Public transit plays an important role in the daily lives of blind individuals. Unable to drive, blind commuters must rely on buses, subways, and other methods of public transportation to travel from one destination to another. Although transit schedules and even real-time arrival information are now readily available and accessible, there are still barriers to overcome. For example, a blind bus rider may find it difficult to locate a designated bus stop. Prior research has shown that, given a set of information about a bus stop, blind commuters will find their bus stop with significantly greater ease and lesser time spent. Our goal is to create a database of useful and reliable information regarding every bus stop in Seattle and make that information accessible to blind individuals. In order to collect such a vast amount of data, we have turned to crowdsourcing, a process that involves dividing work amongst a large group of workers over the Internet. By providing workers with Google StreetView images (ground-level visuals on the appearance of a location) and simple, multiple-choice questions, we hope to collect accurate information to answer questions such as “How many benches are at the bus stop?” or “In what direction is the bus stop relative to the intersection?” After acquiring a sufficient set of bus stop data, we will test the usefulness of this information to blind commuters by providing them with access to our database and analyzing their feedback. We believe that our work in this field will improve the public transit experience for blind individuals by providing them with a feeling of confidence and independence during their commute. Our work in this field may lead to further research in utilizing crowdsourcing to solve accessibility issues.

Humans are exposed to environmental toxins which can contribute to acute or chronic diseases, such as Parkinson's disease. Different people, however, have variable susceptibility to these toxins due to genetic variability within the population. In this project, we will utilize the model organism Saccharomyces cerevisiae(yeast) to investigate the molecular mechanisms of differential responses to environmental toxins that target the mitochondria. Many yeast single-gene deletion mutants will be exposed to mitochondrial toxins using a high-throughput Biosreen C instrument(combined shaker, incubator and plate reader, allowing for growth rate determination of yeast cells) and subsequently, bioinformatic methods will be exploited to identify genes involved in the response to mitochondrial stress and mechanisms of toxicity. We explored optimum concentration of different toxins for mutant yeast, expecting that different mutations will response genotype-dependently to different compounds. Identifying genotype-dependent responses to the environmental mitochondrial toxins may illuminate how mitochondria toxins contribute to disease and identify genetic factors invovled in susceptibility.

Though the rules of chess can be learned in a day, people spend years learning the nuances of the game that can make them masters. Important strategic details often go unnoticed or are not fully understood by novice players. Tactical play refers to maneuvers that limit an opponent’s options, or present multiple problems simultaneously resulting in a tangible gain. Moves like pins, forks, and skewers all fall into tactical play. Positional play refers to maneuvers that strengthen a player’s position on the board or weaken an opponent’s. Space, or how many squares a player controls, is an aspect of positional play. We speculate that by just seeing these strategic details, novice players could play stronger games of chess. We will be designing and implementing a set of visualizations that can be overlaid onto a digital chessboard that may help novice players more quickly and meaningfully see potential patterns, threats, and opportunities in hopes of helping them play more successful games. Our application could serve as a tool for further research on the relationship between visualization and chess learning, but our focus for the remaining quarter is only to design the application through research of chess and collection of feedback from chess players of all levels, and to implement a working application that may run in a web browser. Assuming the project is a success, future work may include a within-subjects study that compared how well novice chess players fared against a consistent chess AI both with the visualizations enabled, and without based on victories, losses, total moves until the end of game, and total value of pieces lost versus pieces captured.

While professionals in the Information Technology (IT) industry are able to read and understand new terms by associating them with previous knowledge and current context, professionals outside of the industry struggle with unfamiliar words and acronyms in dense technical documents. In these circumstances, many people turn to online resources such as Wikipedia to define or explain terms they don’t understand. Yet, switching attention between reading an article and searching for information using various resources can increase cognitive load, thereby increasing perceived stress level and potentially reducing the effectiveness of both tasks. To address this problem, we propose the D-Jargonizer: a web-based tool that assists non-technical professionals as they read complex technical documents by allowing users to select and define technical terms with minimal distraction. We hypothesize that this tool will reduce cognitive load, perceived stress and make it more enjoyable for professionals outside of the IT field to read and comprehend technical documents. First, using a diagramming application, we will create a static prototype that imitates the proposed functionality of the D-Jargonizer. Students at the University of Washington who are unfamiliar with technical documents will be recruited to test perceived stress and enjoyment while using the prototype, as well as provide feedback about the overall user experience. Based on our initial user testing, we will develop a Google Chrome extension that allows users to select a term on a web page, searches for the term in an ontology based on Wikipedia entries and displays the definition in a text box on the page itself. Our tool will be tested again to confirm our hypothesis and verify usability. While the D-Jargonizer currently focuses on helping people understand technical documents, the basic concept could be applicable to medical or legal documents in the future.

