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.

Pre-hospital patient protocols standardize medical procedures for EMTs and increase the quality of care for patients. In Washington state, these protocols vary by county and often contain a section for psychiatric emergencies with variant restraint protocols. The immediate use of restraints in these situations can be seen as dismissive to the patient and can lead to agitation and violence. Verbal de-escalation can enhance provider-patient relations and decrease likelihood of restraints, seclusion, and hospital admissions.  The goal of this project was to explore restraint and de-escalation methods used in WA state county-level EMS pre-hospital patient protocols. To complete the project, a codebook was created with binary variables with definitions that determined whether the procedures listed in the protocol satisfied the definition. Using the codebook, each protocol was independently coded by 2 people and disagreements were reviewed by a third person. Finally, we created descriptive statistics from the restraint protocols and stratified based on rurality. Of the 39 counties in WA state, 77% of counties mentioned verbal de-escalation methods in their pre-hospital patient protocol. The de-escalation method with the highest proportion in all counties recommended reassuring the patient that the providers care for them (28%). The second highest proportion in all counties was to mention the use of de-escalation methods without explicit instructions (23%). Counties that do not have specific instructions and just mention the use of de-escalation methods can be confusing if the provider does not have de-escalation training or has not trained recently. These findings highlight the need for future research concerning the adherence of EMTs to these protocols and to see the what the outcomes are of the different protocols. More research can be done through contacting individual EMS agencies to see if internal protocols exist outside of county protocols.

During embryonic development of the vertebrate central nervous system, innate immune cells, called microglia, migrate into the retina and brain. Microglia are responsible for phagocytosis, monitoring tissues for pathogens, and inflammatory signaling. Several studies in model organisms show microglia also have roles in neural development, particularly in formation of synaptic circuitry. Defects of the neuronal circuitry can lead to vision loss, therefore it is probative to investigate the role and mechanisms of microglia in wiring the retina. The purpose of this project is to investigate microglia migration and activity in the human retina, where very little is understood. To understand if microglia could have similar effects in human retinal development as in model organisms, we first needed to determine when and where microglia are found at different ages. We collected donated fetal tissues from as early as developmental day 40 through 132 to determine the number and distribution of microglia in tissue sections using Iba1, a microglia-specific antibody, and confocal fluorescence microscopy. To test whether microglia are necessary for retinal development we are using our lab’s fetal retina culturing technique that can be used to manipulate microglia populations. Retinal development can be visualized after deletion of microglia using markers for retinal progenitor cells (EdU) and various synaptic antibodies. So far, we have seen from whole retinal tissues that microglia are present as early as day 58, prior to the majority of synaptic development, and survive in retinal cultures. Earlier stages are being investigated, and we are currently determining methods that will deplete microglia in order to study the effects of their absence on retinal development. In conclusion, we know that microglia are present during synaptic development, and persist during retinal culturing. Therefore, microglia are potentially essential for human retinal development and could be targets for future disease research.

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.

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.

Hypoxic-Ischemic Encephalopathy (HIE) is a brain injury that commonly causes mortality in neonates. Current treatment consists of therapeutic hypothermia, but close to 50% of affected infants still have a poor outcome (death or severe disability). In order to discover new effective therapies, it is important to compare how different treatments affect the brain in animal studies. The research laboratory has developed a ferret model of HIE because the ferret brain has more complex gyrification compared to rodents. Animals underwent unilateral carotid ligation at postnatal age 17 days (P17), in which one side of the carotid artery was restricted temporarily and the other was restricted permanently. The animals then received periods of hypoxia and hyperoxia. To better quantify the extent of injury, a system involving measurements of the gyri, sulci, and cerebellar exposure was developed. Ex vivo brain measurements were collected from a population of 63 ferret kits at age P42, and adjusted by the weight and sex of the animal. These measurements included the lengths of: the longitudinal fissure (anterior and posterior), lateral sulci, suprasylvian sulci, coronal sulci, pseudosylvian sulci, ansinate sulci, cruciate sulci, presylvian sulci, lateral gyri, suprasylvian gyri, sigmoid gyri (anterior and posterior), coronal gyri, ectosylvian gyri (anterior and posterior), orbital gyri, and the exposure of the cerebellum. In injured animals, significant changes in the longitudinal fissure, ansinate sulci, left coronal sulci, cruciate sulci, presylvian sulci, posterior sigmoid sulci, and exposure of the cerebellum were seen compared to littermate controls. The implications of this measurement system include the ability to accurately characterize the degree of injury in animals with an hypoxic-ischemic brain injury, which will help to show whether potential treatments are neuroprotective.

The impacts of climate change may be partially ameliorated by positive interactions among species, such as native plants and arbuscular mycorrhizal fungi (AMF). Sea level rise caused by climate change will detrimentally impact saltmarsh habitats by increasing the elevation and rate of terrestrial salt water inundation, thereby reducing effective functionality of ecosystem services provided by saltmarshes. Facilitations, positive interactions between species, is key in determining which species can survive in habitats characterized by abiotic stress, such as salt marshes. Halophytic plants within salt marshes can benefit from symbiotic AMF facilitations through increased inundation tolerance, greater nutrient availability and uptake, and relief from saline stress. This study identifies the presence of AMF across multiple saltmarsh plant species and measures the impacts of AMF within Oregon’s Salmon River Estuary at Cascade Head. I have extracted samples from four monoculture plots within high and low marsh elevations across four species that grow at both elevations: jaumea (Jaumea carnosa), Lyngbye’s sedge (Carex lyngbyei), pickleweed (Salicornia virginica) and salt grass (Distichlis spicata). I have centrifuged soil samples from each plant, and calculated AMF spore abundance at each sample location. I am also processing soil samples for percent water in the sediment, soil salinity and pH. Additional samples from both elevations within polyculture plots have been collected to develop a secondary index to cross-reference my primary findings. Through this research, land managers developing sea-level rise mitigation plans will have data supporting which plants will be most resilient to sea level rise. Potential inoculation of host plants could protect estuaries from sea level rise and increased frequency and intensity of storm events in coastal regions. In identifying plants which host beneficial AMF, fungal inoculation of plants in marshes could help plants grow further into lower marsh elevations, increasing sediment accretion and decreasing erosion and soil degradation.

Increasingly, over the past half century, antibiotic resistant plasmids have spread to a large range of bacteria increasing the demand of new antibiotics. On average, once an antibiotic has been released into the public market, a strain that is antibiotic resistant evolves within a few years. Even though the constant production of new drugs and treatments provides some temporary solutions, a better solution would be to investigate and understand bacterial plasmid mechanisms. Through my research in the UW Biology Kerr Lab, I have been exploring how bacteria maintain plasmids that contain genes encoding for antibiotic resistance. Plasmids are extra-chromosomal pieces of DNA that require the host cell to allocate energy for their general maintenance. Prior theoretical research suggests that, to avoid this allocation of resources, the host should lose antibiotic resistant plasmids over time when the plasmid is no longer beneficial to the host’s fitness, for example when the antibiotic is no longer present. We found that many plasmids across multiple bacterial species persist in their hosts, even in the absence of selection for the plasmid. Currently, I am testing whether changing the environmental conditions experienced by the host/plasmid pairs, specifically from a nutrient-rich to minimal media, will affect the persistence of antibiotic resistant plasmids. This research provides important data that will allow us to have an easier time combating antibiotic resistance.  

The research question this study addresses is: How do community-based promoters contribute to the delivery and utilization of health insurance among marginalized populations in India? The subject of investigation for this study is the insurance delivery model of VimoSEWA, an organization based in Ahmedabad, India that provides health and other social insurance services to self-employed women with limited prior access to financial protection. To address the research question, I investigated the successes and difficulties experienced by VimoSEWA community-based insurance promoters, called aagewans, through field visits and personal interviews in Ahmedabad and nearby rural districts in Gujarat. Both aagewans and insurance members were interviewed during this study to develop a comprehensive understanding of the importance of community-based promoters in health insurance delivery and the various factors that impact their role. The role of VimoSEWA aagewans in promoting and delivering health insurance to self-employed women in Guarat is significant because insurance improves the financial stability of these women and their families. Furthermore, health insurance is effective in decreasing high out-of-pocket healthcare expenses and improving access to quality healthcare services. However, the findings of this study indicate that the benefits of health insurance can only be attained by marginalized populations if insurance is made accessible to these communities through proper delivery methods and sufficient social support systems. VimoSEWA aagewans perform a fundamental role in establishing trust between the community and the insurance provider, making health insurance accessible, and adapting services to the community's needs. 

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!

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Age related immune decline may play a role in susceptibility to parasitic helminth infections among the octogenarian population. Few studies have examined very old age on susceptibility to helminth infections in people. Effects of age on host susceptibility using mouse models also has not been thoroughly studied for older ages of laboratory mice (Mus musculus), such as beyond about one year. In this study, the intestinal nematode (Heligmosomoides bakeri), a model for hookworm infection in humans, was used to infect 1-year-old and 2-year-old Swiss Webster mice. At 40 days post-infection, worms were removed and worm survival, sex ratio, ex vivo egg output, and worm length (as an index of growth) were measured and analyzed. I expect to find an increase in worm survival, ex-vivo egg output, and worm length in older mice. These results will be valuable because they will model the helminths capacity to proliferate in older hosts in comparison to younger hosts during a human hookworm infection.

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.

Photoresist is a viscous light sensitive organic solution which is used to coat the surface of silicon substrates in nanofabrication processes. An essential step in nanofabrication is photolithography. During this procedure, photoresist is deposited in a uniform, thin film over the wafer surface using a tool called the Spin Coater.  The purpose of our experiment is to develop spin curves that will examine the correlation between the different speeds or RPM value that the wafer is spun at and the uniformity of the photoresist coated wafer. The thickness and uniformity are critical to determine the correct UV exposure dose and plasma etch times. We will analyze the results for both positive and negative photoresist. In the case of a positive photoresist, the regions that are exposed to light are dissolved in developer. On the other hand, with negative photoresist, regions that were not exposed to light are dissolved. After the wafers are spun, the uniformities will be measured by an automated thickness mapping system called Filmetrics. Filmetrics is a machine that allows for the surface to be measured at the nano-meter level. The spin curves experiment will allow researchers to obtain wafers using these photoresists to achieve photolithography with their desired thickness.

First-passage and last-passage algorithms are two diffusion Monte Carlo methods that we can use to obtain the charge density distribution on a conducting surface. Usually, we use first-passage algorithms to obtain the capacitance and the overall charge distribution of the arbitrary-shaped conductor. On the other hand, the last-passage algorithms calculate the charge density at a point on a conducting surface by initiating the random walk at that point. The last-passage algorithm utilizes the dipole Green’s function to expedite the diffusion process which starts from the point. Past results determine the initial sitting using the largest hemisphere around that point with a radius that is contained in the surface, which inefficiently starts the random walk if the point is near the edge of the surface. Here, we derive the dipole Green’s function to start the diffusion process from a point on the hemisphere off-centered from the original point using weighted sampling to further expedite the computing process.

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.

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.

A decline in effective mitochondrial functioning of cardiac cells is one the major underlying factors of aging. Many pathological conditions have shown to result in the peroxidation of the final electron carrier in the electron transport chain (ETC) known as cytochrome c. The ETC is constructed of a series of complexes responsible for the transfer of electrons from electron donors such as NADH through a continuity of redox reactions while coupling the electron transfer energy to the transfer of protons across the inner mitochondrial membrane, constructing a proton gradient to stimulate the production of ATP (Adenosine triphosphate). Peroxidation is known as oxidative degradation and causes cyctochrome c to lose its ability to act as an electron carrier through free radicals that steal the electrons from the complex. The SS-31 peptide works to bind to the inner mitochondrial membrane consisting of cardiolipin and prohibits the cardiolipin from converting cytochrome c into a peroxidase, an enzyme that catalyzes oxidation, and continue its function as an electron carrier. Additionally, administration of NMN (Nicotinamide mononucleotide) can help improve the overall bioenergenetics of the mitochondria through an enhanced production of NAD+, therefore increasing the amount of electrons donated into the ETC once NAD+ is reduced, leading to an increased production of ATP. Three different mice treatment groups were constructed for this experiment; the first group was treated with surgical incisions of pumps containing the SS-31 peptide, the second group was provided with the NMN drug administered through water pumps, while the third group was left as the control. Detection of bioenergenetic changes between treatment groups was evaluated through changes in the NAD+ stoichiometric peak evident through 31Phosphorous magnetic resonance spectroscopy. Administration of the SS-31 peptide and NMN through the mouse model provides a potential advantage in the treatment of age-related complications for human patients.

