A common post-translational modification of microtubules is glutamylation, which is a covalent bond between glutamic acid and a residue on the C-terminus of tubulin. Microtubule glutamylation is catalyzed by tubulin tyrosine ligase-like (TTLL) enzymes which modify microtubule functions such as, regulation of centriole stability, neuronal outgrowth, and cilia motility. How these enzymes regulate glutamylation remains unsolved. Caenorhabditis elegans (C. elegans) have five glutamylating enzymes (TTLL-4, -5, -9, -11, and -15) and lack glycylation, making them a good model for studying the function of TTLL enzymes. All five TTLL enzymes have an extended TTL domain suggesting glutamylation activity, TTLL-4, -5 and -11 have cation-enriched regions (cMTBD) which can make direct contact with microtubules, TTLL-9 and -15 lack cMTBDs and may require additional mediating factors to interact with microtubules. In a previous C. elegans study, ttll deletion mutations showed that the loss of an individual TTLL enzyme does not affect embryonic viability or spindle function, which is most likely due to redundancy. However, the triple mutation: ttll-4(tm3310); ttll-11(tm4059); ttll-5(tm3360), results in a male mating deficiency which suggests that glutamylation is required for proper microtubule function during male mating. To further investigate the role of tubulin glutamylation in male mating, we are generating mutant strains that contain deletions in multiple TTLL enzymes and a him-9 mutation to increase the incidence of males. Genetic crosses between hermaphrodites containing mutations in the TTLL enzymes and a male containing the him-9 mutation in the background will be performed. Phenotypic assays addressing the efficiency of male mating and other phenotypes will then be performed in the mutant strains.

Despite the progress made in the health and safety of farm workers and their families, barriers still exist for optimal health and safety, particularly for hard-to-reach populations. Barriers include, but are not limited to, geographic and linguistic isolation which complicates efforts to provide resources such as health and safety education. This project seeks to strengthen farm worker knowledge about occupational exposures and risks, with specific emphasis on pesticides, by engaging and educating children of farm workers (hereafter referred to as migrant children). Engaging migrant children in the form of an interactive class activity would allow them to walk away with increased understanding, thus, translational capacity to improve awareness for their families. The rationale behind an interactive class activity is to understand their experiences and the types of exposures and risks faced by themselves and their family. Additionally, the goal is to introduce these critical concepts to younger members in a community, so they can pursue opportunities that have positive impacts for the health and safety of their family. Pre- and post-assessments will measure change in knowledge and allow for an understanding of the interactive class activity effectiveness in knowledge gained. By engaging and educating migrant students there is opportunity to increase health and safety literacy and capacity to respond to issues among hard-to-reach farm worker populations.

HRI is a serious health risk for agricultural workers that can result from prolonged exposure and overexertion in hot temperatures. The four different types of HRI in increasing severity are heat rash, heat cramps, heat exhaustion, and heat stroke. These conditions are preventable using simple approaches such as proper hydration and limiting one's time in the sun. To better equip agricultural supervisors and safety trainers responsible for conveying heat safety to their workers, I collaborated with members of University of Washington’s Pacific Northwest Agricultural Safety & Health (PNASH) Center to develop a modular flipbook that will serve as training material, covering the following topics: symptoms, risks, and treatments, clothing, hydration, and other preventative measures; as well as where and how to cool off in the home and community. I helped advance this project by taking the lead on the production of the flipbook content under the direction of the Research Scientist. I collated images, researched instructional designs, and developed prototypes of the flipbook, as well as edited the written instructions for facilitators. The educational activities in the book consists of an interactive portion, guiding questions for the facilitator to pose to the group, role-play scenarios, take-home points to reinforce the educational messages, and 3-dimensional educational charts. Modules also contain a “Knowledge Evaluation” section with questions for the facilitator to ask participants both before and after the activities to gauge their change in knowledge and to ensure the material has been understood. As a final product, the flipbook will be a portable and convenient resource for safety trainers to use in the field. My goal is to ultimately make this flipbook accessible to the general public, as it is not only a great safety resource for agricultural workers, but also for their families and surrounding community.

Early recognition and reporting of concussions in youth sports is crucial in ensuring proper treatment and minimizing possible consequences. All US states have passed legislation requiring that youth sport stakeholders be provided with annual education about concussion, ostensibly because this knowledge will help them engage in key safety promoting behaviors, including reporting symptoms of a suspected concussion. By conducting a systematic review of peer reviewed published studies that measure concussion knowledge, we ask how youth athlete concussion knowledge influences concussion reporting. The hypothesis is that better concussion knowledge is positively correlated with increased reporting of concussions. A systematic review of peer reviewed research published between 2009 and 2018 was conducted in November 2017. Inclusion criteria were 1) measuring concussion knowledge using a quantitative survey measure, 2) the athletes were collegiate age and younger. This resulted in 127 studies. Subsequently, studies were reviewed by two independent coders to determine whether they measured concussion reporting behavior or behavioral intentions. Data was collected in order to assess the strength of association between knowledge and behavior. While data synthesis is ongoing, preliminary results suggest that the association between knowledge and concussion reporting behavior or intention is minimal. Interventions are needed to increase reporting of suspected concussions, however, current results suggest that education focusing solely on increasing an athlete's knowledge about concussions may not be sufficient. Future research should focus on motivators of concussion reporting behavior in youth athletes and explore intervention methods that address evidence-based determinants of this important safety behavior.

Central Argentina in the lee of the Andes Mountains experiences some of the most intense thunderstorms on earth. These storms produce large hail, flash floods, and tornadoes, and adversely affect the people living in this region. The initiation, growth and hail production processes in these storms are poorly understood due to the lack of sufficient observations in this region. Currently, the only way to study the climatology of these events is through satellite remote sensing observations. This project examines spaceborne radar data from the Precipitation Radar (PR) on the Tropical Rainfall Measuring Mission (TRMM) satellite for the November and December period for the years 1998-2013. The purpose of this project is to better understand the temporal and spatial evolution of these convective systems near the Sierras de Córdoba in the lee of the Andes. The PR radar observations from TRMM were classified into 4 categories: 1) deep convective cores; 2) wide convective cores; 3) intermediate convective cores; and 4) broad stratiform regions. These categories are based on the height, area, and reflectivity of the storms. Reflectivity is the signal reflected back to the radar by the hydrometeors. It was found that initiation and rapid upscale growth occur in the vicinity of the Sierras de Córdoba. These results are crucial for the planning and execution of the upcoming field campaign in Argentina called RELAMPAGO (Remote sensing of Electrification, Lightning, And Mesoscale/microscale Processes with Adaptive Ground Observations). Knowledge about how convective storms behave in Argentina applies to other regions, such as the lee of the Rocky Mountain in the United States. Another benefit of this study is that legacy computer code that was written in the IDL programming language is now updated to a more structured format with Python making it easily used for future research.

A language game is created when a group of speakers systematically alters the phonological forms of words in their native language in order to disguise the meaning of what they are saying from unwanted listeners. An example of this in French is a language game called Verlan, which is spoken primarily in the low-income suburbs of Paris by adolescents and young adults. This language game obscures the forms of the original French words, typically by reversing the order of the syllables (or through several other phonological methods) in order to create a coded language. It has been suggested by linguistics researchers, such as Natalie Lefkowitz, that language games can be used to “reveal the phonological structure of the languages in which they are played,” as well as to provide corpus-external evidence for underlying phonological rules and constraints that govern the original language. For this research project, I sought to gain deeper insight into the hidden structures that underlie French phonology through native speakers’ use of Verlan. By following similar experimental methods used to study other language games, I proposed an experiment that would examine French speakers’ phonological representations of problematic consonant clusters by analyzing their Verlan productions of nonsense words. Different productions could reveal differences in speakers’ internal grammars that are not readily seen in the native language phonology. This method of analyzing language games could give linguists another tool to use when investigating phonological rules of a language that couldn’t previously be tested on naturally occurring words.

We studied Betta fish and their aggressive behavior in reaction to a perceived threat stimulus at two different distances. Betta fish have been known to display aggressive behaviors when in the presence of other fish and at their own reflection. We hypothesize that the Betta fish will display more aggressive behaviors when a mirror is present and at a closer proximity because a close mirror may replicate the experience of a more immediate threat. To test this, we placed mirrors at one or eight inches away from their tanks and observed. If the Bettas flared their fins and rubbed their faces against the side of the tank, we characterized their behavior as aggressive. We found that our hypothesis was incorrect and there was no signficant difference between aggression presentation at one or eight inches. Additionally, we compared aggressive behavior in Delta Tail Bettas and Veiltail Bettas. We hypothesized that there would be a difference in aggression between the two betta species. Our hypothesis was supported, and we found that Delta Tail Bettas were significantly more aggressive than Veiltail Bettas. For breeders and owners of novelty fish, knowing what stimlui results in aggressive behavior can be beneficial for preventing stress and choosing what species to breed and own. Furthermore, studies on aggression in bettas allows researchers to study how aggression relates to survival and mating, and how bettas compared to related species.

One million children undergo major surgery in the U.S. each year, and many experience significant pain and distress during the weeks and months following surgery. Modifiable psychological and behavioral risk factors including anxiety and poor sleep place children at risk for acute and chronic postsurgical pain. Interventions addressing these factors have the potential to reduce long term pain and improve quality of life. The mixed-methods study aimed to evaluate the usefulness, accessibility, and perceived benefit of a newly developed perioperative psychosocial intervention. Fourteen youth (age 10-18 years, M=14.5; 71.4% female) scheduled for spine surgery and their parents were enrolled into a pilot study testing a family-based cognitive-behavioral therapy intervention targeting risk factors for pain. The intervention consists of 6 lessons delivered online during a 10-week period spanning the pre- and post-surgical periods. Families completed a program evaluation questionnaire assessing the usefulness and accessibility of the program using numeric rating scales (range: 0–5; 0=“strongly disagree”, 5 =“strongly agree”), and participated in individual qualitative interviews assessing their experience with the program. Preliminary results show that both children and parents found the intervention content to be useful (children: M=3.7, range=2-4; parents: M=4.1, range=1-5) and accessible (children: M=4.5, range=3-5; parents: M=4.9, range=4-5). Results from the qualitative interviews indicate that families found the program to be beneficial. For example, one parent stated that “[the program] gave me some ideas to cope with this situation, how to try and relax, and try to think positive thoughts.” Preliminary results support the accessibility, usefulness and perceived benefit of the intervention for families. Future research is needed to determine the efficacy of the program for reducing acute and chronic pain and improving quality of life among children undergoing major surgery.

Mitosis is a process important for the regulated division of cells. In cancer cells mitosis is often dysregulated, which can cause cells to split uncontrollably. One important protein that plays a key role during mitosis is the protein kinase Polo-like Kinase 1 (plk1). The function of Plk1 is to regulate centrosome maturation, bipolar spindle assembly, and mitotic entry, making it a very important protein throughout mitosis. To understand how it functions during mitosis we can use drugs that turn off the activity of Plk1 to mimic what occurs when the protein is malfunctioning. Drugs like BI2536, a small-molecule inhibitor that turns off Plk1 activity in mitotic cells, have provided insight into how Plk1 functions; however, these drugs are not selective enough to inhibit protein activity at distinct locations in the cell. To address this problem, we use a technique called SNAP-tag to localize BI2536 to specific organelles within cells. Using genetic engineering approaches like cloning, virus generation and stable cell production, I helped make cells that express a SNAP protein linked to a PACT domain. PACT localizes to the centrosomes in dividing cells and allows us to bring SNAP protein only to that location. Our modified drug enters cells, binds to SNAP-PACT, and selectively inhibits Plk1 activity at the centrosome of cells. Through experiments I have run, we have shown that we are able to inhibit Plk1 activity in vitro and in vivo. Using immunofluorescences and super-resolution microscopy, I have shown that local targeting of CLP-BI2536 to the centrosomes causes a greater reduction in active Plk1 (p-plk1) than traditional global drug delivery. In the future, I hope to use this approach to investigate the activity of another mitotic protein, Aurora A, in order to further explore the role of mitotic kinases during the cell cycle. 

Communication between social animals is critical for survival. American crows (Corvus brachyrhynchos) form large, often raucous social aggregations. Our previous research has suggested that crow calls have context-dependent differences in the durations of silence between syllables, i.e. gaps. Specifically, we found that longer gap durations were associated with pre-roost aggregations, which are assemblies of crows formed before heading to their nightly roosts. However, other research found that continually decreasing gap durations throughout calls led to the most assembly behavior in this species. Our work tests the hypothesis that crows will show different assembly behavior in response to crow calls artificially constructed to vary in gap duration. We created modified crow calls using recordings of crows made in the wild, shortened the gap durations across trial groups, and played these modified calls back to crows in diurnal activity centers - areas where crows forage during the day - across eight different locations using a repeated measures design. We recorded the number of crows within 0-5, 5-15, 15-30, and 30-50 meters of the speaker every 3 minutes during 30 minutes of call playback at each location. We also recorded the closest approach to the speaker and total vocalizations made. No significant differences were found across these variables; suggesting that calls with decreasing gap durations do not elicit more assembly. Because we saw some evidence of habituation during these tests, we decided to conduct a follow up study in which we no longer use a repeated measures approach, and change locations after every trial. We also altered our playback methods to include overlapping calls, which we often hear from crows in the field, in hopes that this would elicit more assembly. Early tests suggest these new approaches are more successful in generating assembly behavior.

Microplastics are polymers < 5mm, varying in shape, color, chemical composition, and density. Manufactured plastics are primary microplastics which include pellets, fibers, and microbeads. Secondary microplastics are plastics fragmented through photodegradation and/or mechanical weathering. Research has documented microplastics in high densities (e.g., 100,000 items per m3) in marine environments, but little work has been conducted in riverine environments. Our study is focusing on the Puyallup River Watershed, located in Washington State, and its role in microplastic transport. The Puyallup River and its two principal tributaries, the White River and the Carbon River, drain a watershed of approximately 1,040 square miles and stream from several glaciers located on Mount Rainier, including the Puyallup Glacier. During our preliminary research, samples were collected monthly, both upstream and downstream of municipal wastewater treatment plants, from five cities in the lower reaches of the Puyallup River Watershed. Fibers, fragments, and foams were identified, characterized and quantified. Only 1-foam and 5-fragments were found, with the majority being fibers. The concentration of fibers, ranged from 0 to 204 fibers/L, with an average of 22-fibers/L in each sample collected. Results were statistically inconclusive to determine if wastewater treatment plants were a point source of plastic pollution to the Puyallup River Watershed, although more fiber numbers were located upstream than downstream at most sites.

On top of being iconic symbols of climate change, glaciers integrate year-to-year precipitation and temperature variability, which can mask their response to a climatic trend. For this reason, it is vital to identify the variability in their records to better detect regional climate change. With time-varying sea-level pressure (SLP) and sea-surface temperature (SST) fields, we examine the influence of natural climate variability on 14 glaciers in the North Atlantic region by using a statistical method called dynamical adjustment. The SLP and SST fields each explain 50-60% of variance in the winter mass-balances and 30-40% in the summer mass-balances of the maritime glaciers. The continental glaciers are less closely linked to oceanic variability, with SST explaining roughly 30% of variance in winter and summer mass-balances. The glaciers located further south fluctuate with the North Atlantic Oscillation (NAO) in the winter, while glaciers near the Arctic show influence from the Atlantic Multidecadal Oscillation (AMO) in the winter. To investigate how this variability affects glacier trends, adjusted mass-balances are compared to observational mass-balances with no signs of variability forcing trends. The observed and adjusted summer mass-balance trends of the southern glaciers are significantly negative, while the observed and adjusted winter mass-balances of the northern glaciers are significantly negative. This indicates that winter trends are more likely to emerge in glaciers near the Arctic, while summer trends are more likely to emerge in glaciers further south which is consistent with surface temperature time of emergence for global warming.

The nitrogen vacancy (NV) center is a defect in diamond that forms a quantum mechanical system that can be controlled via optical and radio frequency (RF) manipulations. When excited on resonance, the photoluminescence intensity emitted by an NV center decreases as it changes spin state. With an ensemble of NV centers, we can use this feature to create a demonstration that enables this strictly quantum mechanical phenomenon to be observed by the human eye. I created a setup for measuring the change in photoluminescence in order to measure changes in the optical contrast between on and off resonance photoluminescence from varied optical and RF powers. From this data I was able to optimize the contrast in photoluminescence from my sample. Then, I simplified the setup down to the necessary components for visual observation and made the setup portable. This demonstration provides a visual mechanism to understand and observe fundamental quantum mechanical properties while also learning about the NV center and its use in magnetic field sensing.

Hybrid organic-inorganic perovskite films have exhibited power conversion efficiencies (PCEs) over 22% in photovoltaic devices. Despite high PCE, non-radiative recombination at surface defects remains a major material challenge in achieving theoretical efficiency limits. We have recently shown that surface passivation using Lewis bases on model CH3NH3PbI3 perovskite films can increase the external photoluminescence quantum efficiency (PLQE) to 30% and internal PLQE to near unity. This puts CH3NH3PbI3 alongside Gallium Arsenide, currently the highest performance solar cell material, as the only other semiconductor with such high radiative efficiency. Recently, several other alloyed perovskite compositions such as (HC(NH2)2¬)xCs1-xPb(I1-yBry)3 have been investigated for photovoltaic applications due to their increased stability. Preliminary studies have shown that the surface chemistry and effect of Lewis bases on these alloyed perovskites depends on their composition. In order to understand these differences, we investigate the nature of defects, surface chemistry and the effect of Lewis bases on these alloyed compositions. We test a library of Lewis-bases as ligands on alloyed perovskite compositions and use time-correlated single-photon counting and photoluminescence quantum yield measurements to quantify changes in charge carrier lifetimes. We also use glow discharge optical emission spectroscopy to show that the ligands are primarily confined at the surface and thus, act as surface treatments. Furthermore, we use solid-state nuclear magnetic resonance along with X-ray photoelectron spectroscopy to show that the behavior of ligands is consistent with that of a typical Lewis-bases. This study demonstrates the importance of surface defects in alloyed perovskite compositions and the importance of surface passivation in achieving higher optoelectronic quality materials. The information gained in this study will be critical in optimizing the design of alloyed perovskite composition devices.

The dinoflagellate Alexandrium sp. is a source of paralytic toxins in Puget Sound shellfish and a potential cause of paralytic shellfish poisoning in consumers. Paralytic shellfish poisoning not only threatens the livelihood of our Puget Sound and neighboring ecosystems, but largely affects the health of those ingesting marine invertebrates. An individual ingesting shellfish containing concentrations of paralytic toxins might experience mouth and limb numbness, serious illness or death. The University of Washington Tacoma and Washington State's Department of Ecology have partnered together through the Puget Sound Ecosystem Monitoring Program to monitor the presence of Alexandrium cysts throughout the Puget Sound. The Alexandrium cyst research involves processing sediment collected in Bellingham Bay. The sediment samples are sonicated, sieved, preserved using formalin, solubilized using methanol, and stained using Primulin. The samples are then prepared onto a Sedgewick-Rafter slide and cysts are counted using an epifluorescence microscope. Through the identification of cyst distribution throughout the Puget Sound, our research strives to preemptively assess and predict Harmful Algal Blooms and, ultimately, the risk of paralytic shellfish poisoning in consumers. Through our research efforts, we hope precautionary measures can be taken toward preventing paralytic shellfish poisoning in consumers of Puget Sound shellfish, benefiting the health of all Washingtonians.

Developmental epileptic encephalopathies (DEE) are severe brain disorders characterized by early onset seizures, developmental delays, neurological deficits, and regression. The Mefford lab works to find the genetic causes of DEE, which can usually be linked to a single de novo variant in each patient (mutation present in the patient that was not inherited from either parent). De novo variants in candidate genes were discovered through whole exome sequencing (WES). We validated these variants using Sanger sequencing. Of the 291 de novo variants identified by WES, 105 validated. In order to find support for the causative nature of variants in these genes, a cohort of 898 DEE patients is currently being screened for variants in 53 candidate genes identified through WES (T7). The targeted sequencing is done using smMIPs (single-molecule Molecular Inversion Probes) to simultaneously capture all exons of T7 genes in our cohort, requiring over 2,000 MIPs. However, uniform capture of target regions with smMIPS can be problematic. Some easily sequenced areas are over-captured while tougher regions are under-captured, leading to a need for rebalancing. We tested T7 smMIPs at concentrations of 1X and 10X to provide data on capture efficiency and then compiled to provide the best concentrations per smMIP in the final run. The result was 91% of reads falling on-target with 88% of smMIPs producing at least 8 reads. We hope to find multiple variants in the same gene across multiple patients in our cohort to confidently identify new DEE genes. Confirmation of new genes will help to advance our understanding of these severe disorders and pave the way for more effective treatments in the future.

 The atoms in the universe are involved in a constant process of enrichment and redistribution. They cycle violently into and out of galaxies over billions of years. This cosmic cycle of baryons creates a diffuse halo of gas, called the circumgalactic medium (CGM), that exists inside the virial radii of galaxies. Characterized by rich dynamics and complex ionization states, the CGM provides galaxies their star-forming fuel by regulating and recycling the gas supply. The CGM is vital to understanding the evolution of galaxies and the universe, but it is difficult to observe directly. Using high-resolution quasar spectra collected by the Cosmic Origins Spectrograph on the Hubble Space Telescope, we identified absorption features found in the spectrum of the quasar. We classified each absorption feature, identifying its species, redshift, velocity dispersion, and density. We discovered several strong hydrogen systems with metal absorption at redshifts where the light from the quasar had passed through a cloud of metal-rich gas. Using the Sloan Digital Sky Survey catalog, we matched our strong hydrogen systems with several galaxies near the line of sight of the quasar. Now we are starting to characterize correlations between the dynamics of gas in the CGM and its influence on the star formation rate of the galaxy it surrounds.

Brain tumors are the most common form of pediatric cancers after leukemia. Deregulation of the family of MYC (avian myelocytomatosis viral oncogene homolog) transcription factors in some forms of pediatric brain cancer correlates with very poor prognosis. It is believed that overexpression of MYC may play a role in sustaining aggressive brain tumor cell populations in diffuse intrinsic pontine glioma (DIPG), medulloblastoma, and atypical teratoid/rhabdoid (AT/RT) pediatric brain tumor types. A targeted therapy capable of inhibiting MYC transcription factors may be a promising option for children with MYC-upregulated brain tumors. We addressed the role of MYC genes in the tumorigenesis of several patient-derived pediatric cell lines with upregulation of MYC transcription factors. Via a lentiviral delivery agent, we attempted to knock down MYC transcription factions through the expression of doxycycline induced omomyc—a 90 amino acid, MYC-derived, polypeptide that interferes with normal MYC activity by outcompeting for the enhancer binding sites that MYC normally binds to. We found that MYC inhibition, using omomyc, halted the growth of tumor cells in over half of the patient-derived primary cell cultures with MYC overexpression. 6 out of 11 lines showed significant inhibition of tumorigenesis through the induction of omomyc. This suggests that the mechanism of action of omomyc, as a MYC inhibitor, may serve as a model for drug development against MYC for pediatric brain cancer.

Our lives are made up of the choices we make, whether it be choosing to change your posture, choosing an outfit to wear, or choosing a career path. Intertemporal choice is a decision-making process where one needs to change behavioral strategies as the contextual factors in their situation change over time; variables such as working memory, objective and subjective value of the outcome, and motivation influence a subject’s decision in this process. Delayed discounting is an example of an intertemporal choice task, wherein a subject is given a choice of waiting a constant shorter delay to receive a smaller reward (SS, or smaller-sooner), or waiting a longer delay, which increases after a set number of trials, to receive a larger reward (LL, or larger-longer). In the present study, rats are tasked with choosing between waiting 3 seconds for 1 sucrose pellet (SS reward), or waiting 10, 20, or 40 seconds for 4 sucrose pellets (LL reward). Delayed discounting allows investigation into how the Lateral Habenula (LHb) may play a role in integrating signals of objective value and contextual information of the current situation, with internal state information, such as emotion toward and motivation for completing an intertemporal choice, to ultimately allow the subject to behaviorally adapt and make the most beneficial choice. This study predicts that infusion of a combination of baclofen and muscimol via canula into the LHb will inactivate it and subsequently impair delayed discounting in rats, causing them to enter a guessing mode when choosing between SS or LL reward. A dysfunctional LHb could be implicit in clinical disorders such as depression, addiction, or other memory disorder that are characterized by poor control of behaviors; this implication would be able to explain why those with these disorders are unable to switch behavior’s adaptively despite repeated negative consequences.

About 33% of adults age 65 and older and 15% of school-age children (age 6-19) have some degree of hearing loss. Also, 2-3 children in the United States are born with a detectable hearing loss. Although hearing devices like hearing aids and cochlear implants are used by patients with hearing loss to improve hearing, they often complain about the difficulty of understanding speech in a noisy environment. A cochlear implant device sends tiny currents that stimulate auditory nerve fibers which the brain interprets into sound. In this study, filter banks with different number of frequency bands were developed to simulate how people using cochlear implant comprehend speech. We varied the number of bands to investigate the clarity of sound affected by spectrum resolution. When the number of bands increased, the clarity of speech improved, and a spectrum analysis graph showed a visual representation of the result as an improved resolution. In a noisy environment, this mechanism is not capable of attenuating noise in a signal. Noise interference with signal can be resolved with the use of an adaptive filter. An adaptive filter involves the change of a filter parameter over time to adapt to changing signal characteristics. In this research, an adaptive filter would be able to track the harmonics of a signal to separate speech from noise. This algorithm concentrates on specified frequency contents of a signal, and accordingly, noise is attenuated by the adaptive filter. Using the adaptive filter as the means to improve the signal processing technique, noise interference with signals is minimized and patients with a cochlear implant device can improve their understanding of speech in a noisy environment.

Electroencephalograms (EEG’s) are a common form of measuring electrical activity in the brain. Electrical activity from the brain directly correlates to neuronal activity, providing information that can be used for disease diagnosis or research on brain mechanisms. EEG recordings are limited in practicality and efficiency in some circumstances due to poor spatial resolution, vulnerability to noise, and consistency. Subdermal electrodes are unable to capture deep brain activity, which can only be obtained through surgically implanted intracranial electrodes. As a result, for patients in a condition where surgery is not optimal, the subdermal EEG offers little to no information in terms of deep brain activity. Through previous work, we have shown that applying 1050 Hz pulsed focused ultrasound (pFU) resulted in EEG readings above normal physiological frequencies. Natural brain activity frequencies can be derived from the amplitude demodulation of the 1050 Hz signal. The ultrasound is amplifying the electrical activity in the region it is focused upon, allowing the EEG to record these signals. In this study, we attempted to increase the capabilities and specificity of EEG noninvasively through coupling it with pFU. We continued our previous work by applying pFU transcranially to the left visual cortex of a C57BL/6J mouse brain while stimulating the right eye with light. The observed frequencies collected by EEG were analyzed for neuronal stimulation in addition to sensory stimulation elicited from the ultrasound. A technological breakthrough in this field may someday lead to the ability to measure brain activity non-invasively from anywhere in the brain.

