The United States’ major American sports leagues, the NBA, NFL, MLB, and NHL, are turning to franchise expansion to increase their presence in the economic and media markets along the West Coast, including the NHL’s expansion to Las Vegas for the 2017 season and future expansion to Seattle for 2021. However, expansion franchises are very difficult to get off the ground since they require new ownership and management structures, buy-in from the local fan base, and are often subject to much higher scrutiny during their first few years than other franchises. Currently, no universal metric exists to determine whether or not an expansion franchises was successful, and it’s becoming increasingly more difficult to convince leagues to expand when they are unable to evaluate the likelihood of success for potential candidate cities. This research analyzed four major factors I identified that contribute to overall success for a team in any sport: financial prosperity, quality of national media coverage, public and local governmental support, and in-game accolades. Using these metrics as a starting point, I created an index that scored prior expansion franchises using a variety of indicators to quantify their overall success. Additionally, I applied this index to select cities currently under consideration for an expansion franchise to serve as a predictor of their potential success. Going forward, the use of this index as a predictive metric will allow leagues to make more informed decisions about the success of future candidates for expansion.

Over the last decade Seattle has seen the most dramatic population growth of any large American city. The accompanying rapid change in urban form of the city has been called staggering by longtime Seattle natives, causing a state of worry not unlike the feeling of solastalgia, a neologism that describes a form of mental or existential distress caused by environmental change. Longtime citizens can be forgiven for feeling as though their home has been irreparably changed in a way that doesn’t name them as a benefactor. But what has the effect of this rapid change had on the homeless community? Can a stable and strong sense of place have positive influences on the day to day lives of the homeless individuals? Can we facilitate a stronger sense of place as part of our response to the homelessness crisis in Seattle? My study examines the link between sense of place and stability in homeless individuals through interviews with individuals from within the homeless community, hearing perspectives from tiny house villages, tent cities, and the streets of Seattle. Through these conversations I demonstrate the impact that sense of place has on social stability, especially in times of rapid change to the urban environment, and how sense of place differs depending on the method of temporary shelter. The resulting study builds a better understanding of the intersectionality of the existential effects of placelessness in the homeless population, the differences between being homeless in a variety of spaces, and the meaning and significance of place making to people without a place.

Epigenetic proteins modify the chromatin structure to manipulate gene expression, and dysregulated epigenetic modification in cells has been linked to cancer formation. Previous studies on young female Drosophila have shown that after injury, germline stem cells (GSC) are capable of entering and exiting a protective state called quiescence. When exposed to ionizing radiation (IR), the apoptotic differentiating daughter cells send a protective signal to GSC, resulting in GSC quiescence. This survival behavior of GSCs validates them as a potential model for cancer stem cells, which are a subset of tumor cells that are capable of withstanding traditional chemotherapy through reversible quiescence, resulting in future tumor relapse. To identify genes required for GSC survival, we performed a spatially restricted RNA interference (RNAi) screen. Here we show that two members of the repressive epigenetic regulator complex PRC1, Pc and Sce, are required for entry, while demethylase Utx is required for exit of GSC quiescence. Notably, PRC2 dependent H3K27me3 marks are required for PRC1 function, and Utx is required to erase these PRC2 dependent H3K27me3 marks. Importantly, we detected around a 3-fold increase in H3K27me3 marks in GSC following IR, suggesting that the repressive PRC1-PRC2 dependent complex is critical for entry, and elimination of PRC2 dependent marks is critical for exit from the quiescence state. Furthermore, we show that Trx, a writer enzyme which promotes euchromatin formation through H3K4me1 addition, is required for GSC exit from the quiescent. These data suggest that reversible quiescence in GSC is controlled by specific epigenetic states. In the future, more work is needed to investigate gene specificity of the epigenetic regulation.

Humans are incapable of regenerating a majority of their major organs and tissues following traumatic injury, often resulting in an irreversible loss of function. Tadpoles of the frog genus Xenopus can regenerate multiple tissue types in response to injury, however this capability is lost after metamorphosis. This stage-specific regenerative capacity makes Xenopus a uniquely powerful model for studying factors that promote regeneration. Tadpoles develop ex-utero and do not develop mouths until days after fertilization. Before tadpoles are able to ingest exogenous food, they rely instead on maternal yolk stores for sustenance. A regenerative refractory period has been described in tadpoles of Xenopus laevis, in which regenerative capacity is transiently lost. In this study we describe a similar refractory period in the closely related Xenopus tropicalis, and observe that the onset of the refractory period aligns with the transition independent feeding. Based on this observation, we hypothesized that the lapse in regenerative capacity could be due to a lack of metabolic fuel. We used immunohistochemistry (IHC) against the yolk protein vitellogenin (vit) to study the utilization of maternal yolk stores during tadpole development. We find that yolk localization is dynamic over the course of development, and that it is ultimately is depleted by the onset of the refractory period. We additionally used IHC against phospho-Histone 3 (pH3), a marker of mitosis, to study proliferation during development and regeneration. We found that proliferation declines across development heading into the refractory period, in both uninjured and amputated contexts. Lastly, we successfully rescued both regeneration and proliferative rates by feeding tadpoles after they develop the ability to eat. As a whole, this work articulates that nutritive stress may contribute to the loss of regenerative capability in the refractory period, and that alleviation of this stress promotes regenerative ability in this context.

