Bloodborne pathogens are wide spread and can pose risks to health care workers and vulnerable patient populations alike. Conventional diagnostic tests for bloodborne pathogens are costly and time intensive, so fast, affordable, and sensitive diagnostic methods are needed that can be performed under low-resource conditions by untrained personnel. Microfluidic self-digitization technology, developed in the Chiu Laboratory, provides the foundation for such low-cost diagnostics. As undergraduates, we work on the fabrication and optimization of cheap, robust devices used to load samples, as well as dPCR of samples required to detect diseases. As part of a larger research endeavor, we are developing a portable instrument that, in combination with our proprietary microfluidic chip technology, will expand rapid diagnostics to low-resource settings around the world. Expanding diagnostics for bloodborne pathogens will both help prevention as well as monitoring treatment of patients already infected.

The Hanford nuclear site is a 20th and 21st century example of America’s ongoing military industrial complex. Its ties with the aftermath of the Manhattan project shows that its harm was not unidirectional, but rather multidirectional since harm was done to the people of Nagasaki and to the communities within and around Hanford, Washington. Migrant workers have had ongoing misrepresentation regarding the nuclear site’s post-communal health impact; especially within oral and scholarly accounts. In this study, we explore what factors have had short-term and long-term impacts on the health, socioeconomic status, and autonomy of Hanford migrant workers. We use literature review and discourse analysis to understand these complexities affecting migrant health, and by developing these frameworks we reveal to the reader how such human and unalienable rights were undermined for the purpose of global control.

Metal catalysts exhibit greater catalytic activity as nanoparticles rather than bulk-like particles. Metal oxide supports can promote the activity and stability of metal catalysts due to the strong metal-support interaction, which can change the electronic properties and structure of metal nanoparticles. Metal-on-oxide-support systems are important for fundamental research and applications in heterogeneous catalysis. Nickel-based catalysts are widely used in industrial purposes such as carbon monoxide oxidation for industrial exhaust cleaning. However, nickel can rapidly deactivate due to solid carbonaceous material (coke) formation and nanoparticle coalescence (sintering) on the surface during a catalytic reaction. Metal oxide supports, such as ceria (CeO₂), improve metal catalytic performance by preventing coke formation and sintering, and in particular, ceria has a high oxygen storage and release capacity during catalytic reactions. Here, the adsorption energies, growth morphology, and charge transfer of adsorbed nickel on stoichiometric ceria (CeO₂(111)) and reduced ceria (CeO_1.8(111)) thin films at 300 K and 100 K are studied using single-crystal adsorption calorimetry (SCAC) in ultra-high vacuum (UHV) and surface sensitive techniques such as low-energy He⁺ ion scattering spectroscopy (LEIS), X-ray photoelectron spectroscopy (XPS), and low energy electron diffraction (LEED). The initial heat of adsorption of nickel atoms on stoichiometric ceria was ~45 kJ/mol greater at 300 K than at 100 K and ~65 kJ/mol greater than reduced ceria at 300 K. The calorimetry results indicate that nickel prefers step edges over terraces and binds stronger to stoichiometric ceria than reduced ceria due to nickel's oxophilicity. LEIS growth mode measurements indicate that nickel grows as 3D nanoparticles. XPS charge transfer experiments show that adsorbed nickel transfers electron charge to ceria below a coverage of 2 monolayers. These results encourage additional study of the adsorption energetics of other group 8 transition metals on ceria supports.

The narrative of nuclear patriotism was heavily promoted to justify the construction of plutonium production facilities like Hanford, as well as the use of plutonium-based atomic bombs against Japan. Nagasaki, bombed only days after Hiroshima, does not fit into this patriotic narrative and has subsequently been overlooked by the public. Just like the government minimizes the attention on Hanford in the United States, the bombing of Nagasaki is not as well known as the bombing of Hiroshima. As a result, Nagasaki victims have endured health disparities of equal magnitude in silence. We researched this topic further by conducting interview analysis, discourse analysis, critical film analysis, and literature review. We wish to connect Hanford and Nagasaki by focusing on downwinders and atomic bomb survivors. While Hiroshima has had more public exposure than the Nagasaki bombing, we want to bring to light the equally devastating impact of the bomb on the citizens of Nagasaki. Hanford and Nagasaki are tied together not only by association to nuclear weapons and radiation, but also by the silencing of their association to these weapons. These impacts are closer to home than one would expect, and it is essential to bring awareness to the unseen struggles within our international community. Cleanup of nuclear sites and nuclear regulation need to be regarded as national responsibilities to global safety, to ensure that history will not repeat itself.

Legal theorists have long maintained that courts operate beyond their primary function of dispute-resolution and have problematized their characterization as “objective” bodies, noting their significance as powerful social and political actors bestowed with constitutive powers of meaning-making. Virtually absent in this scholarship is an analytical angle examining this constitutive power using theory or methods from performance studies. This is surprising, as courtrooms are highly theatrical spaces. My research seeks to fill this gap in scholarship by marrying theories and methods from sociolegal studies and theatre- and performance studies to examine how courts contribute to the construction of cultural meanings pertaining to identity. This essay treats the European Court of Human Rights (Court), the judicial organ of the Council of Europe and one of the most active, powerful international human rights courts in the world. How does the Court construct notions of identity – especially around nationality, European community, gender identity, and religion? More specifically, my project asks: How are these courtroom constructions conceived and legitimized through narrative performance, and how is their sociopolitical influence shaped by the mechanics of performativity? To answer these questions, I conduct an original research project analyzing both written judgments and video recordings of oral hearings held in the Court’s Grand Chamber. I form my own criteria to analyze these hearings as performances, and create a scheme to evaluate written judgments for their performativity. I also analyze certain structural characteristics of the Court, and some legacies of its case law, as symbolic and embodied performances, examining how identity narratives are reproduced by the Court’s composition as an institution and its behavior over time. In addition to demonstrating what can be gained by critically assessing courts holistically using performance theory and methodology, I hope to illuminate exciting intersections between sociolegal studies and theatre- and performance studies with this work.

From the years 1946 to 1958, the Republic of the Marshall Islands (RMI), a sovereign nation in free association with the United States, endured the nuclear detonation of 67 atomic bombs conducted by US military. As a result of the nuclear testing, many Marshallese were gravely affected by the radiation exposure: suffering multi-generational health problems as well as being displaced from their homes. The unprecedented amounts of nuclear contamination have inevitably forced the Marshallese to abandon their lands, which has severely disrupted their cultural practices and lifestyle that has been passed down for years. The people have suffered countless traumas including birth defects and miscarriages, cancer, and autoimmune diseases. Through interviews, literature reviews, documentaries, and other modes of anthropological discourse, we will be demonstrating how the Marshallese have been affected by the US Government Nuclear Testing Program, and how this may parallel to the detrimental health effects of the people living near the Hanford Facility in Eastern Washington. Given the severity of health problems and involuntary migration in the RMI, we argue that the US government should take more responsibility and initiative to ensure that the Marshallese are granted proper restitution for the irreparable damages these nuclear test operations have caused to them and their culture. By implementing codes of ethics as well as more access to healthcare, we believe the health and wellbeing of the Marshallese will begin to thrive once again.

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

Parametric models are used in demographic research to reduce the number of parameters over those found in a life table, smooth and correct inadequate mortality data, and provide insight into the underlying processes of aging and mortality. One difficulty with many existing parametric mortality models, such as the Siler model, is that they assume that mortality risk is homogenous. We developed the mixed-Makeham model to explicitly model heterogeneity in mortality in the youngest ages. The model divides mortality risk at the youngest ages into “low-risk” and “high-risk” subgroups, as well as a parameter that specifies the fraction of newborns in each subgroup. Senescent mortality in both subgroups is a shared 2-parameter Gompertz model. We apply the model to cohort life table data from 11 European countries from 1876 to 1925 published in the Human Mortality Database. When mortality is decomposed this way, the proportion of high-risk infants declined and the mortality risk for low-risk infants declined for later cohorts, as anticipated. The mortality hazard for high-risk infants, however, increased for later cohorts. These findings suggest that, over time, medical and public health improvements shifted some fraction of infants from the high-risk category to the low risk category. The shift toward higher mortality hazard in the high-risk infants is likely explained by heterogeneous risk in the high-mortality pool, where medical and public health improvements are less effective on infants at the highest mortality risk.

Natural dermal armors are inspiring the development of advanced engineering materials and next generation flexible armors. Fish scales are an exemplary candidate and consist largely of laminated plies of unidirectional type I collagen fibrils. The mechanical properties of fish scales depend on the interpeptide bonds within the triple helix of the collagen fibrils. Adjusting the strength of these bonds to change the performance of the scales has applications to the design and functionality of bioinspired flexible armors. Here, elasmodine scales were exposed to polar solvents to adjust the extent of intermolecular bonding. Changes in the mechanical properties were evaluated in uniaxial tension and at two different strain rates. Results showed that the constitutive behavior was highly dependent on the intermolecular bonds. A significant increase was observed in elastic modulus (stiffness), strength and toughness as a result of increasing the extent of interpeptide bonding via solvents with low affinity for hydrogen bonding. A 300% increase was seen in the elastic modulus of scales soaked in acetone compared to HBSS at the highest strain rate. Furthermore, the importance of interfibril bonding was dependent on loading rate. Overall, results showed that the “protecto-flexibility” of fibrous armor materials can be improved by activating interfibril bonds and that this could spawn approaches for tuning armor performance.

c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinases (MAPKs) family that are derived from three genes: Jnk1, Jnk2, and Jnk3. JNKs have been implicated in several cellular responses to homeostatic insults, including inflammation and apoptosis. We previously reported in a chronic epilepsy rat model significant elevated levels of phosphorylated JNKs (pJNKs), which indicate increased JNK activities. Additionally, we demonstrated that pharmacological manipulations of JNK proportionally affected seizure frequency. In this set of experiments, we attempted to identify which of the JNK isoforms (JNK1, JNK2, JNK3) contribute to the overall increased pJNK levels in our animal model of epilepsy. This would provide us insights as to the role(s) of JNKs in this disease. We measured the phosphorylation levels of the individual isoforms after pJNK enrichment from the CA1 hippocampal tissue of chronic epileptic rats and their age controls. The amount of protein was normalized by pJNK levels between experimental and control samples. We found a significant increase in activation levels of JNK2 in chronic epilepsy at 130 ± 9% (n=6, p=0.018) when compared to naïve, nonepileptic controls but insignificant changes in activation levels of JNK1 (97 ± 14%, n=5, p=0.83) and JNK3 (98 ± 17%, n=6, p=0.92). Previously, we had found in rats that JNK1 predominantly exists in the 46kDa size; JNK3 predominantly exists in the 54 kDa; and JNK2 exists in both sizes equally. We further analyze which of the JNK bands (46 kDa and 54 kDa or both) contribute to the elevated phosphorylated JNK levels. Given the previous pharmacological observation that JNK manipulation does influence seizure frequency in epilepsy, this investigation is imperative as it will allow us to narrow our focus to a specific JNK isoform to study further.