Active learning has often been described as the key to increase retention rates among undergraduate STEM majors because students are engaged in meaningful learning. Common activities associated with active learning include completing worksheets in groups, clicker questions, or discussion questions followed by reporting out by random call during class. Random call differs from cold call as the instructor allows discussion time where students can work together to formulate an answer prior to random call. However, previous research has demonstrated that implementing active learning principles may increase student anxiety. Specifically, answering questions in class, either by volunteering or random call, may cause the highest level of anxiety for students. We have conducted a study investigating how student demographics impact the likelihood of students responding to random call. Our study was conducted in an Introductory Biology course with 576 students, in a lecture-hall style classroom. The instructor utilized random call, then recorded which students either gave a response or passed the question when called upon. A binary logistic regression was performed to create a best fit model in which student demographics could predict which students were more likely to answer or pass. Students who are the first in their family to go to college (1st generation students) were 57% less likely to respond to random call questions compared to other students, even when controlling for incoming GPA. This result indicates that students with diverse demographics participate differently in some active learning activities and further investigations are necessary to determine if this has an impact on their learning. To bridge this “responding” gap between 1st generation and Non-1st generation students, instructors should implement additional techniques such as group random call as opposed to individual random call to increase student comfort during random call, thereby increasing the likelihood of students responding regardless of student demographics.

Inner-shelf (5-30 m water depth) circulation is driven by a combination of cross- and alongshore winds, and anti Stokes drift as a response to onshore directed surface gravity waves. These physical processes control cross-shore exchange of tracers (pollutants/biota/contaminants) from the surf zone to deeper waters, and also movement along the coastline. Their relative role in material movement, along with seasonal variability in local circulation is not yet understood, and investigated here using a long-term (2005-2009) continuous record of inner-shelf (5m water depth) velocity and surface waves off the coast of South Carolina, USA. Alongshore flows are primarily driven by alongshore winds, as indicated by strong correlation between depth-averaged alongshore velocity and alongshore wind variability (r2=0.72). This correlation decreases in winter due to the shelf response to rapid synoptic meteorological frontal passages along the South Carolina coast. Further, the correlation is strongest near-surface, weakening close to the sea-bed, possibly due to near-bed flow reversals. Cross-shore dynamics is not completely explained by wind-forcing, as depth-averaged cross-shore velocity is poorly correlated to cross- and alongshore winds (r2<0.01). However, some variability in depth-averaged cross-shore velocity is explained by the cross-shore depth-averaged Stokes drift (r2~0.11). This correlation is strongest in mid-water column, decreasing near-surface and near-bed. These local flow dynamics will be further explored to determine mechanisms for, and seasonal variability in cross-shore exchange.

 Developmental and epileptic encephalopathies (DEEs) are an early-onset form of epilepsy that result in aggressive and recurring seizures, possibly leading to 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 RNA, generating a protein that is non-functional, partially functional, or aberrantly expressed. If aberrant splicing occurs, it could have pathogenic consequences, but predicting which variants near splice sites will have an effect on splicing is difficult. This raises the need to investigate splice-site variants. My work is concentrated on potential splice site variants in three genes associated with DEE: SYNGAP1, SCN1B, and WWOX. SCN1B codes for voltage-gated channels within the brain, SYNGAP1 is associated with postsynaptic signaling, and WWOX acts as a tumor suppressor and is vital in brain development. DEE genes are primarily expressed in the brain, a tissue that is unavailable from most patients, making splicing studies in these genes difficult. I was able to successfully amplify targeted regions of SCN1B, SYNGAP1, and WWOX in RNA isolated from blood and fibroblast, demonstrating the efficacy of using these more easily accessible tissues in my studies. The lab has now collected fibroblast samples from DEE patients with potential splice site variants in WWOX and SCN1B. I will use RNA extracted from these fibroblasts to confirm whether the splice site variants in WWOX and SCN1B cause aberrant splicing, and what the specific consequences of this aberrant splicing is on the protein-coding sequence of these genes. In the future, we also plan on collecting fibroblasts samples with variants from SYNGAP1 as well.

The vestibular system is integral to reflex behaviors that allow humans to walk and see clearly. For example, the angular vestibulo-ocular reflex (aVOR) stabilizes images on the retina by using input from the semicircular canals to produce fully compensatory rotation of the eye. When these systems fail, patients are disabled. Understanding the vestibular system can help us create effective treatments for vestibular disorders. Our lab is developing a vestibular neural prosthesis based on such knowledge. In this proposal, we are studying large gaze shifts accomplished with eye and head movements. The eyes saccade to a target as the head starts to rotate. During this combined movement, ratio between head velocity and compensatory eye counter rotation (VOR gain) is continually adjusted to accomplish an accurate gaze shift. When the eyes move toward the target, the VOR may be reduced or eliminated. When the eyes reach the target, the gain returns to 1.0 to stabilize the eye on the target. Our study utilizes head free Rhesus monkeys to assess the gain of the VOR before, during, and after a gaze shift. The monkeys are trained to follow a laser target, allowing researchers to induce gaze shifts by changing the laser position. We utilize only horizontal shifts, and only stimulate the horizontal canal. We record change in eye velocity in response to implant stimulation at different trial times. We hypothesize that the gain of the VOR is decreased when the eyes and head are moving toward the target. By stimulating before, during, and after and evaluating the change in eye velocity, we can infer the magnitude of change induced by vestibular input and the instantaneous gain of the VOR. The results of this study will provide insight into how the brain utilizes vestibular information during combined head and eye movements.

As late-night talk shows become largely integrated with standard news sources, their influence on the political arena, whether that be by shaping public opinions of candidates through comedy or inviting candidates on their show, asserts the question of whether they should continue to be treated as entertainment outlets or informational broadcast. This research project examines the relationship between viewers and late-night talk shows in contrast to traditional news outlets and how that translates to the political sphere. Late-night entertainment media has moved away from the secular approach of jokingly criticizing politics from the standpoint of personal scandal and moved into criticism of poignant issues. As a result, I believe we will begin to see proportional accountability between traditional news outlets and late-night entertainment media. By examining jokes through statistical evidence, I evaluate target audiences, bias, and to what level of true political salience this satire is afforded by viewers. An analysis of information spread in correlation to accessibility to late night pundits versus standard news segments, additionally how comedic irony sets the tone of discussion on these topics, allowed me to unveil power dynamics critically by employing the theoretical communication approach of agenda-setting. Research in this field indicates that comprehension of political figures, contemporary legislation or substantive issues, is indeed affected by late night humor which is uniformly categorized as liberal-leaning, though research concurrently suggests that viewers place a steadier credence on late-night talk shows then a traditional news broadcast. Further research will inspect the level of impact on political knowledge and favor and how that leads to an extended understanding of entertainment media consumption as it relates to politics.

Lung cancer is the leading cause of cancer-related death in both men and women in the United States. Smoking is the major cause of lung cancer. While tobacco smoke is well-known to cause mutations in DNA that drive the cancerous phenotype, it also induces epigenetic changes - changes in the regulatory information overlaid on the genome. Smoking has been shown in numerous epidemiological studies of subjects’ whole blood to affect an epigenetic mark called DNA methylation. DNA methylation commonly refers to the addition of a methyl group to cytosine in the context of a Cytosine-Guanine (CpG) dinucleotide. Hypomethylation at several CpGs in the blood has been shown to predict lung cancer risk, but the mechanisms by which DNA methylation changes in blood are linked to cancer in the lung are poorly understood. To investigate this, I used R to analyze 18 published peer-reviewed articles and collected 20,946 unique CpGs that have been found to be statistically significantly differentially methylated in the blood of smokers compared to non-smokers. I then utilized the UCSC Genome Browser and The Cancer Genome Atlas (TCGA) data to compare smoking-induced methylation changes in whole blood with those of non-tumor lung tissue and lung adenocarcinoma. Understanding the relationship between whole blood methylation and lung methylation can reveal if blood DNA methylation patterns are good surrogate markers for DNA methylation that occurs in the lung. Further studies of select differentially methylated lung CpGs can help unravel the mechanism by which smoking-induced epigenetic changes contribute to lung cancer development.

Garbage collection is a method of performing automatic memory management which generally leads to less complex and more maintainable source code, but it has a cost of performance hits and pause times. The D programming language is a newer high-level general-purpose programming language which relies on a garbage collector for several language features, though it consistently receives criticism for this decision due to perceived loss in performance. To increase the efficiency of D's garbage collection procedures, two ideas are explored: using an alternate layout for objects in memory and eliminating the requirement for pause times under certain conditions. The first prototype explores storing objects in memory based on type and not by size, allowing the system to take advantage of type information while caching it at the same time. The second prototype takes this idea and then explores implementing a collection cycle in such a way as to run concurrently with the user program so long as the machine can continue to fulfill allocations. Both prototypes are compared against D’s existing garbage collector using benchmarking tests provided by the language maintainers. These comparisons examine memory usage, allocation time, pause time, scan time, sweep time, and total running time, using an AMD R5 1600X 3.6 GHz and Intel core i7-6800 3.4GHz on Ubuntu 16.04, and an AMD R51600X 6-core 3.6 GHz and Intel i7-4790 4-core 3.6GHz on Windows 10. The findings will show if alternate memory layout allows for new optimizations for allocations and collection techniques and if preventing a total stop-the-world period is worth the overhead costs of synchronizing the garbage collector and program threads.

Chemically induced dimerization (CID) systems, which are systems that involve the dimerization of two proteins only in the presence of a specific molecule, have shown a great potential in studying and controlling cellular signaling pathways. However, current methods for identifying CID systems for any given target based on small molecule-protein interactions remains a challenge in the area of protein design. Our research team proposes a general approach for identifying new CID systems for which may have clinical and therapeutic applications. To do this, we aim to create nanobody-based CID binders. Using a technique known as “Trinucleotide-Directed Mutagenesis,” our team has been able to create a diverse nanobody library of over 109. Phage display allows us to screen this library for specific nanobodies that can bind with high specificity and affinity to a specific molecule. Currently, we are using cannabidiol (CBD) as a target molecule. After performing several rounds of selection, in order to validate our system’s specificity and selectivity, we use ELISA assay tests as well as Bio-Layer Interferometry to measure the binding affinity and binding rate of our system. In order to ensure the specificity of our CID system we tested it against, tetrahydrocannabinol (THC), a structural homolog. To date, we have successfully found three different nanobodies that can bind with high affinity and specificity to our small molecule of choice. As we move into phase two of our project, we are currently working on identifying the second nanobody in order to form a complete CID system. Designed CID systems will not only provide personalized choices for patients showing different drug responses, but also serve as orthogonal chemical control of different cell subpopulations and cell behaviors to improve therapeutic efficacy and safety.

People experiencing homelessness are disproportionately affected by alcohol use disorder (AUD) and involvement in the criminal justice system. These three issues are compounded when they are co-occurring. As abstinence-based alcohol treatments have demonstrated limited effects for this population, Harm Reduction Treatment for Alcohol (HaRT-A) was developed as a compassionate and pragmatic approach to help people reduce alcohol-related harm and improve quality of life without requiring abstinence or use reduction. A recent randomized controlled trial showed that HaRT-A significantly reduced alcohol use and alcohol-related harm. The aim of this secondary study was to test the effect of HaRT-A versus services as usual on a likewise important yet more distal outcome: utilization of criminal justice services. A three-month, two-arm randomized controlled trial was conducted to test the efficacy of HaRT-A compared to a services-as-usual control condition. Participants (N = 168) were homeless individuals with AUD recruited in community-based clinical and social services settings. Administrative data on number of jail bookings and days spent in jail were collected from 24 weeks prior and subsequent to treatment. A Mann-Whitney U test indicated no significant HaRT-A group effects on number of jail bookings (p = .22) or days (p = .57). This study did not demonstrate a significant HaRT-A effect on criminal justice service utilization. This finding may have resulted from the relative statistical rarity of incarceration and the short time period studied.

In the North Creek Wetlands near the University of Washington Bothell campus, an estimated 15,000 American crows (Corvus brachyrhynchos) roost every night. We looked at the density of crows and how much the perimeter of this communal roost changed during the winter season. We predicted that crows would be in tightly packed groups and that the roost perimeter would progressively shrink, as was previously shown in the fall. We first measured the roost perimeter by counting the number of guano droppings within a one square meter area every 20 meters, changing our direction of travel when guano fell below a ten dropping threshold. We circumnavigated the communal roost until we came back to our start location. We measured crow density by placing eight cameras at locations equally spaced in a line running east to west across the entire roost. Photos were taken of the tree canopy, where crows roost, every five minutes from 3pm until 9am for three days at each location. We then moved the cameras due south 50 meters until the entire roost area was completed. We reviewed all photos taken between one hour before and one hour after sunset. We calculated the average number of crows across every reviewed photo. The roost perimeter both shifted southwards and decreased in size from 44,111 to 38,607 square meters over the winter. We are currently analyzing our density data-set and predict that average crow density will increase as the roost perimeter decreases. Utilizing this data, we can develop a better understanding of the changes in roosting habits through a season, which enables us to determine why crows choose to roost in certain areas, which has future implications in the development of crow sanctuaries and wildlife centers.

The South Fork Tolt River is regulated by a dam that provides an essential source of drinking water and hydroelectric power for the City of Seattle. While hydroelectricity is a greener energy alternative, there are still environmental considerations of the influence of dam operations on rivers. Seattle City Light (SCL) has an active program to monitor and mitigate the effects of dam operations on the ecology of streams and rivers within their management domain with a focus on stream flow. In 2003, in response to the new Washington Department of Ecology (WA DOE) water quality standards, SCL developed an improved management plan to emulate natural water conditions on the South Fork Tolt utilizing variable water release heights to meet the new temperature and flow requirements. Initially, temperature data from United States Geological Survey (USGS) river gages were used to monitor how the water releases influenced temperature. In 2015, following an unprecedented dry and hot spring and early summer after a low snowpack winter, SCL installed their own network of temperature loggers in the Tolt Watershed to better understand how operations on the South Fork Tolt translate further downstream and to improve the overall spatial resolution of the data. Sensor data obtained from SCL, along with temperature data from USGS Stream Gages will be analyzed to determine the zone of influence resulting from varying water release heights on the South Fork Tolt. Findings from this analysis will assist SCL in ensuring that the utility is minimizing adverse impacts of hydroelectric operations on stream temperature and will assist in understanding how dams may be used to offset increasingly warmer trends and decreasing snowpack in the future.

Computer science and neurobiology have an undeniable entanglement with one another in the 21st century with the advent of advanced artificial intelligence and attempts to understand the black-box model of a brain. However, most neurobiology research has revolved around understanding existing behaviors in large animals, with commonly researched organisms including zebrafish and mice. Introducing novel behaviors to animals in a controlled environment is undeniably attractive in modern neurobiology. With the use of mass data-collection in the online Aquarium lab environment, this study shows the potential to model and produce novel behaviors in Hydra vulgaris (freshwater anemones with simple nervous systems). We aim to create a high-throughput, data-oriented, model for gene-based behavior analysis and editing in neurobiology research. By creating a single controlled environment to perform all research jobs on mass-produced H. vulgaris strains with clockwork husbandry, extraneous factors affecting the organisms are significantly reduced. By taking data on the success of every modification of these Hydra, we can model the effects of specific factors on these animals and progress toward creating a model organism for neurobiology research akin to knockout mice in medicinal genetics. With these methods we have been able to produce a significantly more efficient process of gene editing in Hydra and with several different kinds of DNA integrants. Over the long term, the wide availability of the online Aquarium lab can yield the discovery of unknown trends in genetic knockouts and the discovery of novel behaviors through analysis of all data collected in this controlled environment. Here we highlight successes thus far and future developments necessary to make this system a viable model for gene-based neural engineering over this century.

The lateral habenula (LHb) is part of the habenular complex in the dorsal diencephalon. Uniquely positioned anatomically to participate in reward-related brain circuits, this nucleus is an important regulator of the midbrain dopaminergic system that is known to be involved in the neuronal circuitry underlying various feeding behaviors. However, very little is known about the precise role of this nucleus in operant food self-administration and relapse to food seeking. Here, we utilized the DREADD (Designer Receptors Exclusively Activated by Designer Drugs) technology that we have successfully used to bidirectionally manipulate LHb neuronal activity associated with motivated behaviors. Male, Long Evans rats were infused with adeno-associated virus expressing Gi/o coupled human M4 (hM4Di) receptors into the LHb bilaterally. Approximately 10-12 days following viral infusion, rats were trained to self-administer food pellets for 10 days on a fixed ratio 1, 20 second timeout reinforcement schedule; food pellet delivery was paired with a compound tone and light cue. Activation of hM4Di by the pharmacologically inert synthetic ligand clozapine-N-oxide (CNO) activates G protein-activated inwardly rectifying K+ (GIRK) currents and results in hyperpolarization of neuronal activity. Our data indicate that activation of hM4Di in the LHb with CNO (1 and 3 mg/kg, i.p) had no influence on food reinforced operant responding, or the motivation to self-administer food under a progressive ratio schedule. Studies are currently underway to determine the effect of activation of Gi/o-coupled signaling in the LHb on the reinstatement of food seeking.

Upper- and lower-limb orthotic devices are prescribed for individuals who have partially lost motor control, such as stroke survivors or those with cerebral palsy, to assist with the stability and function of a limb. Unlike prostheses, devices available for those missing part of a limb, there are few current solutions available for upper-limb orthoses. As a result, options for users can be clunky, expensive, and hard to customize. The goal of this research was to further develop a 3D-printed elbow-driven orthosis that is inexpensive, adjustable, and helps users with impaired dexterity perform two-handed daily tasks. In comparison to traditional devices, which can cost hundreds of dollars, this orthosis can be assembled for approximately $30 predominantly because of the use of 3D printed parts. Originally designed for an individual whose seizure reducing brain surgery limited use of her left hand, this orthosis takes advantage of existing elbow range of motion to operate a clamp near the user’s palm by using a cable extending from the elbow to the hand. Cable tension activates the clamp near the palm in two distinct ways, depending on chosen part placements; the cable can either voluntarily open the clamp, or voluntarily close the clamp with elbow flexion. To compare clamp activation methods, we conducted a study that evaluated muscle activity and time to complete activities of daily living using the adjustable orthosis. These results will help inform which device setting, voluntary opening or voluntary closing, is easiest to control for common tasks and inform future device improvements. Participants involved in this study included individuals with impaired and unimpaired hand function. Through a continuous cycle of prototyping, feedback, and device modifications, we have created a customizable, affordable, 3D printed upper-limb orthosis that will be open-sourced to promote further innovation to support individuals with limited hand function.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and interaction, as well as restrictive or repetitive behaviors and interests. Some individuals with autism demonstrate deficits in face memory and recognition, which may contribute to overall social impairments. Increasing evidence also suggests that ASD is associated with abnormal sensory processing, including within the olfaction pathway, although results vary as to which components of olfaction, including odor identification, might be affected. Both odor identification and face recognition have been associated with activity in the orbitofrontal cortex (OFC), a brain region possibly implicated in ASD. The current study aims to measure odor identification and face memory performance in children with ASD compared to children who are typically developing (TD) and children with sensory processing difficulties (SPD), and assess whether there is a relationship between performance on face memory and odor identification tasks. Odor identification will be measured using University of Pennsylvania Smell Identification Test (UPSIT), a 40 item “scratch n’ sniff” activity, and face recognition will be assessed using the Wechsler Memory Scale III (WMS III); children will complete both the Faces I and Faces II subtests, which assess immediate recognition of faces and delayed recognition of faces respectively. Data collection for this study is ongoing; final analyses will consist of a Student’s t-test to assess for group differences on the odor identification and face recognition tasks, and Pearson’s correlation analyses to detect any significant associations between these tasks, using a significance threshold of α=.05. We hypothesize that children with ASD will show reduced performance on both the odor identification task and face recognition tasks compared to the TD and SPD groups, and that performance on the UPSIT will be strongly correlated to WMS III scores, reflecting the shared underlying role of the OFC.

C. elegans is a prolific model organism that is well established in the field of aging research and age-related diseases. C. elegans can be genetically manipulated to express human toxic proteins associated with neurodegenerative diseases. Its amenability to genetic screening and short lifespan make it an ideal animal model for studying the genetic basis for the neurological health-declines associated with Alzheimer’s disease (AD). Here we introduce new experimental approaches for quantifying the organism-wide impacts of nervous system specific expression of human AD-associated toxic proteins.. The pharynx in C. elegans is an oral pumping structure used in feeding. The pharyngeal nervous system, comprised of only twenty neurons, dictates the rate of pharynx pumping in the animal. Pharyngeal pumping rates have been shown to change and decay with the age of the animal, making it an ideal metric in aging research. The frequency of pharynx pumping can be measured via an electrophysiological recording of the pharynx’s contractions. We plan to use this electropharyngeogram (EPG) as a measure of neurodegeneration to compare wildtype animals with our AD-model mutants. Furthermore, the proper function of extracellular vesicles (ECVs) are thought to be important in the clearance of toxic peptides associated with AD. The only reported phenotype for ECV signaling is the differential development of the cuticle, the animal’s outer-most layer of epidermis. The cuticle’s formation can be assessed through the appearance of the worm’s alae, a set of three lateral stripes running across the animal from head to tail. The appearance of alae has been observed to be different in our AD model mutants, indicating that ECV signaling has been disrupted. Using these AD-model mutants, we aim to establish these novel phenotypes as a means to further investigate the physiological consequences of AD-associated toxic peptide expression.

As the average population lifespan increases in many countries, study into age-associated diseases and the basic biology of aging has become even more important. Studying age-associated changes and lifespan-altering genes in the budding yeast has revealed fundamental insights into the aging process. To measure replicative lifespan of budding yeast cells, we image hundreds of isolated yeast cells trapped in a microfluidic device over the aging process. Using fluorescently labeled strains allows the measurement of protein expression and localization during aging.We observe that Msn2, a general stress-response transcription factor, becomes increasingly activated with age in the budding yeast. Paradoxically, knockout of Msn2 and its homolog Msn4 results in increased lifespan, indicating that the Msn2-driven transcriptional stress response is detrimental to longevity. This effect is mediated by the inappropriate upregulation of a cohort of genes associated with the glucose starvation response despite replete glucose conditions. Deletion of these genes—glucokinase (Glk1), phosphoglucomutase (Pgm2), and glycogen synthase (Gsy1)—also results in increased lifespan. These genes are associated with the accumulation of glycogen during glucose starvation, and by staining old cells trapped in our microfluidic device, we find that glycogen content increases with age. We see that overexpression of the glycogen catabolism gene glycogen phosphorylase (Gph1) increases lifespan, indicating that the mechanisms underlying the detrimental effects of the Msn2-driven age-associated transcriptional program may be driven, at least in part, by the build-up of glycogen in aged cells. Accumulated glycogen is seen in the aged cells of a number of evolutionarily distant species including bacteria and human brain tissue and is implicated in multiple human diseases. Thus, our work may elucidate the details of a fundamental frailty of the metabolic network during aging.

With climate change, it is predicted that plants will experience longer periods of drought followed by sudden heavy rainfall at unpredictable intervals. Using Arabidopsis thaliana as a model plant, we want to better understand how these variable conditions will impact plant communities in face of climate change. As we experience global climate change, this research will allow us to understand how plant communities may respond evolutionarily to the changing environment. We believe selective pressure created by climate change will promote phenotypic plasticity and epigenetic “memory” of their drought experience. This "memory" is passed down through generations and may help plants cope with the environmental stress. My research is part of Undergraduate Phenotyping of Arabidopsis Knockouts (unPAK), a community that strives to better understand genotype-phenotype relationship—how the DNA of an organism influences the way genes are outwardly expressed. My research aims to understand the significance this relationship plays in the adaptive ability of plants when exposed to variable conditions. We will grow 4 generations of 5 different genotypes of A. thaliana we believe have different levels of phenotypic plasticity. Generation 0, 1 and 2 will be exposed to either drought or regular watering, and Generation 3 will receive inconsistent watering. For Generation 0, we exposed 175 plants to drought (little to no watering), and 175 to regular watering (20mL every week). While growing these plants, we collected quantitative phenotypic observations such as chlorophyll content and rosette diameter. Eventually, we will measure fitness by number of seeds produced. For each generation, we’ll extract DNA from these plants and look at methylated regions, allowing us to compare their epigenetic responses to the treatments, analyze whether their plasticity benefits them in adapting to stressful environments, and see if there’s any difference between the parent and the offspring generations at the molecular level.

X-ray diffraction gratings are an array of equally spaced structures with defined width designed to diffract optical waves. These waves create a spectrum that allows for the characterization of the wavelength or angles created by each diffraction. X-ray diffraction is commonly used in x-ray crystallography, where x-rays are diffracted off crystal lattices and give information about its three-dimensional structure. The goal of this project is to develop a microfabrication process for high aspect ratio x-ray diffraction gratings. These devices will expand the x-ray diffraction capabilities of the University of Washington and the National Nanotechnology Coordinated Infrastructure (NNCI) at large. In developing this process, our main objectives are to attain smooth vertical sidewalls for the grating features, minimize gold waste in the plating process and to be highly repeatable. For our research, each fabrication step will be tested, troubleshot, and documented for future use. The microfabrication steps required in our process include photolithography, etching, grinding and polishing, wafer bonding, and electrochemistry metal plating. The main challenges of this project are producing a photoresist pattern thick enough to withstand deep etching without affecting the sidewall profile, attaining precise grinding thicknesses and overcoming wafer bonding complications. The work towards maturing each process through inspection and troubleshooting for fabricating high aspect ratio x-ray gratings will be discussed.

My research poses the following question: how does colorism affect the Mexican immigrant community in Yakima, Washington? Colorism is the allocation of privilege or disadvantage based on one’s skin color. In Yakima, Mexican immigrants suffer marginalization not only based upon their class and citizenship, but also their skin color. However, this latter form of discrimination rarely appears in the scholarly literature or in public discussions of immigrant rights. Moreover, Mexican immigrants often understand this racist form of discrimination as normal or are afraid to report such incidents. This is problematic because, while Mexican immigrants experience discrimination at work, school, or society based on their skin color, physical appearance, and language, such actions often go unreported or undiscussed. Therefore, for my primary research , I conducted two focus groups by partnering with a non-profit organization called La Casa Hogar that provides educational services to the Latino population in Yakima, Washington. I had a total of 13 participants in my focus groups where I posed a series of open questions to learn how Mexican immigrants identify and define racism and discrimination. Through transcriptions and coding, I will analyze my data to create a final report that discusses my findings and future research recommendations. Furthermore, my final report will include a literature review that further examines the history of colorism in the United States and Mexico, race relations between Mexico and the United States, the racialization of Mexican immigrants, and how internalized oppression and discrimination are some consequences of colorism.