Hot flashes affect 75% of menopausal women, leaving them with recurring flushing, sweating, skin blotching, and occasional anxiety, palpitations, and sleep disturbances. 20% of those affected describe the symptoms as “intolerable,” and current treatment methods carry too many side effects or are insufficiently effective. We propose the drug nalfurafine to prevent these symptoms. Nalfurafine has the distinct clinical advantage of being taken orally and targeting κ-opiod receptors outside of the blood-brain barrier, leading to minimal side effects. κ-opiod receptors decrease the activity of Kiss1 neurons, and we believe kappa agonists such as nalfurafine inhibit the Kiss1 neuron activity we hold responsible for hot flashes. To test this hypothesis, we injected nalfurafine in mice and collected blood and brain samples, expecting reduced levels of specific hormones and proteins associated with Kiss1 neuronal activity. Analysis of data collected in this study is ongoing. If our hypothesis is incorrect, we will have a new understanding of how κ-opiod receptors regulate Kiss1 neuronal activity. However, if we find evidence that nalfurafine inhibits Kiss1 neuronal activity, it may alleviate hot flashes in women, thereby providing rationale for clinical studies and potentially leading to a therapy that would improve quality of life for millions of women.

 Our capstone project discusses a redefinition of a social bar experience. Opening and closing tabs at bars is stressful, time consuming and frustrating. Today, the process to order a drink at a bar is tedious: wait in line, order a drink, then hand a bartender a credit card to open a tab. Stand in the same line for each subsequent drink as well as to close the tab. This process is time-consuming and detracting from a customer’s bar experience. With the imminent rollout of mobile payments as a ubiquitous brick-and-mortar payment method, we identified an opportunity to utilize mobile payments technology to develop an elegant solution to order drinks at a bar. One of our goals is to eliminate as much friction from the experience as possible, which will allow users to better enjoy their drinks with their friends. The service will handle ordering, paying and tipping for menu items, as well as offer additional value-added features that are only possible when customers order and pay for drinks from a mobile device. While we will focus on the bar scenario, our technology platform will be applicable to several other verticals including restaurants and stadium venues. By employing the user-centered design process supplemented with usability research, we seek to create a solution that redefines the bar experience.

CO₂ separation from flue gases constitutes to nearly 40% of the CO₂ emission in the United States. Developments resulting from this work address factors key to increasing the transport properties in polymer membrane systems. In particular, this work explores method to engineer porous structure to enhance the selectivity of polymeric membrane. The polymer system of interest in this study is poly(l-trimethylsilyl-1-propyne) (PTMSP), a glassy polymer of extraordinary high free volume compared to conventional polymers. It is “reverse-selective” for CO₂ separation from flue gases such as nitrogen or hydrogen, i.e., transports CO₂ gas faster in respect to lighter flue gases. Based on prior studies that showed that enhanced transport properties for PTMSP if constrained to thin films, here we present our data for PTMSP if constrained in nanoporous functionalized anopore alumina oxides (AAO) “sieve” membranes. Impregnation was achieved via vacuum solution impregnation. The overall CO₂ permeability of impregnated membranes was found to be ~80,000 Barrer, which is almost two times higher than that of bulk PTMSP membranes. Selectivities of CO₂/Helium and CO₂/Nitrogen in impregnated membranes were found to be ~7.0 and 9.0, respectively; these are also noticeably higher than the corresponding selectivities of 6.0 and 6.6 found in bulk membranes. Furthermore, we investigated the temporal stability of these membranes that are notorious for their fast aging in the form of ultrathin films. The origin for physical aging is the collapse of the free volume. A two week aging study of PTMSP revealed a significantly slowed down physical aging process if confined in nanoporous AAO by about a factor of 20 over thin films. The exposure to the radial constraint within the pores helped stabilize the free volume and reduce the occurrence of free volume collapse.

