This study analyzes the color complex which is defined as psychological fixation about color and features that lead African-Americans to discriminate against each other. There is a lack of dialogue around how history has turned African-American women to focus towards hurting each other through colorism - skin color biases. This research asks how issues of colorism within the African-American community lead to concerns of self-acceptance and perception of beauty among young African-American women. I expect to find evidence of the effects of the color complex and determine how young Black women perceive beauty in order to frame their identity. The findings will fill a gap in existing research by challenging the work of earlier researchers, who have looked at the existence of colorism among African-American women today and look farther into how this issue has been and is affecting their perception of beauty in relation to the acceptance of themselves. 

The inequalities and marginalization of people with disabilities is an issue with global scope. Environmental influences and socially derived assumptions shape the way disability is defined and experienced cross-culturally. Statistics shed light on significant disparities throughout various countries. According to United Nations Enable (2006), 10% of people in the world have some type of disability. Of this entire population of people with disabilities, 80% live in developing countries. Further, out of the estimated 200 countries in the world, only 45 have disability-specific laws such as anti- discrimination. In this research, I examined the driving factors behind this disparity through a cross-cultural comparison of disability advocacy efforts. In particular, I looked to countries that have experienced shifts in policy that directly influenced people with disabilities. I identified disability advocacy taking place in South Africa in a post-apartheid context, Ukraine in a post-soviet context, and the US in post-ADA context (Americans with Disabilities Act). Through rhetorical/discourse analysis of the imagery and language used on nongovernmental groups’ websites, I examined how shifting power dynamics have situated people with disabilities in South Africa, Ukraine, and the US and how these patterns manifested in online communications.

 The vast majority of current protein-based drugs involve binding a therapeutic target with an exogenous molecule that neutralizes or blocks its function. A major drawback of this approach necessitates a stoichiometric number of binding sites be administered to the patient, resulting in many caveats such as high dosage, stability, and immunogenicity. Enzymes represent an underexplored avenue for protein therapeutics with vastly enhanced potency. Proteases are essential and ubiquitous enzymes that catalyze peptide bond cleavage. While there are multiple therapies available derived from naturally occurring proteases, currently there are no novel, engineered protease therapeutics. In this work, we seek to establish a highly specific and processive protease system with traits desirable for use as a protein therapy, such as high solubility and thermostability. For this purpose, we have chosen to engineer the small ubiquitin-like modifier (SUMO) protease. The target of this protease, SUMO, is a small protein important for cell cycle regulation in eukaryotes. The mechanism for SUMOylation is analogous to the ubiquitin regulation system; these small proteins are adducted to other molecules and serve as signals for degradation or cellular localization. Removal of these tags is essential to the regulatory process, and is mediated by the highly specific SUMO protease. This inherent specificity makes the SUMO protease an ideal engineering platform. Here, we take the first steps toward unlocking the therapeutic potential of the SUMO protease by enhancing the stability and solubility of the yeast homologue. To accomplish this, we re-engineered surface residues with the Rosetta software suite. Furthermore, we have developed a novel Förster resonance energy transfer assay to allow us to monitor protease activity in real time. In addition to laying a foundation for the creation of highly selective therapeutic proteases, our work has immediate implications for the production and purification of recombinant protein in a laboratory setting.

 Snailfishes of the genus Careproctus are known to deposit egg masses inside the gill cavity of lithodid crabs. Identification of the species responsible has been inconclusive due to the difficulty associated with identifying snailfish eggs or larvae to species. DNA samples were collected from egg masses found in crabs both in the commercial golden king crab (Lithoides aequispinus) fishery and during survey work conducted by the Alaska Fishery Science Center. Egg masses were found in both golden king crabs and scarlet king crabs (L. couesi). Cytochrome Oxidase I (COI) was amplified from egg mass samples and sequenced. Comparison of COI sequences from eggs with COI sequences from positively identified adult vouchers yielded identification of 75 egg masses to species: 38, 29, 7, and 1 egg masses were identified as Careproctus rastrinus, C. colletti, C. furcellus, and C. simus, respectively. Egg masses were determined to contain eggs from only one species. These results are the first positive identification of the snailfish species responsible for laying egg masses in crabs. Identification of species involved may be useful in further attempts to classify the nature of this relationship between snailfishes and crabs.

 The purpose of this study is to determine structure-solvent property relationships in organic photovoltaic polymers, with the overarching goal of increasing the efficiency of organic solar cells (OPVs). OPVs are of great interest due to their flexibility, low environmental impact, and modest cost. Additionally, OPVs can be dissolved in organic solvents and printed using roll-to-roll, high-throughput processing – a feature that lends them a large advantage in the photovoltaic industry. Unfortunately, OPVs fall short within the realm of efficiency; the ~10% efficiency of OPVs can hardly rival the ~40% efficiency of inorganic photovoltaic technology. Improving the efficiency of OPVs is an important obstacle in producing low-area, economically viable solar cells. This project aims to use computational models to study the role of organic solvents in mediating the self-assembly of polythiophenes, a commonly studied class of OPV polymers. These models are generated in GROMACS, a program that uses an empirical potential energy function for the polymer, solvent, and polymer-solvent interactions to predict the molecule’s time-dependent behavior with classical molecular dynamics. In particular, these simulations can predict how physical properties such as the free energy of the polymers change as the torsional angles between monomers are varied throughout the simulation. Moreover, changes in the preferred conformations of the polymer are primarily signified by the lowest free-energy states. If we do discover changes in the preferred conformations of the polymer, simulations can be used to test whether these changes are predominantly due to the solvent or the structure of the polymer. This yields information about the equilibrium and self-assembly of the polymer, which can eventually improve the efficiency of OPVs by allowing more control over the polymer nanostructure during high throughput manufacturing processes such as roll-to-roll printing.

The development of simple and affordable diagnostics is critical to the diagnosis, monitoring, and management of disease. Nucleic acid amplification has become the gold standard for many diagnostic applications due to its high sensitivity, specificity, and low limit of detection. Fluorescent dyes typically detect the success of amplification, but require expensive optical equipment including lasers and filters. A cheap and visually distinctive method for detecting nucleic acid amplification will simplify and lower the cost of molecular diagnostics. This research project aims to develop a simple colorimetric reaction for detection of loop-mediated isothermal amplification (LAMP) reactions. LAMP produces large amounts of pyrophosphate by-product during amplification. Pyrophosphate complexes many metals and can displace dyes bound to metals in solution to create color changes. Our goal is to identify a set of chemicals consisting of colored dye and metal ions that will present an unambiguous color change denoting success (or lack thereof) of amplification. Using knowledge of metal-ligand formation constants, we have determined a group of metal-dye complexes that may be viable candidates for detection and are currently testing them in the laboratory. One example is indigo carmine dye. In the presence of pyrophosphate, the dye stays blue (a positive test), while the lack of pyrophosphate will turn the dye clear (a negative test). We are in the process of fully understanding the chemistry of this reaction and further optimizing the process to improve its viability. Exploration of other metal-dye complexes, as well as continuing investigation of the literature, will be conducted to improve the present results. This colorimetric reaction has the potential to simplify and lower the cost of DNA detection.

Polymeric micelles are nanoscopic structures constructed with amphiphilic diblock copolymers constructed with hydrophobic and hydrophillic portions that spontaneously form micelles in solution. Small hydrophobic molecules, such as cancer drugs taxol and doxorubicin, can be encapsulated in the micelle, which effectively serves as a nanovehicle for drug delivery. Here, we will develop a diblock copolymer integrating polyurethane-based self-immolative polymers (SIPs). SIPs are polymers that sequentially disassemble into their building blocks once the disassembly process is initiated by a triggering event at the trigger head group. By using SIPs, the polymers that make up the micelle are designed to depolymerize which we hope to increase the efficacy of payload release and remove the ability for micelle reformation. For this project, the micelle and all parts of the system will be synthesized from the bottom-up; optimizing the molecular weight of the diblock for micelle formation, investigating the kinetics of depolymerization and thermal trigger activation, and examining the stability of the micelle.

Autism spectrum disorder (ASD) is a neurodevelopmental syndrome characterized by impairment in social interaction and restricted/repetitive behaviors. Perinatal complications, which occur at the time of birth, have been associated with the presence of ASD, including low birth weight, planned caesarian section, and umbilical cord problems. Though these complications and their link to autism have been heavily researched, the variability of perinatal complications has yet to be compared to the genetic diversity within ASD as a disorder. Due to recent advances in genome science, several dozen autism susceptibility genes have been identified that account for 10-20% of ASD cases. The goal of this study is to analyze both prevalence and type of birth complications in a large genotyped sample as a function of co-occurring genetic abnormalities. Using medical history data collected from a population of over 2000 genotyped families, we will determine the prevalence of perinatal complications within the presence or absence of genetic mutation. Autism severity will be examined as a function of presence of perinatal complications and presence of genetic mutations. Results from this study could serve as a starting point to further evaluate the potential shared etiology of autism and birth complications, as well as other potential genetic links among common co-occurring disorders such as gastrointestinal illnesses and epilepsy.

Autism Spectrum Disorders (ASDs) are genetically heterogeneous neurodevelopmental disorders largely characterized by impairments in social interaction. Many with ASD face other comorbidities, including sleep problems. Prevalence of sleep problems in those with ASD are significantly greater than typically developing children and range widely from difficulties falling asleep to parasomnias. Although many studies investigate the link between sleep and autism, none have considered variability in sleep differences as a function of the genetic variability of the disorder. The underlying assumption for this project is that behavioral variability, such as differences in sleep problems, observed in ASD is a function of the genetic variability in ASD. Chi square analysis was conducted using data collected about sleep problems in a medical history interview from a large, well characterized and genotyped sample of children with ASD to determine the prevalence of sleep problems in ASD as a function of genetic subtype. Those individuals with similar, recurring gene mutations were further examined in order to view whether sleep problems (both pervasiveness and type of sleep issue) may be a specific phenotype related to that gene mutation. Using ANOVA, gender differences in sleep presentation were also examined.  Results from this study may serve as a starting point to evaluate other wide ranging comorbidities, such as gastrointestinal illnesses, as a function of the genetic differences present in those with ASD.

Entamoeba histolytica is a water-born pathogen that is estimated to cause 100,000 deaths annually in developing countries. The disease is prevalent especially in tropical areas with poor sanitary conditions, and is treatable with appropriate antimicrobial medication. Therefore, detection of the pathogen is vital in diagnosis. We developed a sensitive electrochemical assay utilizing novel yeast-scFv detection probes targeted at E. histolytica parasite antigens in stool samples. I have previously tested the assay in solution (buffer and stool dilution) with several antigens and proved sensitivity. This project is a stability study of the assay assembled on the electrodes. I tested factors including temperature, pH, humidity, pressure, and light sensitivity to determine the optimal conditions for long-term storage and transport, as well as the limit that one factor can be pushed while maintaining sensitivity. The significance of this project is to maximize the assay’s shelf life and thus to minimize the cost of manufacture and transportation of the assembled product. Consequently, it will benefit clinicians and patients in poor countries where the disease is prevalent, as a broader population of people around the globe.

Dyslexia is a complex disorder that interferes with a person's ability to read and spell with no consensus as to what causes it. The typical person processes language in the left hemisphere and is either right or left handed while very few people have ambidextrous tendencies. Our hypotheses are two-fold. First, that competition between the brain's two hemispheres underlies dyslexia. Second, that this competition is evident in cortical activation during reading tasks as well as performance speeds during hand motor tasks. To test our hypotheses, we collected data from 52 adult participants (19 with dyslexia, 33 controls) who underwent electroencephalography (EEG) measures during a word reading task and also performed an alternating keytapping task.To investigate Hypothesis 1 (lack of lateralization is associated with dyslexia), we categorized our participants' EEG data according to typically vs atypically lateralized language activation patterns. Higher than expected numbers of adults with dyslexia in the atypical hemisphere activation group would be consistent with our hypothesis. To investigate Hypothesis 2 (correlations between the two modalities), we calculated a relative lateralization score for each of these task types and tested the correlation between these two scores for significance. Evidence of correlations between these two measures would yield higher than expected numbers of participants with dyslexia in the ambidextrous group as well. Evidence for both of our hypotheses will provide important insights into the biological underpinnings of dyslexia, pointing to disorganized brain circuitry in affected individuals. 

The world’s future energy needs will almost certainly require extensive use of renewable sources of energy. Organic photovoltaics are a particularly lucrative source of energy due to their cheap materials and ease of production compared to inorganic solar cells. However, organic photovoltaics (OPVs) currently suffer several drawbacks: they have an efficiency of, at most, around 10% and they are unstable – they may begin to degrade within five to seven years. This project aims to alleviate these defects by gaining a greater understanding of the chemical interaction between interfaces within the solar cell. This project is a comprehensive study of the interactions between phenyl-C₆₁-butyric acid methyl ester (PCBM) and calcium. PCBM is an extensively researched molecule which acts as an electron acceptor in OPV devices. PCBM is typically paired with an electron donor such as poly-(3-hexylthiophene) in a working device, and calcium has energetic properties which allow for very good electron transfer at the cathode of such a device. We use adsorption micro-calorimetry under ultra-high vacuum conditions to study the reaction at the interface between calcium and PCBM, and surface analytical techniques to determine growth modes and chemical binding of calcium and PCBM. These experiments will elucidate the mechanisms of interface formation of this understudied but important OPV system.

HIV remains a serious health challenge particularly in developing countries. This can be attributed in part to the fact that many common diagnostic procedures in high-income countries are too expensive and technically complex to be practical in low-income countries. While there are several strategies for diagnosing HIV, one promising method is using the detection of the p24 antigen. The p24 antigen is a viral protein that can be detected within two weeks after HIV infection. This is useful because it allows for the detection of HIV infection sooner than the commonly used HIV antibody detection tests and rivals the more technologically complex nucleic acid detection methods. Our goal is to develop this test using a paper-based lateral flow membrane and a technique called immune complex dissociation (ICD) to reduce cost and increase sensitivity. The laboratory p24 antigen test was adapted into a paper format using the same reagents as the laboratory test. By comparing the results of the respective methods, we found that the paper test performed well compared to the laboratory test. This performance indicates that there is value in using the paper format and in exploring methods to increase the sensitivity of the assay. Test sensitivity can be compromised by the presence of antibodies that form complexes with the p24 antigen. These complexes reduce the amount of antigen that is free for detection. ICD restores this sensitivity by dissociating the antigen from these complexes. We tested the ICD process, to show that it is compatible with the paper format and improves sensitivity, by running parallel tests with and without ICD to demonstrate the efficacy of that procedure. The completion of this project will bring the paper-based assay one step closer to making a previously expensive, technology intensive, and operationally complicated test, accessible to those in low-resource settings.

The purpose of our research is to better understand older adults’ perceptions about fall detection devices. When an older adult experiences a fall, the results can be dramatically life altering or even fatal compared to an individual in a different age group. This led us to question what views older adults have about existing measures in place to monitor and analyze falls, such as fall detection devices or other technologies, as well as what demographic factors may influence these views. Using data from a parent study, we are currently in the process of analyzing focus group transcripts to compare perceptions of older adults from high and low socio-economic status using qualitative descriptive methods. We are analyzing transcripts for common themes that may lead to the identification of areas for further study. By studying older adults’ perceptions of fall detection devices, we hope to gain a better understanding of their needs and preferences when it comes to such devices. We hope exploring and understanding demographic or other factors that affect these perceptions may lead to more open conversations on falls, and thus better our ability to customize fall detection devices and their features, and fall prevention plans for older adults.

Traumatic Brain Injury (TBI) is an issue that seriously affects people of all ages; older adults with TBI have the highest rates of hospitalization and death. Additionally the overall recovery is significantly poorer than a younger person with a similar TBI. With normal aging, there is a reduction in the number of white blood cells (WBCs). However, in certain chronic diseases with an inflammatory component that are more common with older age, such as diabetes, there may be an ongoing activation of available WBCs which could affect viability in response to injury. This investigation used data from an ongoing parent study of the immune response following TBI in order to examine the number of and viability of peripheral blood mononuclear cells (PBMCs) within 24 hours of TBI in both older and younger adults as well as non-injured controls (N=133). Older age was defined as 55 and older for the purposes of this study. Whole blood was collected and processed for plasma and WBCs from subjects using Ficoll technique (separation of blood components). Cells were manually counted and viability of cells was determined using the trypan blue method (type of stain to observe cells). Data analysis is underway. Descriptive statistics were performed along with ANOVA to assess for group differences in cell count and viability. Time from blood draw to processing will be used as a covariate. The results of this study will enable us to determine if lower cell counts or cell viability differ by age and injury status. This will provide support for or refute the hypothesis that the immune response following injury is different in older adults which could impact patient outcomes. By understanding this relationship, we can implement clinical changes to potentially help change the immune response and improve the outcomes older adults experience post injury.

Autophagy is the process in which eukaryotic cells selectively degrade proteins and organelles. Autophagy has been well documented in organisms ranging from yeast to mammalian cells, with demonstrated roles in response to starvation, aging, and stress. However, there has not been an effective method for measuring autophagy in C. elegans, despite C. elegans being a popular model organism for the study of disease and aging. We refined an assay that uses double-fluorescent protein tagged Atg-8/Lgg-1 to measure autophagy in both yeast as well as C. elegans. This assay reports an increase in autophagy in response to starvation in both model organisms. We then applied this to the study of nematodes containing a mutation in Rheb, an important protein in the upstream signaling cascade that regulates autophagy. Autophagy is damped by signaling through the TORC1 pathway. A mutagenesis screen revealed two different worm mutants (ENU9 and ENU10) which are predicted to hyper-activate TORC1 signaling. Using the aforementioned assay we found that ENU9 and 10 mutants have dramatically reduced levels of autophagy. This work has implications for further research in Alzheimer’s, Parkinson’s and related diseases associated with ageing and proteostasis.

The prevalence of HIV cases in the African born national population versus the African American or national population in general is notably high. In Washington state, there are approximately four times more HIV cases for the foreign born black male versus the African American black male along with about eleven times more HIV cases for the foreign born black female compared to the African American female counterpart. Stigma can impact medication adherence, quality of treatment and undiagnosed contributing mental disorders that, when treated, can improve one’s HIV status. However, little is known about how HIV stigma impacts the treatment and intervention outcomes for the African-born population. My lab as well as my individual role in this research project aims to analyze the nature of HIV stigma among this population, which will provide fundamentals of an intervention that is most ideal for African born population. We conducted semi-structured qualitative interviews with African born patients receiving treatment at Harborview Medical Center Madison HIV Clinic and those receiving social service at BABES YWCA network, and then I as the primary coder analyzed the data through ATLAS.ti, analytic software. Preliminary results indicate that stress due to community paranoia and disturbances due to family history of HIV are common obstacles faced by this population. These findings have important implications for focusing on treatment and other interventions for this understudied population.

Tuberculosis is the second-leading cause of death due to a single pathogen, Mycobacterium tuberculosis (Mtb), with an estimated two billion people currently infected. Drug-resistant strains have emerged that are unmanageable even with combination drug therapies. Therefore, the development of novel drugs aimed at previously untargeted biochemical pathways in Mtb is of utmost importance. Among potential candidates is a newly identified proteasomal degradation pathway termed pupylation. In this system, proteins in Mtb damaged by the reactive oxygen and nitrogen species of the host’s immune response are tagged with the small prokaryotic ubiquitin-like protein (Pup) and shuttled to the 20S proteasome for degradation. Pup-mediated degradation allows Mtb to recycle key cellular components and remain virulent. Our interest is to study the two key enzymes required for pupylation: the proteasome accessory factor A (PafA) and the deamidase of Pup (Dop), which is also involved in the reverse pathway known as depupylation where Pup is removed from the substrate. Our interest is to characterize the mechanisms and substrate scopes of both Dop and PafA to facilitate the design of novel inhibitors. We synthesized and employed a model fluorescent probe that mimics the site of pupylation on a target protein to study the rates of the pupylation and depupylation enzymatic reactions. Since the Pup-probe conjugate is a substrate for Dop we also studied depupylation. We anticipated Dop to be the faster enzyme since it had fewer substrates to bind than PafA and our studies have revealed that Dop is much faster. Though the purpose of depupylation is currently unclear, our investigation has determined the relative kinetics of these opposing enzymatic pathways. The quicker kinetics of depupylation indicates pupylation of proteins also serves as a post-translational regulator rather than existing exclusively for degradative purposes.

Marine debris is a prevalent form of environmental pollution in which man-made products are released into oceans and waterways. Debris objects pose a variety of concerns, including entanglement and ingestion by wildlife, toxicity, and introduction of invasive species (biofouling). The Coastal Observation and Seabird Survey Team (COASST), a citizen science program at UW, is currently developing a marine debris monitoring protocol. The protocol calls for field surveys documenting basic site characteristics and attributes of debris objects. Seventeen attributes were chosen as indicators of potential harm to wildlife (e.g. loop presence and bite marks), invasive species threat (biofouling), and debris movement patterns in the ocean (e.g. size, material). Our team analyzed images from a database of over 5,000 marine debris photos collected by COASST at over 200 beach sites in the Pacific Northwest and Alaska. We utilized an iterative approach with two students independently assigning attribute states (e.g. color: black, bite marks: yes) to debris objects from 900 randomly selected photos. We compared results to understand likely sources of human error. Initially, we found that color, malleability, geometric shape, material, intactness, and weathering were attributes that posed the greatest challenges – where surveyor disagreement (error rates) exceeded 15%, with some approaching 50%. After three rounds of result analysis and attribute definition refinement only 5 of the 17 attributes had error rates exceeding 15% (range 16-30%), reducing the likely error volunteers will make. The resultant standardized attribute definitions and state assignment protocol will provide a means of collecting reliable (i.e. low error) baseline abundance and distribution marine debris data as well as risk assessment based on specific attributes of use for further research, conservation endeavors, and resource management.

Esophageal adenocarcinoma (EAC) is a type of cancer with the most rapidly increasing incidence rate in developed nations. EAC occurs as a result of the metaplasia-dysplasia-adenocarcinoma sequence initiated by Barrett’s esophagus. In this sequence of events, patients develop Barrett’s esophagus, wherein the acidic damage of gastroesophageal reflux disease (GERD) causes the esophageal epithelium to take on an intestinal epithelium phenotype. This metaplasia can then progress to Barrett’s esophagus with either low-grade or high-grade dysplasia. Patients that develop high-grade dysplasia (HGD) are at great risk for esophageal adenocarcinoma, and hence there is a need for higher specificity in the labeling of pre-cancerous tissues for endoscopic detection. Current imaging of dysplastic lesions is done through traditional endoscopy with the use of contrast agents for differential staining. However, current contrast agents have a low signal-to-noise ratio (SNR), and dysplastic lesions are often missed. Therefore, for early detection of esophageal adenocarcinoma, we are creating a contrast agent that increases SNR via fluorophore-labeled peptides that bind specifically to tissues with high-grade dysplasia. Peptides are ideal as targeting ligands as they can bind specifically to surface proteins on dysplastic cells and increase the likelihood of clinicians obtaining biopsies of pre-cancerous tissue. In the past year, we have isolated potential peptide sequences that bind immortalized cells lines generated from dysplastic tissues. A bacteriophage library was subjected to subtractive whole cell panning for isolation of phage expressing HGD-binding peptide sequences. The phages were added in vitro to cultured cell lines of normal esophageal tissue and non-dysplastic Barrett’s esophageal tissue to eliminate those that were not selective for dysplasia. After subtractive whole cell panning, left over phage were sequenced to determine the peptide sequences on them. Future work includes binding studies using flow cytometry to demonstrate that fluorophore-labeled peptides bind preferentially to dysplastic cell lines independent of the bacteriophage.

Synthetic biology aims to engineer biological systems that perform complex tasks such as producing therapeutics and biofuels. Synthetic gene networks are developed that interact with an organism’s native genome to modify its behavior, and the design of synthetic gene networks is guided by computational models. However, the ability of computational models to accurately predict gene network behavior is limited by a poor understanding of how individual network components operate; and this often results in repeated rounds of experimental refinement. This work aims to improve the predictive power of computational models by characterizing the function of promoter sequences. We developed methods to easily detect intracellular RNA levels with high accuracy using an RNA-based fluorescence reporter. The method is used to quantitatively measure RNA synthesis rates in E. coli. This technique may be used to enable high-throughput characterization of DNA promoter sequences for use in synthetic biology applications.

Mitochondria are essential organelles in eukaryotic cells and are most commonly known for their prominent role in energy production. In addition, mitochondria are involved in other important cellular processes such as lipid biosynthesis and apoptotic cell death. Mitochondria also have dynamic properties including fusion, division, and movement, which are all essential to maintain mitochondrial function. Given the plethora of essential cellular activities that require mitochondrial function, it is not surprising that defects in mitochondrial function are implicated in many different human diseases and disorders including diabetes and myopathies. Mitochondrial movement is important for the distribution of mitochondria, which is important in all cells, but especially important for asymmetric cells such as neurons. Transport is also required for mitochondrial fusion – the two organelles must move close enough to each other to fuse. Mitochondrial fusion in particular is required to maintain mitochondrial DNA and therefore, mitochondrial function. We are interested in the mechanism of mitochondrial movement and the connection between mitochondrial fusion and transport. Mitochondria move on microtubules using a complex of proteins. Miro 1 and Miro 2 are anchored to the mitochondrial outer membrane and interact with two adaptor proteins, TRAK1 and TRAK2. The TRAK proteins also interact with Kinesin, which binds to the microtubules and mediates microtubule-directed movement. Understanding the assembly and regulation of this complex and the stoichiometry of its components will provide insights into the mechanism of microtubule-directed mitochondrial movement. Our goal is to clone TRAK1 and TRAK2 complementary DNA (cDNA) into expression vectors for protein production in Escherichia coli cells and then to develop a purification protocol for TRAK1 and TRAK2. This will facilitate biochemical analysis of the mitochondrial motility complex.

As the NFL was going into a lockout in 2011, linebacker Ray Lewis made the controversial statement that crime rates would rise if the NFL season was lost. Mr. Lewis said, "There's too many people that live through us," and that without football teams to follow, those people would turn to crime. At the time, there were many arguments provided on both sides of the issue, but no empirical research was done. Studies have shown that professional athletes commit more crimes during a lockout; and that children with access to sports programs are less likely to grow up committing crimes; but no one has ever tested the claim that a professional sports team has an effect on the crime rate in the area in which it is based. My experience living in a Seahawks-enamored Seattle in 2013 has motivated me to take Mr. Lewis's assertion one step further and investigate whether the success of a pro sports team can raise or lower the crime rate in its city. I look at more than just the relationship between winning percentage and change in crime rate (note that I cannot compare nominal crime rates, due to the varying base levels of crime in metro areas as diverse as New York and Denver). Other measures I investigate are margin of victory or closeness of playoff race, as perhaps a more dramatic season gives the fans more to live vicariously through. Despite some relationship between winning percentage and playoff success of a team and the city's crime rate, I can't show a significant enough correlation to conclusively say that the NFL influences the rate of crime. While this doesn't have any direct implications on the NFL or on policy makers, I believe that my results are enough to encourage further study of the issue.

