The Collatz conjecture, named after Lothar Collatz, is one of the most deceptively difficult unsolved problems in mathematical number theory. The use of simple calculations and simple rules has left the mathematical community baffled for more than 80 years. Paul Erdős, a monumental 20th century mathematician, said that: "Mathematics may not be ready for such problems." He also offered $500 for its solution. In 2010, Jeffrey Lagarias claimed that based only on known information about this problem, "this is an extraordinarily difficult problem, completely out of reach of present day mathematics.” The Collatz conjecture’s simple rules are as follows; First, start with an integer. If it is even, divide by two. If it is odd, multiply by three and add one. Then, repeat this process for the result. Simple calculations. The conjecture states that every number will eventually reach one. For example: 5>16>8>4>2>1. This research aims to explore and observe the behavior of the Collatz problem as well as the “Collatz family.” The Collatz family are defined as iterative functions in the form: AX + B (X ≡ 1 (modulo Y)) and X/Z (X ≡ 0 (modulo Y)) Where X, A, B, and Y are integers. The Collatz conjecture is for the case: A=3, B=1, Y=2. This research does not attempt to find novel solutions to the problem using analytic number theory, rather we utilize computer programs to find structures and anomalies within the Collatz familly map. Hopefully, more discoveries surrounding the structure of the problem will give rise to its elusive patterns.

The use of Potentially Inappropriate Medications (PIM) in elderly is common and can lead to increasing risks for adverse drug events, morbidity, and increased utilization of health care resources. Early identification of PIM can improve the quality of care in elders and reduce hospitalizations. This study aims to identify PIM in a sample of N=60 people living with dementia who recently experienced a hospitalization and to evaluate what PIM are most common. We also aim to evaluate correlations between PIM and the number of patient’s chronic conditions and the total number of medications. Our hypothesis is that patients with higher burden of illness (more conditions and medications) can have higher number of PIM. We identified PIMs by evaluating medical records using the STOPP/START criteria. The STOPP/START criteria classify inappropriate medications that should be stopped as well as the appropriate medications that should be started instead.Descriptive statistics was used to describe the sample and the prevalence of PMI, chronic conditions and medications. Correlation analyses was used to explore relationships between the variables. Study findings will inform healthcare providers about the prevalence of PIM and help identify patients who are at higher risk of PIM.

In the Pacific Northwest the Endangered Species Act (ESA) protects wild salmonids from commercial fishing. The current commercial fishing gear, including gill nets but not limited to, disrupts the recovery of these species because fishermen can not selectively harvest the hatchery fisheries without wild salmonids as bycatch, which have high mortality rates. Once ESA quotas are met this can effectively shut down commercial fisheries. The exploration of alternative fishing tools that can select for certain species will lower bycatch mortality rates of ESA species, and in turn allow commercial fisheries to operate longer. On August 26th through September 29th of 2017 Wild Fish Conservancy conducted follow up research, to a 2016 pilot study of Pound nets, in the Lower Columbia River Sub-Basin. Post release survival rates were evaluated in a modified stock selective pound-net. Using Mark Recapture methodology, with a Passive Integrated Transponder (PIT) tags, and genetic clippings for later analysis. Survival rates of control specimen to treatment specimen were captured as they traveled past dams upstream. Data analyzed were total catch, catch per unit effort and covariates of recapture probabilities. The preliminary results show that fishing with stock selective nets can effectively target hatchery fisheries while successfully releasing ESA listed species, reducing mortality rates. In 33 days WFC and a local fisherman captured and released 7,129 salmonids with a post release survival for steelhead and trout ( Oncorhynchus Mykiss) of 94.0%, and 96.6% for Chinook salmon (Oncorhynchus Tshawytscha) listed as ESA species. Hatchery fisheries of these species along with coho salmon (Oncorhynchus kisutch) were effectively selected with viable commercial quantities. Future subset data of genetic clips and a Jolly-Seber analysis will give more precise information of these post-release survival estimates.