Conventional wisdom holds that interregional migration of labor is a stabilizing mechanism for unemployment and wages. For example, labor supply will increase in a high-wage region, as people migrate into that region seeking better compensation; this pushes down wages in the receiving region. However, less often noted is the idea that in-migration may also raise the demand for labor. High rates of population growth will spur demand for housing, infrastructure, services, and other durable nontradables. This increase in demand can, in the short and moderate run, be greater than the increase in supply, which spurs accelerating waves of further in-migration to fill those demands. I focus on this aspect of labor migration, and hypothesize that in the United States from 2000 onwards, both new residential construction and thus the demand for labor in rapidly growing U.S. metropolitan statistical areas (MSAs) were significantly and positively affected by in-migration; additionally, I posit that MSAs with higher in-migration during the decade were more severely impacted once migration stopped. I statistically test these hypotheses, adapting a study by Gonzalez and Ortega on the impact of international migration on Spanish regional economies over the last decade. My regression models, estimating the change in housing prices and change in residential construction in response to migration, add insights from urban economics and investment accelerator theory to the factors used in the Spanish study. I then test these models using data calculated or obtained from the U.S. Census Bureau and the Internal Revenue Service. The central question I seek to answer is whether, in the short to medium run, migration is a stabilizing or destabilizing factor in regional labor markets.

The purpose of this paper is to investigate transnational influence in the poetry of Sarah Piatt, a recently recovered nineteenth century American poet. Piatt’s verse, considered by some to be the best poetry of her time second only to the work of Emily Dickinson, is remarkable for its quantity and breadth, but more importantly, for its subversive use of genteel style. Though her poems are generally divided into four overlapping categories, the two thematic classes of her poetry that will be explored in the most detail here are her Civil War poems and her “Irish poems,” which were inspired by an eleven year experience living in Ireland. These poems are examined through close reading and transnational analysis, as a conceptual link exists between Piatt’s perspective of the South during the American Civil War and her depiction of social injustice in her poems about Ireland and the Irish peasantry. These different contexts illustrate how Piatt brings her experience of civil strife and injustice in the United States to Ireland with her, influencing her understanding of political events in Ireland and her sympathies toward the destitute Irish people. As these conceptual ligaments are rarely one-sided, this paper seeks to illuminate the multi-directional nature of the transnational influence that impacts the way that Sarah Piatt’s poetry negotiates understanding at both local and global levels. By examining the complex dynamics of Piatt’s poetry, we can aid not only in the recovery of a deserving poet’s verse, but also clarify our understanding of nineteenth century women’s poetry as a rich body of work which merits greater consideration.

The vestibular system is responsible for maintaining stable vision and posture by interpreting accelerations of the head in various planes. Impaired function of this system can cause debilitating vertigo, as seen in Meniere ’s disease. Our lab has developed a prosthesis that aims to counteract these deleterious pathologies through electrical stimulation, and our research is directed towards improving the effectiveness of this device. In order to stabilize gaze, the vestibular system must incorporate demands from several neural inputs, many of which are dependent on direction of the line of sight. Additionally, the effectiveness of electrical stimulation may be altered by the background activity of the activated neural pathways, which vary with orbital eye positions. Therefore, in this study, I am focusing on the dependency of stimulation-evoked eye velocities on initial position of the eye. I have collected data from two Rhesus Macaques by stimulating the right lateral, posterior, and superior semicircular canals at different eye positions. My data shows linearly graded velocities depending on stimulus amplitude, so it is clear that eye position must be taken into account when evaluating eye velocities. Speculation into the cause of this phenomenon will help to better customize our implant’s effectiveness according to the physiology of the patient in consideration.