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

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

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

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

The endothelial to mesenchymal transition (EndMT) has been identified as a key part of organ development as well as many disease pathways. EndMT is characterized by endothelial cells, which make up the inner lining of blood and lymphatic vessels and are adhesive and non-migratory, gaining mesenchymal markers and invasive, migratory behaviors. This overall change in phenotype is normal in embryonic development where EndMT is linked to development of organs but has also been linked to numerous diseases in adults including cerebral malformations, Alport nephropathy, fibrosis, heart disease, and bronchopulmonary dysplasia. Whereas it appears that EndMT does not discriminate by organ, it does by sex. The diseases mentioned previously have a significantly higher incidence in males. To understand the role that sex plays on the EndMT pathway, human neonatal pulmonary cells with a gestational age of 18 to 19 weeks from three female and three male donors were routinely cultured and monitored for changes in phenotype. Using angiogenesis sprouting assays, western blot protein analysis and immunostaining, we collected quantifiable data on the reversibility of the EndMT process in each donor. We found that cells from male donors had lower plasticity, characterized as shifting between the two phenotypes, and generally existed in an endothelial state until pushed into a mesenchymal phenotype through a stressor. Female cells were more likely to shift between phenotypes regardless of conditions and exhibited more angiogenic potential, suggesting a heightened ability to transition between phenotypic states. Future experiments include placing cells in environments with differing stressors to mechanistically determine what drives EndMT processes and monitoring cells with time-lapse imaging to quantify the dynamics of the transition.

National calls have been made to strengthen our nation’s STEM workforce by improving preparation and increasing graduation rates. At Portland State University (PSU), Oregon’s largest urban university, over 60% of students transfer from community colleges and the large majority do not live on campus. Transfer students may perceive a loss of support and a drop in GPA during their first term post-transfer, elements of what is known as “transfer shock.” As part of a newly-awarded NSF S-STEM grant, we aim to measure if high-impact STEM support programs can mitigate factors related to transfer-shock and support student sense of belonging. Direct impacts of the S-STEM program are being assessed qualitatively (e.g. focus groups, reflections), and preliminary results for our first cohort of S-STEM Scholars indicate strong bonds among the cohort and feelings of success. To examine how students supported by the S-STEM and other high-impact STEM programs compare to other PSU STEM students, a survey measuring self-efficacy, scientific identity, scientific values, STEM involvement, and sense of belonging was broadly disseminated to students in Fall 2018 and will be repeated in Spring 2019. Initial survey results (n=933) allow us to compare student responses for students supported (n=93) or unsupported (n=840) by programs such as the S-STEM. We will also compare traditional four-year students (n=291), community college transfer students (n=398), and four-year college transfer, returning, and post-baccalaureate students (n=240). Preliminary results indicate that students supported by high-impact STEM programs such as the S-STEM report significantly higher sense of belonging, both at PSU and in STEM groups. Efforts implemented by the S-STEM program to improve STEM student experiences academically, financially, and socially, particularly to the most vulnerable populations, will ultimately improve and diversify the STEM workforce.

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

The geriatric population is the fastest growing population in the U.S. Mental health is crucial to the quality of life of geriatrics and the family members who take care of them. While mental illness is a common health concern in the geriatric population, under-diagnosed and under treatment of mental illness creates challenges for the health and well-being of both elderly patients and their families. Unfamiliarity with psychiatric health, such as recognizing signs, symptoms, and providing appropriate referrals and treatment, may result in myths, the stigma of mental illness, and appropriate and timely psychiatric care. The purpose of this meta-analysis research is two-fold. First, the research provides a summary of the current evidence regarding the cause of geriatric psychiatric issues in nursing-related settings. Second, it highlights the possible solutions to the shortage of psychiatric nurse practitioners. As healthcare practitioners, nurses must have proper training in order to be aware and recognize geriatric mental health illness and provide appropriate care for our patients and their families. Providing patient education to the geriatric population and family members will allow them to assist in identifying the signs and symptoms of potential mental health problems. Lastly, the meta-analysis will examine possible solutions provided by current geriatric researchers for the best way to identify and treat psychiatric problems in the geriatric population.

The physics behind wave-driven mixing of river and ocean waters and current-driven wave breaking are not well understood. The current body of work surrounding river-ocean interactions focuses on large rivers. However, small rivers, which are much more strongly influenced by waves, make up the majority of such systems, and contribute significantly to global riverine discharge. Examining the momentum balance of river flow in opposition to wave-driven forcing from the ocean is necessary to understand how waves influence the travel and mixing of river water. One way to measure this interaction is using instrumental drifting buoys that follow the path of the river water and take temporal measurements of water properties. These leave gaps in our knowledge, as such buoys do not provide a description of the entire system, only specific points. To fill in these gaps, Unmanned Aerial Vehicle (UAV) footage was used to understand broader wave-current interactions at the Quinault River mouth, a small river that feeds directly into the Pacific Ocean. The town of Taholah, WA, is on its banks, and faces challenges due to wave-driven flooding. The size of the surf zone, the nearshore region where waves break at high frequency, was mapped with UAV footage, and related back to local environmental conditions, such as tidal phase. At low water, the momentum from the river is maximized, and so is the cross-shore extent of the surf zone. This decreases salinity around the river mouth, as freshwater is trapped by the surf zone. At high tide, these conditions are reversed, and fresh water streams can be detected past the surf zone, suggesting the river water has escaped from this region of high turbulence. The conditions under which these escapes occur are to be understood by combining analyses of UAV footage with drifter and tidal data.

During embryonic development, a dormancy-like state known as diapause arises during the transition from pre to post implantation. This state of suspended development is a reproductive strategy which favors newborn survival in mammals during nutritional deprivation or stress. Studies from the Ruohola-Baker lab found potential candidate regulators of diapause by establishing an in-vitro diapause model using pluripotent mouse embryonic stem cells (mESC). One of the genes is Activating Transcription Factor 5 (ATF5) which encodes a protein capable of survival-mediated functions such as maintaining mitochondrial activity during stress, modulating cell differentiation, preventing apoptosis and regulating cancer pathway. ATF5 has been known to transcriptionally target mTOR, a mechanistic target of rapamycin. Energy stress in the form of starvation and pharmacological inhibition of mTOR has shown to induce diapause-like state in mESCs in vitro. Our hypothesis is that upregulation of ATF5 under energy stress will reestablish diapause-like state in naïve mouse embryonic stem cells in vitro. We will test our hypothesis by loss-of-function and overexpression experiments. We test if ATF5 gene knockout using CRISPR-Cas9 prevents the mutant lines from entering diapause-like state from energy stress. Using western blots, we will quantify phospho-mTOR levels and its downstream targets in the ATF5 KO lines and compare them with the wildtype lines. For the overexpression of ATF5, we will make rescue lines for the ATF5 KO cells. We predict that overexpressed ATF5 in rescue lines will enter diapause-like state, and have reduced mTOR and its downstream target signals compared to KO lines. Our discoveries of ATF5 function in diapause can be useful in understanding how early-staged cancer stem cells enter a diapause-like state or quiescent state which enables them to escape chemotherapy detection. We can potentially contribute to the development of therapies to target ATF5 mechanism so that these undetected cancer stem cells can be detected.

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

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

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

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

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

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

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

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

Myanmar has been enveloped in seemingly endless civil strife since their independence from British colonization in 1949. The country is comprised of a wide array of ethnic minorities, each with their respective language and culture. Myanmar’s government may publicly announce its pride at the country’s diversity, but within, human rights violations committed by the military abound. The peace process towards a federalist state is long and hard, and has seen many cycles of ceasefires and armed conflict. My time in Thailand during CHID’s Gender, Peacekeeping and Human Rights program addressed this conflict from a myriad of perspectives. As a result, I have learned about the silent heroes of Myanmar’s peacekeeping process: the community based organizations that are actively changing the power landscape of rural areas within the ethnic minority states. There are several community-based organizations operating from the Thailand-Myanmar border that are addressing and spreading awareness of the human rights violations inside ethnic states. Most importantly, they are addressing maternal and child health in high risk areas where maternal mortality rates are some of the highest in the world. Through meetings and interviews with various community-based organizations, I am exploring the relationship between family planning and maternal health programs on the ground and women’s participation in the peace process in the country overall. I am also using content analysis of reports done by the organizations, who have obtained valuable, on the ground data from remote areas within Myanmar. I am interested in whether investing in these programs and supporting this communtiy-based approach could be one possible solution to creating multilateral agreements that last in Myanmar because of the additional involvement of women in politics and leadership.

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

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

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

Mutation produces new variation in populations, and in each generation these variants are copied from parents to offspring. While almost all variants of genes are lost, they may remain in the population for many generations. We use branching process models to analyze counts of gene copies. In a population of constant size, on average, a gene copy produces one offspring copy at the next generation. An advantageous mutant will have a mean greater than 1, and a deleterious one will have a mean less than 1. It is thought that most mutations are slightly deleterious, and with high probability those variants become extinct rapidly. Nonetheless, the few deleterious mutants that are not yet extinct may achieve high numbers. Thus, we have a particular interest in those with a mean slightly less than 1. We use different probability models for the offspring distribution and consider the mutant’s survival about: the extinction probability over k generations, the expected copy count conditional on survival, and the probability of survival additional k generations conditional on surviving k already. We find that variances in addition to means of offspring distributions closely relate these statistics. By adjusting parameters of distributions, we let the mean and variance be approximately the same across distributions. Based on our simulations, when k is large and the mean and variance of offspring are the same, the mutant’s survival condition is uniform throughout. In other words, those statistics above can be estimated by the mean and variance exclusively, and the specific distribution does not affect much the conditional population dynamics. However, at the first few generations, these statistics are different for each distribution. Thus, if we know the mean and variance of a mutant, we can predict the long-term population behaviors conditional on survival without knowing the true distribution of the mutant.