Eclipsing binaries (EBs) are systems in which two stars orbit and pass in front of each other as observed from Earth. They are important astrophysical tools utilized in this project to directly measure the fundamental properties of stars, such as their masses and radii. We create a sample of 35 bright, detached EB targets from the Villanova Catalogue, based on high-quality photometry from the Kepler Satellite and spectroscopy from the Apache Point Observatory Galactic Evolution Experiment (APOGEE). Here, we present mass, radius, and orbital solutions for a subset of these EBs. For each system, we extract radial velocities (RVs), the speed at which each star in the system is moving away from the observer, from the APOGEE spectra. Then, we combine the RV with Kepler light curve (LC) information to simultaneously model the system light and line-of-sight speed as a function of time. Because our model has high dimensions with 18 free parameters, we first solve for the LC and RV solutions separately, and then simultaneously solve them. We use a nonlinear least-squares optimization method to determine the best fit solution and quantify the uncertainties in model parameters running Monte Carlo Markov Chain (MCMC) simulations. The model parameters that we find will further our understanding of fundamental stellar properties and binary star orbital parameters.

The incidence of many human diseases, such as cancer, Alzheimer's and heart disease, increases with age. Studying the aging process could provide insight into new treatments and therapies for these aging-related diseases. Our research uses the yeast species, Saccharomyces cerevisiae, as a model organism to explore the effects of specific genetic and environmental factors on aging. Aging in yeast can be measured in terms of replicative lifespan, which is the number of progeny (daughter) cells produced by a parental (mother) cell. In order to measure the replicative lifespan, we utilize a microdissection microscope outfitted with a fiber optic needle that is used to separate individual mother cells from their daughter cells in order to quantify the number of daughter cells produced. The total number of daughters produced by a mother cell is the replicative lifespan of that cell. To determine which genes play an instrumental role in yeast replicative lifespan, our lab has studied the lifespan of 4,698 yeast mutants containing single gene deletions. Many mutants were identified that increase the lifespan of S. cerevisiae. In this study, we have re-evaluated our data to identify potential false-negative results from our initial work, in order to identify additional genes that may influence lifespan. Identifying the false-negative results will be beneficial in finding genes that may play a role in the aging process and had been previously overlooked. This will allow future research to continue in developing treatments that target the prevention of age-associated disease in humans, potentially allowing people to live healthier lives and decreasing the prevalence of cardiovascular disease and cancers. 

The Kaeberlein laboratory utilizes the budding yeast Saccharomyces cerevisiae to study aging, a progression characterized by the gradual deterioration of cellular components and bodily functions. Aging is a progression every organism eventually undergoes, and by better understanding the molecular mechanisms behind it, we can determine how to delay its progression and increase our healthspan, the portion of our lifespan in which we are healthy and free from serious disease. S. cerevisiae functions as an effective model organism because it contains many conserved biological processes, making lifespan simple and fast to measure. The replicative lifespan assay (RLS) is used to quantify the lifespan of the yeast. Individual yeast cells undergo asymmetric mitotic division producing a daughter cell that is distinctively smaller than the original mother cell. Yeast are incubated on growth promoting plates, and the yeast produce daughter cells that are microdissected, counted, and moved away. The cycle repeats until the original mother cell can no longer produce a daughter. The total number of daughter cells produced by individual mother cells is then used to understand the effect of the gene on the lifespan of the yeast. This technique aids in developing models that can be used to understand the conserved biological pathways that influence longevity. Aging is an underlying risk factor for many non-communicable diseases such as Alzheimer’s Disease, Cancer, and heart disease. Our laboratory has performed thousands of gene knockouts on S. cerevisiae and has identified several genes that modulate replicative lifespan. This research is focused on identifying the genes that play a role in reducing the rate of aging to delay the onset of age associated diseases. By understanding how specific genes play a role in aging, we can apply this research to other organisms, with the ultimate intent of increasing the length of a healthier human life.

There are various groups and organizations that affect the prosperity and integrity of women in India. Whether they are affiliated with a political party or village clans, women are typically placed at the bottom of the barrel. My research highlights how groups such as Hindutiva, Love Jehad, Triple Talaq, etc. oppress women or spark activism within their community. Women regardless of class, race, etc. are affected by some sort of familial system; expected to follow and obey traditional gender roles, and abide by their husbands. Women are also used as a unit of analysis in religious ideologies. A generalization is made that all women are either impacted or not impacted by Islam. For example, the more women do something, such as wear a veil, the more generalizations are made about their rights as women. To understand these issues, I interviewed domestic workers, young women who attend schools, and research activists in India. This research also explores how specific organizations made for women have fought for and implemented laws to strengthen the voice of the oppressed. This project will track the evolution of the women’s movement in India, from its origins to the present, providing insight into how women have worked their way up the ladder, the obstacles they faced, and what they hope to achieve in the future. Hence, it provides a different perspective on feminism—building on Third World Women in contrast to Western feminism.