Antibiotic resistance is a challenging problem in the realm of human health today. As a fundamental evolutionary phenomenon, it provides an excellent system to test adaptive evolutionary theories in a short amount of time. Thus, I explored the rise of antibiotic resistance in two evolution experiments with Escherichia coli. In the first, I asked how differences in genetic background affect the rate of adaptation to a new environment. To address this question, I generated 19 unique antibiotic resistant mutants by evolving E. coli in an environment with low drug concentration, and then exposed thousands of populations of each isolate to a high concentration environment measuring the proportion of populations that survived. Since survival in the high-drug environment requires acquisition of a new beneficial mutation, I hypothesized that high mutant survivorship indicated an isolate with more mutational options available in the high drug environment (we call this “potentiation”). Isolates with low survivorship would have fewer available mutational options (we call this “doom”). Interestingly enough, some observed differences may be due to a phenomenon known as sign genetic epistasis – when mutations have different effects in combination than individually. Preliminary data suggests a few strong cases for potentiation. I also investigated the effect of an initial resistance mutation on the consequent adaptations in a no drug concentration environment. To study this, I generated 23 unique mutants of E. coli and tracked how fitness and drug resistance changed over time in 2,200 populations. Both of these experiments help illuminate the role of historical contingency in evolution, the idea that an initial mutation may dictate an organism’s future mutational trajectory (available mutational options). Therefore, understanding both the effect of initial mutations and the underlying mechanisms of mutation acquisition is necessary in order to combat the emergence of resistant bacteria, a current human health concern.

In addition to having massive environmental and public health impacts, the livestock sector of the farming industry raises important ethical questions about the humane treatment of workers and animals. One response to the industrialized animal food system has been a push to eat ethically sourced meat from family farms. In theory, this allows the consumer to trace back their food to the source, interact with the people handling their food, and support a more humane treatment of animals. Eating locally sourced meat is a part of the larger “local food movement”, or campaign to eat foods from within 400 miles. However, there has been backlash against the local food movement, with critics arguing that the movement itself has its own set of problems. This study aimed to achieve two goals. First, I critically examined the local meat movement to determine whether or not I believed “local” food was a viable solution to the problems that exist within industrial agriculture. Second, I aimed to raise public awareness about family-farmed meat and the broader local food movement. To accomplish this task, I conducted interviews and reviewed the current literature about food issues. I interviewed chefs from local restaurants that serve family-farmed meat to gain a better understanding of their motivations. I also read primary literature, magazine articles, newspaper articles, and books related to the local food movement. I concluded that the local food movement, in addition to “local meat”, offers many benefits that industrial agriculture does not. However, as pointed out by many critics, the movement does not fully address the wide array of environmental, economic, and ethical concerns within the agriculture industry. To summarize my conclusions and raise awareness about the subject, I created a booklet about local food. The problems in the food industry will not be solved overnight and the first step is to generate an educated public that is willing to make necessary changes.

Acute viral respiratory infections are responsible for much of the infectious disease in the world. Of the known respiratory viruses, influenza is probably the most dangerous. In addition to the relative lack of knowledge on how influenza produces systemic symptoms, little is known about how it affects the central nervous system (CNS) and subsequent recovery outcomes. Following an acute viral infection, the body undergoes a state of acute stress response (APR). APR is a complex array of physiological responses that leads to changes in behavior and body temperature, anorexia, immobility, sleepiness, and malaise. Anecdotal and personal experience suggests that sleep becomes more prolonged while one is battling influenza infection. Following an infection, cytokines and other inflammatory regulators affect sleep and body temperature caused by influenza. Cytokines are signaling molecules that are generally involved in the immune response following trauma or infection. IL1β, a focus of this study, is a particular cytokine that has been extensively studied for its involvement in physiological sleep regulation in normal healthy organisms and in those subjected to an immune challenge. IL1β alters the sleep profile post-infection by enhancing non-eye rapid movement sleep (NREMS). Such increase in NREM sleep has been demonstrated to increase the probability of survival due to microbial challenge in rabbits. I will focus on the involvement of IL1β and its receptor (ILR1) in influenza-induced NREMS APR responses. A transgenic mouse strain that selectively expresses IL1β receptors on neuronal cells in the brain will be used for this study. I hypothesize that ILR1 on neuronal cells in the brain is necessary for the virus-induced APR following an infection. Whether more sleep (specifically NREMS) promotes, as enhanced by IL1β, and less sleep impairs, recovery from infection remains to be determined.

 Although we normally place the academic, institutional gallery or museum exhibition space in a separate domain from the virtual space social sites like Facebook, Tumblr, and Pinterest provide, I argue that the motivations that determine our uses of both spaces are the same. Using the writings of theorists such as Foucault and Baudrillard, and the history of Cabinets of Curiosities, I look critically at the creation of online profiles (primarily related to Facebook, but also found in other popular social sites) and traditional exhibitions spaces (for instance, the galleries of the Museum of Modern Art). I examine the logic of categorization and the intended impact this will have on viewers, comparing the nature of collecting and the curatorial impulse to display, showing that ideas surrounding collection function in both spaces. Through this I illustrate that a curatorial impulse is present in each, revolving around some sense of identity, although there are clear differences in ability to create context and exhibition time frames among other things. This will demonstrate that such spaces provide similar outlets for engrained human behaviors that mediate our interaction with and understanding of not only culture, but social interactions and even personal identity. In effect, I show that these spaces are much more closely related than they have previously been given credit for, and that certain social networking sites might even be the next logical stage in the continual development and progression of our understanding of collecting and exhibiting.

Four displaced ethnic groups populate Kyakitanga village in central Uganda. The community collaborates with small NGOs and local ministries to address conditions of “underdevelopment” and at a August 2012 workshop, participants expressed a priority of increasing community wisdom concerning “modern” food production. In a place-based subsistence community, such wisdom may be framed as Traditional Ecological Knowledge (TEK). This research explores Kyakitangan TEK as it already exists, aims to identify the local food sovereignty development model, and the implications of that model for social equity and environmental sustainability. These questions were explored through a participatory action research study involving local-led grand tours, object-and-walking probe interviews, alternative talking circles, and pile sorts. Findings indicate Kyakitangans possess tremendous TEK concerning foraging, agriculture, and pastoralism. This TEK is tied to ethnicity, as different foodways function as survival strategies specific to each group’s ancestral history and environment. Contrary to the 2012 workshop’s “modernist” atmosphere, Kyakitangans actually advocate a development model utilizing knowledge and resources already existent within the community. Implications pose questions about how ethnic groups collaborate moving forward since different foodways entail different land-shaping impacts and the livelihoods of each group are linked to each other. These dynamics are contextualized in the region’s political economic and cultural history, because the question of food insecurity is a by-product of peoples’ physical separation from native lands. This is exacerbated by structural violence and historical trauma of post-independence regimes and neoliberal globalization. Open-endedness in methodology allowed for the surfacing of important issues surrounding gender and reproductive control. Overall, the Kyakitangan context presents alternative models of development which privilege local knowledge. This type of model in broader development discourse is currently marginal, co-opted, or nonexistent.

What began as a practical question for our large, interdisciplinary organization has taken on scholarly weight given active debate in the literature regarding professionalization of peer/student writing tutors -- as studies on beneficial tutoring outcomes turn away from difficult-to-assess outcomes for writers toward outcomes for tutors. What this literature says about professionalization, however, seemed troubling in that it is predicated on the assumption that tutors will necessarily go on to be educators -- patently untrue for this interdisciplinary group of student employees. Existing concepts of professionalism are also (troublingly) opposed to our center’s non-expert, collaborative approach to tutoring. Our team currently investigates two questions: (1) How might our tutors’ actual professional objectives/career paths differ from those imagined for them?  (2) How might tutors’ sense of appropriate professional practice diverge from other visions of professionalism in the context our non-directive center? Phase I of this investigation involved interviews with 50+ active tutors using a standard form we developed; tutors described both short-term goals for tutoring practice and longer-term career goals. Phase II will involve capstone interviews asking graduating tutors to report on specific experiences of professional development (transferable skills). In interviews to-date, tutors openly identified widely-varied short-term and long-term goals. Contradicting existing scholarship, we found that even tutors uninterested in writing-instruction-related careers articulated complex connections between their tutoring work and their future careers. Further challenging commonplace assumptions, interviewees articulated tutoring goals aligned in sophisticated ways with this writing center’s approach, suggesting that thoughtful tutor professionalization need not involve training in more expert, directive tutoring practice but instead can be flexibly self-directed in alignment with tutors’ own professional goals. Our methods and findings have important implications for those interested in: employee motivation and deep learning; grounded planning and programming that avoid administrative assumptions; richer professional development for students across fields.

Are attempts by the United States to improve student educational outcomes by increasing classroom spending worth the effort? How successful have these efforts been in improving the outcomes of public school students? Using data from 2002 to 2010, which includes expenditures allocated to classroom costs per pupil and averaged freshmen graduation rates, I investigate the impact of increased federal spending on students, more specifically on expenditures allocated directly to classroom spending as opposed to administrative and operations expenditures. Major classroom costs include teacher salaries, supplies, special education programs, textbooks, and other various minor costs. After controlling for factors that may influence educational outcomes such as parental educational attainment, years of teacher experience, and teacher-to-pupil ratios in the classroom, my results show that when a higher percentage of a state’s expenditures on education are spent on costs directly related to the classroom, students succeed at a higher rate as measured by graduation rates.

The world faces mounting environmental problems and environmentally-minded citizens are necessary to help find solutions. Education is a critical component in shaping future citizens who think globally and act locally. However, the current system of education often disconnects concepts and ideas from geographic locations. The purpose of this study was to investigate the impact of place-based lesson plans on student learning, and to explore whether or not place-based examples help to stimulate environmental stewardship and engagement in school and local issues. To this end, I conducted qualitative interviews with local high school science teachers and performed a meta-analysis of current literature about place-based education and methods for environmental education. In addition to this research, I developed several place-based biology lesson plans for Alaskan high schools. The results thus far support the idea that place-based examples are effective tools for teaching science, and do in fact help facilitate student engagement in the classroom. Through the process of creating the lesson plans, I found that a real life example contextualized the lessons and gave them greater meaning. The use of place-based examples within science education has the potential to stimulate a connection between students and local environments. It is essential that today’s students, as future citizens and decision makers, have an established connection with the environment to prepare them for creating positive change in the world.

“Permaculture” refers to a design approach for creating resilient and integrated systems using principles and tools grounded in ecology. Permaculture design is usually applied to agriculture and food production, but recent permaculture-based projects in economics, urban planning, and governance have emerged as alternative applications of this design approach. However, there are few examples of applying permaculture to education systems; a gap in the general knowledge of the permaculture community and the field of education reform that I hope to help fill. This study examines how the ecological principles demonstrated in permaculture design can be used to address the problems that standardization has produced in K-12 public education in the United States. Standardization has emerged as the dominant approach of education reform, most visibly manifested in No Child Left Behind and the Common Core State Standards initiative (U.S. Department of Education, National Governors Association). However, as recent research has shown, standardization as a paradigm in education causes more harm than good for students, teachers, and schools (Robinson, Ken). Through research in educational philosophy, curriculum and instruction, development and learning, and systems theory, I justify how permaculture design principles can be applied to educational systems. From this I develop an original synthesis of education theory and permaculture principles as an alternative to standardization. My argument is presented in a three-part paper: a review of the critiques of standardization as a dominant paradigm for education; explanation of the twelve permaculture principles in the context of education; and a demonstration of applying these principles in the re-imagining of American schooling.

Supplementation with “good bacteria” (probiotics) has been promoted for various health conditions. Marketing and over-the-counter (OTC) access has also led to increased availability of these agents. Safety of probiotic supplementation for individuals with weakened immune systems, such as bone marrow transplant (BMT) recipients, is unknown. Since these patients are at increased risk for developing bloodstream infections (bacteremia), we sought to evaluate the incidence and outcome of bacteremia due to organisms common to OTC probiotic supplements in a cohort of BMT recipients. We reviewed all blood culture results from BMT recipients transplanted at the Fred Hutchinson Cancer Research Center in Seattle, WA between 2002-2011. Patients with at least one positive blood culture for common probiotic organisms (Lactobacillus species, Bifidobacterium species, or Streptococcus thermophilus) within one-year post-BMT were considered cases for this study. Patients with evidence of pre-transplant bacteremia from these agents were excluded. Data were collected from center databases, which contain archived laboratory data, patient demographics, and clinical summaries. We found that a total of 18/3799 (0.47%) BMT recipients developed bacteremia with Lactobacillus species within one-year post-HCT; no events with Bifidobacterium or S. thermophilus were identified. Positive blood cultures for Lactobacillus species occurred at a median of 84 days post-transplant (IQR: 34, 127), but the majority (n=12 [67%]) occurred within the first 100-days. The overall incidence rate of Lactobacillus bacteremia was 1.54 cases per 100,000 patient-days, but the highest incidence occurred during the first 100-days post-transplant (3.31 cases per 100,000 patient-days). Incidence did not deviate significantly by year of transplant. Most patients had a singular positive blood culture (n=17 [94%]); one patient developed prolonged bacteremia (30 days). No Lactobacillus-attributed mortality was observed during follow-up. We concluded that organisms frequently incorporated in available OTC probiotic supplements are infrequent causes of bacteremia after BMT. Studies evaluating the use of probiotics among these high-risk patients are needed.

The U.S. food system has been de-localized from decades of industrialization and globalization. There have been many environmental and social repercussions, including loss of farmland, devaluing of farmers, loss of food sovereignty, and a consumer disconnect. How can we support a strong local food economy and shorten the distance from farm to table? Organizations and agencies play a key role in facilitating the increasingly popular local food movement in the Puget Sound region. The purpose of this project was to analyze the capacity and affinity of each group, and investigate how a communication network could lead to greater success. My internship with American Farmland Trust researched these groups and organized them based on focal area. This served as a preliminary effort to map the overarching shared goals of the movement. Supplemental research was conducted through an extensive review of published literature and interviews. The results suggest that defining the “center” of the movement through a formal communication network and regional planning will increase overall success. Additionally, there are severe gaps in the local food supply chain and excessive emphasis in other areas that could be reallocated to better serve the broader community. A local food system with strong coverage from farm to table is imperative for the future of sustainability and food security in the region, and similar efforts elsewhere could serve to strengthen food systems nationwide.

Urban restoration is a burgeoning movement in our increasingly urbanized but ecologically degraded living places. The success of an urban restoration project is usually measured against only ecological principles, such as complex vegetation structure, increasing biodiversity, and improved ecosystem services. The narrow set of performance criteria ignores social factors contributing to successful urban restoration practice, which potentially hinders further improvements on urban restoration projects. The study aims to examine impacts of participants’ cultural awareness and availability of long-term stewardship resources, as two examples of social factors on the outcome of urban restoration projects and also to create representative social indicators that can be adopted in urban restoration evaluations. To understand these two social variables, I conducted surveys on restoration volunteers and interviews with project managers/volunteer coordinators of local restoration groups, as well as extensive literature reviews. My internship as the volunteer coordinator for the Kincaid Ravine restoration project also provided first-hand experience working with volunteers on urban forest restoration. Findings suggest that two factors of urban ecological restoration projects selected can affect the outcome of restoration projects through various means therefore need to be incorporated into restoration evaluations. My research serves as a case study of two specific social factors; further research on the impacts of other social variables on the outcome of urban restoration projects is required. Moreover, it lays the ground for further efforts in developing social indicators to evaluate urban restoration practice, which is a necessary step towards promoting comprehensive urban ecological restoration.

The influence of environmental oxygen level on the development and histological characteristics of mammalian bones has only recently begun to be explored by the biological sciences. By utilizing bone histology as the methodology, this research works to identify and analyze the influence of environmental atmospheric hypoxia on the characteristics of the microstructure of mammalian femora. This study focuses on wild caught animals of the order Lagomorpha and the family Sciuridae, provided by the Burke Museum of Natural History. Data was collected on bone wall thickness and a wide variety of mechanical properties in order observe any possible patterns and trends as the amount of oxygen in the environment decreases. The comparison is intra-species, and each animal is collected from a discrete elevational point and compared to animals from higher or lower discrete elevations. By using paleontological preparation methods we can strengthen our ability to make assumptions through evolutionary history and into the fossil record. The implications of this research are possible inferences about the universal effects of elevation, and as a proxy, oxygen level, on the growth and mechanical properties of mammalian bone. Because oxygen is believed to be a macroevolutionary pressure, identifying the physical manifestations of oxygen’s influence within bones would further our broad level understanding of how an organism’s habitat and environment influences the mammalian body.

Since 2009, students in First Creek Middle School's Environmental Science Club have been collecting water samples from a local creek running behind their campus as a part of an ongoing service learning partnership with the University of Washington Tacoma. These monthly samples, along with samples taken at two other locations along the stream, have been analyzed for several potential contaminants: select metals, nutrients, and emerging environmental contaminants known as perfluorinated organic acids. Analysis was conducted using various laboratory-grade analytical techniques and equipment including Graphite Furnace Atomic Absorption Spectroscopy (GF-AAS), SmartChem Discrete Nutrient Analyzer, and Liquid Chromatography-Tandem Mass Spectrometry (LCMS). The results were compared with data spanning back to the beginning of the service learning project and correlated with rain events in order to track contaminant levels over time and identify the effects of stormwater on pollutant levels. These results are also being used to help Science Club students better understand environmental processes and challenges associated with ecological restoration, while encouraging advanced learning through classroom based analyses which they have conducted themselves. Through improved understanding of pollutant transport and stormwater contamination, results may also be useful in identifying and quantifying the need for further community-based stewardship programs designed to help improve Tacoma’s green spaces.

Women with a history of sexual victimization often have higher rates of alcohol consumption and sexual risk-taking than women with no history of sexual victimization. One explanation proposed for these associations is the self-medication hypothesis which says that women with sexual victimization histories engage in drinking and risky sexual behavior to cope with distress or to increase positive affect. Although popular wisdom and research studies link alcohol and sexual risk-taking, sexual assault victims often experience difficulty with sexual intimacy. Specific motives to consume alcohol in order to cope with or further enhance sexual behaviors have not been examined. Further, it is not known how a history of sexual assault would impact sex-related drinking motives and whether these motives would mediate the association between sexual assault history and both alcohol consumption and risky sexual behavior. We are currently in the process of recruiting undergraduate women through the University of Washington Psychology Department’s Online Subject Participation Pool. Women are asked to complete a forty-five minute online survey about their drinking patterns, history of sexual experiences and sexual assault, and endorsements of sex-related drinking motives. Data collection will be complete at the end of winter quarter, after which we will conduct mediation analyses using bootstrapping to test our hypotheses that sex-related drinking motives will mediate the relationship between a history of sexual victimization and both alcohol consumption and sexual risk-taking. We expect that these motives will partially mediate the relationships between a history of sexual victimization and both alcohol consumption and sexual risk-taking. Results will help inform effective interventions tailored toward survivors of sexual assault.

Despite a narrowing performance gap between women and men in Science, Technology, Engineering, and Math (STEM) in the U.S., women continue to be less likely to pursue degrees or careers in these fields. One potential explanation for this enduring gap may be tied to gender roles, or beliefs about the proper way women and men should behave. Women and men who violate these gender roles are often considered deviants and encounter social backlash. We proposed that women who choose careers in STEM are perceived to deviate from gender norms more than those who simply do well in STEM fields. In the current study, female and male students rated how typical and desirable it is for women to perform well in math and to choose a math-related career. Similar questions were asked about English, a contrasting field not dominated by men. We predicted participants would believe that it is less desirable and less typical for women to choose math-related careers than for women to perform well in math. We did not expect this pattern to appear for English-related career choice and performance in English. Interventions designed to increase women’s participation in STEM fields, therefore, may need to shift from addressing performance to addressing pressures imposed upon women to forsake STEM careers.

Women make up only 25% of employees in the technology industry (e.g., computer science careers, information technology, etc.). One possible explanation for this disparity is that hiring decisions are made based off cultural fit, or the perception of similarities between employers and job candidates. The current research investigates whether perceptions of cultural fit are determined in part by the design of workplace environments, and, as a result, whether stereotypical computer science (CS) environments might influence hiring decisions and contribute to the gender disparities in the technology industry. In our study, undergraduates were asked to imagine that they were hiring a job candidate for a technology company. Participants read a description of either a non-stereotypical (e.g., art posters on the wall, etc.) or stereotypical (e.g., Star Trek posters, computer parts, science fiction posters, etc.) CS workplace, and then read the resume of either a male or female job candidate. Participants then answered questions measuring perceived candidate fit into the company environment and hiring intention. We predict that participants who viewed the non-stereotypical CS workplace environment will be more likely to hire the female job candidate than participants who viewed the stereotypical environment. This work would suggest that the design of company environments can prevent non-traditional candidates from being hired, and that encouraging companies to create inclusive, non-stereotypical environments may reduce gender disparities in the technology industry.

Through the design and implementation of a 2-credit focus group course, my project investigates how theory can be used to understand the impacts of body dissatisfaction. Widely recognized in research as a "normative discontent" for women and a growing number of men, body image dissatisfaction impacts individuals and communities on a daily basis. While many programs and organizations work to improve body image, I have found a lack of theory and criticism of current discourses within body-positive campaigns.Because of this, the goal of these focus groups is to inspire activism and change in the way that society views different bodies through a theoretical lens. The discussion-based, peer-facilitated group of 8-12 students discusses bodies in various contexts: feminism, biopolitics, normalization, medicalization, identity, oppression politics, and sociocultural norms. The results of these focus groups included awareness of the issue of body dissatisfaction and individual activism projects that challenge social, cultural, and political norms surrounding bodies.This project demonstrates an effective way of bringing issues of bodies, identity, and oppression to the community sphere to promote understanding and activism.

Emperor Claudius was a target for gossip and disgust for many Romans in his time. He suffered from what we believe was Cerebral Palsy, an illness for which the Romans had no understanding, nor knowledge of how to manage it. This illness resulted in Claudius having a pronounced limp, poor motor control, and a serious speech impediment. Upon his death, the Stoic philosopher Seneca wrote a satire called the Apocolocyntosis, which detailed Claudius' attempts at deification, his eventual rejection from heaven and his descent into the Underworld. It is not a flattering piece of literature; Claudius is depicted as incompetent, stuttering, and childish, and is poorly treated by his peers within the text. Seneca explores Claudius' condition thoroughly in the Apocolocyntosis and eventually offers his own end to Claudius' power, giving Claudius a social status in his final resting place in the Underworld which Seneca believes is befitting of his condition.The piece provides us with an opportunity to explore Roman concepts of social capability and capacity for power, which were heavily based on the ability to speak well, as portrayed through the lens of Stoic philosophy. Through exploring the main tenents of Stoicism and their connections to Roman social ideals, a combined set of values emerges which can be applied to the Apocolocyntosis in order to better understand the perception of Claudius by his Roman peers. The Emperor embodies a conflict for the ideal social order of Roman Stoics, as he violates what Stoics consider to be "human" but doesn't fit their definition of "animal." This analysis creates the opportunity to explore Stoic Roman ideals for humanity, the way in which mental illness and speech impediments violate their desired natural order, and how Claudius is used to provide a conclusion to this contradiction.

North and South Korea have grown increasingly distant culturally, economically, and ideologically since the division of the Korean peninsula in 1948. Although the 1953 armistice agreement ended the Korean War, North-South tensions have persisted. Yet, North Korea often takes on a dual role in the South Korean national imaginary as not just a threat, but also a lost family member. This project asks why the desire for unification, which might have made sense after the Korean war but has become more difficult to achieve, continues to resonate in South Korea such that there is a fixation on unification as the one true solution to North-South tensions. My hypothesis posits an answer in two parts. First, unification is fixated on because national division represents the continuation of a historical pattern demonstrated by Korea’s internal response to the fall of the Ming dynasty, the colonization of Korea by Japan, and the Korean war. In each case, a traumatic event triggered an anxiety over political legitimacy. I examine how the internal response to each crisis was to remove any member of the nation, construed as family, who threatened the legitimacy of the state, to suggest that unification as a continuation of this pattern symbolizes the reconciliation of this divided family. Second, unification continues to resonate because it perpetuates the problem it attempts to resolve -- that is, unification itself reminds of this historical process wherein North Korea continues to be both family and enemy. To this end, I examine recent South Korean television dramas related to unification: first, to observe how the internal response to threats to Korean legitimacy exhibited by Korea in the historical pattern I have outlined constitutes a repeated narrative trope, and second, to analyze the tension between portrayals of North Koreans as both family and enemy in these dramas.

My experience on a short term medical mission trip to Guatemala in 2010 left me with an uneasiness. In the face of the experience itself, much post-trip discourse has been centered largely on its value as social capital. The goal of my research is to begin to unravel the complex emotions that take place both at the site of contact in the third-world host country and after returning home. In the face of the ubiquity of short term mission trips, their increasing necessity for professional and educational development, and the vast amount of development literature, this emotional ambiguity is left out. I plan to unpack and illuminate this internal conflict as a way to understand the dual nature of its effects. As an overall objective, I hope that this project invites further discussion about short term volunteer programs and their complexities. Additionally, my research questions ask what evidence of this duality in their own experiences there might be in personal accounts of returnees. Additionally, I plan to address the source, context, and representation of this ambiguity, if it does in fact exist for others, as well. My methods consist of revisiting my experience through an autoethnography and collecting data from the trip. I also include personal narratives from several returned volunteers willing to share their experiences, as well as reviewing much of the academic literature about short term trips. I plan to present emergent broad themes and possible significance for others preparing to go on a short term volunteer trip. These themes include mixed feelings about the trip in the form of a duality, the manner in which relationships formed in the contact zone might affect personal beliefs about the work being done on the trip, and the ambiguity of short term mission trips in terms of their helpfulness or harm.

Vaslav Nijinsky, a dance prodigy and the star of Serge Diaghilev’s company Ballets Russes, shocked Europe when his groundbreaking work Le Sacre du Printemps ("The Rite of Spring") premiered in 1913. Choreographed to Igor Stravinsky's musical composition of the same name, Sacre caused a near-riot at its premiere in Paris at the Théâtre des Champs-Élysées and received only six performances. Sacre is an iconic work with enduring legacy even today. Stravinsky's music appears in pop culture phenomena like Disney's Fantasia, and prominent figures in the dance world continue to restage their own versions of Le Sacre to audiences worldwide, but Nijinsky's original steps have not survived. Nobody knows exactly what the original dance looked like. So why do choreographers keep constructing their own versions of Sacre? To answer this question, I researched four different modern versions of the dance: the Joffrey Ballet and Millicent Hodson's 1987 reconstruction of Nijinsky’s original choreography, Pina Bausch's Rite of Spring, Molissa Fenley's State of Darkness, and Jürg Koch's Rite of Spring, which premiered at the University of Washington last winter. I analyzed the sweeping themes apparent in each dance, regardless of the varied choreography, and compared them with what remains of Nijinsky's original ballet and artistic vision. Through interviews, historical archival research, and my own physical embodiment of aspects of each dance, I am making an effort to piece together Sacre's impact and continued allure, positing the history of Le Sacre as anything but a straight line.

