anaerobic bacterium Shewanella putrefaciens strain CN32 has been the focus of many recent studies on U, but there has yet to be a detailed study of its metabolic efficiency across multiple TEA’s. This work quantitatively examined the metabolic efficiency of Shewanella putrefaciens CN32 by comparing the ratio of cells produced to the total mass of protein produced when growing on three different TEA’s: O2, Fe(III), and U(VI). Furthermore, the overall health of the culture was evaluated by measuring the size of cells grown with each TEA. Initial results indicate that both a larger average cell size and larger ratio of cells to protein mass correspond with potential Gibbs energy of each catabolic reaction (in decreasing order: O2, Fe(III), U(VI) reduction). Gaining a further understanding on bacterial U reduction will allow for hazard mitigation methods to be developed and used in at-risk areas around the world. 

The meteorological conditions across the North of Iceland regulate snow metamorphic processes and are therefore the driving factors behind melt-freeze crust formation. The North Atlantic Oscillation (NAO) is a climate system that controls these meteorological conditions. By analyzing the cumulative NAO index over the past two decades, the influence of climate change on Icelandic meteorological conditions can be established: the shifting climate system is stimulating heightened precipitation and increased northern storm cycles. The association of these climate trends with the historical patterns of avalanche cycling in Iceland can help understanding of the causes of melt-freeze metamorphism and can demonstrate the expected effects climate change will have on these processes. According to the cumulative NAO index and the Icelandic avalanche data from 1995 to 2018, melt-freeze metamorphism frequency increased in the early and late months of winter seasons across the North of Iceland and remained less relevant in mid-winter months. The alteration in frequency and seasonality of melt-freeze metamorphism poses challenges to Icelandic communities possibly facing increased risk of slab avalanches and to the vulnerable ecosystems of Iceland. Increased observation and availability of reliable data is paramount to understanding how snow metamorphism will evolve with climate change and consequently what individuals must adapt to.

Stuttering is a fluency disorder which is characterized by prolongations, repetitions, and blocks, which disrupt the flow of speech (Guitar, 2014). There are multiple factors affecting stuttering, including physiological, psychological, environmental, and linguistic (Guitar 2006; 2016; Kang et.al, 2010; Sitek et.al; Smith & Weber, 2017). Self-disclosure has been shown to improve listeners’ perceptions and attitudes towards people who stutter in a positive manner (e.g., Byrd, McGill, Gkalitsiou, & Cappellini, 2017; Byrd, Gkalitsiou, McGill, Kelly & Reed, 2016; Lincoln, Brinker-Katz, 2017). Yet, limited research has explored the physiological and affective changes that speakers who stutter experience when they self-disclose (or do not self-disclose) their stuttering. Bowers and colleagues (2012) examined the relationship between anticipatory autonomic arousal and stuttering during reading tasks. They found that people who stutter presented with decreased skin conductance when stuttering was eliminated. They also reported that people who stutter exhibited increased final heart rate deceleration when a skin conductance response occurred. Bowers et al. (2012) concluded that physiological responses were best determined by the anticipation/possibility of stuttering, rather than speech outcome (fluent or stuttered). These results suggest the importance of further exploring the anticipation of stuttering and its effects on the speaker who stutters in a variety of contexts (other than reading). In the proposed study, we will ask participants to report speaking situations in which they feel least to most comfortable and we will monitor their physiological and affective responses within those situations. Participant self-report of speaking situations will enable ecological validity and inform our clinical practice. We hypothesize that speaking situations participants rate as “least comfortable” will elicit increased heart rate deceleration during a stuttering moment and decreased skin conductance when stuttering moment is finished.

The natural history and morphology of blue mud shrimp, Upogebia pugettensis, burrows indicate that they farm their burrow linings. We tested the farming hypothesis by comparing carbon and nitrogen isotope, Carbon-13 and Nitrogen-15 ratios in tissues of U. pugettensis, their commensal clams, Naearomya rugifera and Cryptomya californica, and their isopod parasite, Orthione griffenis with other species and trophic groups co-occurring in the same mudflat, including the burrowing ghost shrimp Neotrypaea californiensis and Neotrypaea gigas, benthic clams and polychaetes. Ratios of these isotopes can indicate the relative trophic positions of organisms. We found similar isotope ratios among U. pugettensis and their commensal clams and that were different from isotope ratios in other clams and trophic groups occurring outside of the burrows in the same mudflat. The common isotope ratios among U. pugettensis and its commensal clams relative to these isotope ratios in other suspension and deposit feeding species in the same community are consistent with farming of the burrow lining.

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.

With regards to most tissues, humans lack the ability to regenerate, instead scarring in response to injury. This often leads to poor patient outcomes, especially in the event of spinal cord damage. Xenopus tropicalis are capable of avoiding this scarring response as tadpoles but not as adults. They instead fully regenerate tail tissue and are thus an excellent model system for the investigation of how regenerative and non-regenerative organisms differ in their response to injury. Due to the complexity of this process, many transcription factors have been implicated to have a role in regeneration, though the precise roles of many such transcription factors remain unknown. Here, we focus on the transcription factor Hif1α, which is canonically involved in responses to hypoxia and oxidative stress. Using an Assay for Transposase-Accessible Chromatin (ATAC-Seq) we have found that over the course of regeneration, Hif1α response elements (HREs) increase in accessibility. To understand the role of Hif1α during regeneration, I have used echinomycin, a small molecule known to inhibit binding of Hif1α to HREs. Tadpoles treated with echinomycin fail to regenerate, indicating the necessity of Hif1α in regeneration. In order to determine the effects of Hif1α on gene expression, I have queried several genes known to be differentially expressed during regeneration through the use of quantitative polymerase chain reaction. I have shown that inhibition of Hif1α transcriptional activity via echinomycin significantly alters Wnt target gene expression, indicating that Hif1α regulates Wnt target genes. This provides an improved understanding of the regulatory processes that enable regeneration.

With their small genomes, fast evolutionary rates, and clinical significance, viruses have long been fodder for studies of whole genome evolution. One common need in these studies is the analysis of viral evolution over time through longitudinal sampling. This analysis is relevant to basic scientists to understand viral evolution in different model systems, to drug manufacturers to understand antiviral resistance development, and to clinical researchers to understand viral evolution within hosts across space and time. However, there exists no simple tool to automate such analyses. We created a simple command-line visualization tool called LAVA (Longitudinal Analysis of Viral Alleles) originally to survey HPIV1 and HPIV2 adaptations to culture. Our hypothesis was that the culturing process selects for mutations in viral entry proteins (hemagglutination-neuraminidase and fusion) that are never seen during growth in humans. Previously done manually, LAVA cut down the workload for analysis of minor allele variants significantly, and furthermore visualized the results to instantly show that the primary regions of HN and F in which many of the mutations took place were different than those found in the previously studied HPIV3. Further development on LAVA allowed it to grow into a critically useful bioinformatics tool in virology. LAVA allows dynamic and interactive visualization of viral evolution across the genome, over time, and within three-dimensional protein structure. Results are easily shared via a single HTML file that also allows interactive analysis based on read depth and allele frequency. LAVA requires minimal input and runs in minutes for most use cases. LAVA is programmed mainly in Python and is compatible with Mac and Linux machines. LAVA is a user-friendly command-line tool for generating, visualizing, and sharing the results of longitudinal viral genome evolution analysis. Instructions for downloading, installing, and using LAVA can be found at https://github.com/michellejlin/lava.

WMlife Network Technology Company Ltd builds shared bookcases located in kindergartens to rent picture books at a low annual fee. WMlife builds bookcases of different sizes based on the number of students in the kindergartens. For all existing kindergartens in the system, WMlife has been choosing the same set of books for every kindergarten. However, now they are considering supplying different book sets to different kindergartens and exchanging books between them each year to provide new books while reducing total cost. To minimize the time investment by WMlife, we modeled the problem as a periodic traveling salesman problem and used a modified Prim’s algorithm and brute-force to find the route with the shortest traveling time. We also constructed a feasible book exchanging algorithm. With our new strategy, WMlife could get a dynamic instruction for book exchanging instantly with kindergarten locations and starting locations as input. WMlife can exchange books easily according to our instructions and significantly reduce cost by 30% in book reallocation approximately. As WMlife expand their services in more cities in China or adding more new kindergartens to the existing city, they could have a smart start of purchasing the book for future cost saving. The system not only solves a one-time problem but also can support WMlife to provide better books and more book types for kindergarten children, help them to form reading habits, widen their horizon and raise Chinese average reading rate.

The University of Washington High Enthalpy Flow Laboratory (HEFL) has constructed a purpose built laboratory for experimental research on Rotating Detonation Engines (RDE). This refit included the rebuilding of the lab apparatus, the assembly of the RDE and supporting equipment such as downstream piping, vacuum system, gas handling plumbing, and the redevelopment of the experimental instrumentation. The assembly of the lab apparatus consisted of the construction and mounting of fuel, oxygen, and nitrogen lines for the RDE, and the assembly of back pressure controlled exhaust tubes leading to a dump tank and an optical imaging port. A stand for the engine apparatus itself as well as much of the plumbing support equipment was also constructed. The assembly of the RDE consisted of the assembly of the various engine parts, followed by the connection of the various instruments such as pressure sensors, temperature sensors, ion probes to the engine itself. The hardware and software components of the instrumentation systems were also redeveloped to allow for very high instrument density for pressure and temperature sensors on the RDE. The software component of the instrumentation involved developing MATLAB scripts for valve actuation, data acquisition, and sensor calibration. The hardware aspect of the instrumentation involved selecting the sensors to be used on the engine based on their signal conditioning, as well as designing and building power supply and signal processing circuits to connect the sensors to a rebuilt data acquisition computer system.

We previously observed that turmeric could be used to manipulate gut motility in a microbiome-dependent-bile acid-mediated manner via the enteric nervous system (ENS). Bile acids comprise a class of metabolites synthesized by the host and modified by gut microbes. Bacterial bile salt hydrolases (BSH) are responsible for deconjugation, the first step in bile acid metabolism for generation of secondary bile acids. We hypothesized that homeostatic ENS signaling is dependent upon gut bacterial bile acid metabolism. To test this hypothesis, we colonized wild-type gnotobiotic mice with different defined consortia varying in BSH activity and subjected them to a two-week low-fat diet ± turmeric. As a control, one treatment group remained germ-free. mRNA isolated from small intestine and colon was subjected to gene expression profiling returning counts of 68 target genes, including ENS-specific genes, and 7 housekeeping controls. A machine learning algorithm was deployed to identify genes whose expressions were most impactful in discriminating between treatment groups. Glp2r and VIP were highly discriminatory with respect to BSH activity. Enteric neurons express Glp2r, activate the mTORC1 pathway in response to GLP-2, and modulate intestinal epithelial cell growth. We found that Glp2r expression was significantly greater in mice harboring consortia with BSH activity than in germ-free mice. GLP-2 induces VIP neurotransmission from enteric neurons. Indeed, VIP expression is correlated with Glp2r expression. These data suggest that gut bacterial bile acid metabolism regulates homeostatic ENS signaling, with implications for gut motility and colorectal carcinogenesis.

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.

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. 

This study was conducted in order to examine the differences in how themes pertaining to culture are represented in the disciplines of anthropology and psychology. Leading psychological and anthropological databases, PsycINFO and AnthroSource, were used to randomly select and collect 1,018 article abstracts from those published between 2008 and 2018, stemming from the key search term culture. Utilizing the language and data analysis software, Raven’s Eye, a quantitative phenomenology was conducted to explore the overrepresentation and comparison of terms in both psychology and anthropology as they relate to culture. The results identify a substantial difference in terminology associated with culture among the two disciplines. The most frequently overrepresented terms from the PsycINFO database were health, study, mental and immigration. The most frequently overrepresented terms from the AnthroSource database were politics, violence, knowledge and discourse. Both databases demonstrated a difference in gender terms associated with culture. In PsycINFO database abstracts, the term men’s was considerably more overrepresented than any of the terms utilized to refer to women. Abstracts discovered in AnthroSource used gender terms much less often when compared to PsycINFO, with the most frequent gender term being women’s. The implications of this study inform the culturally competent practice of healing and are integral to the understanding of potential prejudice and culture bound terms used to identify gender. The results can inform the science of psychology and anthropology by increasing social awareness of culture and gender representation and decreasing disciplinary biases.

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.

For years, scientists have been baffled by the imbalance between matter and antimatter in the universe. The properties of the neutrino, a subatomic chargeless particle, may ultimately help us explain this anomaly. Double beta decay takes place in an atomic nucleus, and it occurs when two neutrons spontaneously transform into two protons, emitting two electrons and two antineutrinos in the process. However, if the neutrino is its own antiparticle, the antineutrinos could annihilate each other, so that the two electrons are emitted with no balancing emission of antimatter. This is a postulated process known as “neutrinoless double beta decay.” The MAJORANA Demonstrator, a collection of germanium detectors, allows us to search for this creation of matter in a laboratory setting. However, there are naturally occurring background processes, such as gamma rays, which closely resemble that of the creation of matter. In order to accurately distinguish one process from the other, we must understand them extremely well. The Demonstrator relies heavily on the use of simulation software, called Geant4, in order to predict the occurrence of gamma ray backgrounds. Geant4 previously generated the gamma rays’ directions isotropically, but many sequences of gamma emission are emitted in correlated directions. We contributed new code that uses the computation of associated Legendre polynomials to correctly generate the gamma emission directions. This code used a recursive algorithm that was too slow for general use. A speedup was attempted using a cache, meaning it stored computations to avoid repetition. However, the cache was implemented inefficiently and incorrectly. Improved caching should speed up calculations. If it is insufficient, we will unwrap the recursive algorithm into a generative for-loop. For gamma emissions with extremely large angular momenta, the code may still be too slow. In that case, we will explore asymptotic formulae to speed up computations even further.

The delivery of cell and drug-based chemotherapeutics to tumors have presented major challenges in effective cancer treatment. Opportunities to improve current small molecule drug delivery systems exist by increasing overall delivery specificity and decreasing harmful off-target effects. Towards this, we have recently developed a chemical framework for creating user-programmable hydrogels that undergo programmed degradation in response to multiple environmental cues following Boolean logic. Exploiting this methodology, user-specified combinations of environmental inputs (e.g., tumor-presented enzymes, reducing conditions) yield material breakdown and accompanying therapeutic release. To translate these materials for chemotherapeutic delivery in vivo, we established strategies to formulate these stimuli-sensitive materials into nanogels that circulate in the bloodstream before acting on the desired target site. We developed techniques to formulate gels on the 50-250 nanometers size scale, one which should enable circulation in the blood and uptake within tumors based on the enhanced permeability and retention effect. Different ultrasonication conditions allowed us to tune nanogel, size and dispersity. This system is scalable, translational, and simple to recreate. In the future, these materials can effectively hone and selectively deploy small molecule chemotherapeutics to tumors in patients.

c-fos is an immediate early gene that is commonly used to mark cell activation and can be identified using immunohistochemistry techniques. In this project, we optimized immunohistochemistry conditions for a phosphorylated c-fos antibody in brain tissue obtained from the rat lateral habenula (LHb). Male, Long-Evans rats (n=4) were injected with cocaine (10 mg/kg) or saline. Ninety minutes following intraperitoneal injections, rats were perfused with 4% paraformaldehyde. Brains were dissected and 40-micron slices across the rostro-caudal axis of the LHb were collected. We tested two dilutions of the rabbit phospho c-fos antibody (1:500 and 1:800), three blocking agents (normal goat serum, donkey serum and bovine serum albumin) and two secondary Alexa Fluor antibodies (goat anti-rabbit Alexa Fluor 488, and donkey anti-rabbit Alexa Fluor 488) to determine which combination allowed for the best visualization of c-fos in the LHb. Fluorescence microscopy analysis of the tissue sections is underway, and imaging is expected to show differences in brightness and visibility of c-fos with respect to the varying conditions. These results will identify the optimal conditions for more accurate identification and quantification of cell activation in the lateral habenula.

Fibrolamellar carcinoma (FLC) is a life-threatening variant of liver cancer affecting adolescents and young adults. FLC tumors do not respond to chemotherapy, thus, surgery remains the mainstay of therapy. FLC is characterized by a fusion event resulting in a novel chimeric protein that joins the N-terminal domain of DNAJ with the catalytic subunit of protein kinase A (PKAc). However, the underlying mechanism by which the FLC chimeric kinase drives FLC tumor growth remains unknown. Using CRISPR/Cas9 technology, the Scott Lab (UW) has re-created the human FLC fusion protein in a well-characterized and non-transformed hepatocyte cell line. The resulting cells retain hepatocytic differentiation while over-expressing DNAJ-PKAc compared with wild-type PKAc, akin to the human tumors. Using these model cell lines and a computational approach called, Kinome Regularization (KiR), I plan to uncover molecular mechanisms through which chimeric PKAc transforms hepatocytes in FLC. The concept of KiR is built around the fact that most kinase inhibitors are not specific but instead, affect a range of targets. By exploiting the property of polypharmacology in a set of well-characterized kinase inhibitors, we can make use of elastic net regression to compute and deconvolute the kinases that are responsible for a quantitative trait. To do so, we have identified a set of 30 broadly specific inhibitors that give us >85% coverage of the kinases studied. We can then test the effect of each of these 30 inhibitors on cell growth and use the results to identify the kinase important for cell growth. The KiR-based model will also be used to identify kinase inhibitors which can specifically reduce growth of FLC cells. Overall, these studies have a strong translational potential; a new therapeutic option for FLC could give unprecedented hope to the patients who currently face this disease with limited alternatives.

Biomimicry as a practice has generated a plethora of innovative technologies. By observing key processes that evolution has converged upon, we can improve and evolve manmade mechanisms. This literature review addresses the importance of vortices in biological systems and compares their locomotive purposes across a wide range of animal phyla. The development of particle image velocimetry (PIV) has enhanced our ability to study the vortex mechanics of remarkably fast or efficient animals. Such experiments have made great contributions to the human understanding of flow and kinematics. Vorticity studies, for example, have produced results that contradict the paradigm for animal motion-- particularly in how the inherent low-pressure zone associated with vortices can allow animals to maneuver through a fluid. Lampreys and jellyfish have shown to use vortex-based locomotive techniques to “suck” themselves through the water. Additionally, the “hyper-pitching" process of the zooplanktonic sea butterfly is controlled by pressure fields generated by leading edge vortices. Such findings have interesting implications for the future of biomimetic water and air travel, as the utilization of pressure as opposed to thrust may facilitate the creation of more efficient vehicles. Furthermore, comparative biological studies allow for a more in-depth interpretation of animal kinematics that have been difficult to study due to lack of proper technology. By creating qualitative analogies between air travel and water travel, we can reexamine how airborne creatures move.