Digital media and mobile applications used for leisure have become increasingly interwoven into people’s daily lives. Although playful mobile applications and their effects on society have been studied from a psychological, business, and computer science perspective, they have not been heavily engaged in the field of geography. Using Pokémon GO as a case study, this work aims to explore the ties between the corporate history and digital data of Niantic (the company that made Pokémon GO) and the effect it imposes on the “real world”. It aims to conduct a spatial analysis of pokéstops and pokégyms in King County, Washington. In order to do this, a discourse analysis of online documents from Niantic, newspapers, social media, and fan websites recounting the company's history with previous applications and press interviews was conducted. In addition, a hotspot spatial analysis of Pokémon GO (pokéstops and pokégyms) overlaid on American Community Survey data was created. The purpose of this analysis is to see potential spatial inequalities that the application may have created. The findings show Niantic’s lack of ethical consideration by how it deals with users data and privacy and as a result shows how the users have responded to issues in the past. The results also illustrate the skewing of data toward urban tech centers and the relative sparsity in rural areas, rendering use of the app pointless for certain users. Pokémon GO is the first location-based augmented reality mobile application to garner worldwide attention, and many application developers will likely use it as a point of reference when creating their own applications. It is imperative that developers and researchers learn from this application’s successes as well as its failures.

RNA Polymerase (RNAP) is found in all cellular organisms and synthesizes RNA from DNA through a process known as transcription. Using a single-molecule tool, Single-molecule Picometer Resolution Nanopore Tweezers (SPRNT), developed by Gundlach’s Nanopore Lab at the UW, we can track the motion of individual RNAP molecules along DNA at unprecedented spatial and temporal resolution. In this technique, a single nanopore, a biological transmembrane protein, is isolated in a phospholipid bilayer separating two wells both filled with salt solutions. An applied electric field drives ions through the pore, and the ion current is measured. Negatively charged DNA is also driven through the nanopore, partially blocking the ion current. The DNA is sequenced based on the changing ion current as each of the four DNA nucleotides sequentially pass through the pore and block the flow of ions. In SPRNT, the motion of a known sequence of DNA through the nanopore is controlled by a molecular motor (like RNAP), in order to understand how an enzyme moves along DNA. Using this technique, we can detect single base pair steps of RNAP along DNA as brief as 1 ms. In this work, we expand upon initial SPRNT experiments tracking RNAP and analyze the kinetics of RNAP during transcription in biological relevant conditions (1 mM NTPs, 37C) on a long DNA template (up to 6 kbp). We calculate the rate of NTP incorporation and stepping behavior (probabilities of different step types) at many different DNA template sequences using this technique. The results demonstrate how DNA sequences as well as applied force can affect the stepping behavior (probabilities of different step types) and stepping rate of RNAP. A complete understanding of RNAP and its transcriptional regulatory behaviors will enable scientific and medical communities to better understand a variety of genetic diseases associated with transcription.

Prevention of aquatic invasive species transmission by recreational fishing and boating is a fundamental management challenge. These activities can entrain non-native plants and animals via tangled lines, bait buckets, or hull encrustation, leading to introductions into new waterbodies. With hundreds of millions of people participating in fishing trips each year, understanding angler movement behavior can provide critical insight into the most effective locations and scales at which to apply preventative measures. Angler behavior is often inferred from infrequently and sparsely conducted surveys that provide limited spatial and temporal insight into this challenge. Here we capitalize on a big data opportunity provided by ReelSonar’s recently launched iBobber, a sonar-enabled bobber with over 3,000,000 records of fishing location, water depth, and environmental variables collected over three years. By quantifying geographic patterns of fishing activities and assessing how these patterns change seasonally, we explore angler behavior in terms of fishing frequency and distance traveled between sites, and characterize the attributes of fished ecosystems. Our study offers novel insight into spatiotemporal patterns of angler behavior and carries important implications for predicting and preventing future transmission of aquatic invasive species via recreational fishing.