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

Herpes simplex virus (HSV) infects mucosal epithelial cells and can cause recurrent, painful ulcers. HSV is not curable and establishes lifelong latency in host neuronal ganglia. Herpes affects more than 400 million people globally, with an increased risk of genital ulcer disease, HIV acquisition, and transmission of HSV-2 to partners or neonates. Persons with altered T cell immunity have been reported to have prolonged and more frequent lesions, suggesting that the adaptive immune responses are associated with HSV clearance. Additionally, there is evidence of innate cell and T lymphocyte recruitment to the infection site to help clear the lesion. While there is extensive evidence on the role of T cells in these lesion infiltrates, little is known about B cell activation and antibody response during HSV reactivation. The study of B cells and antibodies can be used in developing a HSV vaccine since all licensed vaccines induce robust antibody responses. Antibodies block virus entry and mediate antibody-dependent cell-mediated cytotoxicity (ADCC). That is why a better understanding of local antibody responses against HSV-2 is needed to develop a successful vaccine. My project examines whether HSV antibody-producing B cells are found in areas where HSV-2 reactivates and the potential role that these antibody-producing cells play in host clearance of the virus. To examine this question, ddPCR using B-cell-specific probes were used to identify different B-cell subtypes responding to the HSV infection. Results to date have shown high variability with few emergent patterns. In the future, additional samples will be examined using new protocols for better cDNA synthesis, and more positive and negative controls to increase the accuracy of the data.

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

Due to antibacterial resistance and the high recurrence of urinary tract infections (UTIs), studies have shifted to focus on anti-adhesive therapies as alternative to antibiotics. Often treated with antibiotics, UTIs are caused by uropathogenic Escherichia coli (UPEC). The bacterial adhesin, FimH, found on the terminal end of fimbria, hair like structures expressed on the perimeter of UPEC, is the main etiological factor of UTI prevalence and recurrence. FimH increases the virulence factor of E. coli by mediating the initial binding of the bacteria to glycosylated cells in the urinary tract. FimH has two domains. The lectin domain (LD) recognizes and binds the terminal mannose on glycosylated cells lining the urinary tract, whereas the pilin domain acts as an anchor to the fimbria. Previous studies have shown that α-methyl-mannose (αMM) competitively inhibits glycoproteins, such as horseradish peroxidase (HRP), from the FimH active site. We hypothesize that αMM can non-competitively inhibit HRP through a novel mechanism of inhibition. To determine the mechanism of inhibition of HRP in the presence of αMM, we are using Enzyme Linked Immunosorbent Assays to measure the dissociation of HRP in the presence and absence of αMM, after the FimH-HRP complex has formed. We expect to see an increase in the dissociation of HRP in the presence of αMM. HRP in this case, will act as a model to the glycosylated cells lining the urinary tract. This study aims to assist in the design of innovative anti-adhesive therapies that inhibit binding of FimH once bound to glycosylated cells lining the urinary tract.

Most organisms show a roughly 24-h cycle in their physiological and behavioral processes, called circadian rhythms, generated endogenously through the ~24h cyclic expression of genes known as clock genes. Clock gene expression oscillates in the master circadian clock of mammals – the suprachiasmatic nucleus (SCN) - and nearly every cell of the body. Typically, circadian clocks and the rhythms they sustain are ‘entrained’ by the 24-h light-dark (LD) cycle. Our lab has found that fear can also behave as an entraining factor. We observed that when mice or rats need to leave a safe nesting area to access a foraging area, they forage and feed during the dark phase of the LD cycle. If the foraging area is rendered dangerous with random uncued footshocks during the active dark phase, the animals’ foraging and feeding activity shifts to the light phase. My goal is to understand the neural circuits and molecular processes involved in fear entrainment. I have analyzed the expression of clock genes in animals exposed to nighttime fear and control animals exposed to daytime fear; this allowed me to assess the circadian rhythm of expression of clock genes of interest (Per1 and Bmal1) in the SCN and amygdala, and I found that the amygdala entrains to fear but the SCN does not. I have also performed trials with brain-specific-knockout mice and found that nocturnal fear entrainment requires an intact molecular clock. My current experiments use a more specific knockout strategy of viral injections into the brain to determine whether a functioning circadian oscillator in the basolateral amygdala (BLA) or the SCN is needed for nocturnal fear entrainment. These experiments serve to unmask the molecular mechanism of fear entrainment and could also help understand the mechanisms linking fear and anxiety disorders to problems with circadian rhythms and sleep.

Dravet syndrome (DS) is a severe form of childhood epilepsy caused by a mutation in the SCN1A gene, which encodes the NaV1.1 voltage-gated Na+ channel. This channel is present in most GABAergic neurons, the main inhibitory neurons in the brain. Reduced activity of the channel in DS leads to loss of inhibitory activity in the brain; this, in turn, leads to seizures and developmental deficits. Through previous research using the mouse model of DS, the de la Iglesia lab has demonstrated that DS also affects circadian rhythms, which are the endogenous biological rhythms synchronized to the 24 hour day. These symptoms are likely caused by the loss of NaV1.1 in a sleep regulatory center called the suprachiasmatic nucleus (SCN), a set of cells which functions as the ‘master clock’ of the circadian system of mammals. However, the de la Iglesia lab found that selective deletion of the SCN1A gene from the SCN fails to replicate the abnormal circadian phenotype. We believe that these mutant mice are phenotypically normal either because there is a compensatory increase in the expression of another sodium channel, NaV1.3, or because the targeting strategy does not reach all cells within the SCN. To test the first hypothesis we employed in-situ hybridization to visualize the expression of the genes that code for NaV1.1 and NaV1.3 channels in either SCN-specific knock outs or their wild type littermates. My results will help explain the phenotype seen in the SCN-specific SCN1A mutants and determine whether developmental compensatory mechanisms are important in the SCN of DS mice.

Research has shown that positive outcome expectancy (i.e., anticipated positive consequences as a result of engaging in a behavior) and positive affective responses to exercise play an important role in predicting exercise behavior as well as future exercise intentions. Unlike most research in which the valence (i.e., positive - negative) of outcome expectancy and affective responses are typically assessed through survey items whose valence is predetermined, the current study used a spontaneous word association test (WAT) to examine the subjective meaning of exercise-related outcome expectancy and mood before exercise, and how they are related to exercise intentions and behaviors. One-hundred and eleven undergraduate and graduate students (74 females; 64 undergraduate students) performed an exercise-related WAT in which they were asked to write down the first word or a short phrase that comes to mind when they thought of (a) things that might happen from exercising and (b) their mood right before exercising. Subsequently, they were instructed to rate their subjective valence (i.e., positive-negative) to each of their responses to the WAT. They also completed a series of online self-report surveys that included assessments of exercise intentions and past exercise behavior. Path analyses will be conducted to test our hypotheses that the subjective valence of their mood right before exercising is expected to be directly associated with exercise behavior whereas the subjective valence of outcome expectancy is expected to be indirectly associated with exercise behavior through exercise intentions. This study examines the potential value and usefulness of a spontaneous word association procedure to more accurately measure affective evaluations of an individual’s feelings and thoughts toward exercise behavior.

In the United States, the use of nuclear weapons is often associated with an era of scientific discovery which led to the security of the nation; yet there is another side to the nuclear era, one characterized by loss and irreversible consequences that is often overshadowed. One manner in which individuals connect to nuclear culture is through nuclear tourism: tourism centered around visiting sites associated with the nuclear age ranging from museums, to nuclear storage facilities, and even cities. I found myself intrigued with people’s obsession towards this dark area and wondered what laid beyond the tourism itself and how tourism affects society’s perceptions of nuclear weapons. I aimed to discover what side of the nuclear arms argument is being portrayed, and the potential implications, through analyzing the structure and advertising behind prominent tourist locations in the United States and Japan. After critically evaluating five nuclear tourism locations, it is clear that nuclear culture was largely portrayed with a sense of nationalistic pride which concurrently creates misconceptions about the use of nuclear weapons, numbing society to the humanity and suffering behind the machines. However, there were a few locations that painted the nuclear era in a different light; one that is truthful to the mass destruction and loss created by the nuclear era, sparking conversations that can lead to positive change. Overall, while nuclear tourism allows individuals to explore nuclear issues that face the world today, we must look beyond the technological contributions of the nuclear era and remember the humans whose lives were forever harmed as a result of using these weapons. It is critical to have avenues, such as tourism, to share knowledge about nuclearization that not only generate awareness but also work towards a world where nuclear weapons are simply a thing of the past.

Through mapping the complexities of spatial inequality, I examined the geographic differences in economic and socio-cultural inequality across the state of Indiana. I grew up in Indianapolis, Indiana in an upper-middle class neighborhood that undoubtedly limited my ability to see inequality. Examining inequality in my home state provided me with a deeper understanding of the gap between rich and poor within the state, how Indiana fits into the growing wealth gap in the United States, and how income inequality further impacts access to education, housing, and healthcare. I collected data from the US Census Bureau for Indiana and Indianapolis, as well as the three richest and poorest cities in the state, St. John, Zionsville, Carmel, Gary, East Chicago, and Muncie. Across the state and the seven cities studied, I measured educational attainment, employment status, health insurance coverage, housing costs, and income in the past 12 months. In Indiana, less than 25% of the population over 25 has a Bachelor’s degree. Rates of health insurance coverage vary greatly across the cities studied, but are fairly consistent across racial lines within cities. Income distribution varies drastically across the state, and by race across the seven cities in this study; however, single mothers, regardless of their race or ethnicity, are far more likely to be impoverished compared to the average in each city. In the three richest cities, populations are almost entirely white, while populations in the three poorest cities are almost entirely African American. Economic differences are not the only indicator of inequality in Indiana; socio-cultural differences also underlie many aspects of poverty and inequality. Mapping how inequality varies in terms of race, gender, and location provided a stronger sense of how geography affects the distribution of wealth and resources, and who is impacted the most.

For many Somali refugees in Italy, the journey from Somalia to Italian land is fueled by an overwhelming desire to seek better opportunities in education, employment, health, and lifestyle. As a country previously known for its luxurious beach resorts and affectionately named “the nation of poets,” Somalia has since dramatically shifted to a land inflicted with ongoing violence, terror, and instability. In this research, we will be exposing how the legacy of Italian colonial power has led to numerous detrimental effects on both the people and the government in Somalia. Furthermore, we will be investigating the ongoing refugee crisis in Somalia, focusing specifically on political and colonial history. Using an ethnographic approach, our research project provides insight into the harsh realities that face Somali refugee immigrant populations in Italy. Over the course of six weeks in Rome, Italy, our team has engaged in qualitative research methods in which we collected personal testimonies from current Somali refugees living in Rome through observations, interviews, and daily interactions. The results of our research will uncover the role Italy has had on the ongoing humanitarian crisis affecting the Somali diaspora.