Dogs have been shown to use the direction of humans’ gaze to infer information about hidden food, a behavior referred to as social referencing. We might expect that social dependency towards a handler will be higher for dogs that are more dependent on humans’ presence, especially when faced with uncertain situations. We tested whether there was a relationship between attachment and dependency behaviors and social referencing in companion dogs. Dog owners completed an intake survey that included the previously validated Canine Behavioral Assessment and Research Questionnaire (C-BARQ), which gives a score for the degree of separation-related distress behaviors dogs exhibit which we used as a measure for dogs’ attachment and dependence on their owners. These owners then brought their dogs to participate on-location for our experimental set up. We taught the dogs a location-based discrimination task, in which subjects learned to expect a food reward in one location (the positive stimulus), and no reward in an opposing location (the negative stimulus). When dogs approached the positive stimulus faster than the negative stimulus, we intermittently presented them with ambiguous stimuli, i.e. intermediate between the positive and negative stimuli. We measured social referencing as the frequency of glancing behavior of dogs toward their owner or the handler for each trial. We analyzed social referencing by stimuli in order to assess whether dogs would treat ambiguous stimuli as they do the rewarded location or the non-rewarded location with respect to glancing behavior. We hypothesized that dogs with higher C-BARQ scores for separation-related behavior would exhibit higher proportions of social referencing behavior, particularly when presented with ambiguous stimuli. Our research has implications regarding potential effects of canine dependency on their owners in their decisions in certain situations, such as those that introduce ambiguity.

The threat of influenza, Ebola, Lassa, and Zika (ZIKV) viruses are unprecedented in their current scale and spread, causing enormous global health and economic burdens. The need for effective drugs which are safe for use in humans, including during pregnancy and in children, is critical to addressing this worldwide threat. The antiviral drug Arbidol (ARB) is used clinically in Russia and China as an anti-influenza drug. ARB binds to the influenza hemagglutinin protein to block entry of the virus into human cells. ARB also blocks infection of cells by Hepatitis C virus (HCV), Ebola, Lassa, and ZIKV primarily by suppressing viral entry and potentially by inhibiting post-entry events such as viral replication. The purpose of this project is to optimize and quantitate immunofluorescent detection of the HCV NS5A protein to evaluate the efficacy of ARB against HCV replication. Various dilutions of primary and secondary antibody will first be tested to optimize detection of HCV NS5A in HCV replicon cells. The assay will be miniaturized in 96 well plates. Next, an automated microscope (Biotek Cytation 1) will be evaluated as a method for quantification of immunofluorescent detection by imaging wells for HCV NS5A. HCV replicon cells will then then be treated with various doses of ARB and the antiviral efficacy of treatment quantitated. Defining the various ways by which ARB suppresses different viruses may expand the drug’s use and, thereby, inclusiveness for addressing multiple global viral threats.

Lift-off is a subtractive process used in wafer fabrication of Micro-Electrical-Mechanical-Systems (MEMS) devices to pattern deposited films, often metal, that are challenging to dry etch. To achieve a successful lift-off, the lift-off process begins by depositing and then patterning a photoresist masking material onto a silicon wafer using photolithographic techniques. An important characteristic of the photoresist is undercutting the resist sidewalls after developing, protecting them from being coated with metal during deposition. After deposition, the photoresist and metal layer is removed via solvent. The purpose of our research is to allow for a more varied range of fabrication using positive tone photoresist. Negative tone photoresist is typically used for this lift-off process because after development, this resist naturally forms the desired undercut. Alternately, positive tone photoresist is characterized by a tapered sidewall that is difficult to not coat with the metal film layer, making the removal step via solvent problematic. We hypothesized an advantageous undercut is possible with positive tone photoresist using a white light diffuser that would allow light to enter at angles through our mask during the exposure step. We evaluated resist undercut using the Nikon microscope and resist/metal sidewall characteristics using the Scanning Electron Microscope. We will assess the new resist exposure technique using both line-of-sight evaporation (physical vapor deposition in which a target material’s atoms precipitate into solid form, when heated up under high vacuum, coating everything in the vacuum chamber) and sputtering (metal deposition involving particle ejection of ions) to deposit a thin metal film. We anticipate evaporated metal to lift-off easily with the new technique, which indicates a crowning demonstration of success.

The idea of energy, matter, and motion has perplexed many philosophers and physicists from antiquity to modern physics, from Plato to Einstein. New and developing physical theories raise different interpretations of energy and matter but no complete theory of everything exists at present. However, there is a law we can almost take for granted - the Law of Conservation of Energy, it simply states that energy cannot be created nor destroyed although it can be transformed from one form to another. With an up-to-date history of the first law of thermodynamics, physicists in the field can have a sense of what has been done and what not. A complete overview of the rudimentary law would also provide a continuous timeline in which one can identify flaws in current theories. After establishing the foundational theory and history of conservation of energy, this literature review aims to provide a comparative study between the concept of mass and energy in two of the most profound physical theories - Quantum Mechanics and General Relativity. Subtle implication of numerous laws of thermodynamics and mass-energy equivalence like Dark Energy, Dark Matter, Higgs Mechanism and Blackhole Thermodynamics is studied in an introductory manner for potential history and correlate direct and indirect links to energy conservation.

 Domestic dogs express individual differences in personality and perception, affecting their behavior towards objects they encounter in the world. One of these differences is a form of cognitive bias called judgement bias. Dogs that approach an ambiguous stimulus at a rate closer to that of approach towards a rewarded stimulus demonstrate a positive judgement bias. Likewise, dogs who approach at a rate closer to that of a non-rewarded (or aversive) stimulus have a negative judgement bias. Some dogs refuse to approach the non-rewarding stimulus entirely, which can be defined as refusal behavior. We analyzed whether refusal behavior was related to companion dogs’ judgement bias and general fear and anxiety. Dog owners completed the Canine Behavioral Assessment and Research Questionnaire (C-BARQ), a previously validated questionnaire measuring a variety of individual differences in dog behavior, and, most importantly, fear and anxiety. Afterwards, dogs were brought in for in-person testing. We measured each dog’s latency to approach ambiguous stimuli and compared this to their latency when approaching rewarded versus non-rewarded stimuli. We would expect that dogs who refuse to approach ambiguous stimuli will also exhibit higher C-BARQ scores in fear and anxiety than dogs who do approach ambiguous stimuli. Refusing to approach may also suggest a negative judgement bias. These findings are extremely useful to not only further understand canine behavior and cognition, as refusal to engage with a stimulus may be a future tool to define a canine’s perception of ambiguous stimuli. They also have practical implications for both animal welfare and training efficacy, as individual cognitive differences among dogs may impact how they will respond in behavioral tests and training regimes.

Hydrogen sulfide (H₂S) is a common cause of workplace injuries and deaths for industrial workers. In our project, we use Caenorhabditis elegans (C. elegans) as a model organism for investigating how cells behave under an environmental stressor and the long-lasting effects of that behavior. Previous work in our lab has shown that early exposure to low H₂S (50 ppm) enable C. elegans adults to survive a much higher subsequent exposure by forming a cellular memory known as a “bookmark.” Bookmarked animals survive at high H₂S (150 ppm), while animals without previous exposure do not. In a genetic screen, we identified various epigenetic factors that are involved in this process; however, it is still unclear when in the “life” of the bookmark and where in the animal these factors are required. The required bookmarking gene swsn-4 is part of the SWI/SNF complex, a group of proteins that regulate compaction of DNA and thus the accessibility of genes. We are interested in assessing the spatial requirements for swsn-4 by rescuing mutant animals that lack this chromatin-remodeling factor. For the first part of the project, we use Gateway recombination cloning technology to enable tissue-specific expression of swsn-4. In the next part of the project, we test whether introducing swsn-4 in specific tissues rescues bookmark retention. A recent study identified hif-1, a transcription factor, to be broadly needed to rescue animals exposed to both low and high H₂S, suggesting that the response is needed in most cells to ensure survival of the animal. Because swsn-4 is also present broadly in the body of C. elegans, we predict it will be needed in a similar way to hif-1. We hope that our investigation would lead us to discovering methods in which we can utilize the properties of H₂S as a chemical messenger to help patients.

The tools of mathematical modelling have been applied to many sports where athletes are searching for strategies to improve their performance. Downhill mountain bike racing is a sport that could benefit from mathematical modelling. My research is aimed at developing a computer algorithm that uses mathematical modelling to simulate downhill mountain biking. In a mountain bike race, racers compete for the fastest time to individually ride down a trail with turns and obstacles. The fastest riders are the most efficient at converting their potential energy to kinetic energy. These riders accomplish this by optimizing the amount of their energy expended on braking and friction so they are just below the borderline of crashing throughout the entire trail. The finishing times of the top 10 riders are often very close, indicating that they are approaching a physical time limit to complete the trail. By using mathematical modelling and the GPS profile of a downhill trail as input, I aim to develop an algorithm that optimizes braking at every point on the trail and outputs the minimum time to complete the trail. The results from this algorithm would provide insights into how a rider could improve their performance. In my work, I show that mathematical modelling can accurately simulate the motion of a downhill rider, explain the challenges in developing a computer algorithm that optimizes braking, and discuss the results of an experimentally tested algorithm.

Pulmonary fibrosis is a disease marked by irreversible scarring and thickening of the lung tissue causing significant decline in lung function. Individuals afflicted will struggle to perform simple physical activities and often require mechanical assistance at some point in their lives. Currently, there are no permanent solutions for those with pulmonary fibrosis as most treatments only aim to slow down the progression of the disease. In these studies, we developed a novel therapeutic that could stop the progression through DNA modification of fibrotic gene targets using exosomes as a delivery vehicle. Additionally, regeneration of lung tissue is imperative for reinstating lung function and by using similar technologies we aim to target and overexpress critical regenerative genes. Using CRISPR Cas9 gene editing technology, we were able to knockdown key cytokine specific genes responsible for the development of fibrosis. We specifically targeted TGFß (Transforming Growth Factor ß) and Interleuken-6 (IL-6), both known to play a significant role in pro-inflammatory responses and fibrosis through exosome-mediated delivery mechanisms. CRISPR Cas9 vectors were designed to contain unique guide RNAs that could effectively target specific genes that the Cas9 complex could use to repress TGFß and IL-6. Cell lines were treated with the modified CRISPR Cas9 vectors and assessed for gene and protein expression. This study provides key insight into a novel therapeutic platform using a new delivery mechanism that mitigates and reduces fibrosis and promotes recovery of pulmonary function.

Lung transplantation is currently the only treatment solution for end-stage lung disease in a large cohort of patients afflicted with a range of pulmonary issues including cystic fibrosis (CF) and idiopathic pulmonary disease (IPF). Despite the successes, a major setback is the development of chronic lung allograft dysfunction (CLAD). This is characterized by chronic inflammatory host responses towards the transplanted lung resulting in injury of the donor tissue. Currently, we are investigating the role of cell-derived vesicles or exosomes, in a range of immune responses such as chronic inflammation. The composition of exosome membrane components and internal signaling within exosomes depend on the cell type from where it was secreted and the current immune state. A major benefit is that unlike cells, exosomes do not change phenotype after being secreted by the parent cell due to environmental stimuli, making them ideal targets for biomarkers associated with immune responses. In these studies, we assessed exosome surface markers and investigated exosome function from retrospective patient serum, which provides insight into potential novel mechanisms in the development of CLAD. We developed a novel ExoFlow that qualitatively and quantitatively assesses exosomes at 1, 3, 6, and 12 months posttransplant using CFSE, traditional fluorescent antibodies for T cell and macrophage markers, and ImageStream to generate immune profiles. We then correlated these results to clinical outcomes. In a preliminary study, it appears that macrophage exosome profiles show significance in differentiating patients who develop CLAD, while T cell specific exosomes seem to be unremarkable. This could be attributed to the heavy course of immunosuppression posttransplant. Functional studies show insight in potential polarization capabilities of exosomes as immune modulators and provides another novel area of investigation into the complex pathogenesis of CLAD.

This research involves the design of a system for an unmanned aerial system (UAS) to operate and navigate in an environment devoid of a Global Navigation Satellite System (GNSS) such as the Global Positioning System (GPS). The system operates by interrogating an aviation transponder (either mode C or S) that is carried by the UAS and measuring the time elapsed for the response to multiple, ground-based antennas and using triangulation (multilateration) to locate the transponder and by association, the UAS. The ground-based system then routes this position information back to the UAS via the UAS’s data telemetry link. The autopilot then utilizes this position information for navigation in much the same way it would utilize a GPS-based position report. Our research focused on the system architecture to enable a UAS to operate in a GPS-denied environment. Flight test results are presented utilizing a customized version of the popular Pixhawk/ArduPlane avionics platform and demonstrate that the system is capable of guiding a UAS through a series of waypoints in the absence of GPS signals. Furthermore, the customized controller that was designed to consume this alternate source of position information performed well in highly unfavorable environmental conditions. This success illustrates the feasibility of the system as a practical alternative to GPS.

Previous research has found descriptive drinking norms (i.e., how much someone thinks others drink) are associated with increased risky drinking and intentions to drink among college students. However, this research has mostly focused on self-reports of typical drinking, whereas some students report low levels of drinking except on specific high-risk events such as birthdays. This study expands on previous research by examining how descriptive birthday drinking norms moderate the relationship between drinking on a previous birthday and intentions to drink on an upcoming birthday. We hypothesized a positive relationship between previous birthday drinking and intentions to drink that would be more pronounced in students with increased norms. A total of 248 University of Washington students (aged 18-24) who reported at least one heavy episodic drinking event (5+/4+ drinks for Males/Females) and three alcohol-related consequences in the past month were assessed. Participants reported the number of alcoholic beverages they drank on their most recent birthday, how much they intended to drink on their upcoming birthday, and the number of drinks they thought a typical University of Washington student drinks on their birthday. Results from moderated linear regression demonstrated both previous birthday drinking and birthday norms were positively associated with intended birthday drinking (b = 0.477, SE = 0.063, p < 0.001; b = 0.189, SE = 0.054, p = 0.001, respectively). The cross-product of birthday norms and intended birthday drinking also had a significant effect (b = -0.036, SE = 0.013, p = 0.005), such that the effect between previous birthday drinking and intended birthday drinking was strengthened in those with higher norms, supporting our hypothesis. This research contributes to critical literature addressing high-risk alcohol use among students and helps to better understand the role of norms and high-risk drinking events, such as birthdays, in research.

Aging is characterized by the loss of physiological and cellular functionality, however the mechanisms that underlie this deterioration are still unclear. Emerging evidence indicates that aging is associated with increased cell-to-cell variation in gene expression within tissues: homologous cells within tissues start expressing the same gene at varying levels. The causes of this age-related variation of gene expression are not known. Here, we aim to investigate this age-related dissimilarity in gene expression using C. elegans as a model system. We hypothesize that increase of gene expression variation is an early event during aging that may therefore underlie subsequent deterioration of tissues functionality. By characterizing aging in C. elegans, we hope to provide further insight into the molecular characteristics of aging in humans, and possible points of intervention. Previously, we have found that young C. elegans animals exhibit nearly identical stoichiometry of independent genes expression with very little difference between individual animals of the same genetic background. Our initial results support the idea of increased cell-to-cell and animal-to-animal variation of gene expression with age in C. elegans. Here, I use quantitative microscopy to measure animal-to-animal and cell-to-cell variation of genes expression in middle aged C. elegans using fluorescently-tagged proteins and quantitative microscopy. In addition, I use the methodology of molecular cloning and transgenics developed by the Mendenhall lab to create new transgenic strains of C. elegans. These transgenic strains will be also be used for quantitative microscopic analysis. By examining existing strains and developing new ones, I will determine if increase of gene expression variation represents early event in the aging of C. elegans.

Culturally competent interventions are essential to recruiting and retaining ethnic minority populations. Latino communities are the fastest growing population in the United States. Despite their growing numbers, Latino communities are dramatically underrepresented in clinical trials. As a result, the data from those clinical trials are not representative of the Latino population. There are many factors that make Latino communities very diverse, even amongst themselves. They do not share the same languages, customs, and socioeconomic status. There is a need to investigate the barriers and facilitators of the recruitment of Latinos into research. A survey was developed for Latino families in Oregon. The survey items were informed by a literature search around barriers and facilitators of clinical trial participation for minority and disadvantaged populations. This survey has been translated in both English and Spanish. After finalization of the survey, it was piloted with three representatives from the local community to get qualitative feedback. It will be administered to low-income parents of children enrolled in head-start settings in Oregon over the next five months and expect to have 200 responses. The anticipated results will contribute a better understanding of what commonly impacts recruitment among the Latino families participating in clinical trials and what strategies address those issues. This project can serve as a resource for the wider scientific community that seeks to recruit and study the Latino population for research purposes.

c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinases (MAPKs) family that are derived from three genes: Jnk1, Jnk2, and Jnk3. JNKs have been implicated in several cellular responses to homeostatic insults, including inflammation and apoptosis. We previously reported in a chronic epilepsy rat model significant elevated levels of phosphorylated JNKs (pJNKs), which indicate increased JNK activities. Additionally, we demonstrated that pharmacological manipulations of JNK proportionally affected seizure frequency. In this set of experiments, we attempted to identify which of the JNK isoforms (JNK1, JNK2, JNK3) contribute to the overall increased pJNK levels in our animal model of epilepsy. This would provide us insights as to the role(s) of JNKs in this disease. We measured the phosphorylation levels of the individual isoforms after pJNK enrichment from the CA1 hippocampal tissue of chronic epileptic rats and their age controls. The amount of protein was normalized by pJNK levels between experimental and control samples. We found a significant increase in activation levels of JNK2 in chronic epilepsy at 130 ± 9% (n=6, p=0.018) when compared to naïve, nonepileptic controls but insignificant changes in activation levels of JNK1 (97 ± 14%, n=5, p=0.83) and JNK3 (98 ± 17%, n=6, p=0.92). Previously, we had found in rats that JNK1 predominantly exists in the 46kDa size; JNK3 predominantly exists in the 54 kDa; and JNK2 exists in both sizes equally. We further analyze which of the JNK bands (46 kDa and 54 kDa or both) contribute to the elevated phosphorylated JNK levels. Given the previous pharmacological observation that JNK manipulation does influence seizure frequency in epilepsy, this investigation is imperative as it will allow us to narrow our focus to a specific JNK isoform to study further.

