Meier-Gorlin Syndrome (MGS), a form of human proportionate dwarfism, arises from mutations in proteins needed for chromosome replication, including the origin recognition complex protein Orc4. Yeast cells (S. cerevisiae) with the mutant allele (orc4MGS) have altered origin activity across the genome, but most dramatically, origin activity in the rDNA is abolished. The orc4MGS cells also display secondary phenotypes such as slow growth, temperature sensitivity, and sensitivity to the drugs hydroxyurea and cycloheximide. To deal with the lack of rDNA origin activity yeast with fewer rDNA repeats (about 10) overtake the culture. My research focuses on understanding whether the secondary yeast phenotypes are due to fewer rDNA repeats, or other consequences of mutant Orc4. To explore the distinction, I am using CRISPR/-Cas9, a system for precise gene editing, to replace the origins of replication in the rDNA region with more efficient origins (ARS1 and ARS1^max). CHEF gel electrophoresis provides a reliable way to quantify the copy number of rDNA repeats in my new strains. The copy number of rDNA increased in my mutant strains to about equal, or even above that of the parent strain. With the rDNA copy number of these new strains restored, I am retesting the previously secondary phenotypes of the orc4MGS strain. Testing is ongoing, but the data suggest that the strains I created now display intermediate phenotypes of growth rate, temperature sensitivity, and drug sensitivity. I conclude from the data that fewer rDNA repeats, as well as the mutant Orc4 protein contribute to the phenotypes observed in the original Meier-Gorlin yeast cells. I am currently determining the efficiency of the new origins in the rDNA, and asking how genome wide origin use has changed. With these experiments I hope to gain insights into some of the cellular mechanisms of Meier-Gorlin Syndrome.

Intracranial aneurysms can rupture, leading to hemorrhagic stroke, a devastating and deadly disease. The geometry of vessels plays a crucial role in the onset and molecular pathophysiology of intracranial aneurysm formation. Notably, regions of bifurcation tend to be more susceptible to aneurysm formation. Numerous studies focus solely on the interactions between hemodynamics and vascular geometry or those between hemodynamics and molecular expression changes. Despite the significant relationship between the structure of vessels and the endothelial cell (EC) molecular expression, there has been few investigations tying the relationship between how vascular geometry affects the EC expression, particularly genes known to be related to EC pathological response: ADAMTS-1, VCAM-1, MCP-1, PDGF-B. These genes are implicated in endothelial dysfunction and aneurysm pathophysiology. Here, we aim to see how the geometry of the parent vessel affects endothelial gene expression, using 3D-printed, endothelialized, idealized bifurcation aneurysm models of varying degrees of parent vessel curvature. We then quantify the mRNA and protein expression for the genes associated with endothelial response. By elucidating the relationship between the vessel geometry and EC expression, we hope to contribute in further advancing the modeling of aneurysm pathology.

Beside its academia, University of Washington Bothell (UWB) is also known for its phenomenal nature where more than 15,000 crows roost every evening, especially during the autumn and winter months, in the wetlands. Since these crows have infested these wetlands, and because free living birds can be significant contributors of antibiotic resistant (AR) bacteria to the environment they were chosen for this study. E. coli, which lives as a harmless commensal in the gut of all animal and birds, has proved to be not only an indicator of fecal coliform but also of antibiotic resistance present in the environment. This study seeks to find out the different sequence types(STs) of E. coli found in UWB wetlands using the Multi Locus Sequence Typing (MLST) technique, to find out about the lineage, and potentially how these isolates have ended up in the UWB wetlands. Antibiotic resistance possessed by the isolates was performed against 13 different antibiotics by other students in the laboratory. MLST was performed according to methods specified in the EntroBase database; Specifically 7 housekeeping genes, were amplified and sequenced. Extended spectrum beta lactamase (ESBL) and non-ESBL containing isolates were found. Two non-ESBL isolates, one from water and one from the fecal samples collected on the same date, with the same antibiotic resistant pattern, turned out to be from the human isolated clone ST 58, suggesting a link between crow and water. ESBL E.coli isolate ST 131, a highly virulent, and multi drug resistant isolate was found in 6 fecal and 1 water isolate. Therefore it is concluded that crows are potential vectors of spreading multiple drug resistant strains in wetlands, which poses health risk since these strains may be carried further during the winter months.

The DArk Matter In Charge-coupled devices (DAMIC) group at the University of Washington tests and packages charge-coupled devices (CCDs) that are used to detect dark matter. The CCD pixel array collects the free electrons that originate from collisions between silicon atoms and outside particles traveling through the CCD. The signal from these electrons is then measured and a two-dimensional image is produced, showing the interaction of the outside particles with the silicon atoms. In order to "see" a dark matter interaction, the CCDs have to be isolated from non-dark matter particles that may pass through. To do this, the experiment is operated 2 km underground and surrounded with lead blocks. However, these measures are in vain if there are radioactive particulates on the packaged CCDs. Radioactive isotopes decay and produce an array of particles, which are detected. One opportunity for particulate contamination is when the CCDs are exposed to the air in the DAMIC cleanroom. Therefore, the cleanliness of the cleanroom must be measured. This is done using a sampling procedure that has been standardized by the International Standards Organization (ISO). We used particle counters to count the number of airborne particulates and then analyzed the data using the ISO classification system. From this, we now know the cleanliness of the DAMIC cleanroom. Additionally, electron microscopy is being used to characterize the particulates that land on the CCDs during the wire-bonding process.

Polyglutamylation is a post-translational modification (PTM) of tubulin thought to play a role in a number of key microtubule-related functions across eukaryotic life, such as cell motility, spindle function, and neuronal growth. An inability to perform this modification has been linked to neurodegenerative diseases such as Alzheimer’s and Parkinson’s, as well as diseases caused by dysfunctional cilia and spindles. The modification is mediated by the enzyme family tubulin tyrosine ligase-like (TTLL), which act as glutamate ligases on tubulin. The nematode Caenorhabditis elegans expresses five such enzymes, TTLL-4, -5, -9, -11, and -15, compared to 13 predicted mammalian enzymes. Previous research in C. elegans indicates that the TTLL enzymes act redundantly and may be required for proper function of certain neurons in males. In this research, a C. elegans quadruple mutant with deletions of four of the five tubulin glutamylating enzymes (all except TTLL-4) was confirmed via PCR and assayed for male mating efficiency, viability, brood size, osmotic avoidance, and dye-filling (staining) of sensory neurons, which shows their structural integrity. We predict that male mating efficiency will be found to be significantly reduced compared to a wild-type control and similar to a triple mutant, supporting the hypothesis that the TTLL enzymes act redundantly and that multiple enzymes are required for the proper function of male-specific neurons. Viability will be mostly unaffected in terms of reaching adulthood, but mutant worms appear to grow slower than wild-type controls. Brood size, osmotic avoidance, and dye-filling will be similar to wild-type, as with the triple mutant. The results will need to be compared to a quintuple mutant, and indicate that tubulin glutamylation may be a good target for human brain disease research.

The Yerkes-Dodson law suggests that performance is optimal when physiological arousal is moderate. Prior research has shown that arousal induced by listening to music will affect task performance on a cognitive task. The goal of this study was to test whether different music tempos would affect arousal levels and performance on a cognitive task. We recruited 16 UW undergraduates and exposed them to different tempos of the same song while performing a math test. We tested their accuracy, completion time, and recorded their heart rate. Results suggest that accuracy was higher under moderate music tempo than slow but there was no difference between moderate and fast. Interestingly enough there was no difference in completion time or physiological arousal. Although we failed to establish an effect of arousal and completion time the fact that participants did better on accuracy when music tempo was moderate is in line with what we predicted. Music tempo could still be influential to performance and future research can be done to understand these effects by operationalizing performance differently. Future directions about ways to improve the study will be discussed especially whether music/music tempo affect people subjective arousal and physical arousal differently.

Dementia and learning impairment are associated with increasing age, and age-related diseases such as Alzheimer’s disease. There is evidence to suggest age-related cognitive decline is also associated with increased metabolic stress and disturbances in insulin signaling. Diets high in animal fat and table sugar are metabolically stressful, especially with increasing age, and place greater demands on mitochondrial bioenergetic machinery. This study was designed to show that a metabolically stressful diet would increase the severity of cognitive dysfunction in aging mice. Ten C57BL/6 male mice were fed a high fat and sugar (HFS) diet starting at 21 months of age. The diet consisted of 15% protein (casein), 58% fat (lard), and 27% carbohydrates (sucrose), as well as a vitamin and mineral mix. Nine mice were fed regular rodent chow (RC) diet, consisting of 24.5% protein (balanced amino acid mix), 13.1% fat (soy bean oil), 62.4% carbohydrates (28.2% starch and 3.25% sucrose), and a vitamin and mineral mix, for the same time period. Mice were weighed weekly and assessed for body fat using quantitative magnetic resonance imaging. After 7 weeks, mice were tested for learning impairment using a box maze paradigm. Mice on the HFS diet gained an average of 9.62 grams of body weight, with an average 18.7% increase in fat mass compared to mice on the RC diet. Mice on the RC diet showed moderate levels of learning impairment. Surprisingly, mice on the HFS diet showed very little learning impairment, suggesting that some component in the HFS diet had a sparing effect on cognitive decline. This observation may be unique to mice, and certainly requires additional studies, but still raises an intriguing implication for how clinicians and dieticians might consider alternative intervention strategies for cognitively impaired individuals.

Publication metrics have often played a major role in understanding the interaction between research, popular opinion, and public policy. The field of scientometrics has been especially successful in bridging this gap for hot-button environmental issues, such as global climate change. Here, we used publication metrics to look at another burgeoning environmental topic: marine microplastic pollution. Research into marine microplastics has risen explosively in recent years, and some governments have already introduced anti-plastics policies in response. Here, we looked into the influence of microplastics research in news outlets and public opinion. First, we searched ISI’s Web of Science for articles containing the search terms “MARINE” and “MICROPLASTIC,” and recorded the number of publications over time. Second, we used a web scraper to gather similar publication counts for popular news outlets. Finally, we gathered data on social media interest in microplastic pollution by looking at the frequency of Twitter posts containing relevant keywords over time. Differences in article and tweet lexicons were analyzed using WordSmith Tools. We hypothesized that increased published research on microplastics correlates with stronger media coverage and more social media presence. Overall, the project found a unique interplay between microplastics research and popular sources, and we discuss how this interaction might impact public policy changes.

Mount St. Helens erupted on May 18, 1980, demolishing an area of 600km2 and removing all fauna and flora in the area north of the mountain. The eruption converted the substrate in the area into a mixture of pumice pebbles and ash. Research has shown that ground beetles (Coleoptera: Carabidae) comprise 14% of the total beetle diversity out of 39 families observed making this the second most abundant family in the study area. Ground beetles are often used as bioindicators for ecosystem response along disturbance gradients. Their well-known taxonomy and short reproductive cycle make them effective monitors of ecosystem changes over time. Carabids have unique sensitivity to the changes of microhabitats during the progression of succession, seen through the loss and gain of species in the population over time as the successional landscape changes. My study aims to determine whether assemblages of ground beetles remain a model for relay successional patterns, as well as contribute to the ongoing monitoring of invertebrate biodiversity in this post eruption landscape. Pitfall traps were used to monitor carabid diversity at three locations: along Spirit Lake and two locations on the pumice plains. Traps were put in transects of five set 10m apart and checked weekly to ensure changes in phenology and species diversity over time were recorded. Over 300 carabid specimens and 20 carabid species were caught, with two species not previously recorded in the study area: Pterostichus lama(Ménétriés) and Agonum cupreum(Dejean). Agonum cupripenne(Say) was found in great abundance along Spirit Lake and in much higher numbers than previously recorded. This example may suggest the “boom and bust” model for carabid community assembly remains valid 40 years after successional processes began in this ecosystem.

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.

About eighty percent of the learning in young children happens through use of vision; therefore, any form of impairment may have a significant impact on a child’s ability to grasp information. The goal of the Educating Young Eyes (EYE) research project is to improve our ability to properly identify and assess a variety of potential near-vision problems that may hinder a child’s ability to learn. Once identified, we can then refer the child for a more detailed assessment by a vision specialist (i.e., an optometrist or ophthalmologist). Our research focuses on developing new, cost-effective and accurate diagnostics that will help identify vision problems – and also help provide for effective therapies. The mission of our research project is to work alongside optometrists and other health professional to build a wide range of applications and provide access to children’s near vision assessment and therapy using the latest technologies available. A series of software tools/applications that we are building include: 1) Red Flags – a mobile app that conducts a series of tests to help quickly discover children who suffer from convergence insufficiency, an anomaly of the visual system; 2) Vision Quick Check, a mobile app that provides school nurses with a convenient and efficient way to test near vision and distance acuity for children as well as testing for stereopsis; and 3) the EYE Web Portal which displays student credentials and testing history from the mobile apps – allowing nurses and administrators to communicate with the database and manage the student credentials records. In summary, we aim to increase awareness and provide access for all children to receive effective vision screening and help people better understand the importance of functional vision in children’s learning.