Sometimes speech sounds (phonemes) can be ambiguous, and people have a tendency to interpret the ambiguous phoneme differently in different contexts so that they perceive a real word, as opposed to a non-word. This effect is called "lexical bias." For example, when there is ambiguity between whether /m/ or /n/ is heard, /m/ is more likely to be perceived if it is followed by "uch," because "much" is a word, but "nuch" is not (and vice versa if the context is "udge"). We hypothesized that for people who have hearing loss or use a cochlear implant, there will be additional ambiguity in hearing speech, and that the lexical bias effect would be stronger. We simulated degraded hearing using vocoded speech played to listeners with normal hearing. Participants heard speech continua that gradually morphed from /m/ to /n/ in the "uch" and "udge" contexts, and either had a clear spectral quality or a degraded spectral quality. Results suggest that the lexical bias is stronger when the speech signal quality is less clear, which is consistent with the hypothesis because of the increased phonemic ambiguity in these conditions. By understanding how signal degradation impacts the perception of phonemes, audiological tests for speech reception can be improved to separately acknowledge the effects of hearing from the adjustments that the listener makes to maintain lexical biases in speech perception.

The purpose of this research is to investigate novel techniques for worst-case analysis of electronic circuits. Worst-case analysis is used to ensure circuits work reliably and meet performance specifications. Circuit components have assigned tolerances based on operating temperature, manufacturing processes, expected lifetime, radiation, and various other effects. Worst-case analysis can help detect potential circuit failures that may cause a loss of data and as a result, incur financial loss. The proposed research uses optimization to perform the worst-case analysis. Optimization involves minimizing or maximizing an objective function (such as an expression for an output voltage of a circuit) subject to constraints (which is often an allowed set of circuit parameters). The research applies worst-case analysis to different circuits using the nonlinear optimization function fmincon() of MATLAB. Preliminary results show that optimization under proper constraints is more efficient than conventional methods which rely on statistical methods. The worst-case analysis results from MATLAB using optimization are compared against the results of conventional methods using Multisim, a circuit simulation software tool. The research aims to apply different methods of worst-case analysis to circuits with increasing complexity to determine whether or not one approach is more efficient/accurate than others.

Mechanistic Target of Rapamycin (mTOR) is a highly conserved serine/threonine kinase originally discovered in yeast as a central regulator of cellular growth and proliferation in response to adequate nutrients and energy levels. mTOR is activated in a complex with an essential co-activator called Raptor. Our lab recently discovered that mTOR holds an essential role in early murine B-cell development; B-cell specific disruption of Raptor inhibited mTOR activity and resulted in a complete block in B cell development at the precursor-B (pre-B) cell stage. We hypothesize that B-cell specific disruption of Raptor will inhibit B-cell transformation induced by the Myc oncogene, and/or will inhibit the survival of B-cell lymphoma cells, by inhibiting cell growth induced by mTOR. We conditionally disrupted Raptor using gene targeting strategies in a mouse model of Burkitts Lymphoma whereby the c-Myc oncogene is expressed under control of the immunoglobulin heavy chain enhancer. We found that Raptor deficient mice took significantly longer to develop B-cell tumors when bred to c-Myc transgenic mice; our Kaplan-Meier Survival curve revealed that disruption of Raptor improved survival rates significantly, such that Raptor knockouts rarely showed growth of tumors. To better understand cellular mechanisms by which Raptor may inhibit B-cell lymphoma formation, we utilized flow cytometry to measure cell proliferation and survival of B cell lymphoma cells in the presence or absence of Raptor. Our results revealed a distinct reduction in both cellular proliferation and survival in the absence of Raptor, which suggests Myc driven B-cell proliferation and survival is highly dependent on Raptor and mTOR activity. In the next part of our studies, we will inducibly disrupt Raptor in already established primary Myc-induced B-cell lymphomas to determine whether Raptor and mTOR activity are essential for lymphoma cell survival. Through these results we will be able to determine whether inhibition of Raptor could be utilized as a strategy to inhibit cancer cell proliferation and/or survival.