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.

Metal catalysts exhibit greater catalytic activity as nanoparticles rather than bulk-like particles. Metal oxide supports can promote the activity and stability of metal catalysts due to the strong metal-support interaction, which can change the electronic properties and structure of metal nanoparticles. Metal-on-oxide-support systems are important for fundamental research and applications in heterogeneous catalysis. Nickel-based catalysts are widely used in industrial purposes such as carbon monoxide oxidation for industrial exhaust cleaning. However, nickel can rapidly deactivate due to solid carbonaceous material (coke) formation and nanoparticle coalescence (sintering) on the surface during a catalytic reaction. Metal oxide supports, such as ceria (CeO₂), improve metal catalytic performance by preventing coke formation and sintering, and in particular, ceria has a high oxygen storage and release capacity during catalytic reactions. Here, the adsorption energies, growth morphology, and charge transfer of adsorbed nickel on stoichiometric ceria (CeO₂(111)) and reduced ceria (CeO_1.8(111)) thin films at 300 K and 100 K are studied using single-crystal adsorption calorimetry (SCAC) in ultra-high vacuum (UHV) and surface sensitive techniques such as low-energy He⁺ ion scattering spectroscopy (LEIS), X-ray photoelectron spectroscopy (XPS), and low energy electron diffraction (LEED). The initial heat of adsorption of nickel atoms on stoichiometric ceria was ~45 kJ/mol greater at 300 K than at 100 K and ~65 kJ/mol greater than reduced ceria at 300 K. The calorimetry results indicate that nickel prefers step edges over terraces and binds stronger to stoichiometric ceria than reduced ceria due to nickel's oxophilicity. LEIS growth mode measurements indicate that nickel grows as 3D nanoparticles. XPS charge transfer experiments show that adsorbed nickel transfers electron charge to ceria below a coverage of 2 monolayers. These results encourage additional study of the adsorption energetics of other group 8 transition metals on ceria supports.

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.

Organic photovoltaic (OPV) cells are an emerging technology that is experiencing continued breakthroughs such as reaching a power conversion efficiency (PCE) of 17.3% in August, 2018. OPVs have the potential to become a major source of energy in our future and a more sustainable energy option than traditional solar cells. In addition to contributing a lower environmental impact than common silicon-based solar cells, OPV cells can be made to be flexible, lightweight, and are comparably inexpensive to fabricate. They are also quite customizable via molecular engineering providing the opportunity for much novel architecture. Our research team focuses on innovating a modular processing system for OPV cells in the form of multi-component fibers by continuously coating device layers onto wires and winding the fiber with a secondary electrode. Using a small, user-friendly system allows us to focus on the most important factors that affect the morphology and PCE of the resulting OPV fiber. After characterizing the fibers we are able to consider what changes need to be made to the modular system, allowing us to better advise on the design of a larger-scale manufacturing process for organic photovoltaic fibers.

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.

During a 2013 meeting of the Puget Sound Beekeeper’s Association, two major concerns were voiced regarding the rapid demise of bees. One was overwintering loss of honey bees and the other was Varroa mite infestations. The Puget sound area had an average closer to 40%, and overwintering loss for the nation averaged around 30%. This resulted in 2015 President Barack Obama issuing a “National strategy to promote the health of honey bees and other pollinators.” To reduce honey bee colony losses during winter, an effort was made to assess cause of death in honeybees. After the assessment was made, this sparked the creation of the “Mite Busters,” an elite team of students, and community members who shared their passion in beekeeping and biology. The goal of the “Mite Busters” was to assess the cause of death in honeybee populations during the winter months. The Mite Busters conducted an assessment of 15 characteristics of hives in 100 different colonies around Puget Sound in August 2016, and October 2016. Colony death rates were measured after the winter months had passed. The only measurement that allowed us to predict whether the colony would live or die was the mite counts from nurse bees. Before overwintering, colonies that had over 7 mites/100 bees had a 70% chance of overwintering death (30% survival rate). Colonies that had under 7 mites/100 bees mites had a 4% chance of overwintering death (96% survival rate). The results sparked the creation of the Mite Busters, which has put forth a variety of group based mechanisms to help all bee keepers keep healthy colonies together. Specifically, the focus is on treatment plans and methods to decrease infestation rates. The mite busters conclude that fewer varroa mites leads to better overwintering success rates for Puget sound honey bees.

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.

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.

Many children in the United States experience mental health issues that impact their performance in school. Evidence-based practices (EBP) have demonstrated effectiveness at improving student outcomes for students impacted by their mental health. However, many factors affect the successful implementation of these programs. Mental health services, particularly those for youths with the most mental health needs, typically involve multi-organizational processes to implement EBP. The Inter-Organizational Alignment study strives to examine these multi-organizational frameworks, and how they impact the school mental health services provided. The research study examined the association between race and the degree of inter-organizational alignment on climate for EBP implementation. Researchers surveyed 28 school mental health clinicians and 57 school staff in the states of Washington and Minnesota. The sample included 22 white or Caucasian participants and 14 non-white participants. Non-white participants were either American Indian or Alaskan Native, Asian, Black or African American, multiracial, or other. Implementation climate of EBP in school settings was rated on a Likert scale of 0 (not at all) to 3 (great extent) on a standard, multi-item scale. Researchers evaluated schools on a range from an open and positive implementation climate to a closed and negative implementation climate. The degree of alignment was determined between clinician and school staff scores, with misalignment defined as a difference of one standard deviation. Quantitative analysis of the results suggested more alignment in implementation climate between clinician and school staff of different races, which suggests that racial factors impact EBP implementation in racially diverse environments. An independent t-test determined that these differences were statistically significant. Consequently, these findings suggest that EBP may be impacted when implemented by more diverse organizations.

The engineering of cells to be capable of detecting and responding to multiple input signals has major applications in the area of diagnostics, cancer therapy and biological computation. Current biological signal processing methods rely on single input single output computations. This proves ineffective when detecting and responding to multiple inputs such as determining a pathology based on combinations of different microscopic cues. The aim is to build non-linear computation in S.cerevisiae (baker yeast). A well-known example of nonlinear computation is neural networks, a complex framework of parallel computations talking together to come to a common output signal. The goal is to build several yeast strains that work together to perform these parallel computations. Each individual strain would process multiple inputs and release a singular output signal to another yeast strain. Combining many strains together would create a complex decision tree capable of higher-order computation. With this goal in mind, we decided to edit the native alpha-factor pathway within the yeast cells. Alpha-factor, a signaling molecule involved in yeast mating, is secreted by yeast and detected with surface protein STE2 (a protein in the GPCR family). We also inserted, a non-native version of STE2 from C.albicans yeast cells. This allowed our engineered strains to detect two different alpha-factor inputs (S. cerevisiae alpha-factor and C.albicans alpha-factor). When detected both alpha-factors trigger the pFUS1-yeGFP pathway causing the yeast cells to fluoresce. We investigated how different concentrations of STE2 and C.A.STE2 on the cell surface influenced the output fluorescents of the yeast strain. Mathematical models were used to interpret the data and predict signal response. These models can be used to design and predict more complex networks.

Measurement in Psychology usually assumes continuous dimensions. Correspondingly, theoretical constructs are typically conceptualized as dimensions, meaning that observations differ in degree. However, theoretical constructs may also be categorical, i.e., rather than differing by degree, differing qualitatively. Different construct operationalization’s may lead to different scientific conclusions. Self esteem has long been of interest in Psychology. It has been conceptualized in various different ways, but always dimensional. Some self-esteem measures (for example, the The Rosenberg Self Esteem scale) seek to measure globally how much one values themselves as a person, without focusing on specific domains. On the other hand, other self-esteem measures (for example, the State self esteem scale) focus on perceived capabilities in specific domains, such as performance, social, and appearance. In the National Survey of Youth, participants rated themselves in specific areas, and then again as they would like to be. Using these data, we examined how different operationalization’s of self-esteem are associated with a few psychologically interesting outcomes such as drug use and crime. Specifically, we compared continuous and categorical representations of self-esteem. By examining the assumption of continuous latent variables, we shed light on how scientific conclusions differ based on construct operationalization.
 

 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.

Parametric models are used in demographic research to reduce the number of parameters over those found in a life table, smooth and correct inadequate mortality data, and provide insight into the underlying processes of aging and mortality. One difficulty with many existing parametric mortality models, such as the Siler model, is that they assume that mortality risk is homogenous. We developed the mixed-Makeham model to explicitly model heterogeneity in mortality in the youngest ages. The model divides mortality risk at the youngest ages into “low-risk” and “high-risk” subgroups, as well as a parameter that specifies the fraction of newborns in each subgroup. Senescent mortality in both subgroups is a shared 2-parameter Gompertz model. We apply the model to cohort life table data from 11 European countries from 1876 to 1925 published in the Human Mortality Database. When mortality is decomposed this way, the proportion of high-risk infants declined and the mortality risk for low-risk infants declined for later cohorts, as anticipated. The mortality hazard for high-risk infants, however, increased for later cohorts. These findings suggest that, over time, medical and public health improvements shifted some fraction of infants from the high-risk category to the low risk category. The shift toward higher mortality hazard in the high-risk infants is likely explained by heterogeneous risk in the high-mortality pool, where medical and public health improvements are less effective on infants at the highest mortality risk.

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.

The global network of nature reserves are intended to be refuges for wildlife species around the world. However, nature reserves are experiencing increasing amounts of human visitation each year, and it is critical to investigate how this influx in disturbance is influencing the space use, abundance, and richness of wildlife species in those reserves. We used camera trap data collected at La Selva Biological Station in Costa Rica, to understand how the presence of humans and other environmental factors are influencing the presence and distribution of various wildlife species. We deployed 9 cameras, in three blocks, on 9 different trails and accumulated 208 active camera nights in 2018. A total of 9,692 photos were obtained of 17 different animal species. We hypothesize that the occupancy rate of species will be primarily influenced by human presence on trails within the reserve. The most commonly detected species were Collared Peccaries (Pecari tajacu) with 0.837 average detections per day, Central American Agoutis (Dasyprocta punctata) with 0.409 average detections per day, and Great Curassows (Crax rubra) with 0.173 average detections per day across all camera sites. Collared Peccaries had a 72% diel activity overlap with humans, Central American Agoutis had a 66% overlap, and Great Curassows had a 78% overlap. I will use the package “unmarked” in the program R to determine the influence of humans on species occupancy and richness. These results will help inform managers at La Selva Biological Station on how to best limit the impacts of human visitation on wildlife species.

Semantic ambiguity arises in language when a word or sentence can take on multiple meanings. The resolution process can not only greatly inform theories of language processing, but can also provide novel insights into human general cognitive abilities. There is evidence for basal ganglia (BG) involvement in semantic ambiguity resolution from a breadth of neuroimaging research and clinical populations. The current project focuses on bilingualism, which creates the higher cognitive demand of selecting, shifting, and inhibition information that is co-activated in two language systems. Our study tested 73 proficient bilinguals using a self-paced reading task that contained a lexical ambiguity manipulation. A probabilistic learning task was used as an index of BG functioning. We anticipate that bilinguals with a more balanced use of their two languages train their BG due to frequently managing interference between multiple languages, in comparison to bilinguals who have an imbalanced use of their languages. This should result in a better performance in resolving semantic ambiguities that arise due to low frequency word meanings. Specifically, we expect this better performance to result in smaller increases in reading speed, which reflect interference, for sentences containing low frequency word meanings, relative to control trials. Better understanding of the role of the BG in semantic ambiguity resolution in various bilingual populations will provide novel insights into the neurocognitive bases of human language processing and executive functioning. We see this as an exciting foundation for studies looking into bilingualism as a form of executive function training.

This work replicates previous research used to criticize the use of principle component (PCA) and exploratory factor analysis (EFA). Factor analysis is often used when research is being conducted in a new area and there is limited background knowledge about what one might expect to find. It’s useful because of its ability to reduce the number of variables in a dataset by examining the correlations between items and identifying latent dimensions that account for measured item variance and covariation. A criticism of this method is that it detects patterns in random data where there is no underlying structure. We tested this criticism by replicating the methods in a 1981 paper by Robert Vierra and David Carlson. We generated random data in R Studio and looked at the variance accounted for by the factors identified by EFA and PCA. We also examined the Type I error rate in sample correlation matrices tested with Bartlett's test. Additionally, we have begun a literature review looking at the modern methods similar to exploratory factor analysis, including machine learning, in order to understand how these criticisms have been addressed by these modern approaches.

Music, like language, is considered a human universal. However, like language, individuals learn particular genres of music based on their cultural exposure. Recent behavioral and neuroimaging research on music cognition has shown that individuals can more easily process and remember music that is culturally familiar to them than music that is culturally novel. The goal of this research is to investigate whether individual differences in the ability to learn novel musical structures (or music aptitude) relates to individual differences in the ability to learn new languages, or language aptitude. Our study includes 5 minute eyes-closed resting-state electroencephalography (EEG), language aptitude tests (LLAMA D&F) of phonological awareness (tests participants’ memory of a series of words in a foreign language) and grammatical inferencing (ability to extract underlying rules), and a music learning test in which participants learn a form of foreign music. We predict that phonological awareness will positively correlate with overall memory for foreign music, as it relates to the ability to remember sequences of sounds. In contrast, we predict that grammatical inferencing will positively correlate with the extent to which individuals learn to distinguish between different types of foreign music through statistical learning. This study provides evidence of the connection of individual differences in foreign music comprehension to individual differences in second language acquisition at both a behavioral and neurological level.

Many smartphone users engage in compulsive and habitual phone checking which they find frustrating, yet our understanding of how this phenomenon is experienced is limited. We conducted a semi-structured interview, a think-aloud phone use demonstration, and a sketching exercise with 39 smart phone users (ages 14–64) to probe their experiences with compulsive phone checking. Their insights revealed a small taxonomy of common triggers that lead up to instances of compulsive phone use and a second set that end compulsive phone use sessions. Though participants expressed frustration with their lack of self-control, they also reported that the activities they engage in during these sessions can be meaningful, which they defined as transcending the current instance of use. Participants said they periodically refect on their compulsive use and delete apps that drive compulsive checking without providing sufficient meaning. We use these findings to create a descriptive model of the cycle of compulsive checking, and we call on designers to craft experiences that meet users’ definition of meaningfulness rather than creating lock-out mechanisms to help them police their own use.

Communication on online platforms has become one of the primary methods by which people communicate with one another. Regardless of conversation space, either online or offline, arguments can arise. Through our research, we are studying the ways in which the design of a platform influences the tenor of a conversation and the factors that lead to fights and reconciliation. We conducted in-depth in-person and phone interviews with 23 adults to understand how arguments arise online, how they end in different circumstances, and received input for possible design ideas. We followed up with the interviewees to gather demographic information about them. Through affinity diagramming, we qualitatively analyzed the 23 interview transcripts to uncover recurring themes, such as the role of time, the stages of an argument, the way people move arguments from public to private spaces, and differences between images and text in sparking arguments. Based on these themes and design suggestions from participants, we made sketches for potential design ideas that can be implemented in social media platforms to encourage constructive discourse. We are planning to use the design sketches to create prototypes to test with participants for iteration, which we will describe in a research paper to share our findings and design ideas broadly.

Gravity remains one of the biggest mysteries in physics. Since Einstein’s Theory of Relativity not many new discoveries have happened. There are several big questions remaining about it such as: Why is it so much weaker than the other forces of nature? Is it mediated by a particle like the other forces? Is there a unifying theory between gravity and quantum mechanics? Does gravity have a place in the standard model? There are many theories proposed today which attempt to answer these questions, such as the presence of extra dimensions in string theory. If the effects of these theories exist, they would be present at small length scales (less than 1 mm). In order to test these theories, our lab uses a torsion balance experiment at sub-millimeter lengths. Our torsion balance experiment consists of an attractor mass on a turn table, and a detector mass hanging from a thin wire. Each has wedges cut out of it in the same pattern. The test is run by operating the turntable and measures the gravitational torque experienced by the detector mass. My project is to use a code that simulates the gravitational torque in order to investigate its dependence on different orientations and geometrical aspects of the experiment, as well as to improve on future runs of the experiment. This experiment will shed light on previously unknown aspects of Gravity and hopefully provide new discoveries to the field of gravitational physics.

The basal ganglia, evolutionarily old subcortical brain structures, are not commonly considered to be part of the 'language network' despite mounting evidence of their involvement. The current experiment explores two existing hypothesised roles for the basal ganglia in language, based on their known neurocomputations. These hypotheses characterize basal ganglia function as "control" - (prioritization of competing, stable-valued responses), or as "anticipitory" - (ongoing semantical organization based upon syntactic rules). The current experiment aims to adjudicate between these hypotheses by investigating the role of the basal ganglia using an individual differences approach. We utilize two neuroimaging paradigms targeting these hypotheses via lexical-semantic selection under uncertainty and sentence comprehension under varying syntactic complexities, completed by the same subjects. By correlating the neural responses to these tasks with individual differences in vocabulary and working memory capacity, we will explore the predictions made by two hypotheses. Specifically, if the basal ganglia nuclei are involved in controlling compteting linguistic responses, we expect to see greater levels of activation in the left caudate head when subjects are prompted with ambiguous lexical-semantic word choices, as well as 'spillover' activation in the right caudate nucleus negatively correlated with vocabulary percentile and accuracy; if the basal ganglia nuclei are involved in anticipating meaning via syntactic cues, we anticipate higher levels of activation in the left caudate with more syntactically complex sentences in lower-working-memory-capacity readers.

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.

Gastric dilatation volvulus (GDV) is a life-threatening condition that occurs in large breed dogs. Previous research investigating three candidate genes of major histocompatibility complex (MHC), DLA88, DRB1 and the innate immunity gene, TLR5 found diagnostic markers that could be used to identify Great Danes at risk for GDV. The Endoplasmic Reticulum Aminopeptidase 1 gene (ERAP1), is now known to be an important up-stream component of the antigen-presentation system of the MHC, and human polymorphisms in this gene have been linked to the same inflammatory disorders. I hypothesize that Great Danes with certain ERAP1 single nucleotide polymorphism (SNP) variants on exons 3,7,12,13,16 associate with the risk for GDV in Great Danes. We conduct the experiment on two groups of Great Danes; eighty dogs are recruited for this study. Half comprise a GDV group consisting of dogs that have undergone emergency surgery for GDV, and a second age-matched gender-matched control group is dogs with no history of gastric problems. We perform polymerase chain reaction (PCR) and sequencing on subjects from both groups in the variable regions of the ERAP1, evaluating alleles from the gene for association with GDV while controlling for dog family, ages, and diet intake. The goal of this work is to establish a list of specific “risk”or “protective" alleles of ERAP1 that are associated with GDV in Great Danes. If the dominant genotype that predisposes dogs to GDV can be determined, this canine GDV model marker will provide a means to detect at-risk animals, especially in Great Danes. Early genetic testing, probiotic, drug-based approaches and gastropexy (a surgery to prevent GDV) could reduce the incidence of GDV.