Women in the most underserved area of Seattle experience higher rates of pre-term birth, low birthweight rates, and cesarean section surgeries. The focus of this project is to see if female genital circumcision (FGC) correlates with the cause of these issues, but also if there are other factors that have an influence on high reproductive health disparities such as, racism, access to resources, and any other barriers of the community that are driving these issues. This project works with Somali immigrant and refugee residents in the south Seattle area because it is the most under-served, ethnically and economically diverse area. Somalia has the highest rate of women who have undergone the practice of FGM/C with a leading 98% of the female population between the ages of 15-49 years being circumcised. My project works collaboratively with the Mama AMAAN Project which seeks to test out a community-led, integrative services approach to improve perinatal health outcomes in this population. The goal of my project is to understand why these issues are consistently happening amongst women that come from similar backgrounds, more specific amongst East African women. While trying to reach the goal of this project, we seek to answer the following questions; What are the ways that FGC played a part in their perinatal experience and outcomes for Mom and infant? What is their perspective on the practices of FGC in Seattle as relates to themselves, their families, their community? To accomplish the goal of my research I plan on using qualitative methods by conducting written surveys, participant-observation during child birth education sessions. This project is significant because it assesses the reason for the high rates of reproductive health disparity that we are seeing amongst the women of the Somali community and how FGC is related to those problems, if at all.

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.

Hydrogen is a non-polluting, sustainable energy alternative to fossil fuels. One method of generating hydrogen is by splitting water with sunlight and a semiconductor photocatalyst. In this study, determining the most viable semiconductor in terms of efficiency and safety for the environment is critical for making hydrogen energy available for commercial usage. When the catalyst absorbs UV light, water molecules in contact with the activated surface are split. Hydrogen is produced more rapidly when the photocatalytic crystals have a high surface area to volume ratio. Therefore, greater efficiency can be attained by reducing the size of the photocatalyst crystals. Nanometer-sized crystals can be synthesized within nanopores, thereby avoiding loss of surface area by agglomeration. Particular attention has been focused on placing the most efficient and cost-effective semiconductor inside a matrix of cellulose fibers and introducing doping, quantum dots, and other engineering strategies to improve the suitability of the photocatalyst. Selecting the most fitting photocatalyst candidate for large scale mass production of hydrogen is imperative for providing a viable source of renewable energy.

Headache is common in childhood and can be associated with disability and distress. Family history of chronic pain may increase risk for pain and disability in childhood, although prior research has primarily focused on non-headache pain populations. We aimed to characterize the prevalence of headache, abdominal pain, and musculoskeletal pain in first- and second-degree relatives of youth with headache and determine whether family and parental pain history is associated with children’s headache experiences. We hypothesized that a positive family pain history would be common, and that greater extent of family and parental pain history would be associated with greater headache frequency, intensity, and disability. We enrolled 239 youth (Mage = 14.7, 66.5% female) with headache and their parents. Parents reported whether they and 16 of their first- and second-degree relatives had a history of migraine, tension-type headache, abdominal pain, or musculoskeletal pain. Youth completed a 28-day headache diary to assess headache frequency and pain intensity and completed the PedMIDAS, a measure that assesses headache-related disability. As expected, a family pain history was common: 65.7% of youth had a relative with migraine, 39.3% had a relative with tension-type headache, 44.8% had a relative with abdominal pain, and 66.9% had a relative with musculoskeletal pain. Children’s headache frequency was positively associated with the number of first- and second- degree relatives with a history of tension-type headache (r=.14, p=.04) and musculoskeletal pain (r=.14, p=.04), but not migraine or abdominal pain. We found that youth had greater disability when both parents had a history of headache compared to only one parent with a positive history, F(2,222)=3.27, p=.04. No associations were detected between family history and youth’s pain intensity. Our findings indicate children’s adaptation to headache may be influenced by their family. Further research is needed to understand potential mechanisms of intergenerational transmission of headache.

Mindfulness involves being present, aware, and non-judgmental. The present study investigates the efficacy of a brief weekly mindfulness intervention within the college classroom as a means of increasing psychological well-being among students. We hypothesized that mindfulness would have emotional, cognitive, and social benefits, and that students who participated more frequently would benefit more. Across six 10-week classes, N=800 university psychology students participated in a five-minute weekly mindfulness activity. Students completed measures of emotional, cognitive, and social functioning in both the first and last weeks as well as some questions specific to the mindfulness activities. We found strong support for our hypotheses for emotional and cognitive benefits. Emotional benefits included increased happiness, resilience, and significantly lower anxiety. Cognitive benefits included engagement in the activities, engagement in the class, being more focused in class, and a positive impact on grades. Students who participated more frequently and to a greater degree saw more positive effects from the intervention. We conclude that a brief mindfulness intervention may be an effective way to improve wellness on the university campus.

Currently at the UW Molecular Hematopathology lab, peripheral blood and bone marrow samples stored at room temperature and at 4°C are used to perform molecular testing for clinical diagnoses. The current maximum storage length for both specimen types is established at 4 days, and samples received that are older than 4 days must have degradation and DNA quality assessed, a specimen redraw is requested, or the specimen is even rejected. To test the possibility of extending sample storage life by analyzing DNA quantity and quality of samples older than 4 days, I collected peripheral blood and bone marrow specimens and I stored them respectively at either room temperature or storage temperature conditions. I then extracted DNA from the samples on set days throughout a 14-day period, where I then quantified the DNA by spectrophotometry. Other technologists within the lab then qualitatively assessed the extracted DNA samples by fragment analysis. DNA concentrations appear stable through Day 14 and Day 11 for PB and BM, respectively, well beyond the current 4 day age limit for samples. Temperature did not seem to contribute to decline in DNA concentrations, though did seem to affect DNA quality. It would be beneficial to extend storage beyond 14 days to see when quantity and quality eventually do decline. There is good reason to believe sample holds and quality assessment can now be reliably deferred for samples older than 4 days, at least until the 14 day age mark for peripheral blood specimens and the 11 day age mark for bone marrow specimens. The quantity and quality of PB and BM samples did not decline significantly when held for longer than 4 days, nor did temperature or storage time up to 14 days significantly affect sample viability.

The study of firn is integral to determining past climate from ice cores and calculating present and future melt runoff from ice sheets. The Herron and Langway model is a semi-emperical firn densification model. While the model's simplicity makes it easy to use, it assumes constant temperatures and accumulation rates, but Earth's climate is changing. The goal was to recalibrate the model by adding data from new ice cores to a gap in the model's dataset to create more accurate depth-density curves. Preliminary results show the recalibration is a better fit for 57 percent of depth-density profiles. The recalibration could help determine melt runoff, informing sea level rise forecasts. The recalibration could also increase the precision of timing between past CO2 and air temperature changes.

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.

In human-robot interaction, virtual reality (VR) provides strong potential to aid in the design of social robots. In order to understand teens' perceptions of, and interactions with social robots, we utilized a human-centered design methodology to develop a collaborative VR game for teens. The design process involved interaction studies with a local high school in three phases: (1) Brainstorming and Sketching environments on Paper, (2) Card sort game play for exploring robot design options (3) Developing and usability testing the low-fidelity VR game play. The design goals were to create an inviting game context for teens to engage in collaboration and to elicit and capture the details of teen-teen and teen-robot interactions within VR. From the design process, we found that (1) the human-centered design process engaged teens in the design process (2) teens expressed positive emotions during collaboration and (3) the asymmetric design of the VR game allowed for not only strong engagement, but also unexpected role play as teens identified themselves as the robot during gameplay. Through the design and development of this VR game, we recognized the effectiveness of a VR platform as not only a design tool, but also as an engaging collaborative platform for gathering interaction data from teens. Given this potenial, we anticipate several future applications for the study of teen-teen interaction through VR collaboration.

Homo naledi is a species of hominin that lived in South Africa at between 335-236 ka, around the same time that anatomically modern humans were evolving in Africa. While the lower limb of Homo naledi shares many characteristics indicative of obligate bipedality with modern humans, the upper limb shows a more primitive morphology related to climbing. The distal humerus is one of the more common bony elements found in the fossil record and its morphology directly reflects the functional requirements of the limb, making it a good place to study upper limb function and adaptation. Using 3D geometric morphometrics, we compared seven distal humeri attributed to Homo naledi with distal humeri from great apes, modern humans, Neandertals, and other extinct hominins to place H. naledi in a functional context. We conducted a principal components analysis and partial least squares analysis on anatomical landmark data to investigate variation in distal humeral shape. Preliminary results indicate that H. naledi had a distal humeral morphology broadly similar to gorillas and unlike modern humans. Our results provide new insights into the upper limb mechanics and the role of climbing in the locomotion of Homo naledi, as well as clarify their phylogenetic relationship with other hominins.

As of February 2019, 3,916 extrasolar planets (planets orbiting another star) have been confirmed. A limited number of these planets have published spectral data of their atmospheres. This data comes from transmission spectroscopy taken during the transit of the extrasolar planet: as the exoplanet passes between the earth and its host star, light from the host star goes through the exoplanets’ atmosphere, which shows different absorption patterns based on its composition. The goal of this research is to gather published transmission spectroscopy data on atmospheric compositions of extrasolar planets, and to look for possible trends. In particular, we are searching for trends in relation to the different physical properties of the extrasolar planets: radius, mass, orbital period, temperature, etc. As a first step, our research has focused on hot Jupiters with periods from one to three Earth days, and radii between one and two Jupiter radii. From the 78 planets that fit in this parameter space, seventeen had published spectral data, and out of those only eight had spectra that covered an overlapping large wavelength region (480 to 900 nanometers). Out of these planets, unfortunately only one showed absorption in their atmospheric data, which did not allow us to look for any potential trends. We will present the results of an expansion of this work to a larger parameter space of radius versus orbital period to search for trends between the absorption characteristics of the extrasolar planet’s atmosphere and their physical properties.

Previous research has established extracellular vesicle (EV) signaling as a ubiquitous cell-signaling modality used by all cells. In this modality RNA, peptide, and protein signals are packaged together in small vesicles and directed to specific downstream cell targets. In addition to being necessary for healthy physiology, EVs can also contribute to pathological processes such as neurodegeneration in Alzheimer’s disease through carrying toxic proteins tau, Aβ and β-synuclein between cell types. Recent research in the Kaeberlein and Mendenhall labs has shown that when human tau is specifically expressed in neurons of C. elegans, there is a significant increase in HSP90 chaperone and proteostatic stress reporter expression in the intestine. I hypothesize that the induced human tau neuron-to intestine stress signal is conveyed by the extracellular vesicles. To determine the signal pathway, extracellular vesicle signaling was disrupted specifically in neurons of a transgenic nematode line with neuron-specific human tau and fluorescent intestinal proteostatic stress reporter (daf-21::GFP). RAL-1 is a small GTPase that has been shown to be necessary for EV signaling in the C. elegans hypodermis and intestine. Therefore, RAL-1 function is disrupted though knocking down neuron-specific expression with either a double-stranded RNA ral-1 construct or a dominant-negative form of RAL-1 The degree of daf-21p::GFP expression was compared between the reporter lines and those with disrupted ral-1 function. Many studies utilizing C. elegans have shown that neurons send cellular stress signals to other tissues which strongly affect lifespan, metabolism, and proteostatic stress. Therefore, the results from my experiments contribute to determining whether EV-signaling carries neuronal stress-signals induced by human tau and establish a methodology for using C. elegans as a model for studying this important signaling pathway.

Reactive oxygen species (ROS) are partially reduced oxygen molecules produced during cellular metabolism in all aerobic organisms including plants. ROS derivatives such as superoxide (O2–) and hydrogen peroxide (H2O2) cause several types of cell damage in plants. Chloroplasts and mitochondria are major sources of ROS because of photosynthesis and aerobic respiration in these organelles, respectively. Previously, our lab showed that light-grown maize plants have more damage in plastid DNA (ptDNA) and mitochondrial DNA (mtDNA) than dark-grown plants and that ptDNA and mtDNA levels decline during leaf development. Here, we hypothesize that increased damage to ptDNA and mtDNA in light-grown leaves is linked to increased ROS generation compared to dark-grown and germline stalk tissues. We used absorbance- and/or fluorescence-based assays to quantify levels of ROS in chloroplasts and mitochondria isolated from leaf and stalk tissues during seedling development. Our data suggest that light-grown leaf has more ROS than light-grown stalk, dark-grown leaf, and dark-grown stalk. Our findings indicate that highly damaged DNA is a consequence of ROS generation in light-grown leaves of maize. Overall, this research will help us further understand the oxidative damage caused by various reactive oxygen species during the development of maize plants. 

Legionella pneumophila is a gram-negative, intracellular pathogen that is the primary causative agent of Legionnaires disease. During infection, Legionella utilizes a type IV secretion system to colonize the alveolar macrophages of humans and causes a pneumonia-like disease. Despite this, Legionella cannot be transmitted from human to human, and thus infection of humans by Legionella is seen as an evolutionary dead end for the bacterium. However, it is known that Legionella uses the same mechanisms to colonize macrophages as their natural, amoeba hosts. As a result, we hypothesize that genetic innovation driven by Legionella-amoeba coevolution has resulted in an array of cellular effectors in the Legionella genome that are used to infect and modulate and array of hosts. In this study, we use a Legionella-amoeba system to study the coevolution between Legionella pneumophila, and an amoeba host, Dictyostelium discoideum. In particular, we focus on identifying, and functionally characterizing the evolutionary trajectory of a rapidly evolving T4SS effector gene, MavN. MavN is a transmembrane, iron chelating protein that is critical to infection for all species of Legionella. As a result, we use a comparative evolutionary approach to study the efficacy of various MavN effector orthologs from across the Legionella phylogeny. By doing this, we can begin to trace the evolutionary trajectory of MavN effector evolution and specify sequence specific regions of MavN that have evolved to be more successful during infections.