Incorporating research into the undergraduate experience provides students with opportunities to develop transferable skills by engaging in the process of science. Historically, most students who have participated in research did so through apprenticeships in faculty research labs. However, the apprenticeship model limits the numbers of students who have access to authentic research experiences early in their academic careers. In contrast, Course-based Undergraduate Research Experiences (CUREs) engage larger numbers of students in firsthand research investigating questions that are relevant to the scientific community. CUREs provide access to undergraduates who might not otherwise have the awareness, confidence or social capital needed to pursue scientific research opportunities through traditional pathways. The University of Washington (UW) Introductory Biology CURE provides students with authentic research experiences studying the evolution of antibiotic resistance in E. coli through credit-bearing lab sections. We investigated the CURE’s impacts on students’ personal development as scientists along with their mastery of fundamental biological concepts and principles of experimental design. At the beginning, middle, and end of the first two quarters of the Introductory Biology series, CURE and non-CURE students completed concept surveys to detect changes in their: (1) attitudes about science and their own abilities, (2) competency in experimental design, and (3) conceptual understanding of key evolutionary concepts, such as the relationship between genotype, phenotype, and fitness. Although all students in this study attended the same lectures, we anticipate that students who participated in the CURE lab modules will attain greater gains relative to their peers enrolled in the non-CURE labs. Specifically, we predict that CURE students will demonstrate greater understanding of the mechanisms of evolution via natural selection, and improved ability to design controlled experiments and reason scientifically. In addition, we expect that alumni of the CURE will gain an increased sense of belonging and enhanced retention in science-related fields.

DeafSpace is a style of architecture created in 2005 based on Deaf architecture in 1800's. Using the Deaf experience in architecture, DeafSpace uniquely enhances the elements of hearing architecture to create a positive experience for deaf people. The project discussed the questions of how Deaf Culture influences architecture design, why each of the 5 components of DeafSpace are essential to have for a deaf-friendly building, and how the DeafSpace components can be beneficial to hearing architecture. Methods of approaching this topic included reading several articles, review papers, and interviewing architects about their techniques to create these buildings. Furthermore, the project looks at buildings designed by those mindful of these elements and how these buildings create a welcoming environment for the deaf. DeafSpace also embodies the spirit of DeafGain: how though the deaf experience focuses on deaf people, their experiences can benefit all types of people. By learning more about DeafSpace, other architects can be mindful of these elements and contribute to a universal design that can benefit a variety of people.

Wintertime air pollutant emission trends are poorly understood in comparison to emission trends in the summer mostly due to a lack of available and analyzed data on precursor air pollutants in the wintertime. This creates uncertainty in current atmospheric chemistry models. “WINTER 2015” was an aircraft research campaign launched in February 2015 that was executed to measure pollutant concentrations in addition to other data. All of which were relevant to the transportation, distribution, and chemical kinetics of pollutants and aerosols across the northeastern United States. The colder temperatures as well as lack of available sunlight have significant effects on chemical kinetics in the atmosphere. In particular, during the daytime, nitrogen oxides tend to produce ozone (O₃), a criteria pollutant regulated by the U.S. EPA, but nitrogen oxides destroy ozone at night. Longer nights, and lower sunlight during the day may mean that nitrogen oxides net destroy ozone for much of the winter. Current air quality models do not accurately simulate the nighttime chemistry of nitrogen oxides. I am examining the wintertime relationship between nitrogen oxides and O₃ using data taken in the WINTER 2015 campaign to gain insights into the extent to which wintertime nitrogen oxide emissions produce or destroy ozone. This information will then improve atmospheric chemistry models that are used to forecast air quality in various regions. It is expected that in the wintertime, the amount of reactive nitrogen oxide is limited relative to hydrocarbons. This nitrogen limited regime would mean that reactive nitrogen oxides have a greater role in the destruction of ozone, than the production of ozone.

Anthropogenic climate change is gradually reducing snowpack and shifting the timing and volume of streamflow in the Columbia River Basin. Mountain snowpack plays a key role in the water cycle by storing water in the winter and releasing it as snowmelt runoff in spring and summer. Snowmelt and the resulting streamflow are critical for a variety of sectors: irrigation, hydropower, flood risk management, and ecosystem services, particularly regarding salmon. There is a large network of reservoirs along the Columbia River and its tributaries that water managers use to store water from snowmelt to satisfy the needs of industries and communities. Snow can also be thought of as a reservoir, as it delays the streamflow response to a precipitation event. With anticipated increases in temperature due to a changing climate, the size of that snowpack reservoir is expected to decrease. We will analyze projections of changes in the amount of water contained within the snowpack and determine the volumetric size of the snow reservoir that will be “lost” due to a warming climate. We will compare it to existing reservoirs in the western United States. As the basis for these analyses we will use an ensemble of 160 different hydrologic projections included in the Columbia River Climate Change dataset. We will relate these changes in snowpack to changes in streamflow timing. The results of this study may help inform discussions about the need for changes to reservoir operations on the Columbia River.

The decriminalization of abortion has been a contentious issue in many countries throughout the world. Not only does the issue evoke religious debate, but a country's abortion laws also highlight the relationship between the state and women's bodies. The courts can have a considerable impact even in sensitive issues in society. Governments that have an independent judiciary as well as international courts in particular can provide a means for institutional change to occur. The purpose of this study is to understand the role that international courts' judicial policymaking plays in nations with restrictive abortion laws by examining the interactions between international courts and the domestic legal system. More specifically, the focus is on the case of Ireland due to its restrictive abortion laws and its increasingly independent judiciary as well as the fact that it is embedded in numerous international legal systems, such as the European Court of Human Rights (ECtHR). The HUDOC ECtHR Database, the Curia European Court of Justice Database, the Supreme Court of Ireland Judgement Database, as well as the Irish Statute Book were utilized in order to compare both domestic and international judicial rulings to Irish policy changes. Through examining the progression of the decriminalization of abortion in Ireland, the study concludes that international courts are in a unique position to provide incentive for countries to clarify ambiguity in their abortion policy and to institute domestic services. Although the focus is Ireland specifically, the study provides a general framework for the examination of international courts’ impact on other member states and contributes a more nuanced understanding of international courts' role in policymaking.

This project explores the relationship between anxiety and stimulant misuse. Both hormonal and social factors influence the prevalence rate of anxiety among females, which has consistently been higher than those of men. We hypothesize that anxious women are more likely than anxious men to take stimulant drugs in order to minimize the dysphoric feeling and relieve pressure. College students across 9 campuses who had previously reported at least one non-medical use of prescription stimulants in the last 12 months were invited to participate in a research study. Correlation analysis between anxiety and stimulant misuse and a moderation analysis were conducted. Consistent with our hypothesis, results revealed that women who experience symptoms of anxiety have a higher likelihood of misusing stimulant drugs compared to men who experience symptoms of anxiety. As gender moderated the relationship between anxiety and stimulant misuse, more attention needs to be paid to women with anxiety symptoms. Family members, friends and the society could provide more help and care for stressed females, preventing them from taking more stimulants.

The formation of the universe’s first galaxies is currently not well understood; with the launch of the James Webb Space Telescope (JWST) in the near future, however, it may soon be possible to uncover critical details about how and when the first galaxies formed. In this project, we examine whether it will be possible to discern the clustering of high-mass, high-redshift dark matter halos from background noise when looking at data from the JWST. The ability to detect these halos, which are believed to play a key role in galaxy formation, through their clustering could lead to further breakthroughs in the study of the early universe. An initial test of the effects of projection was run using data from the Illustris simulation at redshifts z=6 and z=10. Halo positions were analyzed in both 3D and 2D at each redshift in order to determine how much projection altered our ability to detect halo clustering. When viewing 2D projections of halo positions, it became evident that projection was significantly reducing our ability to detect clustering. When we made use of the third dimension to eliminate the projection effect, the clustering of high-mass, high-redshift halos become apparent at both redshifts. In reality, it will not be possible to replicate this 3D case; exact measurements for the depths of high-redshift galaxies are not obtainable using the JWST. Going forward, we will work to refine our results by applying real JWST data specifications in order to determine the feasibility of using JWST data to detect early halo clustering. Making use of information such as limits on the detectability of galaxies based on their star formation rates and the uncertainty of JWST spectroscopic measurements will allow us to better determine whether the idea of studying halo clustering at high redshifts using JWST data is worth pursuing.

This project addresses the problem of community membership detection on social media using only text features in a scenario where a small number of positive labeled examples defines the community. For example, if we are given the tweets of chess grandmasters, then the community is defined as chess grandmasters, and the model we propose should identify people likely to be chess grandmasters. We introduce user embeddings (dense vector representations of the users) trained on an unsupervised proxy task: user re-identification. Experiments with 16 different communities show that the resulting embeddings are more effective for community membership identification than common unsupervised representations, measured both by average AUC and 1/MRR measure.

Just as mountain-building from the convergence of tectonic plates changes weather patterns, the opposite, monsoons in southwest Asia, may have also influenced the erosion of the Himalayas. Turbidite sediments collected in International Ocean Discovery Program cores from the Bay of Bengal contain material eroded from the Himalaya, which may have been shaken up during monsoon destruction then resettled. Magnetic particles extracted from those turbidites were tested for magnetic properties and identified using scanning electron microscopy. Magnetic minerals positively identified include magnetite and sulfides. Linking these minerals to their sources in rocks and soils from the Indian Subcontinent and the Tibetan Plateau, we will be better able to model the erosion patterns back from 14,000 years ago, potentially correlating heavy storm activity in one region to massive sediment deposition downstream. This data may suggest whether the erosion from weather over a long period of time creates a negative feedback loop causing more intense climates overall. Further data that refines the ages of sediment layers can also relate how the severity of storms affects the increase in mountain erosion and runoff.

Recent observations of gravitational waves have opened up a new field of gravitational astronomy. Through this new field, many questions, thought difficult to address with electromagnetic astronomy, have become tractable. Gravitational waves allow us to look further back in time than conventional telescopes, and allow us to directly observe the gravitational interaction of compact objects. The North American Nanohertz Observatory for Gravitational waves (NANOGrav) collaboration aims to detect and study gravitational waves using a Pulsar Timing Array (PTA) made of millisecond pulsars. Pulsars are a special type of neutron star that emits radio waves at extremely consistent time intervals. The pulsars are monitored using the Green Bank Telescope in West Virginia and the Arecibo Observatory in Puerto Rico. To help study the signal from these stars, a project called the Pulsar Signal Simulator (PSS) is being built by NANOGrav and is the focus of my research. The simulator is able to calculate a pulsar signal from source to detection. It starts with the initial signal of a pulsar and adds the different effects that alter the signal, before it reaches Earth, such as dispersion, scintillation, and scattering. My project is to work on a portion of the simulator that takes, as input, the name of a known pulsar and automatically simulates a signal with user-defined changes. I aim to increase efficiency as well as validate simulation output. This project is beneficial to the NANOGrav collaboration by characterizing the noise in our galactic scale gravitational wave detector. Progress in gravitational wave astronomy will allow for deeper insight into galaxy evolution, black holes, and the early history of the universe.

Previous studies have shown that adolescents with type 1 diabetes (T1D) benefit from being involved in support groups by significantly decreasing their perceived diabetes burden and effectively increasing their knowledge of the disease. The purpose of this study was to assess the feasibility of Instagram as a platform to build peer-support among adolescents with T1D. Participants (13-18 years old with T1D for >6 months) were asked to post photos each week for three months based on predetermined topics related to diabetes management. At the end of each month, participants attended a focus group to discuss their photos using the Photovoice method. Feasibility was assessed through enrollment and retention, number of Instagram posts, post-study questionnaire, and qualitative analysis of the focus groups. Of 24 eligible participants, 16 enrolled (67%) with 3 dropping out prior to the end of the study. The number of photos posted over 3 months ranged from 13-31, and the number of likes given ranged from 5-34. Among the 11 participants who completed a follow-up questionnaire, 55% reported that they very much enjoyed participating in the program, and 95% of participants reported “relating to the photos posted.” Additionally, several themes emerged from qualitative analysis of focus group transcripts regarding their experience using the Instagram intervention, including: establishment of a diabetes community, change in participants’ perspective of the disease, and efficacy of using Instagram, such as direct messaging and having multiple accounts. The results of this study show that Instagram is both a feasible and acceptable form of social media in which to build peer-support. Future research should investigate the use of social media support groups to examine improvement of self-esteem, benefit-finding, and social support using validated tools in adolescents with diabetes.

Food waste is a pressing global issue. In the U.S. alone, 40 percent of food is wasted. With a 15 percent reduction, we can help feed more than 25 million Americans yearly and provide meals to the 15 percent of U.S. households who are food insecure (USDA). The University of Washington (UW) is taking strides to address this issue by working with food recovery agencies. However, these agencies are overworked and their food recovery program requirements deter some dining halls from participating. Utilizing a user-centered-design approach, our team researched, designed, and built an open source website to facilitate food recovery. Over the last 6 months, we employed six research methods: (1) we conducted a competitive analysis of food recovery systems; (2) we interviewed managers at UW dining halls and food service offices, 50 local shelters, and 6 food banks; (3) we completed a contextual inquiry of current food delivery practices; (4) we incorporated participatory design practices with 4 dining hall managers, 3 shelter managers, and 16 students; (5) we conducted iterative in-person usability tests with 25 participants including shelter and dining hall managers, and student groups; and (6) we deployed an online survey to understand the motivation and behavior of student volunteerism, receiving 78 responses. Among our many findings, we identified the need for improved communication among agencies, consistent and universal donation records, and strategies for utilizing student volunteers for donation deliveries. Currently, we are live-testing our website with one UW dining hall, two shelters, and two student volunteer groups. Our interactive, responsive open source website should prove scalable for global adaptation. Universities and corporations worldwide can utilize this system to improve their own food recovery efforts. Through our work, we are educating the public on the food waste epidemic, while building a network that prompts communal action.

The first-year population, with students transitioning from high school to college, is full of novel experiences. These experiences, be they academic, social, etc., influence the well-being of the student. The purpose of the study is to understand the first-year experience in a data-driven manner to create a cornerstone for institutional change. Although replicating a previously piloted study at Carnegie Mellon University in Spring 2017, this study extends focus to investigating stressful life events of first-years. Over the 2018 Winter and Spring quarters, a participant sample size of around 200 UW first-year undergraduate students (around 50% pre-/engineers) contribute data to the study. Data consists of both active and passive collection methods: participants actively respond to Qualtrics surveys, with questions investigating stressors, and passively via our phone software and FitBits. The two quarters of this study will yield tangible data that can be analyzed to advance the science of behavioral health and trauma. This data is unique in providing a picture of student behavioral changes after stressful experiences. Additionally, this advancement in science can become a basis for institutional change for student wellness. As the first-year population is only a slice of the overall student experience, we hope to expand this study further by encompassing the graduate student experience and the full four-year college experience in addition to a larger sample size.

For centuries, human beings have been using optics, which belongs to the electromagnetic family, to look at the universe. Now, an alternative way has developed, and that is LIGO. Different from the traditional electromagnetic observatory, LIGO (Laser Interferometer Gravitational Wave Observatory) uses gravitational waves to observe the universe. It is measures extremely tiny ripples in the space, which caused by very massive accelerating objects, such as binary black holes. In order to measure such tiny distortion in spacetime approximately 1/1000 of the width of a proton, LIGO has to be very sensitive even to the quantum scale. Therefore, the signal noise would be one of the major issues in the data collected from LIGO. BayesWave is a statistical algorithm which we use to help to analyze the data into different dimensions. Through this algorithm, one of the applications is characterizes the data to find out the non-astronomical-noise source, called “glitches”. For this project, my goal to is to help improve the success rate of finding glitches with this algorithm model. To achieve the goal, I downloaded data from LIGO and utilized it to BayesWave-model computer program. By changing the parameters comparing to the test data set, the success rate of sorting the glitches would be improved. With this algorithm, we are able to optimize the efficiency of sorting the data in a way that we could understand.

Rett Syndrome (RTT) is a neurodevelopmental disorder that is first recognized in infancy and almost exclusively affects females. The syndrome is characterized by normal development in the first 6 to 18 months of life, followed by a regression of developmental milestones, particularly the loss of mobility skills and purposeful use of the hands. Additional features of RTT include severe disturbances in cardiac and respiratory functions. These are characterized by prolonged QT intervals as well as increased respiratory rate and occurrence of abnormal respiratory events such as breath holds. RTT results from mutations in the gene encoding the protein MECP2, which helps to regulate gene activity. The location and type of the MECP2 gene mutation influence the course and severity of the syndrome. Previous animal studies and clinical case reports have suggested that ketamine administered at a low dosage can reduce deficits in brain activity and improve neurological function in RTT. In this pilot study, we sought to determine the efficacy of ketamine in reducing the respiratory and cardiac phenotype observed in RTT. Electrocardiography (ECG) and respiration patterns were recorded before and after treatments of four RTT patients with low doses of ketamine. Examination of these recordings showed that ketamine decreases heart rate variability, respiratory rate, and the number of abnormal respiratory events within the 20 hours post drug administration. These results suggest that low-dose ketamine treatment may potentially serve as an effective future treatment for the cardiac and respiratory symptoms of RTT.

LIGO (Laser Interferometer Gravitational-wave Observatory) is an international collaboration whose purpose is to detect Gravitational waves, and explore their implications on the fundamental physics of gravity and the behavior of our universe. Gravitational waves are a prediction of Einstein’s 1916 theory of Relativity. They are everywhere around us, but only detectable at large magnitudes such as from the collisions of black holes. The Gravitational Wave Astronomy research group at University of Washington contributes to LIGO data analysis and detector characterization. There are two LIGO detector facilities, one in Hanford, Washington, and one in Livingston, Louisiana. The data from the detectors contain gravitational wave signals as well as transient noise, known as glitches. Scientists use the two facilities, and Virgo, a partner observatory in Italy, to pinpoint the direction to the gravitational wave source and to ensure that readings are not just noise glitches at one site. Each facility has its own control room, including computer consoles displaying and processing data. At the University of Washington Bothell, my project was to design and implement a remote control room, modeled after those at the LIGO Hanford and LIGO Livingston sites. My goal was to set up a remote control room that can aid LIGO research by being able to characterize glitches and identify gravitational wave signals. My main role was determining the hardware and software necessary to implement a remote control room, such as Matlab and some LIGO specific programs. The capabilities of our remote control room include access to environmental monitoring channels and the ability to do our own simulated signal injections. We receive a live data feed directly from the facilities, which is exciting because we are able to see the current status of the detectors, including whether or not they are online.

Keeping exotic pets carries considerable risk for both the animals and their owners. Unlike with domesticated pets, acessibility to appropriate veterinary services and adequate care information for exotic animals are often minimal and difficult to obtain. Exotic animal laws vary considerably state-by-state, and even county-by-county; leaving generous loopholes for irresponsible and impulsive animal ownership. In this literature review, I've surveyed the physical and psychological impact that captivity has on exotic pets, as well as the health and safety risks posed on humans by the prevalence of zoonotic disease. I have also investigated the plausible options for decreasing the popularity of exotic pet ownership. High mortality rates, inadequate nutrition and living enclosures, and poor socialization have demostrated that exotic animals are at significant risk of not receiving the care they require. Literature on various exotic animals laws from across the United States show that enforceable, well-communicated laws, as well as easily accessible information on exotic animals concerning their associated diseases can be effective in discouraging people from owning exotic animals. Cohesive interstate laws are needed for easier enforcement, and legally requiring pets wholesalers to explicitly publicize the health and safety risks of owning exotic animals would go a long way in decreasing the popularity of owning exotic pets. 

Neural plasticity is a prominent feature of brain anatomy that is prevalent through various stages of development. However such plasticity is not maintained through the entirety of an organism's lifespan and diminishes at varying rates in different brain regions. As regions of the brain become less plastic, perineuronal net fibers increase, and can be taken as an indicator of the end of the critical period of plasticity. The presence of these fibers have been connected to numerous neurodegenative disorders and appear to be a prominent feature of the disorder group. I hypothesize that different neural regions follow different biological timelines and retain their neuroplastic properties for varying amounts of time. By measuring the growth and development of these fibers in the auditory centers of Eptesicus fuscus, I can establish a comprehensive timeline of their development. This allows me to develop a timeline of the pattern of plasticity within the different structures of the auditory system. This could provide helpful insight into the conditions under which neurodegernative disorders are more likely to occur. 

Familial Platelet Disorder with Predisposition for Acute Myeloid Leukemia (FPD/AML) is an autosomal dominant human disorder caused by germline, heterozygous mutations in RUNX1. RUNX1 is a master regulator of hematopoiesis and has specific roles in megakaryocyte maturation and the production of platelets. Monoalellic mutations in RUNX1 result in haploinsufficiency of RUNX1 protein, leading to thrombocytopenia and impaired platelet function before leukemic transformation later in life. RUNX1 is controlled through direct positive auto-activation and its half-life is tightly regulated through ubiquitin-mediated proteasomal degradation. Tightly regulated auto-regulatory circuits are known to have capacity as centers for epigenetic cellular memory. Cellular memory effect offers the opportunity to transiently manipulate steady state product levels and observe maintenance that continues the newly attained levels.The goal of this work is to determine if the positive feedback loop controlling RUNX1 expression has capacity for epigenetic cellular memory that is responsive to transient RUNX1 overexpression. We hypothesize that increasing the presence of endogenous RUNX1 in RUNX1-deficient cells will correct megakaryocyte maturation and platelet formation. To initially determine if an increase in the half-life of RUNX1 will correct megakaryopoiesis, a series of ubiquitylnation and proteasome inhibitors were administered to HEK 293t cells for 6hr, 12hr, and 24hr periods to determine their effect of RUNX1 production and stability, showing increases in RUNX1 expression at RNA and protein levels. iPSC's derived from FPD/AML patients will be ultimately differentiated and analyzed via flow cytometry to observe the inhibitors' effects on platelet production. Anticipated results from this work hope to confirm a dose-dependant response in the epigenetic programming of RUNX1 that could illuminate novel therapies for individuals with FPD/AML.

Pooideae is the largest grass subfamily, comprising over one third of all grass species. Pooid grasses are dominant in C3 grasslands which were once more widespread, but today are restricted to temperate or high elevation areas. During the last 8 million years, many C3 Pooideae were replaced by C4 grasses as regional climates became hotter and drier at low- to mid latitudes, or by forests when local conditions became wetter. Understanding when and where C3 grasslands first formed and when they were replaced by tropical C4 grasslands or forests is important for reconstructing global ecosystems and tracking climate change through time. Since grass macrofossils are rare, microfossils, particularly phytoliths (solid silica particles formed in plant tissue), which can persist in soils for millions of years, are the best paleontological evidence for the presence and abundance of different grasses through time. Grass phytoliths form highly regular shapes which may be specific to clades at low taxonomic levels; however, phytolith shape variation in Pooideae has not been analysed using quantitative methods. To better understand differences in shape within the subfamily, we extracted phytoliths from 36 representative Pooideae species. The phytoliths were imaged using confocal microscopy, and processed into 3D surface meshes for geometric morphometric analysis. We used the meshes as a reference collection to compare similarly processed fossil phytoliths from paleontological sites. Our goal was to use quantitative methods to confirm that the fossil phytoliths were correctly assigned to Pooideae and then to classify the phytoliths to lower taxonomic levels when possible. We used these results to infer a new time sequence for Pooideae evolution. In the future, this reference collection could be used to study domestication and spread of agriculturally important species in the subfamily (e.g., wheat, rye and oats).

UW's electricity bill is around $1MM per month, making it Seattle City Light's second-largest customer. Solar power represents one way that UW can reduce load on the city's power grid. In 2017, UW Housing and Food Services completed installation of four solar panel arrays to its buildings on campus. How have those panels performed, and has UW benefited from their presence? To gain insights into the effect of these installations, we developed the UW Solar Power Monitor to collect and present data about solar power usage within these buildings. The data was analyzed, interpreted, and integrated into the dashboard. Our hope is that the tools we have developed will enable UW administrators to make informed decisions about power infrastructure on campus, educate the public and promote awareness about solar projects on campus, facilitate the study and analysis of solar power, and encourage increased investment in solar infrastructure at the University of Washington.

Hydrogen fuel is a non-polluting, sustainable energy source that is a very attractive alternative to fossil fuels. A popular way to obtain this fuel is splitting water with semiconductor photocatalysts, which is inexpensive and efficient. This method relies on sunlight alone to activate the water-splitting photocatalysts. Once the catalysts have absorbed UV light, they begin to split the water molecules that are in contact with their surface. As a result of this, hydrogen fuel is produced more rapidly using a given amount of catalyst when the catalytic crystals have a high surface area to volume ratio, which means the smaller the crystals are, the more efficiently they work. To keep these crystals small, our research group uses a unique method developed by Dr. G. Allan to synthesize and store semiconductor photocatalysts. Instead of synthesizing them normally, we form the crystals inside cellulose fibers. This keeps them from losing surface area to agglomeration. The micropores of cellulose force the catalyst to form as small, insoluble, nanocrystals in a cheaper fashion than traditional methods. We then focused on finding the most effective semiconductor photocatalyst to be stored in fiber. The chosen photocatalyst must have specific properties. It must be synthesizable in an aqueous solution at less than 40 degrees celsius to keep the cellulose pores from collapsing or charring, it must be non-toxic, and it must have a band gap between 1.8eV to 2.7eV in order to absorb visible light. Our project group has spent the last few months researching different materials to determine the most beneficial materials, and we have concluded that the best possible candidates are black titanium oxide, niobium pentoxide, bismuth vanadate, zinc oxide, molybdenum sulfide, and tungsten trioxide. We hope to use these findings to promote an alternative source of clean energy into the market.

Probiotics are an area of significant clinical research, as they have been shown to aid digestion, fight infections, and even mitigate irritable bowel syndrome; however, probiotic colonies must grow and thrive in the extreme pH environment present in the human digestive tract. Previous experiments focused on the production of the surface protein Elongation Factor Thermally Unstable (EF-Tu), which attaches to glycoproteins lining the intestines and has been used as a biomarker for probiotic health. The growth of several strains of probiotics (Lactobacillus bulgaricus, Lactobacillus acidophilus, and Bifidobacterium longum) in both lysogeny broth (LB) and De Man, Rogosa, and Sharpe broth (MRS) was evaluated. The fractions of secreted, cytosolic, and membrane proteins were quantified using a Bradford assay. Finally, the relative amount of EF-Tu was determined by tryptic digestion and liquid chromatography-mass spectrometry (LC-MS). LB was found to be a more effective growth medium for the range of bacteria tested, with 24 hours at 37°C the ideal incubation period. To isolate the secreted proteins, the supernatant was drawn off the broth culture after centrifugation. Freeze-thaw lysis was used to extract cytosolic proteins, with three cycles determined as optimal for protein recover. Sodium deoxycholate was used to separate proteins from the membrane. All three protein samples were separated and run through a sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and the EF-Tu bands (roughly 43 kDa) were excised and sent for analysis by LC-MS. Using the information obtained from this research study, pharmaceutical companies can create more suitably tailored probiotic products, and make them more accessible and understandable to the general population. 