In neurons, microtubules are critical for cellular and developmental functions including neurite outgrowth and maintaining stable wiring of the nervous system. Tau, an intrinsically disordered protein, plays important roles in microtubule assembly and stabilization. However, tau can dissociate from microtubules and form amyloid fibrils in a set of neurodegenerative diseases termed tauopathies, which includes Alzheimer’s disease and frontotemporal dementia. Mutations in the tau sequence cause the disease FTDP-17T, providing evidence that alterations in tau alone can cause tauopathies. Most mutations occur in or near the microtubule-binding domain of tau, which suggests that mutant protein may be deficient in its capacity to stabilize neuronal microtubules, more prone to aggregate, or both. In particular, the disease-associated mutation P301L appears to enhance tau’s propensity to aggregate into fibers and alter its pathological activity. Molecular chaperones are responsible for maintaining protein solubility, promoting proper folding, and preventing atypical aggregation. The chaperone HspB1 delays wild-type tau fibril formation by weakly interacting with early species in the aggregation process. It is able to recognize aggregation-prone motifs within the microtubule binding repeat region of wild-type tau. Therefore, we used fluorescence spectroscopy to test the affinity and activity of HspB1 against wild-type and mutant models of the tau microtubule binding region, to see whether changes in the tau sequence alter interaction with the chaperone. In addition, tau oligomers are known to disturb lipid bilayers, a harmful interaction that could lead to potential cell death. Using a vesicle permeabilization assay, we tested the interactions between artificial lipid membrane with our tau constructs, and whether HspB1 can counteract these harmful interactions. This will extend our understanding of the characteristics and behaviors of disease-associated mutations of tau and the ways in which chaperone target aggregation-prone tau species.

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.

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 life history traits of parasites are dependent on the host environment and host immune response. Heligmosomoides bakeri, is an intestinal nematode parasite that infects laboratory mice (Mus musculus). This investigation used rapamycin, an immunosuppressant drug, in the diet of the host. Rapamycin is currently being considered as an over the counter drug to extend life expectancy. The purpose of this experiment was to determine if inhibition of the host immune system by rapamycin had a significant effect on parasite life history traits during a secondary infection. Mice were fed either a rapamycin diet or control diet for two months. Mice were then infected with H. bakeri, drug cleared of the primary infection, then re-infected with a secondary H. bakeri infection. Starting eight days after the secondary infection fecal egg counts were done daily to determine worm reproduction in vivo. Eighteen days after the secondary infection the mice were euthanized and worms were removed, sexed and counted. Length of ten female and ten male worms from each mouse was then measured, and 10 females were cultured to measure ex vivo reproduction. After 24 hours of incubation in culture media, egg output and worm motility (an index of viability) were measured. For this experiment I was involved in recording the worm length and was responsible for performing the ex vivo egg count and motility measurements. Results will provide important information about potential over-the-counter use of rapamycin in humans to slow biological aging and how changes in immune function may affect susceptibility to parasite infection.

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.

Both acute and chronic pain are universal, often debilitating sensations that lead to significant physiological, psychological and economic costs. Drug development and research have worked to counteract these adversities, but current therapies are often inadequate and have dangerous side effects. Targeted drug development, which relies on pre-selecting a target that is subjected to in-vitro testing, has been difficult, costly and ineffective in producing a drug that works to effectively relieve pain with minimal unfavorable consequences. An alternative approach would be to develop an untargeted screen in a system that employs complex pain behaviors. It would act as a means of modeling the nociceptive processes, which are the neural processes of encoding and processing noxious stimuli, in the organism. We utilize an unbiased, behavior-based, novel assay that uses zebrafish larvae to better understand pain sensation. We have screened thousands of small molecules on zebrafish larvae to identify ones that have analgesic properties. The potential analgesics should block sensitized temperature aversion which changes the larvae’s temperature zone inclination meaning we observe no preference between the two zones. Thus far, our untargeted screen identified three novel molecules with analgesic properties. We then performed a series of pharmacology and behavioral experiments to understand the impact of the compounds and to narrow down their effects in order to confirm if it is truly impacting nociception and/or temperature aversion with the intent to validate the compounds as prospective analgesics.

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.

Gravitational wave research comprises an emerging field in physics, as many institutions around the world rely on measurements from the Advanced Laser Interferometer Gravitational Wave Observatory (LIGO), and other interferometers as a vital source of data. Wave parameters provide valuable information about the astrophysical source properties, such as sky localization, source mass, spin, luminosity distance, and orbital inclination, and can also be used for an independent determination of the Hubble constant and tests of general relativity, and the nature of gravity itself. For these reasons, enhancing the absolute accuracy of gravitational wave detectors is essential. The accuracy of these parameters is fundamentally limited by calibration uncertainty. Accordingly, this project researches methods of enhancing the absolute accuracy of gravitational wave measurements to augment the data obtained by interferometers such as Advanced LIGO, to advance gravitational research. One current calibration method relies mainly on photon pressure calibrators (PCals), which are based on the measurement of test mass displacement generated by a periodic force via radiation pressure from the reflection of a power–modulated laser. The technological limit of the absolute calibration uncertainty corresponds to a few percent due to uncertainty in power, and thus limits accuracy in source parameters. The LIGO affiliated Eot-Wash team at the Center for Experimental Nuclear Physics and Astrophysics (CENPA) works to minimize fundamental systematic uncertainty in calibration methods through extended analysis of the combination of gravity field calibrators (GCals) and PCals. GCals make use of a gravity gradient to achieve modulation of the test mass displacement for calibration, providing an alternative source of accurate actuation. The combination of the two calibrators could reduce the systematic uncertainty in GW strain measurements and improve astrophysics with LIGO.

The goal of the Laser Interferometer Gravitational-Wave Observatory (LIGO) detectors is to detect faint ripples in spacetime caused by the merger of massive compact objects, like black holes and neutron stars, using a Michelson interferometer with Fabry-Pérot cavities in the 4-kilometer arms. Because the detectors have length change sensitivity on the order of 10^-20 meters, there are many types of unwanted transient signals that affect the calculated gravitational wave strain signal and interfere with searches for real gravitational waves. These are referred to as glitches; finding the cause of a glitch category is the first step to eliminating it. I searched for the source of 60-200 hertz range glitches known as “scratchy” glitches. I found a correlation between elevated ground motion and detection of scratchy glitches, then estimated false alarm rates for their observed coherence. My research supports on-site efforts to eliminate scratchy glitches.

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.

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.

In the introductory physics curriculum, students are taught induction and inductance by examining the behavior of the current-carrying coil. As electronic devices approach the nanoscale, one might ask a student how would it be possible to fit an inductor onto an electronic chip. A commercial microelectronics solution is the planar spiral inductor, which are conductive thin film patterns deposited on substrates especially used for high frequency applications. Although synthesizing a thin film is beyond the reach of most classrooms, the principles and advantages of a thin film inductor can be taught using very affordable copper tape. An instructional laboratory activity based on this design introduces students to inductors using a geometry not covered in the introductory text and also offers them insight into the solutions necessary to build devices at the micro- and nanoscale, which would especially be useful to careers in engineering and applied physics. In this work, we demonstrate the construction of macroscale planar spiral inductors using commercially available copper tape and compare their behavior to an off-the-shelf inductor

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.

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.

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.

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.

For more than 4,000 years, paper has been made from cellulose, the most abundant natural polymer, for the purpose of recording information. With the incorporation of fillers, such as carbon nanotubes (CNTs) and cellulose nanofibers (CNFs), conventional paper can exhibit enhanced strength, electrical conductivity, and high sensitivity to external stimuli (e.g. strain, temperature, humidity…), which has a great potential for applications in portable electronics and wearable devices. The present research consists of me spinning one or multiple strips of smart papers into highly robust yarns. I also prepare different strips of dried and wet paper. They are prepared from bleached soft wood pulp and are twisted into densely compacted yarns. I then exam their pore structure and strength properties using analytical methods. Results indicate that paper yarns made out of two strips exhibit the highest tensile strength, while the incorporation of additional strips shows only limited strength improvement. This work is important because it can let us know more about the physical ability of smart papers and nanotechnology and how to improve them in the future using yarn method.

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.

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.

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.

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 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.

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

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

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.

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.

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.

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.

There is a common thread among contemporary circus art disciplines that is unique in the performance world. It is a blend of theater, dance, and acrobatic skill that can produce amazingly complex and captivating works. When comparing the choreographic processes of these performance mediums with the creative practices of solo contemporary circus artists, do new choreographic themes exclusive to circus arts become visible? Or does the essence of contemporary circus lie in the combination of standard techniques adopted from theater, dance, and acrobatics? An analysis of well-known work provides viewable examples of contemporary circus choreography, while local artist interviews provided seasoned, close-to-home examples of solo circus act creation on a professional level. In summary of my findings, I discuss the implications of choreographic methods in contemporary circus from the viewpoint of a solo artist and choreographer.

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.

 In recent years, the University of Washington has promoted itself as a leader in sustainability and has made significant strides towards increasing sustainability efforts on campus. One area in which the University has not focused heavily in sustainability is in the curriculum. To address this gap, I am developing a framework for what measures can be taken to implement a sustainability requirement at the University of Washington. In developing this framework, I am researching sustainability requirement policies at other institutions and sustainability policies and initiatives at the University of Washington. My research shows that a sustainability requirement has been implemented at several universities around the nation, some of which are scale-comparable or peers institutions to the University of Washington. Furthermore, a sustainability requirement would support several of the University’s goals and initiatives. Using this research and the UW Diversity Credit as a case study, I am developing a report detailing recommendations and an action outline to details next steps to implement a sustainability graduation requirement. In addition, I am forming a student coalition to gain campus support and work with administration to pass the policy through the appropriate channels. If a sustainability graduation requirement can be implemented, it will not only help the University of Washington emerge as true leader in higher education sustainability, but it will also help develop future generations of graduates who understand sustainability; its applicability to their lives, decisions, future careers, and fields of study; and enable them to tackle the emerging global challenges.

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. 

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.

Memory formation, or plasticity, is the brain’s ability to change and adapt in response to new information through altering the strength and effectiveness of communication at the synapse. Synaptic plasticity plays a major role in the brain’s capacity to incorporate past experiences into stored memories and it has become one of the most intensively researched subjects in neuroscience. Neuroscientists typically evaluate synapse function using enriched, homogenized preparations of synapses, called synaptosomes. However, synaptosome preparations contain a mix of neuronal and non-neuronal contamination along with active and inactive synapses that are impossible to separate, making it difficult to draw specific conclusions about synapse activity. To address these challenges and understand the molecular mechanisms behind synaptic plasticity, my lab has developed a synaptic TAG- an engineered protein that localizes to recently active synapses. The TAG construct, containing an extracellular CD4 protein whose expression is driven by activity-dependent regulatory elements, will be electroporated into the developing motor cortex of mice in utero. The mice will later be trained to run on a rotarod, a test commonly used to assess motor learning. After the mice have learned this task, the differences in their synapses will be evaluated by sectioning and staining the motor cortex with fluorescent antibodies. The number of distinct fluorescent TAGs on the synapses on a given number of neurons will be counted through confocal imaging. My hypothesis is that I will see an increase in the number of TAGs on the synapses of a trained mice, which will demonstrate that the TAG is synaptic in vivo and activity dependent. The completion of this experiment will allow my lab to identify learning-associated proteins using magnetic cell sorting, mass spectrometry, and RNA sequencing. Understanding learning-associated protein interactions will shed light on how their malfunctions contribute to Autism Spectrum Disorders or neuropsychiatric disorders.

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.

Tuberculosis is a major infectious disease with approximately 2 billion people infected worldwide. With the emergence of multi-drug resistant tuberculosis (MDR-Tb), efforts to develop efficient treatments with fewer cytotoxic effects are currently under investigation. Dual host and pathogen directed therapeutics hold promise towards more effective treatments against tuberculosis (Tb) through mechanisms that enhance bacterial clearance and reduce tissue damage and immunopathology. We investigate RGFP966, a drug that modulates the host's immune defenses and directly reduces Mtb growth (a histone deacetylase 3 (HDAC3) inhibitor). The aim of my project is to characterize the effect of RGFP966 on Mtb growth. My hypothesis is that the antimicrobial effects of RGFP966 are specific to Mycobacterial species, and the bacterial target of RGFP966 is required for its survival. Within the experiential growth period, I treated Mycobacterium avium and M. Smegmatis in 7H9 broth with a range of RGFP966 concentrations (0.5 uM, 5 uM, and 50 uM) and incubated in culture tubes and 96-well plates for 3-7 days. Within designated time intervals, I analyzed levels of dose dependent inhibition using optical density, luminometry, and fluorometry methods. Current results through optical density and luminometry demonstrate that RGFP966 controls M. Avium growth in 7H9 broth with an MIC50 of approximately 5 uM. Fluorometry and optical density results indivate no restriction of M. smegmatis growth. Comparing these results to previous findings in our laboratory, where RGFP966 lacked effects against common gram-positive and gram-negative bacteria, indicates possible specificity of the antimicrobial effects of RGFP966 to Mycobacterial species. We will further examine the effects of RGFP966 against mycobacterial growth. A comprehensie understanding of its pathogen directed effects combined with its host directed effects hold promise as an adjunctive therapeutic against Tb infection. 

 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.

The blood brain barrier (BBB) is an almost impenetrable obstacle for therapeutic delivery, hampering the treatment of many neurological diseases. By exploiting natural transport mechanisms utilized by the brain such as iron import via transferrin receptor (TfR), researchers have been able to transport therapeutic molecules into the brain, albeit with a low efficiency. TfR is a transmembrane protein that is highly expressed on the BBB where it binds its ligand, Transferrin. Transferrin-bound iron binds on the blood side of the BBB, is subsequently endocytosed and trafficked through the cell before being exocytosed on the brain side. We have computationally designed a protein that, like the transferrin ligand, can bind TfR and pass the BBB in in vitro BBB models. The goal of my project is to attach existing protein nanocages to this binder which have previously been shown to package therapeutic molecules. I have generated constructs by fusing the binder to these cages, purifying the cages, analyzing their stability, and testing their binding affinity to transferrin receptor. We currently have one cage fusion that successfully binds the transferrin receptor and is being tested for BBB traversal. We are continuing our work to create more variants that can successfully cross this barrier. Using computationally designed de novo proteins has many advantages over traditional protein engineering approaches such as hyperstability and a high degree of customizability. In the future, this project could provide new opportunities for treatment of many neurological diseases.