Supraspinatus tendon tears are a type of rotator cuff tear, accounting for 15% of overhead workplace musculoskeletal injuries. These tears disproportionately affect blue-collar workers and cost millions in healthcare every year, but there is still relatively little known about the appropriate work-rest cycles to prevent the risk of occurrence during work. Directly measuring the rotator cuff in vivo is difficult because the supraspinatus is covered by the bursa sac, the acromion, and the deltoid, making its material properties hard to accurately record. This presents a need for a material that can model an in vivo shoulder tendon. There are many options of what materials can be used: organic and in vitro models are the most common, with relatively new inorganic models being designed. However, none of these models fulfill all modeling needs; overlap between all models is needed to get an idea of how an in vivo tendon accumulates damage. Organic models can provide tissue repair and degradation rates and these can be projected for a human supraspinatus. From in vitro studies stress-strain curves and maximum load can be recorded, and from inorganic models tear propagation can be observed. This work compiles research on candidates for tendon proxy materials by cross-referencing a variety of papers in tendon literature to find the foundational papers. Then builds off those with other works by the foundational authors or other highly regarded works that cite those foundational papers. From the collection of these papers, the shortcomings of current tendon modeling can accurately be seen, showing what research is needed to better model in vivo tendons. For instance, to confirm the hypothesized projection from organic models, psychophysical testing that isolates the supraspinatus needs to be conducted. Better modeling of tendons will allow for better prediction of appropriate work-rest cycles that may slow tendon fatigue damage.

Chronic postsurgical pain (CPSP) develops in 10-50% of pediatric patients after major surgery. Despite potentially severe health implications, little literature exists examining the epidemiology and mechanisms of pediatric CPSP. A barrier to progress in this area is that while definitions of CPSP exist in adults, definitions do not include impact of pain on health related quality of life, a critically important aspect of pain assessment. Consequently, the objective of this research study is to develop a clinically meaningful definition of pediatric CPSP that incorporates measures of pain intensity and quality of life, which can be standardized across clinical and research populations. The aims of the study were to (1) identify and extract common elements of current definitions used for CPSP in the existing literature, and (2) identify clinically meaningful cutpoints for CPSP based on pain and quality of life, through secondary data analysis of two clinical research studies examining pediatric post surgical pain. Literature search found that existing studies employed inconsistent definitions of CPSP, limiting our ability to develop a literature-based definition. Our dataset included 179 adolescents 10-18 years old undergoing surgery for spinal and chest wall deformities. Measures included pain intensity (Numerical Rating Scale), quality of life (PedsQL) and pain interference (Visual Analog Scale) at 4 and 12 months post-surgery. We conducted scatter plots to visually inspect the associations among pain and health outcomes. Cluster analyses of pain and health-related quality of life identified four unique cluster groups differing on level of pain and functional impairment. Next steps will include determining cutoffs for pain and quality of life based on these cluster groups, and validating the newly proposed definition in an independent sample of youth undergoing surgery. A consistent definition for CPSP which incorporates both pain intensity and functional impact of pain will help guide future research and treatment.

Dementia is a neurological condition that impairs memory, cognitive functions, and the performance of daily activities. It is estimated that 5.5 million Americans suffered from dementia in 2018. Currently, the predominant method used to treat persons with dementia is through pharmacological means. However, through reviewing current research, we have found evidence to suggest that cognitive behavior therapies (CBT) may be more beneficial to patients, with the potential to reverse some symptoms of dementia. Our study aims to improve CBT through virtual environments. Virtual Reality (VR) is not merely a visual platform but an immersive environment that stimulates the brain in the same way real environments do. However, in VR we can track certain markers like head and eye movement, metrics that can be valuable in tracking the progression of the disease as well. We have developed a virtual experience that can calm and stimulate seniors while being able to track a person’s ability to perform free recall and spatial recognition through a series of memory games. This experience has the potential to have both therapeutic and diagnostic capabilities, as well as provide insight into how VR can affect memory. Over the past 6 months, our research team has worked with seniors at the Greenwood Senior Center to test different virtual reality platforms such as the Oculus Go and HTC Vive, as well as various virtual environments. Using our experience from the center our team is creating a platform tailored to fit seniors who are affected by dementia. In the near future, our team will be volunteering at a local assisted living facility to work with these seniors. This project will offer understanding of how implementing VR therapy can improve patients’ morale and cognitive capabilities, as well as exploring the use of VR as a diagnostic tool.

Interferons are signal proteins released by cells in response to infections which induce neighboring cells to synthesize anti-viral genes like Mx2, which encodes the MxB protein. MxB was thought to only restrict lentiviruses but recent studies have shown that MxB also restricts herpesviruses. It is hypothesized that herpesvirus and MxB have co-evolved in an ‘arms race’ to compete against each other. This suggests that regions of MxB that are under positive selection may have interfaces for its anti-herpesvirus activity. In order to test this hypothesis, I plan to determine whether different homologs of MxB can restrict human herpesviruses. I created MxB inducible cell lines using MxB homologs from three different primates - humans, rhesus monkeys and owl monkeys. Subsequently, I infected these cells with the following GFP labeled viruses: herpes simplex virus 1 (HSV-1), Kaposi’s sarcoma-associated herpesvirus (KSHV), and human cytomegalovirus (HCMV). I assessed the effect of these MxB alleles on viral replication by measuring viral titer and viral protein production (including GFP). I expect that the MxB restriction of herpesviruses will be species-specific, with only human MxB showing meaningful reduction in human herpesvirus replication. These results will guide future research aiming to understand the physical interactions and mechanisms of suppression between MxB and herpesviruses.

G protein-coupled receptors (GPCRs) contain seven transmembrane domains and are the largest family of cell surface receptors, making up ~1% of the human genome. GPCRs can interact with a variety of ligands, such as odors, pheromones, hormones, and neurotransmitters. At least 30 human GPCRs contain a C-terminal Type-I PDZ ligand that allows for interactions with adapter proteins which can regulate receptor trafficking, stability, and signaling. The Hague Lab has previously found that the α1D-adrenergic receptor, which contains a C-terminal Type-I PDZ ligand, also undergoes an endogenous N-terminal cleavage event, which enhances receptor function and may play a role in which PDZ domain containing proteins interact with this receptor. We propose that this unique observation of the α1D-adrenergic receptor may be prototypical of a new class of GPCRs which contain a Type-I PDZ ligand and undergo an N-terminal cleavage. CysLT2, MAS1, and NPFFR2 are understudied GPCRs and potential members of this family with distinct PDZ ligands, though it remains unknown if their extracellular N-terminal domains regulates receptor function. Thus, I have cloned wildtype and N-terminal truncation mutants of these three GPCRs into the pSNAP vector to create fusion proteins with N-terminal SNAP tags. These constructs were transfected into HEK293 cells and subjected to near infrared PAGE analysis to elucidate the presence of N-terminal processing. Furthermore, dynamic mass redistribution revealed how the N-termini modulate receptor signaling. The combination of biochemical and pharmacological techniques allows me to determine if these receptors belong to this new subfamily of GPCRs. These results increase our understanding of how GPCRs are regulated within the cell, which can lead to the development of more efficient drugs.

Hair cells are sensory receptors responsible for hearing and balance in the auditory and vestibular systems. These cells are surrounded by supporting cells, which are non-sensory cells similar to glia. In non-mammals, hair cells get replaced after damage through conversion of supporting cells. Recent studies have shown supporting cells can also transdifferentiate into type ll hair cells in the vestibular system of adult mice. The signals that control hair cell regeneration in mammals are poorly understood. It is known that the transcription factor Sox2 is utilized for specification of hair cells in the neurosensory domain of the otocyst. This project tests the premise that Sox2 is required in adult supporting cells for their transdifferentiation into type II hair cells after damage. We used time specific gene deletion technology, CreER-LoxP, to delete the gene encoding Sox2 in supporting cells prior to damage. The mice used include the following alleles (genetic segments): 1) the floxed Sox2, or Sox2loxP/loxP allele, which enables Sox2 deletion when Cre is active; 2) the Sox9CreERT2 allele, which targets Cre expression to supporting cells; Sox9CreERT2 is tamoxifen-dependent, so the timing of Sox2 deletion is controlled by tamoxifen injection; and 3) the Pou4f3DTR allele , which enables hair cell killing upon injection of diphtheria toxin (DT). Hair cells were identified and “typed” using several markers, including antibodies to myosin VIIa, neurofilament, and ßIII tubulin. I compared the number of regenerated hair cells of Sox2 expressing supporting cells and Sox2 negative supporting cells. Sox2 deletion in supporting cells resulted in a significantly reduced number of type ll regenerated hair cells. This result provides evidence that Sox2 is required for transdifferentiation of supporting cells. Understanding the function of Sox2 will give insight into potential downstream molecules that can become prospective targets for future research in understanding cellular regeneration in adult mice.

Plastics are a ubiquitous part of modern life, without them many issues in the food, medical, and textile industries would be near insurmountable. However, our failure to consider life cycles of materials containing plastics have led to a global environmental threat. As polymers break down through degradation, they can create microplastics (MP’s) or fibers that can escape into the environment. Microplastics are generally less than 5mm. Recent studies have indicated that endangering levels of MP’s have been found in the oceans. Little to no research has been conducted on the quantity of MP’s found in freshwater bodies and land far from the influence of the ocean. Little is known about the amount of MP’s released during a clothing dryer cycle. To address sources of MP’s created from a clothing dryer, samples of lint were collected beneath the dryer vent exits. Aggregate characterization of the samples were performed using attenuated total reflectance infrared (ATR-IR) which allowed samples to be evaluated based on a measured wavelength of a reflected beam of light. Samples collected were representative of MP’s that would shed from textiles during a drying cycle and be distributed into the air. To effectively characterize and count MP’s in solution a fluorescent dye (Nile Red) was used to stain the samples before imaging with a Fluorescent Microscope. Most dryers have a mesh screen to catch lint which has been useful, but it doesn’t capture all the microfibers during a drying cycle. Still, hundreds if not thousands of microfibers evade the lint filter and are likely being released from the vent. The potential consequences of not regulating the release of MP’s correlate with the growth of the textile industries. An important first step to this problem involves similar research to better understand the origin and release of MP’s into the environment.

Efforts to engineer flying micro-robots (~50mg) are motivated by their potential advantages relative to larger robots, such as greater deployment numbers at the same cost. There are significant developments in flapping wing robots at insect-scale; however, little advancement has been made in the development of robots with ionic actuation using electrohydrodynamic (EHD) thrust. This thrust is generated through the ionization of air particles and momentum transfer of these positive ions with neutral air molecules. EHD thrusters have used collector grids and emitter wires to generate a thrust for controlled flight. In this research, we design and fabricate a 1.8 x 2.5 cm micro-thruster that weighs a total of 43 mg including the carbon fiber collector grid, four blue tempered steel emitters, and eight fiber optic glass tubes. This robot is hand-assembled using a laser fabricated external fixture. Electrodes of the robot are fabricated using a laser based system. The whole robot takes a total of 20 minutes to assemble. Emitters are supplied with a high voltage (~2.5kV) using a bundle of 51-gauge insulated copper wires. Similar wire is used for grounding the collector grid. A parametric study is carried out to optimize the physical parameters of the robot. Experiments performed in this research show that the thrust generated is larger than the weight of the robot. 

For many globular proteins, the sequence and native structure are known. However, less is understood about how a string of amino acids folds into a functional protein. Experimental study of folding presents challenges due to the transience and variability of folding/unfolding transition states and intermediates. Alternatively, computational study of unfolding can provide significant insight into folding. Here, molecular dynamics simulations have been used to study the unfolding pathways of the SH3 domain structural family and to investigate the factors that determine the path and outcome. To separate folding determinants from amino acid sequence, 17 SH3 proteins were chosen with an average sequence identity of only 27%. Six unfolding simulations were performed for each protein, and the unfolding transition state ensemble was identified by locating the large, rapid conformational changes that signal the start of unfolding. Contact analysis was used to characterize the structure of the transition states ensembles. Two general pathways at the transition state were identified, distinguished based on the specific β-sheet structure lost at the transition state. In the first, more populated pathway contacts in the β-sheet containing the N- and C- terminal β-strands were lost while the second pathway was defined by structure loss in the other β-sheet. Though many of the investigated proteins went through both pathways in different simulations, most showed a clear bias towards one pathway. This work demonstrates that similar protein structures can fold through different pathways. The bias of many SH3 proteins towards one folding pathway also suggests the presence of some elements of primary structure that direct folding. Further investigation of the SH3 domain may yield ‘rules’ that determine the structure and folding pathway of the domain, and these rules may inform the study of other, similar proteins.

Platelets seal wounds in blood vessels in order to prevent blood loss. When there is an exposed vascular matrix, platelets bind at the wound site through the glycoprotein (GP) Ib-IX-V complex. Glycoprotein receptors allow platelets to initiate homeostasis by forming attachments to the damaged tissue. Platelets use their glycoprotein receptors to form bridges between other platelets and the surrounding proteins that form the clot within the blood vessel. Aspirin, a common household medication, produces its effects through inhibition of thromboxane production which prevents the formation of these blood clots by meddling with platelet aggregation. Standard doses of aspirin for an adult are 81mg, 325mg, and 500mg. However, there could be differences between male and female platelets, indicating that there may be different amounts of glycoprotein receptors between males and females. Here, we evaluated the force of single platelets without aspirin in males and females and single platelets with aspirin in males and females by using a reference-free traction force microscopy (TFM) platform. This TFM platform contained a grid of a fluorescent protein at known locations and was coated with von Willebrand Factor (VWF) to mediate platelet binding. Immunofluorescent staining and fluorescent imaging was conducted to visualize to platelet f-actin, a cytoskeletal component, and GPIb. Platelet binding, spreading, and contraction is observed on these substrates. By placing the platelets on the substrate, we are able to measure the deflection of the grid and determine the force a single platelet generates. In the future, we hope to measure the force of platelets at 0mg, 81mg, 325mg, and 500mg between men and women and hope to elucidate how GPIb expression, platelet mechanics, and response to aspirin varies in males and females.