Diet, lifestyle, and environment can influence an individual’s behavior and brain function through epigenetic mechanisms. The Lattemann lab is investigating the effect that one factor, high fat diets, has on epigenetic regulation in hippocampus a key area for learning, memory and cognition. Previously, the lab determined that rats fed high fat diets exhibited increased sucrose motivation, and this behavioral effect was later linked to stearic and palmitic fatty acids explicitly. It was also shown that high fat, high sugar diets are associated with impaired place memory in rats. Most recently, the lab has analyzed hippocampal chromatin from rats fed high stearic and palmitic acid diets and is in the process of determining the effect of these diets on histone modifications. Histones regulate gene expression by binding to DNA: modifications to these histones influence how readily the DNA is transcribed, and how the gene expressed. These modifications are being screened for using Western blot analysis. In addition to screening for modifications in histones, the Lattemann lab also directly analyzed DNA for the expression of target genes. This screening procedure included measuring expression of candidate histone-target genes using PCR, and ChIP-Seq (Chromatin Immunoprecipitation and unbiased gene screening) assays. By locating histone modifications and quantitating the expression of hippocampal candidate genes, the lab has provided an epigenetic explanation for the behavioral effect of the diets, and a possible molecular mechanism by which the diets can induce this effect.

Alzheimer's disease (AD) is a neurodegenerative illness responsible for 60-80% of dementia cases in the United States. Studies have shown that the formation of two primary pathologies, amyloid plaques and tau tangles, are present prior to neuronal death that results in this loss of memory and worsened motor function. Our research focuses on understanding the role of tau in disease progression. Tau stabilizes microtubules in the cell, which function to maintain cell structure and assist in intracellular transport. To successfully regulate microtubules, tau is modulated by site-specific phosphorylation. Evidence points specifically to the hyperphosphorylation of tau by certain kinases in playing a key role in neurodegenerative dieases such as AD. One kinase that has been identified as a tau-phosphorylating agent is tau-tubulin kinase 2 (TTBK2). To understand the role of TTBK2 kinase activity in the context of tau, we created double transgenic C. elegans lines expressing both human tau and TTBK2. We assessed behavioral abnormalities in our subsequent populations using locomotor assays of the homozygous crosses. From the data that was generated, we observed a significant difference in the movement of the double transgenic tau/TTBK2 strains as compared to their controls. The crosses moved substantially less than the other strains, and exhibited a more uncoordinated phenotype. These results support the hypothesis that the abnormal phosphorylation of tau by TTBK2 results in worsened motor control and general health of affected individuals. Additional testing of protein levels within the double transgenic lines will enable us to determine the mechanisms underlying this effect, and could eventually lead to information that might inform treatments counteracting the activity of kinases such as TTBK2 involved in hyperphosphorylation of tau proteins. Furthermore, this research has the potential to aid in finding a cure for a currently incurable disease and providing a hopeful future for Alzheimer's-affected individuals.

Imidacloprid (IMI), a neonicotinoid, is being sought as an alternative to the carbamate pesticide, carbaryl to control burrowing shrimp (ghost shrimp, Neotropea californiensis) in Willapa Bay and Grays Harbor, Washington. The shrimp destabilize sediments resulting in poor survival and low yields of the commercially harvested Pacific oyster (Crassostrea gigas). Previous laboratory tests indicate juvenile and adult ghost shrimp are overtly affected (immobilized) when exposed to IMI in artificial seawater (SW) at concentrations expected during control operations, but not killed and subsequently recover. Our objective was to determine if emamectin benzoate (EB) is an alternative to IMI. EB, the active ingredient (a.i.) in Slice®, is currently registered for use in marine waters for the control of sea lice on farmed salmon. We targeted juvenile shrimp because they are likely more sensitive than adults and reside within the upper 10-15 cm of the sediment facilitating control. In an initial test to determine the effective range, we exposed juvenile ghost shrimp (mean carapace length = 2.3 mm) to static concentrations of EB (as the insecticide Proclaim®) ranging from 0.01 to 100 ppb a.i. within artificial SW for 96 h. All shrimp within the 100 ppb treatment died within 48 h and 27% exposed to 10 ppb succumbed by 96 h. In a subsequent 96-h test (static 48-h renewal), we exposed juveniles (mean carapace length = 2.1 mm) to concentrations of EB ranging from 10 to 100 ppb to determine the median lethal concentration (LC50). All shrimp exposed to 100 ppb died within 24 h. The 96-h LC50 was 18.8 ppb compared to >12,000 ppb for IMI. EB may provide more effective control than IMI because it targets the primary neurophysiology of the shrimp. Further tests are required to determine effective concentrations within sediment, assess potential non-target effects, and evaluate environmental fate.