Three generations of immigrant history have led up to my personhood. I’ve inherited the struggle of my mother and my grandmother before her, who have worked themselves to the bone to provide me security. This inheritance is the driving question in my research project RATSKIN, a theatrical play that is in development. How does one honor one’s immigrant history but also break free from the ideologies that were made to trap immigrants within a cycle of destruction? RATSKIN is my intervention. Incorporating literary and theatrical traditions with historical, archival research, the play is an exploration in how to weave together personal experience, genre, cultural theory, and history into a narrative that can be shared to a community in a productive, discussion generating way. RATSKIN draws inspiration and theoretical groundwork from Borderlands/La Frontera by Gloria Anzaldúa; One Hundred Years of Solitude by Gabriel García Márquez; Neo-Marxist theories by Ngũgĩ wa Thiong’o, Louis Althusser, Evelyn Nakano Glenn; Tacoma’s immigrant history; and my own family’s immigrant history. The plot and construction of the story itself is an attempt to physically manifest and represent racialization, assimilation, and the trappings of harmful ideology that is expanded upon in the theoretical foundations. With these lenses, RATSKIN is a presentation of immigrant history and how the theatrical and literary traditions can help reveal how families continue to be affected by immigration. How can this history be refracted within a single family? What are these effects? How have they evolved through generations? How can we make sure these effects don’t limit the growth of our families?

International adoption in the United States began during World War II. It was developed as a humanitarian act to aid those orphaned due to the war. Since then international adoption has remained an option for Americans looking to expand their family. The Hague Convention is an international organization aimed at uniting countries in their laws regarding international adoption policy with the intent to ensure the welfare of the child. Since its founding in 1983, the Hague Convention has influenced a total of eighty - three countries including the United States. Despite the intention of the Hague Convention and its member's international adoption still places a child's welfare at higher risk than those of domestically adopted children. International adoptees are victims of human trafficking, abuse, and untimely death. Even the Hague Convention intended to improve international adoption does not advocate countries to use international adoption as a solution to aiding their orphaned population. Permitting an international adoption is promoted as a last resort for the most vulnerable of an already targeted community. The primary intent of this paper advocates for stricter enforcement and potential temporary stall on future international adoptions within the United States. This stance is taken due to issues of lack tracking of international adoptees, the failure of enforcement of international adoption laws currently in place, and the negative impact of the overtly positive marketing of international adoptions. This work intends to bring further awareness of the systemic issues of international adoption that put a child's welfare at risk. Concerning international adoption, this is highly important due to its primarily positive reputation with the general public. This research also intends to provide a solution society may advocate for or further build upon in order to take the measures necessary to ensure the welfare of a child.

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.

 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.

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.

Obesity is associated with 2-3-fold increased risk of hypertensive disorders of pregnancy and 3-4-fold increased risk of gestational diabetes compared to a normal weight cohort. While obesity is a leading attributable risk factor for hypertension and diabetes during pregnancy, approximately 70%-80% of women identified as obese, based on a BMI, will not experience either disease process, suggesting limited predictability of BMI alone. The purpose of our MEDPREG study is a pilot and feasibility study with the objective to properly differentiate and accurately identify women at risk for metabolic dysfunction in pregnancy. To do this, we are evaluating two physiological processes- a central one that regulates body weight and a peripheral one that evaluates the role of body composition. The first process, known as MBH gliosis, focuses on the presence of inflammation in the mediobasalregion of the hypothalamus which regulates energy homeostasis and influences body weight. The second process measures abdominal fat, specifically visceral and subcutaneous fat, that plays a role in metabolic dysfunction. We are recruiting and enrolling normal (n=5), overweight (n=5), and obese (n=5) women in the first trimester based on first trimester BMI. In the pre and postpartum analysis, we are analyzing the association hypothalamic gliosis/intraabdominal fat and our primary outcome- a composite of hypertensive disorders of pregnancy, glucose intolerance or abnormal fetal growth. We are doing this through methods such as ultrasound fat depth, bioimpedance analysis (BIA), and laboratory data to possibly identify more approachable biomarkers that are accurately reflective of visceral adiposity. Our future directions include 1) assessing the effect of maternal gliosis and visceral fat distribution on the fetus and neonate and 2) to ultimately create a multivariable prediction model that could accurately screen and identify women at risk for metabolic syndrome in pregnancy.

Magnetic fields (MFs) and cosmic rays (CRs) are decidely important aspects of galactic disk and halo evolution, however, their precise roles are not yet completely understood. While there are many simulations studying galactic evolution, few have deeply explored the exact impact of CRs and MFs in the evolutionary process. The current goal of our research is to learn more about how CRs and MFs contribute to the evolutionary process by looking at how MFs grow and change in the circumgalactic medium (CGM) under the influences of CRs. Using a suite of simulated, isolated disk galaxies, we investigated the role of CRs in MF growth and galaxy evolution by comparing different galactic models, each possessing slightly varied CR physics. We present the role of CR transport on the geometry, strength, and growth rate of MFs in these simulated galactic halos.

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.

Inflammasomes are multimeric protein complexes involved in innate immune responses. Inflammasomes include a protein sensor, such as NLRP3 or pyrin, linked to the enzyme caspase-1 via the adaptor protein, ASC. Active caspase-1 is responsible for release of the cytokine interleukin (IL)-1ß and triggering inflammatory cell death. Inflammasomes are crucial in defense against pathogens. However, excess inflammasome activation is linked to diseases such as Alzheimer's, atherosclerosis, and other inflammatory conditions. Although inflammasomes are linked to several diseases, we do not fully understand how inflammasomes are activated. We are researching the role that potassium plays in inflammasome activation. To detect inflammasome activation, I measured released IL-1ß using enzyme-linked immunosorbent assays (ELISAs). I determined whether inflammasome activation requires potassium efflux by measuring IL-1ß released from cells stimulated in high extracellular potassium, which prevents potassium efflux. I found that IL-1ß release triggered by NLRP3 inflammasome activators is prevented when cells are stimulated in high extracellular potassium. However, IL-1ß release triggered by the pyrin inflammasome was not affected by high extracellular potassium. From these results, we conclude that the NLRP3 inflammasome is dependent on potassium efflux from the cell, whereas the pryin inflammasome is not. The implications of our research are two-fold. First, our findings argue against a long-standing hypothesis that high extracellular potassium blocks ASC binding. Both NLRP3 and pyrin need ASC, but our data show that only NLRP3 is affected by potassium concentration. This suggests that potassium affects NLRP3 activation at an unknown point. Second, understanding the role of potassium in regulating inflammasome activity provides a potential therapeutic target. There are drugs that regulate ion concentrations by controlling ion channel activity. Knowing whether an inflammasome pathway is potassium efflux dependent could be beneficial in limiting excess inflammasome activation that is linked to a variety of human diseases.

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.

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 waters surrounding the San Juan Islands in the Salish Sea near Washington state, USA, possess a variety of physical and chemical conditions that combine to support a rich multitude of marine organisms. Five constituents observed and analyzed in this project represent the larger food web found within the Salish Sea: nutrients, phytoplankton, forage fish, seabirds, and marine mammals. I tracked variability in these constituents during the fall over the course of twelve years from 2006 to 2018. This time range was selected to cover the years before, during, and after the North Pacific marine heat wave (2014-2016), and the subsequent return to normal temperatures in the Salish Sea since those years. The abundance and composition of these constituents varied over this time range. We found a significant decrease in both nutrient concentrations and fish condition in the fall of 2014, which had returned to previously observed levels by the fall of 2018. In contrast, the phytoplankton and marine bird and mammal observations remained comparably low in 2018, similar to values observed in fall 2014. The introduction of the marine heat wave into the Salish Sea during 2014 appears to have consequences that span across multiple years after its dissipation in the Pacific Ocean. As marine heat waves are anticipated to become more prolonged and common with global climate change, it’s crucial to understand their short- and long-term impacts on local marine populations. 

The abuse of opioids has become an epidemic in the United States. In 2017 the mortality attributed to opioid overdose was 70,237 individuals which is more than the death toll from the Iraq and Vietnam wars combined. Microdirect laryngoscopy (MDL) is a very common surgery performed among otolaryngologists with varying post-operative analgesia regimens. We aimed to characterize current opioid-prescribing patterns among otolaryngologists performing MDL by using a cross-sectional survey of otolaryngologists at a national meeting. Our eventual goal was to have a standard post-operative opioid prescribing protocol to improve safety and allow early identification of individuals that may be at risk of opioid misuse. We surveyed 57 practicing otolaryngologists: we found that 91% of surgeons routinely prescribed opioids, 84% of surgeons recommended non-opioid analgesics as adjunctive medications, and only 5% of surgeons report never prescribing opioids. When opioids were prescribed, patient preference, difficult exposure and a history of opioid use were the most influential patient factors. Concerns of opioid abuse, the physician role in the opioid crisis, and literature about post-operative non-opioid analgesia were also underlying themes in influencing opioid prescription patterns after MDL. Opioid stewardship should be a consideration for MDL. It appears that over 90% of physicians are prescribing opioids after MDLs, although many are also prescribing non-opioid analgesia. Armed with the knowledge of current practice and influences, otolaryngologists can work to decrease opioid prescribing patterns appropriately to improve patient safety and mitigate the contribution of post-operative prescribing patterns on the opioid epidemic.

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.

Hybrid dynamical systems (HDS) are time dependent systems that have both discrete and continuous behavior, such as a bouncing ball or jumping leg. The BioRobotics Lab studies HDS in order to better understand locomotion and develop controls for robotics. As controllers are developed, they need to be tested in the hybrid dynamical system (HDS) either through simulation or implementing in physical robotics. While simulated system environments are useful in early controller development, they are unable to capture all the intricacies of a physical system. Thus, testing controllers in a physical system can provide better insights for future development. We developed a hopping robot for the purpose of easily implementing controllers through software. The hopping robot is designed to be modular and easily configured for different dynamics. Simulations of the robot were also developed so that researchers can use both simulated and physical environments. This tool will help researchers develop new controllers and could bring new insights to studying hybrid dynamical systems.

Conservative estimates suggest that food production must increase by 60-70% by 2050 to keep up with population growth. This challenge to global food security is compounded by a lack of knowledge of how crop species will respond to a changing climate. The Nemhauser Lab has been studying how the photoreceptor Phytochrome B (phyB) directs the allocation of plant resources in response to environmental stimuli like elevated CO2. I have focused on studying this phenomenon in Brassica rapa, a member of the mustard family that includes a large variety of popular vegetables such as broccoli, cauliflower, Brussels sprouts, as well as varieties used for oil production. B. rapa plants with mutations in the phyB gene make fewer seeds, have a lower chloroplast density, photosynthetic rate, total chlorophyll levels, and stomatal index. To better understand how phyB is involved in seed yield, I am characterizing ovules and gynoecia (female reproductive organ) development in phyB deficient B. rapa plants. To understand how phyB plays a role in other processes relating to or impacting resource allocation such as chlorophyll levels, I will identify genes differentially expressed between wild type and phyB deficient B. rapa plants. This will ultimately lead to the identification of potential targets for engineering more resource-efficient and higher-yielding crop varieties.

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 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.

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.

Freshwater is one of the most valuable resources in Washington State. In recent decades, water supply has been affected due to climate change and population growth. Understanding changes in water supply and demand is crucial for ensuring an abundance of water for residential, economic, and industrial needs. The proposed research analyzes changes in the streamflow regime of the Cedar and Tolt Rivers which provide drinking water for the greater Seattle area. The main goal is to calculate the water budgets for the Cedar and Tolt watersheds and estimate how the inputs and outputs to these budgets change over the 21st century. An existing ensemble of streamflow projections for the Cedar and Tolt Rivers are used to analyze changes in water supply. The mean streamflow for each month is compared between a 30-year control period (water years 1971-2000) and a 30-year future period (water years 2031-2060). For each of these periods, I determine “optimistic” and “pessimistic” scenarios for the streamflow. For the “drought” month the highest streamflow value is considered as “optimistic”, and the lowest as “pessimistic” since the goal is to assess potential shortages. I use existing monthly demand values provided by Seattle Public Utilities and create different future scenarios, based on the predictions of population and employment growth. Supply and demand values are compared to evaluate (1) the potential for water shortage and (2) water management and conservation methods to satisfy the unmet demand. One potential water management method is the construction of a new reservoir. The results of the research are aimed at helping to inform society and water managers about the potential changes in the water system. Based on this information, they might be able to introduce changes in their future plans to accommodate the predicted needs.