Prion diseases occur from the misfolding of the Prion Protein cellular form (PrP^C) under low pH conditions to the infectious scrapie species (PrP^Sc), which can aggregate further into insoluble fibrils. Previous studies have demonstrated that along with other amyloid oligomers, the prion scrapie oligomers cause neurotoxicity by disrupting the membrane, increasing its permeability and affecting calcium ion influx; however, the molecular mechanism for this effect is unknown. Molecular Dynamics simulations were performed to gain insight into the molecular mechanism of PrP^Sc-induced misfolding of PrP^C and oligomer toxicity in a membrane environment. The system was composed of the hexameric bovine PrP^Sc spiral model oligomer and the di-glycosylated human PrP^C attached to a POPC membrane via a glycophosphatidylinositol (GPI) anchor. Prior unpublished membrane simulations of this system have suggested that PrP^Sc induced PrP^C conformational changes as well as significant membrane disruption from oligomer-binding. Here we confirm and build upon these earlier studies demonstrating the reproducibility and robustness of oligomer binding affinity by varying the proximity of the oligomer to the membrane, providing key insight into infectious scrapie propagation and PrP^Sc cellular toxicity.

Microbial communities are essential to numerous biological systems from aquatic and land ecosystems to the human gut. Our understanding of interactions among bacterial strains can help us understand how these communities form and function. Such interactions may depend on the species themselves but can also be sensitive to the abiotic environment. Harsh environments, where mortality is increased, can reverse the outcome of a competition between species. Simple models predict that increasing mortality favors faster growers, and past experiments repeatedly confirmed this prediction. In these pairwise competition experiments, slow growers excluded fast growers in low-mortality environments, but increasing mortality caused fast growers to dominate. A necessary condition for observing the reversal is that slow growers are good competitors in low-mortality, high-density environments. While this tradeoff between growth rate and competitive ability was common in well-characterized lab strains of bacteria, it was unclear if it might exist elsewhere. In this project, we tested for the existence of a growth/competition tradeoff in a natural community of bacteria collected from MIT’s Killian Court. Contrary to past results and some evidence from the literature, we found a weak positive correlation between competitive ability and growth rate, which does not support the idea of a tradeoff.

Self-efficacy has been shown to be associated with fewer problem behaviors in adolescence. However, the research investigating this association has been primarily based on self-report measurements of delinquency. The purpose of this study is to see if this association is maintained with a more objective measure of delinquency by examining juvenile offenders’ self-efficacy, and its predictive relationship with probation violations. Using self-report survey data of juvenile offenders’ self-efficacy along with probation violation data from Pierce County Juvenile Court, we conducted a statistical analysis of self-efficacy measurements and official probation violations. The self-reported self-efficacy measures address feelings in desire of academic and career success, prosocial behavior, and a reduction in the desire to express aggressive behaviors. If self-efficacy is shown to be a good predictor of fewer probation violations, further research can investigate determinants of high versus low self-efficacy, or how to improve self-efficacy, in order to promote probation adherence of juvenile offenders.

Electric propulsion is becoming an increasingly important field due to the rise of microsatellites in education, research, and industry. Because chemical propulsion is impractical for these small-scale satellites, the need for an efficient, long-term electric propulsion solution has become apparent. In response to this, the Dielectric Barrier Discharge (DBD) Thruster was developed. The DBD is a novel electric propulsion system that uses a low power input to ionize Argon gas and accelerate ions to produce thrust. For initial characterization, thrust values and plasma characterization parameters were collected in the far field of the plasma using electric propulsion diagnosics. The experiment was repeated for multiple operational spaces, and data was collected, compiled, and analyzed. Preliminary results indicate thrust values and plasma characteristics comparable to those of other propulsion systems at similar electrical power levels. Further testing with different high voltage parameters as well as implementing additional diagnostic equipment will help fully characterize the DBD system and assess its potential usefulness in a satellite architecture. To increase the versatility of the DBD system, research will be done on developing multi-DBD arrays and incorporating a nanoparticle injection system for demonstrating future space resource utilization.

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.

Organic solar cells (OSCs), particularly all-polymer solar cells, have risen as an exciting alternative to standard inorganic solar cells. Their low-cost synthesis, easily tunable properties, and solution-processable fabrication enable facile scale-up for high-throughput production. For commercial viability OSCs will need to have power conversion efficiency (PCE), which is determined by the material characteristics and energetic properties, comparable to their inorganic counterparts (>20%). The question this research aimed to address is: How do processing conditions govern the electronic properties of the photovoltaic layer? Two primary methods were used to evaluate the energy levels: Cyclic Voltammetry (CV) for the highest and lowest occupied molecular orbitals (HOMO/LUMO) and Ultraviolet-Visible Spectroscopy (UV-Vis) for the optical bandgap. A binary blend comprised of a polymer donor, known as PSEHTT, and a polymer acceptor, N2200, was used as a proxy model. Blends of compositions ranging from 0 to 100 weight % PSEHTT were coated on platinum wires for CV and glass substrates for UV-Vis measurements. The collected data behaved as expected, exhibiting a decreasing trend in HOMO level from -5.29 eV to -4.94 eV as the weight % PSEHTT increased. The evolution of the LUMO level with blend compositions was rather challenging to obtain due to possible photoexcitation in the blend leading to free charge available for continuous current extraction. To verify, the samples were isolated from light over the course of the CV measurements to prevent interference. This should result in more accurate LUMO level approximations which are expected to display a similar trend to the HOMO level. Elucidating the relationship between blend composition and blend electronic properties enables a precise and facile device optimization process for highly efficient OSCs.

Probiotic bacteria grow on the intestinal lining and are essential for optimal digestive health. Understanding the optimal growth conditions for these probiotics is particularly important, since healthy probiotic populations in the gut have been shown to positively impact health in a number of ways. In order to determine the effect of pH and nutrient availability, the following methods were performed; first, probiotic growth was achieved by inoculating Sigma-Aldrich (MRS) and Luria-Bertani media (LBm) at different pH’s ranging from 2 to 7.5. For both MRS and LBm, live cultures of probiotics have been proven to grow successfully in both media while incubated at 37 degrees Celsius at the pH of +/- 6.2. The Bradford protein assay was used to determine protein concentration in samples of both media, and the tryptic digestion of the bacterial cultures were analyzed by liquid chromatography mass spectrometer. These findings will be reported, highlighting important differences in the proteomic data sets in relation to different environmental variables.

Aging is the single largest risk factor for many diseases, including Alzheimer’s disease (AD). Therefore, many of the molecular mechanisms that cause aging may also contribute to the onset and progression of aging-related diseases. Our approach to tackling the progression of AD takes a biology of aging standpoint, where screening compounds that impact lifespan may help identify therapies for AD. For this project, we are focusing on compounds that are either FDA approved or naturopathic. This is not only a novel approach but also has the potential to accelerate clinical translation. This study uses a human Amyloid-beta (Aß) protein expressing C. elegans strain that becomes progressively paralyzed with age. We are also utilizing a novel robotic imaging system (the WormBot) to explore the impact of these compounds on the healthspan of the AD model strain. Recording motility behavior of the nematodes under each compound condition and translating the time-lapse image data into quantitative healthspan curves, we will determine how each compound impacts the progression of paralysis. These results will provide insight into mechanisms of Aß toxicity and could lead to promising treatments that increase the quality of life for Alzheimer’s disease patients.

 The computational modeling aspect of the Kinematics and Impacts Lab seeks to create accurate models and predictions of ice/penetrator interactions during high velocity collisions of the proposed Subsurface Ice and Plume Sampler (SIPS) lander. These penetrator collisions create a collumized plume of ejecta (ice shards and water vapor) that can be used to land an instrument package. Using the data from the models, the ice penetrator design is streamlined. The models are created using ANSYS’s Autodyn software, a hydrocode designed to simulate large material deformations. Generally, the models we create describe the impact of a small, hollow, cylindrical projectile traveling at 1 km/s impacting a stationary block of ice, which necessarily results in severe loading and large deformation as the surface of the ice is pulverized by the impact. Accurate representations of this “pulverization” are desirable for several reasons. First, we would like to know what happens physically to the projectile (depth and deformation for example). Second, we would like to understand how the projectile’s deformation during impact influences the properties of the ejecta produced. Understanding the behavior of the ejecta is an essential part of the modeling - this ejecta plume and it’s geometry are necessary for successful landing of the instrument package. A model that accurately describes the impact process is invaluable, as it allows easy analysis of different projectile designs and impact velocities at different scales without conducting expensive and time-consuming experiments. Once the plume interaction is properly constrained using ANSYS, future work will focus on more accurately modeling the crater morphology using a separate numerical modeling program, iSale.

Thermoregulation, the maintenance of core body temperature in a constantly changing enviroment, is a critical aspect of homeostasis. Despite its importance, the neural mechanism by which thermoregulatory processes occur is not very well understood at the circuit level. Afferent skin temperature information travels through the spinal cord to the parabrachial nucleus (PBN), where it passes on to the preoptic area of the hypothalamus (POA). A subset of prodynorphin (Pdyn)-expressing neurons in the PBN (PdynPBN neurons) are activated when mice are exposed to warm environments, and 80% of these neurons project to the POA. The exact role of PdynPBN neurons has not been characterized, however, and their full projection profile is not established. Using genetic and viral techniques, we inserted a Cre-dependent designer receptor exclusively activated by designer drugs (DREADD) into mouse PdynPBN neurons and labeled their synaptic projections with GFP-bound synaptophysin, an abundant synaptic vesicle protein used for neurotransmitter trafficking. The use of Cre-dependent DREADD and synaptophysin-GFP allowed us to specifically label and activate PdynPBN neurons. We found that activation of these cells increases tail-skin temperature with a concurrent drop in core-body temperature. These data suggest that PdynPBN neurons may convey environmental temperature information that is sufficient to activate heat-defense responses. Establishing the genetic identity of neurons in a circuit that helps to maintain constant core body temperature will allow for the elucidation of downstream nodes in this circuit.

Nearly a century ago, Lothrop Stoddard’s The Rising Tide of Color (1920) articulated his growing concern that the scourge of racial diversity exacerbated by immigration was particularly acute within the United States. This scourge not only threatened to transform America’s national character in terms of religion, laws, and customs, but also served as a profoundly destructive force to white labor and standards of living. Trump’s zero-tolerance immigration policies and the rationale behind them parallel not only Stoddard’s concerns about the threat immigrants pose to the United States, but also Stoddard’s solution of shoring up the “inner dikes” against undesirable immigrants. This study compares the immigration policies of Presidents Bush, Obama, and Trump to explore issues of border control, detention methods, arrest rates, and use of media in shaping public perception of immigrants. It also utilizes statistical data to assess the economic impact of legal and illegal immigration within the United States under the three presidential administrations listed. Findings suggest that the claims made by the Trump administration about the threat immigration poses not only contradict statistical data, but also perpetuate negative racialized stereotypes about immigrants. By drawing on the basic premise of critical whiteness theory--that race as a social construction is an important feature in American society and includes racialized practices of essentializing, colorblindness, and microaggression—this study provides an example of how Trump’s zero tolerance policies on immigration utilize early twentieth-century narratives of race and racialized differences to institutionally normalize discrimination and prejudice as natural features of American society as opposed to social challenges within it.

Enteric diseases, or diseases of the Gastrointestinal (GI) tract, remain one of the most prevalent killers of children in sub-Saharan Africa. The most practical way to prevent such diseases is through vaccination, but antigens for enteric diseases need to be delivered directly to the GI tract to be most efficient, making vaccination difficult. Recent studies by the von Adrian group at Harvard University have found that both T and B cells are reprogrammed to home to the GI tract when they encounter retinoic acid, a metabolite of vitamin A. The King Lab at the University of Washington is working to develop a novel vaccine candidate using recently developed self-assembling protein nanoparticles, that can simultaneously package all-trans retinoic acid (ATRA) and multivalently display enteric antigens. Previous work has suggested that two cystine mutations to Cellular Retinoic Acid Binding Protein I (CRABP-I) create a disulfide bond as a result of the conformational change that CRABP-I undergoes when it binds ATRA. This disulfide bond would essentially lock ATRA into CRABP-I, reducing its dissociation constant in vivo and maintaining the gut-homing properties of the nanoparticle post-injection. In order to assess the efficacy of these cysteine mutations, I expressed two versions of CRABP-I, the wildtype protein with no cysteine residues, and a version with no cystine residues except for the two that create the disulfide bond. After establishing that these new CRABP-I mutants folded into the approximate shape of wildtype CRABP-I via circular dichroism, I designed and tested new assays that measured free thiol concentrations of each protein after binding ATRA, as well as free ATRA concentration overtime. This data will help us determine whether these two cystine mutations make a significant difference in the ATRA binding quality of CRABP-I, which could improve the immune response generated by our vaccine candidate.