Perineuronal nets (PNNs) are a matrix of proteins that surround nerve cells and reinforce the most often used synaptic connections between neurons, essentially hard-wiring neural connections made as a child into permanent pathways that respond to specific stimuli. By dissolving these PNNs, we recreate the plasticity characteristic of a young developing brain, granting us the ability to rewire the brain with respect to any stimulus. In this study, we are looking at PNNs within the vestibular system – the sensory system that, under natural conditions, is primarily responsible for maintaining images on the fovea during movement. Hair cells within the semicircular canals of the vestibular system register head accelerations and then send reflex signals through vestibular afferent nerve endings to extra-ocular eye muscles that drive eye movements. This vestibular ocular reflex aids the maintenance of stability of images on the retina. As a therapy for vestibular loss, our lab has developed a vestibular prosthesis that electrically stimulates the afferent nerve endings of the vestibular system, thereby simulating natural vestibular response to movement. This electrical stimulation, however, spreads to untargeted as well as targeted vestibular afferents and cause inaccurate eye movements as a result. By dissolving the PNNs in the vestibular nuclei and then allowing them to regrow during a period of adaptation, we hope to suppress inappropriate eye movements in response to our prosthesis’ electrical stimulation. If our lab can prove that electrically elicited eye-movements become more accurate after the dissolving and guided re-growing of PNNs, we can show that it is possible to restore plasticity to the brain and shape its neural connections through controlled electrical stimulation to the target system. By extension, such results will ascertain if it is possible to use this method to re-wire a physiological system to accept prosthetic stimulation in place of a non-functioning system.

The project I worked on was part of a larger project in which we examined the activity of O6-methylguanine-DNA methyltransferase activity, CpG promoter methylation, and progression-free survival following alkylating agent therapy in glioblastoma and anaplastic glioma brain tumors. For my part in the research I performed standard biochemical assays to quantify O6-methyalguanine-DNA methyltransferase (MGMT) in extracts of glioblastoma (GBM) and anaplastic glioma (AG) tumor samples from adult patients operated on with consent at the University of Washington Medical Center between 1991 and 2008. MGMT is a DNA repair protein that excises methyl adducts from the O6 position of guanine residues. Chemotherapy and other alkylating agents such as methylating triazene derivative temozolomide (TMZ) are responsible for methylating DNA, or damaging the DNA and thus destory the tumor cell. There has been poor prognosis for GBM due to the intrinsic resistance mechanisms in the MGMT that limit the efficacy of TMZ and other alkylators. GBM and other gliomas display a wide range of MGMT activity and thus the question for research was whether the amount of MGMT in tumors correlated with progression-free survival following alkylator-based chemotherapy. Overall the data strongly supported that MGMT activity in GBM and AG tissue mediates resistance to alkylator therapy.

Research over the years has shown that effective oral hygiene with brushing and flossing can help reduce bleeding, gingivitis and plaque buildup. When bacterial plaque is left alone or removed improperly, it can lead to further dental disease such as caries. During orthodontic treatment, fixed appliances such as brackets are bonded to the teeth and archwires connect the brackets. These appliances make it especially hard for orthodontic patients to brush and floss effectively on their own, and failure to do so leads to an increase in plaque and gingivitis seen in the orthodontic population. A pilot study at the University of Washington’s Center for Pediatric Dentistry (CPD) will assess development of white spot lesions during orthodontic treatments. White spot lesions are the first sign of a caries lesion on enamel that can be detected with the naked eye. Pediatric orthodontic patients from CPD will be enrolled in this pilot study. Study participants will be randomly assigned to one of two oral hygiene regimens. Group A will use the WaterPik Water Flosser with orthodontic tip (dental water jet irrigation system) in conjunction with daily oral hygiene and Group B will use floss with a threader in conjunction with daily oral hygiene. Both groups will manually brush their teeth with fluoridated toothpaste twice daily as part of daily oral hygiene maintenance. The White Spot Lesion Index will be used to evaluate white spots. The primary objective of this study is to evaluate prevalence of white spots in fixed orthodontic cases following these assigned oral hygiene regimens. Secondary objectives include assessment of safety and of plaque and gingival status for both groups. Intraoral examinations will be performed; and visible plaque index and bleeding on Marginal Probing scored at each follow-up evaluation. Study participants will be evaluated at every orthodontic appointment for a minimum of 18 months.