Prior research shows adolescents’ negative pain memories predict greater subsequent postsurgical pain. However, understanding of the content of memories and whether memories change over time is limited. We applied emotional stress theory, which proposes that negatively perceived events are recalled with more central (relevant) than peripheral (irrelevant) details, to examine how post-surgical pain memories change in adolescents and their parents. We hypothesized that 1) central memories would contain more negative emotion than peripheral memories, 2) ratio of peripheral to central memories would increase over time as memories become less negative, and 3) parent and adolescent memories would be associated at each time-point. Nineteen adolescents (12-18 years;63% female) who underwent major surgery and their parents were asked individually at 2-months and 12-months after surgery to recall “everything you remember” about being in the hospital and the initial weeks at home following surgery. Linguistic Inquiry and Word Count software was used to identify negative emotion words and N-Vivo software was used to code central and peripheral memories. Central memories included specific (“going through the doorway was…sheer pain”) and general (“kinda got better”) memories of post-surgical recovery. Peripheral memories ranged from inside (“clowns…visited me”) to outside details (“dad split his finger open”). As expected, central memories contained more negative emotion words than peripheral memories (p’s<.05). Use of negative words and ratio of peripheral to central memories were stable over time for parents and adolescents. In regression analyses, controlling for adolescent age, parent peripheral to central memory ratio was significantly associated with the adolescent peripheral to central memory ratio at 12-months (β=.57;p=.02), but not 2-months (β=.04;p=.88) after surgery. Findings suggest that memories are stable after two months. Associations within parent-child dyads were stronger at later follow-up. Future studies should assess earlier memories to increase knowledge of temporal association between memories and subsequent pain experiences.

Aging is a phenomenon that brings about the onset of many diseases and increases mortality. Understanding aging mechanisms can help us increase longevity and delay the onset of multiple chronic diseases. It has been previously observed that dietary restriction is a method that increases lifespan and delays the loss of function caused by age-associated pathologies. We used the roundworm, Caenhorbabditis elegans, to dissect the mechanisms of dietary restriction-induced longevity. Specifically, we focused on the phenomenon of adult reproductive diapause (ARD). ARD is induced when pre-reproductive juvenile larvae are subjected to starvation. Upon reintroduction to food after prolonged starvation, ARD worms undergo a morphological rejuvenation and resume a normal lifespan. Mechanisms that control post-diapause recovery are still quite unknown. We have found that the TGF-β/BMP signaling pathway is required for post ARD rejuvenation. The TGF-beta signaling pathway is a critical factor for growth processes including cell growth, differentiation, embryonic development, and much more. We aimed to characterize the role of this signaling pathway in ARD maintenance and post-ARD recovery. We hypothesized that TGF-β/BMP mutants accumulate excessive amounts of cellular damage during ARD and are unable to recover from ARD. To address this hypothesis, we analyzed markers of cellular aging among diapaused animals using fluorescent microscopy, in both wild type and TGF-β/BMP mutants. Using transgenic fluorescent reporter strains we examined pH, nucleolar morphology, mitochondria, and cytoskeleton and nucleoskeleton integrity for aging-associated phenotypes. These insights can help us understand the role of the conserved TGF-β/BMP pathway in dietary restriction induced longevity.

Disasters have direct and indirect public health impacts, and often result in healthcare system impacts. Prescription and illicit opioids are now the leading cause of death of Americans under the age of 50. A popular treatment of opioid addiction is called methadone. With more Americans relying on methadone treatment to maintain their sobriety, it is important to ensure that opioid treatment programs (OTPs) remain operational in the context of disaster. Several studies have assessed the impacts of methadone treatment disruption, and have proposed recommendations to minimize such disruptions and their associated impacts. We reviewed the literature to identify the causes and magnitude of the current opioid epidemic. Using the PubMed database, articles on the impacts of natural disasters on opioid treatment programs were identified. The articles selected for analysis discussed the impacts on OTPs that offered methadone services. We reviewed the references of included articles to identify other relevant articles to consider in our analysis. For each included article, we identified the context, the methods, the study area, and the recommendations made through the research. We calculated summary statistics to describe the types of recommendations made by context and area. Sixty-eight percent of the articles suggested the need for a well-defined emergency procedures. Seventy-seven percent of the articles stressed the need for programs to educate clients on disaster preparedness. It is imperative that OTPs remain operational during a disaster. Additional research is necessary to test the effectiveness of these recommendations, and how feasible they are to implement.

Although commensal E. coli is an inhabitant of the normal flora of humans and most animals, including crows, several variants have been found to be the cause of gastrointestinal as well as extra-intestinal diseases, such as in urinary tract infections. Based on previous phylogenetic studies, infection causing strains were more likely to be members of either B2 or D phylo-groups rather than A or B1. This study investigates the most common phylo-groups among crow fecal samples and water samples influenced by crows at the wetlands within the University of Washington, Bothell campus. It is expected that B1 and/or A groups to be more dominant than other phylo-groups because the commensal E. coli is likely to be abundant in these samples. Fecal samples were collected from the UW Bothell wetlands on four different dates. Water samples were also collected on the same dates from four sites within the wetlands; two sites within the crow roosting area and two outside of it. A quadruplex PCR assay was used to detect the genes chuA, yjaA, arpA and a DNA fragment TspE4.C2. Gel electrophoresis was used to determine the presence/absence of these four fragments from which an E. coli strain could be assigned to one of the 8 main phylo-groups. Results of fecal samples showed Group B1 to be most predominant in 37.93% of samples, as expected, followed by B2 with 22.41%. For water samples, phylo-group B1 was also predominant with 26.67% frequency followed by phylo-group B2 with 17.78%. Since the North Creek flows past the roost area, it may bring in strains of the B2 or D phylo group, especially due to storm water runoff following a rainfall. Those E. coli strains that are found to be under the B2 or D phylo groups will be used to look for virulence-associated factors.

Olympia oysters (Ostrea lurida) are the only native oyster species in Washington State. Over the past 100 years populations have dwindled, but due to restoration efforts, Olympia oysters are slowly recovering. So far there is limited information about the behavior during the larval stage. Previous observations suggest that larvae would be more abundant at the surface compared to the bottom of the water column. In this study, we measured the spatial distribution of larvae at surface and bottom depths in Fidalgo Bay, WA during the Summer of 2013. Plankton samples were taken from 4 intertidal and 2 subtidal stations pumping 100L of seawater through a 75 µm sieve. Olympia oyster larvae were identified using light microscopy, measured for shell height and length, and tallied to determine abundance and distribution. As predicted, larvae were not randomly distributed across the bay, and more larvae were found at the surface for each site. We found an order of magnitude of more larvae at surface depths during ebb tide, indicating that larvae are being transported out of the bay. These results are being combined with additional temporal and spatial sampling, as well as environmental data, to fully describe the larval distribution of oysters in the bay. This study will improve restoration efforts as well as inform researchers and local communities about the early life stages of Olympia oysters.

American crows (Corvus brachyrhynchos) settle every night in large groups called communal roosts, which can contain thousands of birds. Song sparrows (Melospiza melodia morphna) hold territories under four communal crow roosts that we have identified in western Washington. Crows are nest predators to these sparrows, and their presence above a sparrow’s territory may influence their behaviors. In this study, we investigated how crow roosts impact song sparrow behaviors by measuring their response to conspecific song and distress call playbacks. We observed the behaviors of song sparrows with territories under crow roosts and non-roost areas during fall and winter. In fall, roost sparrows made more chip calls in response to song playback. Chip calls are vocalizations often given in the presence of predators. Roost sparrows also tended to approach the speaker more closely during distress call playback (p=0.08); this is potentially representative of predator inspection behavior. Fall baseline and stress-induced corticosterone levels in roost and non-roost sparrows were compared to determine if this stress hormone was driving the increase in antipredator responses, but levels did not differ. In winter, roost sparrows approached more closely, spent more time within 1m, made more aggressive movements, and sang more songs towards the speaker in response to song playback. During winter there were no differences in the behavioral responses to distress call playback. We have determined that communal crow roosts impact song sparrow responses to song and distress call playback, and that these changes vary seasonally.

The hindbrain, including vital sensory and motor neurons, develops into the pons and medulla of the brainstem. During development, waves of spontaneous activity (electrical activity present without stimulation; SA) influence neuronal circuitry and change spatiotemporally in a characteristic pattern. The upregulation of a resting potassium channel, KCNK9, mediates the gradual decrease in SA in the hindbrain, beginning at embryonic stage (E)11.5. Cannabinoids derive from marijuana and act on CB1 receptors in the central nervous system to affect motor control, mood and memory through altered neurotransmitter release. Previous reports in the literature have demonstrated that AM251, a CB1 antagonist, binds to KCNK9, opening the channel. The goal of my research project has been to use intracellular calcium imaging to test the hypothesis that cannabinoids act on the KCNK9 channel to alter or regulate spontaneous activity. This involves determining whether cannabinoids affect hindbrain SA by utilizing the CB1 receptor or by binding directly to the KCNK9 channel. To test this, I used both AM251 and a CB1 agonist, ACEA (arachindonyl-2’-chloroethylamide). I predicted that AM251 would open or augment current through KCNK9 channels, either by binding directly to the channel or via CB1 receptor binding, and would slow SA by hyperpolarizing the cells; in contrast, I predicted that ACEA would decrease KCNK9 current, increasing SA. Increasing concentrations of AM251 (ranging from 200 nM to 2 µM) do indeed decrease SA; the effect of ACEA is less clear and requires further study. Should a clear effect on hindbrain SA be found, this will demonstrate that embryonic spontaneous activity can be modulated by use of cannabinoids, perhaps altering the neuronal circuitry during development.

In a warming world, where growing human population continually intensifies demand for agricultural yield, studying genetic and molecular mechanisms underlying plant development and morphology becomes increasingly critical. As in other multicellular organisms, development, growth, reproduction and stress-response in plants are regulated through a complex network of signaling pathways, which, though spatially tiny, have a mammoth impact on organismal-level fitness. In the model angiosperm Arabidopsis thaliana, a symphony of such signals coordinates during early development to dictate the patterning of stomata, small epidermal guard cell–pore complexes that facilitate gas exchange vital for driving photosynthesis and thus biomass production. Several tiers of signal cascades, each executed by a distinct group of molecular players, regulate this process to prohibit two adjacent protodermal cells from becoming stomata, creating a spacing pattern critical for plant fitness and thus our sustenance. In one such tier, perception of several characterized members of the Epidermal Patterning Factor (EPF) peptide family by transmembrane receptor like kinases tunes downstream signaling that regulates stomatal cell fate. EPF1 and EPF2 act in this manner to inhibit a cell from advancing towards a stomatal fate, while EPFL9 acts to promote it, but actions of several other EPF members remain unknown. One such “mystery,” EPFL7, shares closest sequence homology with EPF2, and curiously is expressed in vascular tissue during early plant development. As the epidermis above vascular tissue in Arabidopsis and most other vascular plants is regularly devoid of stomata, it is possible that EPFL7’s expression confers an arresting signal similar to that of EPF2, preventing differentiation of protodermal cells above vasculature into stomata lineage cells. My project evaluates this and two other possibilities: EPFL7 functions in the stomata development pathway, either (1) inhibiting or (2) promoting it, or (3), EPFL7 may be involved in other processes, such as vascular development.

The United States recycles or composts only a quarter of its waste, with the remainder being buried in landfills. Organics, paper, and plastics, which can be recycled and composted, comprise the three largest categories of landfilled materials. It has been demonstrated that familiarizing youth with proper waste disposal methods increases landfill diversion at school and home, resulting in behaviors that continue through adulthood. In this study, I used a solid waste audit to characterize the waste disposal of a large Washington middle school. Initially, I used a survey and focus group to better understand the research needs of this particular school. Targeted goals and specific research questions were then derived from these data, which had been collected from the school’s green team. Fifteen students from the green team completed the survey, while seven participated in a focus group to further articulate their goals and aims. The overall goals were to reduce the school’s total amount of food waste and improve sorting efficiencies. Research questions included: how much waste is improperly disposed of, which materials are misplaced most, and how well do teachers sort their waste compared to students. I then conducted the audit during Spring quarter. Waste was collected from three student lunch periods as well as the teacher’s lounge and was then sorted into disposal categories, examined for contamination, and weighed. Data analysis included identifying barriers to disposal. In collaboration with the school’s green team, I then used my findings to help inform the creation of more targeted and efficient interventions. Participation in the waste audit’s design and analysis helped create a more meaningful experience for students to reflect on their own disposal habits. Hopefully, this research may act as a guide or template so other schools may incorporate waste audits into their own recycling or composting programs.

 Microbially Induced Calcite Precipitation (MICP), or bio-cementation, is a bio-mediated soil improvement process that can improve the engineering properties of granular soils through the precipitation of calcite on soil particle surfaces and contacts. In the urea hydrolysis driven process, soil microorganisms containing urease enzymes can catalyze a hydrolysis reaction that degrades urea, producing total ammonium, dissolved inorganic carbon, and hydroxide ions. In the presence of sufficient soluble calcium, the resulting carbonate production can supersaturate solutions with respect to calcite and initiate precipitation. The process has shown significant promise as an environmentally-conscious alternative to traditional ground improvement methods, which oftentimes rely on high mechanical energy and energy-intensive materials to improve soils. Despite many recent advances in MICP, environmental concerns regarding the fate of nitrogen by-products have remained largely unaddressed. In this study, soil column experiments were performed to examine the transport, removal, and transformation of nitrogen by-products following MICP. Columns were 7.6-cm in diameter, 17.8-cm long, and contained a poorly-graded sand material. Soil columns received identical treatment solution injections over 14 days targeting a post-treatment calcite content of 4% to 5% by mass. During treatments, non-destructive geophysical measurements were completed to monitor changes in soil stiffness and pore fluid compressibility resulting from carbonate degradation. Aqueous samples were obtained from all columns in time to examine changes in solution chemistry related to microbial urea hydrolysis, calcite precipitation, and ammonium sorption and transport. Following cementation treatments, columns received rinse injections of differing ionic strengths and pH values to investigate the effect of rinse solution chemistry on by-product removal. The results of this study will address critical knowledge gaps currently limiting practical application of MICP technology and will guide future efforts to model the transport and removal of ammonium by-products following bio-cementation.

At one point or another, every student is faced with some sort of academic failure that can in turn have negative impacts on self-esteem or future academic performance. Being able to overcome such obstacles requires resiliency and the ability to view failure as a learning opportunity. Growth Mindset (GM) interventions aim to shift a student’s perception of intelligence as a quality that can be developed over time and enhance their approach to overcoming barriers. Originally, the GM was developed as an evidence-based intervention to be delivered by trained professionals. However, bringing this intervention into the real-world calls for a more feasible and accessible model. To bridge this gap, the current study utilizes the role of teachers as a valuable resource in building capacity within schools to attain sustainable, long-term goals regarding student success. The purpose of our research is to explore how a GM intervention delivered by teachers affects students’ beliefs about the brain’s ability to change (neuroplasticity). This project utilized a randomized control design with longitudinal follow-up to evaluate the efficacy of the GM intervention in comparison to curriculum as usual delivered in a rural district in the Pacific Northwest region. At two separate time points, middle and high school students completed an online self-report survey that assessed three constructs: theory of intelligence (whether intelligence can be changed), effort beliefs (the relationship between effort and outcomes), and learning goals (goals towards improving academic abilities). We hypothesize that students assigned to the intervention would show more positive implicit attitudes towards malleable intelligence, beliefs about effort, and learning goals. By understanding how students view themselves within an educational context, we can improve the measures taken to further engage and empower students. Future research should evaluate the quantitative outcomes of academic performance (i.e. grade point average) in relation to a GM intervention.

Black women are known to wear their hair in different ways from braids and locs to weaves and wigs. Black hair is a way of expression and a lot of thought goes into the process and maintenance of black hair. Early African civilizations used hair as a signifier for their wealth, rank, religion, and marital status and the Afro hair was seen as a political symbol for black power and self-love. Hair is so important to black women that a 2016 Perception Institute research found that black women reported spending more on their hair and booking more professional hair appointments than white women. And while our hair means so much to us, it remains a mystery to many non-black people and so we become the objects of inquiry: we are constantly fielding questions about our hair. I examined the ways in which questions like: “can I touch your hair?”; “how often do you wash your hair?”; and “is your hair real?”, affected black women’s self-esteem and confidence. The study first established what was an intrusive question and the historical and political implications of black hair. Through a focus group with 10-15 black women ages 18-24 along with follow-up interviews with some of them, the study highlighted some of the experiences young black women have faced about their hair and the impact of the intrusive questions on how they viewed themselves. I expected the focus group to reveal that those intrusive questions left black women feeling uncomfortable, inauthentic or fake, and stopped them from frequently changing their hairstyles.

Diversity structures within organizations (e.g., diversity awards, diversity training) can create illusions of fairness: the perception that a company is treating all employees equally because of the mere presence of diversity promoting intiatives without confirmation they are being enforced. This leads to both minority and majority group members perceiving organizations as more procedurally just and less discriminatory even in the face of contradictory evidence. This research expands upon such findings by examining how diversity awards influence what types of information people use in determining if sex-based discrimination disadvantaging women is occurring at an organization. Preliminary analyses show that individuals exposed to diversity awards (vs. control condition) are less likely to perceive sexism-disadvantaging women occurring within a company. Additionally, diversity structures lead women and men to seek out different types of information: women are more likely to perceive information relating to formal discrimination as more informative whereas men are more likely to perceive information relating to informal discrimination as more informative. These findings provide insight into what types of information regarding discrimination are acknowledged versus ignored, and they reinforce prior findings that diversity initiatives lead to the perception of a less discriminatory workplace without actual evidence affirming these beliefs.

 Respiratory Syncytial Virus (RSV) is a common respiratory virus for which there is no vaccine. Over 60% of children are infected with the virus during their first season (winter months) and nearly everyone gets the virus before age 2, with reinfection occurring numerous times throughout life. In healthy individuals, symptoms are usually mild, but in young children, especially premature babies, and elderly (older than 65years old) adults, RSV can cause serious bronchiolitis and lead to hospitalization and death. While no prophylactic RSV vaccines are currently on the market, many are in development including the UW IPD Icosavax’s protein nanoparticle vaccine which shows a strong humoral response with 8x better neutralizing antibody titers than antigen alone. A business case assessment and asset valuation for commercial development of the RSV nanoparticle vaccine for adults 65 years of age or older was performed. We calculated the current expected net present value for the asset based on RSV prevalence, the burden it creates, current vaccination practices, and industry standards. Gathering this information required extensive review of published literature and market reports, and the data was used to create a series of discounted cash flow valuation models. These models indicate that the vaccine asset is worth somewhere between $8M and $38M today, depending heavily on competition, public acceptance and vaccine coverage rates, and cost of goods. The valuation models can be used to facilitate conversation with potential investors and acquirers and plan future decision making to profitably operate Icosavax.

People all over the world use forecasts from various sources such as the National Weather Service, local TV/radio stations, or apps on smartphones for a variety of applications. Examples include preparing for routine activities, such as planning outdoor events, or preparing for rare, yet hazardous scenarios like a thunderstorm passage near a sporting event. The most common quantities of interest are maximum/minimum temperatures, wind speed, and rainfall (chance and amount). To approximate these quantities, weather information sources utilize forecasts made from numerical weather prediction models of which there are about ten used in the United States. Numerical models of the atmosphere consist of equations that describe the current state of the atmosphere and how it changes with time and location. These equations are solved on powerful computers as the number of calculations are immense. Using the information from these models, individual forecasts can be made. Atmospheric Science students at UW are practicing forecast techniques through participation in a national competition called WxChallenge—a contest where participants from various academic institutions predict these quantities for selected US cities. For help with forecasting, the UW team has developed a website that holds a suite of model information which easily analyzes and compares that data and assesses the skill of each individual model. This website, however, needs updates and improvements. Therefore, I am converting the existing system to an object-oriented format by creating Forecast objects for individual weather models. For example, I have written a Forecast object for the DarkSky weather model using Python code. This type of improvement will reduce redundant code and allow for future developments to be implemented with ease. I am confident that this updated system will help the UW team improve the accuracy of their forecasts.

Store-and-forward teldermatology (SFT) has grown in use nationwide to increase accessibility of dermatological care especially towards underserved populations. It has demonstrated its cost-effective services by minimizing avoidable referrals to dermatologists and granting quicker overall access to dermatologists for initial interventions. However, due to transportation and other logistics, there are concerns that SFT may have significantly longer delays and lengths of treatment of malignant melanoma than face-to-face (FTF) dermatology. Melanoma is the most lethal type of skin cancer which makes it imperative to seek intervention as soon as possible. We conducted a descriptive comparison of melanoma discovery and timeline for treatment among veterans whose melanomas were discovered and treated through face-to-face and store-and-forward teledermatology. We tested the hypothesis that SFTD is non-inferior to FTF dermatology in discovery and treatment of primary cutaneous melanoma. We ascertained chart data for Veterans diagnosed with melanoma between January 1, 2006 through December 31, 2013 from VA corporate data warehouse (CDW), Veterans Integrated Service Network 20 (VISN 20) and and Computerized Patient Record System (CPRS). To determine possible opportunities to discover a melanoma, and lengths of each episode of care, we retrospectively analyzed 300 cases of melanomas 365 days prior to the date of their biopsy to the date of its definitive procedure. The mean days between the earliest opportunity to discover and discovery, discovery to biopsy, and biopsy to definitive procedure was 90, 39, and 41 days respectively for melanoma cases seen by FTF dermatology and 44, 50, 40 days respectively for melanoma cases seen by SFTD. With no biological significance between the timelines of care, SFTD is non-inferior to FTF dermatology in timeliness to treat melanoma. 

Oysters support a multi-million-dollar aquaculture industry in Washington State and provide important ecosystem services in estuarine habitats. Sustaining aquaculture and restoring native oysters depends on oyster health. Food availability is a driver of oyster health that interacts with environmental effects of global climate change. These global changes may be altered by the effects of local species interactions like association with eelgrass. Measuring essential fatty acids, which are necessary for survival and physiological processes of oysters, can show the level of food availability to oysters in environments with and without eelgrass. We tested the hypothesis that eelgrass alters oyster health by growing oysters inside and outside of eelgrass at 5 sites in Washington state. We used fatty acid composition of tissue from Pacific and Olympia oysters to look at changes of assimilated food in relation to habitat and environment. We predict that eelgrass will slow water flow, resulting in a decrease in food availability and thus essential fatty acid concentration in oysters grown in eelgrass. Looking at essential fatty acids of oysters from different environments, specifically with or without eelgrass, provides a better understanding of environmental impacts on oyster health and contributes to a collaborative effort in Washington state focused on sustaining the valuable food production and ecosystem services of oysters in our ever-changing climate.

Type I and type III interferons (IFNs) are the key modulators in innate immunity that mediate antiviral responses to clear infections. It is known that the two families of IFNs signal through the same JAK/STAT signaling pathway to induce a similar antiviral response despite engaging different receptors. By utilizing the same signaling pathway, the two IFN systems converge upon a common transcription activation complex known as Interferon Stimulated Gene Factor (ISGF3), which induces gene expression once it is fully assembled. Intriguingly, their downstream responses differ greatly. While type I IFN induces a robust but pro-inflammatory response, type III IFN induces a more delayed but sustained response without triggering inflammation. The molecular mechanism governing this differential outcome remains poorly understood. We proposed that such outcome is due to a differential ISGF3 recruitment, which in turn governs the induction of pro-inflammatory chemokines. Since ISGF3 complex consists of STAT1, STAT2 and IRF9 subunits, and its gene transactivation ability is dependent on STAT1 and STAT2 activation, it is possible that differential phosphorylation of these transcription factors accounts for the initiation of the inflammatory responses. To investigate the functional implication of STAT1 and STAT2 activation, we stimulated STAT1-deficient U3A and STAT2-deficient U6A cells with type I IFN, and measured the expression of downstream genes that are known to be pro-inflammatory. Our results show that STAT1 is the crucial factor that accounts for the different outcome between the two IFN systems. Considering that type I IFN are used extensively to treat chronic viral infections, but its pro-inflammatory nature results in poor clinical outcomes, such understanding may elucidate a new therapeutic target that can be manipulated to minimize inflammation associated with IFN treatment.

Nuclear fusion power is one of the best candidates for the next generation of energy. It has many desirable properties such as producing more energy than fossil fuels per kilogram of fuel, zero carbon emission, and producing no long-lived radioactive waste. Therefore, nuclear fusion power is worth pursuing and it has been studied for decades. One of the critical issues in nuclear fusion research is the impurity contamination. The impurities released from plasma-facing components through various plasma-wall interactions can lead to dilution of the fusion fuel. Therefore, it is very important to study impurity content and behavior. The impurity level is an important parameter in the research of magnetically confined plasma and can be quantified by the ion effective charge, Z_eff. Ion effective charge can be derived from bremsstrahlung emissivity from the visible spectrum radiation of plasma. The objective of this project is to set up a calibrated system that yields high precision in measuring bremsstrahlung emissivity. It is important to absolutely calibrate the system because impreciseness of bremsstrahlung emissivity measurements gives the inaccurate values of Z_eff. In our calibration, a Stabilized Halogen Light Source (SHLS), integrating sphere, and a photodiode are used. We collimate the light from SHLS and send it to the integrating sphere through fiber optics. The light in the integrating sphere is captured by a photodiode and a telescope and is transferred to current and voltage signal respectively. Our goal is to get the correct calibration factor that will give us correct values of bremsstrahlung emissivity measurements.

Flowering is crucial to a plant's lifecycle because it determines reproductive success for the plant. Scientific understanding of the molecular mechanisms that direct this process are constantly being revised and expanded as more is discovered about how plants sense their environment and adjust their flowering time in order to optimize reproductive success. In this study we explore the molecular mechanisms involved in the FKF1 photoreceptor signaling pathway. FKF1 is a blue light sensitive photoreceptor that influences FLOWERING LOCUS T (FT) gene expression, which induces flowering in plants. The molecular mechanism of activation of FT expression under high light has not yet been fully characterized. By comparing relative gene expression in cat2 mutants we found six transcription factors that have the potential to bind to the FT promoter and show significantly higher expression levels under high light conditions. Our research focuses on these six transcription factors and their potential impact on flowering time in the plant. To study these transcription factors, we are developing transgenic lines to analyze the effects of knocking down or overexpressing these genes. We will look at the resulting phenotypes of our transgenic plants in order to develop models that explain the suppressive or activating effects of our transcription factors. This will further our understanding of how plants regulate flowering under high light conditions. By achieving a deeper understanding of plant development, we can devise ways to maximize agricultural output in order to feed an ever growing global population.

Studies have shown that both Notch signaling and the transcription factor Sox2 are involved in development of hair cells and support cells in the inner ear, which are essential for hearing and balance. To determine when and where the Notch signaling pathway and Sox2 interact in cells of the cochlea, we observed location of Sox2 and the Notch pathway proteins, Rbpj (transcription factor) and Jagged 1 (ligand of Notch receptors), in mice cochlea at different developmental stages using immunofluorescence labeling. We have observed that Rbpj levels are possibly higher in the floor of the cochlear duct--where the prosensory cells (Jag1+/Sox2+) are--than in the roof of the cochlear duct. This could suggest activation of the Rbpj gene by Sox2 activity or vice versa. To determine whether Sox2 could activate the Rbpj gene or Rbpj could activate the Sox2 gene, we will predict Rbpj- and Sox2-DNA-binding motifs in the open chromatin near Sox2 and Rbpj genes using informatics and our lab’s ATAC-seq data. If Sox2 binding sites are found near the Rbpj gene, then that could suggest activation of Rbpj by Sox2. If Rbpj binding sites are found near the Sox2 gene, then that could suggest activation of Sox2 by Rbpj. These findings will help us understand how Sox2 and the Notch pathway interact to influence development of hair cells and support cells.