If there is one point of consensus in this era of divided and dysfunctional government, it is the U.S. Constitution. However, some scholars attribute institutional paralysis in government to the founding document, such as a Senate with equal representation of states. If this is the case, then improving government will require reforming the Constitution. Whether the American public supports reform will be influenced by preexisting attitudes towards the document. These split on how the Constitution should be interpreted; some support a “living” document and others prefer preserving the original content. To see with which Americans agree, I model public support towards the Constitution based on government job performance from responses to Time Magazine survey from 2011. I find that people who are more dissatisfied with the government’s handling of its jobs are neither more nor less likely to support constitutional reform. This suggests that Americans do not agree with the institutional explanation and are unlikely to support reform based on poor government job performance.

The Hashemite Kingdom of Jordan is currently working to develop a domestic nuclear power capability, to which they are entitled under the Nuclear Non-Proliferation Agreement that they signed in 1970. Jordan’s economy is rapidly expanding and their current path of importing energy is costly and unsustainable. While nuclear politics in the Middle East are complicated, and efforts to build nuclear power plants that do not produce weapons are viewed with suspicion by the world, Jordan generally occupies a favorable view among the Western world, following decades of security cooperation with the United States and their signing of the 1994 peace treaty with neighboring Israel. However, Jordan’s bold advances have been led by a strict monarchy that has been criticized for not representing the people. Furthermore, regional conflict has led to an enormous refugee influx which now makes up the majority of the population. Political upheavals in the region has made others worried if the country has enough stability to insure that nuclear infrastructure always remains in trusted hands. My research includes extensive firsthand experience from a semester in Amman, where I surveyed Jordanians, both inside and outside the nuclear profession, regarding their opinions of progressing nuclear energy in the country, taking into account the regional challenges. The rapid change in Jordan’s demographics and in the security situation of it’s neighbors makes it necessary to constantly reexamine this country. Given the overwhelming focus of Western attention towards hostile regimes, such as Iran, and their nuclear ambitions, this research covers an often overlooked area of global nuclear development.

The 2007-2009 financial crisis and subsequent recession has brought the looming unsustainable debt and deficits of the United States to the forefront of the minds of people everywhere.  This paper will delve into the puzzle of why neither dominant political party has been able to take the large legislative action needed to implement the recommendations of four well regarded institutions (Office of Management and Budget, The Federal Reserve, the Simpson-Bowles Commission, and the Domenici-Rivlin Debt Reduction Task Force) in light of their general consensus regarding goals that need be met in order to avoid a budget/currency crisis.  I ask the question: Why has the Congress of the United States failed to enact the large scale budgetary reforms necessary to bring the US debt/deficit in line with the recommendations?  My hypothesis is that there is some threshold of power balance that must be achieved over the opposing political party to achieve a strong enough majority in order to pass legislation that makes large program or budgetary changes.  I will investigate legislation before the floor of the House and Senate in the areas of Social Security, and Medicare.  First, I discuss the various recommendations regarding the debt and deficit.  Second, I review the literature regarding theories of legislative gridlock.  Third, I research and analyze the passage or failure of bills before the House and Senate floor in terms of size of the legislative change in budget and program, as well as compare this to the party balance of power present.  Finally, I speculate as to what would be necessary for Congress to pass the large budget/programmatic changes recommended.  Having done so, it is our hope that we can provide policy makers and constituents with a deeper understanding of the debt/deficit problem that the country faces.

Songbirds are a model organism of interest to neurobiologists as they are one of a few groups of organisms that display sensorimotor vocal learning, akin to that of humans. Once learned, birdsong is highly stereotyped and while slightly variable, has not been thought to vary systematically from instance to instance. However, biological processes separate from learning mediate the qualities of a bird’s song. It is well known that the amount of singing varies throughout the day with the light cycle, but is not well understood how the acoustics of birdsong vary with light. Recent work has shown that pitch and loudness vary in a consistent manner throughout the day, rising through the morning and early afternoon and falling through the afternoon and evening. Whether these changes in song depend on an internal circadian rhythm or external light cues remains unknown. My project focuses on determining whether finch song is endogenously driven by an internal clock. I collected song data from zebra finches housed under typical light patterns (14 hours of light, 10 hours of dark) and constant light conditions. The fundamental frequency of a sample syllable was analyzed for each bout of singing and then plotted across the span of weeks. Preliminary results suggest that birds under constant light conditions take a few days to unentrain from the light cycle, then sing throughout each 24-hour day, with FF fluctuation around a baseline frequency. I hypothesize that if birdsong acoustics vary according to a circadian cycle, FF fluctuations that occur during constant light conditions are part of a regular pattern that is regulated by an internal clock. Finding that finch song is circadian has implications for understanding how a clock might connect to song system nuclei and demonstrating how complex motor behavior and learning can be influenced by time of day.

Bilinguals outperform monolinguals in tasks measuring executive functions; particularly, in tasks that measure inhibition and flexible behavior (e.g., task-switching), all of which require increased top-down control. One interpretation of this advantage in performance is that bilinguals may approach tasks in a top-down (goal-driven) manner, and given improved performance in certain tasks, top-down control is typically viewed as beneficial. Only one study has investigated the possibility that increased top-down control may result in a cost in terms of the influence on bottom-up (automatic, non-goal-driven) processing. To further explore the potential cost of top-down control on bottom-up processing, this experiment investigated patterns of semantic priming in 50 monolinguals and 50 early bilinguals across three experiments in which the amount of top-down control required varied systematically. If bottom-up processes are impaired as a function of top-down control strategies, we hypothesized that bilingual individuals, who recruit more top-down processes, will exhibit fewer baseline semantic priming effects, and that all participants will exhibit less semantic priming as the top-down requirements of the tasks increase. The lexical decision task was used in isolation to measure baseline differences in automatic, semantic priming between monolinguals and bilinguals. An additional, task-switching paradigm, in which participants either performed a lexical decision task or decided whether the first letter of a word was between A-L or M-Z was created to engender a more top-down approach. Finally, a dual task in which participants identified changes in auditory tones while making lexical decisions, was used to attempt to decrease any top-down influence on the lexical decision task. Preliminary analysis of the data suggests that priming did not change as a function of task or language group. I will discuss the implications of this research for understanding individual differences in executive functioning.

While language delay and speech impairment in individuals with Autism Spectrum Disorders (ASD) have been widely investigated, few studies have analyzed the role that non-verbal forms of communication, such as gestures, may play in augmenting impaired speech in individuals with ASD. One system that has been heavily studied, which has the potential to enhance or inhibit communication, is the Mirror Neuron System (MNS). While the MNS could serve to augment speech, the dysfunction of this system could prove detrimental to those who already possess impaired language skills. If the MNS were to be equally affected by ASD, individuals with this disorder would be unable to compensate for impairments in verbal communication with non-verbal forms of interaction. Although reduced activity in MNS areas in ASD individuals has been identified, the implications of this dysfunction remain unclear. In order to identify if the dysfunction of the MNS impairs non-verbal forms of communication, we recorded 16 typically developing (TD) adolescents and 13 ASD adolescents as they played a game of charades. We utilized charades that were not associated with speech centers, but instead have been shown to rely heavily on an intact MNS and motor cortex to mimic the action. This allowed us to identify whether reduced activation of mirror neurons impacts neural centers that serve to augment language through nonverbal means. Using video footage, two blind coders scored the quality of gestures based upon a 0-8 point scale that was unique to each gesture. Our preliminary results suggest that adolescents with ASD do not have significantly lower scores of functional gesture quality compared to TD individuals. One possible implication of these data is that other regions of the brain may compensate for MNS dysfunction and, importantly, may serve as potential therapeutic targets for strategic interventions to minimize the language impairments associated ASD.

Neurons are specialized cells that receive and relay information throughout an organism, and the compartment that inputs the signal has multi-complex structures known as dendrites. The form of the dendrite is tightly regulated to neuron function; therefore, any abnormality that alters the structure of the dendritic arbor can lead to severe defects in neuronal function. However, the mechanisms of how dendrites develop and maintain their arborization are poorly understood. One mutant allele, Acsl (Acyl-CoA synthetase long-chain), leads to a complete loss of terminal dendrites, which carries a two amino acid change that renders the gene product non-functional. Interestingly, Acsl is also associated with human X-linked mental retardation (XMR). However, to date, little is known about the signaling pathway that may be involved in this unique function of Acsl in neurons. As such, we conducted a modifier screen, which serves to identify functional modulators with genetic interaction of Acsl in maintenance of terminal dendrites. Here we report our results of funcional signaling (and/or) regulatory genes from this screen. We also conducted comparative GC/MS of the lipid profiles in both whole larval body and brains to identify the specific lipid species being affected by acsl mutation. In return, this will reveal to us more about the function and signaling pathway of Acsl in maintenance of terminal dendrites. Results from this project will lead to a greater understanding of dendrite abnormalities in neuronal development and of neurodegenerative disorders.

There has been growing scholarly attention to the fact that most global health projects/research are disproportionately focused on specific locales resulting in temporary restricted interventions. This approach is, in some significant sense a 'betrayal' of the very idea of global health. This study asks how Seattle's various global health institutions and organizations approach Global health in Kenya. I hypothesize that most global health projects promote the production of inequity, unequal and uncaring exchanges between donor institutions and the recipients. I analyze the socio-historical, economic and political histories and ties between Kenya and global health institutions in Seattle drawing on political-economy analysis and feminist care ethical analysis. I also thematically code and analyze ethnographic interviews to investigate the relationship between the responses and the main research topic. I expect to find that global health projects may not necessarily achieve their intended goals because they do not fully consider the four phases of care, which involve attentiveness, responsibility, competence and responsiveness. Understanding the factors influencing the production of unequal and uncaring exchanges in global health is essential as it will impact how global health projects should be conducted.

The cosmopolitan pennate diatom Pseudo-nitzschia is notable for production of the neurotoxin domoic acid. Recently, a virus was isolated on Pseudo-nitzschia multiseries that has a broad host range, infecting many genera of diatoms. This is contrary to previous reports of very specific host ranges amongst diatom viruses, and suggests a nested infection network whereby specialist viruses infect only the most permissive hosts, while generalist viruses can also infect hosts that are well-defended. To explore the infection patterns of Pseudo-nitzschia and its viruses, new Pseudo-nitzschia strains were isolated monthly at a coastal and estuarine location in the Pacific Northwest for one year. Over 100 new strains of Pseudo-nitzschia were identified by sequencing the ITS region. These new strains are then challenged with environmental viral communities that were sampled at each location concurrently. To date, 28 of 47 strains tested are susceptible to infection by at least one viral community. Three strains are lysed by the majority of viral communities, suggesting we have identified permissive hosts. This analysis will continue until all currently isolated strains are challenged. Seasonally, May and July contained viruses that infected the widest range of strains, suggesting either high concentration of generalist viruses in those months, or high concentration of both specialist and generalists together. Understanding the seasonal structure of these infection networks will inform future virus isolation attempts and provide insight into a key component of these diatom-virus interactions.

 The ocean is the largest and arguably the most important ecosystem on the planet. Within the ocean a successful and widespread group of algae, the diatoms, are major contributors to the global carbon cycle with primary production rates rivaling the terrestrial rainforests. Yet in many areas of the open ocean, low concentrations of bioavailable iron limit the growth and photosynthesis of diatoms and other phytoplankton. Marine phytoplankton have evolved several adaptive strategies to compensate for the scarcity of this metal. Here we present a comparative analysis of the molecular repertoire utilized by diatoms to respond to variable iron concentrations. Utilizing sequence data from over 75 diatom transcriptomes, we have identified homologues for key iron metabolism genes. We are using this data in conjunction with environmental metatranscriptomes to map the distribution of these genes in the environment. Here we will demonstrate a selection of our findings. We show that the gene coding for ferritin, the iron storage protein, is expressed in ancient and derived diatom groups and forms a monophyletic clade, sharing a common ancestor with marine cyanobacteria. Several species of diatoms co-express two unique ferritin paralogs, and these show differential transcription in the environment. We also show widespread constitutive expression of the electron transfer protein flavodoxin, which substitutes iron-using ferredoxin under iron limitation. Iron responsive Clade II flavodoxin is expressed by members of coastal and off-shore diatom assemblies. We are now able to examine these and other iron-related genes with a higher taxonomic resolution and utilize them as environmental biomarkers.

Pseudo-nitzschia is a cosmopolitan genus of marine diatoms known for its production of the neurotoxin domoic acid (DA) and resultant harmful algal blooms. The production of DA varies across species; of approximately 37 defined Pseudo-nitzschia species, at least 14 have produced DA in laboratory studies. Previous work based on ribosomal RNA sequences suggested the genus Pseudo-nitzschia could be divided into two major clades, or groups made up of an ancestor and its descendants. With the discovery of new species and identification of cryptic species complexes, the structure of these clades has eroded. We sought to integrate phylogeny, morphology and physiology of Pseudo-nitzschia, by re-examining their phylogeny, using both ribosomal LSU sequences and the rbcL gene, which encodes the large subunit of the carbon fixation enzyme, ribulose-1,5-bisphosphate carboxylase oxygenase (RuBisCO). Trees based on rbcL sequences provided higher resolution to resolve the branching orders of Pseudo-nitzschia species. By mapping physiological characteristics such as cell size, frustule morphology, pigment content and DA production onto the tree we can interpret the evolutionary history of these features and species distributions in the context of our presumed clades.

My research explores the means by which identities of “non-white” Habesha (Ethiopian and Eritrean) immigrants are negotiated through the use of media, community spaces, collectivism, and activism. As “black” immigrant subjects who do not have a longstanding historical past in the United States, Habesha face the challenges of having to re-construct and negotiate their identities within binary, black/white, American racial landscapes. To explore the ways in which ethnic-based collectivism and activism challenge stereotypical portrayals of Habeshaness and blackness which are typically cemented through media, I focus on unpacking mediated representations of Hana Alemu Williams, her death, trial, and subsequent support from the Ethiopian Community of Seattle (ECS). In short, Hana Alemu Williams was an Ethiopian child who died in 2011 from abuse, severe malnutrition, and cruelty at the hands of her white adoptive family in Sedro-Woolley Washington. Through close readings of mediated texts: news paper articles, television news broadcastings, blogs, and interviews of people from the ECS who were used as news “experts”, I will critically analyze the moments in which Habesha immigrants challenge narratives of race and identity in the American context. I hypothesize that Habesha immigrants sometimes assimilate into American constructions of race while at other moments creating counter-narratives of hybridity or exclusive ethnic-based identities like Habeshaness, or maintaining purely national identities as Ethiopian and Eritrean immigrants, in an effort to defer perceived racial stereotypes and oppression that arise with identifying as simply black or African American. Furthermore, I discuss potential steps that can be taken by Ethiopian and Eritrean immigrant communities to address these harmful and limited understandings of race and racism in America. This research enriches the existing academic literature by creating a more nuanced understanding of the Seattle Habesha community’s racial discourses in their efforts to re-imagine Habesha identities.

Humans and other primates have been in contact for the entirety of our evolution and our relationships have been complex and ever changing. Many cultures hold a position of dominance, exploitation, or power over other primates. This often results in turning them into the "Other," which allows humans to use them as they see fit. This research examines the ways in which humans relate to and perceive other primates to understand how these relationships are associated with varied human uses of them. Expanding upon the current research in ethnoprimatology, which examines the human-other primate interface, my work studies the relationships and perceptions that develop in the context of captivity. I investigate these relationships in a biomedical research facility, a zoo, and an animal sanctuary. I use observation, participant observation, semi-structured interviews, and discourse and artifact analysis to determine the human perception(s) of other primates. Qualitative data analysis will be used to discern and interpret similarities, differences, and patterns. What I expect to find from this study is that humans treat other primates as "Others" and assign them a lower status in order to justify their varied uses. This study will help us to understand our hierarchical relationships with other primates, how they allow for exploitation, entertainment, or conservation values, and what this teaches us about the construction of "human nature".

 Depictions of Our Lady of Refuge of Sinners, or La Refugiana, were among the most popular religious images produced in viceregal Mexico since the early eighteenth-century, especially in areas north of Mexico City. Although the iconography of these images did not change, the artists who produced these works adopted a variety of styles—classical, Baroque and even popular folk. It is safe to assume that there is nothing arbitrary about the production of religious devotional images; these objects surely must adhere to specific concepts of theological decorum while, at the same time, meet the religious and devotional needs of the public. By examining an array of early nineteenth-century Mexican retablos of La Refugiana, I will attempt to explain the reasons behind these distinct formal approaches and how they may have been tailored to fit the civic, theological and apotropaic needs of an ethnically diverse population. My research will closely examine how images were produced in viceregal Mexico. Additionally, I will consider how stylistic variety may have been the result of innovation, experimentation or creative competition in reaction to European models. To this aim, I will also explore the hybridization between old and New World artistic traditions, the didactic use of images by the mendicant orders, the use of religious images in private versus public devotional use, as well as the political climate of the time. While my final research paper will not discuss all of these elements in great detail, they will be useful to gain a better understanding of why images of La Refugiana manifested such a wide variety of styles and place them within a much more decisive cultural context.

As our understanding of the genetic basis for the pathophysiology of many diseases has broadened, gene therapy, which is the delivery of genetic material into cells in order to supplement or alter defective genes, is being explored as a potential treatment option. Despite its promise, no gene therapies have been approved for clinical use due to the lack of safe and effective vectors. There are many obstacles that must be overcome in order to successfully transfect a cell with exogenous DNA. First, the vector-DNA complex must navigate through the extracellular environment and be uptaken into the target cell. Then, the genetic material must achieve endosomal escape, be released from the complex, and then translocate into the nucleus where it can be transcribed and translated into functional or therapeutic proteins. In the Pun Lab, we previously synthesized a block-statistical copolymer comprised of different hydrophilic and hydrophobic segments aimed at providing a plethora of functionalities to the formed polyplexes. Due to this polymer’s unique architecture, it exhibits transfection efficiencies higher than branched polyethyleneimine, the gold standard for nonviral gene delivery, but still fails to reach the same level of transfection efficiency as seen with viral vectors. In this project, two additional modifications will be made to the copolymer and a library of well-defined polyplexes with varying formulations and structures will be synthesized and evaluated in vitro and in vivo. These modifications, guanidinylation and conjugation of a targeting peptide, aim to increase uptake into cells through electrostatic interactions and increase localization to the target cell type. From these studies, the ideal method to incorporate both modifications into one system to improve transfection efficiency and the structure-function effects on transfection efficiency will be evaluated.

Bushmeat poaching -- and subsequent consumption -- presents the foremost threat to wildlife conservation in East Africa. To assess its social, ecological and economic magnitude, I interviewed a representative sample of the local population in the Lake Manyara area of northern Tanzania. Illegal poaching was evaluated based on 16 structured interviews of poachers from distinct hunting groups. Both availability and consumption of bushmeat were evaluated based on 185 structured interviews of ethnically diverse local households. Some 38 percent of households admitted to consuming bushmeat on a semi-regular basis. Conservative interpretations of numbers of wildlife species poached show rapid depletion due to illegal hunting. Swift implementation of capacity-building programs must occur to provide poachers with alternative income sources and ensure more caution in factors influencing consumption, education programs emphasizing the importance of conservation for groups with high consumption levels, and strategic enforcement patrols in Community Areas frequented by poachers.

Thin-film solar cells can address the cost barrier of solar power by virtue of less material usage and more efficient manufacturing processes like roll-to-roll printing. The thin-film material Cu/Zn/Sn/Se (CZTS) is of particular interest because it is composed of earth-abundant elements; however, the current record for CZTS device efficiency is 12.6%, which is far from the 20% efficiency that is needed to be commercially competitive. Low CZTS device efficiencies have been linked to low open-circuit voltages (Voc), which are likely due to high charge-carrier recombination. Recombination can be increased by irregularities in crystal structure and composition known as defects. In this project, different microscopies will be used to study the defects present at the interfaces of a working CZTS photovoltaic device in relation to the device's V_oc. The interfaces of concern include those between different material layers and those between CZTS crystal grains, i.e. grain boundaries. A variety of scanning probe microscopies (SPM) will be used to map local electronic properties at these interfaces, relating position on a device cross-section to current and voltage characteristics. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) will be used to correlate these electronic properties with CZTS device structure and composition. In making these correlations between SEM, EDS, and SPM data we hope to better understand the origins of Voc loss in CZTS devices and, in turn, inform more effective CZTS cell fabrication. Thus far, we have acquired SPM, SEM, and EDS images that display the distinct layers of the device cross-section. Further optimization of sample preparation is required to achieve both resolution of grain boundaries and a sample surface that is smooth enough for SPM to obtain reliable electronic data.

Transcranial ultrasound can alter brain function transiently and nondestructively, offering a new tool to study brain function and inform future therapies. Previous research on neuromodulation implemented pulsed low frequency (250–700 kHz) ultrasound with spatial peak temporal average intensities (ISPTA) of 0.1–10 W/cm2. That work used transducers that either insonified relatively large volumes of mouse brain (several mL) with relatively low frequency ultrasound and produced bilateral motor responses, or relatively small volumes of brain (on the order of 0.06 mL) with relatively high frequency ultrasound that produced unilateral motor responses. Our work seeks to increase anatomical specificity to neuromodulation with modulated focused ultrasound (mFU). Here, ‘modulated’ means modifying a focused 2-MHz carrier signal dynamically with a 500-kHz signal as in vibro-acoustography, thereby creating a low frequency, but small volume (approximately 0.015 mL) source of neuromodulation. Application of transcranial mFU to lightly anesthetized mice produced various motor movements with high spatial selectivity (on the order of 1 mm) that scaled with the temporal average ultrasound intensity. Alone, mFU and focused ultrasound (FUS) each induced motor activity, including unilateral motions, though anatomical location and type of motion varied. Of interest is the exploration of potential research and clinical applications for targeted, transcranial neuromodulation created by modulated focused ultrasound, especially mFU’s ability to produce compact sources of ultrasound at the very low frequencies (10–100s of Hertz) that are commensurate with the natural frequencies of the brain. Currently, I am working to incorporate mFU with electroencephalography (EEG) to aid researchers and clinicians in localizing neural activity. Theoretically, the vibro-acoustography paradigm allows a small volume of neural tissue to be tagged with a specific difference frequency; EEG will determine the origin of this signal.

Integration of information over time is essential in our everyday lives. But research in many domains including memory recall, decision-making, language, and motor control shows that the order in which to-be-integrated information arrives strongly affects how it’s processed. A recent set of experiments has extended these findings into the perceptual domain by showing that when estimating the mean position of a group of serially-presented dots, subjects weighted the earliest information presented much more than the rest. However, it’s an open question whether this “primacy” effect is an artifact of task strategy, or if it’s an intrinsic, unchangeable property of integrating serially-presented visual information. Do we always weight earlier visual information over later information? Feedback has been shown to effectively change behavior in a wide variety of psychological contexts, so we conducted two experiments to determine whether the primacy effect was modifiable or not. In both experiments, subjects were shown ten serially-presented white dots that varied in location and were asked to estimate the center of the dots. In Experiment 1, we provided subjects with feedback after each trial indicating their response and the actual, correct center of the dots. In Experiment 2, we attempted to further facilitate even weighting by presenting the dots in a predictable pattern, still using the same trial-by-trial feedback as before. We analyzed our data by fitting a weighted-average model to our subjects’ data, which allowed us to estimate the mathematical weight that each subject applied to each of the ten dots. The weights we obtained showed that feedback did reduce the magnitude of the primacy effect, but subjects still showed significantly larger weighting of earlier presented information. This suggests that heavy reliance on earlier visual information, though susceptible to forces like feedback, may be an intrinsic property of how humans integrate visual information over time.

Localized surface plasmon resonances (LSPRs) can be described as oscillations of large electron densities. Traditionally observed in metals, LSPRs have recently been observed in semiconductors, and have gained more attention because of their tunability over a wide range of energies. Additionally, semiconductor LSPRs could offer a cheaper alternative to plasmonic applications. Here, we aim to observe the effect of band-gap engineering on LSPRs in zinc oxide semiconductor nanocrystals by incorporating Cd^{2 +} and Mg^{2 +} ions into zinc oxide host lattices. Cd^{2 +} -and Mg^{2 +} -doped zinc oxides of different molar dopant ratios are synthesized via base-initiated hydrolysis and air-free hot injection synthesis. The size and structure of the nanocrystals are characterized via transmission electron microscope (TEM), absorption and photoluminescence. The molar dopant ratios of the samples are determined analytically via inductively coupled plasma atomic emission spectroscopy. In order to observe LSPRs in semiconductors, conduction-band electrons are added to the semiconductor nanocrystals via photochemical reduction to give them metallic-like properties. The number of electrons accumulated can be measured by titrating the samples with mild oxidants such as decamethylferrocenium. The LSPRs in the zinc oxide nanocrystals are studied by electron paramagnetic resonance spectroscopy (EPR) and infrared (IR) spectroscopies. In combination with absorption and photoluminescence, EPR is used to measure the conduction-band, valence-band and overall band-gap energies. Using IR spectroscopy, we study how these energies influence the LSPR energies.

Spinal cord injury (SCI) affects approximately 12,000 new individuals in the United States annually and is a significant source of paralysis. Often caused by motor vehicle accidents or severe trauma, chronic SCI is increasingly a target of stem cell therapy as a means to regenerate locomotor function. Human induced pluripotent stem cells (hiPSCs) have the capability of regenerating neuronal components such as astrocytes and glia, which have been proven to aid in functional recovery of paralysis. We performed a pre-clinical study to determine the effectiveness of hiPSC transplantation on cervical SCI in rats. Injury was performed on the fourth cervical vertebrae followed by transplantation of IMR90 fibroblasts at four weeks post-injury. The forelimb reaching task (FRT) was used to analyze forelimb function during the pre-injury, post-injury and post-transplant periods. FRT data showed a recovery in performance at eight weeks after transplantation followed by diminishing forelimb function that became comparable to the control group. Upon histological analysis, neurally derived masses were discovered in the site of IMR90 fibroblast transplantation. These masses indicate that previously unobserved challenges may occur during the clinical treatment of SCI that may result in a lack of improvement in locomotor function.

The 21st century has seen the emergence and re-emergence of novel infectious diseases. Following in the footsteps of its communicable predecessors, the recent emergence in Saudi Arabia of a SARS-like novel coronavirus, or Middle East respiratory syndrome (MERS-CoV), since 2012 has weaved narratives of globally interdependent economic, political, and social intimacies. I will examine the contrasting narratives that reflect investigations and responses to this novel threat from Middle Eastern, European, and North American media networks, the WHO, the global biomedical community, and the Saudi Arabian Ministry of Health through several intersecting discourses: intellectual property rights and viral sovereignty; the deliberation on the taxonomy of the novel coronavirus; and geopolitical differences in information sharing and biosecurity in the context of emergent 21st century epidemics. Using Priscilla Wald’s concept of outbreak narratives and the imaginative hold of myths as a framework, I will explore how the stories on the global effort to investigate and respond to the MERS outbreaks continue to be revealed, repackaged, and transformed as experts around the world scramble to uncover its epidemiological pathways. I argue that the consideration of these counter-narratives are critical for rethinking underlying, potentially harmful, factors beyond dominant epidemiological and biomedical discourses surrounding the MERS epidemics. Such considerations may serve as a microcosm for biopolitical barriers in the response to past, present, and future emergent diseases. These counter-narratives should be regarded in light of uncertainties that still cloud the etiology and transmission of the virus which has since infected 243 people and claimed 93 lives in 11 countries in Europe, the Middle East, and Southeast Asia.