Autism spectrum disorder (ASD) are a group of neurodevelopmental disorders characterized by impairments in social interaction and repetitive behaviors. One of the most common mutations leading to ASD is 15q11-q13 duplication, a CNV mutation where extra copies of a chromosomal region are expressed. The major gene within this region is ube3a. My lab has generated a mice model with increased copies of this gene and demonstrated a novel deficit in the mTOR/AKT signaling pathway. Other mice models of autism have exhibited deficits in this pathway and have rescued behavioral deficits with a drug, rapamycin. Rapamycin is an inhibitor of a key protein of the mTOR/AKT pathway suggesting a similar behavioral rescue could be observed with ube3a transgenic autism model mice. Rapamycin is administered to ube3a transgenic mice to normalize deficits in social interaction and repetitive behavior, two main behavioral hallmarks of autism. Mice are assessed using a three-chamber social interaction and repetitive self-grooming test. Successful behavioral rescue by rapamycin would be seen as increased social interaction and decreased repetitive grooming, similar to behaviors seen in wild type control mice. This would suggest that therapeutic treatment of the mTOR/AKT signaling pathway could be a viable target for patients with 15q11-q13 duplication.

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.

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.

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.

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.
 

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.

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.

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.

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.

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.

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.

Systematic measurements of the resistivity, susceptibility, and quantum oscillations are presented for single-crystal samples of the electron/hole-doped RAgSb₂ (R=Gd,Y,La). Doping the parent compound LaAgSb₂ with Gd and Y explores the effect of hole doping and electron doping the crystal. La_1−xGd_xAgSb₂ exhibits anti-ferromagnetic ordering around 14K, while La_1−xY_xAgSb₂ exhibits charge density wave ordering. This entire doping sequence is likely to create two quantum critical points related to these charge density waves and anti-ferromagnetic states. Such quantum critical points have been linked to high temperature superconductivity in cuprates, so the study of the similar RAgSb₂ crystals may lead to further insights about superconductivity. We use measurements of resistance versus temperature, magnetic susceptibility, and quantum oscillations to explore the effect of the chosen doping sequence. Part of this phase diagram has been determined, and no superconducting phase of RAgSb₂ has been found yet, but further doped crystals with finer spacing need to be grown to resolve the quantum critical points of interest. In addition to superconductivity, quantum oscillations in the crystal lattice are used to track changes in the material’s Fermi surface and effective mass. These oscillations are associated with the Landau quantization of electronic energy in an applied magnetic field. Magnetic-susceptibility data is also studied to locate the divergent temperature of the crystals follwing the Currie-Weiss fit.

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.

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.

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.

The relationship between greenhouse gas emissions and climate change and the dangers of global warming are widely documented. The 2030 Agenda for Sustainable Development was signed by all United Nations Member States in 2015 and calls for the “widest possible international cooperation aimed at accelerating the reduction of global greenhouse gas emissions” with the aim of “holding the increase in global average temperature below 2 °C”. What role do counties have in reducing greenhouse gas emissions? This project aims to develop a granular model of carbon storage and flux in Multnomah County to inform policy interventions that bring the county closer to meeting the goals outlined in the 2050 Climate Action Plan adopted by the City of Portland and Multnomah County in 2009 with a goal of reducing community-wide greenhouse gas emissions 80% by 2050, with a more ambitious goal of being a net-zero emitter of greenhouse gas. One of the first steps in developing a jurisdictional level greenhouse gas accounting is an inventory and projection of carbon stock change. Our study hopes to assess the feasibility of various methods in predicting carbon storage and flux on forested lands in Multnomah County, compare our results against Forest Inventory Analysis (FIA) estimates and gain a better understanding of carbon storage and flux as it relates to land ownership and management on public and private forest lands.

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. 

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.

Recent studies like the Coupled Model Intercomparison Project Phase 5, or CMIP5, have sought to quantify how atmospheric variables will change due to climate change. Even from decades of rigorous study, it is still uncertain how cloud feedbacks will respond to a warming climate. However, it is possible to try and minimize this uncertainty in part by examining deep convection, and specifically anvil clouds, in the Tropical Pacific. Anvil clouds are not simulated well by the current generation of climate models, but by studying both large scale motions and small scale, local cloud structural evolution, Professor Hartmann and I seek in this study to determine the underlying mechanisms of the differences in vertical cloud structure in the Eastern and Western Pacific. I use the ERA-Interim, CloudSat, Calipso, and CMIP5 datasets in addition to climate model output from the Community Earth System Model (CESM) to analyze differences in cloud structure and model output. This is important work, because reducing uncertainty in an era of global warming can mean better advanced warning systems and more informed, ethical policy decisions moving forward.

In the last 30 years temperature has risen 0.6°C per decade in high latitude regions, twice as fast as the global average. This extreme warming is causing perennially frozen ground (permafrost) to thaw, thereby changing subsurface hydrology and exposing previously stored, deep millenial-aged soils to microbial activity. These changes are stimulating greater organic matter mineralization and emissions of potent greenhouse gases (GHG), carbon dioxide and methane (CO₂ and CH₄). The magnitude of soil carbon mobilization is poorly contained, in part because it is unclear what fraction of GHGs are emitted to the atmosphere directly, versus released to above ground aquatic networks. To better define the role of streams in the changing arctic carbon cycle, we explored headwater stream carbon chemistry in 10 individual catchments situated in a remote and understudied subarctic landscape of interior Alaska. We found an unexpected, positive relationship between CO₂ and CH₄ across streams, with concentrations peaking in the summer for CO₂, and fall for CH₄, suggesting stream emissions peaked when soil active layers were deepest and permafrost carbon layers were most hydrologically engaged. The positive relationship between surface water temperatures and the concentration of each gas reflected these strong seasonal shifts in stream GHG content. Organic carbon content in stream water was also linked to CO₂ but not CH₄, indicating potential differences in sources and sinks of each GHG that are currently being explored with ongoing stable isotope analyses. Taken together, our findings show that closer-than-expected coupling of CO₂ and CH₄ may make some streams much greater emissions hot-spots than others, and that accounting for seasonality is critical for understanding the greenhouse gas budget of individual streams. 

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.

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.

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. 

Genes encoding the RNA portion of the ribosome (rDNA) are present in essentially all eukaryotic genomes as tandem repeated arrays. In humans, rDNA copy number is highly variable and an undervalued potential source of genetic disease. Changes in rDNA copy number can occur through DNA breakage and repair as well as through errors in DNA replication. High transcriptional activity at the rDNA locus poses challenges for replication; all tested eukaryotes have evolved replication fork barriers (RFBs), ensuring that replication machinery does not collide with transcribing RNA polymerases. In yeast, the RFB is a specific sequence to which the protein Fob1 binds, blocking replication forks that converge with transcription. Mutants lacking Fob1 have greatly reduced variation in rDNA copy number. There are currently two models to explain how Fob1 binding to the RFB produces rDNA copy number instability. One model suggests that binding of Fob1 actively recruits DNA break and repair machinery which induces recombination between rDNA repeats. Another model proposes that the stalled replication fork at the RFB is inherently fragile, increasing the likelihood of breakage. To distinguish between these two models, I am generating yeast strains where Fob1 binds to the RFB but does not arrest forks. Using CRISPR/Cas9 gene editing technology, I am reversing the direction of the RFB in each of the 150 rDNA repeats in yeast to prevent replication fork stalling. By confirming the absence of replication fork stalling and determining whether rDNA instability has also been reduced, I can distinguish whether Fob1 binding to the RFB in the absence of fork blocking contributes to rDNA copy number changes. Clarifying involvement of the RFB in rDNA copy number changes will additionally provide insights into the connections between transcriptional activity, replication fork stalling and genome instability.
 

Hybrid vigor or heterosis describes superiority of a hybrid compared to its parents; however, the genetic mechanisms underlying this phenotype remain largely unresolved. One potential mechanism is loss of heterozygosity (LOH), a process where there is loss of one copy of a gene or surrounding chromosomal region. In our previous work, we evolved hybrids between two species of yeast, Saccharomyces cerevisiae and Saccharomyces uvarum - which differ in their temperature preference - by growing them in a chemostat at different temperatures in phosphate limited media for several hundred generations. We repeatedly observed LOH events in these hybrids in response to changes in temperature. Each LOH event incorporated the gene region encoding the Pho84 membrane bound inorganic phosphate transporter protein on chromosome 13, which is important when phosphate is limited in the environment. These repeated LOH events all affect fitness based on environmental temperature; however the events span various lengths with some as short as a few kilobases and others as large as 200 kilobases. Because they are different in length we also know that they include different numbers of genes. To investigate whether these varying LOH lengths may include other genes that affect hybrid fitness, we have used CRISPR/Cas9 to create double strand breaks at specific sites along the S. cerevisiae chromosome 13, resulting in DNA repair using the S. uvarum chromosome as a template and formation of LOH events of different lengths. Our aim is to create a pool of hybrids with varying LOH tracts and let them compete in a phosphate limited environment to assess the relationship between the different LOH regions and fitness. This will allow us to narrow down genes that may be responsible for temperature sensitivity or that contribute to higher hybrid fitness in organisms that are heterozygous or homozygous.

Different phenotypes of normal cells may influence genetic and epigenetic profiles and tumorigenicities of their transformed cells. The current study presents a comprehensive analysis of mutations in the whole mitochondrial genome for different immortalized (pre-neoplastic) cell types, which were derived from normal breast epithelial cells with two different phenotypes (stem vs non-stem). Duplex Sequencing, which shows the lowest error rates among currently available DNA sequencing methods, was applied to investigate rare and subclonal (low-frequency) mutations as well as homoplasmic (high-frequency) mutations. We found that the vast majority of mutations in the cells occur at low-frequency and are not detectable by conventional DNA sequencing methods. The most prevalent mutation types are C>T/G>A and A>G/T>C transitions. The overall frequencies of rare and subclonal mutations are significantly lower in stem cell-derived immortalized human breast epithelial cells (SV1) than in non-stem cell-derived immortalized human breast epithelial cells (SV22). The decreased mitochondrial mutagenesis of SV1 cells occurred mainly in the noncoding RNA region (rRNA and tRNA) of the mitochondrial genome. In addition, the predicted pathogenicity for rare and subclonal mutations in the tRNA region was significantly lower in SV1 cells than in SV22 cells. Our findings suggest that different phenotypes of normal cells lead to distinctive mitochondrial mutation profiles of immortalized cells. The identified mutation spectra and mutations specific to stem (versus non-stem)-derived immortalized cells have implications in characterizing heterogeneity of tumors and understanding the role of mitochondrial mutations in immortalization and transformation of human cells.

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.

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.

In order for multipotent stem cells to properly differentiate into specialized cells, specific genes must be expressed at a specific time and amount during development. Many of the factors that regulate expression have been identified; however, it remains unclear how they work together to control the timing and amplitude of gene expression. Non-coding DNA elements, known as enhancers, can increase the the likelihood of transcription of a gene by integrating signals in the cell to provide regulatory logic for gene regulation. To understand how enhancers tune gene expression timing and amplitude during development, our lab has generated a transgenic mouse in which each of the two copies of the T-cell identity gene, Bcl11b, have been tagged with distinguishable fluorescent reporters, providing a sensitive readout for gene activity at the single locus level. Bcl11b turns on during T-cell development, and its activation executes a developmental switch from a hematopoietic stem cell to a T-cell committed progenitor. There is a non-coding region far downstream of Bcl11b which harbors a cluster of putative enhancers. To interrogate the function of individual candidate enhancers, we use CRISPR/Cas9 targeting to generate specific genomic deletions in T cell progenitors. From our preliminary experiments, we have shown that cutting off the entire enhancer region completely inhibits the expression of Bcl11b entirely compared to when we cut out only an individual enhancer peak which only partially inhibits it. This is promising because it shows that we have found an enhancer that controls the probability of activation while not being necessary for the activation of Bcl11b. This work will reveal the cis-regulatory logic that underlies the control of a master lineage-specifying gene. This better understanding will help us identify new strategies to control the expression of master regulatory genes for cellular reprogramming.

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.

Our laboratory, GEMSEC, which operates at the intersections of biology-materials-informatics fields, is developing materials and methods to seamlessly bridge biology with solid-state devices towards establishing the foundations of future hybrid devices, e.g., bioelectronics, bionanosensors, and biomolecular fuel cells. Towards this goal, we use the smallest functional biomolecule, peptide, combined with the smallest functional solid in materials science, i.e., single atomic layer materials. Herein, we study the interactions of genetically designed peptides with surfaces of graphene, a semimetal. A phage display library-selected peptide, GrBP5, is a graphene-binding dodecapeptide that has a wide range of applications. Since peptides have short amino acid sequences, they are known to display intrinsically disordered structures in solution. Here we study the conformational propensities of the WT peptide and its rationally designed mutants under a variety of experimental conditions (pH, concentration, temperature, time, etc.) to understand their behavior on solid surfaces that includes surface phenomena from binding, surface diffusion, intermolecular interaction and self-organization. Molecular dynamics (MD) simulations of WT-GrBP5 and its mutants have been completed in water and on graphene for 200ns, 20,000 timeframes under different temperatures and pH values that range from 5 to 55 oC and 3.5 to 10.0, respectively. The analyses, including the RMSD maps and Ramachandran plots, show explicit folding propensities, stable and unstable structures, for a given sequence under a given set of experimental conditions. The computational modeling, backed up by experimental validations carried out under similar conditions, are leading to the design of novel peptide sequences with predictable behavior under desired environmental conditions. The fundamental understanding of the differences in conformational behavior of GrBP5 mutants are now extended to other solid-binding peptides that are specific to semiconductor and insulator single layer materials providing the much essential information for the design of hybrid devices of the future. The research supported by NSF/DMR-DMREF program.