Due to urbanization and city development, more people are losing contact with nature that earlier generations were more likely to have had. Children who grow up in urbanized, and poverty impacted spaces are likely to have less experience of fully immersing themselves in nature. All children should receive equal or similar benefits from their environment. Hence, for those children attending preschools in the urban grid, we can think about ways to create opportunities for nature-based play and exploration in order to bring benefits associated with nature to all children for an optimal childhood development. Playspace is a space for an outdoor learning environment, where children learn to socialize, wonder and grow. Naturalized outdoor environments offer developmental benefits—psychological, social, physical, cognitive, health—for the growing young child. Children will grow stronger immune system, growth and physical advantages through interaction with nature. Children can also experience increased concentration, reduced stress, better social-communication skills and academic performance. It is where children can reclaim their freedom of exploration in the natural world. My research analyzes how children, in the context of an existing naturalized outdoor preschool, use the space for play and learning in a number of areas of development. I apply this study of the outdoor preschool to a more urbanized project site, University of Washington Children’s Center at Portage Bay. I conduct interviews with teachers from both centers and observe children to gather information on what is missing and what can be supplied. Using in particular the study by Robin C. Moore, Nature Play and Learning Spaces, I propose a framework of playspace elements that can convert a more traditional childcare center’s outdoor space into a place where children can receive a “daily minimum dose”—as Moore states—of natural experiences and acquire love and respect for the natural world.

In Washington State, the goal of the Washington Fish and Wildlife Department’s gray wolf (Canis lupus) conservation and management plan is to not only help wolves naturally re-establish a sustainable population across the state, but also to reduce the conflicts with humans, livestock and other wildlife. A successful implementation of this requires us to understand how the public values wolf management and what factors could shape this kind of value. The purpose of this study is to examine Washington State residences’ willingness to pay for wolf-livestock coexistence projects from a statewide survey including an attribute-based choice-experiment. Willingness to pay shows the maximum amount of money an individual wants to sacrifice to procure a good or service, it can be influenced by personal interests, preferences, incomes and demographic background. In this study, I explore the survey data using random utility maximization (RUM) models to identify both heterogeneity and homogeneity factors that may affect Washington residents’ willingness to pay for wolf-livestock coexistence. I also apply Machine Learning to select covariates that help to generate highly accurate prediction models. An individual’s willingness to pay for wolf-livestock coexistence projects is expected to increase as their income, knowledge about wolf conservation status, and attitudes to wolf conservation increase. The aims of this study are to have a comprehensive understanding of people’s willingness to pay for projects designed to promote human-wolf coexistence and to provide implications for conservation groups and organizations to find alternative funding sources in the future.

Oil-spills are a widespread hazardous environmental issue, often caused by mistakes when drilling or transporting crude oil. The effects are devastating to the ecosystem. There are very few ways to quickly clean up an oil spill efficiently, at low cost and without additional environmental damage, as often they are cleaned by using expensive chemical dispersants. We conducted research on an environmentally friendly and inexpensive solution to this problem by using pearl oyster mushroom mycelium. The pearl oyster mushroom has a lignin decomposing basidiomycotina that produces a set of extracellular ligninolytic enzymes that have bioremediation properties. Our hypothesis is that, oyster mushrooms can be used to clean oil spills. We cultivated the mushroom mycelium in straw on trays with different amounts of oil on them. We grew this in a greenhouse with controlled temperature and allowed 4-6 weeks for the mycelium to eat the oil. We are currently observing the results. After 6 weeks, we will filter out the remaining hydrocarbons with a solvent and determine if the mycelium reduced the amount of hydrocarbons or consumed them entirely. Our anticipated results are that the mushroom will clean up the oil in six weeks. For future work, we plan on conducting this same experiment but in a salt water environment to explore applications for mycoremediation in a simulated ocean environment.

Bisphenol A (BPA) is a lipophilic toxin and an endocrine disruptor that has been shown to interrupt normal hormonal functions in invertebrates. BPA can bioaccumulate in filter feeders like marine mussels, which are both economically and environmentally important species. Previous studies have shown that mussels are sentinel organisms because they can detect toxin contamination in their aquatic environment by producing fewer byssal threads. Byssal threads are necessary for their survival in tidal zones as well as in suspension-culture mussel farming. It was hypothesized that when exposed to high concentrations of BPA, the mussel Mytilus trossulus would produce fewer byssal threads and have higher concentrations of BPA in their tissues. Using a single-subject design, 32 mussels were placed in seawater microcosms for 24 hours and exposed to different BPA concentrations (control and 1-9 ppm BPA). Their byssal threads were counted afterwards. High performance liquid chromatography-photodiode array (HPLC-PDA) analysis was used to determine the BPA concentrations in both the mussel tissue samples and the microcosm seawater. Mussels exposed to high concentrations of BPA produced significantly fewer byssal threads and had higher concentrations of BPA in their tissues compared to the controls. BPA’s lipophilicity allows it to bind to food particulates and mussel gills, resulting in the compound to bioaccumulate in the organism. Without byssal threads, mussels exposed to BPA would experience high mortality in tidal zones as they are more easily dislodged by waves and predators. There would also be massive economic losses in the shellfish aquaculture industry that use suspension-culture farming.

There has been a research effort in exploring RFID (Radio-frequency identification) interfaces. RFID is a form of wireless communication that uses electromagnetic coupling in the radio frequencies to uniquely identify an object, person or animal. By expanding on previous work in paper and RFID technologies, we are able to create new interactive capabilities from paper and RFID. During my time with the Ubiquitous Computing Lab, my goal is to find a technique using capacitive sensing, conductive ink, and RFID tags in order to create an interactive touch surface. An RFID antenna can read an RFID tag and give information pertaining to that tag, for example, tag ID, time, a tag’s doppler shift, tag’s signal strength and more. My research has been exploring the relationship among these variables and creating a quantitative model that can map for continuous interactions. With such a model, one can make that surface customizable for a variety of interactions. 2D Sense strives to enable 2-dimensional touch interactions on paper by applying signal processing techniques towards existing RFID technology.

Oncolytic adenoviruses such as serotype 5 adenoviruses (Ad5) selectively infect and destroy cancer cells and are widely used in preclinical and clinical trials for gene therapy. However, Ad5 has many downsides including preexisting anti-Ad5 immunity in humans, and the Ad5 receptor (CAR) is known to be down regulated in many aggressive tumors. Species B adenoviruses which use a different receptor than CAR are an alternative which shows great promise. These vectors avoid the immune response against Ad5 and show different cell tropism. Our lab has identified desmoglein2 (DSG2) as the main receptor for a group of species B adenoviruses, including Ad3. DSG2 is an epithelial junction protein and is highly expressed in malignant tumors. During Ad3 infection, binding of Ad3 fiber to DSG2 triggers the transient opening of these intercellular junctions and thus supports the lateral spread of the progeny virus. Our lab has recently developed an Ad3 fiber knob mutant (Y250F) which has an enhanced affinity to DSG2. We have shown that an increased affinity is correlated with a stronger ability to open these junctions. In this study, we developed an Ad3 based oncolytic vector containing fibers with enhanced affinity to DSG2 (> 400x higher than wild type Ad3.) We developed this vector using PCR site-directed mutagenesis and cloning the recombinant gene in E. coli. By inserting our gene into a Ad3 plasmid it allowed us to transfect the plasmid into human embryonic kidney cells (HEK 293 cells) and to amplify and recover the mutant oncolytic virus. We are working on in vitro experiments and in vivo tumor xenograft models to test our hypothesis that the oncolytic virus with an enhanced affinity to DSG2 will be translated to a significant improvement to the spreading of progeny virus, and thus a significant improvement to the effectiveness of oncolytic virotherapy.

Degeneration of mechanosensory hair cells in the inner ear leads to complications in hearing and balance. Calcium plays an important role in hair cell function and failure to maintain calcium homeostasis is an underlying cause of hair cell death. We used hair cells in the zebrafish lateral line as our model, to explore the role of endoplasmic reticulum (ER)-mitochondrial calcium flow in hair cell damage. We utilized ER-GCaMP-150 for these studies, a new low-affinity calcium indicator made distinctly to look at calcium concentrations in the ER. Injection of zebrafish embryos with ER-GCaMP-150 expressed under a hair cell specific promoter allowed for visualization of ER Ca²⁺  concentrations under a high-resolution microscope. To date we have confirmed expression of ER-GCaMP in our zebrafish models and quantified Ca²⁺ transfer between the ER and mitochondria. Examining changes in calcium concentrations of hair cell organelles provides the opportuninty to gain more insight into the intracellular mechanisms underlying hearing loss.

 Culture is often characterized through such examples as art, language, or social customs, but researchers who study the influence of culture on individuals have found that that influence can go much deeper, affecting not only the way an individual behaves in social environments, but also the way they experience the world internally. Ethnographies that focused specifically on the emotional concepts members of a culture use to define their experiences suggest that our understanding of supposedly basic and universal emotions might be much more subjective and culturally dependent than previously thought. In recent years, a number of psychological studies have suggested that our concepts of emotion come only from primitive physiological arousal, and any more complex experiences and definitions are entirely culturally and socially constructed. This literature review critically evaluates, compares, and contrasts research on the study of emotions from several disciplinary perspectives to explore to what extent emotional experiences are universal, and whether different methods of studying emotions in culture can inform each other. This literature review examines work by researchers from fields including anthropology, psychology, linguistics, and communication. Recent psychological research on the neurological origin of emotions could have profound implications on how ethnographers understand, study, and discuss emotional concepts in cultures. Combining this psychological approach with future ethnographic studies of emotional concepts in cultures has the potential to deepen our understanding of how emotions are constructed and how they vary in different cultures. More broadly, such a collaboration could shed light on the extent to which culture constructs humans’ internal reality and experiences.

Individuals experiencing homelessness show higher rates of substance abuse than housed individuals, and religious organizations provide many of the recovery services available to these populations. Religious affiliation has reduced substance use, helped individuals manage stressors, and allowed individuals to build relationships around common values. This study investigated the role of religion in recovery in homeless populations. Fourteen individuals (9 men, 5 women, ages 23-69) in recovery programs completed 40-60 minute interviews. Participants answered questions about their substance history, recovery process, religious beliefs, ideas of self, and community. Interviews were transcribed and coded, and emerging thematic frameworks were created. Three raters re-coded interview transcripts according to the frameworks. Participant responses suggest that religion played an individual and social role in supporting recovery. Participants’ descriptions of their substance use history revealed issues behind their addiction and how their faith may have resolved those issues in recovery. Most individuals began using at a young age, and were motivated to use to cope with life stressors. In discussing positive aspects of faith, participants mentioned improved ideas of self, including newfound gratitude and sense of purpose in helping others. Participants credited their religion with providing a new set of coping skills, sense of structure, and set of morals for making decisions; some mentioned being able to “rely on God’s timing” and others mentioned being able to focus on “obedience to God.” Community appeared to play a significant role, within and outside the religious context. Participants stated that their faith community provided an ingroup of people sharing common values, enhancing their ability to trust. They noted that community offered opportunities for mentorship and mutual support. Other positive factors outside of faith included the opportunity for self-reflection. Themes in participants’ responses align with existing literature on individual and social benefits of religion, suggesting that protective aspects of religion extend to homeless populations.

Non-coding regions account for approximately 98% of the genome and play a significant role in regulating and maintaining levels of gene expression via transcriptional and translational control mechanisms. Our lab focuses on the functional characterization of non-coding regulatory regions in the human retina and identifying mutations within these elements that contribute to inherited retinal diseases. In pursuit of this long-term goal, my aim is to establish an in vitro model to dissect non-coding regulatory elements in the human retina. Retinal organoid cultures are a promising new system for studying the development of the human eye, however it is currently unknown if organoids recapitulate all of the features of the adult human retina. Based on similarities of cell types and gene expression, we hypothesized that retinal organoids recapitulate some non-coding regulatory features of the normal human retina. To identify both shared and specific non-coding regulatory elements, I profiled the epigenetic landscape of developing human retinal organoids using a genome-wide method for assessing chromatin accessibility (ATAC-Seq). Chromatin accessibility is a feature of non-coding regulatory elements which ATAC-Seq revealed in human retinal organoids. I then used bioinformatic techniques to compare my organoid dataset to previous data we generated from the adult human retina and published data from the developing human retina. We found distinct sets of non-coding regulatory elements that were shared between retinal organoids and the human retina, as well as elements that were unique to each system. These comparative data will equip us with additional insight on which non-coding elements may influence retinal disease phenotypes. Furthermore, these data will potentially give us a clearer understanding of the epigenetic landscape of the developing and adult retina in a context that may drive progress towards regenerating damaged photoreceptor cells in the future.

Aging is associated with a decline in functionality and cellular organization. These changes are reflected in the morphology of cellular organelles, such as the cytoskeleton, which plays an integral role in cell movement and signaling. Age-related changes in the cytoskeletal system make it a great point of interest in age-related studies. However, its roles in aging and longevity are still largely unknown. We hypothesized that alteration of the actin cytoskeleton results in an accumulation of age-related cellular pathologies. To test this hypothesis, we examined cellular markers of aging in C. elegans worms with deactivated actin proteins. The genes for the cytoskeletal system are well conserved between humans and Caenorhabditis elegans, making it a great and popular model system for examining the role of the cytoskeleton in aging. We used RNA interference (RNAi) to knock down the expression of cytoskeletal actins in the worms. Afterwards, we used fluorescent microscopy to examine markers of cellular aging: pH, nucleoskeleton integrity morphology, and mitochondrial network morphology. We have found that perturbation of actin cytoskeleton partially mimics age-related cellular changes. We expect the results to be of help in the ongoing study of the role of the cellular cytoskeletal complex in the human aging process.

In the brain, the lateral habenula is involved in multiple functions such as stress responses and pain processing as neurons in this area have been found be activated when experiencing unpleasant events. More recently, literature suggests that not only does the lateral habenula respond in a reward-negative fashion, it may also play a key role in positive feedback decision making. To investigate the role of the lateral habenula in the decision-making process, we establish a delay discounting task requiring Long Evans rats to make decisions based on wait time and amount of reward received. Given its function in learning and decision making, the lateral habenula is hypothesized to play an indispensable role in positive feedback decision making. Mature Long Evans rats train and run on an elevated T-maze which is set up with two opposing arms and a base arm in between. Rats are trained on which arm provides a greater reward and are then run through a delay discounting task in which the wait time to access the higher reward is incremented from 10 seconds to 20 seconds to 40 seconds between blocks of trails and the wait time for the low reward is maintained at 3 seconds. Their decision is made after reaching the midpoint between the reward arms and once they have decided, they are blocked for the corresponding duration and then allowed to eat the reward. The rats’ recorded brain activity in the lateral habenula while running the delay discounting task will indicate the significance of the lateral habenula’s role in subjective evaluation. These findings will further our understanding of how different regions of the brain work together to make decisions.

Retinal pigment epithelial cells (RPE) normally reside on the photoreceptor side of the retina; however, they can become dislodged as a result of trauma and surgery. A condition called proliferative vitreoretinopathy (PVR) can occur when these cells undergo an epithelial to mesenchymal transition (EMT) and form contractile scar tissue that results in retinal detachment. PVR is a common complication of retinal detachment surgery occurring in about 10% of cases, and there is currently no effective non-surgical treatment. In-vitro models of PVR have previously been created from surgically excised tissue, but these cultures are difficult to create and maintain. However, one recently isolated primary cell line, fRPE #51, has been noted to spontaneously form contractile bands similar to those found in other PVR models. The goal of this study is to characterize this cell line to determine if it has the potential to serve as a reliable in vitro model of PVR. To fully characterize this fetal RPE cell line, we stained the cells for known markers of PVR. We also completed several assays for proliferation ability of the cells to assess for functional changes consistent with PVR. Finally, in order to characterize changes to the structure of these cells, we assessed the formation of tight junctions by measuring transepithelial resistance (TER) of cells grown on filter membrane inserts and performed transmission electron microscopy to look for other structural changes. Our preliminary data indicate that the candidate cell line fails to establish normal tight junctions. In addition, an initial proliferation assay demonstrates enhanced ability of the candidate cell line to proliferate and migrate in comparison to control lines. Establishing an in vitro model of PVR will allow for screening of potential drugs and other small molecules that may inhibit the formation of PVR.

Within the United States, plea bargaining has become the dominant method of case resolution. The Bureau of Justice estimates that 95% of all cases processed are resolved with a plea. This study seeks to examine the factors that motivate defense attorneys in their plea recommendations. The primary factors that this study was interested in include likelihood of conviction at trial, defendant’s preference over whether they would like to proceed to trial, and length of sentence if convicted. One-hundred and fifty defense attorneys were contacted through listings on the Washington State Bar Association's website, and subjects were mailed both a survey and one of eight randomized scenarios containing a potential case manipulated upon primary variable lines in a 2x2x2 fashion. These scenarios scored responses under a 5-point Likert scale (‘extremely unlikely’ to ‘extremely likely'). Responses were analyzed in a MANOVA. Surveys were analyzed along a 5-point Likert scale ('extremely unimportant' to 'extremely important') which analyzed results through an ANOVA. Results indicate that the length of potential sentence was not significant on an attorney’s recommendation to enter a plea (p=.43); however, strength of evidence (p= <.001) and defendant’s preference (p=<.001) both significantly impacted this recommendation. However, implicit and explicit analyses of factors indicated no significant differences in plea considerations based on defense attorney subtypes. Strengths of the study include the maintaining of participant’s anonymity to protect against social desirability bias, random selection and overt and covert measurement of factors. Our hypotheses lines were drawn in consideration that the 'meet-'em-and-plead-'em' model of case resolutions may have resulted in plea factor habituation. However, despite considerable limitations, assigned counsel continue to evaluate relevant factors and seek to provide the best defense possible.

Mycoremediation is a water cleanup method that relies on the ability of mushroom mycelium to extract or eliminate contaminants in the water. Following a series of controlled laboratory tests that demonstrated how woodchips inoculated with King Stropharia (Stropharia rugusoannulata) mushroom mycelium could significantly reduce E. Coli counts in pathogen-contaminated water, we designed a larger scale experiment to treat contaminated runoff in the UW Bothell/Cascadia College Campus wetland. We created a system that could allow campus runoff to flow into, and then out of, a 55 gallon barrel half full of woodchips previously inoculated with mycelium over the course of 4 to 5 months. We conducted a series of three trials with this system to test its effectiveness at filtering fecal coliform bacteria (FCB). Using a valve to control flow, we sampled input and output concentrations of FCB at times +5min, +30min, +1hr, +2hr, +3hr, +5 hr, +10hr, and +24hr. Our first experiment (Trial One) showed an average of approximately thirty percent decrease in output coliform counts after 1 hour. Trial Two was conducted 9 weeks after Trial One. In that interim, the woodchips sat undisturbed in the barrel in a saturated state. Trial Two sampling and analysis showed no significant change in coliform concentration. Trial Three was conducted 2 weeks after Trial Two. Immediately prior to Trial Three, 10 to 15 gallons of fresh mycelium-inoculated woodchips were added to the barrel. Trial Three showed an increase in output coliform concentrations. Though the first trial indicates that mycoremediation can remove pathogenic bacteria, conditions need to be optimized for the mycelium. The effectiveness of S. rugusoannulata was hampered by long-term inundation. Future implementations of mycoremediation should focus on the sustainable ecology of the fungi and identify environments where it can be integrated to perform wetland services.

Understanding how extracellular environments facilitate the differentiation of stem cells holds much promise for the field of regenerative medicine. Non-muscle myosin II (NMII) plays an important role in cell morphology and also generates forces that alfter biochemical signalling. It has been shown that the activity of NMII controls mechanoreceptors and integrins facilitating stem cell fate. More specifically, mechanotransduction of transcriptional coactivators YAP/TAZ facilitate differentiation of mesenchymal stem cells (MSCs). YAP and TAZ are responsible for upregulating genes associated with stem cell differentiation. Under external stresses mesenchymal stem cells differentiate into osteocytes whereas softer extracellular conditions favor the differentiation into adipocytes through mechanotransduction of YAP and TAZ.To further explore the role of physical forces determining the fate of stem cells, we used a computationally designed self-assembling homo-polymer called 2E01, generated by the Institute for Protein Design (IPD). Mechanical stress and the physical activity of NMII can be mimicked by controlled expression of the length of the E01 protein fiber. We introduced the 2E01 gene under a doxycycline-inducible promoter into the AAVS1 "safe harbor" locus of the induced pluripotent stem cells (iPSC). Expression of the E01 fiber in iPSCs lead to changes in colony morphology and subsequent differentiation of those cells, suggesting that changing the morphology of cells can change their fate. I want to see if I can use the 2E01 fiber as a tool to accelerate differentiation from IPSCs to neuronal cells and cardiomyocytes. In addition, we expressed 2E01 in mesenchymal stem cells, a cell type currently used in lab, and observed the activity of YAP and TAZ as an indicator of differentiation. Utilization of the 2E01 fiber could be benefical to the field of regenerative medicine as a directed agent of physical manipulation towards desired stem cell fate.

The University of Washington prides itself on being a leader in sustainability, but is currently not doing all that it can to reduce waste that ends up in landfills and lower their carbon emissions. While many universities across the United States have banned the sale of disposable water bottles on their campuses, including five Washington State schools, the University of Washington has not made an effort to do the same. Banning the sale of disposable water bottles would help lower the University’s carbon footprint and divert plastic from landfills. I answered the question, what steps does the University of Washington need to take before they can stop selling bottled water at their Seattle campus? To do this I wrote a report where I analyzed the human, environmental, and economic impacts of divesting from disposable water bottles on the University of Washington Seattle campus. After completing this report I created a set of suggestions for the administration, detailing what needs to be done for the University to successfully stop selling bottled water. Disposable water bottles are an often forgotten source of pollution, both in terms of pollutants that enter your body when you drink from them, and in terms of environmental pollution. Pollution from bottled water occurs at every stage, production, transportation, consumption, and improper disposal. Getting the University of Washington to divest from selling disposable plastic water bottles on its Seattle campus will benefit student and environmental health.

The mesolimbic dopamine pathway begins in the midbrain Ventral Tegmental Area (VTA) and projects to the nucleus accumbens (NAc) and is fundamental in regulating goal-directed behaviors. Abnormalities in this pathway are implicated in a number of neuropsychiatric disorders including drug addiction and depression. However, there is still a lot unknown about the specific circuitry and cell types that contribute to these behaviors and diseases. This project aims to provide a deeper understanding of how different dopamine populations in the VTA contribute to reward behavior. We use Cre-driver mouse lines to isolate genetically distinct VTA dopamine subpopulations. Using this strategy, we classified three different subpopulations: Corticotrophin releasing hormone receptor one (Crhr1-Cre), Cholecystokinin (Cck-Cre) and Tachykinin receptor three (Tacr3 Cre). Interestingly, these populations have inclusive and complementary projections to the NAc and it’s two subdivisions, the NAcCORE and NAcSHELL. We utilize optogenetic techniques to activate each subpopulation individually. To test learning acquisition, mice without any prior training were placed into an operant box containing two levers that when pressed would result in optical excitation of the targeted VTA subpopulation. We found that optical stimulation of the Crhr1 subpopulation, which projects to the NAcCORE, can drive lever pressing instrumental learning. Activation of Cck neurons, which project to the NAcSHELL, is unable to promote learning. However, if animals first learned an instrumental behavior to obtain food reward, subsequent activation of Cck neurons would maintain instrumental responding. Interestingly, activation of Tacr3 (projects to both NAcCORE and NAcSHELL), resulted in rapid instrumental learning and maintenance of high levels of lever pressing. These results establish independent roles for Crhr1 and Cck dopamine neurons in instrumental reward learning and motivation, as well as a requirement for co-activation of NAcCORE and NAcSHELL pathways (Tacr3) for maximal reinforcement responding, thus providing more specified targets for therapeutic interventions.

Bivalves, such as oysters, clams, and mussels, have critical roles to play in both the food chain and water quality in Puget Sound. However, if adult bivalve populations are faltering, it is imperative that we learn more about their larval phase, to ensure that the population is sustained. Bivalve larvae are not sessile, and they are not completely mobile, but can orient and move themselves on small scales. The purpose of this project is to determine if bivalve larvae prefer to stay within eelgrass beds depending on the time of day. It is hypothesized that bivalve larvae may stay within eelgrass beds to hide from potential predators. In order to better understand the habitat-level behavior of bivalve larvae, samples were collected during the summer of 2015 at 4 locations around Washington State: Fidalgo Bay, Port Gamble, Case Inlet, and Willapa Bay. Besides the location, key sampling variables included: time of day (light or dark), and substrate (eelgrass or bare). Samples were analyzed by hand-counting all bivalve larvae found through polarized light microscopy. Counts of both specific species, and total bivalves found were collected. The results of this project are still pending; however, this data could be useful to shellfish growers, and any persons responsible for identifying areas for habitat restoration work. With increasing world water temperatures and acidity due to climate change, eelgrass beds, have the potential to be a refuge from these effects. Therefore, this data would be important to predict the effects of ocean acidification and warming on all species of bivalves in all life stages. 

The purpose of this research is to find data patterns of DC motor failure through radio frequency emission. To collect data for classification, three sets of five DC motors were modified to exhibit three common motor fault issues: armature winding resistance variation, brush contact/air gap, and bearing friction. A set of control data from unmodified motors was also collected. The motors were run for a set period of time at the manufacturer recommended voltage and rpm band with no load. The data was collected via a RF receiver and processed digitally. Using a Python-based program, known-good and known-bad data was run through a machine learning program. The program was then tested for accuracy and precision of diagnosis using a wider spectrum of faulted motors, including variation of fault, load, and size of motor. The hypothesis of this research is that radio frequency emissions generated from a defective DC motor show detectable differences from a normally functioning motor, the differences of which may show signature patterns that can be isolated using classification  through machine learning programming and used to predict onset of failure.

Aerosol particles, solid or liquid particles suspended in the air, can affect Earth’s climate by scattering and absorbing sunlight. PM_2.5, particles less than 2.5 micrometers in diameter, are largely responsible for degraded visibility and easily traverse respiratory system pathways causing adverse health effects in humans. Often, a majority of PM_2.5 is composed of organic matter formed through photo-chemical reactions of hundreds of volatile organic compounds (VOC). This process depends on nitrogen oxide radical (NO_X = NO + NO₂) concentrations in the atmosphere, now predominantly contributed by anthropogenic emissions. NO_X and VOC react to produce organic nitrates, thought to be significant contributors to PM_2.5, but for which measurements are generally lacking. My project involves developing a concrete assessment of the role of organic nitrates as contributors to PM_2.5. I am developing an analytical method to thermally desorb organic nitrates from atmospheric particles collected on filters and promptly decompose them into nitrogen dioxide (NO₂). The resulting NO₂ is measured with a Cavity Attenuated Phase Shift (CAPS) spectroscopy instrument. I am establishing whether there is a direct correlation between the concentration of organic nitrates in PM_2.5 and desorbed NO₂. The goal is to quantify organic nitrates without individually measuring each of the likely hundreds present in the ambient atmosphere. Moreover, the thermal desorption process provides information on the physical properties of organic nitrates, such as effective saturation vapor pressure, needed for air quality computer models to accurately simulate their contribution to PM_2.5. As a result, I will help develop a better understanding of how natural and anthropogenic emissions affect the composition of the atmosphere by allowing assessments of how PM_2.5 levels have changed in response to NO_X emission reductions by the Clean Air Act.