This was a study of the prevalence of post stroke fatigue in stroke survivors who participated in the larger Living Well With Stroke study in the Puget Sound area of Washington. Post stroke fatigue can delay progress of physical therapy, and interfere with activities of daily living. Within four months of a stroke, the Living Well With Stroke team approached people who had been hospitalized with a stroke to screen for eligibility to be part of the study. Questions were asked that screened for depression and fatigue. Using SPSS (Statistical Package used for Statistical analysis) we have examined screening data of the 414 patients from the larger study. We have examined the correlation of fatigue to the presence of depression, age, gender, type of stroke, severity of stroke and other variables that are in the literature. Based on existing literature, we anticipate that the presence and severity of fatigue will be correlated with age, gender, severity of stroke, depression, as well as socio-economic status. Using SPSS, data has been interpreted by the use graphs, and tables to best show the correlation between post stroke fatigue and the demographics I have just listed previously. By understanding these correlations, treatment options could be better improved or be tailored specifically to these patients.

Phonic Earth connects communities of the modern world through music, a language that is understood globally on emotional and physical levels. Melody, voice, instruments and timbre hold history within them and also redefine and transform our cultures throughout time. Through music we are able to understand each other’s communities on intimate and transcendent levels. Phonic Earth traveled to Puerto Rico, The Faroe Islands and the Northwest to produce films that depicted social and political histories through musical contexts in different regions. Each location reveals unique cultural stories and information. In Puerto Rico we investigated how the diverse blending of eighteenth century Afro-Caribbean, European and Indigenous groups led to the creation of the musical genres bomba and plena which influence Salsa and Hip Hop. Phonic Earth explored the relationships of music to land, culture and emotion through Faroese contexts. The Kingo Gregorian chant sung in the Faroe Islands preserves the history of French, Norwegian and other North American countries where this historical music has disappeared. The final part of Phonic Earth’s cinematic project, will be filmed inc collaboration with NW Native American/Indigenous communities to document the influence of historical music and storytelling on current Native American music culture. Each community in the world holds a complex identity made up of the individuals of the region. Phonic Earth focuses on empowering these individuals with resources to tell their stories, showcase their music and document local events through film. While the world is made up of an infinite amount of faces, backgrounds and cultures, music is a familiar medium that people connect to on a global scale. It is our aim to connect the viewer to the community on an intimate level which is why Phonic earth looks at the world through sound.

The pancreatic islet β-cell secretes insulin in response to nutrients such as glucose. In type 2 diabetes, insulin secretion by β-cells is impaired, causing hyperglycemia. Our group investigates this impairment, with the goal of identifying and understanding the underlying mechanisms. Pancreatic islets contain an extensive capillary network, including endothelial cells, which produce soluble factors that may modulate β-cell function. Specifically, our group has shown that media from islet endothelial cells cultured under control conditions (5.5 mM glucose) and subsequently incubated with islets enhances insulin secretion from those islets. In contrast, media from islet endothelial cells cultured in diabetic conditions (high glucose; 25 mM) shows no effect on insulin secretion. Thus, we hypothesize that islet endothelial cells normally secrete paracrine factor(s) – signaling molecules produced by one cell that cause particular reactions in nearby cells – that enhance glucose-stimulated insulin release but that in diabetes, production of these paracrine factor(s) is reduced. The goal of this project is to identify one or more of these paracrine factors. We cultured islet endothelial cells under control and diabetic conditions. mRNA was extracted and sent for whole transcriptome analysis (RNA-Seq), creating an expression profile showing the expression amplitude for each gene. Analysis of RNA-Seq data revealed patterns of differential gene expression between control and diabetic samples. Changes in expression for genes of interest identified by RNA-Seq are being verified by quantitative real time PCR (qPCR). Subsequent protein analysis via ELISA or western blot will confirm the RNA-Seq and qPCR data. Viral vectors or siRNA will be used to either overexpress or silence respectively the gene(s) of interest in islet endothelial cells. Media will be collected from these cells and used on islets to determine its effect on glucose-stimulated insulin release. This project should reveal novel mechanisms by which islet endothelial cells influence insulin release.

This research focuses on optimizing the functionalization of cationic gold nanoparticles for use in plasmonic emulsions for treatment of Peripheral Artery Disease. This condition affects approximately 12 million people in United States. Plasmonic emulsions are prepared by self-assembly through the adsorption of functionalized gold nanoparticles in deionized water on the surface of perfluorohexane oil droplets. When irradiated with a near infrared laser, the emulsion is vaporized creating a mechanical pressure wave that can be used in breaking up plaque formation in the arteries. Cationic gold nanoparticles are introduced to produce the emulsion due to opposite charge attraction between the nanoparticles and the anionic perfluorohexane-water interface. In this research, a method of synthesizing cationic gold nanoparticles is explored. First, the gold synthesis is performed in a biphasic system consisting of toluene and water. Once the particle synthesis is complete, mercaptoundecyl-trimethylammonium bromide is added to the gold nanoparticles to form a cationic thiol monolayer over the gold nanoparticles. The cationic gold nanoparticles are then separated by centrifugation and the supernatant is discharged. The nanoparticles are dried and stored until use in emulsification. Preliminary results showed that the average diameter of cationic gold nanoparticles ranged from 4nm to 6nm. The dried nanoparticles were also found to be redispersible in water or alcohol, i.e, methanol and ethanol. These advances create a pathway for the study of spontaneous emulsification with cationic gold nanoparticles and for their use in medical technologies. In future work, the particle size distribution needs to be narrowed for use in plasmonic emulsion operated in vivo where renal clearance requires sizes less than 5.5 nm.

 Using mice as an animal model, we are investigating the possibility that fetal ultrasound exposure in utero has contributed to the observed dramatic increase in the number of cases of autism. A leading hypothesis suggests that autism may arise through a combination of genetic predisposition and exposure to certain environmental factors during a vulnerable period of neuro-development in utero. To test this hypothesis we exposed mice to diagnostic ultrasound in utero during a specific developmental time window to check for possible post-birth induction of autistic-like behavior and neuro-anatomy. Specifically, we exposed anesthetized pregnant mice to ultrasound for 30 minutes on embryonic day 12. When mice pups were three weeks of age, we used a variety of behavioral tests to assay for autistic-like characteristics. Additionally, we performed histology on the mouse brains, analyzing them for neuroanatomical characteristics of autism. Our published results show significant social behavioral differences between ultrasound-exposed and sham-exposed mice. Also, preliminary analysis of the brains found decreased minicolumnar width and variability in the ultrasound-exposed group relative to the sham-exposed group. Both the behavioral and neuroanatomical results are consistent with the hypothesis that diagnostic ultrasound exposure in utero represents a potential risk factor for autism. Future research will target study of possible bio-physical mechanisms that may underlie our observations. Specifically, we intend to tag newborn cortical neurons via injection of BrdU in an attempt to quantify ultrasound’s effect on the migration of these neurons, anticipating a relationship between dose of ultrasound and extent of disruption of the cortical layers within the brains of ultrasound-exposed mice.

Diatoms are an important taxon of phytoplankton that contribute to both freshwater and marine ecosystem function. For example, marine diatoms are responsible for about 14% of global primary production. My research is focused on determining the ability of these algae to regulate the production of chlorophyll a- the core pigment component of photosynthetic complexes. The enzyme light-dependent NADPH protochlorophyllide oxidoreductase (POR) is a key regulator of chlorophyll synthesis. Whereas most organisms have just one POR enzyme, diatoms have two (POR1 and POR2). The goals of this project are to understand how these enzymes are metabolically different from one another in: (a.) their enzymology and (b.) their regulation at the transcriptional and posttranslational levels. To this end, plasmids were constructed encoding the cDNAs of the por genes, adding N-terminal histidine tags to assist in affinity purification. E. coli, transformed with these plasmids, was induced to express the proteins; harvested, and lysed. Recovered POR1 and POR2 proteins were purified from the lysate by affinity chromatography. Antibodies raised against these proteins were used in Western blot protein identification and quantitation of the targeted proteins. Preliminary experiments demonstrate good affinity of generated antibodies for POR proteins, and indicate that POR 2 may be post-transcriptionally truncated. Developing an understanding of chlorophyll metabolism in diatoms has not only ecological implication, but also could prove important in commercial aspects of biofuel development- increasingly important issues driven by changing ocean conditions and the critical need for generating alternative fuel sources. Determining the properties of these enzymes and their regulation is just one step towards understanding the successful productivity of diatoms. Further studies may be required to determine if there are additional regulatory pathways and enzymes that are critical in photosynthetic production.

Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hematopoietic progenitor cells, also known as “blasts,” that fail to both differentiate normally and properly respond to normal proliferation regulators. The consequences include possible organ infiltration as well as impairment of normal blood cell production that can result in fatal infection or bleeding. Retention of leukemia cells within the bone marrow microenvironment enables survival from chemotherapy treatment. This retention is largely mediated by surface membrane receptors, such as the chemokine receptor CXCR4. CXCR4 facilitates cellular migration towards high concentrations of the stromal derived cell factor CXCL12 (SDF-1), a chemokine that is released from bone marrow stromal cells. A CXCR4 small molecule inhibitor, plerixafor, has been shown to improve response to chemotherapy treatment in murine leukemia models, by disrupting interactions with the microenvironment, releasing leukemia cells into the bloodstream, and conferring sensitivity to chemotherapy. Our objective was to assess the functionality of an anti-CXCR4 antibody, BMS-936564, to similarly enhance chemotherapy cytotoxicity. We assayed CXCR4 expression by the leukemia blasts and stem cells, observed the time course of mobilization of leukemic blasts and stem cells, and examined the induction of programmed cell death (apoptosis) in patient samples through analysis for Annexin V expression. Mobilization of leukemia blasts and stem cells was monitored by flow cytometry. We found a significant correlation between CXCR4 expression by leukemic blasts and patient response to therapy, with high CXCR4 expression (≥20%) linked to complete remission (p<0.05). It is intuitive that the antibody to CXCR4 would require CXCR4 to be expressed by blasts. These data provide a method to predict outcomes for patients undergoing combination treatment with anti-CXCR4 antibody and chemotherapy. Our ultimate objective is to overcome adhesion mediated chemotherapy resistance in order to improve outcomes for patients with AML.

Binary chromophore systems contribute to more favorable intermolecular interactions and can significantly enhance electro-optic (EO) activity of EO materials, which have potential applications for telecommunications. Optimization of EO activity of binary chromophore systems consisting of dendrimer host (i.e. PSLD-33) and guest chromophore (i.e. FTC) will be achieved by determining the ideal host to guest concentration ratio. Synthetic schemes for known dendritic systems were proposed and synthesis is currently underway. Linear optical properties, including max absorbance (λmax) and molar absorptivity (ε), of materials in solutions with chloroform will be characterized using UV-vis spectroscopy. These properties have implications in chromophore packing density, which up to a thresh hold can improve EO activity. Additional steps include making films of the materials. EO activity of the materials will be characterized using the Teng-Man method, which has proven to be a convenient way to determine the EO coefficient (r33) in the Dalton lab over the past ten years.

Conservatively estimated, about one in every ten youth experiences severe depression during adolescence. This is concerning because depression is known to be responsive to prevention as well as to early interventions when accessible to youth. Those who experience early onset depression are at increased risk for other negative outcomes including substance use and suicidal behavior. The effects of depression carry over into young adulthood and are linked with psychiatric and medical hospitalizations, suicidal behavior, and lower educational accomplishments. Youth identified as academically at-risk are particularly susceptible to experiencing depression as well as other co-occurring health risks. Research reveals that family processes serve as a protective influence on the development of depression. Few studies, however, have examined the role of familial risk and protective factors in the development or progression of depression for academically at-risk youth. This research was designed to investigate patterns of depression across time and the influence of family-level risk (family conflict, authoritative parenting style and parental substance use) and protective factors (parental involvement/monitoring and family support) on these patterns. These factors will be compared in terms of their strength of influence on depression. This predictive study is based on survey data collected from a randomly selected, ethnically diverse sample (n=149) of students from two Washington State school districts who were subsequently followed from middle into high school (8th-10th grade). The sample includes youth randomly assigned to the control condition in a school-based prevention study. Depression is expected to be positively associated with family risk factors and negatively associated with protective factors. We anticipate distinguishing differences in the relative influence of family factors on adolescent depression. This detailed examination of key factors influencing adolescent depression will contribute to designing new interventions that are more clearly and specifically targeted, and thus more meaningful, for vulnerable youth and their families.

The purpose of this study is to improve biomass processes that utilize renewable feedstock to produce value added chemicals. While much research has been conducted into biomass processing over the last decade, the conversion to small molecules for production of fuels and value-added chemicals is not economically viable and must be improved. Chemical processing is hindered by the robust structure, composed of cellulose and lignin and its resistance to breakdown, which results in expensive treatment methods. In the last several years, ionic liquids have shown by experiment to dissolve recalcitrant biomass allowing for more efficient chemical conversion. Ionic liquids are a class of solvents composed of ions that are liquid at near room temperature. There are a countless number of solvents considered ionic liquids and many have potential to improve biomass processing. The optimal ionic liquid is unknown, and the determination of one is not inspired by molecular scale design principles. My project focuses on providing fundamental knowledge to understand the dissolution of biomass in ionic liquids by using molecular dynamics (MD) in combination with enhanced sampling techniques. Enhanced sampling allows the efficient exploration of the free energy landscape of a system by modifying MD algorithms and without such methods, MD cannot reasonably make conclusions about the effect of ionic liquids. The enhanced sampling method that I employed in this work is Parallel Tempering Metadynamics which is used to explore the conformational free energy of cellulose oligomers. The conformational free energy of short cellulose chains can provide insight to the mechanism of dissolution and eventually optimize biomass processing.

Diagnosing infectious disease in the developing world continues to be a challenge due to the lack of infrastructure and resources needed to conduct state-of-the-art methods of nucleic acid detection. Surface enhanced Raman spectroscopy (SERS) is a potential alternative to current point-of-care (POC) nucleic acid tests because it could offer similar sensitivity. However, current SERS substrates that possess the reproducibility and stability needed for translation to POC applications are too expensive. Electrospinning gold nanorods (AuNR) into polymeric nanofibers was employed as a method to reduce the cost, improve reproducibility and lengthen shelf life of SERS substrates for POC applications. Electrospinning also offers a facile method of aligning anisotropic metallic nanoparticles, which can improve SERS sensitivity over non-aligned particles. AuNR size and dimension was varied alongside fiber diameter to optimize SERS enhancement. For the detection of target nucleic acid (or oligonucleotide), a sandwich-like design was used: Oligonucleotides complementary to the target strand were conjugated to SERS active fibers in a 96 well plate format, allowing for multiplex detection with different probes. After the sample was administered, probe oligonucleotides conjugated to a Raman reporter molecule were washed over the SERS substrate to complex with the bound target strand before Raman testing. Electrospinning produced homogenous fiber meshes with uniformly deposited AuNRs to create reproducible enhancement across the substrate. In addition, the SERS fibers showed prolonged shelf-life suggesting that the polymeric fibers offer stability for AuNRs. Successful conjugation of probe oligonucleotides to the polymer mesh is shown. Initial experiments showed presence of signature Raman spectra associated with the probe molecule, indicating specific binding of the target strand. However, additional experiments are necessary to improve sensitivity. Creation of this technology provides the initial framework that electrospun fibers can offer a mode of translation of SERS to sensitive detection of biologics for POC diagnostic applications.

There has been a lot of interest in fermentation processes utilizing monomeric sugars in lignocellulosic biomass to acetic acid product: a key precursor for many industrial applications such as the production of jet fuel.  The selected microorganism for this study is Moorella thermoacetica (Clostridium thermoaceticum). This strain is a thermophilic obligate anaerobe and can homoferment glucose and xylose to acetic acid using CO₂ as an electron acceptor at temperatures between 55-60°C and pH 6.5-6.8.  This study investigates the production of acetic acid by this homoacetogen from a 1:1 mixture of glucose and xylose, the two major monomeric sugars in lingnocellulosic biomass. The research is a necessary step to further study of fermenting a sugar model of lignocellulosic hydrolysates and hydrolysates. Additionally it facilitates application of Raman spectroscopy as quantitative measurements in real-time during fermentation.  This is unlike the traditional way of using High performance liquid chromatography (HPLC) which is used in this study. Compared with current analytical techniques, Raman Spectroscopy (RS) allows analytes in samples to be measured simultaneously. Utilization of xylose and glucose as the main sugars for producing lignocellulosic acetic acid proves useful as a foundation for building industrial applications such as jet fuel through bioconversion of lignocellulosic biomass.

Moving to a retirement community is a major life change, and may either be precipitated by or cause changes in health status. Different surroundings within a retirement community might also influence self-assessment of health.  We hypothesized that moving into a retirement community would, after controlling for relevant sociodemographic and health-related variables, be associated with a general decline in self-rated health.

 We analyzed data from 58,272 participants in Cohort 3 of the Medicare Health Outcome Survey.  Individuals answered questions regarding living status and health at baseline (2002) and two years later (2004). The primary outcome was change in self-rated health over the two-year period.  We developed linear regression models for change in self-rated health: Model 1 adjusted for sociodemographic characteristics, and Model 2 adjusted for changes in health as well.

 2,520 (4.4%) individuals had moved into retirement communities at follow-up. There were no substantial differences in the mean change in self-rated health between those who moved and those who did not.  In neither regression model was movement into retirement communities significantly associated with changes in self-rated health.  In an analysis stratified by self-rated health, and adjusting for all covariates, those with the best self-rated health (Excellent) had a significant decline in self-rated health during the move to a retirement community. All other groups had neither improvement nor decline.

 Independent of accounting for changes in health, there was no significant global change in self-rated health when older adults moved.  Those with Excellent self-rated health experienced a slight decline in self-rated health during the move, but those with less than Excellent baseline self-rated health did not experience a significant improvement, which argues against a social comparison aspect on health status.  There was no evidence that moving into a retirement community had any consistent consequences for individuals’ self-perceptions of health.

Nucleic acid amplification tests (NAATs) performed in the laboratory are the gold standard for pathogen detection due to single copy sensitivity, and could be a useful tool for widespread diagnostics in a global health setting. Unfortunately these assays tend to be expensive and complex, but new developments in isothermal NAATs will allow for cheaper, simpler diagnostics to be possible. Another problem is that current NAATs require a preparation step of cell lysis to release DNA, which traditionally requires bench top equipment or harsh chemicals that can interfere with the assay. My research addresses this barrier in the diagnostic ability of NAATs through development of a low-cost, cell phone based point-of-care device capable of efficiently lysing cells in through mechanical agitation. By placing a sample tube with beads and a magnet into a coil of wire and using a portable audio device to play an audio signal that feeds power through said coil, the alternating magnetic field produced in the coil spins the magnet and agitates the beads. The spinning of the magnet also produces an alternating magnetic field of its own that can be used as real-time feedback. Thus far, experiment results have had moderate variability, potentially because they are carried out with a live model organism, Staphylococcus Epidermidis: a common and moderately difficult pathogen to lyse. Conventional NAATs are used to measure success of this new methodology, and results so far have shown up to 60% efficiency from the experimental device compared to a bench top standard. This device may also be capable of DNA shearing, where larger DNA strands are broken into smaller pieces, but more research is needed to confirm and quantify the process. Additional research will also look into developing a theoretical model for lysis, isolating potential sources of variability, and reducing negative control background noise.

Vascular calcification, the accumulation of calcium-phosphate salts in blood vessels, is a common complication associated with atherosclerosis and type II diabetes mellitus (T2DM). We have shown that reprogramming of vascular smooth muscle cells (SMCs) into osteochondrogenic cells is important in T2DM vascular calcification, and endothelin-1 (ET1) and its type A receptor (ETA) were found in the reprogrammed SMCs. Along with the in vitro study that showed a substantial inhibition of the high glucose-induced SMC calcification upon ETA antagonism, we hypothesize that signaling through ET1 and ETA may play an important role in ectopic calcification of atherosclerotic blood vessels of T2DM. To test this hypothesis, we fed low-density-lipoprotein receptor knockout (LDLr-/-) mice with a customized diet for 18-24 weeks to induce T2DM, atherosclerosis, and vascular calcification. Upon 5 weeks diet fed, LDLr-/- mice developed hyperglycemia with no detectable atherosclerosis and vascular cartilaginous metaplasia and calcification. Half of these mice were then treated with an ETA antagonist, atrasentan, to inhibit ET1-ETA signaling. Mice were terminated at 18 weeks under the diet for histological analysis and 24 weeks under the diet for quantification of vascular calcification. We found that atrasentan significantly reduced fasted blood glucose levels of the T2DM mice but not affecting their body weight. Surprisingly, quantitative analysis showed no difference of calcium amounts in aortic arches between the treated and untreated groups. We are currently in the process of analyzing the lesion sizes of atherosclerosis, cartilaginous metaplasia and calcification of 18-week diet-fed mice via morphometric analysis to determine whether atrasentan affects vascular calcification at an earlier time point and whether vascular calcification is correlated with atherosclerotic lesion size. Finally, our finding of ETA antagonism in the control of hyperglycemia provides a new therapeutic role of atrasentan in improving T2DM, which may be beneficial in alleviating the hyperglycemia-related complication.

Maltreatment occurring early in life has been shown to cause life-long emotional and physical problems. The topic of Infant and Toddler Mental Health (ITMH) is therefore important in ensuring that infants and toddlers develop into healthy, well-adjusted children and adults. Properly trained nurses can make an immense impact in recognizing and encouraging relational health for this age group. The problem is that there is a gap in the baccalaureate nursing curriculum in regards to training nurses to recognize concepts of ITMH, subsequently affecting the way nurses are able to work with children ages 0-3 and their caregivers. This BSN honors project addressed the question: what are the key ITMH principles and concepts that should be included in baccalaureate nursing curriculum? Semi-structured interviews were conducted with 2-5 Infant Mental Health Specialists from a variety of nursing backgrounds with open-ended questions about ITMH in the context of BSN curriculum. Data from the interviews was analyzed to identify themes, which comprised the essential concepts of ITMH to be included in BSN curriculum. Interviewees were notified of the identified concepts so they may endorse the results and a final literature review was conducted for validation. In addition, a survey of UW BSN nursing students, and new pediatric nurses with less than one year of experience at Seattle Children’s Hospital, was conducted to gauge their knowledge of ITMH concepts. The survey featured a short video depicting a relational health challenge followed by an opportunity for respondents to provide open-ended written reflections. Survey results were analyzed to determine which ITMH concepts the surveyees recognize and where BSN curriculum could be strengthened. The results of this two-part research project is being used to suggest potential improvements to nursing curricula, which in turn will improve the quality of life of infants, toddlers and their families.

Thermosensitive hydrogels have been actively investigated as a potential approach to preventing the recurrence of tumors after surgery. However, current hydrogels remain limited by their low drug retention rate and non-degradability, preventing their use in neural applications. Using a trifunctional dibromomaleimide-alkyne based cross linker, this project aims to synthesize a thermosensitive, biodegradable polyethylene glycol (PEG) hydrogel for the delivery of anti-tumor drugs. The crosslinker is synthesized through condensation of dibromomaleic anhydride with propargylamine and substitution of bromine groups with cysteamine. Our trifunctional crosslinker will provide the following properties: (a) crosslinking of two thermosensitive, PEG based polymers, (b) reducible to allow for triggered degradation and (c) site for biologic conjugation by click chemistry. With the site for biologic conjugation, we will be able to physically attach the drug to the gel and make drug release dependent on the more sustained gel degradation rather than passive diffusion. The liquid, thermosensitive gel will be able to fully fill the neural cavity after tumor removal and release a drug over a sustained period of time. Preliminary synthesis of crosslinker using cysteamine shows the fluorescent color indicative of substituted maleimide in addition to active amine reactivity. Initial crosslinking of thermosensitive polymers indicate an increase in hydrophillicity and swelling with increased temperature. Future experiments will include increasing length of crosslinker arms with PEG spacers for more effective linking and attaching a biomolecule to the alkyne group of the crosslinker. The toxicity and release profile of the crosslinked polymers will be characterized to retune the polymers to create a hydrogel with high localization and minimal toxicity.

The majority of the world’s population resides in the developing world where infectious diseases are the leading cause of mortality and morbidity. Due to the lack of affordable and accurate diagnostic tests in low-resource settings, proper treatment of patients with infectious diseases such as malaria, HIV, and tuberculosis is greatly limited. As a result, there is an urgent need for point of care (POC) diagnostic tools targeted for low-resource settings that are inexpensive, rapid, portable, accurate, and require little to no training to operate. Paper-based diagnostic tests are portable and low-cost, and have shown promise for POC diagnostics appropriate for the developing world. The Yager Laboratory is currently developing a paper-based POC diagnostic platform for methicillin-resistant Staphylococcus aureus (MRSA) that utilizes an isothermal strand displacement amplification (iSDA) technique. The amplification method operates at a constant temperature and uses a mutant restriction endonuclease that cleaves only one strand of DNA, which is then displaced by a strand displacing DNA polymerase. While the incorporation of iSDA in the POC platform has been promising, it has been challenging to optimize performance in the paper matrix without a full understanding of its operation. The purpose of this investigation is to develop a kinetic model for iSDA. The model currently considers the major steps associated with the amplification technique and incorporates kinetic rate constants that have been selected from other published studies. Next, simulation results for various conditions will be compared to experimental results to validate the developed model. A successful kinetic model will provide a better understanding of the iSDA method and should enable optimizing the amplification technique. Ultimately, the information produced from this project could be used to improve paper-based POC devices that utilize iSDA technology.

Women in the US are at risk for sexually transmitted infections (STIs) including HIV/AIDS when they engage in sexual risk behaviors (SRB), especially failure to use a condom during sexual intercourse. Women face unique pressures when the decision whether or not to have protected sex is made, and deal with these pressures using a variety of coping strategies. This ongoing study is designed to investigate the hypothesis that women who use coping strategies based on avoidance (e.g., escaping, forgetting, ignoring stressors) in their everyday lives are more likely to have sex without a condom. The study also examines the hypothesis that women who generally use coping strategies based on problem solving (e.g., confronting, planning for, and working to resolve stressors) are less likely to have sex without a condom. We recruited women from the University of Washington Psychology Department’s Online Subjects Pool. Data have been collected from 327 women during fall 2013 and winter 2014 quarters. Participants completed an online survey including a measure of coping strategies (i.e., Coping Strategy Indicator), read a hypothetical sexual scenario, and responded to questions about their intentions to engage in unprotected sex. Data were analyzed using linear regressions and we predicted a relationship between coping strategies and intention to use a condom. We predicted that those who reported using more avoidance coping strategies would be more likely to have unprotected sex, and those who reported using more problem solving coping strategies would be less likely to have unprotected sex. If a relationship between coping strategy and failure to use a condom is established, then interventions focused on teaching new coping strategies could be implemented to help decrease sexual risk behaviors and increase women’s sexual health.