The endothelial to mesenchymal transition (EndMT) has been identified as a key part of organ development as well as many disease pathways. EndMT is characterized by endothelial cells, which make up the inner lining of blood and lymphatic vessels and are adhesive and non-migratory, gaining mesenchymal markers and invasive, migratory behaviors. This overall change in phenotype is normal in embryonic development where EndMT is linked to development of organs but has also been linked to numerous diseases in adults including cerebral malformations, Alport nephropathy, fibrosis, heart disease, and bronchopulmonary dysplasia. Whereas it appears that EndMT does not discriminate by organ, it does by sex. The diseases mentioned previously have a significantly higher incidence in males. To understand the role that sex plays on the EndMT pathway, human neonatal pulmonary cells with a gestational age of 18 to 19 weeks from three female and three male donors were routinely cultured and monitored for changes in phenotype. Using angiogenesis sprouting assays, western blot protein analysis and immunostaining, we collected quantifiable data on the reversibility of the EndMT process in each donor. We found that cells from male donors had lower plasticity, characterized as shifting between the two phenotypes, and generally existed in an endothelial state until pushed into a mesenchymal phenotype through a stressor. Female cells were more likely to shift between phenotypes regardless of conditions and exhibited more angiogenic potential, suggesting a heightened ability to transition between phenotypic states. Future experiments include placing cells in environments with differing stressors to mechanistically determine what drives EndMT processes and monitoring cells with time-lapse imaging to quantify the dynamics of the transition.

There has been significant concern regarding the global effects of climate change, especially on plant communities, which are influenced by individual plant species responses. Warming temperatures are having large repercussions for plant biodiversity, with rapidly changing environmental conditions causing shifts in species ranges and phenology. To better understand the implications of this phenomenon on plants, many studies have investigated responses of individual species to climate change. One approach that has grown in recent decades is the use of functional leaf traits, which are indicators of plant performance and reproductive capacity. Specific leaf area (SLA), the ratio of fresh leaf area to dry leaf mass, is one such trait that is attributed to plant growth and photosynthetic capacity, and found to be correlated with climate. We assessed the relationship between climate and SLA for Vaccinium ovalifoilum, a shrub that is prevalent in the montane ecosystems of Mt. Rainier. To accomplish this, we gathered SLA using samples from the Burke Museum’s herbarium collection whose distribution will be delineated across three elevational bands. Altitude was used as a proxy for climate due to variable environmental conditions found across elevation—namely temperature and precipitation—and the collection location of specimens allowed us to obtain temperature and snow accumulation data. With this information, we compared the variation between the three established elevational bands in which the specimens fell under. We hypothesized that as elevation increases, SLA will decrease, attributing this trend to a limited growing window to support high photosynthetic capacity as a result of later snowmelt and lower temperatures. Our results offered insight to understand how climate change may potentially affect plant functionality and guide future research to analyze how changes in individual species may influence community coexistence in the upcoming years.

A hatchery’s purpose is to supplement falling populations of wild fish, mitigating human impact. However, the effect operating a stream-based hatchery has on the immediate stream environment is not well understood. Varied hatchery designs make it difficult to find a consistent way of assessing an establishment. This project used the idea that consistency is key to evaluate the impact hatcheries made by examining water of the the influent and effluent flow. Water was sampled from where it entered, transitioned, and exited three different fish-bearing hatcheries. Hatcheries were classified into three general water-system types, gravity-fed, spring-fed, and flow-through. Water status was evaluated by measuring electric current, dissolved oxygen, pH, temperature, and bacterial content. In addition to unique location characteristics, containment mitigation measures and extenuating circumstances were considered when evaluating the data. The results showed the trend of influent to effluent water in all three hatcheries increased in temperature while the levels of dissolved oxygen, electric current, and pH decreased. Similar result trends were also found between alike water-system types, although with the small sample results are inconclusive. This study is not meant to be a stand alone. With the inclusion of more locations the data will begin to form an averaged scale which could be referenced for the effectiveness of certain hatchery designs and contaminant mitigation techniques. Having this data-set would eventually serve as a resource for future hatchery construction projects.

Water temperature is one of the largest factors of hatchery efficiency, and this can vary greatly depending on the source of the water. Warming waterways is thought to be a problem with salmonid hatcheries in the Pacific Northwest. For this study, we compared the effects of water source (Lake Aberdeen vs VanWinckle Creek) as well as temperatures on the mortality rates of Oncorhynchus mykiss. Water temperature data was collected from 2015, 2016, 2017, and 2018 to compare the effects of temperatures and water source on the mortality rates of O. mykiss. Microscopy was also used in an attempt to find and identify Tetracapsuloides bryosalmonae, the parasite known to cause Proliferative Kidney Disease in salmonid fishes. This parasite is believed to be a major contributor to high summer mortality rates. We collected multiple morbid and recently deceased juvenile O. mykiss, and examined these samples using a hematoxylin and eosin staining of the kidneys and gills. Initial findings suggest no significant impact of lake versus river water for this specific disease, however gram staining and biochemical assays indicated a presence of a bacterial fish pathogen: Flavobacterium columnare. Because of this, future directions include broadening the scope to a greater variety of infectious diseases. If factors influencing development of PKD can be identified, preventative actions can be taken to lessen the mortality rates and allow for a larger amount of fish to be successfully raised each year.

Many plant species are known to undergo masting, where individuals within a species all produce a large amount of seed in a single year, with a sharp drop off in reproduction in the following years. Masting may be beneficial to plants by suppressing seed predator populations in low seed production years, allowing for seeds to escape predation in high seed production years. Masting is likely associated with climate, although this is poorly understood. In this study, I will use herbarium specimens to tackle questions related to masting in five plant species: Tsuga heterophylla, Pseudotsuga menziesii, Thuja plicata, Rubus spectabilis, and Rubus parviflorus. Specifically, I will note the number of cones, seeds or berries on herbarium specimens, as well as specimen size and the year it was collected. I will use these data to 1) examine patterns of masting in focal species as compared to field data from Mount Rainier. I hypothesize that herbarium specimens will show a similar pattern of masting as field data, with trees showing stronger patterns than shrubs. Next, I will use these data to 2) compare masting patterns to annual climate. I hypothesize that warm temperatures lead to masting the following year, and that masting has increased in frequency. Finally, I will 3) assess the relationship between masting and bird species that eat seeds and berries (e.g. grouse, jays), to determine whether masting influences population dynamics of higher trophic levels. I will do so by comparing masting patterns with bird count data from the Audobon Society. I hypothesize that population sizes of birds that rely on seeds and berries will be greater in mast years. This study provides additional information for how we might expect entire ecosystems to be affected by climate change, including resource distribution and population health.

Reactive oxygen species (ROS) such as the superoxide anion (O₂-) and hydrogen peroxide (H₂O₂) are produced by enzymes such as NADPH oxidases (NOX), which have been identified in most cell types and tissues. Additionally, ROS is identified as a second messenger which regulates the activity of G-protein-coupled receptors. For example, ROS decreases the sensitivity of the kappa-opioid receptor (KOR), a signaling pathway in the brain involved in drug addiction. Thus, a fluorescent ROS sensor protein would allow us to monitor KOR signaling in animal models of drug addiction. However, the best performing ROS sensor called HyperRed is not suitable for in vivo studies due to the weak amplitude of fluorescent signal output. Therefore, the overall goal of the project is to increase the magnitude of fluorescent change of HyperRed, ease the detection of low H₂O₂ concentration, and decrease the time of fluorescent response after the addition of H₂O₂. First, using the structure-based engineering approach with the help of Dr Berndt, I construct a library of thousands of semi-randomized HyperRed variants, where mutations are only introduced to the amino-acid linkers between the main domains. Then I test the fluorescent output of all the variants in the library at high throughput utilizing a novel protein engineering platform. This approach allows me to rapidly identify the best performing ROS sensors and optimize their signal amplitude in several rounds of repeated mutagenesis mimicking an accelerated evolutionary process. The expected result is to detect one variant with the signal amplitude having at least a 100% change of fluorescence over baseline values which has been determined to be the minimum for applications in animal models. The improved sensor enables direct measurements of ROS signaling during drug-seeking behaviors and could potentially facilitate the development of novel therapeutic approaches.

DNA polymerase (Pol) proofreading and mismatch repair (MMR) cooperatively guard against DNA replication errors and cancer. Defects in these activities produce “mutator” phenotypes characterized by elevated levels of base-substitutions and frameshifts. Haploid yeast with combined defects in these activities rapidly go extinct, in a process termed error-induced extinction (EEX). Organisms adapt by duplicating their genome without dividing (polyploidization) or by lowering their mutation rate via antimutator mutations. In evolution experiments with haploid mutators that display a synthetic-sick phenotype due to Pol ε proofreading and MMR defects we found that polyploids routinely beat out antimutator mutants. To investigate whether polyploids arise during the evolution of mutator diploid strains, we propagated diploids defective in Pol δ proofreading and base-base MMR, which have a mutation rate an order of magnitude below the diploid error threshold. Our mathematical modeling predicts that EEX mutants will overtake mutator cultures by 250 generations. We found only a single tetraploid in 89 independent cultures evolved for 300 generations. We then measured mutation rates of isolates from cultures that remained diploid and repeatedly found antimutator phenotypes. Whole genome sequencing of independent isolates from each culture revealed a single dominant antimutator clone that caused significant changes in mutation spectra. Thus, spontaneous antimutator alleles and polyploidization rescues haploid and diploid cells from EEX with markedly different efficiencies. Differences in the relative frequency of each escape mechanism may reflect the nature of the mutator alleles, the starting ploidy of the cells, or the magnitude of the initial mutation rate. Our findings in diploids suggest that mutator cancer cells near the edge of error-induced extinction may similarly be under selection for spontaneous antimutator mutations and polyploidization. 

In countries with developing economies, economic activity and progress are often considered only in numeric terms such as wages, Gross Domestic Product (GDP) or utilization of credit. Proponents of economic empowerment as a vehicle for economic development emphasize the social and educational aspects of development such as financial education, gender equality and agency. I investigate how existing research defines “economic empowerment,” in the context of economic development, and observe various programmatic approaches to economic empowerment in Kenya. For this project specifically, I focus on how one organization, The Hope Foundation for African Women (HFAW), fosters economic empowerment through financial education and financial services. In addition to advocating for gender equality, HFAW provides finance and literacy trainings primarily for women using the “Popular Education” model and “Social Change Communication.” The organization provides programming in five counties located in Southwestern Kenya. The goal of this project is to highlight existing financial education methods used by HFAW to empower communities and individuals, and to prompt discussion regarding vehicles of economic empowerment. This paper highlights effective teaching methods within the organization and illuminates areas where further research might help improve outcomes for HFAW participants. Based on areas of need identified by HFAW staff in interviews, and informed by my background research, materials will be provided to support the organization’s financial education programming. Funding is made possible by the Ottenberg-Winans Fellowship. This project will foreground further research that can identify and improve upon effective future economic empowerment programming.

Transient receptor potential vanilloid-1 (TRPV1) ion channels are polymodal signal integrators of noxious stimuli including heat, vanilloids such as capsaicin, peptide toxins, acid, and inflammatory mediators. It is unknown whether activation of TRPV1 by different stimuli is achieved through the same structural mechanism or if different stimuli activate the channel through different structural mechanisms. Clinical trials using TRPV1 antagonists resulted in patients exhibiting hyperthermia, suggesting that TRPV1 plays a role in maintaining body temperature, and highlighting the need to ensure that therapeutics targeting the channel do not disrupt thermal homeostasis. Hence, knowledge of different structural mechanisms for channel activation would aid in the design of therapeutic agents targeting TRPV1. To address this, we have expressed a series of functional single-cysteine rat TRPV1 channels for spectroscopic analysis, with techniques such as electron paramagnetic resonance, double electron-electron resonance, and Förster resonance energy transfer spectroscopy. By probing several structural regions within TRPV1 we can determine which regions of the channels move during activation and whether those are the same for different noxious stimuli.

Blood transfusion is a cornerstone of modern medicine, with a transfusion performed every 2 seconds in the United States. It is critical to accurately determine both patient and donor blood type prior to transfusion, as mixing non-complementary blood types can trigger life threatening reactions. While the ABO antigen system was first described over a century ago by Nobel Laureate Karl Landsteiner, to this day safe transfusion remains burdened by the nuance of blood type. Many of the current blood typing tests over simplify classification and often disregard ABO subgroups, despite widespread recognition of their significance. Moreover, our understanding of the ABO blood types (A, B, AB, and O) is still incomplete, as the full structure and microheterogeneity of these ubiquitous blood group antigens is not yet fully described. This project characterizes the biochemistry of ABO blood types through an interdisciplinary collaboration between UW Bioengineering, Medicinal Chemistry, and Bloodworks Northwest (the regional blood center). Our study employs exhaustive isolation of red blood cell (RBC) membranes from genotyped donors for comprehensive biochemical and biophysical analysis. The RBC membranes are treated with cocktails of enzymes - namely PNGase F, EGCase and Neuraminidase - to cleave glycan structures at specific locations. Reactivity to different antibodies and lectins provides insight into the structure of the glycan antigen. Results have shown that the clinical anti-A antibody binds disproportionally to N-linked associated antigens. These findings inform ongoing mass spectrometric and biosensing work to further elaborate ABO structure and bioactivity, with implications for transfusion and transplant medicine.

Bloodborne pathogens are wide spread and can pose risks to health care workers and vulnerable patient populations alike. Conventional diagnostic tests for bloodborne pathogens are costly and time intensive, so fast, affordable, and sensitive diagnostic methods are needed that can be performed under low-resource conditions by untrained personnel. Microfluidic self-digitization technology, developed in the Chiu Laboratory, provides the foundation for such low-cost diagnostics. As undergraduates, we work on the fabrication and optimization of cheap, robust devices used to load samples, as well as dPCR of samples required to detect diseases. As part of a larger research endeavor, we are developing a portable instrument that, in combination with our proprietary microfluidic chip technology, will expand rapid diagnostics to low-resource settings around the world. Expanding diagnostics for bloodborne pathogens will both help prevention as well as monitoring treatment of patients already infected.

Globally, poor and underserved countries tend to have an elevated incidence of infectious disease, often contributing to increased mortality rates. One health issue resulting from this is diarrhea, the 6th leading cause of mortality in developing countries.  Because pregnant women are already vulnerable to infections due to an immune system that is rapidly adapting to a developing fetus, they may be more susceptible to diarrhea and the complications that come with it.  We sought to identify whether diarrhea during pregnancy was associated with adverse birth outcomes, such as preterm birth and being small for gestational age. We used data from a prospective longitudinal study of maternal influenza immunization of pregnant women and their infants conducted in rural Nepal from 2011-2014. Diarrhea episodes were defined as three or more watery bowel movements per day for one or more days. The chi-square test, two-sample t-test, and log-binomial regression were performed to evaluate baseline characteristics and the association between diarrhea during pregnancy and adverse birth outcomes. From our study, we found that average weight and BMI at enrollment for women with diarrhea was significantly lower than those without diarrhea during pregnancy (47.6kg vs. 48.5kg, p=0.01, 20.72 BMI vs 21.06 BMI, p=0.01) and women with diarrhea during pregnancy were significantly more likely to have small for gestational age infants (42.6% vs. 36.8%, p=0.03). We also found that the incidence of non-live birth, preterm, and low birth weight did not significantly differ between mothers with and without diarrhea. By understanding the risks diarrhea during pregnancy poses for both mothers and infants, we can assess the severity of this problem, and whether or not a possible means of prevention should be prioritized. Further research should examine whether methods to improve weight and BMI during pregnancy prevents diarrheal illness and thus negative birth outcomes. 

Legal theorists have long maintained that courts operate beyond their primary function of dispute-resolution and have problematized their characterization as “objective” bodies, noting their significance as powerful social and political actors bestowed with constitutive powers of meaning-making. Virtually absent in this scholarship is an analytical angle examining this constitutive power using theory or methods from performance studies. This is surprising, as courtrooms are highly theatrical spaces. My research seeks to fill this gap in scholarship by marrying theories and methods from sociolegal studies and theatre- and performance studies to examine how courts contribute to the construction of cultural meanings pertaining to identity. This essay treats the European Court of Human Rights (Court), the judicial organ of the Council of Europe and one of the most active, powerful international human rights courts in the world. How does the Court construct notions of identity – especially around nationality, European community, gender identity, and religion? More specifically, my project asks: How are these courtroom constructions conceived and legitimized through narrative performance, and how is their sociopolitical influence shaped by the mechanics of performativity? To answer these questions, I conduct an original research project analyzing both written judgments and video recordings of oral hearings held in the Court’s Grand Chamber. I form my own criteria to analyze these hearings as performances, and create a scheme to evaluate written judgments for their performativity. I also analyze certain structural characteristics of the Court, and some legacies of its case law, as symbolic and embodied performances, examining how identity narratives are reproduced by the Court’s composition as an institution and its behavior over time. In addition to demonstrating what can be gained by critically assessing courts holistically using performance theory and methodology, I hope to illuminate exciting intersections between sociolegal studies and theatre- and performance studies with this work.