In this study we looked at the presence of streptomycin resistance genes, strA, strB, and aadA and the insertion sequence IS133 for the bacteria Escherichia coli obtained from the wetlands located within the University of Washington Bothell. The wetlands serve as a roost for more than 15000 crows all through the autumn and winter months. The hypothesis of this study was that the presence of antibiotic resistance may be able to spread through the vector of American crows. The genes tested in this study encode for factors that play a role in streptomycin resistance (Sugiyama, Masanori, and Osamu Nimi). The IS was tested because it would indicate presence of transposon TN5393 which in turn would suggest the presence of strAB genes on conjugative plasmids (Zhao, J., and H. Dang) and thus capable of horizontal gene transfer among the bacteria. The samples were collected from crow feces and water runoff within the wetlands. 23 water samples and 37 fecal samples, were testedby TaqMan™ quantitative PCR for the presence of the three streptomycin resistance genes, strA, strB, and aadA. Once the streptomycin genes were detected, the samples were tested to see whether the genes were located on a plasmid by testing for IS133 insertion and the TN5393 transposon. Our results show that 53% of the isolates tested were positive for strA, 57% were positive for strB, 5% were positive for aadA, 22% were positive for IS133, and 22% were positive for both strA and strB. Plasmids isolated from one water runoff sample and a fecal sample showed the presence of aadA and strB. The plasmids were successfully transformed into DH5 Alpha E. coli and were ampicillin resistant but not streptomycin resistant. These results indicate that there may have been other plasmids in the cell that rendered the samples resistant to ampicillin.

Asteroid sample return has potential to impact research and how humans collect resources, but sample return missions remain prohibitively expensive and complex. We propose a device to retrieve a preexisting sample container from the surface of an asteroid or other extraterrestrial body, focusing on simplicity, repeatability, and reliability. Taking inspiration from a classical design, the bear trap, we created a functional 3D printed prototype, which is mechanical and capable of capturing a 1.5x15 in cylinder resting on a flat surface. Consideration was given to potential rocky terrain or an awkwardly positioned return container, and to sealing the sample container to prevent contamination upon return to earth. Future prototypes will be constructed from stronger, lighter weight materials and will be further developed during active field tests on debris at a penetrator impact site in Eastern Washington.

Cerebral palsy is a congenital disorder which impacts movement, muscle tone, and cognitive ability. This disorder affects 2-3 people per 1,000 births annually. My lab is currently developing a technology to assess motor learning. We’re working on quantifying motor planning deficits in cerebral palsy to aid in targeted therapy. However, the small test population combined with the nature of cerebral palsy means it can be difficult to bring these subjects into the lab to verify our technology. I developed a “simulation” of the controller we use to interface with our technology that can be downloaded onto android devices and can connect to a subject’s bluetooth enabled computer wirelessly. This allows subjects to test our technology remotely in a setting which best suits their needs. Upon testing this virtual controller against the currently used controller, the virtual controller offered a lower mean-squared error to the normal controller, and was proved a viable option for remote testing. This development allows us to expand our testing pool to those who may not be able to physically come to the laboratory for testing, and can be expanded to future developments which require unique controllers.

Clallam County has recently been experiencing concerning air quality conditions due to smoke drift from wildfire events in nearby areas. The objective of this study was to assess the wildfire smoke health-risk communication needs of organizations that serve the public in Clallam County. Communication needs were assessed by surveying 10 organizations that serve sensitive populations. Surveys were conducted in person or over the phone, and summary statistics were calculated. In addition, a low-cost air monitor was installed to track summer time air quality. The low-cost air monitor was installed adjacent to a nephelometer administered by the Olympic Region Clean Air Agency (ORCAA). This was done to determine the accuracy of the low-cost air monitor by comparing air quality values registered from both devices. The majority (60%) of organizations responding to the survey reported that they had not received information about the health risks of wildfire smoke. Nearly all organizations (90%) reported that they have the capacity and are willing to communicate the health-risks of wildfire smoke to the people they serve in Clallam County. Analysis of air quality data shows the low-cost monitor may be a useful device in determining air quality conditions. The correlation coefficient for the daily averages (from July 12 to August 24) between the ORCAA nephelometer and the low-cost air monitor was determined to be 0.98, but closer examination of data for hourly averages show a correlation coefficient as low as 0.82. Future wildfire smoke events in Clallam County require public health interventions to address health-risk communication needs of sensitive populations. Implementation of a low-cost air monitor network accessible by the public is a promising prospect to protect sensitive populations in Clallam County.

We present a study on 13 years of HPOL optical linear spectropolarimetry of the famous star P Cygni. P Cygni is a Luminous Blue Variable, an important transitional phase in the lives of the universe's most massive stars. We revisit previous findings on the nature and variability of P Cygni's observed linear polarization and report on discrete features in P Cygni's observed polarization spectrum. Using this dataset we also test the assumption that line blanketing effects suppress all intrinsic polarization from strong emission lines. This assumption is vital in determining the wavelength dependence of P Cygni's intrinsic polarization. Our results allow us to constrain the geometry of the polarizing region to better understand the circumstellar material around P Cygni.

 In vivo animal models are an advanced tool for testing complex biological phenomena and functions in humans, yet are difficult to adapt due to high cost, biological and anatomical differences, and ethical concerns. As an alternative to in vivo models, in vitro organotypic models have been created that can accurately and efficiently reproduce biological processes, allowing researchers to probe specific factors without the difficulties associated with in vivo models. We present further development of a novel microfluidic platform, called Stacks, which uses open and suspended microfluidic principles to enable spatial and temporal manipulation of 3D cultures in suspended collagen plugs. We are developing the Stacks platform to accurately reflect morphology exhibited in the air-liquid interface (ALI) of the epithelial layer of the lung and allow analysis of lung pathophysiology, cell signaling, and immune responses of the lung in both monoculture and coculture. Furthermore, using the flat faces of the device that allow for stacking, we have connected a layer of human lung endothelial cells, representing a model vascular system, with a second layer of immune cells and mycobacterium, representing a model infection system, to study soluble factor signaling in granulomatous infections. Through the modification of the Stacks device, we can achieve granuloma formation and utilize soluble factor analyses (e.g., immunoassay) to observe and characterize infection-dependent changes in vasculature resulting from the exchange of chemical signals generated by the infection model. Future development of the platform will build on these newly developed lung models to combine them for studies involving signaling and disease mechanisms between the lung ALI and the underlying tissue layers.

Roborun is a simulation game that utilizes crowdsourcing to identify legged movement patterns for land-based robotic movement. By using a game controller, keyboard, or by providing a set of instructions to execute in order (e.g. “rotate front leg X degrees”, “move back leg forward Y meters”, etc.), players can control joint torques and leg movements in order to navigate a virtual two-legged robot through several 2D obstacle courses that contain varied terrain and movable boxes. The game can be played through a web browser on either a computer or smartphone, making the game accessible to players across multiple platforms. In future development, we intend to implement a scoring system based on efficiency and speed of course solutions and will replicate the best scoring solutions from players on a commercially-available robot in our testing laboratory. It is our hope that their solutions will help develop reliable robotic movement algorithms and shed some insight into the dynamics of land-based movement.

The use of mindfulness for emotion regulation has led to its adoption as a strategy to manage emotion and mood. Studies on eating behavior have utilized mindfulness exercises for those with eating disorders and Type 2 diabetes and found that mindfulness improves healthy eating habits. This study extends prior work by examining a mindfulness-based eating intervention among college students. Participants were randomly assigned to a weekly 30-minute mindfulness group or relaxation control group for six weeks. Mindfulness exercises ranged from meditations on nonjudgmental self-acceptance to advanced mindfulness procedures utilizing common snack foods. These exercises encouraged the use of mindfulness strategies to help regulate emotional eating, mood, and eating strategies in daily life. Mindful eating participants reported significant decreases in depressive symptoms compared to controls. However, there was no significant differences between mindful eating, anxiety symptoms, and emotional eating in response to stress over time in mindful practicing participants and compared to controls. Results suggest that a mindful eating intervention for a non-clinical sample helps maintain mindful awareness of dietary behavior and decrease depressive symptoms, but has little effect on emotional eating and mindfulness.

Assessments of tropical insect diversity largely lacks known groups from which appropriate interpretations can be made, and ultimately undervalues the taxa of some regions. The ecology of Diptera within the tropics constitutes largely on the roles of nutrient breakdown, recycling, and pollination; as numerous Orchidaceae rely on pseudocopulatory mechanisms for effective pollination. Our study was conducted to explore and investigate the nocturnal diversity of the Order Diptera, with a special emphasis on Mosquitoes (Family: Culicidae), across multiple habitat types. The study site is in Cocha Cashu biological station along the Manu River in the Manu National Park, Peru. Sampling was conducted in early September during the dry season where we sampled several areas of varying vegetation communities, canopy coverage, and disturbance: river-side sample, lake-side sample, second-growth forest, and high-altitude cloud forest. We hypothesized that the highest diversity of morphospecies would occur in closed canopy areas with closer proximity to water bodies. Insects were collected using traps baited with a visual lure and soiled socks. Samples were filtered of other insect orders and individual dipterans were categorized using visual differences and similarities to create morphospecies groupings. Due to numerous variables, primarily trap efficacy and testing, our sample size was limited and as a result, our data could be expanded upon for further collection and analysis. The proceeding decreases in samples across a time-scale is largely due to bait methods. Overall, our hypothesis was supported by results indicating a higher species richness and diversity at sites in dense canopy coverage in proximity to a larger water body. Calculated Shannon diversity indices of 1.574 at the river closed canopy sampling site compared to 0.689 in the open canopy river site. These results may reflect habitat affinities of Dipterans in the tropics. Future testing will allow for increased understanding of Diptera communities in the tropics, taxa, and environmental health using certain species as indicators.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that involves challenges in speech and nonverbal communication, social interaction and repetitive behaviors. ASD can manifest in a variety of ways hypothesized to be the result of multiple environmental and genetic factors. Two such genetic factors are disruptive mutations to genes ADNP and DYRK1A, which have been associated with ASD and other developmental problems. While both genes are known to impact neuroplasticity, DYRK1A mutations impair dendritic spine growth and ADNP mutations impact the cytoskeletal system. Little is known about the behavioral phenotypes resulting from DYRK1A and ADNP. The aim of this project is to illuminate phenotypes associated with disruptive variations to both genes by comparing learning, memory, verbal and adaptive skills of people with mutations to these genes to each other. In this study, participants included individuals who have either a disruptive mutation to ADNP (n=9, ages 4-13 years) or to DYRK1A (n=10, ages 4-24 years). The following assessments were administered to each participant: Vineland Adaptive Behavior Scales II (adaptive behaviors), Differential Ability Scales (cognition) and California Verbal Learning Test (speech and learning). These assessments provided a selection of different behavioral phenotypes related to neurological functioning and development. We hypothesize that DYRK1A and ADNP will have differing impacts on phenotype due to their varying contribution to early brain development. This study will contribute to a better understanding of how disruptions to different gene functions can lead to differences in learning, memory, verbal and adaptive skills. In addition, examining these mutations’ differing phenotypes will give a better idea of the implications of living with these gene events and may inform treatment recommendations for families and individuals affected by rare mutations.

In this research, we looked at the possible use of an Air Breathing Pulsed Plasma Thruster (AB-PPT) for propelling an aircraft that could potentially act as an atmospheric satellite at atmospheric altitudes > 25 km. One of the advantages of operating at such altitudes is that the aircraft is not subject to highly variable weather conditions. An atmospheric satellite is an aircraft that can perpetually fly around the same area, and can be launched at significantly reduced cost when compared to conventional satellites while providing similar services such as communication and imaging. At the desired altitude, conventional blade-based propellers are too inefficient due to low background pressure, but it is still too low of an altitude for conventional space propulsion, prompting the use of AB-PPT. The AB-PPT is an adaptation of the conventional PPT which is a pulsed device that uses an electric discharge to ionize and expel the solid propellant such as PTFE at high speeds. For the AB-PPT, a large amount of voltage discharge generated across the two coaxial electrodes ionizes and expels the background air instead. In order to identify the most efficient AB-PPT design, three different configurations were tested using a pendulum-based thrust stand to measure the thrust efficiency, a Rogowski coil to measure the current per discharge, and high-speed video. One configuration has been identified, and we are currently investigating an alternative electric connection to further increase the amount of thrust per discharge. Future work includes plasma diagnostics of the AB-PPT such as Langmuir probe, and B-dot probe, in addition to the development of more robust electronics capable of delivering higher power, and the development of the final version of the AB-PPT for patenting purposes.

The James Webb Space Telescope (JWST) has the power to resolve many unanswered questions in the field of astronomy. The new telescope, which has taken many years and large amounts of resources to build, will have a limited lifetime so it is imperative that it is used as efficiently as possible. The unprecedented power of the JWST means that for the first time it may be possible to detect the clustering of high-redshift galaxies, and this could help to clarify uncertain details about the early universe. The purpose of this project is to determine the ability with which the JWST will be able to detect the clustering of early galaxies and the most efficient survey strategies for realizing this capability. Using simulation data, we are able to take into account JWST detectability limits and analyze clustering at different redshifts (z=6, z=8, and z=10). By comparing the simulation galaxies to a random test case, we have come to the conclusion that the clustering of high-redshift galaxies will likely be detectable with the JWST. Simulating different survey strategies then allows us to determine how to maximize the JWST's efficiency. The amount of time that the JWST spends pointed in a specific direction determines the depth of the survey. For a given amount of time, a deeper survey will be able to pick up on dimmer galaxies, but it will cover a smaller area. Our next step is to determine an ideal combination of depth and of area for the detection of early galaxy clustering at different redshifts in order to best plan for the JWST's launch.