Targeted Tutoring is a program designed by our writing center to support English language learners in reading- and writing-intensive courses. The program was first piloted in 2010-2011 in response to students’ requests and to provide a space to encourage peer conversation. Targeted Tutoring is currently offered for courses in departments including English, Philosophy, International Studies, and Political Science. In Targeted Tutoring, three to five students meet for weekly sessions in which the tutor facilitates peer discussion. Group tutoring sessions are qualitatively different from the Center’s usual one-to-one sessions and tutors need to learn and apply new skills. This project is designed to further develop training for tutors, investigate effective models of group tutoring strategies, and explore what the differences and similarities are in skills useful in one-to-one sessions vs. those useful in group discussions. This research will be conducted by observing group sessions, crafting transcripts of successful group interactions in these sessions, and interviewing tutors and students to discover which strategies are effective. The project will be presented in a poster format that will include the models, guides, and strategies found to be most useful for tutor training and group facilitation. These results have significance for all those interested in peer education models and more effective small-group, discussion-based learning.

Macrophages of our immune system can be broadly classified as pro-inflammatory M1 or anti-inflammatory M2 macrophages. Imbalance in the ratio of these two phenotypes has been associated with various chronic diseases, suggesting that targeting drugs to specific populations of macrophages may achieve therapeutic benefit. Phage display is one method of identifying peptides that can be used for targeting cell populations. In whole-cell peptide phage display, a library of bacteriophage, in which individual phage display a unique peptide sequence on a coat protein, is applied to target cells. Phages that preferentially bind target cells are isolated, and their peptide sequences can then be obtained by DNA sequencing. Targeting M1 macrophages has possible applications in treating arthritis, diabetes, and atherosclerosis. Recently, we identified a novel phage-bound peptide sequence (hM1pep), using phage display, that exhibited selective binding to M1 macrophages. I synthesized the peptide form of hM1pep and evaluated its selectivity of M1 macrophage binding in vitro using flow cytometry; however hM1pep showed insignificant binding. Tumor-associated macrophages (TAMs), a type of M2 macrophage, have been shown to facilitate tumor growth and are associated with decreased survival of cancer patients. Previously, we identified a peptide that preferentially bound to TAMs in mice. We demonstrated that peptide-mediated TAM elimination improved survival in mice, suggesting that an analogous strategy in humans could be a potential cancer therapy adjuvant. In this work, I attempted to identify human M1 and M2 macrophage binding peptides by panning against human M1 and M2 macrophages, while using M2 and M1 macrophages as a subtractive panning step, respectively. Targeting M2 macrophages has potential uses in treating diseases associated with increased tissue levels of M2 macrophages, including cancer, fibrosis, and asthma.

As the world becomes more interconnected, health issues that may once have been considered local problems are increasingly of international concern. While a number of academic institutions have made efforts to incorporate global health topics into their curricula, the role of global health in nursing education remains relatively undefined. As one of the nation’s top nursing schools, the University of Washington’s School of Nursing (UW SON) is in a position to embrace this opportunity. The goal of our research is summarize existing practices, explore linkages between international experiences and global health educational programs, and gauge student interest in global health topics at the UW SON. A mixed methods approach will be used. Quantitative data will be obtained via a brief anonymous survey of three current 2012-2014 UW SON baccalaureate cohorts. Qualitative data will be collected through online program reviews and semi-structured interviews. Online program reviews will assess global health course offerings in the top ten US nursing schools, as well as pre- and post-Peace Corps educational opportunities including the Coverdell Fellowship and Masters International Program. Interviews will be conducted with three purposively selected global health professionals who previously served with Peace Corps. Summary statistics (frequency and percent), including 95% Confidence Intervals, will be presented. Program reviews will be presented in summary tables, and interview findings will be coded into themes with assistance of a social scientist. Results will demonstrate interest level among current nursing students in global health in general, as well as in specific topics. We also seek to identify themes linking Peace Corps experiences with awareness of global health topics, educational choices, and professional development. We will use our findings to inform the UW SON leadership of possible recruitment strategies and curriculum content to enhance global health offerings.

A crucial segment of sustainable jet fuel production is the fermentation of lignocellulosic-based sugars to acetic acid. Biomass from non-food sources such as wood, switch grass, and waste materials can be fractionated into their raw sugar components (glucose, xylose, mannose, arabinose, and galactose). These sugars can later be fermented to acetic acid, reduced to ethanol, dehydrated to ethylene, then oligomerized and hydrogenated to produce jet fuel. Moorella thermoacetica is an obligate anaerobe that exclusively ferments sugars to acetic acid. Thus far, fermentation using M. thermoacetica has been achieved with synthetic glucose and xylose. It is essential to investigate the fermentation of all five sugars in order to validate lignocellulosic biomass as a feedstock for this process. In this work five synthetic sugars were fermented in flasks at 58°C without pH adjustment. Samples were taken every 4 to 6 hours over a period of 48 hours and were analyzed offline by high performance liquid chromatography (HPLC). The trend of sugar consumption shows that M. thermoacetica has a substrate preference of xylose over glucose, and glucose over other sugars. The sugar consumption was 100% for xylose, 98% for glucose, and 30 - 40% for the rest of the sugars. Successful five sugar fermentation suggests a concrete potential to upscale the bioconversion process and build a feasible market for jet fuel produced from lignocellulosic biomass.

The Northwestern Crow (Corvus caurinus) and American Crow (Corvus brachyrhynchos) are difficult to distinguish using morphological or vocal characters. The Northwestern Crow is considered ecologically distinct, occupying only coastal and shoreline habitats from Central Washington, north through much of coastal Alaska. The more widely distributed American Crow occurs throughout greater North America, including Pacific coastal habitats north to Central Washington, potentially overlapping and hybridizing with Northwestern Crow in this region. Until now, no comprehensive genetic analysis has been performed to examine crows in this potential zone of overlap. This study examines Pacific Northwest Corvus species distributions with minimal spanning networks and phylogenetic analyses via the mitochondrial DNA ND2 gene. Mitochondrial DNA is inherited maternally and does not recombine giving a minimally distorted view of an individual's ancestry. Our data show that the Northwestern Crow occurs from Alaska to Southern British Columbia, and not in central Puget Sound or along the southern coast of Washington. The American Crow occurs throughout the continental U.S. and comes into contact with the Northwestern Crow in southern B.C. Further analysis is required to reveal the possible extent of this contact zone north of Vancouver and/or into northern Washington. A better understanding of this overlap zone will allow science to update natural history species distributions and further explore the effects of human impact on biogeography.

Photothermal heating of nanoparticles by electromagnetic radiation, which has potential applications including cancer treatment, requires consideration of the the electric field produced inside the nanoparticles. For most particle geometries, the electric field cannot be solved for exactly, so numerical methods are required. One such method is the Discrete Dipole Approximation (DDA), which models a target as an array of interacting point dipoles whose polarizations can be solved for. In this research, the DDA is used to simulate the electric field inside silicon and gold nanoparticles with spherical morphology. Particle sizes simulated range from 100 nm to 1000 nm, with a wavelength of 1000 nm. It is found that the particles exhibit morphology dependent resonance (MDR) at certain sizes. This is indicated by an increased electric field strength relative to the incoming wave, as well as an electric field  pattern corresponding to constructive reflection in the spheres. These resonances would lead to increased heating if the particles were used for photothermal applications.

 Over 90% of cancer-related death is caused by metastasis of invasive cells from one organ to another. Discovering more about this proliferative capability will be influential in creating new cancer therapies that will not only diagnose cancer, but may soon eventually fight it. Cancer metastasis involves migration of cells along bundles of extracellular matrix (ECM) fibers. In this context, understanding topotaxis through various kinase pathways which regulate cell migration is essential. An example of a kinase pathway is the PI3K pathway, one of the most mutated and well-studied pathways. When this pathway is over-expressed, proliferation of cancer cells is increased, while apoptosis of the cells is decreased. Additionally, cancer cells exhibit a more rigid nature suggesting that there are durotaxis involved for metastasis. Understanding these two mechanotaxes and how a particular oncogene influences the cellular response to these factors are vital in our quest to understand the process of cancer invasion. In our experiment, we studied two specific oncogenes in this pathway: PIK3CA and PTEN. Since PIK3A and PTEN are up-regulators and down-regulators of the PI3K pathway respectively, they will be an excellent model to investigate how PI3K is regulated by oncogenes. We hypothesize that cells not containing the down-regulated PTEN oncogene (knockout) and cells containing up-regulated PIK3CA oncogene (knock-in) will result in directional cell migration and increased migration speed and persistence time. To test this hypothesis, we utilized nano-scaled platforms of increased stiffness to simulate the ECM collagen fibers found on cancer micro-environments. Coupled with polymers such as polyurethane acrylate, polydimethyl siloxane, and poly(lactic-co-glycolic) acid, these platforms can vary the stiffness of cancer microenvironments, ranging from kiloPascals of normal tissue to gigaPascals of cancerous tissue. Thus, these platforms give us the opportunity to design a cancer tissue model to study effects of oncogenes on cancer invasion.

Emulsions of oil droplets decorated with gold nanoparticles can be used to enhance contrast in ultrasound and photoacoustic imaging. Plasmon resonance in the gold nanoparticles enables absorption of near infra-red (NIR) light, which can penetrate two to three centimeters below the skin in the human body. Upon irradiation with a NIR laser, oil droplets with a shell of gold nanoparticles will heat and vaporize as the gold absorbs the light. The vaporization of the oil creates a microbubble, providing contrast enhancement in imaging as well as a mechanical pressure wave which could be used to deliver mechanical forces inside the body. If the gold nanoparticles are functionalized with ligands that are designed to target specific areas or threats inside the body, the process could also be used to deliver targeted therapy. Emulsions are thermodynamically unstable and will coalesce over time without external stabilization. We utilize gold nanoparticle surfactants to stabilize the oil-water interface. We investigated a charge based stabilization of perfluorohexane emulsions with cationic gold nanoparticles. Size is characterized by Dynamic Light Scattering (DLS). Successful adsorption of the cationic gold nanoparticles to the oil-water interface is represented by zeta potential, which approximates surface charge. Emulsions of oil have a negative surface charge and the presence of cationic gold at the interface will result in a positive charge. Ultra-Violet Visible Spectroscopy (UV-Vis) is used to measure the NIR absorbance of the emulsions, which should be maximized to enable rapid heating of the gold nanoparticles and subsequent oil vaporization. Stability over time is determined by changes in the DLS and UV-Vis curves. The results of the investigation are analyzed in terms of size, stability, and NIR absorbance in order to determine the potential effectiveness of a charge based stabilization mechanism in creating plasmonic emulsions for contrast agents and therapeutics.

The purpose of this research is to investigate hidden health narratives on campus regarding the use of tobacco products to contextualize the legitimacy of smoke-free and tobacco-free university initiatives. This academic endeavor will also reveal the structural and institutionalized violence of the tobacco industry which targets marginalized communities to entice the uptake of regular smoking habits. An analysis of biopolitical power, structural violence, and social theory will help to reveal the hidden narratives of these populations, twice-targeted by the social stigmatization of tobacco use and the manipulative advertising of the tobacco industry. By exposing, analyzing, and deconstructing patterns of profit-driven tobacco marketing directed at student demographics, it is possible to examine geographies of blame regarding tobacco use, impact of tobacco use on non-smoking populations, and the misleading agendas behind the dominant narratives of tobacco industry advertising. By identifying and bringing to light these messages, it is possible to legitimize the anti-smoking and anti-tobacco movements happening at the University of Washington, and U.S. universities at large, with a critical analysis of the health risks involved.

This paper analyzes the juxtaposing narratives between various documents and media portrayals from mining corporations, the Peruvian government, and the affected indigenous populations, focusing on how many of the more dominant narratives can often be misleading in reflecting the serious health effects from mining. Peru’s mining industry significantly influences the health of surrounding indigenous communities due to high levels of air and water pollution. Unfortunately, there is not a great deal of sincere concern for the wellbeing of these communities from either the corporations exploiting their land or the Peruvian government. Despite their efforts to express their suffering through protests, indigenous communities have seen few results. The mining industry and its detrimental health effects are often overlooked, and therefore many of these dominant corporate narratives and our own capitalist desires are all that we have to shape our understanding of how mining industries operate in other countries, such as Peru. However, the subaltern counter-narratives from indigenous populations concerning their health and rights can more accurately shape our understanding of the severity of these health effects caused by the mining industry.

To address the growing international attention on the high rates of obesity in the Pacific Islands, this project examines the discursive patterns that play a role in both fueling and quelling the outbreak of obesity among the Samoan population. I will provide a historical account of the diet and lifestyle during the pre- and post-colonialism periods in American Samoa. I am especially interested in tracing the racialization of food and the differences in perceiving food. I draw on theorist Michel Foucault’s interpretation of biopower in  to further illuminate the narratives that perpetuate the issues of power inequality, colonialism and the racialization of obesity towards the Samoan people, and what exactly defines “health” and “wellness”. The sources of these narratives are extracted from everday popular media, news articles, and even film or artwork. The project also uncovers the various counter narratives from Samoan Americans in the local Seattle community as well as Pacific Island authors and educators to shed light on work counteracting obesity in the community, the significance of cultural preservation and indigenizing health and incorporating de-colonial movements. This leads into the movement towards individualized risk management awhile not losing sight of community and relationship. The implications of this analysis lead us to consider the correlation between discourse and body governance in the context of a growing global health and food industry.

Large chromosomal amplicons and deletions or copy number variation (CNV) are found in many different cancers. However, the inheritance, stability, and fixation of these amplicons and deletions within a population are widely debated and poorly understood. In an effort to better understand how the stability of this large chromosomal rearrangement, I analyzed the stability of a large segmental amplification in the yeast S. cerevisiae. This amplification is commonly observed in clones evolved under sulfate-limited conditions and contains the sulfate transporter SUL1. This amplification is an important adaptive strategy used by the cells to improve their ability to extract the limited supply of sulfate available in the media. High copy number of this gene confers a competitive fitness advantage over other clones that have only one copy of the gene. We used a GFP marker integrated next to SUL1 to differentiate green clones, which contain a single copy of the SUL1 gene, from “super green” clones that have multiple copies of the gene. A super green evolved clone was grown in steady state growth vessels for ~30 generations in media that is non-selective for adaptation and our selective media as a control. I monitored the population using flow cytometry and quantitative PCR to find clones that have lost the amplification. These green clones were isolated using flow sorting and then had their genome sequenced to look at the scar that was left behind. This tells us how efficiently the cells can remove amplifications without causing detrimental effects to their fitness.

Genetic conflict ensues between two parties that have an antagonistic relationship, where fitness gains in one party necessitate fitness losses in the other. As a result, there is constant selective pressure on both parties to maintain evolutionary dominance. One such conflict may exist internally between the mitochondrial and nuclear genome. This arises from the difference in DNA inheritance patterns between the two parties. Nuclear DNA is transmitted maternally and paternally in Mendelian fashion whereas mitochondrial DNA is only transmitted maternally, leaving males as an evolutionary dead end for mitochondrial DNA. This suggests that male-harming mutations could arise and fixate in mitochondrial DNA as long as those mutations are beneficial or neutral to female fitness. One way for males to counteract such mutations is for the nuclear DNA to evolve suppressors of these mutations. This conflict may not commonly exist in nature because males with mutant mitochondria would appear wild-type if their nuclear genomes contain suppressors of these mutations. To reveal if a conflict exists, we took an experimental evolution approach, using Drosophila melanogaster, to break the coevolution of mitochondrial DNA and Nuclear DNA and allow mitochondrial DNA to evolve on its own. After 34 generations, we performed a variety of assays and sequence analysis to identify any mitochondrial male harming mutations. We isolated a single mutation and an associated fertility decrease in males. We are currently trying to identify if any suppressors of this mutation exist in nuclear DNA of other strains of melanogaster by introducing the nuclear genome of these strains into a male with the mutation. We predict that if such nuclear genomes exist, then the fertility of mutant males should be restored when this nuclear genome is introduced. This study will provide an evolutionary insight into disease and defects of males associated with mitochondrial mutations.

Childhood Apraxia of Speech (CAS) is a rare, severe, persistent pediatric motor speech disorder of largely unknown genetic cause that affects the ability to acquire intelligible speech and coordinate the volitional production of sounds by sequencing muscle movements for the production of words. Developmental Dyslexia is a common and specific childhood learning disorder defined as a significant impairment in reading ability that cannot be explained by deficits in intelligence, learning opportunity, motivation, or sensory acuity. Various dyslexia studies suggest that slowed global processing speed, especially when sequential modes are involved, may be a brain-based endophenotype of dyslexia under genetic control. Impaired sequential processing, hence, may be a biomarker shared by CAS and Developmental Dyslexia. Our group recently identified a de novo heterozygous deletion of a single gene in a proband with severe CAS, raising the question whether similar deletions are causal in other cases as well. Here we report a genome-wide Single-Nucleotide Polymorphism (SNP) and CNV findings in a cohort of 20 affected individuals in nine multigenerational families with well-characterized CAS and six unrelated individuals with Developmental Dyslexia. All participants met clinical research criteria for CAS as part of a larger study on familial motor speech sound disorder or Developmental Dyslexia. The genome-wide copy-number variation study of the selected individuals was completed using the Illumina HumanOmniExpress-24 BeadChips and Human Exome BeadChips. Analysis of the SNP content and CNV for overlapping variations across the genomes of these affected individuals give us insight into genomic regions associated with the clinical phenotype of sequential processing deficit in multiple domains.

Throughout time historic records have been heavily influenced by the victorious and their self-promotions which can be likened to propaganda. According to Merriam-Webster dictionary, propaganda is defined as “the spreading of ideas, information, or rumor for the purpose of helping or injuring an institution, a cause or a person.” The goal of my project is to demonstrate how Euro-American depictions of early American landscapes, during the migration westward in the nineteenth century, were a form of propaganda used to shape American history. During my research I learned that artists were constructing compositions based on ideas that glorify the migration. Since the majority of the audience was unable to travel West the paintings being brought back from expeditions were seen as accurate depictions. This research analyzes works by painters Albert Bierstadt and Thomas Cole, two distinct examples of propagandized landscapes. Through the examination of primary and secondary sources I will show how Bierstadt uses fantasized landscapes as a way of engaging the audience and how Cole portrays the untamed nature of the West as uncivilized. These paintings were used to promote opportunities found in cultivating the new land and highlight the prosperity of those already settled. My research will conclude that our history has been shaped negatively due to images being accepted as true representation. I hope to have shown how images are one sided and should not always be taken as they initially appear.

In this paper, I consider Timothy Morton's idea of ecological thinking and Dipesh Chakrabarty's arguments about humans as geological agents. Both scholars argue for a new mindset in the face of the current climate crisis. For example, Morton attributes our present ecological predicament to the misunderstanding that nature is a separate entity — an object ready to be exploited. We can no longer afford to think this way because industrialization of natural resources has led detrimental effects, everything from climate chaos to species extinction. For Morton though there is hope. If we were able to think more broadly then we could perhaps understand that ecological thought is about coexistence. Similar to Morton, Chakrabarty emphasizes the complex interconnectedness of humans and nature. He maintains that humans can no longer differentiate between human history and natural history, especially since human activity and consumption turned us into geological agents. Guided by these theories, I turn to art — which as Morton states has “something to tell us about the environment.” Art, he suggests can “make us question reality.” To further his point, I compare Albert Bierstadt’s Mount Sir Donald, a late nineteenth century painting, to three contemporary works: Subhankar Banerjee’s Caribou Migration (2002) and Spencer Tunick’s Aletsch Glacier #4, Switzerland (2007), and Camille Seaman’s Grand Pinnacle Iceberg, East Greenland (2006). I use the comparison to question the extent to which our thinking about nature has become transformed — from a nineteenth century notion of the picturesque to a twenty-first century ecological awareness of the environment.

The dominant values that were depicted in American and Japanese World War II poster propaganda helped to rally support from the respective countries’ populations. One chosen value, or objective, for the propaganda posters in America was found to be the unifying of the American people through promoting the desire to aid American soldiers, whereas a common objective of Japanese posters was to unify Asian people throughout the world. How these objectives were represented determined if the posters were successful at gaining support from each country’s population. The objectives of American and Japanese propaganda posters are found through a comparative analysis of a single poster from each country. The objective of the American poster is depicted through the representation of American people doing what they could on the home front to support their troops. The objective of the Japanese poster is represented by showing the coming together of Asian people throughout the world. The objectives depicted had a major impact on how each population viewed and thought about the war. Propaganda, the new weapon of the twentieth century, especially poster propaganda, unified the communicating function of art with the influential power of media to broadcast the dominant values of each nation through imagery to both the soldiers on the battlefield and the civilians in their home countries. These posters allowed the populations of each country to identify with the dominant objectives of their country. If the populations could not identify with the objectives they would not be able to rally under one cause and help their country during a time of war.

 According to the World Health Organization, low-income countries have ten times fewer physicians than high-income countries. This gap in health care access contributes to numerous global health disparities, including differences in mortality rates, disease transmission, and life expectancy. In Madagascar, health care access has improved due to the implementation of integrated health care systems, which incorporate traditional medical practices with allopathic health care strategies. My research uses qualitiative data gathered from interviews and lectures to explore the ways in which these systems in Madagascar provide health care in an affordable and accessible manner, while also promoting cultural sustainability and the conservation of biodiversity. Understanding and implementing integrated health care systems can lead to further discoveries of new medical treatments, the protection of biodiversity, advancements in traditional and allopathic remedies, and ultimately, improved access to health care.

Influenza A viruses have two main surface proteins that usually have opposing functions. Hemagglutinin (HA) is traditionally thought of as the receptor-binding protein which binds to sialic acid on the surface of the target cell, while neuraminidase (NA) is a sialidase that removes sialic acid receptors to allow for viral release. However, recently, it was discovered that a mutant NA can function as a receptor-binding protein when a single amino-acid substitution (G147R) is made near the active site. Thus, to study the effects of a mutant receptor-binding NA in a controlled fashion, we sought to produce virus-like particles (VLPs), which express only NA, but not HA on their surface. Initially VLPs were made by co-transfecting 293T cells with a plasmid expressing the mutant NA and a plasmid expressing the influenza matrix genes. This method of producing VLPs gave a lower yield than what was required for further experiments. In order to optimize VLP production, I hypothesized that I could instead use the HIV Gag polyprotein which alone can cause membrane budding and scission. By comparing the VLP production efficiency of particles which contain either the influenza matrix genes or the HIV capsid protein, I hope to develop a method which allows us to produce large quantities of VLPs for receptor-binding studies. If using HIV Gag polyprotein does prove to be more reliable, I will begin using this technique to produce VLPs in order to identify the receptor for the NA-binding mutant previously discovered. I will then begin testing the NAs of contemporary human viruses to determine if the phenomenon of NA-binding occurs in nature. Overall, this work aims to better understand a newly recognized mode of influenza infection.

Cyanide-bridged transition metal complexes serve as model systems to study photoinduced charge transfer reactions. These complexes are important to understand because they play a major role in processes such as photosynthesis and the conversion of light to electronic energy in solar cells. Using RuCl₃•XH₂O salt, 2,2':6',2"-terpyridine (tpy), 2,2'-bipyridine (bpy) and KCN we synthesized [Ru(tpy)(bpy)CN]²⁺, [(tpy)(bpy)Ru-{CNRu(tpy)(bpy)]³⁺ and [(bpy)₂Ru-{CNRu(tpy)(bpy)]⁴⁺. These multistep syntheses were monitored using FTIR, UV-vis and ¹H NMR in order to verify that the compounds of interest were made. These compounds are interesting because of their metal-to-ligand charge transfer and metal-to-metal charge transfer processes when excited with visible light.  In the future these complexes will be studied using nonlinear spectroscopies in the visible and infrared regions of the spectrum in order to investigate their charge transfer capabilities.

Multi-layer circuit boards are expensive; each additional layer significantly increases their production cost, however multiple layers are commonly necessary to avoid routing conflicts. Due to the large number and high density of pins on some components, a design issue is determining the minimum number of layers required to resolve all routing conflicts. Some buses must be assigned to consecutive layers, which add further complexity to the routing problem. We propose an improvement to an algorithm based on branch-and-bound for designing an optimal layer assignment for printed circuit board (PCB) bus escape routing. We use concepts from vehicle routing and scheduling algorithms to efficiently traverse the branch-and-bound tree. Our algorithm is guaranteed to provide a feasible layer assignment for each bus with the minimum number of layers.

Understanding the energy expenditure required for the activities of daily living is a critical step in assessing the caloric needs both of those individuals whose body mass exceeds recommended standards and those who are chronically under/malnourished. Knowing how much energy people require to accomplish their activities of daily living, which typically includes walking with burdens (carrying excess weight) and on sloped surfaces, is a critical component in developing guidelines for appropriate caloric intake. Activity energy expenditure is the second largest component of daily energy use, after the energy required to maintain bodily function (usually called resting metabolic rate (RMR)). This study allows us to understand the relationship between burden, gradient and walking which is necessary to accurately account for the daily caloric needs of humans. To evaluate this relationship, data is collected from a large number of female participants. Participants walk at three self-selected velocities (slow, normal, and fast), on five gradients (flat, slight uphill and downhill at a gradient of (6.7%), and steep uphill and downhill at a gradient of (12.6%)) and two burdens (no burden and a burden of a 10 kg backpack).“Self-selected” velocity means that the subjects are able to choose their own pace, be it slow, normal or fast. This approach allows flexibility for the subjects to choose speeds that reflect their normal routine. The energy consumption is measured by the volumetric rate of oxygen consumption (VO2, inspiration) and carbon dioxide (VCO2, expiration) with a portable Cosmed K4b2 device. Unlike previous work that has used treadmills, this study is completed outside in an urban setting. Preliminary results indicate that walking outside requires different energy expenditure than walking on a treadmill. This study provides data collected from real-world experience, thereby providing more accurate understanding of the caloric needs to achieve more day-to-day activities.

As social movements, technology, and political periods change through time, so does the young adult and their personal values. However, since the industrialization of the United States, one of the most enduring facets of American society is its system of capitalism and the overemphasis on having, or striving for, a materialistic lifestyle. With that being said, it has been found that one of the major drivers of change in personal values is materialism, and my study shows what effects materialism has on peoples' life goals and what life goals my sample has. The purpose of my study is to explore, using a convenience sample of Bemidji State University (BSU) students, how a materialist identity (or lack thereof) affects BSU underclassmen life goals (such as private wealth, self-fulfillment, family life, and public interest), using the 1991 Easterlin and Crimmins study for comparison, and as a way to see how levels of materialism have changed over time.

Malaria, due to parasitic infection by Plasmodium protozoa, is a severe global disease with 300 million annual cases leading to 1-2 million deaths. While a few anti-malarial treatments continue to work, the continual emergence of new drug resistant parasites is an urgent public health concern. Previous studies in the Rathod laboratory suggest that chemical tools can be used to distinguish variations in evolutionary capabilities of different malaria parasite strains. Some strains such as Dd2 display the Accelerated Resistance to Multiple Drugs (ARMD) phenotype, whereas the HB3 strain displays the non-ARMD phenotype. In previous studies, Dd2 strain acquires resistance to several antimalarials at a significantly higher frequency than the HB3 strain. In this experiment, a cyclopropyl carboxamide (GSK2645947), a novel class of antimalarial agent, was used to select for resistant parasites from Dd2 and HB3 with the aim of comparing their relative frequencies of resistance to GSK2645947. A series of selection experiments were carried out utilizing different concentrations of GSK2645947 and different numbers of starting parasites. The parasites acquired resistance to GSK2645947 at similar frequencies in Dd2 and HB3 cells. The extent of resistance to GSK2645947, measured using EC50 assays, was similar in Dd2 and HB3 resistant clones; resistant parasites from neither lines showed cross-resistance to other antimalarial drugs. The present results point to a novel mechanism for rapidly acquiring resistance to GSK2645947, a mechanism that is equally prevalent in Dd2 and HB3 strains of P. falciparum parasites.