The Genetically Engineered Materials Science and Engineering Center (GEMSEC) labs revolve around designing and synthesizing genetically engineered peptides for inorganic materials (GEPIs). Experimentally characterizing GEPIs can be slow, and therefore a computational method that can predict functionalities would greatly accelerate the development of bio/inorganic interface design and implementations. The Pairwise Similarity Score is a proven predictor of relative binding affinity and has been used to predict GEPIs specific for quartz, gold, hydroxyapatite, and MoS2. In previous work, a similarity matrix was updated based on whether a peptide (Strong or Weak binding) had higher similarity to strong peptides and less similarity with weak peptides. Our method instead obtains the most ideal similarity matrix via stochastic gradient descent to best predict the relative binding affinities. The values in an amino-acid similarity matrix are randomly initialized and subsequently updated until convergence by minimizing the errors in binding affinity prediction. 5-fold cross-validation is used as a metric to evaluate performance on test data. We expect to observe higher predictability with this learned similarity matrix than using a literature matrix. This would compound work done by the high throughput screening, confirming count numbers observed during phage display are correlated with their actual binding affinity, while using a novel large dataset to test known successful predictive models. All in all, the work carried out in this project accelerates the development pace of bio-nano-devices of the future. The research is supported by NSF/DMR-DMREF program under the Materials Genome Initiative.

The goal of this project is to encode peptides, i.e., short amino acid sequences, in terms of smaller molecular components such as their VSEPR (Valence Shell Electron Pair Repulsion) features for training interpretable models with reasonable predictability of functionality. This enables us to go beyond the limitations imposed by treating peptides as sequences of letters, thereby enabling a generalized encoding that works for lipids and other biomolecules that are of interest in a comparable scenario. Biological processes are rarely disjoint and often complicated which lends justification to our approach. Current methods for binding affinity prediction, such as one-hot encoding, where letter-based sequences are converted to a binary representation, do not take into account molecular level features. Combined with a neural network, such a simple encoding is better at predicting affinities of short peptides, e.g., 5-9 Amino acids long, but with an increase in length from 9 to 10, the predictability suffers an exponential drop. Several alternatives have been employed in literature, but they also suffer from the negative impact of distal effects. In the VSEPR approach, encoding peptides in terms of their component functional-group geometries enables us to encode the actual physical length, rather than the number of amino acids. This leads to an overlap between peptides of different length, thereby reducing the fall in predictability. In this encoding, we create 5 channeled matrices with each channel corresponding to ‘central-atom connectivity’, ‘bond-types’, ‘bond-lengths’, ‘bond-angles’ and ‘lone-pairs’ that is then fed through a Deep Residual-Neural-Network. The metrics used to evaluate the models are Pearson-Correlation, Spearman-Rank-Correlation-Coefficient, and Area-under-Receiver-Operating-Curve. With this technique, we were able to consistently predict binding affinities of peptides without an appreciable loss between 9 or 10 length peptides. This method would allow one to create length invariant encodings, not limited to just peptides, significantly improving the practicality of using such a model. The research is supported by NSF/DMR-DMREF program under Materials Genome Initiative.

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.

The foraging patterns and populations of predators can provide a better understanding of the nutrient dynamics in ecosystems. Brown bears (Ursus arctos) are a particularly difficult species to study. However, brown bears are a key predator species to study due to their close relationship with Pacific salmon (Oncorhynchus spp.) populations. Noninvasive methods like hair collection and camera traps are emerging as effective ways to study brown bear populations, diet, and behaviors. This study aims to determine whether the use of these methods in the Wood River system (Aleknagik, AK) are unbiased and characteristic of the resident brown bear population. The data used in this study are part of a long-term study (beginning in 2012) taking place in this area involving brown bear predation on sockeye salmon (Oncorhynchus nerka) and other population studies. Using video footage from the 2016 field season, this study analyzes brown bear reactions and avoidance of the barbed wire used to collect hair samples. Expected results are a higher frequency of wire avoidance in adult bears, single bears, during daylight, and equal frequency of avoidance between creeks. The results of this study can establish whether these methods of studying bear populations are accurate, or if they need to be modified to collect more inclusive and representative data. Further study is required to develop a comprehensive appreciation for brown bear populations, habitat use, and other behavioral patterns.

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.

Many environmental factors can influence foraging strategies of predators, such as availability of prey sources. Brown bears feed on many species of animals and plants but Pacific salmon are especially important to their diet. For example, brown bears in the Lake Aleknagik, Alaska ecosystem forage on sockeye salmon as well as other food items. Direct observations and motion-activated cameras have documented bears foraging on salmon but do not reveal variation among individual bears. This study used the distinctive carbon and nitrogen isotope signatures in salmon as a way to assess brown bear diet by processing samples of bear fur collected during the salmon spawning season. As fur sample collection is noninvasive, it provided the opportunity to “resample” bears (individually identified by DNA analysis) multiple times within a season and over the course of multiple seasons. This study demonstrated how various factors, including salmon availability, gender, and location, influence the extent of bear consumption of salmon over time. Understanding the association between brown bear diet and these factors can provide better insight into the importance of both sockeye salmon and alternative food sources to brown bears.

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.

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.

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.

All over the globe, an escalating number of people are developing distressing sensitivities to our environment’s everyday intoxicants. Multiple chemical sensitivity (MCS)—also termed idiopathic environmental intolerances (IEI), among other names—is an acquired disorder characterized by a wide range of symptoms and reactions to low-level chemical exposures. Studies conducted in Japan, USA, Sweden, and Denmark found that 12% of the population has been diagnosed with chemical hypersensitivity, while total underreported prevalence is estimated between 15% and 27%. More importantly, research states that prevalence has increased by 300% within the past decade. People diagnosed with MCS experience a range of symptoms, examples including asthma, heart irregularities, headaches, dizziness, confusion, skin irritation, and fatigue. Abundant in our everyday environment, commonly reported triggers include pesticides, building or renovation materials, car exhaust and chemical smog, smoke, perfumes and fragrances, and cleaning supplies, among others. With a myriad of proposed titles, contrasting research perspectives and approaches, and a staggering dissensus on physiology and diagnosis, it is critical that we compare and contrast the existing literature by geographical region. Three primary research hubs generate the majority of contrasting MCS research; these regions include the United States and Canada, Scandinavia, and Japan. The problematic inconsistencies include (1) a lack of consensus definition or diagnosis for the illness, (2) varying perceptions on pathophysiology, and therefore (3) contrasting treatment strategies. This research aims to examine the global, contrasting research approaches, proposals for treatment or action, and subsequent healthcare experiences within the geographical regions of focus. Preliminary results suggest that inconsistencies in the medical diagnosis of MCS lead to deficiencies in research and ineffective healthcare. By any given title, the escalating number of chemically hypersensitive patients is a growing global health concern. Integrating the globally contrasting approaches and diagnosis criterion is the first step to developing efficient healthcare strategies.

Overdoses induced by fentanyl-laced cocaine are skyrocketing today. Meanwhile, in 2017, cocaine was reported as the fourth most prevalent substance used on college campuses. Even more alarming, research shows a modest decline in young people’s disapproval and perceived harmfulness of experimental cocaine use. Favorable depictions of cocaine use in the media contributes to these trends today: the entertainment industry continues to advertise cocaine as a drug of privilege, partying, and success. Conversely, studies investigating Adderall use found college students view cocaine use negatively. Students harshly judged their peers who exposed themselves to cocaine’s hazardous nature and high risks. This contradictory evidence makes it difficult to judge how problematic college students’ views on experimental cocaine use may be. This study aims at sorting this puzzle. The project tests the hypotheses that students think one-time use results in more benefits than risks to the individual. To assess this hypothesis, I use a web-based survey adapted from the so-called “prototype-willingness model” (PWM). The PWM is built on the idea that young people share very clear social images of risky behaviors. The favorability of these images is positively correlated with willingness to engage in risky behavior. Willingness, rather than planned intent, is the primary factor responsible for engaging in risky behaviors if presented with the opportunity. I examine the social image of experimental cocaine use and its favorability in order to predict willingness to use. Predicting how a college student may react when given the opportunity to use is crucial for future prevention planning, as cocaine use is a more pressing issue than ever.

 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.

Individuals with ambivalent and avoidant adult attachment styles are more likely to use negative coping strategies such as denial and disengagement, while individuals with a secure adult attachment style are more likely to use positive coping strategies such as reappraisal and support seeking. Certain negative coping strategies are linked with mental health problems such as depression and anxiety. Most research regarding the relationship between coping strategies and adult attachment style has been done on undergraduates and veterans. No research to date has examined gender as a moderator of the relationship between adult attachment style and coping strategies. However, research suggests that both coping strategies and adult attachment styles vary by gender. In the present study, a series of multivariate regression analyses were conducted to determine whether gender moderated the relationship between close, and anxious adult attachment styles and emotional support seeking, and substance abuse coping mechanisms. Participants (N=385) completed self-report measures of coping strategies and adult attachment styles online. This project may reveal that gender changes the relationship between adult attachment style and coping strategies. This information may help inform psychological interventions for individuals with maladaptive coping strategies and improve our ability to predict who might engage in maladaptive coping strategies.

Scholars recognize that politicians’ perceptions of their electability influence their home style, or the way in which they present themselves to their constituents. Marginality, or the proportion of a politician’s co-partisans in the electorate, is common indicator of electability. However, marginality fails to capture how polarization of the electorate augments politicians’ vulnerability. This study introduces a new indicator of electability that captures statewide polarization in the electorate. Building off the finding that more marginal Senators emphasize support for appropriations to build non-partisan support, I expect that Senators in more polarized states will emphasize their support for appropriations after controlling for marginality. Appropriations credit-claiming builds non-partisan support without alienating more partisan voters. I employ multilevel linear regression analysis to examine the relationship between state-level partisan polarization and topic expression in Senate press releases systematically. A positive relationship between partisan polarization and appropriations credit-claiming may reveal a mechanism by which polarization paradoxically minimizes the partisan content of Senators’ home styles.

Since the 1920s, plea bargaining in the United States criminal justice system has become status quo. Today, over 95% of federal cases have resulted in plea bargains and never been tried in court. The power of the prosecutor within the legal system has also increased substantially over the last century leading many scholars to believe that the proliferation of plea bargaining is a direct result of heightened prosecutorial power. Prior literature has addressed the increased power of the prosecutor and the need for reform if plea bargaining rates are to change, but has not yet provided an empirical observation as to whether prosecutorial reform makes a significant impact in plea bargaining. In this paper I theorize that the prosecutor’s discretion over exculpatory evidence plays an integral part in states’ reliance on plea bargaining and that states that attempt to reign in prosecutorial power experience reduced rates of pleas. To test this theory systematically, I have run a multivariate analysis at the county-level to compare rates of plea bargaining across states that have reformed prosecutorial discretion and states that have not. If states with a model rule suppressing prosecutorial power show a statistically significant difference in plea rates, criminal justice reform advocates should turn their attention to prosecutorial reform.

For this project, I examine why the majority of white women voted for Trump in the 2016 election, a fact that came as a shock to many observers. However, with few exceptions, white women have been shown to support conservative candidates in presidential elections since the 1950s. Yet, Donald Trump’s election can be considered unique as he was still able to gain most white women’s support despite his displays of various behaviors that could be regarded as overtly sexist. In this research design, I analyze white female voters using data from a 2016 Pilot Study by the American National Election Survey and hypothesize that racial resentment and internalized sexism are the primary factors that drove white women to support Donald Trump, controlling for partisanship, economic anxiety and other factors that might influence vote choice. I employ linear regression models using R programming software to examine a relationship between 2016 vote choice, racial resentment and internalized sexism systematically. In doing so, my analysis takes an intersectional approach, where both race and gender dynamics are useful in providing an explanation for white women’s support for Trump.

One of the most common questions that scholars of democratic theory address is how to best allocate and balance power across the different structures within a government. Historically, many theorists and philosophers have postulated that structures with separation of power are more effective at resisting tyrannical rule. Though researchers have established the effects of an imbalance of power between two branches of government, no study has attempted to systematically account for the relative balance of power among all three branches working in tandem or develop empirical metrics to this end. In this study, I theorize that designing separate branches of government that are equally strong strengthens conflicts across institutions, which ultimately leads to more robust protections against tyranny. I evaluate this model quantitatively by developing and introducing a new measure, the Separate Powers Index (SPI). My SPI assesses the balance of power between the three branches of government as postulated in a sample of 130 of the world’s constitutions. Using multivariate regression methods, I compare the SPI with a cross-national index of free expression in a cross-sectional analysis during the year 2008, I can systematically examine whether there is a relationship between structural provisions of institutions that distribute power and their outcomes to protect their citizens. In addition to providing a novel measure of tripartite power balance in national constitutions, the result of this study has a large impact on all scholars of constitutionalism and civil liberties.