In the fabrication of integrated circuits and microscale devices a technique known as electroplating is often used to deposit thick layers of metals such as gold and copper. The electroplating process requires a conductive layer to facilitate electroplating, commonly referred to as a “seed” layer. In many cases, the seed material will not bond well with the base materials, necessitating the use of an intermediate “adhesion layer” to improve adhesion between the substrate material and the plated metal. In this project, Electron Beam Physical Vapor Deposition (EBPVD) was investigated as a means to deposit a 25nm titanium adhesion layer followed by a 300nm copper seed layer to promote the adhesion of electroplated copper to a silicon dioxide substrate. EBPVD is a process in which a collimated beam of high energy electrons is used to boil metal atoms off of a target and deposit them on a substrate. These systems operate in high vacuum to increase the mean free path of metal atoms ejected from the target surface, allowing for highly anisotropic deposition on the substrate. The stress states of EBPVD deposited seed layers and electroplated wafers were also observed as residual stress can adversely affect the performance of active circuitry that IPDs are bonded to. The deposition of this seed layer, followed by electroplating of copper, is but one step in the fabrication of prototype signal filtering devices for mobile applications. These micrometer scale inductors and capacitors, referred to as “Integrated Passive Devices,” are built directly atop silicon wafers, with the intent of eliminating the need for larger surface mounted signal filtering devices in applications where working volume is at a premium, such as in mobile phones and tablets. We hope our research will allow for production of higher quality prototypes and accelerate development of this emerging technology. 

In Hollywood, an industry that is proclaiming “Time’s Up!” there is a burgeoning movement to change both the ways women are treated in film, and the ways their safety is prioritized.  The initiative focuses on sexual harassment in the workplace, specifically, the entertainment industry.  There has been a recent initiative by women in the industry in response to what’s known as the “Weinstein effect,” a recent trend of men in Hollywood being revealed to be sexual harassers and rapists.  They call their initiative “Time’s Up.”  The movement combats rape culture, a concept that names the act of sexual harassment being normalized.  In my literature review I ask: how and why does rape culture permeate the American film industry? First, the research delves into the history of film production, and how various time periods saw paradigm shifts of women's involvement in the process of filmmaking.  The research also examines how women were portrayed during these shifts, and connections between the two.  To understand influences film had during these times, I examined human rights movements that parallel changes in film.  The literature review also explores the economic aspects of filmmaking.  Specifically, how it influences what films are produced, how they’re advertised.  Additionally, legal matters, such as contracts that mandate silence, are also looked into as reasons for lack of response to perpetuators of harassment and assault. The last part of the literature review examines the latest paradigm shift.  The research evaluates the outing of powerful men in the film industry as perpetuators of sexual violence, and the proceeding action that has been taken since.  Women’s involvement in production, as well film themes in the past ten years is analyzed for comparative studies. To conclude, the movements such as Time’s Up is studied to explore further action that is being taken.

Modifiable psychosocial and behavioral factors place youth at risk for severe and persistent pain after major surgery. Opportunity exists prior to surgery to intervene with youth and families to prepare them for surgery including helping to manage distressing cognitions and teaching non-pharmacologic coping strategies, to reduce acute pain and prevent chronic post-surgical pain. This study aims to evaluate the feasibility of delivering this cognitive behavioral program remotely to youth undergoing major surgery. Fourteen children ages 10-18 years (M= 14.5), 71.4% female, scheduled for major spine surgery, and their parents, were enrolled into the study. 73% of eligible families were approached for potential participation. Enrollment rates were excellent with 88% (14 of 16) of families approached agreeing to participate in the study, with a range of 4 to 16 weeks (M = 6.3, SD = 1.3) until surgery at the time of enrollment. Teens and their parents completed three pre- surgical modules containing surgical preparation and relaxation tips during the month preceding surgery. Participants completed three post-surgical modules during the 6 weeks following surgery containing tips for managing pain and returning back to school and activities. Each module was accessed online and followed by a coaching phone call with a trained study team member to ensure comprehension of module content. All of the participants completed all pre-surgery and post-surgery modules within the prescribed time frame. The majority of parents and children (79%) completed the study phone calls within the prescribed time period. Preliminary results indicate excellent program feasibility. Additional analyses will examine the efficacy of the program in reducing acute and chronic pain in the final sample.

Patients with cerebral palsy tend to have altered muscle activations during walking compared their unimpaired peers. Quantifying these changes is important for clinicians to be able to proscribe treatment protocols. Every brain injury with cerebral palsy is unique, requiring patient specific measures of motor control. Muscle synergies are used to quantify a patient's motor control by using the electrical activity of individual muscles during walking. The resulting electrical activity of the muscles, electromyography, are processed using matrix factorization algorithms. These algorithms identify weighted groupings of muscles which are commonly activated during activities such as walking. However, across clinical institutions differences in data gathering protocols and resources, as well as muscle selection can make the interpretation of synergies challenging. Moreover, calculation of synergies requires programing and data processing expertise not uniformly available to clinicians. The aim of this research was to design a web application that could intuitively represent synergy results for clinicians and patients based upon the data they collect at their institution. This web application uses processing and factorization scripts in Python and integrates the results into JavaScript and HTML for an accessible and flexible display. The application allows the user to select the muscles they want to include in the analysis, as well as how many synergies they want calculated. Each synergy solution is displayed by presenting the weighting of every muscle in each synergy. Additionally, the application shows how accurately the synergies reconstruct the electromyography signals. Generated results from the application can be exported as a report for the patient and clinician to refer to. Because of the differences in data gathering practices across institutions, this research also looked to identify if there are specific ways to quantify how individual muscles impact synergy results so that synergy results can be more translatable across institutions.

The US homeless population is disproportionately affected by alcohol use disorder (AUD). This disparity leads to greater health and behavioral problems which precipitates greater utilization and associated costs of publicly funded services, such as the emergency healthcare and criminal justice systems. To address AUD in this population, researchers worked with homeless individuals with AUD and agencies that serve them to develop the Harm Reduction Treatment for Alcohol (HaRT-A). HaRT-A participants evinced improved alcohol outcomes compared to treatment-as-usual control participants. The present study’s aim was to test a secondary research question: Does HaRT-A significantly reduce the high costs from emergency healthcare and criminal justice system utilization in people experiencing homelessness and AUD? Participants (N=167; 24% women) were recruited for the parent HaRT-A study. Cost data were collected from participants’ use of the King County Correctional Facility and Harborview Medical Center. Jail costs included the costs of booking, days spent in jail, and use of supplementary jail services. Emergency healthcare system costs included the costs of emergency department visits and inpatient hospital admissions. All costs were added up for the 24 weeks prior and subsequent to study participation. Mann-Whitney U tests were conducted to assess group differences on post-pre cost change scores. Analyses indicated no significant group differences on post-pre changes in costs associated with utilization of emergency healthcare and jail services (ps > .58). There are several possible explanations for the lack of significant group differences. First, the time frame was likely too short to detect differences in statistically rare outcomes. Second, HaRT-A had a statistically significant impact on proximal outcomes; however, the brief nature of the treatment (4 sessions) might have limited its ability to impact the more distal variables measured in this study. Finally, homelessness creates multiple challenges that may require more intensive and multilevel interventions to fully address.

Synthetic polymers such as polyester fleece have been used in garments for decades without realization of the significant amount of microscopic fibers that they shed, or the impact of that pollution on our ecosystem. Water samples were collected to determine the presence and chemical composition of plastic microfiber waste in various local water sources such as Lake Washington, the Puget Sound, different tap water sources, and at various stages in the local waste water treatment process. Plastic microfiber waste has been found in surface and tap water around the world, and in this project the degree of plastic microfiber contamination in local waters was determined. To do this, water samples were collected at a variety of locations and filtered, and the resulting filtered matter analyzed using optical and scanning electron microscopy to determine the presence and size of plastic microfibers.  FTIR (Fourier transform infrared) spectroscopy was used to determine the plastic's chemical composition.  The results of these tests indicated the origin of these microfibers if they are of a type of plastic commonly used in garments (polyester), and the size and presence in samples from different sources indicated if current water purification infrastructure is adequate to remove these microfibers from the water supply. The information gathered can be used to determine the magnitude of the problem and effectiveness of current solutions at a local scale. Recommendations are made regarding the curtailing of this problem.

An Inductively Coupled Plasma fluorine (ICP-F) reactor is used to anisotropically etch silicon dioxide with octafluorocyclobutane (C4F8) and argon (Ar) gas. Microelectromechanical system (MEMS) and microelectronics applications require several micron wide features with high-resolution and precision features made on silicon wafers. The ICP-F is a fundamental of the pattern transfer process called a damascene process where a precision pattern is formed and then filled with metal and planarized to remove excess metal and leave the intended pattern. This step of the damascene process consists of lithographic resist patterning and subsequent plasma etching of the underlying material. In this work, C4F8 plasma with Ar additives are used to etch silicon dioxide to create patterns in the oxide that will later be used molds for copper electroplating. In this design, the ICP-F must have a consistent etch rate with high selectivity to achieve constant depth for the copper layer with high resolution patterns. Variables such as DC bias, Ar flow, and O2 flow were optimized to achieve a repeatable etch rate. Furthermore, wafer stress was measured at every step in the process as the varying stress of the IPD could adversely affect the electronic circuits that the IPDs are connected to. Compared to Discrete Surface Mount Devices (SMD), IPDs allow for high-density trench capacitors, Metal-Insulator-Metal Capacitors, and high-Quality inductors which are enabled by ICP-F technology. In addition, new radio frequency (RF) circuits for 5G applications are employing the use of Integrated Passive Devices (IPDs) for making RF filters.

Oral swab analysis (OSA) is a possible alternative sample type for tuberculosis diagnostics. It has been observed that tongue swabs contain greater amounts of Mycobacterium tuberculosis DNA than cheek swabs (p<0.0001). This project investigates whether other oral microbiota follow the same pattern by analyzing oral swabs from healthy controls and TB patients from South Africa. To determine the oral bacterial load, the first step was to optimize a universal bacterial PCR protocol that could be used on real samples. The Com1/769R primer set that amplifies the 16s region of prokaryotic DNA (Dorn-In, 2017) was selected after a literature review and tests with DNA from 5 different bacterial species at known amounts to compare sensitivity. Next, samples were collected from 5 healthy volunteers from Seattle. They provided two swabs each, one from their tongue and one from their cheek, which we then analyzed by PCR. Oral swab samples from South Africa were also analyzed by PCR. We found that the tongue swabs contained greater amounts of total bacterial DNA than the cheek swabs. For the healthy Seattle volunteers, the tongue swabs had an average of 294 times more DNA than the cheek swabs. For the South African samples, the tongue swabs had an average of 13.2 times more DNA than the cheek swabs. Our results suggest that there may be more prokaryotic DNA on the tongue than cheek. Our next steps are to test additional samples from South African subjects. This research could impact the development of future diagnostic tests that detect pathogens within the oral cavity.

Atherosclerotic vascular disease and its resulting myocardial infarction (MI) is the leading cause of death in subjects with diabetes. Additionally, patients with a history of a MI are more likely to experience a recurrent MI, however the mechanism is not yet understood. Previous work from our laboratory, and others, has demonstrated that diabetes accelerates atherosclerosis partly by affecting monocytes and macrophages, resulting in increased inflammation and macrophage accumulation in the artery wall. Work from others has shown that experimental MI can also accelerate atherosclerosis in non-diabetic mice by increasing the number of blood monocytes, which enter the artery wall to become inflammatory macrophages. Thus, we wanted to ask if diabetes and experimental MI have synergistic effects on macrophage accumulation in the artery wall. Experimental MI, or sham surgeries, were carried out in an atherosclerotic-prone, transgenic mouse model of type 1 diabetes that relies on viral mimicry (Ldlr-/-Gp+) and in non-diabetic controls. At the end of the study, cross sections of the dissected brachiocephalic artery were used to quantify macrophage accumulation by measuring areas of Mac-2 immunoreactivity on sections adjacent to the largest cross-sectional lesion. If macrophage accumulation is synergistically increased with diabetes and experimental MI, attempts will be made to understand the underlying mechanism. Atherosclerotic macrophage accumulation is a dynamic process that involves monocyte recruitment and local proliferation. Macrophage proliferation and monocyte recruitment will be analyzed by staining with proliferation marker Ki67 and estimating the number of previously labeled monocytes that enter the atherosclerotic lesion, respectively. To mechanistically test the role of monocyte recruitment on macrophage accumulation, Mac-2 staining will be quantified in mice (diabetic and non-diabetic with and without MI) deficient in a key adhesion molecule (CD49D) required for monocyte adhesion to activated endothelium. These results should yield important information on potential synergistic effects of diabetes and MI.

Oncology trials often entail high-stakes interventions where the potential for morbidity and for fatal side effects, as well as for life-prolongation or cure, intensify bioethical issues related to informed consent. These challenges are further compounded in multistage randomized trials, which are increasingly prevalent in oncology. We sought to elucidate the major challenges in achieving true patient understanding of informed consent documents in high-stakes oncology trials in general and the best consent practices for multistage randomized trials in particular. We queried the PubMed database for original studies published on 1-1-1990 to 4-1-2017 that focused on readability, quality, simplicity, complexity or length of consent documents, sickness level of participants, or interventions and enhancements that influence informed consent. Additional articles were identified through comprehensive bibliographic review. Twenty-four articles were retained as the basis for the narrative review; 18 enrolled participants and 6 examined samples of consent documents. This body of literature provides useful information about the pitfalls of the informed consent process as currently practiced in most high-stakes interventional oncologic trials. The understanding level of study participants is examined as impacted by the readability of documents, the complexity of the documents, the length of the forms and the “what’s at stake” nature of oncology trials. The length of the informed consent documents has increased from 338 in 1987 to 3982 in 2010 and patient understanding has been shown to be inversely proportional to the page count of the documents. Additionally, patients’ belief in the “therapeutic myth” also has a negative effect on true patient understanding. The unique challenges of obtaining consent in multistage trials are noted and examined. Though no studies specifically addressed the additional problems posed by multistage randomizations (such as change in risk-benefit ratio due to time-varying treatment responses or organ toxicities), the findings are likely applicable and especially relevant in that context. 

Older adults are at high risk for fall-related injuries that contribute to decreased quality of life and higher health care costs. Risk for falling is especially high during everyday activities involving turns and transitional movements. However, little is known about movement strategies that older adults use when turning. Therefore, the purpose of this research is to identify turning strategies in older adults. In this study, we examined movement strategies used for 180 degree turns during a clinical test of functional mobility, the Timed Up and Go. The Timed Up and Go test measures the time it takes to stand up from a chair, walk, turn around, walk back to the chair, and sit down. Thirty-one older adults (means age 85.6 years) were studied using Qualisys Motion Capture laboratory-based quantitative motion analysis (eight-camera system) and APDM portable body-worn sensors (inertial sensor system). Five distinct turning patterns were identified through frame-by-frame observational analysis of the Qualisys output. Quantitative methods were then applied to characterize parameters of turning in older adults, including turn duration (seconds), turn angle (degrees), and peak turning velocity (meters/second). Finally, we explored relationships between turning patterns and predictive tests of functional mobility and falls in older adults. These measures will be vital in identifying early signs of fall risk in older adults. As a result of this research, we can classify and quantify turning strategies using innovative technology. The results of this research have clinical implications, for healthcare practitioners, to identify people who are at risk for falls and construct therapeutic activities to prevent fall-related injuries.

Carbon fiber-reinforced composites are widely used in the aerospace industry due to their light weight, high strength, and fatigue resistance. However, these materials are expensive due to the painstaking manufacturing processes involved and the inability to recycle. There is growing interest in discontinuous fiber composites (DFC), which are made from small chips of unidirectional prepreg fiber, distributed at random. However, its material properties and behaviors are not well understood. An investigation of DFC was performed to characterize the effect of platelet size on the fracture behavior of the material in various structure sizes. A manufacturing process leveraging computer numerical control fiber cutting and a heated platen press was developed to produce test specimens composed of randomly-oriented platelets from unidirectional carbon fiber prepregs. Three different platelet sizes (25x4, 50x8, and 75×12 mm) were investigated. Single-edge notched tension tests showed that in larger structure sizes, the material exhibited a reduction in strength along with increasing brittleness and notch sensitivity. It was found that decreasing platelet sizes shortened the critical notch length at which this embrittlement of the material occurred. These findings indicate that while minimizing platelet dimensions may be advantageous in the fabrication of complex DFC parts, proper design will require an optimal compromise between manufacturability and structural integrity.

Rapamycin is a drug that has shown to extend lifespan across many model organisms including laboratory mice. Although the drug’s effect on extending lifespan has been investigated, it’s effect on transport of metabolic hormones across the blood-brain barrier (BBB), including insulin, are unknown. Rapamycin extends life by impacting whole body metabolism by acting as a caloric restriction mimetic inhibiting a cellular signaling molecule, mammalian target of rapamycin (mTOR). Insulin transportation into the brain via the BBB has been seen to increase during periods of starvation. Therefore, we wanted to investigate whether treatment of rapamycin would increase insulin transport across the BBB into the brain by inducing a 'starvation state'. I gave IP injections of 8 mg of rapamycin per kg body weight to two-month old male CD-1 mice for two weeks daily. A control group was given IP injections of vehicle for the same duration and amounts. At the end of the two weeks, I gave the mice IV injections of radioactive insulin and albumin (a vascular space marker) that circulated for various times (1-10 min) before collecting blood samples and performing whole brain removals. The radioactivity in the serum and whole brain was measured. The rate of uptake of the radioactive insulin into the brain was calculated and compared between chronic rapamycin treatment and control groups. Two-week rapamycin treatment showed elevated insulin levels in whole brain tissue when compared to the control group suggesting that rapamycin may have an effect on insulin transport.

Interactions between HIV-1 and dendritic cells (DCs) have been suggested to play a role in HIV-1 pathogenesis. DCs are antigen presenting cells that take up, process, and present foreign material to T-cells. Previous research suggests that HIV-1 can exploit this process by binding to DCs, allowing HIV-1 virions to relocate to lymph nodes where infection of T-cells can occur. HIV-1 mediates this interaction through binding of the HIV-1 envelope glycoprotein (Env) to DC-SIGN, a glycan binding protein located on the surface of DCs. Env contains a high amount of oligomannose glycans, enabling Env to act as a binding partner for DC-SIGN. Due to high sequence variation, HIV-1 strains exhibit variability in glycan presentation. A gap remains in our knowledge of where DC-SIGN binding occurs and how glycan presentation across various isolates modulates these interactions. In this study, we applied a combination of biophysical and structural approaches to characterize Env:DC-SIGN interactions across multiple HIV-1 strains. Biolayer interferometry experiments measuring binding affinity demonstrate that DC-SIGN binds with strong affinity towards Env from different isolates. This suggests that DC-SIGN is capable of recognizing different oligomannose glycan presentations and may not have a well defined epitope. However, preliminary results using electron microscopy illustrate that Env glycoprotein structure can be disrupted and altered via binding to DC-SIGN. This appears to be an isolate-specific response, as some strains remain unchanged. Using single particle approaches, we identified potential epitopes in heavily glycosylated regions of Env where additional densities are attributed to DC-SIGN. We infer that in addition to binding HIV Env, DC-SIGN may shield key neutralizing epitopes within these glycosylated regions. Our results provide further insight into the interactions that occur between HIV Env and DC-SIGN, and suggest a mechanism where HIV-1 hijacks DC’s normal immune function allowing HIV-1 trafficking while shielding neutralizing epitopes.

Lakes cover a greater fraction of boreal and arctic landscapes than anywhere else on the planet. Collectively, northern lakes re-mineralize massive quantities of organic material into the greenhouse gases (GHGs) carbon dioxide and methane, forming an important link between the biosphere and the atmosphere. Rapid climatic changes in northern circumpolar environments are changing the physical structure of many boreal and subarctic lake ecosystems, and in many cases are substantially shortening the duration of ice cover. A clear understanding of contemporary, under-ice GHG production is needed to fully appreciate future trajectories of change in northern lake carbon cycling. Yet the field, in general, is missing direct, ecosystem-scale estimates of greenhouse gas production, especially during frigid and dark periods of ice-cover when field sampling is particularly challenging. Here, to provide a better understanding of greenhouse gas cycling in northern circumpolar lakes, we conducted a cross-lake survey of under-ice methane and carbon dioxide production in twelve lakes of the Alaskan portion of the remote Yukon River basin. We use this survey to first quantify rates of GHG buildup from fall to late winter. Second, we identify the physical and chemical lake features that best explain the cross-lake differences in rates of gas accumulation. Ultimately, these findings will help to improve our understanding of carbon cycling in remote and understudied northern aquatic ecosystems and will help to constrain northern carbon biogeochemical budgets.

Millions of art images have been digitized over the last several decades. This has created new opportunities for art scholars and historians. However, searching and navigating these art images is difficult because of the sparsity of the metadata and contextual information used to describe these images. Unless one knows the exact title and artist, finding related paintings is a difficult task without the metadata. The research in this project addresses this challenge by developing unsupervised computer vision methods that will extract metadata automatically from paintings. Our dataset will include more than 2 million art images from Arstor, a non-profit organization that distributes art images to libraries and universities. If successful, we plan to build an interactive interface for exploring the extracted features and for developing a recommender system that could be used on platforms such as Artstor.

In plants, the hormone auxin plays a crucial role in the regulation of many different genes during growth, embryogenesis, differentiation, and many more developmental processes. The promoters of auxin responsive genes are bound by a transcription factor called an Auxin Response Factor (ARF), which is repressed by a protein complex consisting of a linker protein called an IAA and a corepressor known as TOPLESS (TPL). In the presence of auxin, the IAA is degraded resulting in the dissociation of TPL and subsequent activation of transcription of these auxin responsive genes. IAA20, IAA30 and IAA31 are members of a closely related sub-clade of IAAs that are known to be auxin insensitive. These genes are transcribed at low levels in nearly every cell type, yet their role in the auxin signaling network is completely unknown. I hypothesize that the auxin insensitive IAAs create an auxin concentration threshold to reduce the noise of auxin signaling output. In this model, auxin insensitive IAAs interact with all ARFs to generally increase the concentration of auxin required to elicit a transcriptional response. To test my hypothesis, I examined phenotypic changes in single, double and triple-mutants for the auxin insensitive IAAs, which I have generated via CRISPR/Cas9 mutagenesis combined with existing mutations. I am currently testing whether these mutants have quantifiable auxin-related defects in the highly stereotyped root development and arrangement of organs along the stem, or phyllotaxy. If I observe that mutants in the auxin insensitive IAAs have defects with these processes, it will suggest that these IAAs buffer noise present within the auxin signaling network. This work will enhance our understanding of how auxin coordinates transcriptional repression and how signaling noise is reduced in a multi-component molecular system.

Recent advancements in North Korea’s nuclear program prove that it will soon be capable of targeting the US mainland. The Trump administration's imposition of aggressive sanctions and threats towards Pyongyang have been met by retaliatory statements from the Kim regime. Aside from these threats, lack of communications between the two nations have raised international concern over the possibility that war will resume on the Korean peninsula. Therefore, this student-run task force team takes up a detailed study of this emerging crisis using open-source data with three main objectives: 1) to determine the goals of NK's nuclear and missile programs by studying the historical relationship between the US and Korea; 2) to gauge threat potential by analyzing North Korea’s offensive capabilities; 3) to use local perspectives to determine how this crisis affects relations between the US, China, South Korea, Japan and how each nation views the NK threat; and 4) to learn from past mistakes in order make viable recommendations for the current US administration to de-escalate current tensions and provide a new framework for a peaceful solution to the North Korean crisis.

Over the past few years, the presence of smart homes has increased rapidly. Previous research has observed that people make errors in smart home programming with their mental models differing from their actual programming implementation which can cause serious security and safety concerns. The most common errors include missing half-rules and the incorrect use of conjunctions in triggers. For example, if users desire to program a rule for turning on the light when they are at home, they might program a rule such as “when I come home, turn on the lights”, forgetting to program the rule for “when I leave home, turn off the lights”. Our research focuses on reducing user errors in end-user programming by using programming by demonstration. Our hypothesis is that when users physically demonstrate a trigger-action rule, they are less likely to commit the trigger-action programming errors explained above. We compare the number and types of errors made within the IFTTT (if-this-then-that) interface that does not implement programming by demonstration and two interfaces that we built that implement programming by demonstration: a web interface and an augmented reality based interface within the Microsoft HoloLens. If our hypothesis holds true, we might observe that programming by demonstration significantly reduces programming errors in end-user programming in the case of both missing half rules and incorrect trigger conjunctions. We postulate that there might not be a difference in the case of error reduction between both the web and augmented reality interface; however, the augmented reality interface might provide for a broader range of programming by demonstration interfaces such as those related to temperature, humidity etc. Moreover, if our hypothesis holds, we might further suggest that smart home providers incorporate programming by demonstration models in their programming processes for end users within smart homes.

The timber industry gave birth to most of the cities in the Pacific Northwest including Seattle and it naturally supplied the building materials for homes and businesses. However with the development of steel and concrete construction, timber was quickly abandoned in exchange for the more fire resistant materials and their ability to reach greater heights. Now with the turn of the twenty first century, timber is back to claim its rightful position in the building industry. The development of engineered mass timber products like cross laminated timber (CLT) has made a profound impact on the building industries of Europe, Australia, Japan and Canada but the building code of the United States has not yet accommodated the use of this material. The current code allows six stories of wood frame construction over a one story concrete base level. Structural mass timber elements like CLT have similar limitations despite being capable of doing a lot more work. This project looks at the changes in the building code that are going to be implement in the coming years regarding the use of CLT in highrise construction. These changes will enhance the construction industry in the Pacific Northwest due to its potential of increasing regional economic growth and reconnecting the construction industry to its cultural roots of timber milling. After analyzing the building code revisions that will be implemented in the year 2021 I created visual representations of construction assemblies and details to provide a cohesive understanding of how CLT could be applied to the design of future structures. Having proven its potential in other parts of the world, it is time to employ mass timber in the United States.

Core-collapse supernovae (SN/e) are the spectacularly violent deaths of evolved young massive stars, which expel a shock wave into the intergalactic medium that in turn can spark star formation and disperse heavy elements into their host galaxy. While a SN event can be classified by its spectral signature, determining the nature of a supernovae progenitor depends upon chance photometry taken prior to the event. By turning to the study of SN host environments and their surrounding interstellar medium within the unique and rare population of galaxies that have hosted three or more SN events within the last century, we are granted the opportunity to study the locations and environmental properties of stellar populations prone to supernova progenitor production. Using moderate-resolution optical slit spectra taken with the Apache Point Observatory 3.5m DIS spectrograph, we aim to map metallicity, ionization parameter, and star formation rates using emission line diagnostic ratios across each SN-rich galaxy in our sample. Dubbed the “Fireworks Galaxy” at a distance of 5.6 ± 1.5 Mpc, NGC 6946 is of particular interest as it has uniquely produced ten core-collapse supernovae (CCSNe) and several other massive star transients within the last century. We present spatially-resolved metallicity and Hα star formation rate (SFR) maps of NGC 6946, tracing fifty-five slit orientations which span the face of the galaxy and cover all CCSN host sites. Future work will include stellar population synthesis modeling to determine stellar populations, ages, and SFR histories in NGC 6946 and a further expansion of this analysis to the other SN-rich host galaxies in our sample.