The construction of the Hanford Nuclear Site was to aid the production of the atom bomb for the United States in World War II. This led to an era of secrecy, especially for the Hanford workers. A whistleblower is someone that brings about safety concerns about nuclear production to the public, but only with the risk of losing their job. Recent trends have shown that there are major consequences to whistleblowing, as many in the past who whistleblowed lost their jobs. However, whistleblowing is crucial to sustain the safety and health of many workers. Our purpose is to identify the motivations of these workers for either speaking out against the program or staying silent. Through analyzing interviews, literature and discourse, we hypothesize that whistleblowers at Hanford spoke out when they felt their moral obligations outweighed any monetary or social gain. Because the government heavily suppressed the voices of workers, we wish to better understand how society fosters environments where people are comfortable to speak out as opposed to promoting an environment of secrecy.

The most effective semiconductors used as absorber layers for solar cells have concerns regarding high capital expenditure (CapEx) for new manufacturing facilities, earth abundance, toxicity, or cost-volatility of the materials. Solution processing is a low cost, low temperature development method leading to lower CapEx. The exploration of new photovoltaic materials seeks to develop an earth abundant, non toxic semiconductor via solution processing with efficiencies comparable to materials like silicon or CdTe. Bismuth rudorffites (chemical formula A_aBi_bX_a+3b) are an interesting category of new materials, proven to be solution processable, to have high absorption, and to be capable of cell efficiencies over 4%. My project seeks to optimize the thin-film morphology and the open circuit voltage (V_oc) of bismuth rudorffite layers, both of which are crucial to achieving high efficiencies. A good morphology will be phase-pure and densely packed, with large grains. By determining the effects of each parameter of the thin-film deposition process (spin-coating, in our case) through Scanning-Electron Microscope imaging and X-Ray Diffractometry, I have determined an optimized deposition procedure leading to good morphology. The utilization of Absolute Intensity Photoluminescence techniques (AIPL) allows for prediction of the V_oc to a high degree of precision without building an entire solar cell, instead only measuring the absorber layer. By illuminating the absorber and detecting the re-emitted light, models can determine the density of "radiative recombinations" of electrons and holes, which correspond to electrons that would be capable of generating a voltage and providing electrical power. By using this method and by building an understanding of rudorffite crystal growth, I have attempted to reduce "non-radiative recombinations," increasing the PL and hence increasing the capacity for high V_oc in rudorffite cells. Here is presented current data, results, and recommended experiments necessary for rudorffites to be a successful photovoltaic material.

Dysregulation of the dopamine system is a central mechanism driving substance use disorders. Our laboratory has shown that chronic cocaine consumption decreases dopamine release in the nucleus accumbens of the rat, which is a brain area that is important in reinforcement learning. This study also found that restoring dopamine transmission through the administration of the dopaminergic drug, L-DOPA, decreased their cocaine consumption. Recently, we have also shown that acute administration of L-DOPA decreases ethanol (EtOH) intake. Thus, the present study sought to examine the effects of chronic L-DOPA on operant responding for EtOH in adult male rats. Rats were presented with a 2-bottle choice between an EtOH (20%) solution or water, daily for 21 days. Next, animals made nose poke responses (FR1) for 0.2 mLs of an EtOH (20%) solution over 1-h daily sessions for 35 days. On Days 26-35, rats consecutively received either vehicle or L-DOPA (30 mg/kg) for 5 days, counterbalanced across days, and L-DOPA decreased operant responding for EtOH compared to VEH. We are presently examining the effects of L-DOPA on dopamine release during operant responding for EtOH. Together, these data may suggest the efficacy of L-DOPA as a treatment for patients with alcoholism.

With the discovery of radioactive materials, many institutions have conducted numerous radiation experiments in order to further understand the effects of radiation and radioactive contamination on human bodies and their environments. While doing so, there has been a great amount of unequal health disparities among the different communities involved. Institutions, like the University of Washington, while held in high regard, have participated in experiments that have affected the livelihood of many people. To this day, common knowledge of the University of Washington’s participation is still obscured. There are many institutions in the United States that are like UW and are known for their extensive and groundbreaking research; with the funding and power they hold, people often don’t question their research or their ethical approach to conducting it. From our research, we obtained a greater understanding of what occurred throughout the experiments - thus our goal is to bring attention to the actions of the University of Washington researchers’, C. Alvin Paulsen’s and Lauren R. Donaldson’s, unethical research practices in the Marshall Islands and UW Walla Walla Prison Radiation Experiments. Our methods include analyzation of interviews with Tom Carpenter - the Executive Director of Hanford Challenge, discourse analysis, reviews of relevant literature and interpretations of visual elements. Because the research of C. Alvin Paulsen and Lauren R. Donaldson is locked away in UW’s Special Collections Library, we were unable to analyze their research directly. We anticipate that this project will ensue more curiosity and lead to the general public learning more about the University of Washington’s participation in human radiation experiments.

There are countless times in the past where people have attempted to expose systematic injustices committed by the U.S. government. Despite the fact that Hanford was a critical site in producing plutonium for the atomic bombs dropped during World War II, the contamination and subsequent health disparities remain shrouded in mystery and present dangers to future generations. In this project, we explore how the Hanford facility and the release of radioactive waste impacted the culture and daily activities related to diet, health, and faith of indigenous peoples in Washington State, as well as efforts by the government and native tribes that have been made in regards to cleaning Hanford and protecting tribal lands. By comparing interviews of Native Americans affected by the Manhattan Project, their oral histories, literature, public speeches, and using website discourse analysis of governmental sites, we made several important observations. Through our research, we found that among the devastating results of the Hanford contamination, the most common theme was the upheaval and marginalization of indigenous culture and the resulting inability of Natives to take part in community building activities such as wild game hunting, fishing, spiritual ceremonies, and trade with neighboring tribes. Not only did contamination tarnish relationships that local natives had with each other and the land, but there was and remains a strong correlation between subsequent cancer-related health disparities and bioaccumulation in natural resources. Nuclear radiation resulting from the Manhattan Project is not an issue of the past; its effects are far-reaching and will continue to mutate the physical and cultural conditions of the Native American tribes who lived in the area, relied on its resources, and were biologically affected by the processes involved at Hanford.

Domoic acid (DA), a common marine neurotoxin found in marine organisms such as shellfish and finfish, is gaining public attention with increasing outbreaks in the USA, Australia, China, and some countries in Europe. Most DA outbreaks are observed along coastal regions, increasing the risk of exposure by seafood consumption. However, little is known about the effects of low level prenatal exposure of DA. To address this growing public health issue, we administered behavioral and cognitive tests on 27 Macaca fascicularis infants prenatally exposed to 0, 0.075, and 0.15 mg/kg/day of DA. Their cognitive capacities were analyzed based on their speed of learning new tests using the Wisconsin General Testing Apparatus (WGTA). The WGTA requires testers to present stimuli to the infant and, depending on the response, reward the infant for a correct response. I was one of several testers that worked with the infants during testing sessions 5 days per week. I also worked with the investigators and data analysis team to analyze the results of the WGTA tests. Results from early cognitive tests of object and spatial discrimination did not indicate a statistically significant detrimental effect of DA on these basic learning tasks. This suggests that DA does not have an impact on basic discrimination learning in the early stages of life (< 1 year). However, due to the potential for delayed toxicity of DA, more complex learning and memory tests are being administered as the infants mature. The results of this study will provide insights into future research and influence policies being implemented regarding seafood consumption and food safety.

Currently in Latin America, there are no nuclear weapons. In 1967, the Treaty of Tlatelolco was created and signed by Latin America and the Caribbean. This treaty prohibits the possession of nuclear weapons of any kind, making Latin America a non-nuclear weapon state. The research question I will be addressing is: Even though there are no nuclear weapons in Latin America, does nuclearism play a role in shaping its culture? As a native Spanish speaker, I am able to use my knowledge of the culture by using methods to analyze popular music, language and literature regarding nuclear weapons. I studied the lyrical and visual aspect of music to look for themes of the naturalization of nuclear weapons, as well as finding how language plays a role in its normalization. I analyzed literature in order to find commonality of nuclear cultures between nations that possess nuclear weapons and those that do not. My initial findings show that there is a strong presence of a nuclear culture existing in Latin America despite the fact that the region does not own nuclear weapons. Research also shows that nuclear culture is normalized through important themes such as gender and sexuality. Its normalization is often not obvious and is a part of daily life. These results were unexpected because I hypothesized for a nuclear culture to be nonexistent in a region that prohibits nuclear weapons. It is important to conduct further research on how nuclear weapons affect regions that are non-nuclear weapon states because it would create a broader understanding of the effects that nuclear weapons have on everyone and how it is a global issue that needs to be addressed. 

Neonatal mammalian heart tissues possess regenerative capabilities after injuries like myocardial infarctions that are mostly lost in adult mammalian tissues but conserved through adulthood in other vertebrates like zebrafish. Previous studies have shown that regeneration in ventricular cardiomyocytes (CM) occurs through de-differentiation and proliferation, but the underlying mechanisms that cause cardiomyocytes to enter the primed cell-cycle are unknown. Here we show that amino acid and metabolite levels in injured cardiomyocytes result in a primed state for regenerating cells. In chemically ablated zebrafish, it is shown that the amino acid profile activates the mTOR pathway to drive regeneration. Amino acid activation of mTOR is a result of high glutamine and leucine levels post-injury and in early heart regeneration in adult zebrafish, which is lost in adut mammals. Inhibition of the Wnt/β-catenin signaling pathway upstream of mTOR shows down regulation of mTORC1, showing that mTOR is necessary for CM proliferation in regenerating heart tissue. How Wnt signaling gets activated upon injury is unknown, and this study aims to understand the pathways upstream of Wnt signaling for activation. It is known that scarring needs to occur before regeneration occurs in heart tissue. This study also investigates why macrophages are essential for scar formation in ablated heart tissue and its underlying mechanisms. Further, single cell RNA sequencing one-week post injury is used to determine cell fates of the heart tissue. Cardiac cell types like CMs, endocardial and epicardial cells, and bulbus arteriosus (BA) cells were activated post-injury, with epicaridal cells promoting CM regeneration and BA cells activating signaling pathways during heart regeneration. This study demonstrates the signaling and metabolic pathways that activate cardiomyocyte regeneration in zebrafish hearts.