Pre-erythrocytic malaria vaccines may need to target numerous sporozoite (spz) and/or liver-stage proteins to be effective. If the protective antigens could be definitively identified, multi-component subunit vaccines could be produced. Using a novel high-throughput T cell screening system, we recently identified a CD8 response against the Plasmodium yoelii L3 ribosomal protein in sporozoite-immunized BALB/c mice. Unlike the CD8 T cell response against the circumsporozoite protein (CSP) that increases with each parasite exposure in our system, the L3-specific response is not boosted by repeated exposures to attenuated sporozoites. We have shown that L3 -specific cells have no cell intrinsic defects that counteract their re-expansion or function but rather that broad anti-sporozoite immune responses in secondary or later exposures eliminate expression of L3, thereby preventing any opportunity for activation of memory L3-specific CD8+ T cells. This T cell outcome following immunization may be emblematic of other T cells with liver-stage targets as well. Here, we tested the L3-specific T cell response in another species (P. berghei) and also employed heterologous (cross-species) prime-boost approaches. We explore the difference in parasite load and L3-specific CD8+ T cell responses between homologous and heterologous immunization regimens. We screened mice against 37 liver-stage proteins and found that cross-species immunization boosted more responses than homologous immunization. The identities of the specific targets are under investigation. Cross-species boosting may be useful as we work to identify antigens that promote an L3-like CD8+ T cell response for inclusion in a novel multivalent malaria vaccine.

Tyrosinemia Type II is a genetic disorder caused by a mutation in the enzyme tyrosine aminotransferase (TAT), which leads to an elevated level of tyrosine in the blood. If untreated, individuals with tyrosinemia develop life-threatening clinical symptoms that include an increased tendency to bleed, damage to the nervous system, damage to the eyes, and organ failure. Unexpectedly, mutation of TAT in the nematode Caenorhabditis elegans results in animals that are long lived in comparison with wild-type (WT) worms. This study aims to elucidate the cellular mechanism and workings of TAT in the mitochondria, its role in the pathology of the disease, and its possible links with aging in C. elegans. Thus far, we have developed a simple method to measure the CO2 output of the worms and shown that the TAT mutant’s metabolism is about 50% compared to WT. This significant decrease in CO2 output was matched comparable to a strain deficient for mitochondrial Cytochrome C Oxidase, which served as a positive control. Cytochrome C Oxidase, or Electron Transport Chain Complex IV, is one of the three complexes that create the proton gradient inside the mitochondrial matrix upon accepting electrons. Notably, mutation of the gene acting downstream to TAT in the tyrosine degradation pathway, which causes Tyrosinemia Type III in people, or any other mutation in tyrosine metabolism that we have tested, causes no significant change in CO2 output of C. elegans. Furthermore, through our preliminary metabolomics assay we have identified three metabolites that are accumulated to extremely high levels in comparison to positive and negative controls. The future steps will include determining whether these metabolites play a direct role in the effects of TAT mutation on mitochondrial function and aging.

In modern society, film has become an incredibly influential form of media and cultural currency. From childhood, we have a constant interaction with film and with the narratives and messages that it communicates. In this project, I propose that there is an absence of female representation in children’s films, and that the resulting lack of exposure through film to strong female characters during childhood has a direct effect on societal outlook in adulthood, and by extension, on American culture, and on the subconscious sexism inherent within. In order to make this argument I will be utilizing the Bechdel test, which is an informal set of criteria with which to analyze the level of female representation in film. For a film to pass the “test” and achieve an adequate level of equal gender representation, it must have at least two named female characters, the two characters must speak to each other, and they must speak to each other about something besides a man. With these criteria in mind, I will analyze a number of popular children’s films, and attempt to highlight the potentially negative effects that gender misrepresentation has on American society.

Barack Obama's historic election to the United States presidency in 2008 focused national attention on the first Black president and his family as living and unequivocal proof of the triumph of equal opportunity and the end of centuries of racial strife. The visible role of elite women like Michelle Obama and Oprah Winfrey has often been explored, while less well understood is the role of everyday portrayals of Black women as they normalize colorblind paradigms of post-racialism and “neoliberal multiculturalism" (Goldberg 2009, 23). This paper analyzes three media texts, all released in 2008 - Neil LaBute's Lakeview Terrace, Tyler Perry’s The Family That Preys, and Beyoncé’s “If I Were A Boy” music video - focusing on representations of Black women as sexualized objects involved in interracial relationships with white men. The paper reveals that these ways of seeing serve the privileged white male gaze while falsifying racist and sexist realities. Offering key insights into the "post racial gaze," the paper exposes how Black women are being positioned to normalize pleasurable post-racial fantasies and to facilitate discursive shifts toward neoliberal multiculturalism.

The aim of my presentation is to explore a unique approach to cinema called ‘a cinema of transvergence,’ as theorized by Will Higbee, as a means to glean the effectiveness of the work of three women directors from the Middle East/North Africa region, in suggesting possibilities for challenging the fixed positionings typically offered by the hegemonic structures of knowledge and power. When applied to the films of directors Raja Amari, Annemarie Jacir and Samira Makhmalbaf, a transvergent approach provides an open ended framework for understanding of interconnections which bind the filmmaker to a given film culture/national identity, the intentions, approaches and material conditions behind the production of their films, and the international reception of these films. The understanding of these factors, in turn, reveals the difference and imbalances of power exist between various film cultures and film industries.

Bottom water hypoxia is a feature of many coastal embayments and fjords in the Salish Sea. Ongoing research in Bellingham Bay (Bellingham, WA USA) by Northwest Indian College and Western Washington University has identified a seasonally recurring area of low dissolved oxygen near the center of the bay. Similar to other regions of the Salish Sea, hypoxia in Bellingham Bay may be a naturally occurring phenomenon, yet the extent of eutrophication and anthropogenic nutrient loading’s influence on patterns of hypoxia is poorly understood. The present study has continued an established monitoring program documenting the range, duration and severity of hypoxia in Bellingham Bay, while adding an experimental component investigating factors that regulate respiration of heterotrophic bacterioplankton. Profiles of water column parameters and sample collection were performed on six regularly scheduled cruises. Dissolved oxygen concentrations below the hypoxic threshold were observed in bottom waters in the center of Bellingham Bay for most of the summer, although the layer of hypoxic water appeared to migrate upwards into the water column in late July. Manipulative experiments were conducted on collected water samples to investigate effects of temperature and organic carbon on water column respiration. These experiments revealed that temperature had a negligible effect on water column respiration, while organic carbon stimulated oxygen consumption and was thus identified as a possible limiting factor. The study’s findings broaden our knowledge of factors regulating oxygen dynamics in coastal embayments of the Salish Sea and provide further insight into the potential effects of anthropogenic stressors and climate change on Salish Sea water quality.

 In the last decade, and especially since the 2013 Supreme Court Ruling on Shelby County, AL v. Holder, there has been amplified discussion of voter access policies- particularly those potentially restrictive in nature. Much of this discussion has been centered on the supposed need for photo identification, shortened registration and voting periods, and the efficacy of absentee ballots. The discussion of these policies is in direct contrast to the movement to expand voting rights of the 1990s and largely anecdotal in nature. Never the less, many states have considered or adopted more restrictive policies. Using Census data, this paper will utilize regression analysis to examine the effect of voter ID requirements, limited registration and voting periods, and absentee-only balloting on turnout rates by state across race, age, and income groups in General Elections from 1992-2012. Researchers undergoing similar types of analysis have found the policies in question to have non-appreciable or no effects on total turnout rates, but have neglected to consider potential disparate impacts upon certain groups. In addition to considering such impacts, this paper will also examine factors that lead states to consider restrictive policies, such as rising minority populations or swing-state status. Research into voting practices has obvious policy implications and is particularly relevant as we approach the 2016 Presidential election.

For many practitioners within the field of dentistry, providing local anesthesia that is both effective and comfortable for the patient is a challenging art that requires great skill and the right product. Nonetheless, unsuccessful local anesthesia can oftentimes leave the patient in discomfort and the administrator waiting periods of time before a local anesthetic effects appears. Addressing these complications, this review of past and present literature examines reasons for which traditional local anesthetic products and techniques within dentistry can fail and assesses possible solutions to these failures. Findings suggest that some anesthetic agents may be less effective than others with respect to onset time, duration, and relative strength. Products with lower concentrations, fat solubility, and proportions of HCl and vasoconstrictor (e.g epinephrine), tend to produce slower, weaker, and shorter-lived effects. In addition to ineffective anesthetic agents, local anesthesia in dentistry can also fail by means of anatomical and technical intricacies such as the impermeability of the dense cortical bone in the mandible (lower jaw), and the inability of administrators to successfully perform nerve blocks such as the inferior alveolar nerve block (IANB). In assessing these failures, the results of this literature review support the use of bupivacaine with HCl and 100:000 epinephrine for a quick, strong, and long lasting effect, as well as the use of intraosseous anesthesia, a technique that delivers the local anesthetic solution directly into the cortical bone, as an effective primary anesthetic technique for procedures involving one to two teeth. Compared to traditional local anesthesia injection techniques, recent studies accredit intraosseous anesthesia with high success rates, easy administration, fast onset times, strong effects, and significant patient comfort. When performing local anesthesia in dentistry, patient comfort during and after administration is imperative. The results of this study indicate that intraosseous anesthesia attains this objective. 

The blood-stage of infection with the parasite Plasmodium induces clinical malaria. Murine infection with Plasmodium chabaudi provides a physiologically relevant model of the immune response to infection. Blood-stage parasites express Merozoite-Surface Protein (MSP) 1, which undergoes a series of proteolytic cleavage events. The remaining c-terminal MSP1-19 region is necessary for erythrocyte endocytosis and serves as an immunogenic target. Control of parasitemia and resolution of clinical malaria has been shown to be T cell dependent, both through secretion of signaling molecules and through activation of B cells. To understand how T cell populations develop in a manner specific to the parasite and the contribution they make to the overall immune response, we have developed a novel system to identify MSP1-19-specific CD4+ T cells using a peptide: major histocompatibility class II (pMHCII) tetramer of our own design and magnetic bead-based enrichment techniques. Enriched fractions are stained with fluorescent antibodies against phenotypic surface markers and analyzed by flow cytometry to identify previously described CD4+ cellular subsets. T follicular helper (Tfh) cells that are required for B cell antibody production are formed around day 8 post-infection near the peak of parasitemia. Surprisingly, the number of Tfh cells decreases between days 12-15 post-infection and begins to return by day 20, persisting during chronic, low-level infection. We hypothesize that Tfh cell death is driven by high levels of antigen presentation by B cells. To address this hypothesis, we will assess markers of cell death in both TCR signaling reporters and various transgenic mice that lack important CD4+ T cell signaling molecules. Characterization of T cell depletion could elucidate mechanisms of immune evasion critical to parasite survival and persistence of infection, possibly implicating new therapeutic targets.

The surface of Mars is dominated by wind-blown processes and sediment deposits. Dune fields are especially ubiquitous on the surface and record important information about atmospheric circulation patterns, chemical and mechanical weathering, and sediment deposition. Therefore, dune fields are crucial in an understanding of Martian properties such as surface processes, past and present climates, and geologic history. This research investigates the thermophysical properties of sediments composing equatorial dune fields using data from the Thermal Emission Imaging System (THEMIS) on board the Mars Odyssey spacecraft. These data are accessed through JMARS, a geospatial information system developed by Arizona State University. The data are then used with other tools, including Hugh Kieffer’s KRC model, to derive the apparent thermal inertia of the fields. These thermal inertia estimates are the primary way of studying the grains for this research. A material’s temperature response during a diurnal, or daily, cycle can be used to approximate thermal inertia and subsequently be converted to an estimated sediment size. A variety of sizes is expected to be found within the dune fields. Grain size is an important characteristic that can indicate sediment source (local or regional), wind speed, and weathering history, ultimately leading to a better understanding of the surface and climate of Mars. Future research will focus on locating sediment sources and defining textural maturity for Martian sediments, which includes grain size and rounding. It will also focus on identifying inactive dunes, which may preserve historical climate indicators.

 The mitochondria are cell organelles that perform important cellular functions such as energy production, regulation of the cell cycle, and cell death. Therefore, proper mitochondrial function is critical for healthy aging of an organism. Paradoxically, attenuation of mitochondrial function in the nematode worm Caenorhabditis elegans has been observed to extend lifespan. It has been proposed that induction of the mitochondrial unfolded protein response (UPRmt) is responsible for this enhanced longevity. The UPRmt is a response to proteotoxic stress in the mitochondria that results in induction of nuclear-encoded mitochondrial chaperones, proteins that stabilize and fold misfolded and aggregated proteins. However, the mechanism(s) by which proteotoxic stress is recognized in the mitochondria and signaled to the nucleus, resulting in the UPRmt response, remain largely unknown. To further understand the UPRmt pathway, we carried out a genome-wide RNAi screen to search for RNAi clones that specifically reduce UPRmt signaling under conditions of mitochondrial stress. To do this, we used a mutation in the electron transport chain (ETC) gene isp-1 to cause constitutive activation of the UPRmt GFP reporter, hsp-6p::gfp and screened for RNAi clones that reduced GFP fluorescence. We expect that positive hits in our screen will target signaling components of the UPRmt. In total, we identified approximately 60 RNAi clones that reduce the UPRmt response in isp-1(qm150) worms. Currently, we are re-testing positive hits after sequence validation and determining if the targeted genes specifically signal the UPRmt or non-specifically affect expression of GFP reporters. Once we identify genes that are specific to the UPRmt, we plan to test the role of these genes in mitochondrial function and lifespan. A better understanding of the UPRmt pathway could provide significant insight into mitochondrial biology, which impacts healthy aging and several age-related diseases.

Sleep apnea is a common syndrome where a person has an irregular breath rate only during sleep, making it difficult to be detected and diagnosed. Yet, in the U.S. about two percent of children are affected by this syndrome and thus at risk of some health issues. There are some prevalent breath detection products on the market but they remain inaccessible due to the undesired prices and limited range of detection. In the breath detection project I was participating in, we intended to detect the breath rate by wireless technology, e.g. home-based WiFi. Our design would ease the cost of production by zero assembly and installation of the hardware components and would achieve the detection for anywhere inside a house (whole-home detection) by wireless signal transmissions in line-of-sight, none-line-of-sight, and through-the-wall scenarios. The detection system broadcasts the wireless signals in a home environment, receives the reflected signals from the targeted person, and then computes the frequency of the target’s breathing over a period of detection. We expected that frequency plots would be uniform for a normal person but irregular for a patient with sleep apnea. One practical implication of performing such frequency analysis in the whole-home environment is that children’s health monitoring can still happen without parental interference.

CT and MR imaging are widely used for the staging of a newly diagnosed H&N cancer, where treatment decision highly depends on imaging findings. Currently, there is no data regarding whether or not the TNM staging is routinely incorporated into radiology reports. We conducted a national survey to determine whether radiologists routinely address the staging, in particular regards to T (primary), and N (nodal). In addition, we explored the barriers to and perceived values of the reporting incorporating TNM staging among radiologists. A total 199 responses were submitted within a week (25.4% response rate). Over 60% of the responders were at an academic practice, having more than 8 years of experience. 73% of the responders were subspecialized in H&N radiology. Only 26% stated that they routinely assigned TNM staging in radiology reports. The most common barriers were a) unable to remember the staging classification (58%), b) afraid of inaccuracy (57%), followed by c) time consuming (46%), and d) not required (37%). All responders who assign TNM staging indicated that the reasons for such practice are a) believe in added values (31%) and b) help treatment decision (26%). 75% indicated they measure a primary tumor in three dimensions. Approximately half (49%) of the responders thought that incorporating TNM staging is important, 33% were neutral, and 17% thought it was not important.

 The Gram negative, opportunistically pathogenic Gammaproteobacterium Pseudomonas aeruginosa has a propensity to form biofilms. Biofilms are surface associated or aggregated bacterial communities, embedded in a self-derived, extracellular matrix (EPS). One major component of the P. aeruginosa biofilm EPS is the polysaccharide Psl. Psl plays a structural and protective role in P. aeruginosa biofilms by mediating attachment to abiotic surfaces and mammalian cells, conferring protection from components of the host immune response and a variety of antimicrobials, as well as promoting cell-cell adhesion. More recently, Psl has also been shown to function as a cell-cell signaling molecule that activates two diguanylate cyclases through an unknown mechanism, which results in an increase in intracellular levels of c-di-GMP. The secondary messenger c-di-GMP is central to the P. aeruginosa virulence regulatory network, and promotes biofilm formation, in part, by inducing the production of EPS components, including Psl. Thus, presence of environmental Psl appears to act as a feed-forward signaling molecule that enhances biofilm formation. In order to further understand this function, this investigation will employ mini-Tn5 mutagenesis to define the signal transduction pathway(s) responsible for activating the diguanylate cyclases through a novel feed-forward mechanism of Psl-dependent signaling in P. aeruginosa.

Neurological outcomes for premature infants with cerebellar hemorrhages are poor, but the mechanisms of injury are not understood. We hypothesize that the addition of blood to cerebellar slices would decrease external granule layer (EGL) proliferation and impair migration of cells leading to developmental disruption. Our objective is to develop a slice culture model for understanding the effects of cerebellar hemorrhage on cerebellum development. Postnatal day six mice were decapitated and trunk blood obtained using a heparinized syringe. Whole brains were removed and 200 µm thick sagittal cerebellar slices were obtained using a Vibratome. Slices were placed on a cell culture insert with serum containing media. Trunk blood (4µL) was applied directly to treatment slices. Slices are incubated for 48 hours. Media samples were collected for lactate dehydrogenase (LDH) assays. BrdU was added 24 or 2 hours before fixation. Slices were fixed in 4% paraformaldehyde overnight. Immunohistochemistry for calbindin, BrdU, GFAP, PCNA was performed. Slices were processed with LacZ and Nissl staining. Images were taken on a confocal microscope and analyzed for EGL cell counts and thickness. LDH, a marker of cell death, increased in the media of blood-exposed slices than control slices for 4, 24, and 48 hours. Blood-exposed slices have thinner EGL (control 141 versus 120 µm blood-exposed). Bergmann glia were more disorganized after blood exposure and lacked the radial appearance of control slices. Purkinje cell arborization was decreased after blood exposure. Cell proliferation was lower in blood-exposed slices than in control slices (control 77 versus 26 blood-exposed for PCNA; control 80 versus 55 blood-exposed for BrdU). In conclusion, the addition of blood to neonatal mouse cerebellum slice cultures decreased proliferation of cells in the EGL after 48 hours. Additional experiments are underway to better characterize the mechanism of action.

Mitochondria, the energy producing organelles in eukaryotic cells, play a critical role in cell metabolism and regulation. Interestingly, mitochondrial dysfunction promotes lifespan extension in Caenorhabditis elegans. One proposed mechanism is that the induction of mitochondrial unfolded protein response (UPR^mt) increases the expression of mitochondrial chaperones, nuclear-encoded enzymes that assist in folding of misfolded or aggregated proteins, to maintain mitochondrial protein homeostasis. In an effort to elucidate genes involved in the UPR^mt pathway, we performed a genome-wide RNAi screen in transgenic animals expressing mitochondrial chaperone GFP reporter hsp-6_pr::gfp. Unexpectedly, we found that knockdown of genes involved in the pentose phosphate pathway (PPP) activates hsp-6_pr::gfp expression. The PPP is a metabolic shunt off of glycolysis that produces NADPH, a reducing equivalent used for glutathione reduction and lipid metabolism, and ribose 5-phosphate for nucleotide synthesis. In addition, knockdown of transaldolase, a gene in the reductive phase of the PPP, increases the lifespan of C. elegans. Through lifespan epistasis analysis, we found that transaldolase deficiency promotes longevity by a mechanism that is genetically distinct from known longevity factors such as the insulin-like/IGF-1 target (DAF-16), the hypoxia inducible factor-1 (HIF-1), AMP kinase (AAK-2), the UPR^mt transcription factor (ATFS-1), or the germline signaling (GLP-1). This suggests that the PPP inhibition promotes longevity through an uncharacterized pathway that may respond to mitochondrial dysfunction. In addition, we found that transaldolase knockdown alters expression of fatty acid desaturase, an enzyme that oxidizes fatty acid chains. We hypothesize that dysregulation of lipid metabolism by inhibition of the PPP may cause a defect in mitochondrial lipid composition, which may increase mitochondrial proteotoxic stress, inducing the UPR^mt. Understanding the genetics behind the UPR^mt and the PPP’s role in aging has enormous benefits to human health as both the PPP and mitochondrial dysfunction are highly correlated with many age-related diseases including cancer and neurodegenerative diseases.

My project is a study of urban form, not as it exists in any particular real place, but as an amalgamation of realism and idealism. The goal of this work is to depict a snapshot of an imaginary city, its buildings, people, spaces, and history. In creating this project, I did an extensive amount of research into the urban form in action, relying on direct observation, images from the internet, and studies of cities from architecture, urban planning, and design. The City of Atlas Bay is not a real place, but it does include references to diverse locations such as Seattle, New York City, Chicago, Los Angeles, Philadelphia, Washington D.C., London, and Shanghai. Despite the final product’s large scale, the work is also meant to be examined in fragmented sections, a half-way intentional product of the way it was created, which was in fragments. Just as one would not immediately grasp a large city all at once, the work is best viewed in fragments, through examination of its individual and distinct constituent neighborhoods. To foster this, I have included a large amount of detail in every part of the work, encouraging the viewer to linger on the streets as if in a real place. What impression the work leaves with the viewer depends on how the viewer interacts with urban life, whether it be a fast-paced inventory of major artifacts, or through a leisurely stroll examining their surroundings. This project is related the studies in my major, Community Environment and Planning, a bachelor’s program in the Department of Urban Planning, College of Built Environments.

America welcomes people from all over the world, enriching the country with a diverse range of cuisines. Unfortunately, Americans also have some of the highest rates of obesity in the world. We are interested in whether this diversity in cuisines might be contributing to the obesity epidemic. Specifically, our study examined whether having diverse options of ethnic cuisines influences people’s decisions to eat out. We hypothesized that people will be more likely to eat out if they were given diverse options of ethnic cuisines. Psychology students (N = 330) were asked to imagine they were moving to a new city and viewed a map that either had a diverse option of ethnic cuisines (2 Mexican, 2 Italian, 2 Chinese, and 2 American), only Chinese food, or only American food. Participants then indicated the number of times they would eat out in a week and how much they wanted to try all of the restaurants. Participants who were given diverse options of ethnic cuisines were more likely to report they would eat out and want to try all of the restaurants than participants who were given a limited option of ethnic cuisines. Thus, the results from this study support our hypothesis that having diverse cuisine options causes people to eat out more. Future research should examine whether diverse options lead to weight gain because of this greater desire to eat out.

While it is acknowledged that individuals of intersecting marginalized identities experience compounded prejudices, most of the research on intersecting identities has focused on the intersections of gender and race. In two studies, we seek to explore the intersection of weight and race on perceptions of American identity. This study builds on previous research findings that Asian Americans are perceived as less American than people of any other racial group. Furthermore, because Americans are stereotyped as overweight, we hypothesized that heavier Asian Americans would be perceived as more American and less likely to be in the US illegally than their thinner counterparts. Photos of Asian American and White American men were edited to create heavier and thinner versions of each man. University of Washington students viewed either a heavier or thinner version of one of the men and assessed his American identity and perceived documentation status. The heavier Asian American men were perceived as more American and less likely to be in the US without documentation than thinner versions of the same men. Weight did not influence perceptions of White men’s American identity or documentation status. These studies demonstrate that Asian Americans who gain weight may surprisingly be buffered from prejudice directed at those who are perceived as less American.

 The human retina is a complex, post-mitotic tissue where the visual process is initiated. More specifically, it begins when photoreceptor cells absorb light. When these photoreceptors are lost due to damage or disease, irreversible loss of vision results. One potential therapy is cell transplantation of newly generated photoreceptors to replace these lost cells. Regardless of where these stem cells are derived from a common obstacle faced is the proper integration of the transplanted cells with the surrounding native cells. Here we investigate wheat germ agglutinin (WGA) as a potential tool to detect proper integration of photoreceptors by exploiting WGA’s known capacity to serve as a transsynaptic tracer among integrated neurons. Recombinant adeno-associated viruses (rAAVs) were generated encoding WGA conjugated to red flourescent proteins (DsRed) under either a ubiquitous (CMV) or photoreceptor specific (IRBP) promoter.The rAAV genomes also contained another fluorescent protein (GFP) to identify infected cells. Negative controls for transsynaptic movement (where WGA is absent) were included. These rAAVs were delivered via subretinal injections in 2-3 months old mice. The murine eyes were then harvested after 4 days, 2 weeks, and 3 weeks post injection and examined for red florescence, indicating transsynaptic movement. In an attempt to increase transsynaptic signaling, mice were housed in constant darkness and compared to their light-adapted controls. We have been able to show modest WGA-dependent transsynaptic signaling from the infected photoreceptors to their second- and third-ordered neurons (bipolars and ganglion cells, respectively). These transsynaptic signals appear to occur from robust cellular expression of WGA and were not affected by the housing conditions for the mice. These results support an accumulation requirement for transsynaptic movement. Further investigation into enhancing the WGA expression in photoreceptors are needed so that it could become a more powerful tool to examine the integration capacities of transplanted cells for future transplantation studies.

Asians have been one of the fastest-growing populations to immigrate to America for over a century. As a marginalized minority, they still face a variety of problems, including, but not limited to, dehumanizing stereotypes, questioning of citizenship, and alienation from social expectations. Studies on ethnic populations have divulged Asian American and other minority experiences, focusing on what it means to be discriminated against. In discrimination against Asian Americans, certain stereotypes can easily be misinterpreted as positive, painting Asians as ideal students, laborers, or spouses. However, such stereotypes are too incorrect to be useful, in that they put unreasonable ideals and expectations on Asians, meanwhile glossing over the realities of anti-Asian racism. American colleges and universities have taken measures of varying degree to address and better accommodate minority groups. Even with universities implementing diversity pedagogies and equal opportunity policies, problems with racism and alienation for Asian Americans may remain salient. If Asian American college students experience racism, are there common themes of discrimination that come up when they talk about their racial experiences? Additionally, are these stereotypes and themes shared amongst ethnic groups? This qualitative research takes an ethnographic approach by interviewing Asian American college students about their experience as self-identified Asian Americans. These interviews are transcribed and coded, by highlighting themes consistent with those found in past literature, including common stereotypes and degrees of racism severity. Ascription to the popular stereotypes, including the “model minority” and “perpetual foreigner” stereotypes, are predictably a commonplace occurrence throughout the lives of Asian American students, while degrees to which the racism occurs – from aversive to more overt actions – may vary amongst individuals. This ethnography is inspired by the need to further address experiences of discrimination within Asian American populations, in order to better define their place in the racism literature.