This research focuses on dissecting the molecular mechanism of cardiac regeneration in the animal model, zebrafish, upon a myocardial infarction like injury. Zebrafish are one of the few vertebrates that can fully regenerate their hearts after an injury in 30 days. This phenomenon is not seen in humans, who generate scar tissue after this injury with reduced circulatory efficiency. However, there is evidence that neonatal mice under 7 days old can regenerate their hearts, but this is lost upon adulthood. Determining this pathway is the first step to develop therapeutics in order to provide relief to people suffering from cardiac injuries. In this research, we used chemically ablated transgenic zebrafish to generate a 30% injury. We determined that upon an injury, both the Wnt pathway and the mTOR pathway are sequentially activated and upregulated to restart cardiac proliferation to regenerate the heart. Wnt pathway proteins like Axin and β-catenin are activated 3 days post injury and mTOR proteins like pS6 are activated gradually over 7 days post injury. The inhibition of the Wnt pathway using DKK showed a downregulation of the mTOR pathway and downregulation of cardiomyocyte proliferation. Inhibition of the mTOR pathway using Rapamycin also stopped cardiomyocyte proliferation from occurring. Mass spectrometry data showed a decrease in glutamine and an increase in leucine during the proliferative phase. Since leucine is one of the activators of the mTOR pathway, we see that the glutamine-leucine transporter is also upregulated post-injury. Thus, we show that heart regeneration in adult zebrafish occurs via cardiomyocyte proliferation by using the Wnt and mTOR pathways to upregulate cardiomyocyte proliferation upon injury.

The Polycomb Repressive Complex 2 (PRC2) is an important epigenetic remodeler in developmental transitions and cell fate determinations. PRC2 is responsible for the addition of H3K27me3 marks that repress developmental gene expression. The catalytic subunit of PRC2 is the methyltransferase (Enhancer of Zeste 2) EZH2 which binds to EED (Embryonic Ectoderm Development) to methylate H3K27 on gene promoter regions. To investigate the requirement of PRC2 in different developmental transitions, a computationally designed protein was utilized to inhibit EED-EZH2 interaction. The novel designed protein is named EED binder (EB) and competes over endogenous EZH2 on the EED binding cleft with 300 times greater affinity than endogenous EZH2. We cloned EB-GFP under heatshock inducible promoter and injected this construct to one cell zebrafish embryos to generate a germ line transmissible insertion. To study the requirement of PRC2 in early developing embryos (0-3dpf), we applied heatshock (HS) on EB-GFP positive and negative embryos. Western blot analysis revealed global downregulation of EZH2 and H3K27me3 in EB-GFP positive, but not control embryos. Additionally, Co-Immunoprecipitation experiments showed EB-GFP binding to EED. Finally, to test the requirement of PRC2 in caudal fin regeneration, adult (5 month old) EB-GFP positive and negative animals were fin-amputated and the regeneration growth rate was measured for 14 days. Our results show that EB-GFP positive fish were able to regenerate their fins faster, resulting in a large fin size compared to either negative or non-HS clutch mate. Overall, we have developed a computer designed inducible PRC2 inhibitory system to study PRC2 function in Zebrafish, at the whole animal level. In the future, we will utilize EB-GFP to explore PRC2 and other epigenetic modifiers that are required for tissue and organ regeneration before and after injury.

Anxiety symptoms are common in children with attention deficit hyperactivity disorder (ADHD). It is unknown whether the neurobiological origins of comorbid anxiety and ADHD symptoms are shared or distinct. The current study addressed this using an event related electrophysiological potential (ERP) component, the error-related negativity (ERN), which occurs after an individual makes a task error. ERN amplitude has opposite associations with ADHD and anxiety symptoms: it is weaker in association with increased ADHD, but greater in association with increased anxiety. We tested whether 1) anxiety symptoms and ADHD have separate neurobiological origins, indicated by greater anxiety being associated with increased ERN in children with ADHD or 2) anxiety and ADHD symptoms share an origin, as evidenced by no effect of anxiety on ERN in children with ADHD. The current study investigated the association between ERN amplitude and anxiety levels in a sample of 7- to 11-year-olds with ADHD (n = 98) and without (controls; n = 26). Participants completed two ERP tasks of varying difficulty. ERP data were segmented around incorrect task responses, and mean ERN amplitude was extracted. Data on child anxiety and ADHD symptoms was collected via parent report. Linear regression analysis was used to estimate the associations among ERN amplitude, severity of anxiety, and ADHD symptoms. Preliminary results (n = 73) indicated that ADHD symptom severity was associated with smaller ERN amplitude (r =.31, p =.007), but anxiety symptoms were not associated with ERN in the ADHD group. Preliminary results indicated that the ERN is not a marker of anxiety in children with ADHD to the same degree it is in controls. This is consistent with shared neurobiological etiology for ADHD and anxiety symptoms in children, which has clinical implications for conceptualization and treatment of anxiety symptoms in childhood ADHD.