Protein kinases are enzymes that take phosphate groups from adenosine triphosphate (ATP) molecules, the energy in your body, and add them to other specific molecules inside the cell. This transfer of the phosphate group can activate or deactivate the target molecule, thus regulating cellular activities such as growth, replication, and respiration. The kinases studied here are hemopoietic cell kinases (Hck kinases) under the class of Scr kinases. Hck kinases are present in bone marrow and are often associated with myeloid leukemias and myeloproliferative disorders. Studies have shown that in the active conformation, the Hck kinase detaches two of its domains, SH2 and SH3, resulting in a more extended conformation. Using a Waters Synapt G2 HDMS, ion mobility mass spectrometry (IM-MS) techniques were used to probe the size of inactive and active Hck kinases by measuring drift times of their gas-phase ions traveling through a neutral background gas under the presence of a weak electric field. Drift times were then converted into collision cross section (CCS) values, which depend on the size and shape of the ion of interest. Eight different small molecules (< 500 Da) were used to inhibit Hck kinases, and changes in conformation were investigated using IM-MS. Preliminary data shows no significant changes in global conformation or size, conflicting with the previous studies. To investigate more subtle changes in conformation, collision induced unfolding (CIU) methods are used. By selecting an ion of interest using a quadrupole mass filter, protein unfolding is monitored using ion mobility as a function of ion activation prior to ion mobility analysis. This process allows an investigation of the subtle conformational changes in the Hck kinase upon the binding of small inhibitor molecules.

 Transition-metal ions promote a wide range of vital enzymatic biological and chemical processes involving dioxygen (O₂), including photosynthetic H₂O splitting, biosynthesis of neurotransmitters, and DNA replication and repair. These are some of the most fundamental processes of life, and yet they are also some of the most poorly understood. A complete grasp of how these processes function at the chemical level is therefore of critical importance to our development of technology that improves our lives and the world around us. For example, understanding how to efficiently oxidize H₂O to O₂ is essential to the development of renewable solar fuels and fuel cells. The challenge for research lies in that these transition-metal containing enzymes are inherently difficult to probe by traditional spectroscopy methods because of their structural complexity. The difficulty in characterizing these species and their reactions, coupled with their importance in the natural world, has made them a subject of intense research across all scientific disciplines. The Kovacs research group studies the structure and reactivity of these transition-metal containing enzymes, or metalloenzymes. Our research method involves modeling a metal ion’s local environment with a ligand scaffold and implementing changes to these so-called biomimetic models that may elucidate how reactivity corresponds with various structural and electronic modifications. Spectroscopy is more diagnostic in these simpler models because the complex proteins that obscure the active site in the actual enzyme are not incorporated into the model. By comparing similarities in reactivity between the biomimetic model and the actual enzyme, we may help elucidate properties and chemistry of the enzyme itself. Preliminary work has been undertaken with a novel series of thiolate ligated, coordinatively unsaturated Co(II) complexes; the reactivity of these complexes with O₂ and O₂^- is currently being probed.

One of the functions of the vestibular system is to engage neural reflexes, which ensures the stabilization of a visual image during head movements. This is accomplished through the stimulation of vestibular hair cells, which respond to accelerations, and then produce compensatory eye movements opposing head motion. This called the vestibulo-ocular reflex (VOR). Hair cell loss results in vestibular deficits, and for these individuals, this loss of function is debilitating and results in vertigo and decreased visual acuity. To address these deficits, the Phillips lab has developed a vestibular prosthesis, which aims to use electrical stimulation to restore function by artificially activating individual branches of the vestibular nerve. However, it is not known precisely how the system changes after hair cell loss; this may have implications for the effectiveness of the prosthesis in treating vestibular loss. To explore this, we examined the interaction between the electrical activity and residual vestibular activity after vestibular loss. We first introduced a vestibular deficit in a rhesus macaque through successive gentamicin injections into the middle ear to destroy vestibular hair cells, and measured VOR responses to verify the progressive vestibular loss. Next, we recorded eye velocities in response to electrical stimulation to characterize changes in the efficacy of stimulation, thus providing insight into the prosthetic mechanism. Finally, modulated electrical stimulation was provided during rotation of the rhesus macaque to test the efficacy of the prosthesis in restoring VOR in conjunction with residual vestibular activity. Characterizing prosthetic function during increasing vestibular deficit is important in determining the mechanism of stimulation, the physiological responses succeeding hair cell loss, and ultimately a model for the prosthetic efficacy for human patients.