Pain is a major contributor to disability, and is more prevalent among low income groups. Rehabilitation care can be an effective treatment, although access and improvement may be associated with social factors. We examined the association of social factors (English proficiency and income) with rehabilitation use, improvement in rehabilitation, and meeting treatment goals among older adults in bothersome pain. We hypothesized: 1) participants with lower English proficiency will experience less improvement and achieve treatment goals less often than participants who are proficient in English and 2) participants with lower incomes will experience less improvement and achieve their treatment goals less often than higher income participants. This is a secondary analysis of the National Health and Aging Trends Study (NHATS), a cohort study representative of Medicare beneficiaries. Participants are interviewed yearly with a self-reported health and socioeconomic survey. We included community dwelling participants who indicated being bothered by pain in the last month. Participants reported how well they understood or spoke English. “Not well” or “not at all” was considered not proficient. Income was self-reported as total household income. Outcomes reported are rehabilitation use for pain related reasons in the next year, improvement with rehabilitation, and meeting treatment goals. Descriptive analysis suggests participants with lower English proficiency had higher rates of rehabilitation improvement. Rehabilitation users have a median income about $6,000 higher than non-users, however there is no difference in income between improvement groups or those that do or do not meet rehabilitation goals. We found lower income is associated with lower rehabilitation use but not improvement among participants in bothersome pain. These results indicate improvement is consistent among rehabilitation users however, access is limited for lower income participants. More work is required to determine how barriers can be eliminated to improve access to rehabilitation care for people in pain.

Hydra vulgaris are some of the simplest animals with neurons and have only two thin, near transparent layers of tissue: myo-endodermal and myo-ectodermal layers. Each cell in the animal can be examined simultaneously due to their small size, simple body pattern, and stereotypical (regular and defined) behaviors. This makes Hydra great animals for examining simple signal transmission pathways from which the complex pathways in vertebrates derive. Cells in the ectoderm and endoderm use calcium signaling to coordinate contractions and cause the animal to move, but how this mechanism of cell-to-cell calcium signaling functions is not well understood. Invertebrate gap junctions, intercellular proteins that cells use to send signals to adjacent cells, are coded from the innexin gene family. It has been found that the genome of Hydra magnipapillata has fourteen predicted innexin genes. Recent data suggests some of these innexins are expressed in the ectoderm, specifically innexins 1,4,5, and 13. I hypothesize these proteins are necessary for the animal to perform coordinated contractions. To determine the role of these proteins, I used shRNA techniques to knockdown innexin expression. After examining wild type Hydra, I examined an existing line of transgenic Hydra which express GCaMP in ectodermal cells to identify when cells use calcium to signal other cells. In these animals, signals can be viewed as a wave of fluorescence passing across the ectoderm. I knocked down the genes by electroporating shRNA molecules into adult animals who express GCaMP, and will image these animals’ behavior. There should be quantifiable differences in the fluorescent waves, as I postulate that some cells will be excluded from these waves if an innexin is knocked down, and analyzing these differences should clarify the role of innexins in gap junction signaling.

Indoleacetic acid(IAA) is a common and well understood auxin class phytohormone that promotes plant growth by increasing cell division and elongation. IAA has also been shown to increase infectious adhesion and filamentation in certain strains of Saccharomyces cerevisiae. Increased IAA production by the plant’s microbiome has been demonstrated to stimulate host and symbiont growth. The IAA production in multiple strains of S. cerevisiae from the USDA ARS library was quantified using the Salkowski colorimetric technique, then the highest IAA producing strains were treated onto corn to examine the effect on biomass growth. Preliminary results have shown greatly increased root mass and moderately increased shoot mass in treated corn. This symbiotic yeast treatment could have agricultural applications, increasing crop yields without increased application of fertilizer, pesticides, or other products that could have a negative ecologial impact or detrimental effects on the crop.

Economics connects to our daily lives. It is not only about the money in the market but also people in the society. Wealth and income inequality is one of the examples. In some countries, such as in the United States, differing levels of income lead to varied benefits. This phenomenon impacts not only the quality of people’s lives but also their happiness. However, having a large amount of money is not the most important reason to increase their happiness. In this literature review, economic principles can help to understand the relationship between happiness and money. Examining Jeremy Bentham’s idea of the greatest happiness of the greatest number, the paper explores the impact of utilitarianism. There is also recent economic research related to money and happiness that is considered. One significant finding is that people’s happiness can be increased by sharing their excess income and wealth. The study of happiness and money is complex, and there are many factors not included in this paper. But, the idea above is still important to be considered and can be one way to improve economic inequality. The solutions to the problems of economic inequality may be found in this research.

Infection of the central nervous system (CNS) greatly contributes to and increases the risk of developing epilepsy. Individuals who present with seizure during a CNS infection are 22 times more likely to develop epilepsy in their lifetime than individuals who do not present with a seizure. Infection of mice with the Theiler’s murine encephalomyelitis virus (TMEV) is a preclinical model that is useful to understand the mechanisms underlying acute seizures and the development of epilepsy following CNS infection. In the present study, we aimed to determine how diet sterilization (autoclaved versus irradiated) impacts the development of acute seizures and chronic behavioral comorbidities. We infected C57BL/6J mice with an intracerebral (i.c.) injection of TMEV or sterile saline, and then fed the mice either an autoclaved or irradiated diet. Next, we monitored the mice for the incidence of acute handling-induced seizures 3-7 days post-infection. Under both dietary conditions, mice developed handling-induced seizures in the acute infection phase. There were 8/13 (61%) irradiated diet fed mice that developed acute seizures whereas 9/13 (69%) autoclaved diet fed mice developed acute seizures during this period (p >0.05). We then assessed behavioral comorbidities associated with chronic epilepsy 4-5 weeks post-infection by evaluating anxiety-like behaviors in an open field test, working memory in a novel object recognition test, and electroconvulsive seizure thresholds. Mice fed an irradiated diet demonstrated preserved working memory function compared to mice fed the autoclaved diet, who demonstrated significant reductions in working memory and increased anxiety-like behavior, suggestive of worsened disease severity. At the conclusion of in-life testing, animals were euthanized, and tissues collected for histopathology and immunohistochemistry to assess the extent of TMEV-induced neurodegeneration and neuroinflammation. Our findings highlight the potential for the sterility of diet to modify disease severity in the TMEV model.

Could women’s strength of gender identity direct them predominantly to awards open only to women, leaving other awards less gender-diverse? We examined whether women’s awards could steer women away from more lucrative all-gender awards and if women’s strength of gender identity moderates this decision. Undergraduate women (N=169) decided between two fictional scholarships valued at $2500 and $5000. In the control condition, both awards were open to all genders. In the experimental condition, the $2500 award was only open to women. A chi-square test showed that in the control condition, women were more likely to pick the $5000 all-gender award, while in the experimental condition they were more likely to pick the $2500 women’s award. Women’s likelihood to apply to the $2500 award in both conditions was not moderated by identification with their gender. This indicates that women’s identification with their gender was not driving their tendency to select an award targeted to women. Low-value women’s awards may decrease the number of women applying for higher value all-gender awards, potentially contributing to higher proportions of male applicants and winners to those awards.

Manufacturing workers are often subjected to many rigorous and repetitive shoulder and arm motions, usually leading to shoulder injuries. Assessing the likelihood of an injury before it occurs and adjusting practices accordingly can keep the individual from the severe pain that shoulder injuries can cause. This research focuses on creating such a predictive model to warn individuals before they sustain an injury. I created a mathmatical model to assess critical positions that would cause the most stress in the shoulder joint. A Kinect sensor locates the arm joints in space and my Matlab code calculates the expected reaction forces in the shoulder. My current results focus on single, static positions defined by common industry working positions. Future work will focus on dynamic positions and comparing the results from the mathematical model with biological indicators to determine if this predictive model is indicative of injury.

The idea of a basic income, money distributed unconditionally and regularly by the government to the people on an individual basis, has been gaining more attention in recent years. The prominence of poverty and potential increases in technological unemployment have become popular justifications for the introduction of a basic income. Questions pertaining to basic income are: (1) Why should it be adopted? (2) What are the effects of it? (3) How could it be implemented? By reviewing the literature of poverty dynamics and technological unemployment, past basic income and unconditional cash transfer experiments, and different proposals of funding and distribution, these questions were examined. Reasons for adopting a basic income program are to alleviate the effects of poverty on individuals and society, and to provide a safety net for the economically displaced due to technological advancements. Past basic income pilots and unconditional cash transfer experiments showed an overall increase in welfare and no significant changes in work hours. Prominent proposals of funding include replacing the current welfare system, adopting a progressive tax system, and taxing robots. This research can be used to assess the significance of adopting a basic income, understand what should be further studied in future experiments, and understand the challenges associated with basic income implementation.

In a majority of low- and middle-income countries (LMICs), resources for mental health care are extremely limited. For children and adolescents especially, there is little to no mental health care available. In a recent large randomized controlled trial, an evidence-based treatment (EBT) was delivered in two LMICs, Kenya and Tanzania, using trained lay counselors in a task-shifting/sharing model. Over a 12-week span consisting of weekly group meetings, this EBT, trauma-focused cognitive behavioral therapy (TF-CBT), was delivered to orphaned children who had posttraumatic stress (PTS) and/or grief symptoms, along with their guardians. The effects sizes were large for child PTS/grief, but little is known about how to scale up and implement TF-CBT to benefit more children. The current study uses data from a large TF-CBT trial implemented in 10 schools and 10 communities in Kenya by existing staff who served as lay counselors (teachers in schools and community health volunteers [CHVs] in communities). After the delivery of the treatment, qualitative interviews were conducted with the lay counselors from 6 of 10 sites in each to better identify efficient implementation practices and policies (IPPs) that supported TF-CBT delivery. The goal of studying the IPPs is to identify those that support the effective adoption and fidelity of TF-CBT. This study pinpoints which IPPs are most critical for the different settings, sectors, and populations that this study encompasses. We analyzed the IPP resource provision to be able to compare the difference in resource allocation in urban versus rural settings in regards to transportation, materials, etc. This study allows us to gain a better understanding of the necessary implementation strategies to better tailor to the needs of communities to support evidence-based mental health care in specific sectors and settings in LMICs.

Patient reported outcomes (PRO) are becoming increasingly important in the follow-up of patients after cancer treatment. The specific aim of this study was to investigate the time taken and completeness of PRO questionnaires. Study subjects were identified from an institutionally approved database of patients who had undergone surgical management of esophageal cancer with curative intent (1991-2018). Patients that were alive in April 2018 were asked to complete six questionnaires, including: Digestive Symptom Questionnaire (DSQ, 23 questions); Dumping Syndrome Rating Scale (DSRS, 25 questions); SF36 (36 questions); EORTC-QLQ-C30 (30 questions); EORTC-QLQ-OG25 (25 questions); and EuroQol 5D (6 questions). Patients were offered either hard-copy (paper) or Electronic versions of the questionnaires. Electronic questionnaires compiled in RedCap were completed consecutively by patients allowing for accurate quantification of the time taken to complete each questionnaire. In total, 144 patients were asked to participate, 117 patients (81.3%) agreed to complete questionnaires, of whom 60 (51%) of the patients choose the electronic version. Completion rates for all of the questionnaires was 91% (52 patients) and 85% (51 patients) for paper and electronic versions respectively. The average age of patients choosing electronic questionnaires was 74 (range 55-96) years compared to 71 (range 53-91) years in the paper questionnaire group. On average, the 6 questionnaires, consisting of 145 questions, took 26.9 (range 10-55) minutes to complete: 7.5 minutes for DSQ, (range 1-39 min), 4.4 min for DSRS, (range: 1-19 min), 6.8 min for SF-36, (range: 3-18 min), 3.7 min for EORTC-QLQ-C30, (range: 2-8 min), 2.7 min for EORTC-QLQ-OG25, (range: 1-5 min), 1.7 min for EuroQol 5D, (range: 0-6 min). In conclusion, the high response rate in the study, indicates that it is feasible to ask patients to answer multiple PRO questionnaires after cancer treatment. Continued focus on PROs is warranted to further increase the knowledge of cancer survivorship.

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.

 Diabetes is the 7th leading cause of death in America and occurs when blood glucose levels are too high. The body regulates blood glucose levels with a hormone called insulin, which is made and secreted by pancreatic β-cells. Type I diabetes occurs when these β-cells cannot produce insulin. Type II diabetes occurs when the body does not respond to insulin efficiently. Our goal is to study how the protein phosphatase PP2B (also known as Calcineurin) impacts insulin release in pancreatic β-cells. Previous work in cells and genetically modified mice has found that PP2B signaling regulates insulin release, but the mechanism remains unknown. We are taking advantage of CRISPR/Cas9 gene-editing to replace a PP2B-anchoring protein with a modified version that allows biochemical labeling of proximal proteins. When combined with mass spectrometry analysis, this approach enables identification of PP2B substrates in β-cells. Future work will test these candidates for their impact on insulin production. Our long-term goals are to uncover how insulin is regulated and to find new targets for diabetes treatment.