There are several approaches to treating Acute Myeloid Leukemia (AML) relapse after an allogeneic stem cell transplant. We were curious about the efficacy of the different types of treatments commonly deployed for patients with post-allograft AML relapse. Eligible patients included those who underwent allogeneic stem cell transplant for a diagnosis of AML and then relapsed between 1/1/2005 and 12/31/2015. We abstracted information about their treatments, GVHD status, immunosuppressive drugs, response (ie relapse or remission) events and vital status from their medical records. Among 120 patients, we found a median number of 2.6 and a mean of 2.9 relapse-directed lines of treatment, while 21% received no treatment. The types of treatment deployed were tightly correlated with the patient’s malignant blast count and the time that had elapsed since first transplant. There were 74 induction chemotherapy attempts, 64 hypomethylating therapy prescriptions, 19 donor lymphocyte infusions (DLI), and 16 second transplants, for example. Ongoing work includes completing data entry on the remaining 186 subjects, and analyzing the relative efficacy of the different treatment options. Importantly, we found that patients whose relapse presented with very low-level disease burden (<5% malignant blasts) still had a dismal prognosis, with only 20% being alive in remission at last follow-up. By contrast, patients relapsing with >5% blasts had an even worse prognosis – only 7% alive in remission at last follow-up. Closer surveillance for post-transplant relapse might catch more patients relapsing at low disease burdens. Initiating treatment when the disease burden is low may be more effective. Our ongoing work will identify the best sequences of treatments (leading to the longest relapse free survival), taking into account the blast burden, time elapsed since transplant, and other predictive factors.
 

The acrosome is a sperm-specific organelle required for the fertilization of the ovum in most animals. However, the molecules required for its formation during development are largely unknown. Toward identifying the function of candidate proteins, we are testing a system known as deGradFP in Drosophila melanogaster which targets fluorescently-tagged fusion proteins for degradation. This system depends on the ubiquitin-tagged proteasomal degradation pathway. Currently, we are testing whether this system works at different stages of spermatogenesis by targeting Yellow Fluorescent Protein (YFP) tagged Rabs, a small GTPase required for vesicular trafficking. Our preliminary results suggest successful targeting of the YFP-tagged Rab6. We are currently testing additional YFP-tagged Rabs, as well as sperm-specific proteins. The results should reveal whether the proteasomal pathway is working in all stages of spermatogenesis and aid in the understanding of proteins required in the acrosome biosynthesis pathway. Overall, our findings will expand our knowledge of sperm formation and function.

The Laser Interferometer Gravitational-Wave Observatory (LIGO) is one of the most sensitive experiments ever developed, it can detect distance changes to about a width of a proton. The first detection of a gravitational wave signal was from a binary black hole merger on September 14, 2015. First predicted by Albert Einstein’s Theory of General Relativity in 1916, gravitational waves carry energy through space due to collisions of compact objects, usually black holes or neutron stars. However, noise transients, also known as glitches, mimic astronomical gravitational wave signals decreasing the sensitivity of the detectors. Glitches occur due to a variety of reasons, including environmental noises or instrumental malfunctions. In this research, I work to improve the quality of the collected data and eliminate as much noise as possible in the interferometers. I participate in detector characterization that uses tools and methods to identify, characterize, and remove noisy data in the analysis time. Performing data quality shifts enhances the ability of the instruments to probe some of the most exotic objects in the universe, including black holes and neutron star mergers. The search for gravitational waves opens a new era in astrophysics enabling us to observe events that an ordinary telescope can’t. In addition to seeing how our universe is altering, we now can also hear these changes, like sound waves, caused by vibrations that are audible to the human ear.

In recent years, researchers have dedicated much effort to overcoming the ~250nm spatial resolution limit of light in order to reveal biological details that have been obscured by diffraction. A new form of super-resolution microscopy called expansion microscopy (ExM) has enabled ~65nm image resolution or better by physically expanding fixed specimens in a swellable hydrogel polymer. While ExM allows researchers to achieve high resolution with standard microscopes, the technique requires the use of water-immersion lenses, rather than higher-resolution oil-immersion objective lenses, when imaging more ~5 µm deep due to spherical aberrations caused by refractive index mismatch with oil lenses and water-based hydrogels (n=1.5 vs n=1.3). Oil-immersion lenses also collect more signal than water-immersion lenses, enabling higher signal to noise with oil-immersion lenses under the same excitation conditions. I have developed an index-matching technique that significantly reduces spherical aberrations when imaging with oil lenses and expanded specimens, facilitating improved resolution (~1.12x lateral improvement and 1.5x axial improvement) for depths of up to 25 μm. Expanded specimens are index-matched by simply incubating the specimen in a high-index iohexol solution which equilibrates with the specimen in approximately 18 hours. A modest ~17.5% shrinkage of the hydrogel is produced as a result in the current implementation, which I can in principle compensate for by tuning the hydrogel recipe to achieve a slightly higher expansion factor. I found that the iohexol solution on its own accelerated the rate of fluorophore bleaching and led to some fluorophore quenching. However, the addition of the triplet-state quencher n-propyl-gallate effectively mitigated this chemical bleaching. Ultimately, this iohexol-facilitated index-matching procedure not only combines the utility of ExM and the high collection efficiency of oil immersion objectives but allows researchers to use common chemicals and readily available instruments to obtain images that reveal a previously inaccessible wealth of information.

Previous research on JNK-mediated stress signals demonstrated that stem cells in the posterior midgut of Drosophila Melanogaster only undergo compensatory proliferation or apoptosis. However, our group discovered that the stem cells can also undergo the process of basal extrusion and dissemination, resulting in the cells being eliminated from the tissue into the hemocoel, the blood containing intertissue body cavity. The JNK signal promotes the cells to exit the epithelium of the gut, move through the muscle layer, and be released to the hemocoel, which resembles the process of metastasis in human cancer. In order to understand the mechanism of this extrusion process, we carried out an RNA Interference (RNAi) screen and sought to find genes that are necessary for the stem cell extrusion in the JNK activator, HepCA, expressed flies. We used the ESG-GAL4, UAS-GFP, TUB-GAL80TS(EGT) genetic system to study the knockdown effect from the RNAi of each gene. We selected 215 lines of kinases and phosphatases of flies to test if the knocked-down gene results in suppression of cell elimination by the JNK stress signal. After 4 days of inducement, which is the sufficient time for the JNK signal can promote complete extrusion of the intestinal stem cells, the intestines were dissected, fixed, mounted, and examined with a fluorescent microscope for any presence of stem cells. Through this screen, we could find 33 lines that had strong suppression of cell elimination, 39 lines that had a moderate effect. Our results suggest that the knocked down genes with strong suppression of cell elimination are involved in the mechanism of basal cell extrusion, and future research dictates an investigation into the molecular function of each of these genes.

This project seeks to understand tidal circulation between Puget Sound and the Pacific Ocean using data captured by sensors on board Washington State Ferries traveling across Admiralty Inlet. As the most important passage between Puget Sound and the Pacific Ocean, understanding circulation across Admiralty Inlet is critical to monitoring water quality in Puget Sound. Data from this research is being used by the Washington State Department of Ecology to manage water quality issues such as nutrient enrichment, algal blooms, dissolved oxygen concentrations, and transport of toxic chemicals across the region. In addition to managing existing data, my role has been to develop a tidal-energy dissipation map of Admiralty Inlet. While site specific energy dissipation has been calculated in areas of Admiralty Inlet, a cross-channel model has never been developed. Understanding tidal-energy dissipation at the mouth of Puget Sound will benefit future large-scale tidal-energy research by assisting tidal-energy forecasting, characterization, and assessment.

Underwater noise pollution has increased greatly in recent years due to human activities. Such noises have adverse effects upon marine life. However, there is limited information on long term exposure to low-intensity man-made noise such as bridge traffic as well as how man-made noise propagates through water. The main goal of this study is to learn about the impact of the noise pollution generated by the SR-520 and I-90 bridges on Lake Washington. To record samples of the noise an underwater recording packing was engineered, this system possesses a hydrophone that records ambient noise levels, a Raspberry Pi to serve as a microcontroller with remote access capabilities, and an integrated cellular device to upload all relevant data to Microsoft Azure’s cloud computing database. The Audio was recorded during predefined intervals of the day and can be easily accessed from the cloud for further analysis. Along with this the user is able to remotely control the system giving them a low maintenance device to work with. To make this package self-sustaining, solar panels were installed on the buoy to recharge the deep cell batteries and super capacitors which were used to power this system. The goal when engineering this device was to design a low maintenance durable machine that could accurately record audio underwater. With these features the user could explore the long-term effects of underwater sound resulting from human activities and their potential effects on aquatic life. Once the acoustical data is collected, a compound analysis will involve studying the ambient noise levels and possible ecological effects of low intensity, constant traffic at multiple distances from the source.

Alzheimer’s disease (AD) is a progressive degenerative disorder that affects over 5.5 million Americans, resulting in memory loss and cognitive decline over time. AD is characterized by the accumulation of neurofibrillary tangles composed of pathogenic proteins, such as alpha-synuclein. Recent findings suggest that extracellular vesicles (EVs), which primarily function in intercellular communication, may play a critical role in the propagation of these pathogenic proteins in the brain. However, the cellular pathways that load AD-associated toxic proteins into EVs remain unknown. This research project aims to investigate the cellular pathways that influence the biogenesis, secretion, and uptake of EVs carrying AD-associated toxic proteinsusing the powerful genetic model system Saccharomyces cerevisiae. This simple brewer’s yeast has already been proven to be a useful model for understanding AD-related toxicity. When alpha synuclein is overexpressed in S. cerevisiae, it localizes to cell membranes and results in cytoplasmic aggregation that is observed in humans. We purified EVs from yeast expressing human AD-associated toxic proteins (Tau, alpha-synuclein) to establish whether they contain the human transgenes using Western blot analysis. We developed an immunohistochemistry protocol to rapidly quantify the levels of proteins secreted into the extracellular enviroment. We cultured yeast, optimized Western blotting conditions, purified extracellular vesicles, and used imaging techniques in our project.

My presentation reviews existing literature on the use of boron clusters in liquid crystals. Liquid crystalline substances are usually composed of long, thin carbon-based (organic) molecules and have applications in electronic display technology and chromatography. Many compounds with liquid crystalline phases contain rigid substituent groups. The rigidity of inorganic boron clusters and their ability to form linear compounds by attaching groups to atoms on opposite ends of the cluster make them an intriguing starting point for the synthesis of new liquid crystalline materials. Work conducted on the synthesis and properties of boron cluster-based liquid crystals in comparison with organic cyclohexane- or benzene-based analogues is discussed. In addition, new derivatives of a specific boron cluster, CB11­H12­-, synthesized in our lab using microwave and stardard Schlenk line techniques, are presented, along with an evaluation of their potential as precursors for new liquid crystals. We present a relaible pathway to a new difunctionalized carboxylic acid derivative.

Understanding the principles that underlie physiological problems can help students succeed in the mastery of a wide range of physiology topics. Understanding the principle of flux, which governs pressure gradients, can greatly improve a student’s ability to solve problems related to bulk flow and pressure in a variety of physiological systems. In general terms, the principle of flux describes the rate of movement of a substance from one compartment to another. It is defined as the magnitude of the driving force (gradient) divided by resistance. We examined how students in an introductory physiology class think about flux in the context of a pressure gradient within the cardiovascular system. We began by incrementally refining a variety of gradient-related questions through successive rounds of think-aloud interviews with individual student volunteers. Using these responses, we generated a cardiovascular pressure gradient question that elicited a wide variation of student answers. We collected responses from 200 introductory physiology students both before and after relevant course content to be sure our question captured both novice and advanced reasoning. We examined the responses and constructed a rubric to categorize student responses into a hierarchy of response sophistication and completeness. Generally, level 1 represents the most novice responses, while level 5 represents the most advanced. In our rubric, level 1 answers relied on vague reasoning relating to homeostasis, equilibrium, or intuition. Responses categorized at levels 2 and 3 showed an understanding of the components that contribute to pressure without successfully identifying how they connect to changing pressures. Lastly, answers at levels 4 and 5 showed an understanding of these components as well as the ability to successfully relate them to changes in pressure. Identifying patterns in student responses to a pressure gradient problem can give instructors a starting point from which they can target common misconceptions to ensure conceptual mastery in their classrooms.

Cycle tracks have been proven to be one of the safest forms of bike infrastructure in terms of car-bicycle collisions. Otherwise known as bikeways, a cycle track is a form of street-level bike infrastructure that uses a variety of methods for physical protection from passing traffic. This study examines individual perception of safety while biking and how it varies with different buffers. Through an online survey, individuals, both bikers and non-bikers, will be asked to rank their safety perception of cycle tracks with different types of buffers. Results from this survey will determine which kind of buffer; between planters, raised concrete curb, two-to-three foot painted buffer with plastic flex posts, two-to-three foot painted buffer with parked cars, and grass with trees, has the highest ranking of safety perception. My findings will act as the evidence necessary to recommend that the City of Seattle's Department of Transportation implement more of this type of cycle track to ultimately increase ridership.

The global focus on health equity and the injustice of health disparities highlight the need to explore social determinants of health. While socioeconomic differences in alcohol use are well documented, the socioeconomic differences of those that have experienced positive outcomes from drug and alcohol treatment remain largely unexplored. Per the Stress Process Model and Fundamental Cause Theory, we would expect treatment’s ability to reduce substance use to be significantly influenced by access to resources—time, energy, and both economic and social capital). Moreover, if class-based disparities in recovery from addiction exist, this important dimension of inequality must be incorporated into our understanding of stratification in health outcomes. Using pooled cross-sectional time series data over 6 years on adults over 25 from the National Survey on Drug Use and Health (N = 118,392), this study aims to answer the question: Does socioeconomic status (SES) moderate drug and alcohol treatment’s ability to reduce substance use? We operationalized measures of SES and receiving treatment as independent variables, the number of binge drinking days (five or more drinks in a day) in the last month as the dependent variable, and controlled for demographics and characteristics of past use. Additionally, we extend this research by comparing results from three years of low unemployment (1999, 2000, and 2001) and three years of high unemployment (2009, 2010, and 2011) to explore how the economic climate interacts with SES’s impact. Initial findings support the Stress Process Model and Fundamental cause theory by revealing that those of higher SES see a greater reduction in binge drinking after treatment. We expect times of high unemployment to exaggerate these findings, revealing structural barriers to recovery. The goal is to add to the academic understanding of social stratification, aid in targeted resource allocation to improve health, and promote health equity.

Hydrogen sulfide (H₂S) is a gas most commonly known for its pungent scent and toxicity. However, administered in low doses, H₂S can be tolerated, and it can even facilitate the acclimation to higher doses in the nematode Caenorhabditis elegans, a model organism with relatively short generation times and extensive tools for genetic manipulation. Furthermore, H₂S could have important medical uses due to its function as a vasodilator and chemical signal in cellular signaling, such as conserving donor organs, extending the time prior to an ischemic response, and decreasing nociception in severe injuries (Miller, and Roth). Data from our lab suggest that a low dose exposure to H₂S during early stages of development forms a “bookmark” which permits the survival of the animal at high doses of H₂S during adulthood. Through a genetic screen, epigenetic factors including spr-5, set-2, swsn-4, and swsn-1 were discovered to be involved in the bookmark. The ease of bookmark formation and the short time between formation and manifestation of phenotype present a unique opportunity to dissect a complete epigenetic pathway in addition to understanding cellular responses to H₂S. Our project aims to develop tools that will help understand temporal and spatial requirements for the protein products of these bookmarking genes. To achieve this, we intend to use CRISPR to attach a tag to the endogenous loci of target genes that allows for auxin-induced degradation (AID) (Zhang, L. et al.). Our targets will include both bookmarking genes and previously identified H₂S response elements such as hif-1. Thus far, we have tested the efficiency of the tag on Green Fluorescent Protein (GFP). Presently, we are working to create the transgenic lines of nematodes that carry the AID tag alongside proteins involved in the formation or maintenance of the H₂S bookmark.

Early antibiotic administration is a critical intervention in sepsis; however, identifying infection in the emergency department can be challenging. We hypothesize that emergency clinicians over-treat for infection overall, even when non-infectious etiologies are felt most likely. In two academic Emergency Departments (EDs), we prospectively investigated clinician gestalt – the use of historical facts and physical examination findings to recognize disease patterns and make a clinical decision – for infection and antibiotic administration to assess 1) the frequency in which clinicians administer antibiotics to patients felt most likely to not have infection, and 2) the number of patients felt to have infection and received antibiotics, who ultimately did not have infection. We enrolled subjects at both the University of Washington and Harborview Medical Centers. We included patients with signs of critical illness, defined as 1) two or more systemic inflammatory response syndrome criteria and organ dysfunction, 2) systolic blood pressure < 90 mmHg, and/or serum lactate levels greater than 4.0 mmol/L. At the time of admission, attending physicians were surveyed regarding the etiology of illness (infectious or non-infectious). Patient demographics, medical history, and ED interventions, including antibiotics, were abstracted by chart review. Ultimate determination of diagnosis was adjudicated by chart review by an attending emergency physician. We enrolled 405 patients, 191 (47.2%) with infection by final adjudication. Physicians identified 199 (49.1%) as most likely non-infectious, of whom 79/199 (39.7%) received antibiotics. Of these, 53/79 (67.1%) did not have the infectious etiologies. Of the 206 patients whom physicians suspected to most likely have infection, 185/206 (89.9%) received antibiotics, and 37/185 (20%) were adjudicated to non-infectious etiologies. Emergency clinicians mitigate diagnostic uncertainty by administering antibiotics. Improving the identification of infection among critically ill emergency patients may be a meaningful target for antibiotic stewardship efforts.

Immigrants experience many challenges prior to arriving in the United States and face ongoing challenges associated with migration and the assimilation process. Despite the multiple challenges and difficulties, immigrant people show enormous strength, courage, and self-determination. Resilience is defined as the process of moving forward from adversity, developing new skills and creative ways of coping and becoming stronger. I conducted a systematic literature review, using key terms such as immigrant, asylum seekers, coping mechanisms, and resilience. I incorporated multidisciplinary lenses including psychology and sociology to identify and understand the major contributors to immigrants’ resilience as well as major factors that hinder resilience. Research suggests factors such as family strength, cultural and community support; religiosity and spirituality help to build resilience. In contrast, factors such as language barriers, discrimination, punitive policies and the labeling of trauma by experts are known to hinder resilience. The research implies that the experts lack awareness of their labeling and understanding of trauma stories. Additionally, studies suggest that contrary to popular beliefs, immigrant people are resilient and motivated, and value education and hard work. Further research in methods of developing policy systems that support and facilitate resilience is desperately needed.

Deep Reactive Ion Etching (DRIE) is used for high aspect ratio etches in silicon wafers. The process is effective at achieving deep etches with high anisotropy and selectivity, however more process development is required such that side wall profile angle is selectable based on etch parameters. The goal of this study is to manipulate process variables (including pressure, etch time, and temperature) to allow the production of tapered, reentrant, or vertical side walls as needed. The SPTS-DRIE will be used to etch silicon targets with a repeating array of test patterns using a standard etch and deposition recipe. The standard etch recipe used will cycle between polymer deposition steps and plasma etching steps at low pressure using C4F8 and SF6 gases. Etch depths will be verified using a Bruker DekTak profilometer and sidewall angles will be measured using a Jeol scanning electron microscope. The parameters of the etch recipe will then be adjusted depending on the previous etch profile. Depending on the profile and aspect ratio of the etch, different parameters will be studied, including the process pressure, temperature, gas flow rates, and etch/deposition times. This process will be repeated until results within a reasonable margin of the target are reached. The goal will be to obtain an etch profile with sidewall angles of 90° ± 0.1° for use in industry and to determine parameters for reentrant and tapered profiles.

Past research shows that white and wealthy men are the most prevalent donors to local and state political campaigns, maintaining political influence through ineffectively regulated systems thereby threatening the quality of American democracy. As regulation-based campaign finance reform has been unable to mitigate the influence of large donors in local campaigns, city councils and grassroots organizations have started to present incentive-based policies to provide average Americans with the means to donate, though few have actually implemented them. Budding reforms like that of the Democracy Voucher program in Seattle, though showing promise, demand the attention of researchers to analyze their efficacy. Through comparing both the demographics and the histories of political engagement between donors, program participants, and other voters, this study seeks to determine the initial success of the Democracy Voucher program in Seattle. It concludes that one can observe a minimal increase in donors and more diverse donors, suggesting that the Voucher Program was marginally effective in achieving its goals of diversifying the donor pool. This research contributes to the literature available to policy makers and other researchers interested in developing public campaign financing reforms at the municipal and, potentially, state level.

In this work, we solve nonsmooth minimization problems on a convex set. These kind of problems arise from real applications. Such applications, for example, include mechanics, economics, computational chemistry, engineering, machine learning, and data mining. To solve these problems, we combine the spectral step length with two sub differential schemes to develop the Spectral Projected Subgradient (SPS) and the Projected Spectral Simplex Gradient (PSS). These methods use a nonmonotone globalization condition, and do not required estimates of the optimal solution to compute the step length. For the SPS method, a subgradient has to be supplied. On the other hand, the PSS method is a direct search method that only requires function evaluations to build an approximation to the gradient direction. The proposed methods have many advantages such as easy to implement, and low memory requirement. For both algorithms, we present numerical results on a set of nonsmooth test functions. The results indicate the spectral step length can improve the practical performance of both methods.

In Silicon Valley, only 5% of the software developers are women and the technology industry is mostly white, English speaking males. As of January 2015, 60% of Google employees were white. Because of this lack of diversity, there is reason to worry that the products produced by technology companies might perpetuate exclusion of identities that then result in ethnocentric design. Design scholarship and practice needs to cultivate diversity within current design techniques in order to more productively demonstrate inclusion. In this literature review, I found that there is a lack of knowledge about diversity, systemic biases and prejudices against certain groups in the design field that brings adversity and inconvenience to the casual user. There are many situations in which the lack of diversity is affecting the result of the product. For instance, the gamer culture and the technology culture have perpetuated sexism, misogyny, and false gender representation as evidence by the Gamergate controversy. Games are designed by people who either believe the gamer culture (predominantly young and male) is the social reality or are part of this culture themselves. These people are incorporating their own biases and beliefs in their design. Additionally, many social media are designed in ways which make it easier for people to harass and treat others badly. Everyone should be able to use technology without the design preventing them from having a positive experience. Ultimately, groups excluded in a particular design may think of themselves as the “outsider.” Along with this, there are conscious and unconscious social and cultural biases that the designer might be applying to the design process. Conclusions from this research could be used to make more inclusive design.

Plasma, the fourth state of matter, is created by introducing a gas - in this case, helium - to an electric field. This field ionizes the helium atoms, which in turn ionize other molecules, creating a wide variety of highly reactive species. Previous work at Edmonds Community College demonstrated the efficacy of an atmospheric pressure plasma jet (APPJ) in killing endospores of Bacillus atrophaeus for the purpose of spacecraft sterilization for NASA (Bernard et al., 2017). With increasing rates of antibiotic resistance, there is interest in using an APPJ in healthcare settings to eliminate harmful pathogens and therefore promote wound healing. However, given its destruction of endospores, it is unclear if the APPJ would damage living tissue. The purpose of this research was to analyze the effect of an APPJ on multicellular eukaryotic organisms. The impact of different exposure times of the APPJ upon both germinated and ungerminated Zinnia elegans seeds, and the effects on plant growth, was studied. The optimal exposure time for germinated seeds was between one and two minutes, while treatments greater than 2 minutes may increase germination rate.

Etching is one of the critical process steps in the fabrication of micro- and nano-scaled devices. Prior to etching, a pattern, usually defined in a temporary photo-sensitive polymer mask material called photoresist, is transferred onto a silicon wafer. One way to etch material, is through the use of plasma. Inductively Coupled Plasma (ICP), is distinct for its coil that shapes plasma and DC bias coupling for directionality. The machine has high etch rates and is used to etch oxide. Specifically for this project ICP-F (Fluorine) has been used. During etching, a photoresist reticulation problem has occurred. With this reticulation, features on the wafer are degraded, when reticulation is wide spread, the whole wafer must be stripped and restarted. This problem affects the speed and quality of production of wafers. In attempts to fix this problem, different variables such as the DC bias, chuck temperature, He backing, and RF power are monitored. Furthermore, the effects of varying pre-etch conditions, such as wafer bakes and different wait times, are examined to determine if there is a correlation between moisture in the photoresist film and resist reticulation or if the issues are predominately related to the etching system. Different inspection steps are made to ensure the quality of the etch, such as visual inspections and measurements of etch depths. These inspection steps concludes how much reticulation has occurred and what it has affected. ICP-F etching is just one step of the process in of fabrication of micrometer scale inductors and capacitors directly on the top of silicon wafers referred to as Integrated Passive Devices (IPD). This process decreases the amount of space used and increases the bandwidth of radio frequency (RF) analog filtering and the speed of digital information transfers. 

Environmentalism has often been considered a moral commitment. However, this paper investigates the hypothesis that environmentalism is not just a moral commitment, but a highly logical economic commitment. I argue that environmentalism is not contrary to economic motivations: instead, states fund their departments of ecology when they stand to gain economically from doing so. This paper compares the percentage of each state’s budget that went towards funding their ecology department to the tax revenue generated by two types of state resources: the outdoor recreation economy in each state and each state’s proven crude oil, shale gas, and natural gas reserves. When states receive more tax revenue from the outdoor recreation economy, they allocate a larger percentage of their budget to ecology departments. On the other hand, the presence of proven crude oil, shale gas, or natural gas reserves will decrease the amount of funding for state ecology departments because states generally gain more economically from the exploitation of those resources than from the outdoor recreation economy. Broader implications of this paper include the conclusion that the best way to ensure that states will be environmentally conscious is to make it economically advantageous to do so as states act primarily on economic incentives. This study uses data sets from Ballotpedia and American FactFinder and is supplemented with data from the National Conference of State Legislatures and the Outdoor Industry Association.
 

The ease at which we appear to recognize and assess faces belies the difficulty underlying face recognition. Faces possess similar features (i.e. eyes, nose, mouth), yet we are able to identify separate individuals based on their featural configuration (i.e. T-shaped arrangement of features). Prior research using fMRI shows that featural and configural information is processed in different face-specific brain regions. Evidence suggests that the FFA responds to both featural and configural information, compared to the OFA and fSTS, which only respond to featural modification. However, precise response time of featural and configural face processing is unknown. Featural processing may occur before configural processing, or configural processing may occur before featural processing; conversely, they may occur simultaneously. Using a 2x2 factorial design we assessed the effects of changes in featural information, configural information, as well the interaction between the two. Participants saw four versions of a face: intact faces, faces with removed features, faces with distorted configuration, and faces with both modifications. Stimuli were presented while the brain activity of subjects was recorded using electroencephalography (EEG). This study specifically looked at temporal changes in a face-specific event related potential (ERP) called the N170, which consistently fires when presented with anything that resembles a face. We assessed the magnitude of the N170 to determine whether the face-processing brain regions explicitly processed information regarding features and configuration. In addition, timing of face-processing was assessed to detect any differences in how long it took the brain to process faces with featural or configural modifications. We tied together evidence from fMRI (spatial) and the N170 (temporal) to see how precise timing and location interact in the brain during face perception of facial features and feature configuration.