Traumatic spinal cord injuries may lead to devastating loss of neurological function and there are currently no effective clinical methods to regenerate damaged nerve tissues. Besides, the inflammatory response can cause secondary injuries and inhibit regeneration. Novel treatments like cell therapy and localized drug delivery have shown greater efficacy when delivered by hydrogel scaffolds. However, effective scaffolds that can both culture neuronal cells and deliver therapeutic drugs are rare. Therefore, there is a need for an effective treatment of spinal cord injury that can locally deliver therapies with anti inflammatory properties to the spinal cord, as well as provide a support material for neural stem cell therapy. Here, we report a hydrogel composed of peptides that can self-assemble into a hydrogel in physiological conditions. The self-assembling peptide is conjugated to a polymer that enables drug loading and bioactive properties. Self-assembling peptides and a drug loading polymer were synthesized and characterized, loaded with bivalirudin, a model anti-inflammatory peptide drug, and assembled into a hydrogel formulation. The hydrogel was used to encapsulate neural stem cells to assay its efficacy as a support material. The gel was also assayed for its ability to release the anti-inflammatory drug when exposed to enzymes upregulated during inflammation. We anticipate seeing effective ligation of the polymer with the self-assembling peptide, successful hydrogel formulation, and neural stem cell viability when encapsulated in the hydrogel. A successful self-assembling formulation will ultimately work to provide effective cell therapy and anti-inflammatory drug delivery to the spinal cord, with potential for broader drug loading applications in the future.

Ethics and diversity are critical components of engineering training and practice, but most undergraduate engineering programs do not address these issues in-depth. We describe the design and implementation of a novel curriculum that allows early engineering students to explore the interplay of diversity and ethics in an engineering context. Although upper-division bioethics courses may also address this relationship, we chose to implement this curriculum in a large, introductory course. We intend to provide an accessible opportunity for early engineering students, particularly underrepresented students interested in engineering, to engage with this material early and to impress upon a broad audience that diversity and ethics are critical topics in engineering. Engaging these students in meaningful discussion about the intersecting roles of diversity and ethics in bioengineering enables them to apply course competencies to their future engineering practice. Our learning objectives include: (1) Summarize key case studies regarding diversity-related ethics in STEM, (2) Identify how cultural concepts of race, gender, sexuality, and disability have shaped scientific thought (and vice versa) through history, (3) Critically evaluate literature regarding ethics and diversity in bioengineering, (4) Analyze how engineers handle implicit bias during research and design processes, and (5) Propose approaches to promote ethics and diversity in engineering practice. Course activities cover the importance of diversity and ethics competency in engineering; historic and current case studies of diversity-related ethical issues and how historical perceptions and contexts still influence modern scientific thinking and engineering design; advocacy and representation of minorities in engineering; evidence supporting the value of inclusive teaching and diverse teams; and best practices for advocacy and representation of diverse peoples in engineering. We assess the effectiveness of these teaching innovations through student surveys, student performance on assignments, and instructor observations. Additional supporting data is provided by excerpts of student work.

Working with the Northwest Avalanche Center (NWAC), the Trailhead Outreach Project researched levels of avalanche awareness, education, and preparedness of different demographics and user groups who enter avalanche terrain in the winter backcountry. Washington state itself is responsible for 54% of hiker avalanche fatalities nationwide in the past ten years. This statistic, combined with the increasing popularity of mountain recreation, made it necessary to understand who uses the backcountry and how they can be reached with the education required to make informed decisions when traveling near or in avalanche terrain. It was believed that backcountry skiers are generally well versed in avalanche risk and protocol while snowshoers and hikers are not. To obtain this information, NWAC set up a tent staffed with volunteers at four popular backcountry trailheads in the Cascade mountains on 12 separate weekend days (three at each location) over the winter of 2017-2018. Users were asked to take a survey that consisted of 14 quick questions to identify their mode of travel and levels of education, awareness, and preparedness. General demographic questions were also included. Preliminary results indicated that hikers and snowshoers do in fact have lower levels of avalanche awareness, education, and preparedness than skiers, and that people are heading into the backcountry with low levels of avalanche education at astounding rates. The results from the survey help the Northwest Avalanche Center direct their education and awareness programs toward the user groups shown to be less informed and potentially more vulnerable to an avalanche related accident.