There is a critical lack of knowledge regarding the effects of human immunodeficiency virus (HIV) and zika virus (ZIKV) coinfection in respect to ZIKV pathogenesis, vertical transmission and current vaccine strategies. ZIKV has received global attention because of its clinical complications including congenital malformations during vertical transmission and Guillain-Barré syndrome, a neurocognitive disorder in adults. Recently, ZIKV outbreaks have occurred in tropical and subtropical regions endemic with HIV, therefore it is imperative to understand the impact HIV-ZIKV coinfection may have when moving forward with ZIKV vaccine design. Furthermore, in humans and non-human primates (NHPs) frequencies of blood monocytes increase during HIV and simian immunodeficiency virus (SIV) infection and monocytes are early targets of ZIKV infection. Therefore, we hypothesize that cells from HIV infected individuals have the capacity to harbor increased ZIKV replication and could lead to enhanced ZIKV viremia and pathogenesis. For this study, we use a NHP model to determine the impact of acute SIV infection on ZIKV pathogenesis. We determine ZIKV cellular targets in the blood and preliminary results show an increase in NHP blood monocyte within the first six weeks of SIV infection. We evaluate whether SIV infection increases the susceptibility of cells to ZIKV infection by isolating cells from SIV- and SIV+ animals, infecting them in vitro with ZIKV, and assessing viral replication by plaque assay. Our preliminary findings suggest that in vitro ZIKV replication may increase in cells from SIV+ NHP blood when compared to SIV- blood. Future studies will look at the impact of SIV infection on in vivo ZIKV replication and whether ZIKV replication is enhanced in cells from HIV-infected individuals.

The Penrose process is a theoretical method for extracting energy from a spinning black hole. This study clarifies the conceptual framework and underlying mathematics of the physics involved. Working within the context of General Relativity, we begin with the metric for a spinning black hole (Kerr metric) and discuss the meaning of the space-time variables employed. Next, by considering particle trajectories, the effect of “frame dragging” is derived, whereby spacetime itself is “dragged” along in the direction of the black hole’s spin. This effect ultimately is what allows a net positive energy to be extracted from the black hole. To calculate the amount of energy, first the appropriate expression for energy is obtained from the Kerr metric via variational calculus. Finally, the Penrose process is explained, where payloads of matter and antimatter annihilate just outside the event horizon, producing light. A light pulse travelling in the opposite direction of the spin falls into the black hole, while a pulse travelling in the opposite direction escapes. Bringing everything together, the net energy produced by the Penrose process is calculated.

Dynamical systems are ubiquitous in science and engineering. Inferring the mathematical laws that govern dynamical systems typically requires a 'scientist-in-the-loop' to guide the discovery process, via their expert knowledge and intuition about the system. Getting computers to perform this task automatically, without the guidance of a domain expert in the loop, is a grand challenge in the field of data science. A number of algorithms have been developed to infer such laws. One leading algorithm is Sparse Identification of Nonlinear Dynamics (SINDy), which applies simple linear regression coupled with sparsification to optimize a model over a large library of candidate functions. This algorithm is purely data-driven and makes no use of information that may be known previously about the dynamical system, such as symmetries and conservation laws. In this work, we develop a framework for incorporating and enforcing symmetries and conservation laws in SINDy so that the inferred models are consistent with prior domain knowledge. We analytically show how to propagate symmetries and conservation laws through the SINDy function library, and from this analytically derive linear constraints on the resultant linear regression. These constraints can be incorporated into the regression problem using options available in standard quadratic optimization packages. We implement this method and show that it provides improved accuracy and robustness on the task of inferring several canonical dynamical systems.

Armadillidium vulgare are terrestrial isopods characterized by their ability to conglobate (roll into a ball) as a mechanism of defense from predation. It is theorized that conglobation functions as both a defense mechanism against predation and a means to avoid desiccation in arid environments. This project tests conglobation as a mechanism of water conservation. Water-loss in A. vulgare, was investigated in the free and conglobated states. In experiment one, 40 specimens of A. vulgare were suspended in their conglobated state using dental rubber bands and kept at 30.5°C and 30% relative humidity for 22 minutes along with a control group of additional 40 specimens of A. vulgare in their free state. Water-loss rate decreased by 16.5% when specimens were in their conglobated form. In experiment two, we first varied the humidity and then temperature to test whether different conditions triggered voluntary conglobation. Four groups of 15 specimens of A. vulgare were kept at 25°C in environments of varying humidity: 18%, 30%, 46%, and 99% respectively for one hour. No voluntary conglobation was observed in response to humidity change. Finally, we observed that high temperature triggered conglobation beginning with 6% conglobating at 31.5°C and 100% at 50°C. Our findings suggest that while conglobation behavior may help to conserve water, A. vulgare conglobate primarily as a defense mechanism. Further research is needed to clarify the function and purpose of the conglobation response in A. vulgare.

Malaria is a disease associated with a significant global burden of illness, including hundreds of thousands of deaths every year. Severe malaria is most often due to the Plasmodium Falciparum species of parasite, the pathogenesis of which involves avoidance of host detection through endothelial sequestration. This process allows infected erythrocytes (red blood cells) to adhere to the vessel wall and avoid filtration via the spleen. Severe cases of malaria are often also associated with endothelial activation and release of the adhesive glycoprotein, von Willebrand Factor (VWF). Preliminary data from our laboratory suggests that erythrocytes infected with P. Falciparum may be able to bind to VWF fibers formed under in vitro conditions, and we believe that VWF binding may prove to be a novel mechanism contributing to endothelial sequestration. This study was conducted in order to understand the interactions between plasmodium infected erythrocytes and VWF fibers formed following endothelial activation. Because of the high demand for technical replication for such a project, and the labor and time expenses associated with the lab’s commonly used microvessel system, modifications were made to the geometry and housing to characterize it for the high-throughput platform for the study of VWF’s role in the binding of infected erythrocytes to activated endothelium. By utilizing nanofabrication techniques and soft lithogaphy with Polydimethylsiloxane (PDMS), we have successfully completed design and manufacturing of the novel devices that have allowed an increase in speed and efficiency up to three times that of previous assemblies. In these newly fabricated devices, we saw consistent formation of robust VWF fibers upon activation and aim to continue their use to observe and quantify binding of plasmodium infected erythrocytes in VWF-rich regions within vessels.

Cellular growth and aging requires constant replication of the genome. The processes of genome replication and segregation must be carefully regulated to prevent DNA damage which can cause cell death or oncogenic transformation. Damage can arise from errors in cellular processes, as well as environmental factors such as UV radiation or chemical agents. In mammals, the protein Retinoblastoma (Rb) prevents cells from beginning the process of DNA replication for cell division if internal conditions are not suitable for replication. This function is disrupted in virtually all cancers, and mutations in Rb have been widely studied as a result. Whi5 is the functional analog to Rb in S. cerevisiae. Whi5 activity is modulated by phosphorylation at 4 different sites, triggering Whi5 export from the nucleus and allowing transcription of DNA replication genes. Previous research suggested Whi5 export initiates irreversible progression through cell division. However, using single-cell observation technology, we show that Whi5 can re-enter the nucleus prior to cellular division, arresting the cell cycle. Cells that undergo Whi5 re-entry events exhibit a longer average replicative life span, counted in number of divisions. Additionally, cells without a functional copy of Whi5 have a reduced replicative lifespan. Our results suggest Whi5 may play a role in arresting the cell cycle in response to DNA damage to prevent the cell from making fatal errors during replication and ensure healthy aging. To investigate the role of Whi5 in response to DNA damage, I am using CRISPR gene editing technology to modify the phosphorylation sites on the Whi5 gene, modulating Whi5 activity. The ability of modified Whi5 strains to recover from UV induced DNA damage and their relative replicative life spans will clarify the role of Whi5 in DNA damage response. Our results may help us better understand the interactions governing Rb dysfunction in cancer cells.

Okanogan County, Washington is known for unpredictable and persistent wildfires. In 2014, it had the largest wildfire known in Washington State history. Over the past few years, N95 masks provided by the Public Health Department have been given out to community members at 72 different distribution locations throughout the county in order to protect against some of the harmful airborne contaminants caused by wildfire smoke. In order to determine the effectiveness of the N95 mask distribution system and the public service announcements regarding N95 masks, a survey was given to residents and visitors of the county. Focus areas of this survey were the availability and use of free N95 masks, knowledge of the N95 mask distribution locations, desired information on the N95 masks, and the awareness of public service announcements regarding N95 masks during wildfire smoke events. Results showed that many are still unaware of the free N95 masks in the county and those who picked them up had unresolved questions about them. Of the total 87 respondents, 34.5% were not aware that there were free masks available to them throughout the county. Of those who were aware, 81.3% wanted to know how long the masks could be worn before disposing and 56.3% wanted to know for who the masks were not appropriate for. The survey also found that 40% of people prefer to receive their information through Facebook. In order to combat the issues found, an N95 mask infographic was created for distribution along with the masks.

Natural proteins often assemble into various complex geometric structures based on their interactions with each other. These structures can hold and transport "cargo" as well as display antigens, making them extremely useful in vaccine design. The King Lab at the University of Washington uses the way these proteins assemble to develop computational models that help them design novel self-assembling protein cages, or nanoparticles. These nanoparticles are then used to develop vaccines or treatments for diseases. Components of the designed protein cage can be modified and expressed individually before being assembled together into the nanoparticle. I am working on stabilizing one of these protein cages known as T33DN2, so it can be used towards creating a vaccine. T33DN2 is a tetrahedral cage comprised of two trimeric proteins known as T33DN2A and T33DN2B. When expressed individually through E.coli, DN2A is produced in a soluble form while DN2B is produced in a mostly insoluble form. T33DN2 is currently an unstable cage, as only the A component is expressed solubly. Soluble proteins are generally more stable and thus easier to work with than their insoluble counterparts. To increase the solubility of DN2B, I have been making mutations to specific amino acids in the DNA that produces this protein, as well as expressing and purifying this component to determine its stability.

As our climate continues to change, science is becoming increasingly focused on replacing environmentally-harmful agricultural methods with a more natural approach. One approach steadily gaining traction is the use of bacteria found in plants that confer benefits to their plant hosts. The benefits range from drought tolerance to increased growth and more. In this study, I focused on two species that confer significant anti-fungal activity to the plants they inhabit. The goal was to obtain a high-quality whole-genome sequence and analyze the sequence with a variety of bioinformatics software. This would provide both clues about the genes possibly confering the anti-fungal benefits, and useful characterization needed for the strain's eventual commercialization. 

Alzheimer’s Disease (AD) leads to a progressive loss of neuronal function and ultimately death. Age is the greatest risk factor for AD; thus, a compound that slows down the aging process can help delay AD. In the lab, we use a Caenorhabditis elegans (C. elegans) model of AD in which human amyloid beta (Abeta) is expressed in body wall muscle cells resulting in age-onset paralysis. When combined with a robotic image acquisition device (the WormBot), we can analyze 144 different treatments simultaneously. The drug Istudying is Alpha Lipoic Acid. It is an antioxidant and cofactor for metabolic reactions required for oxidative metabolism. It has been previously reported to increase lifespan in C. elegans. My project focus on determining if Alpha Lipoic Acid reduces paralysis in the Abeta model. I investigated the mechanism of action of Alpha Lipoic Acid using RNAi knockdown of specific genetic pathways that are known to modulate aging. Ultimately, I have determined the optimal dose and a mechanism of action.

Uruguay’s history as a place of refuge for European Jews fleeing antisemitism during the first half of the twentieth century and the rise of global fascism has been understudied. As survivors and children of survivors are now in their 70s, 80s, and 90s, there is an urgency to record their stories. Some of these migrants fled Europe as early as the 1920s, while others arrived in Uruguay shortly after the war, surviving alone or with family members. Working with a team of student and faculty researchers who are studying the experiences of Jewish migrants now residing in the Hogar Israelita, a former orphanage and home for the aged founded in 1937 and current nursing home in Montevideo, I have translated primary and secondary documents for my non-Spanish-speaking professor as well as conducted historical research. I am helping build the photos and recordings that we collected in January into a digital project. I’ve worked to situate these individual stories within a greater history to understand how political tensions of the time period and ideology of the government affected individuals and their families. US immigration policy, which significantly restricted Jews from entry beginning in 1924, directly affected Uruguayan policy, which remained largely open to Jews until 1937. As Jewish immigrants arrived, the presence of antisemitism increased through restrictive policies and pressure from the Catholic Church, despite the government’s denial of racism and antisemitism. Study of previously recorded testimonies recorded in Spanish of Jewish immigrants, both before and after fleeing Europe, reveals the creation of organizations aimed to ease the transition of immigrants as well as women’s associations and orphanages. The newly collected testimonies of the residents of Hogar, their families, and the staff, bring additional insight and nuance into our understanding of the Holocaust, the Jewish diaspora, identity, and migration.

Food trucks in the United States have grown exponentially in the past decade. In many major cities, these mobile kitchens have given entrepreneurs the opportunity to start a business at a relatively low start-up cost, provided consumers with more diverse dining options, and improved the overall quality of life in their communities. However, due to their design, these operations also produce a lot of waste, particularly in regards to plastic packaging and leftover food. The City of Bellevue, a community with a robust food truck culture, is looking to revise its current food truck permitting process and is interested in incorporating a sustainable waste management component. This policy analysis will identify successful existing sustainable food truck practices as well as barriers to these best practices in order to provide sound recommendations to be included in Bellevue’s new permitting process. To identify current practices, a framework based off of pre-existing literature will be used to assess successful sustainable food truck operations around the country with the goal of elucidating best-sustainable food truck practices. This formative research will then be used to formulate interview questions about the main barriers to waste prevention, waste reduction, and food rescue for food trucks. Informational interviews will then be conducted with key stakeholders in Bellevue and will include food truck operators, waste management contractors, food donation organizations, and customers. Findings from this research will be used to inform key recommendations to the City of Bellevue as well as the creation of a deliverable to be provided to food truck operators such as a map, infographic, brochure, etc. The goal of this research is not only to improve the sustainability of Bellevue’s food trucks but to hopefully serve as a guide for other cities who are looking to incorporate sustainable practices into their own food truck programs.