While some high school students are able to make the transition to higher levels of education, if they so aspire, other students have great difficulty achieving the goal of higher education. This study broadly examines barriers to higher education for students who face challenges graduating from high school and continuing to higher education. For example, students who become truant, attend poorly funded schools, of color, and/or are court-involved face real challenges and barriers in the transition to college. This research explores a variety of sustainable education-driven interventions that have the potential to widen the pathway wherein these populations of young adults can find success in transitioning to a college or university setting. Through multiple interviews with community stakeholders (including governmental, non-governmental, for-profit, and non-profit agencies), I have explored and assessed interventions and programs that are making an impact. These include student to advisor ratios, being surrounded by diversity in leadership positions, family support, neighborhood environments, and additional outside of school influences that ultimately effects these students’ lives every day. Yet, for all these interventions and programs some students still fall through the cracks. There remains a significant lack of equity. This research contributes by drawing attention to the best programs and practices that successfully widen the path for young adults to achieve higher education.

Substantively engaging with local communities is critical to ensuring effective quarantine response and treatment to disease outbreaks. This engagement involves the integration of international-based aid with religious and government leaders to reach affected residents and treat disease while respecting local cultures. Significant gaps in community engagement by international humanitarian organizations were observed during the 2013-2016 West Africa Ebola epidemic. These shortcomings hampered trust in aid collaborators, impacted dissemination of disease information, and disrupted the daily lives and community frameworks of residents. Such issues continue to have relevance as the Kivu Ebola epidemic in the Democratic Republic of the Congo enters its third year. This research explores how humanitarian organizations operating in Kivu incorporate community engagement procedures into their work. Institutions such as the World Health Organization and Red Cross are qualitatively analyzed using an evaluation matrix designed to measure the scalability and implementation of community-based integration and participation. Indicators are drawn from official directives and policies. General patterns of cultural understanding and respect of local traditions are observed but vary across organizations. Applying similar collaborative procedures to future epidemics may aid organizational response in engaging affected populations.

Long-term exposure to traffic-related air pollutants (TRAPs) has been associated with multiple adverse health effects. However, many TRAPs, such as ultrafine particles, are poorly measured and thus their association with health outcomes is difficult to characterize. Our objective is to identify geographic characteristics that distinguish diurnal trends in TRAP concentrations at monitoring sites in order to estimate spatial contrasts in long-term average concentrations. Mobile monitoring (driving to many locations with multiple instruments) permits us to measure many TRAPs at many locations, but these measurements have short durations and may not capture the pollutant’s underlying trends. Therefore, these measurements may not reflect a site’s true long-term average due to our inability to fully sample the diurnal trend of the pollutant. In order to quantify the role of diurnal trends on annual averages, we use hourly measurements of CO, NO₂, and PM2.5 from California Environmental Protection Agency’s (CalEPA) monitoring sites where the true long-term averages are known. Using Principal Component Analysis (PCA) to reduce the number of dimensions, we will regress the pollutant levels against the time of day, the physical covariates and their interaction terms. The geographical variables include, but are not limited to, distance to a highway, distance to bodies of water, Normalized Difference Vegetation Index (NDVI), and population density. We utilize Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) as our model selection criteria and we assess model performance via leave-one-out cross-validation. We identify the most influential geographic factors that are associated with two to three categories of similar diurnal trends for each pollutant. With these variables, we will be able to group Seattle monitoring sites and distinguish their diurnal trends. Appropriate adjustment for diurnal trends in our mobile measurements will permit us to estimate spatial contrasts more accurately.

Previous studies on plant phenology have found that shifts in the timing of life cycle events are connected to changes in the surrounding climate. Alpine and subalpine wildflowers are of particular interest, considering that the initiation of flowering often depends on the timing of snowmelt, which has been occurring earlier as temperatures warm. However, we often lack the information needed to predict exactly how much wildflower phenology will shift in response to warming. Herbaria, collections of plant specimens collected over the last 100-200 years, have recently been paired with climate data (from the geographic locations and dates of specimens) to examine the relationship between climate and plant phenology. I aim to answer 1) How does climate influence the timing of phenological stages in wildflowers? and 2) Do species vary in their responses according to their average bloom time after snowmelt (e.g. early season vs. late season bloomers)? This study involves five alpine/subalpine species that very in the timing of blooming relative to snowmelt date: Western pasqueflower (Anemone occidentalis), Sitka valerian (Valeriana sitchensis), Sickletop lousewort (Pedicularis racemosa), Rainier pleated gentian (Gentiana calycosa), and Glacier lily (Erythronium grandiflorum). I will access specimen data from the University of Washington Herbarium and the Consortium of Pacific Northwest Herbaria. Phenological stage will be recorded with the date of collection, geographic locations will be determined using GEOLocate coordinate and elevation data, and climate conditions will be spatially modeled using ClimateWNA historical records. I predict that there will be an overall trend of earlier flowering for all four species over time, but that species with later bloom times will experience less deviation from their historical average than those with earlier bloom times. This study is significant in providing information that will help the preservation of wildflower meadows in the high mountains of the Northwest.