An often conceptually difficult topic learned in early engineering courses is known as the angle of twist. The angle of twist is necessary for two reasons: to analyze reactions along a shaft where traditional equilibrium equations do not suffice, and in designing a shaft when twisting is restricted. In this project, the purpose is to design and build a device that will be an aid in classroom demonstrations of the concept and applications of the angle of twist. The prototype of this device is designed to test foam shafts of a certain length and with a constant applied torque. The device will need to support, hold, and twist foam shafts while providing precise measurements of the applied torque and the resulting angle of twist. Two markers will be put in place before twisting. The shaft will be fixed at one end, where one marker will be in place, and twisted at the opposite end where the mobile marker will be used to determine the angle between the two. It must be durable to withstand regular classroom handling and have an appropriate interface for students of varying levels of proficiency in the topic. Its design must also be inexpensive and replicable so that it can be built and used within a low classroom budget. Students will be able to calculate, measure, and observe the applications of polar moment of inertia, angle of twist, and torque using the measurements from the apparatus. From the measurements, the shear modulus of the shaft material will be experimentally determined, allowing for an active learning experience of this key concept.An often conceptually difficult topic learned in early engineering courses is known as the angle of twist. The angle of twist is necessary for two reasons: to analyze reactions along a shaft where traditional equilibrium equations do not suffice, and in designing a shaft when twisting is restricted. In this project, the purpose is to design and build a device that will be an aid in classroom demonstrations of the concept and applications of the angle of twist. The prototype of this device is designed to test foam shafts of a certain length and with a constant applied torque. The device will need to support, hold, and twist foam shafts while providing precise measurements of the applied torque and the resulting angle of twist. Two markers will be put in place before twisting. The shaft will be fixed at one end, where one marker will be in place, and twisted at the opposite end where the mobile marker will be used to determine the angle between the two. It must be durable to withstand regular classroom handling and have an appropriate interface to be used by students of varying levels of proficiency in the topic. Its design must also be inexpensive and replicable so that it can be built and used within a low classroom budget. Students will be able to calculate, measure, and observe the applications of polar moment of inertia, angle of twist, and torque using the measurements from the apparatus. From the measurements, the shear modulus of the shaft material will be experimentally determined, allowing for an active learning experience of this key concept.

Glycans are ubiquitous in biology and play a crucial role in cell to cell signaling, immunity, and disease. The A, B, and O blood groups are differentiated by different glycan structures and linkage patterns presented on either glycoproteins or glycolipids. To date, the exact glycan structures that differentiate blood types remain unknown. A clear understanding of these structures would increase the success of transfusion procedures and reduce the risk of complications. Our lab is currently examining glycans from glycoproteins isolated from red blood cell membranes, however we do not have the enzymes needed to remove glycans from glycolipids. ECGase I is an enzyme that was recently shown to effectively cleave glycans from a wide range of glycolipids. We have cloned the gene for ECGase I into a GST fusion vector for recombinant bacterial expression. With this we have been able to generate high yields of purified ECGase I. The EGCase I produced was more active than commercially available product. The ability to grow EGCase I enables large scale investigation of glycolipids involved in the ABO blood group system.

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.

The US/Mexico border is a politically polarized and militarized place where each year millions of people cross, both with and without authorization. As a militarized border that divides two nations, the border region is prone to violence for at least two reasons: the presence of armed state officials on both sides of the border, and the presence of drug trafficking. National treaties such as the North American Free Trade Act (NAFTA), soon to be replaced by the United States–Mexico–Canada Agreement (USMCA), impact industries in Mexico. NAFTA removes trade tariffs, creating investment opportunities for the United States in their border countries (Canada and Mexico). These industries employ high numbers of womxn in their facilities. Notably, there is a history of high rates of murders and disappearances of womxn in border towns such as Tijuana, Ciudad Juárez, Mexicali, El Paso, etc. Many of these murders, disappearances, and other acts of violence are ignored or denied by local and state officials. My research explores the violence that is enacted through the actions and inactions of state and local officials. I will conduct an analysis of declassified documents, released by the United States and as well as related research publication. My research contributes to a larger conversation about how accountability can be upheld for the victims of violence who have been dismissed by state officials and the media. I also hope to contribute to a larger conversation about how to prevent such violence. Keeping a research focus on these questions also mitigates against the further violence of forgetting about the victims and their families.

The cooling process for aluminum cast molded parts impacts the material properties and quality of the final product.  Understanding what microstructure and properties produced by a given mold is critical for the mass production and design of consumer and industrial parts.  This research analyzes the cooling of a pure aluminum cast molded part under variable corner geometry, in order to predict properties of the finished aluminum product.  This project goal was to create a flexible, three dimensional model of the cooling process for an aluminum cast part, using finite volume analysis. The model takes into account both static and dynamic material states and properties.  The model's goal was to be robust and flexible enough to be utilized for a wide range of material properties, as well as various corner geometries, including chamfer, fillet and a 90˚ corner.  In order to verify the accuracy of the model, and assess microstructural effects, the cast geomtry has been tested with a real mold and aluminum.  Temperature readings for the mold are taken in order to assess the models accuracy.  We predicted that the fillet geometry will cool the slowest of the three geometries, with the chamfer being second and the 90˚ corner being the fastest. With this in mind we predicted that the fillet will have the the greatest cooling continuity, with the chamfer being second and the 90˚ corner being last.

Ankle range of motion (ROM) is frequently measured in clinical settings for the purpose of diagnosing and treating foot and ankle pathologies. Gastrocnemius equinus (GE), a condition in which isolated gastrocnemius contracture inhibits ankle ROM, contributing to foot pain in otherwise neurologically healthy individuals. Controversy surrounds the definition of GE, however, and the reliability of goniometer-based measurements of dorsiflexion—and consequently identification of gastrocnemius contracture—is untested. This study examines the reliability of using a goniometer to measure ankle dorsiflexion. Two observers (KR and CG) measured ankle dorsiflexion in 14 neurologically healthy individuals (6M/8F; ages 20-56 years; 6 participants measured by both observers) with the knee in fully-extended and flexed positions. Three measurements were taken for each position with the goniometer fulcrum on the lateral malleolus; stationary and moving arms aligned with the fibular head and fifth metatarsal, respectively. Inter- and intra-observer reliability was assessed using Cronbach’s alpha. Intra-observer Cronbach’s alpha was 0.230 (CG) and 0.533 (KR) for dorsiflexion with the knee extended, and 0.805 (CG) and -0.350 (KR) for dorsiflexion with the knee flexed. Inter-observer Cronbach’s alpha was 0.656 for extension and -0.245 for flexion. Little correlation exists within or between observers for goniometer-based ankle dorsiflexion measurements in either a flexed-knee or extended-knee position. The clinically-accepted practice of using a goniometer to determine ankle ROM, and consequently to diagnose and treat GE, may be unreliable and needs further evaluation.

Rehabilitation research has demonstrated the benefits of early powered mobility intervention for children with disabilities, from improving developmental skills to empowering children to better participate in family and community life. However, traditional powered mobility devices are often stigmatizing, costly, and require specialized transportation due to their size and weight. One alternative early powered mobility option that has sought to address several of these concerns, The Go Baby Go Mobility and Socialization Project, provides children with disabilities a means of socially welcoming, early independent mobility experiences through custom safety and accessibility modifications to commercially available toy ride-on cars. The Go Baby Go project has resulted in promising pilot research along with community-based outreach and education in collaboration with families, clinicians, and engineers. However, a means to efficiently track car performance in real-world environments without the presence of a researcher has been lacking. Therefore, the purpose of our project was to develop a customized data logger and companion Arduino code with the ability to collect real-time data from the cars as families use them in their homes and communities. Our multidisciplinary team has created and implemented a system which gathers car performance data automatically via integrated sensors, including the number and duration of switch activations, frequency and duration of use, outdoor location, distance traveled, and driving terrain. Housed in a simple, waterproof food storage container, the data logger is integrated into the car’s electronics and powered by the car battery, with data stored on a micro-SD card. Preliminary analysis of results from eight cars in local communities is ongoing and will be shared; initial feasibility of our system for real-world tracking without undue research presence or caregiver reporting burden is promising. Future research goals include full quantitative analysis of car use patterns to improve technology design and implementation in community settings.

Pollution from human influences is a growing problem in the Chehalis River and tributaries causing deleterious effects on stream health. Stream microbiomes are composed of diverse collection of microbes that play an important role in keeping the surrounding riparian zones and life within the streams healthy and thriving. Stream water has been facing a decline in quality from the leading cause of pollution from agriculture and manufacturer run-offs. Although there have been many studies relating to run-off pollution affecting streams, there are few in-depth studies done on the taxonomy and functionality of microbes in urban water ecosystems, so it is important for this to be further investigated. With the use of 16s rRNA sequencing, each sample site presents two years of data included to indicate differences both by season (Fall, Summer) and sample site. At the phylum level, every season consists of a primary microbial signature shared amongst the sites. These phyla are Proteobacteria, Bacteroidetes, Actinobacteria, Firmicutes, Verrucomicrobia, and Tenericutes. From the family data, common to nearly all sites are the Flavobacteriaceae, Comamonadaceae, and Oxalobacteraceae. Families prevalent at many sites in various combinations include Flexibacteraceae, Crenotrichaceae, Chitinophagaceae, and Verrucobacteraceae. This project presents a two-year microbiome analysis of Alder and Fry Creek to develop trends for the seasonal variation in urban water ecosystems due to human impacts.

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.

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.

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.

The physics behind wave-driven mixing of river and ocean waters and current-driven wave breaking are not well understood. The current body of work surrounding river-ocean interactions focuses on large rivers. However, small rivers, which are much more strongly influenced by waves, make up the majority of such systems, and contribute significantly to global riverine discharge. Examining the momentum balance of river flow in opposition to wave-driven forcing from the ocean is necessary to understand how waves influence the travel and mixing of river water. One way to measure this interaction is using instrumental drifting buoys that follow the path of the river water and take temporal measurements of water properties. These leave gaps in our knowledge, as such buoys do not provide a description of the entire system, only specific points. To fill in these gaps, Unmanned Aerial Vehicle (UAV) footage was used to understand broader wave-current interactions at the Quinault River mouth, a small river that feeds directly into the Pacific Ocean. The town of Taholah, WA, is on its banks, and faces challenges due to wave-driven flooding. The size of the surf zone, the nearshore region where waves break at high frequency, was mapped with UAV footage, and related back to local environmental conditions, such as tidal phase. At low water, the momentum from the river is maximized, and so is the cross-shore extent of the surf zone. This decreases salinity around the river mouth, as freshwater is trapped by the surf zone. At high tide, these conditions are reversed, and fresh water streams can be detected past the surf zone, suggesting the river water has escaped from this region of high turbulence. The conditions under which these escapes occur are to be understood by combining analyses of UAV footage with drifter and tidal data.

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. 

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.

Synthetic CRISPR–Cas transcription factors enable the construction of complex gene expression programs, and chemically–inducible systems allow for precise, rheostatic-like control over the transcriptional dynamics. We have constructed a bio-orthogonal, chemically–inducible synthetic CRISPR regulatory system to activate and repress gene expression in yeast. By fusing chemically inducible transcriptional regulators to specific RNA binding proteins, we have expanded the tunability of this system of constructs. The RNA binding proteins are fused to half of one chemically-inducible system while the other half is fused to an effector. Upon addition of drug, the two halves come together to form the complete chemically-inducible system and either activate or repress the target gene. We use reporter gene assays to probe the dose-dependence, time-dependence, and reversibility of the systems. The use of multiple, orthogonal chemically-inducible systems and unique guide RNAs allows for more sophisticated, multi-gene programs that still maintain precise control of gene expression dynamics independently at different sites.

During embryonic development, a dormancy-like state known as diapause arises during the transition from pre to post implantation. This state of suspended development is a reproductive strategy which favors newborn survival in mammals during nutritional deprivation or stress. Studies from the Ruohola-Baker lab found potential candidate regulators of diapause by establishing an in-vitro diapause model using pluripotent mouse embryonic stem cells (mESC). One of the genes is Activating Transcription Factor 5 (ATF5) which encodes a protein capable of survival-mediated functions such as maintaining mitochondrial activity during stress, modulating cell differentiation, preventing apoptosis and regulating cancer pathway. ATF5 has been known to transcriptionally target mTOR, a mechanistic target of rapamycin. Energy stress in the form of starvation and pharmacological inhibition of mTOR has shown to induce diapause-like state in mESCs in vitro. Our hypothesis is that upregulation of ATF5 under energy stress will reestablish diapause-like state in naïve mouse embryonic stem cells in vitro. We will test our hypothesis by loss-of-function and overexpression experiments. We test if ATF5 gene knockout using CRISPR-Cas9 prevents the mutant lines from entering diapause-like state from energy stress. Using western blots, we will quantify phospho-mTOR levels and its downstream targets in the ATF5 KO lines and compare them with the wildtype lines. For the overexpression of ATF5, we will make rescue lines for the ATF5 KO cells. We predict that overexpressed ATF5 in rescue lines will enter diapause-like state, and have reduced mTOR and its downstream target signals compared to KO lines. Our discoveries of ATF5 function in diapause can be useful in understanding how early-staged cancer stem cells enter a diapause-like state or quiescent state which enables them to escape chemotherapy detection. We can potentially contribute to the development of therapies to target ATF5 mechanism so that these undetected cancer stem cells can be detected.

New techniques in genome mapping have revealed a high degree of 3D spatial organization in the nucleus. Long-range loops connect enhancers to their gene targets to regulate expression. In order to assess the mechanisms and functions behind 3D spatial organization of the nucleus we need a system that allows us to engineer DNA loops. We use programmable CRISPR-Cas DNA binding domains to target specific sites in the genome. The CRISPR-Cas complex is tethered to a targeting domain (TD) that can dimerize with another TD at a distant DNA locus. To promote interactions between TDs that are bound to DNA, we have designed an allosteric switch that assembles the TD only when the CRISPR-Cas complex has engaged its DNA target. To validate that our switch proteins can act as a DNA sensor we have developed a simple reporter assay; upon successful switch protein activation on DNA a transcription factor is recruited to drive expression of a fluorescent protein. Our results indicate that the protein switches activate when they are recruited to DNA, effectively acting as a sensor for DNA binding. Future steps include optimizing our reporter assay design and modifying the design for DNA looping.

Since 1982, with the introduction of insulin as the first recombinant protein therapeutic, peptide and protein drugs have grown to encompass 10% of the pharmaceutical market and are the fastest expanding class of drugs. Advantages of using peptides over small-molecule drugs include high potency, selectivity, and capability to be engineered for a diverse range of targets, most commonly to disrupt or facilitate key protein-protein interactions (PPIs) in the human body for a therapeutic effect. To search for strong binders for a therapeutic target, combinatorial peptide libraries of up to billions of different sequences are synthesized and screened against promising targets. Due to the enormous library size, screening for high affinity binders often requires multiple rounds of enrichment in order to isolate the most potent molecules, a laborious and potentially bottlenecking step in developing protein drugs. Current approaches that have strategies for enrichment, such as phage display and yeast surface display, are limited to screening a library of binders against one target instead of multiple targets (library-on-library). This proposal describes the development of a peptide binder screen utilizing a simple workflow of repeated mating and sporulation of genetically engineered S. cerevisiae, or baker’s yeast. This technology improves the throughput of established screening methods through a library-on-library format that efficiently isolates high-affinity peptide binding interactions.

Precise spatiotemporal control over biochemical cue presentation is necessary to mimic the complex, heterogenous environments found in biological systems. Achieving this level of control within engineered microenvironments would allow for the manipulation of cell growth and differentiation, which could be utilized in tissue engineering and drug delivery. To this end, we developed a method that utilizes fusion proteins made from a novel PhotoCleavable protein linker (PhoCl) and a protein of interest (POI). This method allows for spatiotemporal control of POI release from hydrogels in response to cytocompatible violet light (λ = 405). This system is flexible, as PhoCl can be conjugated to many different POIs, including fluorescent proteins, enzymes, and growth factors, and was found to not affect protein function. Additionally, PhoCl undergoes a green-to-red transition after photocleavage, allowing for real-time tracking and quantification of POI release. As PhoCl cleaves in response to visible light, which is less damaging to cell function and has a greater tissue penetration depth than the traditionally used UV light, PhoCl fusion proteins hold promise for use in vivo. To demonstrate the feasibility of this system, PhoCl fusion proteins were formed with several fluorescent proteins (e.g., mRuby, sfGFP, mCerulean). Conjugating these fusion proteins into gels and exposing them to patterned light produced spatiotemporal localized release of proteins with micron scale resolution, which was demonstrated through fluorescent imaging of the photopatterned gels. To support the potential in vivo applications of this system, PhoCl was also used in mammalian cell studies with epidermal growth factor (EGF). These studies showed the expected increased cell growth in response to photomediated EGF release. This illustrates the potential versatility of the PhoCl system in biological applications, thus supporting the relevance of this novel system to tissue engineering and drug delivery methods.

While there is an abundance of computational tools for protein design, the vast majority of them focus on static structures. Data for the most probable rotamers of an amino acid are often obtained from mining its appearances across crystal structures, which do not take into account the native dynamics or conditions of a protein. Additionally, conformational secondary structure propensities are often derived from the frequency that an amino acid appears within a certain range of dihedral backbone angles in static structures. However, these data do not emulate realistic conditions, because proteins are dynamic and surrounded by solvent; thus, incorporation of dynamic data should improve the design process. Wrangler, our in-house software for peptide design, integrates dynamic data for both rotamers and secondary structure propensities. The data are obtained from molecular dynamics (MD) simulations in explicit water, taking into account interactions with surrounding solvent to better sample the most probable conformations. Several amyloid peptide aggregation inhibitors were designed using Wrangler’s scoring metrics to validate the software. These inhibitors were shown via MD simulations to better retain secondary structure than our current standards. Future work involves synthesizing the peptides in the wet lab to determine whether they experimentally perform better than our current inhibitors.

Amyloid diseases are characterized by the aggregation and buildup of proteins in vital tissues and organs. Insoluble β-sheet amyloid fibrils were previously thought to be the major underlying cause of tissue degeneration and cell death. However, recent experimental evidence suggests that soluble oligomers, which form during protein aggregation and before polymerization into fibrils, are the principal cause of toxicity in mammalian cells. These toxic oligomeric protein assemblies are believed to share a common sequence-independent secondary protein backbone structure known as α-sheet. This project proposes the investigation of a synthetic peptide known as AP3 that is capable of forming toxic oligomers and β-sheet amyloid fibrils. This peptide was de novo designed with a completely randomized sequence which preserves the underlying chirality that produces α-sheet character leading to its exhibition of amyloidogenic properties under acidic conditions. Furthermore, AP3 aggregation was shown to be inhibited by three naturally occuring amyloid proteins implicated in their respective dieseases: Amyloid Beta (Alzheimer’s), IAPP (Type II Diabetes), and Transthyretin (Cardiac Amyloidosis). Analysis using dot-blot assays, soluble oligomer binding assays (SOBA), and BLITz assays will provide additional insight into the behavioral, binding, and kinetic properties of AP3. Upon further evaluation, we aim to demonstrate the ability of AP3 to serve as a synthetic model for naturally occuring amyloids and provide a better understanding of amyloidogenesis as well as the interactions between amyloidogenic species. This research will prove useful in the creation of more effective amyloid inhibitors and treatments for amyloid diseases.