Although legislative partisanship has traditionally been studied through measures like floor votes or debates, scholars have found that social media also provides a conducive environment for negative and positive displays of party politics. This project codes Tweets from both Washington and Texas State legislators in 2017 as either “partisan” or “neutral” in order to create a proportion for each category and correspondingly identify the extent to which these legislators participate in partisan behavior online. Then, these proportions are compared with an individual legislator’s roll call votes, markers of their general level of polarization, in order to view whether or not they are behaving in a more partisan manner online than their votes would indicate. My paper posits that the unique conditions of social media cause legislators to behave differently, resulting in a comprehensive increase in legislator partisanship. This research holds importance in future studies by shedding light on how social media is used by those in our state governments, especially as it pertains to their party posturing online.

This project deals with human robot-network collaboration for synchronization to desired reference velocities. A human interacts with the network of mobile robots by sending virtual source inputs to the leading robot. The information propagates through the network from each robot sensing its nearest neighbor. This research proposes a visual interface design to develop a real time, wireless communication channel between a human operator and the robot-network. The model developed introduces real time feedback from the human operator via a graphical interface of the relative positions of each robot in the network. The human operator’s ability to move the network cohesively with desired velocity trajectories require rapid information transfer, which is achieved using a delayed self-reinforcement (DSR) technique. We expect the human operator’s ability to move the network cohesively to improve with DSR hence enabling easier operation for the operator. The human-swarm interface designed has applications for semi-autonomous networks such as vehicle platoons. We can improve modern freight transportation safety and efficiency with a human remotely operating a robot-network of trucks.

Robotics combines machining and artificial intelligence to create real world humanoid models for task automation and industrial applications. We have designed an in-house robot prototype having microprocessor controlled motion. The robot has lasers for eyes and has a position sensor with camera attached. We designed the gear box, track assembly and robot parts and have written software to control the motion of the robot. The robot is good model for Roomba like vacuum cleaner. We create random walls using Monte Carlo simulations and used vector directed motion to control its motion for avoiding these random walls that the robot encounters to simulate real world experience. We have also studied robotic arm kinematics, using matrix algebra and trigonometry to help design a robot arm that we can rotate or translate to any point in three -dimensional space. We study both forward and reverse kinematics and have written software for the arm motion. Our studies provide an elegant educational platform for studies of robot motion along with simulating real-world experience.

The ability to eat our meals how and when we want is often taken for granted, but is not a reality for some with limited upper body mobility. Current haptic sensory inputs for autonomous robotic feeding systems are inconvenient and expensive. We propose using GelSight, a fingertip tactile sensor capable of providing rich haptic feedback. Built with silicone and 3D printed parts, GelSight uses a camera to track a grid of dots embedded in the silicone and estimate forces. GelSight is accurate and inexpensive to manufacture and overcomes many of the limitations of currently available and previously tested options. Based on laboratory tests and feedback from potential users we continue to improve our hardware and software, seeking to generalize our solution to any food.

Article 32 of the United Nation’s Convention on the Rights of Persons with Disabilities (CRPD) represents a major innovation in international law by recognizing the human rights of persons with disabilities (PWD) to participate in international development on an equal basis with others. Implementation of Article 32 in policy and practice, however, lag far behind, despite widespread adoption of the CRPD. This report evaluates the dissemination of the inclusive development norm across international development organizations and nonprofits by assessing knowledge of Article 32, understanding of its obligations, and integration of inclusive development practices into organizational policy, priorities, and program implementation. We argue that the obligations of Article 32 have not disseminated, thus excluding millions of PWD from development aid and programs. This failure makes the field of international development exclusive and ultimately discriminatory towards PWD. To test our hypothesis, our research team surveyed international development nonprofits in a major West Coast city to identify the baseline of inclusive development knowledge that most agencies operate with. Our findings are gleaned from a case study of 22+ members organizations of a local membership association of international development organizations headquartered in a major city on the West Coast. We compile our report’s data from a variety of sources: (1) review of international development aid agencies’ published policies, (2) review of organizations’ published education materials and grant proposals, (3) a survey circulated to the 200+ member organizations of a local membership association of international development organizations and (4) in-person interviews with CEOs of several of the member organizations.

New Caledonia is a French collectivity in the South Pacific that transitioned from colony to territory in the 1940’s, like many other former French colonial holdings. However, unlike other overseas territories of France, New Caledonia has been on an unofficial transition towards decolonization that began in 1998 with the Nouméa accords, stipulating a vote to take place in twenty years that would decide whether or not the islands would remain French. Despite a slim loss for independence when this long-awaited vote took place last year in November 2018, future referendums to challenge this decision are on the horizon. The objective of this research is thus to understand why the situation in New Caledonia is so different from that of other French territories. In particular, how do contemporary issues in the archipelago and the question of race complicate the decolonization process? To effectively answer this question, this study will analyze academic literature comprising subjects on foundational postcolonial theory, New Caledonian history, and race in the French–controlled South Pacific. Peculiarities of New Caledonia include its relatively late colonization compared to other French territories and the fact that the native society residing on the island continues to hold a strong presence. These factors along with a turbulent past may explain in part why New Caledonia finds itself in a slow process of decolonization. However, rich mineral reserves and the rise of neocolonialism may also complicate this event. Ultimately, this research hopes to bring a better understanding of New Caledonia to a wider public while serving as a foundation for continuing conversations around neocolonialism and efforts to combat it in the French territories and elsewhere.

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.

HIT-SI, also know as steady-inductive helicity-injected torus experiment, uses three coplanar inductive helicity injectors to form and sustain a spheromak equilibrium. Spheromak is a configuration of the plasma that forms  into a shape of smoke ring and it is a promising approach to nuclear fusion energy based on its long confinement time and the confinment achieved by the self-induced current. This project is centered around data analysis from a new tomography diagnostic system to assess the symmetry of spheromak plasma density while varying the key current drive parameters of the HIT-SI3 plasma physics and fusion energy.  The tomography diagnostic system consists of four toroidal chord fans and three sets of three poloidal fans that provide 3D plasma emission information. Each fan expands from 130 degree wide angle lenses coupled to bundles of fiber optics. The light collected by the fiber optics is split, filtered at 668 nm and 728 nm, and imaged by a high-speed camera. Since the ratio of the 668/728 nm emission has a strong plasma density dependence within the range of typical HIT-SI3 plasma parameters, the 3D emissivity profile constructed by inverting line-averaged emissivity along chords can be related to the plasma density profile. The objective of this project is to find the correlations between parameters affecting wall conditioning and the plasma density profile, then use the results from the analysis to maximize the performance of the plasma toward the goal of improving confinement. The initial analysis will include all available data covering a variety of experimental plasma conditions. After the correlation is established from the initial analysis, a series of carefully controlled experiments will be conducted to test and improve the certainty of the initial results. In the controlled experiments, plasma discharges will be taken under more specific settings so the effects of different conditions on the plasma profile can be isolated and better understood.

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.

The Lyman-alpha power spectrum has previously been used to constrain the Universe’s initial conditions and particle constituents (such as the amount and mass of the dark matter) and the temperature of intergalactic gas (which constrains reionization processes). To further improve these constraints, we use another Lyman series transition (Lyman-beta). The Lyman-beta absorption cross-section is lower than that of Lyman-alpha so it probes the intergalactic medium at higher densities where Lyman-alpha features are saturated. Therefore, the Lyman-beta forest allows for a better measurement of the slope of the temperature-density relation, allowing additional constraints on reionization and the subsequent thermal evolution. In this work, we present an analysis of the Lyman-beta power spectrum using the VLT/XSHOOTER XQ-100 Legacy Survey.

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.

Current data storage elements have reached their threshold capabilities due to extensive data and limiting size requirements. Digital storage in DNA has aroused considerable interest as the next generation miniaturized high capacity storage device. Deoxyribonucleic acid (DNA) forms the genetic blueprint of life and is the primary carrier of genetic information in living cells and organisms. Data storage in DNA involves encoding of digital binary data into synthesized DNA strands. Here, we employ calculus-based methods to provide a comparative study of data storage capacities of conventional CD ROM and DNA. We use parametric equations to model the spiral structure in CD ROM and double helix of DNA and employ calculus-based methods to study the arc length, curvature and topological properties of DNA. The data storage densities for binary, base 3 and base 4 in DNA are estimated. The calculated data storage densities are found to be in good agreement with reported estimates. Recent studies demonstrate that magnetic nano-knots can be used for data storage. The topological properties of DNA including twists, links and knots thus provide additional attributes which may in future be used for data storage.

The use of magnetic nano-knots and Brunnian links for data storage and communications, makes understanding the geometric and network topology of knots and links very important. Recent reports suggest that DNA and other halogen networks self-assemble into exotic Borromean ring molecular topologies. Borromean rings form a Brunnian link with three rings linked in such a way that no two alone are connected. Only when all the three rings come together does the linkage occur. Borromean links form the current logo of the International Mathematical Union and they display strength in unity. Understanding knots, links and their networking is central to our understanding of DNA, protein folding, polymers and other soft materials. We have used a 3D printer to print and design a Borromean Math puzzle. The puzzle falls apart when a link is pulled out and is an excellent learning tool for studying Borromean link topologies. We use mathematical methods using parametric equations to study Borromean rings and trefoil knots. We wrote computer visualization code using SAGE to display trefoil knots and complex Borromean links for distorted circular, elliptical and other geometries. The SIEFERT surface of Borromean links are sketched using SeifertView and provide an aesthetic 3D view of the rings which can be oriented on a plane. The Seifert surface of a knot is a knot invariant; it is the characteristic of the knot with the knot as a boundary. The adjacency matrix and topological connectivity of the links are studied using vector directed graph models. A computer program is written to unravel the complex linking and intriguing connectivity properties of the trefoil knot and Borromean networks.

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.

This presentation seeks to summarize a solution to helping the visually-impaired navigate new areas. While previous solutions have been relatively successful, many lacked two key features that we hope our solution addresses: being affordable and allowing customization towards those with compounding disabilities. Our solution consists of two main parts: (1) a user-interface created for Fusion 360, a popular 3D-modeling application, that is built upon an existing framework detailed in Hofmann (2018) called PARTs (Parameterized Abstractions of Reusable Things), and (2) an optimization algorithm to generate maps that are tailored for its users. Through PARTs, we developed different variations of modular pieces of map (e.g., roads, buildings, and sidewalks), which increases ease of customization. After the user specifies personal information and preferences through the PARTs UI—such as the width of their finger, their physical limitations, their understanding of braille, and their desired map features—the optimization algorithm will select the best combination of features from the PARTs database for that specific user. At the end of the process, users have a model of a tactile map in Fusion 360 which can be printed out with commercially-available 3D-printers. With 3D-printers becoming more affordable, this solution is significantly less cost prohibitive than other means of generating tactile maps, which required an initial investment upwards of a thousand dollars. Through user studies, we also test how blind users interpret these maps, which helps us guide design improvements in the future. In this presentation, we discuss the efficacy of our solution by comparing it to previous works and detail our plans to improve the system by making the PARTs user-interface more accessible and incorporating user feedback about the map itself. 

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.

Many adults with Autism experience sensory processing sensitivities as a part of their diagnosis. Research shows that 94.4% of adults with Autism report co-occurring sensory abnormalities. These sensitivities can create accessibility challenges for the autistic community, especially for autistic individuals with hypersensitivities. This study will explore how these sensory sensitivities are experienced as barriers to accessing public spaces and the impact that limited access has on quality of life experienced by autistic adults. The author will develop a self-report survey to assess the frequency, diversity, and intensity of these barriers and create a publication which will include the photographs and narratives of the participants experiences of sensory dysregulation as a barrier. The survey and the publication will be reviewed through the process Community-Based Participatory Research (CBPR). Data will be obtained through using photovoice, narratives, and surveys highlighting the subjective experiences that hypersensitive autistic adults encounter in their everyday lives in the public sphere. We anticipate that multiple barriers to access will be reported by participants though we recognize these may differ in form, place, and intensity. The outcome of the proposed study will be used to center the voices of the self-advocating autism community about the barriers they experience daily and to promote policy change to create more sensory friendly public spaces.

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.

Wildfires play a major role in the structure and composition of landscapes and the general ecology of the Pacific Northwest. The Klamath-Siskiyou eco-region in northern California and southern Oregon has been experiencing an increase in the frequency, scale, and intensity of wildfires in recent years. Understanding the effects of wildfires on small mammal communities is an important, yet understudied, aspect of the response of wildlife to wildfires. In 2014, two wildfires burned areas on and adjacent to a long-term study area of wildlife. We will investigate the effects of these wildfires on the occupancy of small mammals such as Neotoma fuscipes, Glaucomys sabrinus, and Tamiasciuris douglasii, using occupancy analyses of data collected during fall field seasons using track plate stations. The longitudinal data set that we have includes years of data before the fires occurred, allowing us to disentangle any effects of the wildfires from any naturally occurring variation. This research is important in determining what lasting effects these increases in wildfire frequency are going to have on predator-prey dynamics.