The most recent National Vital Statistics Report reports that approximately 9.85% of babies in the United States are born preterm, with 72% of those born late-preterm (at 34-36 weeks of gestation). Using neonatal ferrets at age 17 days old, the Juul lab in the Division of Neonatology at the University of Washington Medical Center has developed a preliminary model of brain injury to mimic late-preterm neonatal injuries. In this species-specific adaptation of the Vannucci Model, the left carotid artery is permanently ligated, along with a temporary (4h) occlusion of the right carotid artery. Ferrets are then exposed to periods of hypoxia and hyperoxia. By looking at data and outcomes from our surgeries, I aim to examine the effects of certain surgical parameters on ferret mortality. These parameters include: time the animal is exposed to isoflurane, the length of surgery, and the amount of time the animal is given to recover between surgery and hypoxia. Aside from mortality, I will also analyze the effects of these parameters on respiratory rate after surgery as well as gross brain injury and data from behavioral testing in an attempt to discern the level of injury in living animals and the most common predictors of death in those that died prior to their determined endpoint.

A DNA screening tool is being developed to allow rapid DNA testing in the field to identify endangered species of timber and wildlife. This work describes the design and testing of a chip holder and a gasket to improve the performance of this tool in the field with the consideration of usability, manufacturability and functional constraints. The chip holder is composed of a cradle with a hinge, two glass chips and one gasket. This chipset contains all reagents required to perform a DNA amplification test and features microfabricated heaters with electrical contacts to drive this reaction. Prototypes for chip holders with different hinge thickness and designs were fabricated in polypropylene using a Lulzbot Taz-6 3D printer with an Aerostruder tool head. The hinges were tested manually to ensure that the design parameters provided a stable joint. Gaskets were created by pouring Smooth-On Liquid Silicone Oomoo 25 into 3D printed molds. Silicone gaskets and chips undergo thermal testing on hot plate at 95 °C for 25 minutes to test if adhesion changes. Leakage testing for the gaskets is done through placing 0.2 g of water between gasket and chip and pressure are added between the chips to check water loss. We found the optimal material for gasket under DNA testing condition is Liquid Silicone Oomoo 25, and the best adhesive for the gasket and glass chip is silicone based adhesive GE Silicone II. Future work would be finding a more efficient method to produce the gasket, apply adhesives and adhere the gasket and glass chip. For the chip holder, the next step would be choosing the manufacturer, and select the specific polypropylene for mass production.

BiI₃ is a nontoxic and relatively abundant material with a bandgap of ~1.8eV that displays promising photovoltaic properties. However, BiI₃ solar cells have not reached efficiencies of greater than 1%. One of the major problems is the existence of deep defects in the materials which serve as trap states and increase non-radiative recombination. Here, defect engineering by both isoelectronic and non-isoelectronic doping of BiI₃ is studied to reduce the concentration of deep defects and increase the concentration of free charge carriers, aiming to improve the photovoltaic properties of BiI₃ solar cells. To evaluate the effect of dopants on defect passivation in BiI₃ films, photoluminescence and photoconductivity measurement are applied to determine quasi-fermi level splitting (QFLS) and carrier diffusion lengths, respectively. Additionally, dark photoconductivity measurements are used to determine carrier concentration. Preliminary results have shown an increase in QFLS under an iodine rich environment, though not significantly enough to drastically impact BiI₃ solar cell performance. There is much room for further exploration of dopants and their effect on BiI₃. With every dopant tested we learn more about the properties of BiI₃. This work will deepen our understanding of optoelectronic physics and defect chemistry of BiI₃ solar cell materials, optimize the quality of BiI₃ thin films, and increase the efficiency of BiI₃ solar cells.

Building upon our rat testicular o-culture system developed to improve evaluation of chemicals and identify their potential adverse health effects on humans, we have designed in vitro mouse system to expedite such assessments. Models of in vitro cell cultures are, however, limited in their approach typically using a monoculture of single cell types. Using a 3 dimensional organotypic approach can provide a framework for evaluating systematic interactions between cells with a goal to reduce the need for in vivo assessments. We utilized a novel organotypic, in vitro model of testicular development that mirrors the development shown by in vivo studies. We used isolated testicular tissue harvested from C57BL/6 male mice on post-natal day 9 and digested into a single cell suspension. Testicular co-cultures were maintained for up to 16 days in 24 well plates. Data collections occurred at days in vitro (DIV) 3, 7, and 16. These timepoints represent “windows of potential susceptibility” for testicular development. Plates were stained with antibodies providing markers corresponding to morphological features of specific cell type; six different primary antibodies were used as markers to visualize the change in cell populations; markers for Sertoli cells corresponded to Vimentin, Leydig cells with 3b-HSD, Germ cells to DAZL, SCP3 and c-kit, and proliferation with PCNA. We used an immunofluorescence dual staining technique with Scanning Laser Image Cytometery (iCys) to quantify the proportion of cell types and to determine changes in phenotypic distribution of the cell population. Our observations in vitro demonstrated concordance of changes in Sertoli cells, Leydig cells and Germ cells throughout testicular development with similar trends in vivo. Our observation of similarities in testicular development in our 3 D in vitro experiment and in vivo studies is important and supports the current trends in minimizing the need for in vivo studies for chemical toxicological.

Current methods of modeling tissues rely on two-dimensional (2D) cell cultures which fail to incorporate the three-dimensional (3D) aspect of native tissues in the body and therefore cannot mimic tissue-specific conditions in vivo. The inability to accurately mimic the native properties of tissues in vitro makes characterizing physiological cell behavior challenging and limits the applications of these models. As such, the lack of sufficient in vitro tissue models necessitates the need for a more advanced engineered tissue models that accurately recapitulates the native morphology and function of cells in vivo. Previously developed in vitro platforms that attempt to model human vasculature in vivo have been limited in their ability to imitate the circumferential architecture of smooth muscle cells which surround the veins and arteries. Through the production of a more advanced vascular tissue engineered platform that accurately recapitulates biomimetic conditions of native tissue, we could better study cardiovascular biology, disease modeling, and drug-response in a dish. We propose the fabrication of an architecturally-controlled multi-layered 3D smooth muscle cardiovascular model that mimics the tubular structure of blood vessels in vivo to study structure-function relationships. Utilizing a thermoresponsive nanopatterned film, we are able to direct cell alignment and layer sheets of cells to create a circumferentially aligned 3D smooth muscle tissue model that mimics the physiology of the vascular tunica media. Furthermore, we have designed a fibrin gel casting method to produce tubes with a hollow intraluminal space that has mechanical properties that are physiologically relevant to human tissue. We aim to determine how anisotropic alignment of smooth muscle affects vascular compliance. This model is highly versatile in nature and can be functionalized with a wide variety of cell types to accommodate different tubular tissue structure throughout the human body.

Giardia lamblia, a microscopic flagellated parasite that causes giardiasis, is a highly divergent eukaryote in which conventional Golgi, endosomes, lysosomes, and mitochondria are absent. Similar to other parasites of medical importance, Giardia lamblia has two life cycle stages - proliferative trophozoite form and water-resistant, nonmotile, infectious cyst form. During encystation when Giardia trophozoites transform into infectious cysts, they secrete cyst wall proteins (CWP1-3) that are trafficked and processed in Encystation Specific Vesicles (ESVs). These vesicles are thought to be stage-induced Golgi in Giardia. Previous work in the lab has shown that the signaling activities of G. lamblia’s single Rho family GTPase, GIRac play an important role in regulating this encystation process. The aim is to characterize proteins in Giardia lamblia that potentially interact with GIRac, currently focusing on homologs of known players in membrane trafficking by examining their order of arrival using morphology of the ESVs based on CWP1 staining. Since this is subjective, there is a need for stage-specific molecular markers. In other eukaryotes, Rab GTPases have been established as markers of membrane identity and directionality of trafficking. Only two out of nine Giardia’s Rab GTPases have been localized and reportedly found at ESVs and based on published images, they appear to be recruited at different stages of ESV maturation. By tagging the N-terminus of all 9 Giardia Rab GTPases with fluorescent tags, we can screen them for their localization to ESVs and perform multi-color imaging to determine the order of arrival of these markers. Ultimately, this finding of stage-specific molecular markers could be a powerful tool to further suggests its potential as a novel target for drug development to treat giardiasis.

Galaxy clusters are collections of galaxies that form the largest gravitationally bound structures in the universe. Because these galaxies are clustered together, they undergo a wide variety of processes and operate under a multitude of mechanics, differing from non-clustered galaxies, like our own Milky Way. One such example is ram pressure stripping. A galaxy that falls through the hot and dense Intracluster Medium (the space between clustered galaxies) is subject to a "wind" force that can strip it of its gas, usually producing a long gaseous tail emanating from the galaxies causing it to be dubbed a Jellyfish Galaxy. This phenomenon can be incredibly impactful as it can "quench" star formation in the galaxy or, in other words, it can cause the galaxy to “die.” A galaxy is considered quenched when it has insufficient gas to form stars, and it is still not well understood why some galaxies become quenched and others do not. Learning more about this process can inform us on the life cycle of both the galaxies themselves and the cluster as a whole. We used the RomulusC simulation data, run on the NSF Blue Waters Supercomputer, which simulated a large galaxy cluster in high resolution. This simulation has allowed astronomers to study ram pressure stripping in a realistic setting for the first time. Comparing the results of this simulation to observations will supplement our understanding of galaxy clusters and the movement of matter in these colossal and highly dynamic systems.

In 1997, South Korea and many other Asian countries were hit with a large currency and financial crisis, with the IMF providing a $58 billion bailout program to South Korea involving large amounts of reforms and corporate restructuring involved, along with a very contractionary fiscal and monetary policy that intensified the crisis. The IMF loan had conditions of higher interest rates, higher taxes, and lower government spending, among others, on hopes that the contractionary policies will restore the foreign investors’ faith in Korea. After the crisis, the conditions of the IMF loan have been subject to much criticism in both Korea and abroad. This raises a question as to whether the IMF’s response and the conditions of the loan to Korea was appropriate for the situation. For this research, I am collecting information from many sources both from the US and in Korea, including books, journals, and newspapers. I am also acquiring various types of data as part of the research. Some of my findings are that the IMF’s response for the crisis was inappropriate as the IMF’s diagnosis of the situation was inappropriate. It is because South Korea’s situation was different from the other countries of the Asian Financial Crisis as the crisis did not arise due to overvalued exchange rates and government debt. Additionally, part of the IMF’s response in Korea can be said of as carrying over from past crises which involved the government accumulating large amounts of debt, as opposed to the Korean case, where the chaebol and the financial institutions lending to them accumulated large amounts of short-term debt and the government had almost no debt and was operating at a balanced budget. The uniqueness of the Korean crisis meant that the IMF should have reacted differently in imposing its conditions for the loan.