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.

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.

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.

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.

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.

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.

The stories and activities of children are usually disregarded in the archaeological record. However, at the nineteenth to early twentieth century Grand Ronde Agency Schoolhouse, excavated by the Field Methods in Indigenous Archaeology field school, it is hard to ignore the presence of children in the material remains. Using historical records, objects of personal adornment, and school-related artifacts, I examine how children at the Grand Ronde schoolhouse stayed connected to their culture and community. Analysis of these objects convey information about identity and cultural practices of the children at schoolhouse. I analyzed artifacts excavated at the schoolhouse privy like buttons, barrettes, beads, and other accessories subject to personal choice as well as child-sized scissors and pencils. The current knowledge and research about reservation schools has been focused on the tragedies that happened at reservation and boarding schools, but the Grand Ronde material and historical records are stories of survival and optimism during the reservation periods.

Studies have shown disparities in environmental justice as manifest by the variation of air pollution exposure based on race and socioeconomic status (SES) on a national scale. This study focused on determining whether a similar association exists in Washington. I hypothesized that in areas where people of color are the majority residents, exposure to air pollution as measured in PM2.5, will be higher. I also hypothesized that there would be a higher average concentration of PM2.5 in low-income areas. PM2.5 are solid particles with a diameter smaller than 2.5 micrometers. In this cross-sectional study, I used linear regression and analysis of variance to evaluate my hypotheses where I treated income as a continuous variable and majority residency by race as a categorical variable. Overall, I found a negative association between PM2.5 and income, which supports the hypothesis. I estimated that PM2.5 is expected to decrease by 0.03 µg/m3 on average per 10,000 dollars increase in income [95% CI: -0.032, -0.02.8]. I controlled for urbanity and education. When I considered effect modification, I found that the negative association was not present in rural areas. In descriptive analyses, I considered four different racial categories (White, Black, Latinos, and Asian). I observed that for areas where black people are the majority, the PM2.5 exposure is the highest, with a mean of 6.86 µg/m3 [95% CI: 6.82, 6.87], with a maximum of 7.65 µg/m3 and a minimum of 6.06 µg/m3. In comparison, in areas where white people are the majority population, the mean was 6.12 µg/m3 [95% CI: 6.11, 6.13], with a maximum of 8.12 µg/m3 and a minimum of 3.54 µg/m3. I conclude that there is a disparity in air quality based on ethnicity and SES in Washington State. Directly or indirectly, environmental injustice contributes a greater risk of health issues and diseases.

Calcific aortic valve disease (CAVD) is a disease that results in aortic valve thickening and calcification, leading to valve stenosis. It is commonly experienced by aging people, especially those suffering from type II diabetes mellitus (T2DM). There is currently no effective drug therapy to prevent or treat CAVD, mainly due to the poor understanding of its etiology. The proposed study will explore the cellular and molecular mechanisms of diabetic CAVD, focusing on transcription factors Sox9 and Runx2. As the disease progresses, Sox9-expressing cells differentiate into procalcific Runx2-expressing cells, resulting in valve calcification and stenosis. We hypothesize that Sox9-expressing cells in T2DM aortic valves are reparative. To test this hypothesis, I will feed a diabetogenic high-fat diet to a mouse model susceptible to developing CAVD, which will enable genetic fate mapping of Sox9-expressing cells upon administration of tamoxifen intraperitoneally. Aortic valve sections will then be stained with X-gal, a substrate used for detection of the transgene used for the genetic fate mapping of Sox9 cells. X-gal staining will identify cells that once expressed Sox9 and immunofluorescent staining will identify Runx2 expression in cells. Quantification of Runx2+ cells with or without X-gal+ Sox9 will determine if Runx2+ cells are derived from Sox9-expressing cells and, if so, to what extent. If Sox9+ cells indeed give rise to Runx2+ cells, colocalization in staining by X-gal and Runx2 antibody is expected. This research will help identify cellular and molecular targets that may be used as a basis for future diabetic CAVD drug therapies.