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.

High rates of forest conversion and fragmentation have placed many endemic species in the rainforests of Sri Lanka under threat. Ceratophora is an endemic and endangered/critically endangered genus of lizards containing five species, and C. aspera has the widest distribution spanning four forest regions, making it an ideal candidate species for broader conservation management projects. The goal of this project is to study the phylogeography of C. aspera across its range in the forests of southwest Sri Lanka to assess the genetic variability of the remaining populations across two lowland areas, the submontane zone (Sabaragamuwa Hills), and the montane forest zone (Central Hills). Analyses of genetic data are important for understanding the relationships between geography and genetics and to determine where populations are connected and fragmented. During the 2018 and 2019 field seasons, tail clippings were collected from wild lizards. In the University of Washington's Biology Department, DNA sequencing of mitochondrial DNA (ND4 gene) was used to measure genetic diversity within and among populations, and to estimate phylogenetic relationships. Genetic diversity is highest (6%) between the population from Hiyare (lowlands) and the Sabaragamuwa Hills (submontane zone). There is also strong evidence for highland and lowland groups. Populations from Hiyare, Sinharaja and Gilimale show no intra-population variation. Sri Lanka has pledged to reforest 200,000 ha of degraded forest to create forest landscapes under the Bonn Challenge, and to increase forest cover to 30% unde the Paris Climate Agreement. Phylogeographic profiles of endemic species, such as C. aspera, are critical for forest restoration strategies as they identify priority areas for reforestation and inform connectivity strategies based on the need to maintain metapopulation structure and genetic diversity. 

Genetic diversity and gene flow are important to long-term viability in wild populations. In migratory species, gene flow (i.e. dispersal between disparate populations) is inherently influenced by the spatial and temporal components of their migrations. Recent findings have revealed the importance of fine-scale population structure in both space and time in Sockeye Salmon (O. nerka). However, the fitness consequences of this fine-scale structure are unclear. Here we evaluate the biological relevance of fine-scale spatial and temporal homing by examining their effects on a quantitative trait, individual lifetime reproductive success. Salmonids are well-known for their extensive journey from the freshwater stream where they hatch, to the ocean, and back to their home stream (i.e. ‘homing’). Homing behavior is associated with individual fitness; individuals are locally adapted to their natal streams, and dispersers between non-natal streams can have reduced reproductive success. Population structure within individual streams is generally assumed to be random (panmictic). However, individuals may be locally adapted on a finer scale than previously known, both in space (homing within their natal stream) and return timing. Fine-scale spatial and temporal homing may play a role in individual fitness; therefore, it is important to investigate this relationship. We used zero-inflated negative binomial models and a multi-generation pedigree, reconstructed from two populations of Alaskan Sockeye Salmon, to estimate the impact of homing on individual reproductive success (number of offspring per fish). Our results suggest that fine-scale dispersal in both space and time may reduce lifetime fitness. These results have broad implications for fisheries management and habitat conservation: recognizing the connection between reproductive success and return timing could inform within-season fisheries management, helping maintain the genetic diversity associated with local adaptation; likewise, recognizing the connection between individual salmon success and their habitat may promote maintaining natural heterogeneity in salmon streams.

Acoustic signals are essential for communication, advertisement, and reproduction in a variety of organisms. However, their successful transmission is limited by the environment in which they are produced. My research investigates the acoustic adaptation hypothesis, which proposes that to maximize transmission efficiency, animals evolve vocalizations with characteristics that minimize degradation and attenuation (loss of volume) in their native habitat. This hypothesis predicts that birds of open habitats will exhibit vocalizations with higher frequencies and larger frequency ranges than birds of forest understory habitats, because fewer obstructions and more low-frequency ambient noise in open areas favor successful transmission of higher-frequency signals. I tested this prediction by recording and analyzing the vocalizations of 63 bird species living in open and forested habitats around Monteverde, Costa Rica. I found that on average, bird species of open habitats vocalized at significantly higher and broader ranges of frequencies than birds of forested habitats, suggesting that vocalization transmission efficiency helps shape avian communities and their response to habitat transformations.

Cleaning is a mutually beneficial relationship, where the cleaner removes and consumes ectoparasites from its clients. Among fishes, the cleaning behavior has evolved several times as a juvenile or facultative feeding strategy, and is often lost in adults. However, a minority of taxa clean almost exclusively across their ontogeny (obligate cleaners). The largest radiation of obligate cleaners are the Caribbean neon gobies (Elacatinus), that evolved with several congeneric non-cleaners, and in parallel with a closely related lineage of facultative cleaners (Tigrigobius). We suspect that obligate cleaning is a specialized trophic ecology tied to an equally specialized feeding morphology that facilitates improved cleaning performance. We coupled micro-CT scanning with the clearing and staining of museum specimens to compare several functional predictors of feeding performance between cleaner gobies and non-cleaners in a phylogenetic context. We also used geometric morphometrics to compare relative changes in head shape and mouth orientation. Obligate cleaning evolved once, and is characterized by a specialized scraping dentition, stouter cranial features, and a more subterminal mouth position relative to non-cleaners. Meanwhile, facultative cleaning evolved at least 2-3 times, and while some species display similar tooth morphologies as the obligate cleaners, they share more in common with non-cleaners. Obligate cleaners also exhibit fewer sexual dimorphic differences, suggesting that the demand for an efficient cleaning morphology trumps sexual selection.

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.

My guiding question is, “how we can I use storytelling to empower the stories and experiences of the black community in the Central Area that has been displaced through gentrification?” Redlining has historically made it harder for people of color to obtain a mortgage or buy a property in certain neighborhoods, and it continues to exist as gentrification. As tech companies like Microsoft, Amazon, and Airbnb among others continue to expand their presence in the greater Seattle area, rent prices have risen and property owners have started building expensive apartments and living complexes for the influx of workers with a high income. This expansion has displaced people of color who have historically lived in the Central Area. Currently there are stories of resilience in communities that have been displaced by gentrification, but they are often not showcased in the public eye and media outlets. I want to focus on the use of radical storytelling as an act of defiance against erasure, and the role of tech companies in the greater Seattle area in displacing communities. Inspired by the interactive digital stories like “Trump Wants a Border Wall. See What’s In Place Already” in the New York Times or “Microsoft By the Numbers” on Microsoft Story Labs, I hope to create a visual digital story about the ways and means of gentrification, and I hope this story can be used to educate the public about the mechanisms of gentrification and where communities move. By conducting interviews with activists and community members in the Central Area and highlighting their perspective through direct quotes and testimonials, I hope to educate everyone about the strength of communities in the Central Area. My goal is to create a project that focuses on empowering people of color and their stories through community activation.

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.

This presentation explores an array of literature, theater, and cinema in order to understand the evolution of transgender expression in Spain. Throughout the modern history of Spain, from before the Franco regime until present day, there is an observable change in the language used to discuss transgender identity and the way gender expression is represented in Spanish media. This presentation examines the various ways media displays the performance of gender and seeks to understand how transgender identity reflects aspects of history or societal events and human experience as a whole. Through exploring several stories and learning about the experiences of characters as well as the directors and authors behind the characters, we can better understand the truly fluid nature of gender expression and performance. From Pedro Almodóvar’s La mala educación and La piel que habito, to Federico García Lorca’s El público, to the Ventura Pons documentary Ocaña, Retrato Intermitente, with support from gender theory and historical context, one can trace the full panorama of transgender identity in Spain. This presentation will discuss the lives and art of drag queens, forced gender reassignment surgery, the celebration of gender fluidity, and more. Through these unique stories we gain a deeper understanding of the various ways individuals can perform gender and how authors and directors utilize these identities to help audiences more deeply understand transgender identity and more broadly, human experience.

Scholarship on American Buddhism has, from its beginnings, struggled with defining “who” and “what” makes an American Buddhist. American Buddhism has thus been split off into two branches: one “ethnic,” which is defined as being practiced by Buddhist immigrants and their descendants, the other “convert,” which makes up Americans of all races and ethnicities who decide to convert to Buddhism. However, temples like the Tacoma Buddhist Temple, a Jodo Shinshu temple located in downtown Tacoma, is one of these many communities with varied membership that falls outside of the two-branch model and is thus why scholars have disputed the model for its inability to fully describe American Buddhists. The dualism of these the two terms create a divide within the American Buddhist community and also racializes the two categories since the term “ethnic Buddhist” is highly associated with the Asian community. As a result, the two terms fail to recognize many of those who fall outside the model, such as non-Asian Buddhists whose parents were convert Buddhists themselves and Asian Buddhists who grew up in a non-Buddhist household and chose to convert to Buddhism later on in their lives. The terms also have a tendency to polarize communities, making it seem as if “ethnic” communities and “convert” communities and thus “ethnic” and “convert” Buddhists have little interaction. The Tacoma Buddhist temple, however, is a community of not only “ethnic” and “convert” Buddhists practicing Buddhism side by side, but also those who the model fails to recognize. Therefore, through the research gathered at the Tacoma Buddhist Temple, it becomes evident that the two-branch model fails to capture the diversity of American Buddhism.

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.

 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.

With the adoption of the 2030 Agenda for Sustainable Development, United Nations Member States committed to ensure international development that “leaves no one behind,” and pledged to reach “the furthest behind first.” Recognizing that globally persons with disabilities as a group are often among those left furthest behind, the Executive Office of the UN Secretary General and the Special Rapporteur on the Rights of Persons with Disabilities are reviewing how UN operations can better integrate and promote the rights of persons with disabilities. To support that review, a study was commissioned to assess the current state of disability inclusion within UN operations at the headquarters and country levels. In December 2018, a research team led by the School for Global Inclusion and Social Development at the University of Massachusetts and supported by undergraduate students at the University of Washington completed a baseline assessment of disability inclusion within the 40 UN agencies, funds and programs which are members of the UN Sustainable Development Group, and 40 UN Country Teams. Although the assessment is not currently public, this presentation discusses the results of our research which focused primarily on evaluating UN entity disability inclusion through public sources alongside staff survey responses.

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.

Small insect-inspired robots have much potential in exploration and have been experiencing a wave of innovation in recent years. Small robots have promise especially in space exploration where each kilogram costs $10,000 to launch, but tiny robots tend to weigh under a gram. However, some problems persist, such as difficulty with landing after flight and hopping mechanisms wearing down after a few uses. Our work focuses on developing a hopping robot that is capable of attaching to an overhanging surface when it jumps and that has durable mechanisms to optimize the number of jumps per bot. The hooking mechanism differs from previous work, usually electrostatic patches, and instead is inspired by the hooked feet of beetles, which is lighter and does not require constant electrical power. For optimizing jumps, we are working to develop a jumping body constructed from and designed for carbon fiber rather than the previously used fiberglass. Carbon fiber has a higher strength to weight ratio and is more elastic than fiberglass, making it efficient for flight and the repetitive motion carried out by the body when bent by the onboard actuator. All designs are created using an iterative design process where parts are micromachined and assembled, then tested for desired qualities. From this, we are aiming to develop an autonomous hopper capable of completing multiple jumps and grabbing without maintenance on any part of the bot.

After the establishment of a new democratic government following the US invasion in 2001, the Taliban has provided a parallel court system across Afghanistan. Rebel forms of justice may appear highly coercive, but prove particularly appealing to civilians if they are quicker, more straightforward, easier to access, or more in line with their preferences than formal state courts. Under what conditions are citizens more likely to support the legal authority of the formal government’s judicial systems compared to rebel groups’ alternative forms of law? In this research, I expand the framework of competitive governance by focusing on the decision of individuals to support various legal institutions based on views of government legitimacy founded in the evaluation of public service provision. I hypothesize that as individuals view the government as more legitimate, they demonstrate support for the formal courts, and as they view the government as illegitimate, they are less likely to support the formal judicial system. I address this question by analyzing two data sources. First, I have identified active Taliban courts by district from 2011-13. Second, I have access to the ANQAR survey data, an extensive nationwide survey addressing perceptions of government legitimacy and rule of law. Preliminary findings suggest a zero-sum dynamic between the institutions - that successful rebel governance may not only increase compliance with the rebels, but may actually decrease civilian compliance with state institutions. The policy implications of this research are twofold. First, this informs formal governments that building a judicial system is not just a function of strength and access, but rather that civilians are assessing the government’s service capacity as a whole. Secondly, understanding civilian behavior and preferences will assist nascent democracies in determining how it is most efficient to spend their limited resources to increase the support of the civilians.

Mapping is a powerful tool to visualize space and data. However, working with historical data and maps is problematic as spaces change across time. Given this, the scope of this research is to create visual maps using GIS software that accurately represents the Baghdad-Basrah region of the Ottoman Empire in the late nineteenth century. Our key research question is: how can cholera data from primary sources in the nineteenth century be visualized through mapping? We gathered the data for this research from the diaries of Joseph Svoboda, a resident of the region who traveled frequently up and down the river system and recorded information about numbers of deaths and quarantines from cholera in the cities he passed. The method we used for mapping the data includes a comprehensive reading of the diaries currently being transcribed to assess which information is important for mapping purposes, including the location and time period of the event in question. We mapped the data using Geographic Information Systems (GIS), a software that is used to analyze and represent data through maps, to geocode locations and include cities and other features as they appeared in the nineteenth century. Anticipated results include an interactive choropleth and dot maps that are accurate to the specific time period and show deaths from cholera in specific locations over time. One key implication for further work would be a standardized way to map disease data from primary sources and to increase the number of individuals who use data visualization with historical data. Additionally, our mapped data can be used for other types of GIS analysis that may be of interest to those studying the history of cholera or historic epidemics.

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.

With more than a million arrivals in Europe in 2015, the mass migration has impacted the continent politically, economically, and socially. According to Europol, a law enforcement agency, in 2016 more than 90% of migrants going to the European Union have experienced some kind of smuggling during their journey. Many articles aggregate human smuggling with human trafficking. However, there is a lack of empirical examination and of different types of smuggling. In this study, I focus on migrant smuggling. Nevertheless, human smuggling is often seen as a crime that is organized, where a new “service” gets added to their principle activity (drug smuggling, money laundering…), as stated by Finckenauer, and performed by people who have never been involved in transnational criminal organizations. I assess this puzzle: How does human smuggling differ from human trafficking and organized crime, by examining primary and secondary sources such as scholarly literature and local newspapers? I argue that human smuggling has some traits of organized crime; however, considering entirely as it, limits the study of smuggling, as a business activity, and limits the prevention of illegal immigration. Human smuggling has traits of organized crime: the structure, the persistence, and violence have shown that these elements are not voluntarily present in the activity of smuggling. Nonetheless, the main purpose of this activity is treated as a business: where demand and supply meet and where price fluctuates depending on these factors. Migrant smuggling needs to be seen as a mutually consenting act between a migrant and a smuggler: the migrant is looking to flee because of instability in his/her country for the hope of a better life while the smuggler is considering smuggling as a business. This project aims to give a nuanced understanding of human smuggling to better intervene at the source of this mass migration.

At the UW tandem particle accelerator located at the Center for Nuclear Physics and Astrophysics (CENPA), a program is searching for new physics though precision measurements of electron spectra from radioactive decays. The most sensitive searches require very pure Neon-19, which has a halflife of about 17 seconds. Accordingly, we have designed and constructed a system that produces Neon-19. We first bombarded Sulphur Hexafluoride (SF₆) with protons from the accelerator. We then metered the SF₆ and Neon-19 mix out into a cryogenic trap where it freezes only the SF₆. After the trap, we transported the remaining Neon-19 with a turbomolecular pump into the detector. Once the trap had filled with solid SF₆, it was valved off from the target, then heated, at which time the frozen SF₆ sublimated into to a storage tank before refilling the target. By using a pair of traps, the experiment can be run continuously; one trap thaws while the other freezes. Through models based on nuclear cross-section data from previous experiments, the system will produce on the order of 10¹⁰ Neon-19 nuclei per second. Our system will contribute to an effort to better describe the interactions of particles and refine the Standard Model of particle physics.

Isotropic scattering in various spatial dimensions is considered for arbitrary finite-range potentials using non-relativistic effective field theory. With periodic boundary conditions, compactifications from a box to a plane and to a wire, and from a plane to a wire, are considered by matching S-matrix elements. General relations among (all) effective-range parameters in the various dimensions are derived through a functional relationship, and the dependence of bound states on changing dimensionality are considered. This research was conducted by matching the effective range parameters in one dimension to the particle scattering within another dimension. This relationship ultimately leads to the immediate functional relationship of the effective range parameters in varying dimensions. Generally, it is found that compactification binds the two-body system, even if the uncompactified system is unbound. For instance, compactification from a box to a plane gives rise to a bound state with binding momentum given by ln(1/2(3 + √5)) in units of the inverse compactification length. This binding momentum is universal in the sense that it does not depend on the two-body interaction in the box. This research will in the future allow for the calculations of practical and important thermodynamic variables such as pressure, energy of Bose gases with varying lengths of a three dimensional box.

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.

Our research group performs one of the highest-precision tests of Einstein’s equivalence principle, perhaps the most fundamental property of gravitation, using a sensitive rotating torsion balance. Among the leading experimental challenges are temporal and spatial temperature variation. Notably, horizontal temperature gradients across the apparatus, if not properly characterized, can emulate an equivalence-principle violating signal. We have implemented thermal shielding and run tests to measure the thermal effects on our measurement. Past tests have shown a need for both absolute and differential temperature sensors with higher sensitivity. Hence, my research project focuses on investigating the effect of temperature gradient on our experiments by constructing a thermal monitoring system. I have designed, laid out, constructed, and tested sensitive bridge thermistor circuits that can function as both absolute and differential temperature sensors. Current tests of our prototypes have shown that temperature sensitivities reaching 10 micro-Kelvin in one second (10^-5K/Hz^0.5). We are scaling-up these sensors and plan to deploy them in this academic year. Successful completion of this project will yield improved understanding of the temperature gradients within our experimental apparatus, allowing us to test the equivalence principle with yet higher precision.

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.