Climate change will have significant impacts on Pacific Northwest hydrology. Rising temperatures and shifts in precipitation will lead to changes in snowpack, runoff, and streamflow timing, impacts that will have implications for water and environmental resource management. The Pacific Northwest’s Green River Basin is a valuable water supply and provides habitat to several cold-water aquatic species including the threatened Puget Sound Chinook salmon, but also has a major flood risk. Streamflow in the basin is seasonally regulated for flood prevention and ecosystem health, and changes in the annual hydrologic cycle will have consequences for flood risk and ecosystem habitat. To investigate the implications of climate change on streamflow, snowpack, and stream temperatures in the Green River Basin, climate sensitivity analysis and future climate impacts are simulated using two watershed models with varying spatial and process complexity: 1) the conceptual Snow17/Sacramento Soil Moisture Accounting model (Snow17/Sac) implemented with two elevation zones and 2) the process-oriented Structure for Unifying Multiple Modeling Alternatives (SUMMA) model implemented using twelve USGS HUC-12 subareas. Stream temperature climate sensitivities are modeled using the River Basin Model (RBM) Semi-Lagrangian Stream Temperature model. Future climate change impacts on basin hydrology and stream temperatures are assessed using an ensemble of statistically downscaled climate projections from 34 Global Climate Models (GCMs) run as part of the Intergovernmental Program on Climate Change 5th Assessment Report. The future warming scenarios show moderate changes in streamflow volume, shifts in streamflow timing, and reductions in snowpack, which differ depending on the watershed model. The presentation provides key results and findings from the study, and comments on potential impacts on stream temperature and fish.

Diabetes and cardiovascular disease play a significant role in disease and mortality in the US, especially among underrepresented groups. Lack of physical activity and unhealthy eating can lead to cardiovascular disease (CVD), diabetes, and other adverse health outcomes. This project will utilize community based participatory research to develop a wellness program from American Indians in San Diego County. This will be done through conducting focus groups, and interviews with community members and through conducting surveys on health and wellness. Further, a wellness program will be developed from community feedback. We expect to observe an increase of physical activity, better diet, and higher knowledge about healthy behaviors with the program.

Hybrid landscapes are the colonial, regulated plots of land (like reservations), that Native peoples have adapted to ultimately create new senses of Indian self-hood, through their ability to survive and thrive, despite the colonial process that displaces them to those regulated lands. The vanishing Indian narrative is one example of the colonial violence enacted through those regulated spaces as Western institutions and discourses confine Native peoples to notions of the past and primitivity, to ultimately claim that they have vanished in the wake of modernity. And while Western museums have helped perpetuate the vanishing Indian narrative, tribal museums have combated this harmful narrative. Museums, as institutions that present knowledge to the general public, are sites that can present counter-narratives and tribal communities can use these spaces to present proper representations of themselves. One such tribal museum is the site of my research project. The Suquamish Museum is located on the Port Madison Indian Reservation and opened in 1983. This research is interested in how this museum has made, and continues to make, a difference for the Suquamish community and particularly analyzes the Museum’s relationship to the reservation. Over several months I have spent time in the Museum and researched the Museum’s history through its grants, reports, programs, and exhibits. I argue that, as an institution that has continued to adapt to the community’s needs, the Suquamish Museum has facilitated the construction and continued development of the reservation as a hybrid landscape through owned representation as a means of confronting the vanishing Indian narrative, thus perpetuating Native agency and sovereignty. This research is important because looking at the Suquamish tribe as its own entity, with their own representations, addresses the colonial violence that treats all Indigenous peoples as homogenous, unadaptable peoples from the “past,” ultimately highlighting their agency as place-makers.

 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.

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.

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

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

Tuberculosis (TB) kills more than one million people annually. Bacteria of the Mycobacterium genus, including M. tuberculosis, build a complex cell wall containing mycolic acids. This cell wall is difficult to penetrate, so specialized antibiotics are needed. Even with newly developed drugs, bacteria adapt quickly and exhibit resistance at an alarmingly rapid pace. One adaptation that allows the community to survive is production of biofilms. Formation of biofilm is one of many quorum sensing behaviors known in pathogenic mycobacteria. This additional layer surrounds a microenvironment where bacteria can thrive with a very low concentration of antibiotic. Thus, one alternative method to treat TB is to control biofilm formation. In this research, a set of marine bacterial strains, including several bacteria that exhibited swarming behaviors and several from the same environmental samples that did not, were cultured, extracted, and analyzed by 1H NMR and LC-MS as well as in newly-developed biofilm and growth inhibition assays. Initial results showed one group of bacteria produced an organic compound that induced biofilm production in mycobacteria. This was an unexpected result. One representative strain producing a strong biofilm inducer was grown on large scale (10L) then extracted using progressively less polar eluents on a reversed-phase SPE column. The biofilm-inducing fraction was then separated using flask column chromatography. One major component was analyzed spectroscopically using 1D and 2D NMR techniques along with Mass Spectrometry. This compound could result in a strategy to interfere with biofilm formation in mycobacteria, thus making antibiotics more effective.

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.

Glutaredoxins (GRXs) are small oxidoreductase enzymes that can reduce disulfide bonds in target proteins. The genome of the model plant Arabidopsis thaliana has more than 30 GRX genes, but the biological function of most of these GRXs is unknown. We previously found that a small group of Arabidopsis GRX genes is specifically activated by nitrate, a common source of nitrogen in the soil. In order to better characterize the function of one of these nitrate-regulated GRXs, AtGRX660, we generated transgenic Arabidopsis plants that continuously overexpress the AtGRX660 gene. We isolated RNA from 12 independent transgenic lines and quantified AtGRX660 mRNA levels via real-time reverse transcriptase PCR. Three elite lines displaying >100-fold increase in basal AtGRX660 transcript levels were selected for further analysis. AtGRX660-overexpression lines and wild-type plants were grown on soil in a controlled environment growth chamber for characterization of shoot phenotypes, and on vertically-orientated plates of plant growth media for characterization of root phenotypes. All AtGRX660-overexpression lines displayed a dwarf shoot phenotype, with significant reductions in shoot biomass, total leaf area, and silique length compared to wild-type plants. In addition, root system architecture was highly altered. While primary root growth was normal in the transgenic plant lines, lateral roots were almost completely absent. Phase contrast microscopy demonstrated that lateral root primordia develop in the transgenic lines, but these primordia do not elongate and emerge from the primary root. Overall, these results suggest that AtGRX660 acts a negative regulator of shoot organ development and inhibits lateral root elongation. Our findings could have agricultural relevance in plant drought tolerance, since AtGRX660 differentially affects primary root system growth (root system depth) and lateral root system growth (root system breadth).

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.

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.

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.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) have great potentials in biomedical research and can be used extensively in drug screening and heart simulations. To understand the cardiomyocytes, we need to perform functional analysis on these muscle cells. Therefore, we need a simple, controllable, yet biocompatible and high throughput tool to measure the cellular traction force. At the Sniadecki Lab, we are developing a new technique to measure the force generation of hiPSC-CM: dotted traction force microscopy platform. To create the platform, fluorescent proteins were first absorbed to a dotted polydimethylsiloxane (PDMS) negative and stamped onto a polyvinyl alcohol film. The film was then transferred to a soft PDMS substrate and subsequently dissolved using phosphate buffered saline solution while the patterned fluorescent proteins stained the substrate. Since the stiffness of the soft PDMS substrate is known, the force generation of the cardiomyocytes can be calculated in real time by optically tracking the deformation of the fluorescent dots. Currently, we are able to manufacture the platform with high fidelity and uniform alignment with a production time of less than 2 hours. Moreover, the cardiomyocytes can fully spread out to their in vivo state on the substrate which ensures the force measurement is valid and accurate. Potentially, this method is not limited to cardiomyocyte research and can be applied to study the interaction between force generation and cell performance of other cells. We are also exploring the possibility of automated manufacture and integration with 96-well to enable mass production.

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.

Auxins are a class of bioregulatory hormones which impact nearly every aspect of plant growth and development. Indole-3-acetic acid (IAA) and one of its corresponding receptors (TIR1) have been shown to be involved in seed germination, lateral root formation, stem elongation, fruit set and development, along with numerous other developmental processes. In an effort to more effectively study auxin-dependent pathways, Torii et al. developed a synthetic version of the IAA/TIR1 receptor pair which was shown to act independent of the endogenous pair in Arabidopsis. Here, I extrapolate our synthetically engineered auxin-receptor pair into a model system with agricultural and environmental implications (e.g. Solanum lycopersicum- tomato) and aim to test whether we are able to 'hijack' endogenous auxin signaling in tomato to precisely modulate auxin-dependent, spatiotemporal developmental outcomes. These findings could shed some light onto the vastly complex, auxin-dependent developmental process in Solanum lycopersicum and provide a tool to study auxin's specific role in varying developmental processes such as stomatal formation, leaf morphology, temporal flowering and fruit setting.

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.

Augmented reality (AR) for the consumer market is gaining momentum and public attention. Besides smartphone platforms, early-stage head-mounted displays such as the Microsoft HoloLens are now publicly available. Many compelling uses of these AR technologies are multi-user: for instance, in-person collaborative tools, multiplayer gaming, and telepresence. Although multi-user AR technologies enable new forms of interaction, they also raise new security and privacy challenges, not only from untrusted applications but also from other users’ malicious or unthinking behavior. It is imperative that these challenges be addressed while the technology is still new and highly malleable. In this work, I explore emerging challenges in securing multi-user AR content sharing from user-to-user threats. I argue that supporting secure and private AR content sharing when users can augment each other’s reality requires careful consideration of AR’s tight integration with the physical world. I systematize design goals for security and functionality that an AR content sharing module should support, and I design and prototype an application-level module for the HoloLens that meets these goals. By evaluating my module against representative application case studies, I show that it meets desired security and functionality goals flexibly across a range of use cases. I further demonstrate that applications’ content sharing needs can be achieved in relatively few lines of code and with low performance overhead. I am currently converting my research prototype into an open-source toolkit so that developers can address these challenges in practice. This work opens up directions for future research on supporting developers in effectively addressing these issues in practice, including making recommendations on how these underlying paradigms should manifest in user interface design. By building foundations for secure multi-user AR content sharing, my work takes steps toward allowing AR to securely reach its full potential.

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.

Maternal Health is an important topic, especially in developing countries, because of the significant inequality in access to healthcare in places such as the Ivory Coast (West Africa). This presentation presents a one-month research conducted in the Ivory Coast, with the aim of analyzing how sociocultural, political, and historical factors affect maternal health i.e. quality and access to care. To conduct this research the history of the country dating from its independence to his present day were assessed. Secondly, sociocultural factors such as one’s culture norms were also covered by talking to hospital staff and local women about their experiences. Additionally, the political state of the country such as the civil wars that it has endured were discussed. All the data for this project were gathered using ethnographic field research methods such as site visits and key informant interviews with two politicians, two physicians and locals. In order to provide a comparative analysis, the research was conducted in two distinct locations, Korhogo and Abidjan which have differing economic status and government help. Interviews were audio recorded, transcribed, and analyzed to look for common themes around barriers to maternal health. Site visit notes were transcribed and analyzed, and pictures were documented for further descriptive analysis. Key themes from analysis include high healthcare costs and culture barriers as negative impacts on maternal health. The study revealed that when treating a patient, it is important to take into consideration their culture norms and it will also be beneficial to have free care for pregnant women which will in turn hopefully encourage them to seek care. We hope to conduct further research, which allows governments and people to recognize that community health is crucial in healthcare and that breaking the inequitably cycle in access to healthcare is essential.

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.

My research is on the intersectionalities of racism and sexism as they apply to the healthcare of women of color, and specifically that of African-American women’s maternal mortality rate. African-American women die of after-birth complications at a rate that is three times higher than that of White women. I am using Critical Race theory and Intersectional Feminism to analyze how racism and sexism are interconnected, and how they together implicitly bias many healthcare professionals. I am working from the viewpoint that racism is widespread throughout American society, and highly influences the way that people of color, and white people, live their lives. However, I also believe that an intersectional approach is necessary to fully understand the influences on women’s healthcare, and that examining the sexism inherent in women’s care is vital to understanding the full extent of the bias society holds against Black women. I am creating a literature study on the history of bias in the medical system with a focus on historical methods of medicalizing racism, researching the explanation for Black women’s historical distrust for the white healthcare system, and a focus on current research on implicit bias among healthcare professionals. I am hoping to discover whether the underlining differences in Black women’s maternal mortality rate, due to their societal positionality, is being addressed by their doctors in their healthcare strategies. I am hoping to show that a healthcare system which addresses bias and the biological and psychological effects of racism and sexism rather than ignoring them and treating every woman the same is vital to ensuring every woman’s optimal health outcome.

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.

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.

With the global refugee crisis, resettlement agencies do important work to insure successful refugee resettlement. Previous research suggests that some refugee families struggle with segmented assimilation, which is when a child assimilates faster than their parents, disassociating from their culture of origin, creating conflict with their parents. Building on this research, this qualitative ethnographic study investigated segmented assimilation concern among families through semi-structured interviewing. Refugee families and childcare providers for refugee children were interviewed to understand the needs of families in managing segmented assimilation and to gain insight from childcare providers serving those families. While it was hypothesized that families would be concerned about segmented assimilation, the recently arrived families in this study were not experiencing segmented assimilation. This is due to a lack of resources which maintains daily stresses of supporting themselves. The resettlement agency in the city where interviews were conducted solely provided housing and employment placement services, meaning that refugees had no resources for civic engagement, education, community building, and other necessary programs. While families are now physically safe, in terms of not being in a war zone or crowded refugee camp, their lives are still extremely strained, in part due to the lack of adjustment resources. Many families work long hours simply to have enough money to live in their apartment and feed their children. The lack of resources given to resettlement agencies, especially in the recent years under the Trump administration, have profound impacts on the lives of hundreds of refugees that are being resettled, and the thousands more that have not been allowed into the United States due to restrictions under the Trump administration. After refugees move to America, it takes time for them to establish their lives in their host country, and the lack of resources allocated to refugee resettlement impedes this process.