In 2015, the WHO reported 27.4 deaths for every 100,000 people per year in Uganda were attributable to road crashes. Road crashes are one of the top ten causes of premature death in this East African nation of about 41 million people. While youth and young men are at the highest risk, the ripple effect of even a single death includes costs of treatment, lost wages, and compromised health of a whole family. We used roadside observational methods to measure the frequency of phone use while driving. In a roadside spot survey of Ugandans, we also asked about attitudes, knowledge, beliefs, and personal usage of cellphones while driving.While it is illegal in Uganda to talk on the phone while driving, drivers' frequency of phone use was comparable to rates seen in the U.S. In our survey, those who admitted to using their phone were more likely to be educated on the law and believe their behavior was dangerous compared to those who did not use their phones while driving. One explanation for this finding is that businesses are requiring employees to use their phones while driving, and those with these jobs could be more aware of the law in order to conceal their behavior. The Ministry of Health, police, business, and many other transportation related departments all have a policy role in reducing distracted driving. Action from these groups has been shown to influence and reduce risk behavior.

Artifacts associated with popular culture have potential to reveal activities, interests, and societal influence amongst a community. This is especially true on Native American reservations, where families balanced participation in dominant economies with preservation of traditional practices. This project examines a 1930s comic book fragment excavated during the 2017 Field Methods in Indigenous Archaeology field school conducted on the Grand Ronde Reservation in Oregon. The comic book is a unique find that provides historical information about Grand Ronde children growing up on the reservation. This research provides a better sense of students’ activities at the schoolhouse site and explores the impacts and influence of pop culture on the students of Grand Ronde. We use several methodologies for this project, including: paper conservation, archival research, and analyzing physical artifacts collected via the excavation. By sourcing and dating the comic book, we make inferences about the entertainment experience of students at the Grand Ronde school through exploring the influence of popular culture at this site and the impact that mainstream media had on those attending Bureau of Indian Affairs scholastic institutions. This research contributes to knowledge of the cultural interplay of mainstream influences within a reservation schoolhouse environment.

Archaeological studies of Native American communities focus primarily on pre-colonial periods. Analysis of nail types and styles from Native sites are thus quite rare. Recent fieldwork conducted by Field Methods in Indigenous Archaeology (FMIA) on the Grand Ronde Reservation in northwestern Oregon provides more information about colonial life and gives more attention to reservation inhabitants. The nails excavated by FMIA offer a glimpse into reservation life during the nineteenth and early twentieth centuries. This project focuses on nails recovered from a property in the east central reservation that was occupied by reservation families from the 1850s through at least the 1920s. I developed a typology of the nails recovered from the site and compiled this information into a comprehensive database. This database provides unique insight into the builders, inhabitants, and significant events that took place at the site. Nails shed light on builders’ access to resources, while their building paradigms can tell us of their cultural backgrounds and ideologies. Nails also tell us about the day-to-day lives of inhabitants and whether buildings sustained damage and consequentially required repairs. This project adds clarity to our understanding of the built environment at Grand Ronde. This archaeological analysis offers an approach to tracking construction projects on the reservation in the absence of maps and written records about these structures.

Archaeologists have long used ceramics as evidence for reconstructing what people ate, what they did, and how they impacted the world. However, few studies examine the use of Euro-American manufactured ceramics by Native communities. For this project, I examined decorated ceramic pieces recovered from the Grande Ronde Agency schoolhouse archaeological site from 2015 to 2017. A wide variety of ceramic artifacts were found at this site, which illustrate everyday activities within the schoolhouse. This schoolhouse was in operation from the late nineteenth to early twentieth century, and the decorated pottery gives a significant illustration of when, where, and how ceramic pottery was acquired and utilized on the reservation during this time. To determine this, I examined the physical characteristics of the ceramics such as sherd form, paste, and decoration. The results suggest that students had access to utilitarian, medium-quality dishware, and some higher quality porcelain of various decoration styles. This project provides significant insight into mealtime activities and other aspects of student life at the schoolhouse.