Developmental Epileptic Encephalopathy (DEE) is a severe form of epilepsy in children and infants characterized by prominent EEG (electroencephalography) abnormalities disrupting brain function. Identifying the genetic causes of DEE will help researchers develop medical treatments for affected patients. Approximately 5% of DEE cases involve a copy number variation (CNV), where a region of DNA has been duplicated or deleted in a gene, causing the disease. Historically, this type of mutation has been difficult to detect using sequence data. To analyze the large amount of sequence data available in the Mefford Lab, I am creating an algorithm that will analyze smMIP (single molecule molecular inversion probe) data to identify CNVs in patient DNA that are likely causal for DEE. The algorithm is a two-step process. First, z-scores are assigned to the number of smMIP reads at each target site of each patient sample to numerically assess how many standard deviations it is from the mean. Next, regions of contiguous significant z-scores will be extracted as areas of top interest to verify as being a CNV. I will run the completed algorithm with smMIP data from the Mefford Lab's unsolved DEE cases. Since CNVs have historically been difficult to detect, it is unclear what percent of these unsolved cases will contain a CNV. It might be that, due to previous lack of detection, CNVs play a more significant role in DEE than previously thought. The opposite might also be true if a large majority of unresolved cases are due to other types of mutations, e.g. point mutations. Regardless, the algorithm will shed light on new causative CNVs and allow the Mefford Lab to solve more patient cases. Additionally, a successful CNV calling algorithm can be shared with other labs to aid them in their research.

Developmental and epileptic encephalopathies (DEEs) are epileptic disorders characterized by severe, recurrent seizures and intellectual disability. The Mefford Lab works to discover novel genetic causes of pediatric DEEs. We hypothesize that early-onset DEEs in severely affected patients with two healthy parents are caused by pathogenic de novo variants—disease-causing variants in the genome of the patient that are not inherited from either parent. Comparing sequence data in a trio that consists of an affected patient (proband) and two unaffected biological parents allows for efficient detection of de novo mutations and suggests a genetic cause for the associated phenotype. Trios are submitted for whole exome sequencing (WES) to obtain sequencing data from all the protein-coding regions of their genome. Occasionally, exome sequencing is unsuccessful for one or more members of the trio and alternative methods are needed to sequence and identify potentially pathogenic variants in these trios. I am working on identifying potentially causative variants in patients for whom one or more parent(s) did not successfully complete WES. I analyzed WES data to identify likely pathogenic variants in 10 probands by filtering for protein-changing variants that are not present in >100,000 healthy individuals. I used single molecule molecular inversion probes to perform simultaneous, targeted sequencing of the identified variants in the complete trios to determine which variants were de novo. The existence and inheritance of de novo variants was confirmed using Sanger sequencing. I have identified and confirmed a de novo variant in one patient in HIVEP2, which encodes a transcription-regulating protein expressed in the brain. I am currently completing the process of sequencing and filtering variants on additional trios. The further identification of de novo variants in these patients will be useful in better understanding the complex genetic causes and genotypic-phenotypic associations of epilepsy, and helpful in the clinical setting for improving and individualizing treatment of the disorder.

Diabetes is increasingly prevalent in the world, and there are currently over 29 million people in the United States with diabetes. Type 1 diabetic patients depend on insulin injections to maintain their blood insulin within a certain level so that their cells are getting enough sugar for energy production. Type 2 diabetic patients mostly rely on diet treatments and combinations of insulin and other drug treatments to avoid hyperglycemia. Moreover, type 2 diabetes often leads to different complications such as cardiovascular disease, blindness, and kidney failure. The goal of our study is to investigate insulin effects on the activation of macrophages, which are immune cells with important roles in inflammation. Since a pro-inflammatory state of macrophages can enhance insulin resistance and lead to cardiovascular diseases, it is crucial to understand if insulin changes the macrophage activation states that can cause off target effects leading to other medical complications. The experiments for this project are performed using RAW 264.7 cells, an immortal cell line derived from mouse macrophages. A dose experiment of insulin stimulation was performed to test if phosphorylated STAT1 (pro-inflammatory or M1) and phosphorylated STAT6 (anti-inflammatory or M2) were detected via western blot. Additional experiments determined the intensity of the macrophage response by measuring downstream signaling proteins (PI3K or IRS2) via immunoprecipitation and western blot. Also, RNA extraction and qPCR were performed to see if the gene transcription of macrophage polarization is activated by the above transcription factors. For example,  TNFα and IFNγ were measured for M1 polarization and IL-4 and IL-10 were measured for M2 polarization. Finally, NF-κB, another transcription factor was measured to determine if phosphorylation occurred, which should lead to M1 gene transcription. Together, these experiments revealed whether insulin affects key pro-inflammatory and anti-inflammatory signaling pathways in macrophages.

Connecting patients to the appropriate health or social service intervention is critical for their long-term health and well being. The 911 system is increasingly being utilized for non-emergency medical situations that originate with non-acute health issues and poor health care access. This diverts resources away from the core mission of fire departments which is to respond to emergencies in a timely manner. This study utilized data from South King County’s 911 dispatch center, Valley Communications, and the American Community Survey to identify socioeconomic factors that may correlate with non-emergent 911 responses. Ultimately, this demographic study identified areas with high primary health needs that are ineffectively addressed and characterized their demographic profiles. Of particular interest are high frequency non-emergent callers that rely on the 911 system for chronic and reoccurring health issues. This information was mapped and related to health care facility locations to determine how health access played a role in this behavior. Researchers and policymakers can expand upon the conclusions of this study to create more targeted, effective, and efficient alternatives to the emergency medical system that can serve regions with the greatest health access and health delivery needs.

Scholars continue to be perplexed by the low rates of Asian American political participation despite their relatively high levels of education and income, two factors which have been shown to be strong predictors of political behavior among whites, African Americans, and Latinos. What is different about Asian Americans that make them largely unaffected by these factors? If their low rates of participation remain unmoved, they risk being systematically neglected from the democratic processes of the government. This study hypothesizes that the deeply rooted Asian cultural values of respect for authority and hierarchy dampen defiance and encourage passivity, therefore causing Asian Americans who are closely tied to their Asian culture to be less politically active. This study will measure political participation through self-reported voting and registration, while using a series of variables to determine levels of engagement with Asian culture. The dataset used from National Asian American Survey captures Asian Americans’ political attitudes and behaviors during the Presidential elections of 2008.

The development of neurodegenerative diseases, such as Parkinson’s, Huntington’s, and Alzheimer’s affect millions of people every year. Previous studies have shown that an enzyme found in the endemic Herpes Simplex Virus (HSV-1); UL12.5, degrades the mitochondrial genome, which we hypothesize may predispose patients to neurodegenerative conditions. A majority of the human population is infected with HSV-1 and other herpesviridae, which encode similar enzymes, and their reactivation is commonly seen throughout life. We have found that the degradation of mitochondrial DNA by UL12.5 activity is widely conserved and when UL12.5 is expressed in the model organism, Caenorhabditis elegans (C.elegans), mitochondrial DNA content drops nearly 10-fold. Interestingly, we find that activation of the HSV-1 UL12.5 enzyme alters cellular proteostasis; the cell’s mechanism for maintaining properly folded and functional proteins. This change in proteostasis alters the aggregation of misfolded proteins, especially those involved in the cause of neurodegenerative diseases, and leads to neurological phenotypes like paralysis, which we can quantify in the worm. To study the enzymatic activity of the UL12.5, we used modified worms expressing the protein using an inducible transgene that can be verified by fluorescent microscopy. The effects of the UL12.5 activity is determined by tracking lifespan of worms, performing paralysis assays, and counting protein aggregates with controls that use a catalytically inactive version of UL12.5. We have also found that Emodin, a compound found in traditional Chinese medicine, which has previously been shown to inhibit UL12.5, alters the activity of UL12.5 in a worm model of Huntington’s disease. We hypothesize that activation of this enzyme may cause similar pathologies in the human brain and may be a causative factor in human neurodegenerative disease. Further, inhibitors of UL12.5 like Emodin may prove useful therapeutics for treating neurodegenerative diseases.

King County is home to many non-English speaking populations. Language and cultural barriers must be accounted for in risk communication materials to limit adverse health risks following extreme weather events. During the summer of 2017, Washington experienced a heat wave and increase in air pollution from wildfires. In King County, exposure to extreme heat has been shown to increase risk of all cause mortality by 10%, while poor air quality contributes to 16% of all deaths worldwide.. Despite the growing evidence about communication with non-English populations during extreme weather events, research has yet to examine ethnic media outlets’ approaches to communicating health risks. In Washington state, Spanish, Vietnamese, and Somali are the top 5 non-English languages spoken. In response, we sought to assess if and how local ethnic newspapers disseminated risk communication information during the 2017 heat wave and air quality event. We used descriptive statistics to compare the number of ethnic news media messages to the Seattle Times, the predominant newspaper in King County, and assessed the messages communicated based on air quality day. The research findings show that non-English newspapers included fewer risk communication messages, including on days with air quality levels known to increase health risks. On the other hand, the Seattle Times included messages about health prevention methods, daily weather forecasts, and informational articles on the cause of the events. Our findings suggest that there is a need to improve risk communication during wildfire and heat events to populations with limited English proficiency in King County. We recommend engaging members of non-English speaking communities to identify the best communication methods, and work with newspapers serving these communities to promote awareness during future extreme weather events.

Aging is a major risk factor for the most common causes of death in the developed world which include cancer, heart disease, and neurological disorders. Because of this, therapies that target the hallmarks of aging are a promising area of study. The mechanistic target of rapamycin (mTOR) kinase is a major regulator of growth, aging, and survival in cells. Inhibition of the mTOR signaling pathway is associated with increased longevity in organisms including yeast, nematode worms, fruit flies, and mice. Inhibition of mTOR can be achieved through pharmacologic intervention, which is a promising strategy to extend healthy lifespan. To better understand how mTOR inhibitor response varies between genetically-diverse populations, we utilized a set of 90 wild and domesticated yeast strains. We tested a set of mTOR inhibitory compounds on these strains to identify strains with increased sensitivity or resistance to mTOR inhibition. We have identified genetic variants that drive drug sensitivity or resistance in these strains. We then engineered mutations into laboratory strains to confirm that these mutations recapitulate the phenotype of interest. By understanding drug response across genetically-diverse populations, we will create the framework for a precision medicine approach to developing healthspan-enhancing compounds that can be translated to humans.

At a time of heightened global attention to the threat of misinformation, disinformation, political propaganda, and the role of technology in facilitating their spread, this research addresses the media ecosystem encompassing the Syrian Civil War. We examine the competing narratives surrounding the role of Syria Civil Defence, a volunteer humanitarian organization popularly known as the White Helmets, working in war-torn Syria. Mainstream media articles sympathetic of the White Helmets and their efforts brought global awareness to the plight of Syrian people, especially those resisting the Assad government. However, this narrative was not aligned with other views of the complex geopolitical landscape of the Syrian conflict, and in response counter-narratives challenging the White Helmets emerged and spread to other online communities. Using a mixed-method approach based on seed data collected from Twitter, and then extending out to the websites cited in that data, we examine content sharing practices within news articles across distinct media domains that functioned to construct, shape, and propagate these narratives. We articulate a predominantly alternative media “echo-system” of websites that repeatedly share content about the White Helmets. Among other findings, our work reveals a small set of websites and authors generating content that is spread across diverse sites, drawing audiences from distinct communities into a shared narrative. This analysis also reveals the integration of government-funded media and geopolitical think tanks as source content for anti-White Helmets narratives. More broadly, the analysis demonstrates the role of alternative newswire-like services in providing content for alternative media websites. Though additional work is needed to understand these patterns over time and across topics, we provide insight into the dynamics of this multi-layered media ecosystem.

 Fault zones are dynamic structural regions in the Earth’s crust that can constrain fluid flow in the subsurface. The presence of fluids in fault zones changes local stresses and can result in coevolving relationships between fluid migration and faulting. Because of this complex behavior, fault zone architecture is difficult to define, but two broad regions of deformation can be differentiated by material differences to describe permeability and other fluid-rock relationships. The fault core is the narrow, highly pulverized, often impermeable area of the fault closest to the slip surface. The damage zone is the wider, fractured, outer region of the fault which can allow fluid flow through fault-related cracks in the host rock. Although these these definitions describe general fluid-rock properties across fault zones, they do not fully capture the complex nature of fluid migration and compartmentalization in faults. Because fluids are difficult to observe in the Earth, mineral precipitates can be used as geochemical tracers for fluids. We analyzed carbonate precipitates in fault rocks from the fault cores and damage zones of three normal faults in Central Italy to characterize the fluids present in the area and the structural influences of fault architecture on fluid compartmentalization. Preliminary ¹⁸O and ¹³C standard stable isotope analysis aided initial fluid characterization and informed carbonate powder sampling for D47 clumped isotope analysis, which allowed us to reconstruct fluid temperatures and compositions. We present a spatial analysis of fluid compositions relative to structural units within the three fault zones.

Pregnant women often get their bellies touched without their permission by people ranging from family members, to coworkers, to strangers. While usually well-intentioned, people who touch pregnant bellies are unaware that their actions may be unwanted and invasive. Previous works, such as Asta Roseway’s Printing Dress, have shown that wearable computing can bring attention to social issues by provoking discourse. Those works lead us to our wearable design that highlights the issue of personal space for pregnant women. We implemented a maternity shirt that reacts to inappropriate touches upon contact in various ways, such as displaying messages, vibrating, and setting off an alarm. We plan to deploy this shirt on experimental participants and gather qualitative data in addition to the quantitative data collected through the shirt about when and where touches occur. Moreover, findings from the experiment will provide insight into pregnant women’s experiences, and how to design wearables that benefit to pregnant women. Our future goal is to have the shirt deter the toucher as they approach the belly. Through this interactive design piece we hope to raise awareness and provoke conversation around themes of consent, inappropriate touching, and women's bodies.

Epilepsy is a wide classification of neurological disorders that vary in symptoms, severity, age of onset, and demographics. Developmental and epileptic encephalopathies (DEE) are severe forms of epilepsy that involve both early-onset seizures and cognitive and behavioral impairments. One major cause of DEE is genetic variation. However, only 24-40% of DEE cases receive a molecular diagnosis. Our goal is to identify novel genetic variants that cause DEE via sequencing. In DEE, many of the variants associated are de novo, meaning they are novel mutations not inherited from either parent. Because of this, we are able to utilize segregation testing to identify the inheritance of a variant and determine if a variant is potentially pathogenic. From whole exome sequencing data on 200 patient and parent trios, we identified de novo variants in genes not previously associated with DEE. We then narrowed down our list of potential DEE genes to 53 candidate genes via Sanger sequencing. Using a sequencing technique called single molecule Molecular Inversion Probes (smMIPs), we simultaneously and accurately sequenced these 53 potential DEE genes in our cohort of 898 DEE patients, looking for additional de novo variants. These variants include missense mutations, frameshift insertions and deletions, and premature stop codons. Once potentially pathogenic variants are identified in the patient genome, we screened the parents using specific smMIPs selected for the patient-determined target regions to determine inheritance. If the gene validated as de novo, we can investigate the potential role of the affected protein in the phenotype. Our hope is that by identifying additional de novo variants in some of these 53 candidate genes, we can identify novel genes associated with DEE and provide answers to families about the cause of their child's condition. In the future, we hope the genetic understanding of DEE could lead to better, genotype-driven treatments.

River ecosystems depend on services salmon populations provide. Coho salmon, Oncorhyncus kisutch, supply valuable nutrients for mammals and birds and offer economic benefits for the Pacific Northwest. Salmon rely on water quality in freshwater streams during successful seasonal spawning. However, for over the past 15 years, research determined that urban stormwater results in the mortality of Coho salmon. Exposure to urban stormwater is toxic to Coho salmon, killing them in hours. This phenomenon is known as pre-spawn mortality (PSM), and it kills salmon before they reproduce. If this phenomenon continues, Coho salmon could go extinct. Previous studies have linked highway runoff and pre-spawn mortality. However, they indicate that basic water quality parameters such as temperature and pH and “typical” stormwater toxicants such as metals and pesticides are not the cause of PSM. Current hypotheses point to an unknown organic contaminant that is linked to urbanization and is probably present from roadways or cars. Previous studies have also shown that bioinfiltration of stormwater through a mixture of sand and compost can protect Coho salmon. The goal of this study was to investigate removal of organic contaminants in a pilot-scale compost-amended bioswale (CABS). The pilot-scale CABS was based on a field-scale bioswale that is operated by WA DOT and located on SR-518. In this study, we developed methods to extract water with suspended sediment (whole water), as well as extract filtered water and total suspended sediment (TSS) separately. Whole water and filtered water were extracted by solid phase extraction (SPE), using Infinity® SPE cartridges. TSS was measured using EPA Method 160.2, and captured solids were extracted with methanol. Extracts were then analyzed by liquid chromatography-high resolution mass spectrometry. These methods were then applied to evaluate removal of organic contaminants in the bioswale, including performance at multiple hydraulic retention times.

The North American beaver (Castor canadensis) is a keystone species and ecosystem engineer, capable of modifying the landscape and creating diverse habitats for other species. Through dam-building, beavers impound streamflow and create ponds and wetland complexes behind dams. The presence of beavers has been shown to increase biodiversity, reduce downstream flooding, and improve water quality. While beavers alter landscapes greatly, often in ways beneficial to native habitats and species, their dam-building can also create conflict with human land-use and infrastructure. One way to reduce human-beaver conflict is to adopt non-lethal approaches such as the use of pond leveler devices. Pond levelers, consisting of a pipe through the beaver dam with a cage around the inlet, control the water level of the pond by establishing a desired level while allowing beavers to persist, thereby reducing flooding. Little observational evidence exists on whether pond leveling devices create fish barriers or otherwise impede fish passage for migrating salmon. The objective of this research was to evaluate whether migrating salmon can pass through or around beaver dams fitted with standard pond leveling devices, under high flow conditions. We tested this by observational analysis collected from five pond levelers on Big Spring Creek, King County, Washington during the 2017 autumn salmon migration. Target migrating species include Chinook (Oncorhynchus tshawtscha) and Coho salmon (Oncorhynchus kisutch). During prolonged precipitation events it was determined that stream stage overtopped dams, providing unhindered passage in our study areas. Additionally, during the 2017 migration period, over-dam stream velocity and through-dam velocity (i.e. within the pipe) were passable by salmonids during 100% of the flows we observed.

Radiation emitted from supermassive black holes in the early universe (quasars) is absorbed by hydrogen in the intergalactic medium. Hydrogen absorbs light at certain resonant frequencies in the spectra of quasars. Statistics of Lyman-alpha absorption (the most studied resonant frequency of hydrogen) probes the cosmological parameters governing the universe (e.g. mass of dark matter) and the temperature of intergalactic gas (which constrains how the universe was heated). To further improve these constraints, I will be using another Lyman series transition (Lyman-beta). Due to the smaller absorption cross-section of Lyman-beta, we may probe higher densities than measured with the Lyman-alpha transition therefore increasing the number of data points to analyze. By including the Lyman-beta transition, our analysis allows for a better understanding of intergalactic gas which provides for more robust cosmological constraints.

Dopamine neurotransmission is thought to be involved in economic decision making. One aspect of the decision making is the vigor by which a decision is made, and its concomitant action. Previous studies have found baseline/ambient dopamine levels to be connected to vigor, however much is still unknown about ambient dopamine. The lack of understanding of the role of ambient dopamine is due to technical limitations. The limitations of fast scan cyclic voltammetry (FSCV) lead us to fuse FSCV with fast-scan controlled adsorption voltammetry (FSCAV) which will allow us to take direct measurements of ambient dopamine. Here we seek to develop a new technical approach to better study ambient dopamine and its involvement in decision making. To test our hypothesis, we used fast-scan cyclic voltammetry to measure levels of dopamine by applying two triangle waveforms at 1Hz to measure electrodes. The electrodes were tested in vitro against different concentrations of dopamine (0.0625-1M), one time with a 50kOhm resistor and one time without. Subsequently, the ability to predict concentrations was tested on electrically evoked dopamine, in vivo. Here we demonstrate that the standard curves collected are significantly linear. We also tested the effect adding 50 kOhm resistor to the measuring circuit in order to mimic brain tissue impedance. As a result of adding this impedance, we found a significant drop in sensitivity. Moreover, preliminary data suggest that unknown concentrations can be predicted using this approach., however more work needs to be done both in vitro and in vivo. Through this analysis, we can extend our results to the investigation of dopamine transmission functions and assess decision making. This will help us determine the different alterations of dopamine transmission and behavior in hopes to further advance development of therapeutic strategies for mental illness.

Between 2000 and 2010, self-identifying Asian Americans either alone or in combination with another race group reported a population growth of 45.6%; whereas an increase of 13% in population growth was observed in the total U.S. population. Within this group, Cambodian and Vietnamese refugees together comprise the largest resettled refugee population in the country since 1980. In this project, I am investigating whether social support and discrimination impact the mental health of Cambodian and Vietnamese immigrants and refugees. I hypothesize that social support will buffer against the effects of both discrimination and mental health, whereas discrimination will adversely affect one's mental health. Two waves of cross-sectional data, wave 4 (baseline for this study) and wave 5 (follow-up), will be obtained from the Cross-Cultural Families Project, a longitudinal study of 327 Cambodian and Vietnamese immigrant families in Washington State. I used logistic regression to examine potential association between discrimination and maternal caregiver's mental health, and its relationship to social support. Anticipated results include a positive correlation between discrimination and mental health, and a negative correlation between social support and discrimination, as well as social support and mental health. A greater understanding of the role that social support and discrimination play in relation to mental health in Cambodian and Vietnamese immigrants and refugees can lead to the development of culturally sensitive interventions. Furthermore, more conclusive research of these relationships can lead to a better understanding of resettlement experiences and how it has a role on one's mental health.

Watering is a necessary process in the horticulture field, and optimizing watering volume can help farmers save a lot of water and generate greater value. Traditionally farmers determine if a plant needs more water by observing their plants or by using a timer or sensor value. In the last decade, Machine Learning has gained popularity due to its effectiveness and efficiency. A database with 30 images of sufficiently-watered and 27 under-watered leaves is used for classification. This paper describes using a Support Vector Machine Learning algorithm to detect if a plant is under-watered or not from a new picture of the plant. The results show that current system has a success rate of 80%. In the future, this project can expand to provide more information on a plant status, including the presence of blights, stage of life, and ripeness of fruits, and mineral deficiencies.

Imidacloprid is the most widely used agricultural pesticide in the world. As a neonicotinoid, it is highly potent against insects while having low toxicity to mammals. One area of concern is its effect on honeybees, possibly playing a role in colony collapse disorder (CCD), a sudden disappearance of worker bees from an otherwise healthy population. Bees are known to be sensitive to imidacloprid at high concentrations, but what is unclear is whether chronic exposure to the low doses used to protect crops can also be harmful. The E.U. and Canada have taken steps to ban the use of imidacloprid as a precaution, and the U.S. EPA has warned users of its potential for leaching into groundwater. It may also persist for years in soil, pollen, and nectar. Due to its low volatility, high boiling point, and high solubility in polar solvents, imidacloprid can be difficult to reliably detect in environmental samples using current gas chromatography (GC) methods. To address this, we evaluated GC-MS detection of imidacloprid in methanol standards, spiked water, and spiked honey. Samples were evaluated after clean-up with both C18 solid-phase extraction (SPE) and dispersive solid-phase extraction (DSPE) methods, using two different GC columns (Restek Rxi-5MS and Rtx-1701). Samples were also subjected to a range of pH conditions, and ionized by both electron ionization (EI) and chemical ionization (CI). As GC is typically faster, cheaper, and easier than liquid chromatography, currently the method of choice for detection of neonicotinoids, our research could benefit the study of imidacloprid toxicity by reducing the attendant time, cost, and training requirements. Preliminary results have shown reliable detection of imidacloprid-urea, the main hydrolysis compound of imidacloprid, at pH 5-7.

Our work is an attempt to revolutionize the building industry by rethinking concrete formwork by eliminating dimensional timber formwork and replacing it with a combination of the existing PERI modular formwork system, fabric, and various constructed inserts. Not only would the customizable secondary systems we have studied are cheap to construct either on site or in a factory alongside PERI modular parts, but they would also be reusable, perhaps indefinitely. In the long run this system could minimize cost on a single job site as well as overall - as the formwork is reusable, highly mobile, flexible, and quick to install. Our system also introduces controlled organic forms, often avoided in concrete due to the difficulty of shaping rigid formwork. By using fabric, complex curvatures can be achieved that are created wholly by setting parameters (fabric excess, insert pieces, etc.) And letting the forces of hydrostatic pressure naturally dictate the ultimate form and aesthetic.

 Recently, there seems to be news about blizzards striking East Coast cities nearly every year. However, most reports simply claim that the frequency and intensity of large snowstorms on the East Coast are increasing without providing convincing evidence. Are they telling the truth? We decided to statistically test if the frequency and intensity of large snowstorms in coastal North America have increased in recent years. In our research, we encountered many difficulties during the data collection and cleaning processes. For example, most cities only have records since around 1950 and the Canadian snow data are hard to clean. We first plot frequency of large snowstorms for each city and detected that there is actually a downward trend of snowstorm frequency in coastal North America. To further verify our finding, we also permuted the time-series data and performed permutation tests on the slopes of the linear regression of extreme snowstorm frequencies versus year. In our current progress, the permutation tests suggest that, for all East Coast cities studied, the hypothesized increases in annual frequencies of extreme snowfall are not statistically significant at any reasonable level of significance for looking at exceeding both the 75% and 90% quantiles of annual snowfall. Thus, our current results imply that the frequency of large snowstorms in many East Coast cities has not been increasing in recent years, which is different from the media claims.

An important and under-explored component of information exchange and diffusion on social media involves permutations—i.e. how information changes, or more accurately, is changed as it flows. In this research paper, we aim to identify the various rumors and narratives that exist within a conversation surrounding Omran Daqneesh, the ‘Aleppo Boy’, on Twitter, and to investigate the actions that users take to propagate a certain permutations of these narratives. Before we can see how narratives propagate, we must first seek to understand these narratives at various levels of analysis, representing both the individual and society more generally. To this end, we examine narratives within the conversation at various levels: the micro, meso, and macro, representing individual actions and rumors, context-specific narratives, and a higher-level beliefs and worldviews. In this research we adopt a mixed methods approach. We quantitatively analyze our data to gain insights into the key events and influential actors in the space, and qualitatively code tweets to identify 1) rumor permutations that contribute to larger narratives surrounding the Syrian conflict; and 2) specific actions that help us to understand how individuals interacting within this information space. We aim to build a deeper understanding of how rumors are spread, how disinformation effects the online information space, and to develop a robust coding scheme that is transferable and can be applied to other rumors outside of the Syrian context in the future.