This study evaluates whether more punitive state welfare policies depress rates of voter turnout in communities with high concentrations of welfare recipients. While scholars have studied the influence of demographic group belonging and the effects of state institutional contact (prison, welfare, etc.) on political participation and voting, researchers have not studied how voting behavior shifts in response to policy-level variations in welfare states. To address this gap in the literature, I use data from the Urban Institute's Welfare Rule’s database to generate a novel index of state welfare punitiveness that will be broadly useful for scholars interested in state welfare policies and political socialization. I use multivariate regression analysis to test whether high concentrations of welfare recipients in more punitive states systematically affects voting behavior. Results of this study will be relevant for scholars concerned with voting behavior, political learning, institutional contact, and democratic participation.

This study seeks to understand how to best support low-income, urban employment mobility through transportation. While scholars have studied the effects of urban planning, access to a private vehicle and public transportation for low-income residents, there is no consensus in the academic community for which method of transportation is most effective. Utilizing responses from the 2004 General Social Survey, the study measures perceived access to public transit, car ownership and employment mobility—the ability to switch to an equally desirable job— among low-income residents. Additionally, I employ census data measuring willing job-to-job transfers, car ownership and low-income public transit commuting time as a proxy for transportation access. I expect to find a positive relationship between car ownership and employment mobility, while I predict no relationship between public transportation and mobility. I utilize a multivariate regression analysis for the census data. This study has important implications for transit policy, as it can help inform how to better fund public transit to help low-income individuals and may lead to experimental policy like low-income car subsidies.

Since the 1990s, legislation in many US states has increasingly criminalized and restricted undocumented immigration. However, despite these restrictive policies, the population of undocumented immigrants has increased and overall immigration flows from Mexico to the US only began to decline following the 2009 recession. This research responds to decades of increasingly punitive policy and intends to test the efficacy of these policies. Many studies have focused on the efficacy and implications of federal policies, but far less attention has been given to state-level policies in the US. This paper analyzes the efficacy of punitive, state-level immigration laws from 2010 to 2016 in the United States. I hypothesize that there is no significant relationship between the passage of punitive state-level immigration policies and the year-to-year change in state populations of undocumented immigrants. However, I also hypothesize that the introduction of punitive state-level immigration policies affects yearly immigration flows—or the number of people immigrating from Mexico to a specific US State. To conduct this study, I created an index that aggregates a broad spectrum of laws, including policing, licensing, education, public benefits and labor. I then selected a few high-profile state laws intended to deter or curb undocumented immigration. I used multivariate regression analyses to test whether the introduction of punitive policy immigration policy systematically influences migration flows and changes in migrant populations while controlling for relevant economic and demographic factors.

Chemically induced dimerization (CID), in which two proteins dimerize only in the presence of a small molecule, has been widely used to control cell signaling, regulatory, and metabolic pathways, and used as logic gates for biological computation in living mammalian cells. However, few naturally occuring CID systems and their derivatives are currently available. Creating a CID system with desired affinity and specificity for any given small molecule remains an unsolved problem for computational design and other protein engineering approaches. To address this challenge, we have used a novel strategy to select CID binders from a vastly diverse combinatorial nanobody library. We have created new CID systems that can sense cholecalciferol and artemisinin. We are validating CID biosensors by a yeast three-hybrid system and built structural models to understand the small molecule-induced dimerization. Our work is a proof-of-concept that can be generalized to create CID systems for many applications.

Single-cell gel electrophoresis, or a Comet Assay, can be used to assess DNA damage in cells as it liberates single-strand DNA breaks (SSB), alkali labile sites (ALS), and DNA cross-links, then uses microscopy to determine levels of chromosome damage. Various methods have been used to detect DNA damage; advantages of this assay include its capacity to detect low levels of DNA damage, the small number of cells required, low cost, and the ability to utilize various cell types. Our lab used lymphocytes withdrawn from elderly patients as we targeted quantifying the effects on an individual’s DNA due to aging, stress, and drugs. Lymphocytes were suspended in low-melting point agarose and placed on a slide pre-coated with regular agarose. Once cells were fixed on the slide, they were placed in lysis solution to remove membranes and liberate DNA. Lymphocytes then went through an alkaline treatment to unwind DNA super-coils. The assay has been tried under neutral conditions however, we used the alkaline method because it is known to increase reproducibility and specificity. The cells were then placed in an electrophoresis chamber at 5 V/cm for 30 minutes, the SSB’s, ALS’s, and DNA cross-link fragments traveled towards the anode, forming a comet like appearance behind the cell. The cells were then neutralized, stained with ethidium bromide, and the comets were visualized. Data can be quantified using software provided by Instem Technologies. A comparison of Comet values derived from varying cell densities as well as untreated control samples are also presented, confirming good reliability using this technique.

Telomeres represent the structural ends of genomic chromosome molecules and are composed of hexamer repeats of the form [TTAGGG] which play a protective role against DNA damage and genetic information loss. The telomere length of normal diploid cells decreases over time and can be correlated with issues related to cancer and the aging process. Our preliminary work utilizes methods developed initially by Cawthon and O’Callaghan and is applied to DNA samples obtained from research studies involving the elderly as well as those with aneurisms. In contrast to standard measurements which use real-time PCR in order to calculate relative telomere lengths, our method uses absolute quantification through the use of standard curves generated with a synthetic 84-mer telomere (control gene) and another synthetic oligomer (36B4 ‘housekeeping gene’). Through the use of both synthetic standards in a typical RT-PCR experiment utilizing SybrGreen and specific primers for either telomere sequence or housekeeping gene, the true length of a diploid telomere can be calculated by extrapolation from standard curves. Telomere lengths obtained through this method have been compared to results derived from commercially available test kits which used relative RT-PCR as a quantification measure. Results obtained through the use of this technique can be incorporated in research studies encompassing cell apoptosis, processes involved with aging. This technique can also be used to ascertain the effects of environmental impacts involving DNA damage on plants, bacteria, and animal cells.

Von Willebrand Disease (VWD) is a bleeding disorder in which von Willebrand Factor (VWF), a polymeric blood protein, is either completely absent or in a dysfunctional state within the circulatory system. VWF’s function is to respond to shear force through an unfolding conformational change, and it is this unfolding and consequential exposure of platelet binding sites that initiates the blood clotting cascade. Affecting 1% of the entire population, VWD is the most common inherited bleeding disorder. However, few effective treatments exist. A major barrier to understanding VWF function is the absence of human cellular and vascular models that can accurately reconstitute complex phenotypes and molecular mechanisms. Studies of VWF at the cellular and vascular scale can provide important insight into physiological factors that regulate VWF. Human cells are particularly attractive and provide a highly accessible, species-specific model that can be more flexible than mouse models. Current cellular models for VWF functional studies are primarily limited to endogenous VWF secreted from human umbilical vein endothelial cells (HUVECs), which are not immortal, making it difficult to engineer disease models. This project serves to directly address these barriers through the creation and characterization of stable VWF knock-out human pluripotent stem cell lines (hPSC). These cells are immortal and can differentiate into numerous lineages including endothelia. VWF knock-out cells differentiated normally into endothelial cells, as expected, based on cell morphology and endothelial marker expression. The VWF knock-out cells have been confirmed through immunoblot and immunofluorescence to be deficient in various VWF-associated proteins, such as Factor VIII and Angiopoietin-2. We are currently investigating the mechanisms behind these deficiencies and how they relate to the absence of VWF. These findings will enable us to better understand the function of VWF, which will ultimately guide us to discover effective treatments for VWD.

Hemoglobin A1c (HbA1c) is an important marker to aid in the diagnosis and monitoring of diabetes, as it is a measurement of average blood glucose concentration over the previous two to three months. The current instrument used at Seattle Children’s Hospital to measure glycated hemoglobin is the DCA™ Vantage Analyzer. The DCA™, being a point of care (POC) device, can only run one sample at a time and requires a significant amount of tech time to run a batch of samples. With that, there is a desire to validate HbA1c on the Vitros 4600 as it would improve utilization of tech time and potentially provide more accurate and precise results. A correlation study was first done by running 30 different samples across the Analytical Measurement Range (AMR <14%) on the Vitros 4600 and compared to the original values run on the DCA™ using the statistical program in EP Evaluator. The overall bias of the two methods was -3.265%, but after closer analysis, the bias <9% HbA1c was -0.509%, while the bias >9% HbA1c was -5.026%. Another method comparison was done by running high HbA1c samples (8-14%) on the DCA™ and Vitros 4600 compared against ion exchange HPLC, which is the gold standard for the measurement of HbA1c. The Vitros 4600 had a better correlation with HPLC (bias of 1.075%) on the high end for HbA1c compared to the DCA™, suggesting the DCA™ actually has a high-end bias with higher HbA1c values compared to HPLC. Thus, by using the Vitros 4600, there can be more accurate results for HbA1c levels especially when managing diabetes, while also increasing productivity by having the ability to run multiple samples compared to a POC device.

For women to have protection from unintended pregnancy and human immunodeficiency (HIV), current lead prevention options use oral antiretroviral drugs (ARV) for pre-exposure prophylaxis (oral PrEP) along with a form of contraception. Failure to adhere to these drug therapies will increase the risk of contracting HIV or pregnancy. We have proposed to integrate drug-eluting materials onto a copper-intrauterine device (IUD) that could provide both HIV prevention and contraception. We will evaluate two methods to formulate a matrix release drug delivery system. Injection molding is a method to inject material into a mold that can be used for constructing drug-eluting medical devices with low drug degradation. For our purpose, we injected a polymer and drug combination into a mold to construct a solid slab. Whereas, electrospinning is a method that uses electric force to formulate stable and high surface-to-volume ratio nanofibers with high drug encapsulation and porosity compared to the molded slab. Both delivery systems will be used to administer ARV drugs to the female genital tract for a year. We optimized the molded slab and electrospun nanofibers technique for maximum polymer-loading, and used 3-D printing and nanofiber wrapping technique as a process for slab integration and fiber integration onto the IUD respectively. The polymer and drug combinations for both electrospun nanofibers and molded slabs were chosen to have the maximum drug-loading and stable mechanical properties. Drug release was measured in vitro to predict daily release rates out to three years. The ideal matrix release drug delivery system method for the dual HIV prevention and conception IUD is determined based on the mechanical properties and drug release rate of the polymer and system combination. We also investigated the drug delivery systems for cytotoxicity to verify dosage safety.