Likelihoodism is the conjunction of the following two statistical principles: (1) the Law of Likelihood (LL) which characterizes when a piece of evidence “favors” one hypothesis over another; and (2) the Likelihood Principle (LP) which characterizes when an agent ought to draw the same inference about how likely two competing hypotheses are, given a piece of evidence. Elliot Sober has argued that some of the greatest scientific achievements of the last two centuries – from Darwin’s arguments for common ancestry to Eddington’s argument that the bending of light during an eclipse favors Einstein’s theory of relativity – are applications of likelihoodism. Many proponents of likelihoodism maintain that it provides an “objective” standard for evidence, and we first provide a precise account of the sense in which LL and LP are objective. We consider a statistical principle more objective if it is acceptable to agents with more diverse beliefs and/or values. We argue that LL and LP meet this type of objectivity by showing that all Bayesian agents endorse LL/LP. However a statistical principle is clearly not objective if it is acceptable only to agents meeting stringent rationality constraints. The typical formulations of LL and LP rely on the probability axioms, but one can show that requiring agents to cohere to these axioms requires agents to be logically omniscient. This unreasonable constraint makes LL/LP unacceptable for any human agent. Our paper resolves these issues by restating likelihoodism in a formal representation of qualitative probability and proving the corresponding theorems in this new context. This work elucidates how likelihoodism is objective and how it plays into a Bayesian framework.

Latent class models are frequently used to classify observations into homogeneous albeit qualitatively different sub-groups. Typically, these models are unrestricted, meaning there is no a priori structure or restrictions on model estimates. This approach is similar to many cluster analysis approaches. The study examines modeling conclusions when an unrestricted model is applied to data generated from a highly restrictive population model through a simulation study. We expect that a researcher will conclude fewer classes than the true number specified in the population. Simulated data for this work is based on a substance use example identified in other research. The population was generated based on six classes, but with a within class error rate fixed to 5%. Preliminary analyses indicate that commonly employed model selection criteria indicate that models with fewer than six classes are preferable. This is important because most analysts using latent class models use unrestricted models with little apparent consideration to what realistic error rates may be. In research domains where smaller error rates may be plausible, restrictive models of the sort used to generate the data for this study may be worth considering.

The goal of clustering is to partition a dataset into subsets (“clusters”) such that observations in the same cluster are similar and dissimilar from observations in other clusters. We think of the clustering problem as a graph problem. The vertices of the graph are the observations. Any two vertices are connected by an edge. The weight of the edge is the dissimilarity between the observations. We can form clusters by progressive graph thresholding. We repeatedly break the longest edge until the graph has two connected components. These two connected components form clusters in the sense described above. We then apply the same procedure recursively until we have obtained the desired number of clusters. We propose a method to efficiently find the connected components and their memberships.

Mathematical knots are non-intersecting closed loops which may be tangled; links are knots that are possibly intertwined. These 3-dimensional paths often resist description, so mathematicians choose nice ways to describe them. One such way is to project them onto a plane. Even more, it is interesting to build knots in discrete ways such as placing them on tiles in a plane. In this poster we are considering hexagonal mosaic knots, knots that are projected on a plane tiled by the honeycomb hexagonal tessellation. In this way, knots can be built from a small collection of hexagonal tiles with loops. We create an interactive tool which presents hexagonal tile types, a grid on which to lay them, and options for analysis. The researcher uses a point-and-click tool to lay down a mosaic grid, and in so doing, creates an underlying data structure representing the segments contained in the mosaic. When requested, the software traverses this data structure like a linked list. In this manner, one may determine if the data structure represents a suitably connected hexagonal mosaic knot or if it contains dead ends or stray segments; that is, determine if a data structure represents a knot/link or not. This process helpfully assigns segments to their respective knots, distinguishing not only ‘over’ and ‘under’ but also ‘self’ and ‘other’. We hope to continue exploring automatic generation of information about knots from their tiled representations. Once more developed, we hope to be able to answer more questions about the knot or link represented by the data structure. We also hope to continue exploring the use of rapid, flexible feedback from prototypes in aiding exploratory research.

The associations between toxic stress, adversity, and mental health are widely documented in public health, medicine, and social science research. Much of this work stems from the findings of the CDC-Kaiser Permanente Adverse Childhood Experiences (ACE) Study from the late 1990s. The results of this study showed that individuals who experienced significant childhood adversities and traumas were at a higher risk for depression and suicide attempts, health risk behaviors, and adult diseases such as cancer and heart disease (Felitti et al., 1998). This research has been invaluable in improving the health of populations who have faced such severe stress, but it is somewhat limited in that it does not acknowledge other aspects of health, such as immune function and frequency of acute illnesses. It also does not take into account adversity that occurs after childhood and adolescence. Recent studies demonstrate that toxic stress and adversity in different stages of the life-span can have negative effects on immune function. This indicates a need for more emphasis on the immune impacts of adversity in future health interventions and research, as well as a need for integration of trauma-informed practice into clinical settings. Although more research is needed to thoroughly establish the causal pathway between adversity and immune dysfunction, the studies discussed in this review demonstrate a strong correlation between these variables, thus providing justification for these interventions.

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.

The formation of dental biofilm (plaque) is promoted through the consumption of dietary sugars, which serves as a precursor to the metabolic process that bacteria must undergo. Organic acids are byproducts of this metabolism, and encourage the demineralization of the enamel which if left untreated leads to formation of dental caries (tooth decay). Evaluation of the acidity of plaque deposits on patient’s teeth can be used as a preventative measure to allow dentists to detect areas vulnerable to dental decay. A ratiometric fluorescence pH sensing device has been developed using an FDA approved dye, Fluorescein, and blue LED excitation. Fluorescent spectral profiles were collected using a spectrometer and analyzed with a spectral unmixing algorithm for calibration over the pH range of 4.5-7, the ideal range to measure the acidic environment of the mouth. A 420 nm LED housed with an electronic driver served as the fluorescein excitation source. Spectral profiles were collected within the 450-650 nm range. In an in vivo pilot study, we found that the dye solution which consists of fluorescein powder and deionized water causes retention issues on interproximal areas. In order to achieve accurate results from the spectrometer, the fluorescein dye must penetrate and diffuse through the dental plaque. To allow enough time for the fluorescein solution to adhere, glycerol was added to increase viscosity. Tests were performed to evaluate the effect of the glycerol addition on the spectral data. Solutions ranging from 0%-50% glycerol were measured. Glycerol addition increases the peak wavelength of the spectra by no more than 1%. The pH of the solution has no effect on this trend. An in vivo case study was performed for high caries risk patients to validate the device. The pH device has the potential to predict early caries, reducing oral restorative procedures and dental expenses.

Approximately 25% of inpatients in a hospital setting receive a catheter during their stay. This statistic corresponds to a diverse group of practitioners inserting catheters which, if done improperly, can lead to urethral trauma and catheter associated urinary tract infections. My undergraduate research at the Center for Research in Education and Simulation Technologies is aiming to address the gap between practitioners in the hospital by developing a high-fidelity urethral catheter simulator, CREST Sim. Modified elastomeric materials were developed to simulate the male genitourinary anatomy and mechanical behaviors. Quantitative studies between the CREST Sim and LifeForm Male Urethral Simulator were conducted using a uniaxial load cell to measure the force of insertion of a lubricated Bardex catheter. In collaboration with the UWMC OR nursing staff, the integration of CREST Sim in the onboarding training of nurses provided feedback in the form of a survey. Similar insertion forces were observed between CREST Sim and LifeForm Male’s simulator. Preliminary results from the survey have reported positive training responses regarding the state of the CREST Sim. Through our collaboration with UW Willed Body, we will characterize the biomechanical properties from genitourinary tissues of deceased males in-situ. This data, along with more robust survey data, will be integrated into the next generation of CREST Sim.

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.

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.

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.

 The United States’ participation in “othering” is nothing new. Government policies for centuries, including executive orders, have long targeted minority populations living in or seeking refuge within the U.S. These populations are often the scapegoats in politically turbulent times and are treated as such in order to not deal with greater issues. During World War II, Japanese Americans—including citizens and legal residents—were sent to internment camps not knowing when they would return home. This was the “solution” to war hysteria post-Pearl Harbor. Similarly, current immigrants from non-European populations are targeted by ICE and taken away from their families with no promise of return. Although the rationale is complex, this rhetoric often revolves around jobs and criminality despite any significant statistical back-up. My presentation seeks to compare these two situations: what is currently happening with Latin American and Southeast Asian immigrants in the U.S. to the incarceration of Japanese Americans during WWII. These families, whether nearly 80 years ago or today, have and are being systematically stripped of their livelihood and humanity for the sake of political scapegoating. Through intensive archival research—including collecting historical photographs, first-person accounts, and government propaganda of and against those incarcerated in the Japanese Internment Camps and current U.S. detention centers—, I examine the similarities in these families’ plights, the situations’ causes, and their inevitable long-term impacts. Through this analysis, I seek to interrogate the broader structure of U.S. immigration policies and our place in these events as global citizens. It is only through such analysis that we can began to understand the cyclical nature of rhetoric and trauma and have a chance to stop it.

The focus of this study is to examine the motivation behind organizing conservative and counter-conservative events and the meaning students attribute to their involvement. Furthermore, the study also addresses the extent to which such coordination is related to group influence. In other words, how do participant relations within and outside of their organization shape their decision to organize political events on campus? This study explores how students understand and interpret their actions. Data for this study will be collected by conducting structured interviews with 10 participants (n = 10). The intended population is college students from a Southern California college campus. Half the participants will identify or have identified with a conservative campus organization while the other half with a counter-conservative organization at the time of a campus political event. Convenience and snowball sampling will be used to recruit participants. This methodology follows what sociologist Max Weber (1914) referred to as,“Sociology is a science concerning itself with the interpretive understanding of social action and thereby with a causal explanation of its course and consequences.” An interpretive understanding of the meaning and drive behind the formation of these political events is crucial to developing an explanation for what triggers social action. By studying the dynamics by which the group members interact and interpret one another, we can understand the role of in-group cohesion and out-group bias in politically-related communication. My study aims to contribute to the following 1) increase our knowledge of the motivations and meanings college students place on organizing events with controversial speakers, as well as protesting them, 2) how students weigh the consequences of their actions, especially as it relates to social relations (stigma or approval), campus climate, safety and property damage, and economic costs (e.g. security, police, taxes).

Climate change is divisive among Americans. Among scientists, there is virtually a consensus affirming climate change; the political scene, however, has been polarized, and polarization appears only to be growing. Though different segments of the population may understand the issue at varying levels of detail, the majority of these understandings must stand consistently for America to take decisive action on the matter, whatever action that may be. To address polarization, this research frames the issue as a national conflict in two parts: 1) a relational problem among America's constituencies, which sets the stage for 2) problems of communicating climate change information, which is difficult given gaps and complexity of information, amidst misinformation. Together, these two components explain the standstill of climate change initiatives. This research sets outs to address the question: “to what extent have opposing climate change views become polarized and dialogue been disabled, and how do internal and/or external narratives influence individual perspectives?” Possible research methods include: a quantitative analysis measuring political polarization, and qualitative close readings of two texts, each representative of the polarized constituents. Predicted results: 1) America has become increasingly polarized, so much so that it significantly interferes with academia, policy, and daily life, and 2) Narratives among Americans, on all sides of the conflict, are complex combinations generated by individuals, the media, and the forces that shape the media itself. Far from ordinary, these conflict-conditioned narratives perpetuate and escalate conflict, while also further disabling intergroup communication. The implications of this research entail how the current political impasse can be overcome, which thereby enables climate change initiatives to proceed uninhibited.

The ability of an organism to dissociate environmental cues for either safe or threatening situations is key for survival. Generalized fear is an adaptation in which behavioral responses for threatening stimuli are produced to non-threatening cues. In mice, discriminative or generalized fear responses are modeled using a fear conditioning paradigm of two shock intensities, 0.3 mA or 0.5 mA. Mice trained at 0.3 mA intensities could discriminate between safe and threatening cues, yet mice trained at a 0.5 mA intensities displayed generalized fear behavioral responses. Previously, we had identified that dopaminergic neural activity was critical for the ability to discriminate between cues when shocked at 0.3 mA. Dopamine neurons express Kv7.3 potassium channel subunits, which modulate neural activity. I hypothesized that Kv7.3 subunits on dopamine neurons would be critical to threat discrimination and mice that had undergone mutagenesis of Kv7.3 would show generalized fear discrimination. My approach used transgenic mice expressing Cre-recombinase and viral-mediated gene delivery of cre-inducible CRISPR-Cas9 plasmids targeted for the specific mutagenesis of Kv7.3. Mice underwent a three day paradigm known as fear conditioning. Baseline freezing behavior was assessed by playing two tones, A and B. This was followed by fear conditioning trials where at the end of tone A, mice received a shock of either 0.3 mA or 0.5 mA (CS+) and at the end of tone B, mice received no shock (CS-). On the third day, mice underwent a probe trial to assess final ability to discriminate between threatening and non-threatening cues. These findings could provide insights into the mechanisms underlying neurological disorders and serve as a guide for future pharmacological interventions.

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.

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.

Stem cells are known for their ability to self-renew and differentiate into specialized cells. A key factor that drives self-renewal and differentiation is the specific localization of cell-fate determinants inside the cell cytoplasm. In this work, we focused on a protein called Numb, commonly known to inhibit the Notch signaling pathway responsible for the regulation cell-fate. We sought to understand the correlation between cell spreading, morphology and Numb localization. We studied human adipose-derived stem cells (HADSCs) in two conditions: 1) Cells fully spread after 24 hours and 2) Cells that were actively spreading or retracting. In each condition we analyzed the distribution of Numb fluorescence expression inside the cell cytoplasm. We found that in cells that were allowed to fully spread, Numb was highly localized only on cells with pseudopodia (“arm-like” cytoplasmic protrusions). Numb was evenly distributed when cells were fully spread, had a large area and circular morphology. In the second condition, cells that were actively spreading or retracting were small and circular in morphology. Interestingly, these cells had a high fluorescence expression of Numb specifically localized at the cell edges. These results seem to indicate that Numb localization was found in areas of membrane activity, such as pseudopodia and spreading/retracting cells. This could be due to the fact that Numb has been found to participate in integrin turn-over (cell adhesion). Based on these results our next step will be to modify membrane activity and cell adhesion and observe the effects on Numb localization and stem cell differentiation. Regulating stem cell fate via protein localization will allow us to enhance the production of differentiated cells for regenerative medicine applications.

Herpes simplex virus (HSV) infects mucosal epithelial cells and can cause recurrent, painful ulcers. HSV is not curable and establishes lifelong latency in host neuronal ganglia. Herpes affects more than 400 million people globally, with an increased risk of genital ulcer disease, HIV acquisition, and transmission of HSV-2 to partners or neonates. Persons with altered T cell immunity have been reported to have prolonged and more frequent lesions, suggesting that the adaptive immune responses are associated with HSV clearance. Additionally, there is evidence of innate cell and T lymphocyte recruitment to the infection site to help clear the lesion. While there is extensive evidence on the role of T cells in these lesion infiltrates, little is known about B cell activation and antibody response during HSV reactivation. The study of B cells and antibodies can be used in developing a HSV vaccine since all licensed vaccines induce robust antibody responses. Antibodies block virus entry and mediate antibody-dependent cell-mediated cytotoxicity (ADCC). That is why a better understanding of local antibody responses against HSV-2 is needed to develop a successful vaccine. My project examines whether HSV antibody-producing B cells are found in areas where HSV-2 reactivates and the potential role that these antibody-producing cells play in host clearance of the virus. To examine this question, ddPCR using B-cell-specific probes were used to identify different B-cell subtypes responding to the HSV infection. Results to date have shown high variability with few emergent patterns. In the future, additional samples will be examined using new protocols for better cDNA synthesis, and more positive and negative controls to increase the accuracy of the data.

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.

Long non-coding (lnc)RNAs have multiple biological functions, including recruitment of kinases to regulate signaling pathways involved in tumorigenesis and other human diseases. Of particular interest is the proposed interaction between Long Intergenic Noncoding RNA for Kinase Activation (LINK-A) and the membrane component phosphatidylinositol-3,4,5-triphosphate (PIP₃). The proposed interaction between PIP₃-LINK-A would be the first example of a direct interaction between a non-coding RNA and phospholipid. I investigated the proposed interaction between LINK-A and PIP₃ using Nuclear Magnetic Resonance (NMR) spectroscopy. Multiple NMR-based experiments were performed to assess the degree of binding on the basis of line-width broadening of NMR spectra. Wild-type and mutated RNA constructs were titrated into a 100 uM solution of PIP₃, but the NMR data showed no evidence of line-width broadening, indicating that no direct interaction occurs between wild-type or mutated RNA constructs. Presumably, the reported cellular interaction is not direct and might require an additional mediating factor. I determined the 3D structure of the LINK-A RNA hairpin, required to recruit PIP₃, using biophysical molecular modeling and NMR data. My results provide a biophysical foundation to elucidate the functional role of LINK-A in PIP₃ recruitment and kinase activation.

A person’s age is one of the greatest risk factors for many age-related diseases, such as Alzheimer’s disease, heart disease, and cancer. Developing interventions that target this common risk factor may allow us to slow down the progression of all age-associated diseases. One promising target for aging research is the mTOR (mechanistic Target of Rapamycin) signaling pathway, which is a master regulator of cell growth that allows the cell to fine tune its response to various environmental conditions. Inhibition of mTOR pathway has been shown to extend lifespan in yeasts, worms, fruit flies, and mice. In addition of being a target in aging research, the mTOR pathway is also a well-known effective target in some human cancers to prevent cancerous cells from dividing uncontrollably. We have previously developed a yeast-based system to identify mTOR inhibitors by comparing the growth of yeast strains that are differentially sensitive to mTOR inhibitors; a wild type strain, a tor1Δ mutant, and an fpr1Δ mutant. However, the system is not able to identify a few known ATP competitive inhibitors that have been shown to inhibit mTOR in human cells. This could be due to dissimilarities between yeast and human mTOR protein kinase domains. To address this issue, we are developing a humanized strain of yeast that should allow for identification of additional mTOR inhibitors that are effective in human cells. I am developing a novel hybrid gene containing the human mTOR kinase domain fused with the N-terminus of the yeast TOR2 gene. This new humanized strain will be utilized in our yeast-based assay with the goal of first detecting mTOR inhibitors known to be effective in human cells but unable to inhibit yeast mTOR. Successful completion of this goal will facilitate high-throughput screening of novel compounds that may have mTOR inhibitory and cancer fighting effects.