Asymmetric cell division creates diverse cell-types that are critical for stem-cell maintenance and tissue patterning in multicellular organisms, including ourselves. Therefore, understanding the mechanism of asymmetric divisions can have a huge impact on regenerative medicine. In plants, asymmetric divisions are important for producing proper patterns of stomata, which are microscopic valves that regulate proper exchange of carbon dioxide and oxygen while simultaneously minimizing water loss. A precursor of stomata, called a meristemoid, divides asymmetrically and renews itself, while its daughter cell, called a stomatal-lineage ground cell (SLGC), shows rapid polar expansion and loses stomatal precursor fate. How can a meristemoid create two daughter cells with contrasting characters? Lines of evidence suggests that rapid expansion of SLGC associated with polar localization of novel proteins is essential for cell fate determination. In this study, I will test this hypothesis within Arabidopsis thaliana by expressing a known regulator of cell polarity, Rho-GTPase2 (ROP2), in stomatal cell lineages. I have generated transgenic plants expressing green fluorescent protein (GFP) tagged Rho-GTPases (ROPs) driven by the stomatal-lineage specific POLAR promoter, which is short for POLAR LOCALIZATION DURING ASYMMETRIC DIVISION AND REDISTRIBUTION (POLAR) in order to view potential ROP localizations using confocal microscopy within stomatal cells. I expressed three forms of ROP2: a wild type form, a constitutively active form (CA ROP2) that always binds GTP and causes isotropic cell expansion, and a dominant negative form (DN ROP2) which always binds GDP and in inhibits cell expansion. Visualization of these ROPs may provide evidence indicating their presence is a requirement for meristemoid differentiation. Because ROPs are present in both plants and animals, this study is an important player in understanding stem cell differentiations, which may resolve the modern challenges we face with respect to regenerative medicine, world hunger, and biomechanical operations.

Breast cancer continues to be a major threat to women’s health. For survivors, breast cancer often recurs 2 to 15 years after the initial treatment, either locally in the same or contralateral breast or at a distant recurrent site (metastasis). Currently, the performance of traditional methods, such as mammography and genetic markers, for screening breast cancer recurrence is limited, and alternative methods is strongly desired. Because of their sensitivity to biological status, metabolite markers may provide better diagnostic accuracy and earlier detection. Therefore, metabolomics, which focuses on the parallel measurement of hundreds of small molecule metabolites, has emerged as a powerful methodology for understanding biochemical systems and metabolic changes due to cancer. The Raftery group identified 11 metabolites (lactate, glutamic acid, etc.) that are useful for breast cancer recurrence detection. This model provides an earlier and more accurate approach to detect recurrence compared to the current standard, cancer antigen 27.29 (a FDA-approved blood immunoassay for breast cancer treatment monitoring). Recently, they have developed a targeted liquid chromatography mass spectrometry method (LC-MS), which enables us to simultaneously monitor changes of more than 150 metabolites in 25 different metabolic pathways (such as Glycolysis and the TCA cycle) that are of potential significance to breast cancer. In our present work we are validating their previous results and expanding this research to investigate a more comprehensive metabolic profile. Our specific task in this project is to prepare the samples and analyze them using the LC-MS platform. Using commercial serum samples from recurrent and non-recurrent breast cancer patients, we anticipate additional metabolite biomarkers that will be very valuable for developing a better diagnostic test for detecting breast cancer recurrence. In the long run, these markers should be useful for improving survival rates of breast cancer patients and thus for reducing social and financial burden. 

Aging in the budding yeast Saccharomyces cerevisiae can be measured by its replicative life span, which is defined by the finite number of mitotic divisions of mother cells. The Kaeberlein lab measures the replicative life span of S. cerevisiae through the microdissection of dividing mother cells. This laborious process separates daughter cells from their mothers, which quantifies the replicative life span. We are assessing how various environmental factors affect the replicative life span of the cells. Our research project involves paraquat, a commonly used pesticide that produces reactive oxygen species within cells. This substance is normally considered to be toxic, and as expected, we have observed that the replicative lifespan of yeast is decreased in the presence of high concentrations of paraquat. However, we have also found that low concentrations of paraquat increased the replicative life span of the yeast. This observation is an example of hormesis- a phenomenon where beneficial effects are obtained at low doses of an agent that is otherwise toxic when given at higher doses. These findings are significant because a similar effect has been published with the nematode worm, Caenorhabditis elegans. C. elegans and S. cerevisiae are evolutionarily separated by approximately one billion years, suggesting that there is a conserved mechanism of life span extension influenced by paraquat. We are currently characterizing the effect of paraquat and other environmental conditions that will help us to find conserved pathways that modulate longevity.