In eukaryotes, conserved mechanisms ensure that cell growth is coordinated with nutrient availability. Overactive growth during nutrient limitation (“nutrient-growth dysregulation”) can lead to rapid cell death. Here, we find that cells can adapt to nutrient-growth dysregulation by evolving major metabolic defects. Specifically, when yeast lysine auxotrophic mutant lys- encountered lysine limitation, an evolutionarily-novel stress, they suffered nutrient-growth dysregulation, and a sub-population repeatedly evolved to lose the ability to synthesize organosulfurs (lys-orgS-). The purpose of this study is to identify the types of yeast cells that recovered by being lys- and orgS- and their frequencies through generations. Using 96-well plates, we inoculated single colonies into three separate conditions (control, +lys, +lys+orgS) to test for auxotrophs. Surprisingly, we found drastically different frequencies of lys-orgS- when lys- evolved as a monoculture in lysine-limited chemostat versus in a coculture with a lysine-releasing strain. We also found mutants defective in synthesizing glutamine and arginine. Our work suggests that under stressful conditions, multiple metabolites are released, which can facilitate the evolution of new interactions and mechanisms. 

Embryonal rhabdomyosarcoma (ERMS) is a devastating pediatric cancer that affects soft tissue such as skeletal muscle and connective tissue. Currently, there is no effective treatment for patients with ERMS. Mutations in the gene PTPN11 are found to have cancer-promoting roles in leukemia, lung, and breast cancers, but its role in ERMS is virtually unknown. PTPN11 codes for the SHP-2 protein, which is a component of the RAS/MAPK (mitogen-activated protein kinase) signaling pathway. Abnormalities in this pathway are known to transform normal cells into cancer cells when certain proteins are upregulated. My central hypothesis is that PTPN11 promotes RMS tumor growth by allowing cells to proliferate and differentiate out of control. To test the hypothesis, I used CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas gene editing technology to disrupt PTPN11 gene function in two models. I designed constructs that express guide RNAs that target the PTPN11 locus in the zebrafish or human genome. If PTPN11 has a tumor-promoting role, I expect targeted disruption of zebrafish PTPN11, delivered via microinjection, to result in reduced RMS tumor formation and growth compared to zebrafish tumor with no PTPN11 gene disruption. In the human ERMS cell lines, I will use virus-mediated transfer to introduce the CRISPR DNA construct in vitro. My hypothesis will be supported if the cells harboring targeted disruption of PTPN11 have reduced growth and less self-renewal capacity compared to the control cells. My findings will elucidate the role of PTPN11 in RMS, which will allow further research into the potential therapeutic benefit of targeting PTPN11 in pre-clinical RMS models.

Previous study found that neural oscillations recorded in the resting-state electroencephalogram (EEG) can predict the learning rate of monolinguals. However, it is unknown whether bilinguals’ learning rates can also be predicted by their resting EEG. This study investigatesd to what extent the brain oscillations in the resting-state EEG of bilinguals and monolinguals would predict the learning rates. The resting-state EEG were used to predict the learning rates of native English speakers and Chinese-English speakers in three experiments. In each experiment, an eyes-closed and an eyes-open resting-state EEG were collected for each subject before participants completed two learning tasks (map and vocabulary). The relationship between power oscillations in alpha (8 to 13 Hz), beta (13 to 30 Hz), and theta (4 to 8 Hz) bands and learning task performance were investigated. The differences in bilinguals and monolinguals resting EEG are hypothesized to predict and reveal the variations in individual learning rates. The results of this study can contribute to the research of brain patterns observed in the resting-state EEG on investigating the impacts of individual linguistic abilities on predicting learning rates.

Parkinson’s Disease (PD) is a neurological disease that affects motor function. Symptoms include muscle rigidity, tremors, slowed movements, and altered voice. Deep Brain Stimulation (DBS) is a therapeutic intervention addressing PD symptoms, by implanting an electrode into the brain, delivering electrical impulses to areas affected by PD. DBS patients, however, must come into clinic every few months for multi-hour reprogramming sessions to adjust DBS settings according to the progressions of their symptoms, making DBS treatment an arduous and expensive process. This significantly limits the accessibility of DBS, because only limited locations/providers who can offer this service. Our lab has developed a computer algorithm that can derive digital biomarkers, indicators for the severity/presence of a disease, for PD from voice samples. We aim to investigate the correlation between patient voice and physical symptoms, with manipulation of stimulation in the on/off states. Our findings could aid clinicians in their monitoring, management and adjustment of DBS protocol, without the need for patients to come into clinic. We tested this by obtaining motor scores via the Unified Parkinson’s Disease Rating Scale (UPDRS), and gathering voice samples with DBS turned on and off, during patients’ visit at UW clinics. Voice samples were analyzed for specific biomarkers, using our machine learning algorithm. We expected to observe different voice-associated biomarkers present with DBS turned on/off, to demonstrate a correlation between DBS and voice/motor symptoms. Once the relationship between DBS and voice is established, the ultimate goal is to develop a closed looped DBS device which can auto tune itself based on patient voice alone. In an age where audio collection devices, such as smartphones are so accessible, the use of voice data has exciting potential as a clinical tool, optimizing DBS therapy protocol and efficiency for administering clinicians and patients with PD.

Studying zebrafish embryos allows us to understand features of vertebrate embryonic development. Neuro-mesodermal progenitor cells at the very posterior end, or tailbud, of an embryo are bipotential. This is because the presence or absence of Wnt signaling commits them to either neural or mesodermal fate. Directed by environmental cues, mesodermal cells exit the tailbud, migrate anteriorward, and become somites, structural segments from which muscles differentiate. The Kimelman lab has found that Tbx16/Spadetail, a major driver of mesodermal morphogenesis, downregulates Arhgap29 and Arhgap35, members of Rho family GTPase activating proteins. This suggests Arhgap29 and Arhgap35 may be involved in mesodermal cell movement. My work in the lab is focused on finding out what roles these two genes play. I used heat shock promoter hsp70 to overexpress Arhgap29 and Arhgap35 in transgenic fish lines. Previously, our lab showed that sustained Arhgap35 affected somite morphology, and that sustained Arhgap29 also decreased the number of somites. In my experiments, I carried out in-situ hybridization in wild-type, Arhgap29- and Arhgap35-expressing embryos to examine genes regulating specification/differentiation of muscle cells and genes involved in transmembrane cell adhesion. I will present data on cell tracking and cell protrusions collected from Arhgap29- and Arhgap35-expressing embryos. These results will help me compare cell migration between Arhgap-expressing and wild-type embryos. The purpose of these analyses is to understand how these two proteins control cell movement in the embryo. In the future, I will continue to investigate cellular mechanisms underlying vertebrate posterior elongation.

During the early stages of vertebrate embryonic development, blocks of muscle tissue called somites form progressively along the anterior-posterior (head to tail) body axis. As the embryo grows in length, new somites are continuously added at the posterior end until the tail reaches its final length. Our work focuses on a subset of genes called the hox genes. These genes encode transcriptional regulatory proteins that are involved in controlling the formation of the body plan along the anterior-posterior (AP) axis. In vertebrates, these genes are present in four major clusters (A, B, C and D) and within a cluster they are expressed temporally from 3’ to 5’ of DNA, with hox13 being at the very 5’ end and thus the most posteriorly expressed hox genes. In this study we use zebrafish as a model organism. Zebrafish embryos are excellent for investigation because: 1) the genome has been fully sequenced to a very high quality allowing the use of CRISPR mutagenesis; 2) the zebrafish embryos are transparent and so very easy to study using live microscope imaging; 3) much of the early development is similar among all vertebrates including humans. The role of the hox genes during the somite-forming states has almost entirely been characterized based on the overexpression of individual hox genes in previous research. We developed a zebrafish loss-of-function hoxa13 CRISPR mutant and are investigating the roles of this gene on the formation of the body plan. My research focuses on understanding how a loss of hoxa13 gene affects cell movement as the AP axis forms using spinning desk confocal microscopy to capture cells and Imaris software to track them, and I will present the results of this analysis. We expect to observe abnormal or reversal of cell movement in the prognitor area of the tailbud.

PTEN is a tumor suppressing protein that carries out important cell functions such as inhibiting cell growth and promoting genomic stability. Somatic variants of PTEN can lead to cancer, and PTEN mutational status has shown to be an indicator of patient survival and prognosis. However, it is not clear whether cancer-associated PTEN variants affect cell growth, genome stability, or both. Here, we demonstrate that simple competition assays can quantitatively assess PTEN variants for their effect on these two important cellular functions. Cells expressing cancer-associated PTEN variants tagged to blue fluorescent protein are mixed with cells expressing wild-type (WT) PTEN tagged with a red fluorescent protein. The proportion of blue and red cells are analyzed over several days using flow cytometry. If the variant does not repress cell growth, variant (blue) cells will outcompete their WT (red) counterparts. To modify the competition assay for genome stability assessment, cells are treated with a PI3K inhibitor and the genotoxic chemotherapeutic temozolomide. These drugs isolate the genomic stability function of PTEN by removing its role in cell growth and causing genome instability, respectively. Here, cells harboring variants that cannot repair temozolomide-induced DNA lesions will be outcompeted by their WT counterparts. The assay generates a score that is based on the rate of change of variant populations relative to the WT population to quantitatively define the phenotype. Results can be interpreted to establish a relationship between a PTEN variant and its quantitative effect on the cell growth or genomic stability functionality of PTEN. Furthermore, the growth-based nature of these assays means that in future work they can be adapted to a pooled library format, allowing the simultaneous, quantitative assessment of thousands of PTEN variants. Data from both low-throughput and high-throughput experiments bring clarity to the relationship between specific PTEN functions and patient prognosis.