Modern cells discriminate among the amino acids chosen to be included in protein synthesis: some, like leucine, serine, glycine, and alanine appear in most proteins across most cells, whereas other amino acids, like (g)-aminobutyric acid and aminoisobutyric acid do not appear. This raises the question of how selectivity among amino acids arose – does the selectivity rely on modern protein machinery or could it have arisen in the first protocells of the Early Earth? For example, could certain amino acids have, by some mechanism, associated more strongly with protocell membranes, increasing their chances of being integrated into the first peptide chains? To test this hypothesis, our group assembles rudimentary protocells from molecules that would have been present on the early-Earth: decanoic acid (a fatty acid), sodium mono-phosphate, salt, and water. Vesicles of the decanoic acid spontaneously form. We then add different amino acids to the solutions and measure their turbidity to determine whether each amino acid causes the number of lamellae in the vesicles to increase or decrease. Increased lamellarity correlates with a sturdier vesicle. If certain amino acids increase lamellarity of protocells, that could serve as a method of selection for certain amino acids rather than others. Our results are that particular amino acids (most notably serine, glycine, and alanine) do in fact increase the lamellarity of fatty acid vesicles significantly, whereas other, less common, amino acids do not. We are currently exploring the plausibility of a mechanism for this occurrence involving ease of rotation around the alpha carbon of the amino acids, and we are investigating other ways in which interactions between amino acids and fatty acid membranes might be manifested, for example by a shift in the solution’s critical vesicle concentration. Our results will fit into the overarching goal of understanding peptide formation and protocell stability in order to gain insight into the origins of life on Earth.

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.

Membrane trafficking in the eukaryotic cell is a highly controlled and significant process that is related to various inherited disorders and cancers. Among numerous regulatory proteins, Uso1 protein – an essential, long, coiled-coil protein – plays a key role in the tethering process, capturing and pulling the vesicle toward the target membrane. Despite many years of work, the tethering mechanism has not been fully understood. Although several tethering models have been proposed, none of them were tested with Uso1 protein. Hence, to test these models, we engineered a mechanically deficient version of Uso1 protein, which lacks the critical tethering region for functioning. After the protein characterization, in cell survival tests and in test tube tests in chemically defined fusion system have been performed. The failure of the trafficking event, which would support our hypothesis, along with other functional test data, would provide a promising demonstration for the tethering mechanism of the long coiled-coil tether and the role of Uso1 protein.

Due to antibacterial resistance and the high recurrence of urinary tract infections (UTIs), studies have shifted to focus on anti-adhesive therapies as alternative to antibiotics. Often treated with antibiotics, UTIs are caused by uropathogenic Escherichia coli (UPEC). The bacterial adhesin, FimH, found on the terminal end of fimbria, hair like structures expressed on the perimeter of UPEC, is the main etiological factor of UTI prevalence and recurrence. FimH increases the virulence factor of E. coli by mediating the initial binding of the bacteria to glycosylated cells in the urinary tract. FimH has two domains. The lectin domain (LD) recognizes and binds the terminal mannose on glycosylated cells lining the urinary tract, whereas the pilin domain acts as an anchor to the fimbria. Previous studies have shown that α-methyl-mannose (αMM) competitively inhibits glycoproteins, such as horseradish peroxidase (HRP), from the FimH active site. We hypothesize that αMM can non-competitively inhibit HRP through a novel mechanism of inhibition. To determine the mechanism of inhibition of HRP in the presence of αMM, we are using Enzyme Linked Immunosorbent Assays to measure the dissociation of HRP in the presence and absence of αMM, after the FimH-HRP complex has formed. We expect to see an increase in the dissociation of HRP in the presence of αMM. HRP in this case, will act as a model to the glycosylated cells lining the urinary tract. This study aims to assist in the design of innovative anti-adhesive therapies that inhibit binding of FimH once bound to glycosylated cells lining the urinary tract.

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.

Trigger-action platforms enable end-users to program their smart homes using simple conditional rules of the form: if condition then action. Although these rules are easy to program, subtleties in their interpretation can cause users to make errors that have consequences ranging from incorrect and undesired functionality to security and privacy violations. Based on prior work, we enumerate a set of nine error classes that users can make, and we empirically study the relationship between these classes and the interface design of eight commercially available trigger-action platforms. Particularly, we examine whether each interface prevents (e.g., via good design) or allows each class of error. Based on this analysis, we develop a framework to classify errors and extract insights that lay a foundation for the design of future trigger-action programming interfaces where certain classes of errors can be mitigated by technical means or by alerting the user to the possibility of an error. For instance, we identify that an analysis of a dataset of functionally-similar trigger-action rules could be used to predict whether certain types of error patterns are about to occur. We believe that this work is a first step towards trigger-action interface designs that significantly mitigate user error.

In computer graphics, a voxel (volume element) is a point in a 3D world coordinate system (i.e. the coordinate system of a virtual world). In games like Toca Blocks or Minecraft, voxels are used to store the texture of a particular terrain. Sometimes, voxels next to each other have the same texture. When voxels of homogeneous textures form polygons, rendering systems will optimize memory storage by storing the polygons' vertices rather than every single voxel in the polygon. The process of choosing polygons that cover the voxels is known as meshing. We refer to these polygons as quads and the collection of quads as a mesh. Current methods for polygon meshing require too much data storage or require a drastic change in the mesh after a small change in the world coordinate system. We propose the Greedy Face Meshing (GFM) Algorithm, a linear time algorithm for meshing voxels into quads. We prove that our algorithm is within a constant factor of the optimal solution (in terms of number of quads) and can update in constant time for a single-voxel change in the world coordinate system. We also show how the GFM Algorithm can be implemented using the Segment Tree data structure. Rendering systems can use the GFM algorithm to mesh polygons since its storage is no worse than any existing algorithm and its updates take constant time.

Within the domains of graphic and video game design, there is often need for tools to quickly develop convincingly realistic models of plants. A common tool applied to this problem is L-systems, a kind of rewriting system that can be used to define rules for iteratively transforming plant models to increasingly fine detail. However, the connection between L-systems and the graphics they generate can sometimes be unintuitive. To enable more intuitive development of plant models, we propose a method for generating models of branching structures from simple specifications of a few given iterations of the model. Our approach involves encoding plant models as bracketed L-systems and applying SMT (Satisfiability Modulo Theory) solvers to solve a form of the inverse L-system problem. Iterations of growth in the form of simple vector graphics are compiled to formal constraints for an L-system that can indefinitely generate further growth iterations. The satisfactory system is then found using an SMT solver. This technique allows for branching structures to be conveniently developed by providing meaningful specifications.

Black womxn in the United States have a long-standing history of creating community-based support networks and utilizing strategies of resilience to thrive in an oppressive society. Black feminist scholars have formulated useful frameworks such as “transformative work” and “intersectionality” to help contextualize long-standing practices of resistance, resilience, and transformation. As a medical anthropology student, the aim of my project is to understand how Black womxn in Seattle make sense of and advocate for the health, well-being, and safety of their communities. In order to answer this question, I collaborated with a diverse network of Black womxn who are initiating conversations about health and social justice in their churches, workplaces, and advocacy groups. Mount Zion Baptist Church, a predominantly African American church in Seattle, functioned as a community center for a network of Black womxn actively working to advance health equity. To learn about the ways that Black womxn in Seattle express, communicate, and act on their personal and political views regarding health, I engaged in participant observation at health-centered church events, advocacy meetings, marches, and health equity committee gatherings. Furthermore, I conducted structured and unstructured interviews to understand how Black womxn in Seattle perceive societal conditions and rely on support networks to radically better their lives. Through the experience of listening to Black womxn’s life history narratives, I learned about the vital role that solidarity, collaboration, and faith have in creating positive social change. My ethnographic research process has enlightened me to the importance of listening to and learning from the lived experiences of Black womxn who consistently work to transform their own health and the health of their communities.

Millions of people across the United States struggle with disordered eating. For the proportion of those who have been clinically diagnosed with “eating disorders”, many will continue to fall in and out of the grasps of their illness - even after the privilege of receiving comprehensive treatment and therapeutics. The issue of “chronic relapse” amongst individuals who have attended inpatient, partial hospitalization, and/or intensive outpatient care for disordered eating necessitates a thorough questioning of “treatment”, “illness”, and “recovery”. Despite so many years under the “medical gaze” of research in medicine and psychology, as well as in sociology and feminist scholarship, little has been done to make space for the voices of those affected. Therefore, the intent of this project is to strip away hegemonic discourses on disordered eating, and radically listen to those who have traditionally been silenced, isolated, and reduced to statistics in other literature. Drawing from subaltern and feminist theory, I seek to illuminate the lived and embodied experiences of women who have attended and returned to clinical treatment for disordered eating on multiple occasions. A phenomenological, (auto-)ethnographic approach is adopted to explore the liminal period between their treatment cycles. Having personally returned to treatment for disordered eating numerous times, I will use reflections from my own experience to inform my engagement and collaboration with other women who have embarked on a similar journey towards healing to produce a collection of narratives. Deeply listening to these individuals and juxtaposing their narratives may shed light on the ways they resist, negotiate, and perform relationship and identity in the sphere of “recovery”. Contextualizing healing trajectories in this way has implications for a new lens through which “relapse” and “recovery” are discussed, and could reveal what may be missed in the realm of current therapeutics for disordered eating.

Pottery is ubiquitous across all levels of civilization, with distinct styles and patterns that can be used to give insight into the nation from which it was crafted. Looking deeper than what the eye can see, the mineral and chemical components can also reveal origins by mapping the components of the pottery piece to likely locations of where that mineral or element is commonly found. Ceramics may have many layers of interest, including the glaze, the slip, and the main body, that can be studied with minimal invasion and destruction of the artifact. Holistic analysis and characterization of these historical pieces requires a multidisciplinary perspective, incorporating fields such as materials science, history, and archaeology. The methods involved in this experiment include x-ray fluorescence (XRF) and scanning electron microscopy (SEM) in order to determine chemical composition and microstructure, respectively, of artifacts (circa 8000 BCE to 1250 CE) found in modern-day Iran. However, not all artifacts are made in the area they are found, hence the need to establish provenance. Preliminary XRF data shows certain samples may contain seashells, owing to their calcium components. This suggests that provenance could in fact be from Iran because Iran is not landlocked. In this we see that provenance is established in part by determining the composition of the artifact and where those materials most likely came from. In attempting to trace the origins of these particular artifacts, a protocol is also developed for mapping other samples and ensuring repeatability while doing so.

What does it take to burst the “bubble” of white privilege...what are the moves? Awaking to one’s complicity as a white person who benefits from racist systems of unearned privileges that mark a white supremacy culture can be a difficult experience. This research is the result of one person’s willingness to enter the transformative journey of following the auto-ethnographic process of dissolving and reconstituting their understanding of a white-self through the lens of indigenous scholarship and growing relationships with people of color whose voices and stories told of a reality that was unlike her own. In choosing to resist resisting the fear that is bound up in entering conversations about white privilege and racism, and holding space in an uncomfortable process, the researcher turned to her 89.7% predominately white community of Bainbridge Island, Washington to examine the culture of relationships between communities of color and those who identify as white. She asks the question “can, and if so, where, when and how are white identities transformed from positions of White Fragility and white supremacy into identities and relationships with people of color, of solidarity, allyship, accompliceship and race-traitorship in denouncing white privilege in order to create a culture that is equitable and inclusive for all people? Centering the methodology of relationships as sites of knowledge, the researcher engaged in cultivating cross-racial friendships with community members who were actively working in spaces of racial equity, inclusion, and social justice. In documenting the intersection of their lives and stories, valuable knowledge was gained in the accounts of privilege, fragility, oppression, hope, despair, joy, adversity, and triumph that is embodied in their collective experiences. This research contributes to the ongoing discovery and scholarship of the ways in which white identities move through the stages of transformation in relationship with communities of color.

This project is a portion of my honors research, which attempts to decipher the unknown nature of the first Arsacid kings. The Arsacid Dynasty ruled Iran from 246 BCE – 224 CE in the wake of the Hellenistic wave ushered in by Alexander the Great’s conquests. This topic is largely dismissed in academia due to general disinterest and the paucity of textual and archaeological data. This is a gross oversight, as the Arsacid empire controlled the land between the Indus Valley and Anatolia and fostered international exchange for over four centuries. Given the lack of traditional data, the primary source for the early Arsacid kings – those who ruled before their empire’s relationship with Rome began at the dawn of the 1st Century BCE – is the coinage they minted. These coins show the pictures and words Arsacid rulers choose to represent themselves, which evolve as their state expands. I analyzed detailed sketches of these coins – drawn and compiled by historian David Sellwood in his seminal 1980 volume – with special attention to the kings’ image, their titles, and the picture of the royal archer imprinted on the back of nearly every Arsacid coin. I matched the observations I made of the coins with what textual and archaeological data exists to conclude that the first Arsacid kings synthesized Hellenistic and Iranian symbology to craft a cultural status quo for their remarkably diverse empire. For this presentation, I focus primarily on the picture of the royal archer. The early Arsacids instilled the figure of the archer with traditional Persian motifs and depicted him seated on a Greek religious symbol (the omphalos) in a move that exemplifies their coinage-based propaganda program.

Detection of uncomplicated mild traumatic brain injury (mTBI) is difficult because there are no visible brain lesions that are often associated with more severe forms of TBI. New biomarkers would allow doctors to more sensitively screen for mTBI using neuroimaging methods. One promising biomarker technology is resting-state functional connectivity, which is brain activity measured at rest using functional magnetic resonance imaging. One particularly salient resting-state network is the Default Mode Network (DMN). Our research focused on identifying differences in resting-state functional connectivity between individuals diagnosed with mTBI and healthy controls. We examined mTBI in 254 U.S. military personnel deployed to a combat theatre in the Middle East from 2010-2013. Each subject underwent initial magnetic resonance imaging and screening for TBI following medical evacuation to Landstuhl Regional Medical Center (LRMC), the primary triage center for all evacuated combat casualties, up to 30 days post-injury. We used four distinct groups for our analysis; Blast/Non-Blast (n=79, 44) TBI, and Blast/Non-Blast Control (n=35, 96) while covarying for age and gender. We hypothesized that resting-state networks will be disrupted in TBI and blast populations when compared to controls. We used two different methodologies; the first was a seed-based analysis examining group differences in the correlations from the Posterior Cingulate Cortex (PCC, a key hub within the DMN) to the whole brain. The second analysis used the Yeo Seven Network parcellation to compute correlations between all seven networks to the DMN. We were unable to distinguish any group from controls, suggesting that early differences in functional connectivity are not a robust biomarker of injury.

Most organisms show a roughly 24-h cycle in their physiological and behavioral processes, called circadian rhythms, generated endogenously through the ~24h cyclic expression of genes known as clock genes. Clock gene expression oscillates in the master circadian clock of mammals – the suprachiasmatic nucleus (SCN) - and nearly every cell of the body. Typically, circadian clocks and the rhythms they sustain are ‘entrained’ by the 24-h light-dark (LD) cycle. Our lab has found that fear can also behave as an entraining factor. We observed that when mice or rats need to leave a safe nesting area to access a foraging area, they forage and feed during the dark phase of the LD cycle. If the foraging area is rendered dangerous with random uncued footshocks during the active dark phase, the animals’ foraging and feeding activity shifts to the light phase. My goal is to understand the neural circuits and molecular processes involved in fear entrainment. I have analyzed the expression of clock genes in animals exposed to nighttime fear and control animals exposed to daytime fear; this allowed me to assess the circadian rhythm of expression of clock genes of interest (Per1 and Bmal1) in the SCN and amygdala, and I found that the amygdala entrains to fear but the SCN does not. I have also performed trials with brain-specific-knockout mice and found that nocturnal fear entrainment requires an intact molecular clock. My current experiments use a more specific knockout strategy of viral injections into the brain to determine whether a functioning circadian oscillator in the basolateral amygdala (BLA) or the SCN is needed for nocturnal fear entrainment. These experiments serve to unmask the molecular mechanism of fear entrainment and could also help understand the mechanisms linking fear and anxiety disorders to problems with circadian rhythms and sleep.

Heterotopia are organized structures consisting of mixed cellular and neuronal elements arranged in a clear architectural pattern inappropriate to the considered tissue. Heterotopia are observed in the cerebral cortex and the cerebellum as a feature of many neurological disorders yet the we know little about the mechanisms driving their formation. We have analyzed a substantial number of Dandy Walker malformation (DWM) human fetal cerebella and found that a significant number of cases contain heterotopia. DWM is the most common structural birth defect of the human cerebellum and is characterized by an enlarged posterior fossa, enlarged fourth ventricle, and cerebellar vermis hypoplasia. A subset of cases are caused by loss of FOXC1, a transcription factor expressed in the mesenchyme during development. Our group has previously shown that loss of FOXC1 in mice causes loss of the mesenchyme-secreted factor SDF1alpha. Further, loss of SDF1alpha is sufficient to cause cerebellar heterotopia. This emphasizes the importance of mesenchymal signaling in the maintenance and development of the clear laminar architecture of the mature cerebellum. We hypothesized that granule neuronal progenitors (GCPs) are the primary cellular target of SDF1alpha mesenchymal signaling and therefore the main cell type causing heterotopia formation. To test our hypothesis, we excised the receptor for SDF1alpha from just GCPs in mice. Our findings show that loss of SDF1alpha in GCPs causes them to prematurely migrate into the developing cerebellar anlage and also caused other cerebellar cell types to form structured heterotopia. We observed defects in cerebellar foliation in the treatment group. Our data emphasizes the importance of SDF1-alpha dependent mesenchymal signaling in cerebellar development and identifies heterotopia as a new phenotype in DWM.

Dravet syndrome (DS) is a severe form of childhood epilepsy caused by a mutation in the SCN1A gene, which encodes the NaV1.1 voltage-gated Na+ channel. This channel is present in most GABAergic neurons, the main inhibitory neurons in the brain. Reduced activity of the channel in DS leads to loss of inhibitory activity in the brain; this, in turn, leads to seizures and developmental deficits. Through previous research using the mouse model of DS, the de la Iglesia lab has demonstrated that DS also affects circadian rhythms, which are the endogenous biological rhythms synchronized to the 24 hour day. These symptoms are likely caused by the loss of NaV1.1 in a sleep regulatory center called the suprachiasmatic nucleus (SCN), a set of cells which functions as the ‘master clock’ of the circadian system of mammals. However, the de la Iglesia lab found that selective deletion of the SCN1A gene from the SCN fails to replicate the abnormal circadian phenotype. We believe that these mutant mice are phenotypically normal either because there is a compensatory increase in the expression of another sodium channel, NaV1.3, or because the targeting strategy does not reach all cells within the SCN. To test the first hypothesis we employed in-situ hybridization to visualize the expression of the genes that code for NaV1.1 and NaV1.3 channels in either SCN-specific knock outs or their wild type littermates. My results will help explain the phenotype seen in the SCN-specific SCN1A mutants and determine whether developmental compensatory mechanisms are important in the SCN of DS mice.

 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.