Pathways by which bacteria interact likely have a large effect on the bacterial communities that are present in the lungs of cystic fibrosis (CF) patients. CF is a genetic disorder that leads to an inability to clear out viscous secretions in the lungs, allowing bacteria to thrive. Pseudomonas aeruginosa (P. aeruginosa) is one of the most detrimental opportunistic pathogens infecting CF patients. The genome of P. aeruginosa encodes the type VI secretion system (T6SS), a toxin delivery system widely found in Gram-negative bacteria. P. aeruginosa outcompetes other organisms using the T6SS. Interestingly, P. aeruginosa targets more efficiently when the other organism has an active T6SS as well, suggesting that P. aeruginosa has a mechanism for sensing the activity of the T6SS in other organisms. The goal of this project is to find if this phenomenon is unique only to P. aeruginosa and whether it is dependent on the organism it is targeting. Another laboratory found that the threonine phosphorylation pathway (TPP), which is known to regulate the T6SS activity in P. aeruginosa, is required for T6SS-sensing. The TPP is only found in a subset of organisms with a T6SS, and I am characterizing which of these organisms exhibit this neighbor sensing behaviour. I hypothesize that this phenomenon is found in the group of organisms that have a TPP. Burkholderia cenocepacia, another bacterial species with a T6SS, is lacking the TPP, and I have found that it does not have T6SS-sensing ability. This suggests that not all T6SS positive organisms exhibit the sensing phenomenon. Additionally, I am investigating whether P. aeruginosa T6SS-sensing occurs with all recipient species. Since the T6SS is conserved among many Gram-negative bacteria, it is important to determine how widespread T6SS-sensing is, ultimately allowing us to better understand targeting among microbes in CF and other polymicrobial infections.

The type VI secretion system (T6SS) is a molecular export pathway that is widely conserved in Gram-negative bacteria. It mediates interbacterial competition by translocating antibacterial effector proteins from the donor bacterial cell to a neighboring bacterial cell in a contact-dependent manner. The T6 amidase effectors (Taes) are a superfamily of lytic enzymes that degrade the bacterial cell wall by cleaving amide bonds in the peptidoglycan (PG) layer. Taes also have cognate T6 amidase immunity proteins (Tais), which prevent intraspecies intoxication by binding and inhibiting Taes in the periplasm. We hypothesize that this pathway can be exploited for an antibacterial strategy. Specifically, we aim to engineer a P. aeruginosa strain that harbors a novel Tae/Tai pair that can escape recognition by native Tai proteins and predict that this strain will be able to outcompete its wild-type counterpart through the T6 pathway. Towards this end, our group previously generated a mutant library of Tae from P. aeruginosa and screened for variants that escape inhibition by Tai (Tsi1) in E. coli. I am currently experimentally validating several potential escape variants (Tae*) identified by this screen by testing Tae* toxicity in the presence of Tai1 in an in vitro bacterial lysis assay. I will also measure potential changes in in vitro Tai1-binding affinity by isothermal titration calorimetry (ITC).

The role jellyfish play in marine food webs is not fully understood. We investigated whether the trophic level of lion’s mane jellyfish varies with size, month, and type of tissue sampled in an individual. To investigate these questions, we used stable isotope analyses to trace the values of 13C and 15N. We found that isotopes do not change with size or month, and the effect of tissue type is unclear.

Why does the United States continue to pursue and support failed counternarcotics efforts in Latin America? What are the incentives, and who are the beneficiaries, in the foreign War on Drugs? Using the theory of the Iron Triangle relationship between Congress, industry, and bureaucracy, this paper investigates the union between private defense contractors and legislative decision-making in regards to military funds appropriations under Plan Colombia (2000) and the Mérida Initiative (2008). Although the multivariate regression model used to test my hypothesis showed no statistical significance between the number of defense contractors in a Congressional district and a Congress member's vote, it did illuminate other factors that influence legislative decision-making - specifically campaign contributions by the aerospace industry and representative ideology.

For years, politicians have claimed that elementary reading scores can predict prison populations, despite a lack of credible evidence. Although the existing criminal justice literature does draw a connection between higher educational attainment and lower crime rates, this relationship has not been widely examined at the elementary level. Do early reading scores actually predict future incarceration rates? Using 4th grade reading scores and prison admission rates, I examine this question through linear regression. Controlling for other factors that could influence educational outcomes and prison entrance, such as socioeconomic status and harsher sentencing laws, I find that lower average reading scores at the fourth grade level are predictive of future prison admissions. 

Glacial advances and retreats are largely responsible for the current landscape of the Puget Lowland. Of interest to this study was a period of glacial retreat 15-60 thousand years ago. Nonglacial sediments deposited during this time, known as the Olympia Beds, are discontinuous throughout the South-Central Puget Sound region. Here we attempt to correlate between discontinuous outcrops of Olympia Beds based on mineralogy. Sediment samples were taken from outcrops along the SW shore of Commencement Bay and analyzed using X-ray powder defraction (XRD) to determine whether or not the mineral assemblages of each outcrop were of the same origin. The mineral groupings consistent within the sampling area included quartz, muscovite, plagioclase feldspar species (andesine and albite), or potassium feldspar species (sanidine). This implies similar provenance for all outcrops and is consistent with deposition during the same episode of glacial retreat. These data were collected in support of an anisotropy of magnetic susceptibility (AMS) study. Mineral assemblage information coupled with AMS can provide a glimpse of past streamflow conditions within the Olympia beds, suggesting a broadly N-S pattern of streamflow. The combined mineralogical and magnetic results suggest a way forward for mapping streamflow in the Puget Sound region during glacial retreats, eventually leading us toward a better understanding of present-day glacial retreat. 

Finding threads of commonality among stories from multiple gallery participants, "Intersections" takes intimate memories and brings them to life. Participants sit alone in a secluded room and share real and imagined stories while navigating through a series of prompts. Speech is recorded in fragments and also converted to text to drive the compositional process. Important words, as determined through parts-of-speech and repetition analysis of the text, are entered in a Flickr tag search. Images thoroughly tagged and described by Flickr users, which often capture personal experiences, are then saved. In the public gallery space, three video monitors display a dynamic sequence of these images while two speakers (with left, right, and center channels) play back the speech fragments. Neurobiological principles of memory consolidation provide an underlying functional framework that determines probabilities and sequences of the image and speech output. Images and speech associated with frequently used words have a higher probability of occurrence and a greater longevity inside the system. Patterns emerge over time as commonly shared memories achieve a monopoly on the output. Ultimately this system functions as a collective mind where shared memories are fragmented and juxtaposed to form narrative re-appropriations of the original stories. In the end viewers are left with remnants of the original speech and continuously changing visual representations. The new system of memory is constantly in flux and becomes a new form in itself, a collective reminiscence.

The prevalence of smartphones has dramatically increased over the last several years, and with this comes an unparalleled medium for data collection. Smartphones are constantly transmitting data, and with an approximated 56% of American adults owning a smartphone, we now have a data medium that encompasses the majority of the population. One of the most valuable data that we can obtain through this medium is location data. By measuring the signal strength of a smartphone from a number external access points, we can collect accurate, real-time location data about a given user. This system has wide spread applications, whether it is being used academically for research purposes to measure travel patterns of users, or commercially to develop automated systems for building control. However, there is yet an easily accessible way to utilize the valuable information that surrounds us. Inexpensive, readily available hardware and software can be configured to develop a system that can be used to harness this data, and successfully doing so offers many opportunities. This can be done by using wireless adapters as access points, and calculating the location with triangulation with multiple nodes.

Ocean circulation is a complex and important component of the marine environment. By understanding the dynamics of ocean circulation, including upwelling, one may be able to accurately predict future ocean conditions. Using hindcast output from a Pacific Northwest (PNW) circulation model developed by Parker MacCready and Neil Banas, relationships between wind stress and coastal upwelling in the PNW were examined. Wind stress was analyzed using several different indices, and then these indices were correlated with biogeochemical water properties throughout the coastal domain of the model. Examinations were focused on which indices were most correlated with which water properties and how these correlation patterns varied spatially. Differences in correlation were found for coastal Oregon, the mouth of the Columbia River, and coastal Washington/Canada near the Juan de Fuca Canyon. These findings indicate that different wind patterns are needed to provide biologically favorable conditions in different areas of the PNW, and they help increase the accuracy of upwelling predictions throughout the PNW. The variability in optimal wind conditions point to differences in biogeochemical properties in the coastal PNW that have important implications for U.S. west coast fisheries.

Economic inequality in the US is the most unequal amongst all advanced economies in the world- and it is larger than we often perceive. In 2013 President Obama declared economic inequality as the “defining challenge of our time.” The problem now is that this “defining challenge” is growing. Currently, the top 1% own about 40% of the entire wealth in the US while the bottom 80% own about 8%. But who is influenced more by significant changes in the economy? Do the rich continue to grow richer even during periods of economic decline? With data collected from the Federal Reserve Survey of Consumer Finances, I compare the impact of the Great Recession on changes in wealth for different socioeconomic levels. I find that on average, individuals with lower incomes at the start of the recession saw greater declines in their wealth than individuals higher income, but the more assets individuals had, the more adversely the recession affected them.

Living Independently for an elderly person is very important.  No one wants to live in a nursing home, but living alone can be dangerous for some people with health problems. I am creating a prototype of a free app that is aimed at serving elderly people who live by themselves, especially those that have medical conditions. Once the app is downloaded, the user will be asked several important questions such as: if they have a Microsoft Health Vault, medical history, medication being taken, allergies to medicine, blood type, personal contact(s), residence, secondary personal telephone numbers (optional feature), Independent Living email address, and voice activated password.  The app allows the phone to be sensitive to shock set to a sensitivity level determined by the user to detect incidents such as a fall. It can also be voice activated using the voice activated password or manually activated by a press of a button. The user will also be able to set a predetermined amount of time to deactivate a distress signal to authorities in case of accidental activation. The app will also be capable of using the phone’s GPS capabilities to help authorities locate the person, if available. If a distress signal is not terminated, the app will notify predetermined personal contacts and 911 that Police, Fire, and Medical needs to be dispatched to the person’s location and the app will provide necessary details to adequately aid the individual. The app will be a free alternative to more expensive medical alert systems.

Hair cells (HCs) are the sensory cells of both the hearing and balance systems. HCs that die due to trauma or certain drugs are completely replaced in non-mammalian animals but replacement is extremely limited in mammals, including humans, causing permanent loss of hearing and/or balance function. In the balance system, HCs reside in five sensory organs in the inner ear and respond to changes of head and body position for balance regulation. HCs in the non-mammalian balance system undergo cell “turnover,” a process by which cells naturally die and are replaced. To investigate whether turnover occurs in a mammalian model, I studied utricles, one of the five balance organs, of adult mice. Utricles were immuno-labeled with antibodies to several cell markers, and I collected images of them using confocal microscopy. I observed that actin rich rings, called phagosomes, are prevalent in mouse utricles. These phagosomes seem to be engulfing HCs and likely belong to supporting cells, which surround HCs, instead of macrophage cells that professionally clear dying cells throughout the body. Some phagosomes have HCs inside of them, but most appear empty. This suggests phagosomes target dying HCs or HCs destined to die, and then clear the HCs from the sensory organ. I also observed that many phagosomes have actin rich spikes that may aid in finding the targeted HCs to be removed. These findings suggest that HC death occurs in normal mammalian utricles, which was not previously thought to happen. Because HC numbers remain unchanged in adult mouse utricles, this suggests that new HCs could be added during adulthood. I am currently looking for evidence of HC addition in adult mice. If HC turnover occurs, then the mechanisms responsible can be characterized and potentially manipulated to grow HCs back after damage in human hearing and balance systems.

This project examines the role of gender inequality in HIV/AIDS and how this inequality perpetuates the susceptibility of women to contract the virus. Focusing on Ghana and Brazil, I explore how culture and society shape an imbalance that potentially increases risks to women in becoming sick through analysis of the relationship between social determinants of health, risk factors and vulnerability. I argue that preventative measures intended to fight against HIV/AIDS have failed to consider the social circumstances that place women at greater risk than men. In my analysis, I draw on and interpret Michel Foucault’s concept of biopolitics using feministic critique and gendered perspectives. I reference anecdotes from Stephanie Nolen’s “28: Stories of AIDS in Africa” to present personalized perspectives of the painfully multifaceted reality of the HIV/AIDS outbreak, while Silvana Paternostro’s personal accounts of sexual culture in Brazil in “In the Land of God and Man: Confronting Sexual Culture in Latin America,” serve as a framework for my examination of gendered social constructs in Brazil. I examine gender relations and the dynamic of marital relationships that often disproportionately allow the male greater power over the female, and how a male dominant ideology is reinforced by politics, culture and social norm. Distinguishing between gender and sex, I look at how gender inequality, the inequality of opportunities and power that follow being a certain sex, may expose mothers, daughters, sisters, and other women at risk in ways we may not have imagined.

Calcium carbonate deposits precipitate in ocean sediments when biochemically-produced bicarbonate ions react with calcium ions in seawater. Bicarbonate is the product of a reaction that consumes methane derived from thermal and biological degradation of organic matter. In areas of the Washington margin where tectonic activity squeezes water and entrained methane up through the subseafloor sediments, methane flux is very high. During a research cruise on the Washington margin in August 2013, we discovered a field of unusually large carbonate deposits at a depth of approximately 1000 meters in close association with active methane seeps. As previous studies of carbonates in this area have been limited to dredge sampling, our study will be the first to utilize sonar mapping and in-situ photos acquired with remotely operated vehicle (ROV) Jason. In order to address questions regarding the spatial extent and formation of these carbonates, we will 1) assemble photomosaics from the ROV photos, 2) process multichannel seismic data to assess whether the methane driving the formation of our carbonates was transported though the sediments via linear faults, single vents, or diffuse venting, and 3) create a large-scale sonar map using both bathymetric and acoustic backscatter data of the area. Multichannel seismic data reveals faults and other subseafloor structures through interpretation of reflected seismic waves that travel through the sediment. Acoustic backscatter data provides us with an image of the seafloor through interpretations of reflected sonar waves. We are also attempting to date the growth of the carbonates by testing embedded mineral grains for the presence of volcanic ash from the Mazama volcanic eruption that occurred 6000+ years ago. With these four datasets, we anticipate gaining an understanding of how these carbonates formed and over what time scale, ultimately contributing to the growing geological knowledge of the Washington margin.

Random fractal patterns exhibit an overwhelming distribution throughout the natural world, from the smallest scale we can see, to the most universal scales we can imagine, and appear to affect everything in between. In order to explore some small-scale examples of this, we used high voltage to burn surface tracking patterns into various media, then analyzed the fractal dimension of some of the better samples. Next, we theoretically modeled radial diffusion-limited aggregation clusters (DLA) and a linear dielectric breakdown model by computer simulations, and analyzed the Hausdorff dimensionality of those, as well. Similar to previous experiments by Kim and Roh, and Niemeyer et. al., the experimentally and physically modeled results agreed in their dimensionality. This comparative analysis model implies a method of non-destructive analysis for a broad spectrum of insulating materials. These processes could help engineers design more robust dielectric components or safer airplanes, help geologists better understand fault-fracture spreading and aid in earthquake prediction, or enable atmospheric scientists to study elusive lightning structures known as sprites.

Giant low surface brightness galaxies (GLSB) are a class of spiral galaxies with larger and fainter disks than typical spirals. Previous theoretical work suggests that their formation history is distinct from that of normal spiral galaxies. Two main theoretical models for GLSB formation have been proposed. One possibility is that they begin as ordinary spirals and undergo a face-on impact with a small satellite, creating a compression wave (i.e., a collisional ring) which excites star formation throughout the neutral hydrogen disk and results in a large, faint stellar disk. A competing possibility is that GLSBs begin as elliptical galaxies or normal spirals and acquire disks through tidal disruption and accretion of a satellite galaxy. Preliminary investigation of these objects has shown that they possess bulges which are morphologically and photometrically similar to typical elliptical galaxies, suggesting that the GLSB disks could be the remnants of a satellite accretion event. Using the Apache Point Observatory, we have obtained longslit spectra of the central bulges of two GLSBs, Malin 2 and UGC 6614. Combining these data with spatially resolved spectra of the disks taken at the McDonald Observatory allows us to compare the disk and bulge kinematics and distinguish between the possible formation scenarios. Our analysis reveals that disk and bulge kinematics are closely correlated in both targets, which is consistent with both possibilities but may favor the collisional ring galaxy scenario.

 Most kinematic studies using modern human gait to provide insights into the movement of extinct hominins collect data from shod participants. Given that our hominin ancestors were habitually unshod, this methodology is potentially problematic if the kinematics of shod and unshod gait differ. We investigate whether or not differences are present by comparing the movement profiles of the lower limbs in shod and unshod walking. Kinematic data was collected on 20 women using an eight-camera motion capture system. Participants walked at self-selected slow, medium, and fast velocities, performing 30 shod and 30 unshod trials. Average velocities were calculated for each trial, as well as the maximum and minimum angles made by the foot, calf, and thigh during the stride cycle relative to the horizontal (foot) and vertical (calf, thigh) axes in the sagittal plane. Paired t-tests indicated that for all individuals, velocities differed between shod and unshod trials (p<0.01). Linear regression comparing shod and unshod lower limb angles was thus performed including velocity as a variable. Foot (p<0.001) angles differed between shod and unshod trials at all velocities. Additionally, the magnitude of the differences is positively correlated with velocity in all individuals (foot: p<0.001). These observed differences warrant a second look at previous kinematic studies. Future studies should consider using unshod participants to obtain data that is applicable to extinct bipeds.

The precision of a measurement can be enhanced by reducing the experimental cycle time, thus allowing a greater number of measurements for a given amount of time. In our apparatus, we utilize a coherent atomic source, Bose-Einstein condensates (BEC), for a precision interferometric measurement of a fundamental physical constant - the fine structure constant, which lies at the heart of atom-light interactons. The cycle time and therefore precision of these experiments is limited by the production time of BECs. A critical number of atoms must be collected in our atom trap for BEC production. This project explores the effectiveness of doppler cooling and collimating the transverse motion of a ytterbium atomic beam in reducing experiment cycle time. Transverse cooling is done using four lasers oriented orthogonally to the path of the beam and detuned from the resonant frequency of the 1S0 to 1P1 transition in Ytterbium. The optical pressure alters a significant fraction of trajectories to lead into the trap, as opposed to being lost due to large velocity components orthogonal (transverse) to the beam path. We have created a computer simulation of the doppler cooling technique to motivate design parameters such as the detuning frequency of the lasers. We will report on the experimental implementation of transverse cooling and compare it to our theoretical simulation

Burkholderia thailandensis uses acyl homoserine lactones (AHLs) as quorum sensing (QS) signals. Broadly, QS is a communication system that, at high cell densities, allows bacteria to coordinate group activities. Recent work from our lab has shown that in B. thailandensis, QS controls contact dependent growth inhibition (CDI). CDI is an intraspecies bacterial competition system  where CDI-proficient bacteria (CDI+) contain a three-protein system of CdiA, CdiB and CdiI. CdiA is a toxic protein displayed by CdiB, and CdiI neutralizes the toxic activity of CdiA. We predict that QS-control of CDI is a means of eliminating QS mutants from the population. B. thailandensis has three QS-systems; QS-1, QS-2 and QS-3, which each comprise of a specific transcription factor and a cognate AHL signal synthase that produces a specific AHL. A B. thailandensis mutant in all three synthase genes (btaI1-3) is defective at growth, inhibiting a cdiAIB mutant. However, we do not know the specific contribution of each AHL signal synthase. Thus, we sought to test the CDI activity of synthase mutants against cdiAIB mutants within a competition. We compared the starting and ending ratios of the different strains tested in each competition. Preliminary results have demonstrated that the btaI1-3 mutant is CDI defective, relative to wild type. However, signal synthase mutants are not defective at CDI. QS is required for WT levels of CDI. Additionally, we are investigating the dynamics of how CDI controls the growth advantage of QS mutants. A btaR1 mutant has a growth advantage when co-cultured with wild type in liquid but not during growth on a solid surface, which allows for CDI to occur. Thus, we are evaluating if CDI is responsible for restraining the growth advantage of the btaR1 mutant during growth on a solid surface.

Sepsis is a medical condition characterized by potentially fatal generalized inflammation, typically resulting from infection. Despite previous attempts to identify mechanistic therapies, no targeted intervention has impacted survival rates. Prior hypotheses focused on immunologic mechanisms, but this project investigates metabolic responses in sepsis using a mouse model. The current target of investigation is a nuclear hormone transcription factor called PPARalpha. PPARalpha regulates the expression of proteins and enzymes associated with inflammation, stress, lipid metabolism and is related to both human and mouse survival in sepsis. We hypothesize that PPARalpha is necessary to maintain energy production sufficient to support organ function in sepsis and that deficient PPARalpha activity results in organ system failure. Because cardiac tissues preferentially use fatty acids as an energy source, we hypothesize that it is the organ that will be most affected in sepsis. Sepsis was surgically induced in mice, tissues were harvested at specific time points and gene expression was quantified using real time qPCR. Seven genes involved in fatty acid metabolism were analyzed at time points 0, 24, 48 and 72 hours. PPARalpha expression was higher in wild-type tissues, but it was down-regulated in both wild type and knockout mice. In addition, wild type mice showed greater expression of fatty acid oxidation genes than PPARalpha-knockout mice at every time point though this group of genes was down-regulated in both cohorts. Knock out mice also showed increased cardiac PPARgamma expression at 24 and 48 hours, which is a marker of reduced survival in other models. Our findings indicate that wild type mice are better able to maintain energy production necessary to preserve tissue function. These results support the hypothesis that the major cause of death in septic mice is cardiac failure due to impaired PPARalpha expression and therefore inability to sufficiently metabolize fatty acids.

This project examines the ethical and social frames which facilitate environmental conditions that fuel the rampage of tuberculosis in India. Three key components of the basic biomedical outbreak narrative that are often overlooked will be brought forth to attention: the tuberculosis outbreak as more than just a bacterial spread, social constructs which shape the bacteria’s accessibility to victims, and socioeconomic determinants of treatment (and lack thereof). India accounts for approximately one-fifth of global tuberculosis occurrences, and with over 2 million cases in the country, tuberculosis is a continuously growing health concern, posing a major threat to the well-being of the population. Due to India's developing health care system, pollution, and poverty, these conditions amplify the ease of transmissibility and rate of infection. As treatment regimens are abandoned due to social stigma, medical side effects, and overwhelming price tags, the bacterium which causes TB (mycobacterium tuberculosis), tends to mutate and become drug-resistant to varying degrees; increasing the difficulty of containment and scientific development of effective medicines. Furthermore, the capitalist structure of the pharmaceutical industry contributes to the financial challenges which prevent the eradication of tuberculosis. Drawing on the theory of biopolitics while using sources of statistical information and analytical discourse,  my presentation seeks to explore various properties of the disease and discover how the complex interconnectedness of these underlying issues attribute to forms of structural violence, perpetuating the growth of tuberculosis in India.

Arm swing length has been observed to vary with walking velocity. The mechanical function of arm swing as a counterbalance to leg movement has been suggested as an explanation for these observations. If this explanation is valid, then step length should be a better predictor of arm swing length than velocity, even though velocity and step length are correlated. We hypothesize that the variation in arm swing length can be explained more by step length than by walking velocity in shod and unshod walking conditions. Thirteen women completed 30 shod and 30 unshod trials at self-selected slow, medium, and fast velocities. An eight-camera system collected kinematic data by tracking infrared reflective markers placed on participants. For each trial, we calculated average walking velocity and step length from the calcaneal tuberosity and measured two distances that the distal arm travelled in a step: arm swing length measured from the travel of the radial styloid process (RSAL) and the ulnar styloid process (USAL). Arm swing length does not differ between shod and unshod conditions (RSAL: p<0.69; USAL: p<0.74). Using linear regression, arm swing length is significantly associated with both step length (RSAL: p<0.001, r2=0.46; USAL: p<0.001, r2=0.53) and walking velocity (RSAL: p<0.001, r2=0.37; USAL: p<0.001, r2=0.43). In stepwise regression, walking velocity and the interaction of walking velocity with step length were removed in favor of step length. Our hypothesis is not rejected: arm swing length is more closely associated with step length than walking velocity in both shod and unshod walking conditions.

Although our pre-hominin ancestors almost certainly were climbers, most species of hominins infrequently used this ability. Recently, however people have begun to climb for recreation. With the growing popularity of rock climbing, we were interested in learning how the human body changes under these new forces. This study was designed to understand the relationship between hand proportion and hand strength in rock climbers and non-climbers. We hypothesized that rock climbers have stronger hands for their size than non-climbers. A hand dynamometer was used to test hand strength. The lengths of the carpals and metacarpals from the radial and ulnar styloid processes to the distal ends of each ray and the lengths of each digit and each phalanx were measured. In addition, the width and circumference of each hand was taken from the proximal phalanges, with the fingers resting against each other, and the circumference of each digit was measured around the proximal interphalangeal joing. We also measured the basic anthropometric variables of stature, body mass, and age and asked climbers how long they had climbed, the level of difficulty they usually climbed, and how often they climbed. Unsurprisingly, Student's t-tests revealed that the hands of men are bigger and stronger than those of women (all p's </= 0.004) and climbers are stronger than non-climbers (all p's </= 0.01). The circumference of the digits is ia significant predictor of hand strength when sex, side, and climbing status are controlled (all p's </= 0.03), with 67% of the variation in hand strength explained (r²=0.67).

M dwarfs are small stars with masses between 10 and 50% that of the Sun. They are also the most common, making up about 70% of the stars in our galaxy, and are noted for their high levels of magnetic activity. Stellar flares are a dramatic manifestation of this activity, and occur frequently on M dwarfs. Flares are explosive events resulting from rearranging magnetic fields on the stellar surface. We used data from the Kepler satellite to search for flares from a binary M dwarf system, named GJ 1245. With more than 8 months of continuous imaging, taken every 1-minute, we detected over 3,000 flare events from these twin stars. We conducted a by-eye search of this data to validate our automatic flare-finding code. We present the energy distribution and morphology for flares on these stars, and compare them to other well studied flare stars from Kepler. The long term goal is to train the automatic flare-finding code to run without the need for human validation, and thus to study tens of thousands of stars. By studying the statistical properties of flares on many M dwarfs, we will further our understanding of stellar magnetic activity and how flares are affected by the internal magnetic dynamo.