Marine terraces are geomorphic features created by wave erosion of the land, which is modulated by crustal uplift or past sea level changes. In this study, I consider possible driving mechanisms that could have generated the marine terraces on the archipelago of Haida Gwaii, Canada. Southwest of the island, there is a young subduction zone that was only initiated ~6 Ma. This subduction has generated a M_w 7.8 earthquake in 2012. From this study, we can find out more information about the plate boundary, including uplift and deformation histories. The island has also experienced ice coverage during the last glacial maximum. Since then, the ice has melted. As a result, the island may have uplifted in response to the ice melting during the Holocene. To obtain the data needed, I am using newly released LIDAR data which contain high resolution elevation topography to map the landforms digitally. The purpose of this project is to provide a resource for locations of the terraces and also to find patterns in distribution and in elevation of marine terraces in Haida Gwaii.

Physiological and behavioral rhythms are controlled in mammals by a central circadian clock located in suprachiasmatic nuclei of the hypothalamus (SCN). This master clock has outputs to other organs and tissues crucial to keeping the organism properly synchronized. The SCN clock is synchronized by environmental cues, most importantly is the light-dark cycle (LD). Fearful stimuli (i.e. presence of predators) can also present cyclic variations. The de la Iglesia lab has recently shown that timed fearful stimuli during the night can switch the locomotor activity rhythms of mice to the light phase, overriding their natural nocturnal behavior. Interestingly, while the expression of the so-called “clock genes” (which sustain the circadian rhythms at the molecular level) remains unchanged in the SCN, it displays a complete inversion in the amygdala, the brain region that encodes fear. Currently, we aim to determine the pattern of expression of clock-genes in peripheral organs of mice subjected to cycling fear stimuli. Using qPCR, we will assess RNA expression of the clock genes bmal1, per1, and per2 in the adrenal gland, kidney, and liver to determine whether entrainment of activity by cyclic fear also impacts peripheral clocks at the molecular level. We hypothesize that the pattern of expression the clock genes in the liver and kidneys will be modified in mice subjected to nocturnal fear, due to altered feeding and drinking patterns. However, the adrenal gland is difficult to make predictions about the pattern of expression of the clock genes given the fact that preliminary data from our lab showed that cortisol shows two peaks in mice displaying diurnal activity after nocturnal cyclic fear exposure compared to the single peak displayed by nocturnally active mice. Thus, it is unclear if we will observe an inversion peak, much like the amygdala, or a peak similar to the LD cycle.

Tubal ligation, or tubal sterilization, refers to a set of permanent female sterilization procedures that bilaterally occlude or remove the fallopian tubes, typically to prevent conception. These procedures range in invasiveness, cost, and popularity, and comprise the first or second most popular contraceptive method in the world. Current scientific literature emphasizes the methods by which tubal sterilization can be achieved, but lacks the perspective of the women receiving them. As a result, women have turned to social media to share their experiences, ask questions, and gain insight into what tubal sterilization is like. My research compiles the tubal ligation experiences of women from the United States to explain, via personal experience and surgical methodology, what women can expect from the moment that they ask for a tubal ligation to the time that they heal from their procedures. Ethnographic interviews were conducted with 13 women who had previously used social media to discuss their tubal ligation stories. These interviews suggested three main themes: firstly, that regret among electively sterilized women is incredibly low; secondly, the lack of support for women seeking tubal sterilization from medical professionals is so profound that the majority of my participants felt fortunate to simply have been listened to; and thirdly, that social media allows for women to simultaneously normalize elective sterilization, advocate for their own bodily autonomy, and support other women who seek sterilization. This research provides a glimpse of tubal ligation from the patient perspective to inform medical professionals and women alike.

Endothelial cells within the pancreatic islet produce key factors for survival and functionality of insulin-secreting β cells. Laminin is one such factor, thought to be responsible for enhancing insulin release. Laminin is a heterotrimeric protein composed of three isoforms: α-chain, β-chain, and γ-chain. Islet endothelial cells from diabetic (db/db) mice show a significant decrease in the expression of laminin α4, β1, and γ1, and show a reduced ability to secrete insulin. To test the correlation between these in vivo observations, we used an immortalized islet endothelial cell-line (MS-1 cells), to decrease genes of interest; and generate conditioned media (CM) in which to culture isolated islets to test their insulin secretion. Islets cultured in CM from MS-1 cells with decreased laminin α4 expression did not have blunted insulin release. However, we found that that decreased laminin α4 increased expression of laminin α1, perhaps as a compensatory mechanism. We inhibited expression of laminin α4 and α1 in MS-1 cells, and cultured islets exposed to this CM also did not have decreased insulin secretion. Therefore, we hypothesize that reducing all three isoforms of laminin in MS-1 cells is necessary to cause a decrease in insulin secretion in islets exposed to this CM. To determine if the knockdown of laminin-411 is sufficient to impair islet insulin release, CM will be collected from MS-1 cells exposed to oligonucleotides designed to inhibit the expression of laminin-411 or a nonspecific control oligonucleotide for 24hrs. After the media is collected, glucose concentrations of the two types of CM are matched. Isolated islets are exposed to these CMs for 48hrs and insulin secretion will be determined for basal and glucose stimulated conditions. We anticipate that CM generated by cells with reduced laminin 411 to decrease insulin secretion in isolated islets, replicating the results observed from db/db mice.

Spinal cord injury is known to cause an inflammatory immune response in the central nervous system (CNS), activating local immune cells microglia and astrocytes as well as recruiting circulating macrophages. Previous studies have shown that distinct populations of macrophages can exhibit either neurotoxic or reparative effects, depending on the cytokines activating them. Injury to the CNS also results in enzymatic breakdown of extracellular matrix (ECM) molecule hyaluronic acid (HA) into lower-molecular weight glycoproteins. It is known that after injury, many of these cleaved glycoproteins from the spinal cord extracellular matrix act as damage-associated molecular patterns to modulate immune response. However, it is still unclear which facets of the inflammatory response are subject to control by HA, a key ECM component. In this study, we seek to determine whether the breakdown of HA causes proliferation and activation of microglia and astrocytes. Introducing the enzyme hyaluronidase that degrades HA to an uninjured spinal cord decreases the levels of HA in the local area. Subsequently, we used double immunohistochemistry with markers for either microglia or astrocytes in combination with a marker for cell proliferation, to analyze cell activation and proliferation after treatment with either active or heat-inactivated hyaluronidase. We expect hyase treatment to result in both increased activation and proliferation of microglia and astrocytes. The expected data would indicate that the breakdown of ECM HA leads to activation of microglia and astrocytes. Understanding these cells’ activation could lead to future treatments for spinal cord injury focused on modifying the ECM to induce beneficial rather than neurotoxic inflammation.

All-trans-retinoic acid (RA) serves an important role in maintaining tissue health, either deficient or excessive levels can lead to health issues. Aldehyde dehydrogenase 1A1 (ALDH1A1), is generally believed to be the main enzyme responsible for the conversion of retinaldehyde (RAL) to RA in the liver, requiring the cofactor nicotinamide adenine dinucleotide (NAD+). However, previous studies indicated that after WIN18,446, a potent inhibitor of ALDH1A enzymes, was administered to mice; liver RA concentrations were not significantly altered, and in vitro the RA formation in mouse liver was only inhibited by about 50% suggesting other enzymes except ALDH1A1 synthesis RA in mouse liver. Mouse aldehyde oxidase has previously been proposed to synthesize RA. Hence, in the current study we tested the hypothesis that aldehyde oxidase (AOX) also contributes to the formation of RA in human liver. Our data shows that purified human recombinant AOX catalyzes the oxidation of RAL to RA. The K_m (indicating substrate binding affinity to the enzyme) and k_cat (indicating maximum enzyme velocity) values were determined by enzyme kinetic assays as 1.4 μM and 3.5 min-1. In the absence of NAD+(AOX mediated activity), RA formation was observed in human liver S9 fractions (HLS9) and the RA formation rate was, on average, 60% lower than that measured in the presence of NAD+(n=4). In addition, hydralazine, a selective AOX inhibitor, inhibited about 55% of RA formation in HLS9 in the presence of NAD+ while combining hydralazine and WIN18,446, more than 85% of RA formation in HLS9 was inhibited when compared to the control. In conclusion, this data shows that AOX and ALDH1A1 each contribute about 50% of RA biosynthesis in human liver. This research helps us better understand the regulation of retinoid homeostasis in humans.

Cystic Fibrosis (CF) is a genetic disorder associated with chronic, polymicrobial lung infections. One of the most common treatments for these infections involves inhalation of the antibiotic Tobramycin, used to treat Pseudomonas aeruginosa infections. Tobramycin’s effect on other members of the CF respiratory microbial community is unclear. The Tobramycin inhaled powder (TIP) study assessed the effect of Tobramycin on the entire respiratory microbial community before, during and after one month of therapy and demonstrated that, on average, Staphylococcus aureus viable counts dropped during the first week of therapy before returning to pre-therapy levels. However, there was variability in the response in viable counts to antibiotics in different patients with some that did not change at all throughout the course of drug therapy and no individual clearing their S. aureus infection. The purpose of this study is to better understand why Tobramycin did not clear S. aureus in people with CF as well as determining why patients responded differently. We initially hypothesized that the infection was not cleared due to antibacterial resistance to Tobramycin. I answer this question using standard susceptibility tests on Tobramycin, Cefoxitin, Sulfamethoxazole and Levofloxacin. The use of four different antibiotics help determine if the bacteria are resistant to Tobramycin and if there is a viable alternative to Tobramycin. We anticipate that results will show a shift from susceptibility before therapy to resistance after week one due to the proportion of resistant bacteria increasing. CF lung infections can be a model for many other diseases as well and we hope that this study may provide more insight into how to treat these infections better.

Solar steam generation has received considerable attention as one of the most promising solar energy harvesting technologies for applications in water desalination, sterilization, distillation, and power generation. Recent research suggests that plasmonic metal nanocrystals can be used as efficient light-to-heat transducers in solar-to-steam applications due to their strong localized surface plasmon resonances; however, large-scale implementation of solar stream generation based on plasmonic metal nanostructures is restricted due to their high cost, structural stability, and low recycling rates. I propose to develop earth-abundant copper iron sulfide nanocrystals as alternative photothermal transducers and apply them in solar steam generation. These nanocrystals can be engineered for efficient light-to-heat conversion and strong, broadband solar absorption. Moreover, they not only consist of earth abundant elements but also have high recycling rates. I plan to work towards enabling large-scale solar stream generation for the sustainable development of our society.