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.

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.

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.

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.

Ischemic preconditioning (IPC) is a robust, neuroprotective phenomenon in which a brief ischemic exposure confers resistance to injury from subsequent prolonged ischemia. Characterizing IPC may provide insight into better treatment options for those at high risk of ischemic stroke. Microglia, the immune cells of the brain, play an important role in the immune response to IPC. Previously, our laboratory found that the type 1 interferon signaling pathway in microglia is important in IPC-mediated neuroprotection. This signaling pathway is dependent upon activation of Toll-like receptor 4 (TLR4) and type 1 interferon receptor (IFNAR1). We hypothesize that in this pathway, damage-induced molecular patterns (DAMPs), which are released by brain tissues under ischemic conditions, activate TLR4 resulting in a signal cascade that activates IFNAR1, leading to phosphorylation of signal transducer and activator of transcription 1 (STAT1). Phosphorylated STAT1 (pSTAT1) then forms a complex with other proteins and induces transcription of multiple interferon-stimulated genes (ISGs). ISG expression alters the microglial phenotype, leading to neuronal and axonal protection against subsequent ischemia-related brain injury. The kinetics of type 1 interferon signaling in microglia are not yet fully understood. We aimed to further characterize this pathway by culturing primary microglia from wild-type mice, exposing them to TLR4 agonists or type 1 interferons directly, and quantifying pSTAT1 levels using flow cytometry at multiple time points. A time course of STAT1 phosphorylation in response to innate immune stimuli will provide a clearer picture of the kinetics of microglial type 1 interferon signaling in the setting of ischemia. These findings will enable us to optimize experimental timing for future experiments involving more complex and physiologic stimuli. Optimization of the kinetics of the pSTAT1 assay will also allow us to investigate how genetic ablation of specific innate immune signaling pathways (like TLR4 or IFNAR1) might modulate the microglial response to ischemia.

Microglia, the immune cells of the central nervous system, are long lived. In mice, microglia have an average lifespan of 15.5 months. When microglia are experimentally depleted from the mouse brain, microglia populations quickly return to steady state levels. The mechanisms of this observed repopulation are unclear. More importantly, the mechanisms of microglia replenishment in the healthy brain are not well understood. The literature supports two competing hypotheses. One is that microglia proliferate simply by dividing. Another possibility is that pools of microglia progenitor cells within the central nervous system divide and differentiate into microglia. I hypothesize that microglia proliferate primarily through the differentiation of progenitor cells. Available data to date suggest CD133 as a potential marker for microglia progenitor cells. In order to study these putative progenitor populations, I used a genetic reporter mouse line in which administration of tamoxifen induces TdTomato expression specifically in CD133-expressing cells. TdTomato, a red fluorescent protein, allows these cells to be visualized under a fluorescence microscope. Importantly, all the progeny of these cells also express TdTomato, allowing us to determine whether CD133 cells generate new microglia over time. After tamoxifen treatment at the age of 10 weeks, mice were sacrificed at three and nine months of age. Brains were fixed, sectioned, and labeled with antibodies to a microglia specific protein and to TdTomato. Daughter microglia that differentiated from CD133-expressing cells express both markers. Using a fluorescence microscope, I identified several microglia daughter cells of CD133-expressing cells. This suggests that microglia populations replenish in the healthy brain at least in part through the division of CD133-expressing cells. We can apply this new knowledge about how new microglia are generated in the healthy mouse brain to further our understanding of how microglia population dynamics are affected in both health and disease.

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.

 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.

Developmental and Epileptic Encephalopathies (DEEs) are a group of severe epilepsy disorders in children and infants characterized by prominent EEG (electroencephalography) abnormalities that disrupt brain function leading to cognitive decline. Identifying genetic causes of DEE is a key step to help researchers develop and personalize medical treatments for affected patients. Approximately 5% of DEE cases are caused by a copy number variation (CNV), where a region of DNA involving a disease gene has been duplicated or deleted. Historically, this type of mutation has been difficult to detect using sequence data. To address this, I have written a multi-step algorithm that analyzes smMIP (single molecule molecular inversion probe) targeted DNA resequencing data for known DEE genes to identify CNVs in patients’ DNA that are potentially disease causing. I have run this algorithm on the large collection of smMIP data for 1158 DEE patients available in the Mefford Lab and identified several potential CNVs. Among these, three CNVs ranging in size from 250,000-2,790,000 base pairs, each involving a DEE gene - GNB1, GRIA2, and UHRF1BP1L - were validated by a second method, array CGH, the current gold standard for CNV validation. To date, the validation rate of high-confidence CNV candidates is 50% or higher. Currently I am expanding the algorithm’s functionality to include the ability to selectively search for single-exon CNVs, which are as small as 500 base pairs, are more challenging to detect, have largely been missed by all CNV detection methods, but could still be pathogenic. To do this, I am leveraging the power of intersecting duplicate smMIP datasets to improve the sensitivity of single-exon CNV detection. As any disruption of a pathogenic DEE gene could be disease causing, inclusion of these smaller CNVs will increase our ability to solve DEE cases and improve patient care.

In recent decades, increased nitrogen (N) pollution in coastal aquatic ecosystems caused by increasing agricultural and urban activities has led to extensive habitat degradation and loss, change in the structure of aquatic food webs, and higher frequency of hypoxia. Nitrogen is ubiquitous in the biosphere, entering coastal environments through multiple pathways including ground- and surface waters, plus atmospheric deposition. The fate of much of the N entering coastal environments is not well established. In particular, the magnitude of N consumed at coastal margins, versus exported to downstream estuaries is poorly constrained. It is widely recognized that inland wetlands are important N sinks, as they are sites of fixation of reduced N to inert dinitrogen gas, however the role of coastal wetlands as N sinks is more difficult to establish due to the dynamic nature of these tidal environments. Here, to better understand the role of coastal wetlands in the global N cycle, we established a high-resolution budget of nitrate (the most abundant form of reduced N) from 9/12/2017 to 10/12/2017 at First Mallard Slough within the Suisun Marsh complex, a brackish tidal marsh in the San Francisco Bay Estuary. We modelled nitrate concentrations at 15-minute intervals using a submersible ultraviolet nitrate analyzer (SUNA), and matched these estimates with simultaneous hydrodynamic measurements of water flux. Data were synthesized in Python to establish 15-minute resolution estimates of nitrate mass exchange, showing that the wetland exported a net total of 2.54 Mg of N as NO₃^2- over the complete measurement period, or 84.6 kg N per day. Contrary to other studies showing wetlands are important nitrate sinks, our result revealed that the Suisun Wetland complex was an important N exporter to the San Francisco Bay Estuary, at least over the period measured here. Longer-term observations are needed to confirm this pattern at a complete annual scale.

Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. The survival outcomes are poor for patients with relapsed and metastatic disease. Embryonal RMS (ERMS), a major subtype of RMS, is driven by genetic mutations in the RAS pathway. Cancer stem cells (CSCs) drive the process of self-renewal to recapitulate the heterogeneity of the cancer and are thought to be responsible for cancer relapse due to their resistance to conventional chemotherapy. In ERMS cells, a population of CSCs has been identified and is believed to play a critical role in tumor relapse and metastasis. A previous screen of all known human kinases identified candidates that played a role in regulating self-renewal of ERMS CSCs. I have prioritized two most promising candidates, ERN1 and MAPK10, for further characterization. I hypothesize that these kinases regulate the self-renewal capacity of CSCs but do not affect growth of non-CSC tumor cells. Using the gene-editing tool, CRISPR (Clustered Regulatory Interspaced Short Palindromic Repeats)/Cas9, I knocked out ERN1 and MAPK10 in ERMS cells and assessed their role in regulating ERMS CSC cell growth and self-renewal. To assess whether the effects of gene disruption are specific to the changes in the CSC population in vitro and in vivo, I used an ERMS CSC reporter cell line that specifically expresses Green Fluorescent Protein (GFP) in CSCs. The ERMS CSC reporter cell lines harboring ERN1 or MAPK10 gene disruption are subjected to self-renewal assays in cultured ERMS cells in vitro and ERMS xenograft model in vivo. My findings will provide new insights into the biological mechanism underlying as well as new potential targets against relapse and metastasis of ERMS.

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

Every year 26,000 pounds of human waste left by Mt. Everest climbers is disposed in pits near Gorak Shep (elevation 16,942ft.), a village close to Everest Base Camp in Nepal. The Mount Everest Biogas Project (MEBP) is working to build an anaerobic digester (AD) adapted to the extreme conditions of Mount Everest to treat this waste. All project materials must be carried by foot, including the biologic seed for starting the reactors. Thus, identification of a near-by seed is a critical step in the project’s success. Archaeal microbial community from five anaerobic digesters in Nepal were profiled. House-hold digesters and a mid-sized municipal digester in Katmandu were compared. The goal was to determine if methanogenic populations critical for establishing anaerobic digestion were similar among the potential seeds. Between 65,511 and 94,602 archaeal sequences were recovered from each sample. The sequences clustered into 580 operational taxonomic units (OTU). Species richness and Shannon-Weaver diversity indices ranged from 238-320 and 2.38-3.03, respectively. Significantly lower proportions of Methanosaeta, an important genus of acetoclastic methanogens, were detected in the municipal AD sample than in household AD samples (31% and 43%, respectively; t-test p=0.05). Conversely, the other known genus of acetoclastic methanogens, Methanosarcina, represented < 0.2% in all samples. Methanogen populations (phylum Euryarchaeota) dominated all samples (73 to 97%). However, household AD samples contained a significantly higher proportion (21% versus 3%, t-test p=0.007) of poorly characterized archaeal phylum with unknown function in anaerobic digesters. Principle Component Analysis (PCA) revealed that 2 of 3 household AD were similar. Thus, while all systems contained the Methanosaeta and other methanogenic species desired for startup of the MEBP AD, continued study of anaerobic digester is needed to understand how microbial communities evolve in response to the extreme temperatures of Mount Everest to assess the prolonged sustainability of the system.

Spatial variation in soil abiotic conditions at plant range limits may be important in determining how plant range limits will respond to climate change. One reason for this is that plants are known to change many characteristics of the soil around their roots in ways that influence the growth of other plants.The range limit of subalpine fir is expected to shift into subalpine meadows as the climate warms. Our goal for this project is to describe the abiotic soil qualities of a subalpine forest habitat and a subalpine meadow habitat on Mount Rainier to explore how these characteristics may affect the predicted range shift. We hypothesize that soils from subalpine meadows will have less organic matter and therefore less phosphorus, a lower carbon to nitrogen ratio, and less water holding capacity than soils from the subalpine forest. We will develop a protocol for measuring water availability and implement it on soil samples obtained from around the roots of subalpine fir trees in both the forest and meadow sites on Mount Rainier. We will use standardized tests to obtain the organic matter and phosphorus measurements. If our hypothesis of lower nutrient availability and water retention in meadow soils is supported, this may suggest that subalpine fir growing in the meadows have a greater dependency on fungal symbionts for obtaining soil resources. This would have important management implications given that suitable fungal symbionts are expected to be rare or absent at range limits.

Fetal Alcohol Spectrum Disorders (FASD) encompass medical conditions resulting from prenatal alcohol exposure (PAE), including brain-based central nervous system deficits and physical impairments. Previously, FASD conditions that did not meet Fetal Alcohol Syndrome (FAS) diagnostic criteria were diagnosed as having Fetal Alcohol Effects (FAE). Beginning in 1974, Ann Streissguth, Ph.D. and colleagues at UW led multiple studies on FAS and FAE. The primary investigation was conducted from 1992 to 1996 among over 400 diagnosed individuals age three to 51 years old, with the purpose of examining types and magnitudes of secondary disabilities, i.e., problems not present at birth but occurring across the lifespan as a consequence of PAE. In a study recently funded by NIH, UW researchers are recruiting prior study participants to ascertain current physical health, mental health, and functional status. During online searches for former subjects, researchers discovered that many with FAS or FAE were deceased. Among 438 diagnosed subjects, 23 (5.25%) were deceased (mean age at death 36.8 years), compared to one of 60 (1.67%) control subjects (age 35 years). Death certificates have been obtained for 18 individuals. Causes of death among the diagnosed included physical health conditions: heart-related (27.8%), cancer (16.7%), kidney-related (5.6%), liver-related (5.6%), diabetes (5.6%); and conditions related to mental health: alcohol and/or drug abuse (16.7%), accidents (11.1%), suicide (5.6%), and violence (5.6%). Cause of death for the control was cancer. These data indicate a three-fold greater proportion of deaths among FAS/FAE diagnosed individuals compared to controls in this study population. Death certificate information suggests a high proportion of FAS/FAE deaths were related to physical and mental health conditions known to be associated with PAE. Our findings speak to the importance of preventing PAE, early diagnosis among the exposed, and medical and social interventions to reduce risk factors associated with FASD.

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