Autism Spectrum Disorder (ASD), including previously diagnosed Autistic Disorder, Asperger’s Syndrome, and Pervasive Developmental Disorder-Not Otherwise Specified, are all biologically based neurodevelopmental disorders that are characterized by an increased lack of social communication, social interaction skills, and restricted, repetitive behaviors or interests. College students who are either diagnosed with ASD or have similar behavioral traits might have a tougher time coping with the demands of a college lifestyle. In the past, little empirical data have shown if there is a link between Autistic traits found in the general population of college students and academic factors. For my project, I will briefly survey approximately 200 college students using similar questions taken from the Autism Quotient and Social Responsiveness Scale to test and see if the presence of Autistic traits affects college students academic performance and adjustment to college life. Additionally, I will interview students who are registered with Center for Disability Services with an ASD diagnosis at Everett Community College to better understand their challenges. Because of the difficulties Autistic students have to face in a college campus, such as social communication, navigating the campus, and a change in their once regular routines, it is hypothesized students who display Autistic like characteristics will decline in their academic performance compared to those who show an absence of Autistic traits. Suggestions for transitioning and coping to college life are discussed

The Western honey bee (Apis mellifera) is the principal pollinator for commercial agriculture and is estimated to provide over $200 billion in pollination services worldwide per year. In 2006, observations of widespread honey bee colony collapses initiated research on the cause or causes of their decline. Since then, pesticides, such as neonicotinoids (a class of newly popular agricultural pesticides), have received attention as a possible leading component in colony collapse disorder (CCD). However, regulations and research on neonicotinoids have been inconsistent in the United States (US) and the European Union (EU). The aim of this study was to compare registration and labeling standards for pesticides, and to review recent regulations to prevent bee declines in the US and the EU. I researched US pesticide regulations in chapter 40 of the Code of Federal Regulations and EU pesticide regulations published in the Official Journal of the European Union. I also compared published CCD research in the US and the EU in order to find correlations between pesticide regulations and instances of CCD. From my research I found that CCD is a complex issue with multiple compounding causes; neonicotinoids appear to be only one of the factors involved in colony collapse. I also found that some of the major differences in pesticide regulations are caused by the speed and extent of invoking the Precautionary Principle, which would support limiting the use of a pesticide with unknown effects; the EU tends to use the Precautionary Principle more often and implements it earlier. This research is important because the success of honey bee colonies has a large effect on worldwide agriculture and economics. By evaluating different approaches to CCD in the US and the EU, I have found certain regulations and farming methods that appear to have an effect on the number of cases of CCD.

Phylogeography is the study of the geographic and spatiotemporal distributions of populations, and it is an important tool for investigating the evolutionary history of species. Determining when and where species originated, merged, or moved is critical in understanding the factors that generate biodiversity. Novel Bayesian phylogeographic methods provide a useful tool for obtaining accurate estimates of these important population dynamic parameters. West Africa is a global biodiversity hotspot with a high number of endemic species, and Agama lizards are a diverse and prominent member of this distinctive ecoregion. To investigate the phylogeography of Agama lizards, I constructed phylogenetic trees from over 300 unique samples of Agama lizards from 20 countries using Bayesian phylogeographic inference. Molecular genetic data from a quickly evolving gene (16S rRNA) provided sufficient variation for estimating the divergences between distinct populations. Visualization of the phylogeographic history for the populations was conducted with Google Earth. This group of species is predicted to have originated in the central part of West Africa (i.e., Cameroon, Nigeria, and Equatorial Guinea). At least five distinctive species formed across the region from that one ancestral population, and one paraphyletic group requires further investigation. Outlining the history of species formation in subtropical West Africa, with an emphasis on when and where populations divided, moved, and reconnected, serves to show the benefits of phylogeographic studies as they can reveal patterns that are otherwise too difficult to detect using other approaches. These studies also serve as tools in providing information for the detection of distinct species.

Purkinje cells are large neurons with intricately elaborate dendritic spines inside the cerebellum of the brain, where they play an important role in controlling motor movement. The migration of Purkinje cells during morphogenesis of the cerebellum requires multiple signaling pathways. Prior research has shown that the extracellular matrix protein Reelin promotes Purkinje cell migration by triggering tyrosine phosphorylation of the cytoplasmic adaptor protein Dab1. Reelin signaling is terminated by the proteasomal degradation of phosphorylated Dab1. Cullin5/RING ligase (CRL5) is the E3 ubiquitin ligase that targets active Dab1 for degradation and its absence causes Dab1 accumulation and promotes Purkinje cell mispositioning. SOCS (suppressors of cytokine signaling) proteins are substrate adaptors for CRL5 that bring phosphorylated substrates to the ligase. SOCS7 has been previously described to be the substrate adaptor that recruits phosphorylated Dab1 to CRL5 during neocortical layering. However SOCS7 is not required for ubiquitylation and turnover of Dab1 in the cerebellum. Thus, the identity of the SOCS protein that regulates Dab1 in Purkinje cells during migration remains to be explored. A novel in utero electroporation method in the cerebellum enables us to manipulate expression level of different genes without the need to generate mutant animals. We will inject specific shRNAs to silence SOCS expression in Purkinje cells to address which SOCS recruits phospho-Dab1 to CRL5 in the cerebellum. Our expectation for this experiment is that knockdown of one or more SOCS proteins will mimic the same misposition phenotype of the Purkinje cells as described for CRL5 mutant animals. Thus we will identify the SOCS-CRL5 complex that regulates the migration of Purkinje cells during cerebellum development. Purkinje cell mispositioning may contribute to diseases like spinocerebellar ataxias and autism, pointing to the exigency of conducting experiments on the mechanism of Purkinje cell migration.

Pharmacogenetics is the field of biomedical science that studies how variation in a person’s genetic composition affects his or her response to drugs. Glucocorticoids are a group of signaling molecules that include endogenous hormones such as cortisol, which the body produces naturally in response to various forms of stress, as well as drugs with strong anti-inflammatory properties that are used to treat diseases ranging from asthma to cancer. The goal of this study was to identify correlations between interpersonal genetic variability and alterations in glucocorticoid receptor (GR)-mediated signaling. Salivary cortisol concentrations were measured in healthy volunteers (n=66) in order to determine differences in circulating cortisol concentrations and cortisol response following simulated physiological stress. Statistical analysis indicated inter-participant cortisol (CORT) variability was not correlated to participant demographics, health history, or single nucleotide polymorphisms (SNPs) in genes encoding the GR (NR3C1) or the essential GR chaperone protein hsp90 (HSP90AA1). Two participants with highly similar demographic profiles and opposing CORT responses (a matched pair) were selected for exome sequencing—the sequencing of all coding regions in the genome. A filtering algorithm identified candidate SNPs in approximately 30 genes involved in mediating the cortisol response and GR signaling. Interestingly, corticotropin releasing hormone receptor 1 (CRHR1) showed a difference of over 20 SNPs between the matched exome pair. CRHR1 regions were then sequenced from the larger participant group. Participants with average cortisol concentrations that slightly decreased following CORT stimulation most commonly exhibited a unique SNP profile—they shared many of the same SNPs in CRHR1. We speculate participants with SNP profiles associated with altered cortisol response may share a corresponding sensitivity to corticosteroid-based drug therapies.

Microfluidic devices containing microposts, which are used to measure platelet contractile force, are fabricated using a flexible polymer called polydimethylsiloxane (PDMS). PDMS possesses many advantageous characteristics including being non-toxic, optically clear, and typically desirable mechanical properties. However, PDMS is limited as a microfluidic device given its hydrophobicity, or strong ability to repel water. This characteristic is especially problematic when PDMS is used in microfluidic devices intended to analyze blood samples. Blood is protein rich, so the hydrophobicity in PDMS leads to significant biofouling, or biological accumulation, on the surface. Moreover, the range of mechanical properties available with PDMS is limited. This limits the utility of microposts as a platelet force sensing tool since the microposts may be either too stiff or too soft to adequately measure contractile force. The work presented herein sought to circumvent these challenges by replacing PDMS with polyurethane (PU). PU was chosen because its mechanical properties can be modified to adapt to a range of platelet contractile forces from, for example, hyper- and hyporeactive platelets. First, a range of PU types was explored. From these, a commercial grade PU entitled ClearFlex was found to be the best. As a result, it was used in subsequent characterizations, and an optimized protocol for casting microfluidic devices from ClearFlex was developed. The next steps are to test the mechanical, optical, and biological properties of ClearFlex compared to PDMS. The final PU microfluidic device will be developed into a diagnostic tool specifically for clotting disorders.

A major application of micropost technology is the measurement cellular traction forces to quickly diagnose potential medical issues. Currently, polydimethylsiloxane (PDMS) is the material used to fabricate micropost arrays using an intensive three-day double casting procedure. The process begins with casting a negative PDMS mold from a very delicate silicon master array. Negative molds cast from this master require surface treatment overnight via silanization in a vacuum, and then final casting requires an additional overnight cure. The silanization step cannot be forgone in the current process; doing so would result in a micropost array that is inseparable from its negative mold. Additionally, the double casting process must be repeated for every new array in each experiment since PDMS negative molds are not reusable due to degradation by repeated surface treatments. In order to improve upon the micropost fabrication process and widen the scope of applications beyond academia, my colleagues and I are developing a technique to cast PDMS micropost arrays directly from a reusable polyurethane negative mold. Our primary goal is to determine the reusability of polyurethane negative molds in casting PDMS micropost arrays without repeated silanization. To characterize reusability, I will use scanning electron microscopy to measure and quantify the dimensions of the microposts in the arrays in comparison to the silicon master. This step will be repeated for each array reproduced from the polyurethane negative mold as a quantitative measure of its reusability. The creation of a reusable polyurethane negative mold would completely eliminate the intermediate PDMS negative mold and subsequent silanization requirements. Therefore, this replacement would reduce the time required to create a PDMS micropost array from three days to eight hours. Moreover, a polyurethane negative mold could also allow for the simultaneous fabrication of multiple arrays, thus further reducing the time requirement for fabrication significantly.

Merkel Cell Carcinoma (MCC) is a rare, yet aggressive skin cancer with a disease-associated mortality of approximately 40%. Although surgery is typically a component of standard care, it is unclear how often patients should also receive radiation to control disease at the primary site. One retrospective study of 1254 patients found that of the patients who received surgery alone, 39% recurred locally compared to only 12% of the patients who received surgery in combination with radiation therapy. In contrast, in a cohort of 243 patients from New York treated with surgery alone, only 3.8% recurred locally. In order to establish a better standard of care for low risk MCC patients and attempt to resolve this discrepancy in the literature, we identified low risk patients within our cohort based on the following inclusion criteria: 1) primary tumor ≤1cm in diameter, 2) microscopically negative margins on the surgical excision, 3) absence of lymphovascular invasion in the primary tumor, 4) absence of profound, chronic immunosuppression, and 5) no microscopic evidence of nodal metastasis in the sentinel lymph node biopsy. Of the 29 patients who met these criteria, 17 were treated with surgery alone, while 12 received adjuvant radiation to the primary site after surgery. We found that 4 patients recurred locally (24%) among the patients treated with surgery monotherapy, while there were no recurrences among patients treated with surgery and adjuvant radiation. Even patients with low-risk MCC still have an appreciable chance of local recurrence if treated with surgery alone. While this risk may be acceptable to some patients, adding radiation therapy can lower the chance of local recurrence.

Traumatic Brain Injury (TBI) is a leading cause of mortality and permanent neurological disability. Microglial activation and inflammation contribute to the onset and progression of TBI-induced pathology. In this study we aimed to identify the factors that activate brain inflammatory pathways in the early responses to TBI, and the mechanisms by which inflammation is sustained during the late stages of pathology. We have previously demonstrated that the microglial expressed receptor, CX3CR1, regulates microglia activity. We have also shown that lack of CX3CR1 leads to deficits in cognitive function and synaptic plasticity. Here we hypothesized that the loss of the CX3CR1 receptor - and consequently, the loss of normal microglia function - would increase pathologic conditions in the brain after TBI and cause measurable defects in behavioral and cognitive abilities. To this end, three month old male CX3CR1 wild type and CX3CR1 knockout mice were subjected to a mild TBI (0.5mm depth) using a controlled cortical impact (CCI) animal model. Control mice (sham operations) received the same anesthesia and craniotomy, but were not subjected to CCI. All animals were humanely euthanized and transcardially perfused at fifteen and thirty days following TBI. I specifically participated in assisting TBI surgeries, behavioral testing, transcardial perfusions, brain sectioning, and immunohistochemistry. Our results indicate that lack of CX3CR1 at early time points protects neuromotor function, reduces cell death, and is associated with expression of microglia that have an anti-inflammatory phenotype. However, the long term effect of CX3CR1 receptor loss following TBI induces neuronal cell death, as well as neurobehavioral and cognitive deficits, which are associated with an increase in expression of microglia that have a proinflammatory phenotype. These results point to the presence of CX3CR1 in the early stages following a TBI as essential in slowing the progression of the neuropathology. In conclusion, CX3CR1, the fractalkine signaling receptor, plays a central role in regulating neuroinflammation after a TBI.

Intra-articular calcaneal (heel bone) fractures are common tarsal injuries that can require months for recovery. There are a few different treatment options available for these fractures including nonsurgical immobilization treatments, open reduction and internal fixation (ORIF) and percutaneous fixation. Classification of fractures can be a useful tool for medical professionals for communication and treatment planning. The existing calcaneal fracture classification systems used in clinical settings are subjective and not reliable tools for determining the best treatment for patients especially for highly fragmented (comminuted) calcanei. Calcaneal fracture treatments have high complication rates which compounds the need for a better treatment planning tool. The project goal is to develop a new calcaneal fracture classification system that utilizes CT image data to objectively calculate fracture severity metrics of the calcaneus, namely free bone surface area and the volume of surrounding soft tissue swelling. These metrics will be included on a calcaneal fracture report in addition to a model of the fractured calcaneus with fracture lines indicated. The software is developed using the Visualization ToolKit (VTK)  and the calcaneal model generated based on Simpleware ScanIP segmentation of the CT images. In the future, the software can be used to develop an index for the best treatment option for each fracture classification giving medical professionals a tool for aiding in treatment planning and a means of communicating fracture severity.

According to the World Health Organization, cardiovascular diseases are the leading cause of mortality worldwide. The low regenerative capacity of the heart renders it ineffective in healing itself after heart failure. Our lab has developed efficient methods to derive cardiomyocytes (cardiac muscle cells) from human embryonic stem cells (hESCs). However, it has become apparent that the cardiomyocytes derived using current differentiation methods exhibit immature morphological and functional properties. An important characteristic of mature cardiomyocytes is the presence of T-tubules, which are invaginations of the plasma membrane into the cell interior. These subcellular structures are critical for synchronized calcium release and contraction of mature cardiomyocytes. The protein caveolin-3 is a critical component of T-tubules, and thus its visualization can be used to assess the development of these important subcellular structures. I am currently evaluating the expression of caveolin-3 in hESC-derived cardiomyocytes using immunostaining techniques. For these studies, I expose the sample to anti-caveolin-3 as the primary antibody followed by a complementary secondary antibody conjugated to a fluorescent marker for visualizing the protein. Titration of several parameters, such as time of incubation and dilution of the antibodies allows for staining optimization. I have obtained detailed images of T-tubules aligning with striations in control heart tissue, but the staining is diffuse for the hESC-derived cardiomyocytes grown in standard 2D cultures. I am currently exploring whether this is a technical issue or the result of developmental immaturity. To assess the latter, I will stain hESC-derived cardiomyocytes that are more mature due to mechanical conditioning in 3D constructs. Optimization of this technique will facilitate our efforts to find novel agents that can accelerate the maturation of hESC cardiomyocytes. Finding ways to mature these cells will then provide a better platform for therapeutic applications such as drug screening, disease modeling and cardiac repair.

 Little is known about the conditions that permitted photosynthetic life to survive the global glaciation events known as Snowball Earth events. During this time, sea glaciers covered the Earth’s oceans, prohibiting the transmission of light. Without liquid water and sunlight, where did photosynthetic life survive? Research has shown that under certain climatic conditions, areas of sufficiently thin ice known as refugia could have existed at the landward ends of narrow channels where sea glaciers would be unable to penetrate. The idealized channels used in sea-glacier flow models allow for refugia under a restrictive range of climate conditions. However, experiments varying the channel entrance width have shown that a less restrictive range of climate conditions are needed for these refugia than has been previously thought. I hypothesize that moderate variations in channel entrance and sidewall geometries could both 1) expand the range of climate conditions that allow for a refugium at the landward end of the sea glacier and 2) generate thin ice zones in additional locations within the channel, likely near the entrance and on leeward sides of promontories. Utilizing finite element modeling techniques to simulate rectangular, trapezoidal, and round-sided channel entrances and promontories,  I will determine the locations of regions of zero or near-zero ice thickness in idealized channels. Combined with reconstructions of real-world Neoproterozoic geomorphology, these results could help us understand the conditions under which photosynthetic life survived Snowball Earth and even help to locate evidence of Snowball Earth-era photosynthetic life on the modern Earth.

Giardia lamblia is a protozoan parasite common in mammalian hosts and belongs to one of the earliest diverging eukaryotic groups. Subsequently, Giardia has a simplified and highly divergent genome that lacks classical actin associated proteins, yet has retained a conserved microtubule (MT) cytoskeleton. This unique cell biology could provide a window into ancient cellular processes, particularly cytoskeletal function and regulation. Giardia has evolved novel and elaborate MT-arrays that mediate important stages in a complex life cycle and assemble into structures critical to its virulence, motility, and cellular organization. Like most eukaryotes, Giardia possesses a superfamily of five tubulin paralogs (gene duplicates) that constitute the MT cytoskeleton (alpha, beta, delta, epsilon, and gamma-tubulin). Interestingly, the Giardia genome contains multiple paralogs of the alpha- (TUBA1, TUBA2) and beta- (TUBB1, TUBB2, and TUBB3) types. It remains unresolved why multiple, highly conserved TUB paralogs are maintained in the Giardia genome. To address this question, we localized tubulin proteins by expressing GFP-tagged tubulin under its native promoter in a pGFPa.pac expression vector. These constructs were transfected into cells and proteins were localized using 3D fluorescence microscopy. Microscopy of fixed cells revealed that TUBA and TUBB proteins localize similarly in interphase cells and are largely interchangeable (ventral disk, median body, flagella), yet display differential levels of expression. Namely, GFP::TUBB3 and GFP::TUBBA1 signal is much brighter than that of GFP::TUBB1, GFP::TUBB2, or GFP::TUBA2. Microscopy also demonstrated delta-tubulin is diffuse throughout the cytoplasm, epsilon-tubulin localizes faintly to the ventral disk, and gamma-tubulin appears to track the internal axonemes of the flagella and concentrate at the flagellar tips. This data could suggest Giardia utilizes alpha- and beta-tubulin paralogs in different stages of the life or cell cycle, which has not yet been demonstrated. This data will also inform the development of a robust live cell marker for Giardia’s MT-arrays.

Public health concern in the U.S and across the world regarding the impact of environmental hazards on human health is becoming more evident as we develop tools to see disparities in exposure and health outcome. Pollutants in the air and water can have lifelong consequences for the quality of lives of many people. Therefore, our toxicology laboratory is examining the result of pesticide exposure and toxicity in children, and how it may cause harm to normal development. Our research centers on studying exposure using blood, urine, and oral buccal samples obtained as part of a Children’s Health study on Yakima Valley. We have determined blood pesticide, urinary metabolite concentrations, cholinesterase activity, paraoxonase activity, and genome wide variation in 200 families. We have analyzed buccal samples from farmworker and non-farmworker families that were collected during different pesticide spray seasons. We are studying these buccal swab samples of children and their parents to identify bacteria present within them. We are utilizing targeted 16S ribosomal polymerase chain reaction (PCR) to determine the phylogenetic composition of the microbiome in saliva samples. The microbiome refers to the vast colonization of microbes within the body. There are more bacterial cells in our bodies than human cells even though they are only about 10% of the total mass. We hope to find a difference in microbe composition and metabolism for samples from agricultural seasons (pesticide use and non-spray seasons), and for child and adult samples. We have already analyzed pilot samples and found consistent results. Recently, we have begun PCR-based analysis and sequencing the remainder of the cohort buccal samples to characterize the diversity of oral microbiomes. If a link is found between the microbiome, pesticides, metabolic traits, and host genotype then we can more fully describe risk and metabolic biomarkers for exposed populations. 

On September 1st, 1991 a large nation state of Soviets died, giving birth to the Republic of Uzbekistan. As a result, thousands of non-Uzbek people became citizens by default in the newly independent republic. They had no chance but to stay in Uzbekistan – now their only homeland. Uzbekistan is a highly understudied region, especially when it comes to the national identities of Russian-speaking population that used to be labeled as the Soviets. The main research question is how linguistically russified non-Russian youth identify their national/ethnic identity in Tashkent, Uzbekistan today? I hypothesize that the majority of this population in Tashkent connect themselves to the Uzbek culture while integrating Russian cultural culture in their everyday lives. Russian speaking population today, though varying in gender, ethnicity and class, has similar experiences thus forming an identity that we can name as “Central Asians.” Methods I have employed are my positionality (I am a Russian-speaking citizen of Uzbekistan), interviews (informal interviews conducted in Uzbekistan with 5 adults), and participant observation (done in the summer of 2013 in Tashkent, Uzbekistan). The research sample are young adults between the ages of 20 to 22, raised after the collapse of the Soviet Union with Russian as their native tongue, but mixed ethnic backgrounds (linguistically russified non-Russians) who live in the capitol of Uzbekistan, Tashkent. The findings provided by this research are a significant step in understanding national formations in understudied Uzbekistan. Theoretically, studying independent formation of national identity of ethnic minorities in the post-Soviet nation-states can help understand identity formation of ostracized groups at the time of the mobilized nation building promoted by the government in the region. Urgent need for such research in post-Soviet territories is highlighted by the recent events in Ukraine and Crimean territory.

College student drinking continues to be a concern due to high consumption rates and negative consequences associated with excess use. Both male and female students are at risk for heavy alcohol use and related consequences. Symptoms of depression are also reported frequently amongst college students, particularly female students who tend to be at higher risk than males for depression. Evidence suggests that depressive symptoms are often correlated with increased alcohol use. Alcohol consumption has also been related to perceived social norms of peer drinking, i.e. the perceived amount of drinking that other students and peers typically engage in. Injunctive norms, which refer to perceived approval or disapproval of a behavior by other students, may be highly regarded by students as important for decisions regarding their own behavior. Furthermore, it is hypothesized that this relationship may shift with an increase in depressive symptomology in females. Injunctive norms-indicating approval from others-have been linked to increased alcohol use in this population. Prior research also suggests that female drinking tends to be more strongly correlated with typical same-sex student alcohol injunctive norms more than their male counterparts. Thus the proposed study examines the moderating role of depressive symptoms and gender on the relationship between injunctive norms and alcohol use in college-age students. The goal of this study is to further understand the nature of the relationship between injunctive norms and alcohol use, and whether depressive symptoms enhance risk from injunctive norms in females more than males.

This is an ethnographical account about a topic of little exploration, indigenous martial arts of the Philippines. Filipino cultures are a plurality of multi-stratum genealogies that merge and occasionally, disrupt one another. Filipino martial arts (or Eskrima) are a collection of Indigenous martial arts that has existed in the Philippines since pre-contact to today. Over the centuries, these arts have distilled into various systems, each with their own styles and codes. Through the methods of ethnographic data collection such as direct participant observation, shadowing, interviewing, literature review, journaling and self-analysis, I will document the shared phenomenological experiences and present a grounded theory based on the sorted material. My qualitative focus will be on one particular Filipino martial art system, Balintawak Cuentada. My presentation will convey the significance of heritage practices along with analytical insight into embodied anti-colonial perspectives while asking; how do practitioners, while living our everyday lives as Americans of Filipino decent maintain this embodied perspective? My study population is a group of practitioners dedicated to the Balintawak Cuentada system. Nearly all of the participants of this research, including myself, began our training because we wanted to connect to our ancestry in a way that could pragmatically fit into our modern lives. In our quest to reconnect with our heritage we have connected with each other. The preliminary results of this ethnography will have implications of significance to other social sciences concerned with place-making, identity, postcolonialism, embodiment, cultural memory, health and politics of the body including gender norms and performances as well as asking the philosophical questions of what are movements of the body without meaning, and what is a community without traditions. My expectation for this research is to document an example of deepening an understanding of the self through the physical engagement of ancestral habitus and ceremony.
 

 Embryonic stem cells can be used to study development and diseases. Mouse embryonic stem cells (mESC) are used as a model in developmental research and display several pluripotent properties not seen in the current human embryonic stem cell (hESC) lines. A newly derived line of naïve hESCs is thought to recapitulate an earlier stage of development, and resemble mESCs. To understand how the naïve hESCs differ from typical hESCs we are investigating DNA methylation, a form of epigenetic regulation, on a global scale at nucleotide resolution. The underlying genomes of cells are highly similar, yet their epigenomes change with cellular differentiation and development. Epigenetic modifications are important factors controlling gene regulatory elements. To analyze whole genome DNA methylation of the naïve hESCs, I am using MethPipe, a computational tool, to determine how the naïve hESC line differs from a later stage hESC line, and if the naïve line is more similar to mESCs at the epigenetic level. I will compare global methylation levels, hypo/hyper-methylated regions, and partially methylated domains. I will determine which regulatory elements, such as promoters, enhancers and CpG islands, show similarities and differences. We also expect to determine differential non-CG methylation (a characteristic of ESC). This characterization of naïve hESCs will provide a foundation for studying the earliest stages of human development.

Brain-computer interfaces (BCIs) are an emerging technology that uses neural signals to communicate with external electronic devices. Leveraging this technology for a variety of rehabilitative purposes has become a popular focus of research. One application is in guiding spike-timing dependent synaptic plasticity, a physiological mechanism where the strength of connection between two neurons is shaped by the precise temporal relationship of firing between them. Using a BCI to exploit this principle may offer a means of strengthening spared pathways after neurological trauma. In studies using rat models of spinal cord injury (SCI), a recurrent BCI called the Neurochip has been used to translate electromyographic signals (EMG) from impaired forelimb muscles into precisely timed intraspinal electrical stimulation at associated sites in the cord. Data recorded from forelimb reaching tasks have shown significant recovery of motor function following stimulation therapy. This is thought to be due to spike-timing dependent synaptic plasticity, but the fundamental mechanisms of behavioral improvement have yet to be elucidated. This investigation explores the role of gene expression in the stimulation treatment. Rats were given the same unilateral spinal contusion at vertebral level C4 and stimulated with the Neurochip device for 2 weeks of treatment. RNA from the rats was then isolated and analyzed using either Affymetrix GeneChip® or RNA-seq technology. Certain genes that have been implicated in neural plasticity were evaluated for expression levels. Of particular interest is the regulation of the mTOR and Wnt signaling pathways. Genes for mTOR and upstream mediators, such as AKT and PTEN, are important regulators of process outgrowth, regeneration and synaptic plasticity. The Wnt family of glycoproteins play critical roles in neuronal targeting and may guide synapse formation. Results of this study will contribute to understanding the cellular changes undergone during treatment.

Recent developments in research on Human Papillomavirus (HPV) have allowed for an increase of strategies that prevent the onset of cervical cancer within communities of little economic privilege. This project will compare preventative measures taken in India and those currently called for within the U.S., primarily examining how cultural and economic limitations are taken into consideration. As a “space of negation and the socially dead, produced by expropriations and alienations in and outside European nation-states” necropolis or low and middle income countries have historically been perceived as a necessity in order to maintain the priorities set by biopolis. However, organizations such as PATH are beginning to look into more cooperative methods. I will analyze the onset of preventative practices that promote self sufficiency in a format that maintains economic functionality and decreases potential dependency for aid. One significant limitation however is that western corporations still hold much of the control regarding economic leeway of vaccination use and price on a global scale. In this project I explore alternative methods that advocate information as an alternative or supplemental method for prevention. This project will continue by examining how circumstances in low economic environments are taken into consideration through efforts of vaccination or treatment. This includes the incorporation of cultural awareness, provision of knowledge and communication within the community, and how this leads to a stronger awareness of what limitations remain.