Atherosclerosis, the underlying cause of most heart attacks and strokes, results from lipid accumulation in cells of the artery wall. Gene therapy, delivered directly to the artery wall, has the potential to prevent and reverse atherosclerosis. However, lipid accumulates primarily in cells below the endothelium, which are difficult to reach with gene therapy vectors. Our goal is to remove lipid from these cells by delivering therapeutic microRNA (miR) that increases cholesterol export from the cells. We hypothesized that if we introduced a therapeutic gene expressing the miR to endothelial cells (cells along the artery lumen), the endothelial cells would release this miR (anti-miR-33a-5p) via extracellular vesicles (exosomes) that transport miR between neighboring cells. We also hypothesized that smooth muscle cells (SMC) and macrophages would take up the therapeutic miR-containing exosomes, leading to higher expression of a critical cholesterol export protein (ABCA1) and increased cholesterol export. To test this in vitro, we introduced a therapeutic gene encoding the miR into endothelial cells and used RT-qPCR to test if the miR was released into the endothelial cell culture medium (CM) via exosomes. After confirming the presence of the therapeutic miR in exosomes purified from CM, we treated SMC and macrophages by incubating the cells with the exosome-containing CM. After incubation, we measured ABCA1 protein expression and cholesterol export. Expression of ABCA1 protein increased by 1.6- and 2.2-fold in SMC and macrophages, respectively, while cholesterol export increased by 1.4- and 1.6-fold. We conclude that gene therapy delivered to endothelial cells can produce therapeutic miR that is transferred to neighboring artery wall cells via exosomes, and increases cholesterol export in these target cells. If also effective in vivo, our approach has potential for reducing the severity of atherosclerosis by delivering therapeutic miR to cells that are difficult to reach with gene therapy.

 Alcohol use disorder (AUD) is associated with both acute and chronic alcohol-related harm. Marginalized populations, such as those experiencing homelessness, are both less inclined to successfully achieve abstinence and at higher risk of experiencing alcohol-related harm. Identifying strategies for safer use are thus particularly important for this population. To this end, we analyzed interview data collected from 86 adults experiencing homelessness and AUD who received harm reduction treatment (HaRT-A) during the parent randomized controlled trial. Participants were administered the demographic and alcohol measures at baseline (week 0) and were provided with HaRT-A, at which point interventionists introduced a list of safer-drinking strategies. Participants’ endorsement of safer-drinking strategies was assessed at HaRT-A appointments at weeks 0, 1, 2, and 6. For the current analysis, we conducted a mixed methods approach to characterize and evaluate endorsement and implementation of safer-drinking strategies at week 0 and week 6. Findings indicated use of strategies to buffer the effects of alcohol (e.g., eating while drinking), change the manner in which one drinks (e.g., counting drinks), and reduce alcohol use. Quantitative analysis indicated all participants were able to successfully endorse and implement safer-drinking strategies over the course of the study. These findings support that people experiencing homelessness and AUD adopt strategies that minimize alcohol-related harm, including ways that change the amount and manner of drinking and buffering the effects of alcohol. This extends the findings from our parent study among chronically homeless individuals to people experiencing transitional or episodic homelessness.

The HIV Vaccine Trials Network (HVTN) has flow cytometry labs at both the Fred Hutchinson Cancer Research Center (FHCRC) and the Cape Town HVTN Immunology Lab (CHIL) which both perform testing on HIV vaccine clinical trial samples. There can be a significant level of variability in the performance of flow cytometers, potentially leading to inconsistent data. The large degree of intra- and inter-instrument variability necessitates a quality assurance (QA) protocol be followed to standardize new flow cytometers to the instruments currently in use in both HVTN laboratories to ensure accurate, consistent results between instruments. Using a modified version of Perfetto et al.’s protocol which utilized sets of standardized calibration beads as well as singly stained CD4 T-cells, we successfully optimized, calibrated, standardized, and qualified a new BD FACSymphonyTM (Becton-Dickinson, San Jose, CA) flow cytometer for future use at CHIL. The successful completion of this QA protocol ensures that this instrument will be able to collect accurate and reproducible data for HIV vaccine clinical trials. It is iimportant to guarantee the quality of the data collected during these clinical trials so that the effectiveness of candidiate HIV vaccines can be properly assessed.

Dravet syndrome (DS) is a form of intractable epilepsy that manifests itself in infancy. It is comorbid with behaviors resembling autism, motor deficits, and premature death. Human infants with DS also experience both febrile and non-febrile seizures. Therefore, research into the mechanistic pathway of DS in mice may shed light on the alleviation of DS symptoms detrimental to the human quality of life, as well as help to identify avenues for gene therapy and further research. Symptoms of DS have been shown to recruit certain immunologic entities such as microglia, a type of glial cell. Glial cells, or non-neuronal brain cells, have traditionally been thought to merely play the supportive role of providing nutrients to neurons. However, recent studies have shown that glia play a more active role in stabilizing information processing, brain function, and maintaining brain homeostasis. Following microglial recruitment, another type of glia, astroglia, are activated. Astroglia form the blood-brain barrier and collaborate with microglia to produce neuroinflammation through gliosis. Gliosis has been shown to interfere with normal neural function, which is postulated to contribute to Dravet phenotypes. Thus, DS symptoms may produce either hypertrophic astroglia or increased distribution of astroglia, both of which interfere with the ability of inhibitory interneurons to adequately regulate neural excitation as a result of induced neuroinflammation. Investigation into the link between glia and Dravet syndrome is the core of this research and has revealed sex differences in the distribution and size of astroglia. In particular, immunohistochemical staining of brain tissue on Dravet females have shown greater astroglial concentrations in the DG relative to their male counterparts, when coupled with behavioral analysis and EEG readings. This difference has implications in Dravet syndrome research and treatment.

Our current research with the Kinematics and Impacts Lab at the University of Washington entails the design, buildup, and field testing of an asteroid sampling system. These field tests include the buildup of two stage closer rockets, which are highlighted in this presentation. This asteroid sampler field testing helps characterize the sampling process of impacting an asteroid at high speeds- necessitating our rocket system be capable of stable, high speed flight, even at an inverted trajectory. The booster stage, or primary stage, of the system consists of a single large motor to allow the system to reach between 3000-4000 feet above the ground. The sustainer, or second stage, consists of eight smaller motors clustered around a central body tube, allowing the second stage to be hollow. Finally, a hollow point steel nose cone caps the sustainer. Inside the nose come assembly a sample dive is attached, designed to eject during impact. Field testing of this system occurred in December 2018, with preliminary results being compiled.

Cancer is increasingly a global health issue. Access to radiation therapy, the primary method of cancer treatment, is limited in low- and middle-income countries due to difficulty translating technologies in resource-limited settings. We are developing a new generation of cost effective IMRT (intensity modulated radiotherapy) devices for low- and middle-income countries. The current IMRT is performed using linear accelerators with multi-leaf collimators (MLC) which is very expensive and challenging to maintain in low- and middle-income countries. As a team, we are replacing the current technology with an alternative one using physical compensators which have lower commitments in terms of cost, overhead, and complexity. During my time working in the Imaging Lab, I have implemented all of the custom scripting protocols in a Python script (IronPython Interpreter) which is connected to the treatment planning system (RayStation - RaySearch Laboratories). Treatment planning systems are at the heart of radiation therapy systems and the key to improved patient outcomes. My script has enabled the creation of a compensator map and contour from the fluence data of the beamset. To test validity and correctness of the equations derived - I created a treatment plan based on the CT image for a head and neck cancer patient. The preliminary results of my script on this treatment plan indicate that compensators with ray lines divergent with the radiation source can be constructed for use in the treatment planning system. My contribution satisfies a key requirement of the project. A prototype of the compensator will be developed in commercial and partner sites in India, validating the script with a large number of patients.

Mushroom bodies are paired structures in the brains of invertebrate phyla. They are characterized by densely packed neurons that are essential for facilitating learning and memory. Previous research using anatomical observations and immunohistology on mushroom body-like structures across arthropod species supported genealogical correspondence over convergent evolution of these learning and memory centers. The data collected so far, however, lacks representation from certain taxa, namely the crustaceans. To continue gathering evidence to further support or refute genealogical correspondence of mushroom bodies, we will examine neuroanatomical features as well as the presence of proteins required for learning and memory formation in a class of crustaceans called the malacostracans. Protein kinase A catalytic subunit alpha (PKA-Cα) is one such protein that is highly conserved in amino acid sequence and in learning and memory function across insects and mammals. Its conserved nature makes it a useful indicator for mushroom body homologs across phyla as its expression is known to be enhanced in mushroom bodies. We will be utilizing antibodies raised against PKA-Cα on brains of crustaceans closely related to insects in order to reveal structures that may genealogically correspond to mushroom bodies. Evidence suggesting that mushroom bodies are linked through homology would be supported if paired brain structures of crustaceans in multiple lineages are found to resemble mushroom bodies in morphology and protein expression patterns. By identifying mushroom body-like centers across invertebrates, we are able to make a comparison of the structures in context of the sensory environments of each animal in hopes of understanding the role of mushroom bodies in the evolution of learning and memory.

Self-disclosing personal stress is an effective way of managing stress. Previous research has shown that high school students disclose more when prompted by robot that discloses vulnerability. Thus, disclosure reciprocity in human-robot interaction (HRI) provides a promising way of offering stress intervention. The current study examines how different types of disclosure from a social robot affect reciprocal human disclosure and other user outcomes through a stress-disclosing activity. Using a between-subject design, 36 young adults were randomly assigned to converse and engage in a stress-disclosing activity with a robot that shared technical facts (technical condition), feelings from other users (by-proxy condition), or feelings from itself (emotional condition). We hypothesize that emotional robot disclosure will elicit longer and deeper participant disclosure, and higher robot attributional ratings (such as likeability, perceived safety, user satisfaction, and intention for future use) than technical disclosure or by-proxy disclosure. Participant self-disclosure was measured by word count and depth of response during the robot interaction. User satisfaction, intention for future use, robot likeability, and perceived safety were captured using 5-point Likert scales. Our multivariate generalized linear model revealed that participants who experienced the technical robot disclosure condition gave the robot significantly higher rating for perceived safety, but no significant differences in other variables, such as length and depth of participant disclosure among robot disclosure conditions. Surprisingly, we found that people with higher perceived stress significantly disclosed less in both breadth and depth, and rated the robot as less likeable, had lower future intention to use and user satisfaction. This study demonstrates the complexity of designing robot for stress-intervention and the importance of capturing perceived stress as a predictor for stress intervention in HRI. Future research will examine how high stress and low stress group might perceive and interact with a social robot differently in long-term repeated interactions.

In 1980 Mt. St. Helens erupted, felling nearby trees into Spirit Lake. Today the remaining logs make up a floating mat covering 20% of the lake’s surface. This unique habitat niche has the potential to host various types of photosynthetic organisms. One such organism is cyanobacteria that has the ability to fix nitrogen from the atmosphere. A previous study on the nutrient budget in Spirit Lake suggested that nitrogen outflow was greater than inflow, and this study aims to investigate the potential role cyanobacteria has on the lake’s nitrogen budget. Our hypothesis is that cyanobacteria growing on these floating log mats, and possibly other benthic habitats in the lake, are the source of the larger outflow of nitrogen. Gathering samples from plankton tows, and artificial substrates anchored to the logs, we counted and calculated the relative abundance of the cyanobacteria compared to other phytoplankton. We found that the average relative abundance of cyanobacteria is about 13.08% across plankton tows and log mats. Over the sampling season relative abundance was low until early July then peaked in early August dropping off slightly over the month. Species richness of phytoplankton also increased significantly in August and remained high to the end of the month. We predicted based on the surface area of the log mats and fixation rates for an oligotrophic lake that the cyanobacteria only accounted for 0.01% of the excess nitrogen output. These results suggest that the dominant taxa on the log mat are not cyanobacteria, and that further investigation needs to be done into other potential habitat that might be more important for cyanobacteria. More extensive sampling needs to be done over the full length of the algal growth season, and the effects of seasonal weather patterns on nitrogen fixation need to be further investigated.

It is well known that nonlinear optimization can lead to a local minimum of the loss function. As such, different initial values of the model parameters can give different values for the loss function. In other words, the existence of local minima introduces a source of variability in the loss function. Additionally, model selection often involves resampling, which in turn introduces a second source of variability. In this work, random effects models are employed to estimate these two variance components. More specifically, a neural network model is employed to examine the behavior of these variance components as a function of the variance of the initial weights and the number of hidden nodes (H). It is found that when H is small, weight initialization has a larger effect on variation of loss than cross-validation, and when H is large, these two factors contribute comparably to the variability in loss.

What drives a space program? As more and more countries search for new areas of expansion, we must ask ourselves: who among them will be the leaders of space exploration in the 21st Century? This question has become extremely relevant due to the presence of a possible Modern Space Race. 2018 – 2020 will see more space missions from more countries than at any time since the Cold War Space Race. Although it is not a race to score firsts, there is a definite air of competition in the current space exploration scene. This literature review examines the driving factors behind the first space race and the current state of the emerging actors in space exploration. Studying the Cold War Space Race is important in helping us understand what sustains such a large-scale competition for space, along with the consequences that it might bring. For example, space and culture formed an interdependent relationship that seemed to feed into each other in a closed and self-sustaining cycle in that the space race generated a space-based culture in the United States, which in turn supported the US space program’s continued existence. Comparing the two different races may lead to a better understanding of the state of the Modern Space Race.

T-cell immunotherapy is a treatment utilising the body’s own immune system to target cancer cells. Dr. Marie Bleakley’s immunology lab at Fred Hutchinson Cancer Research Center uses T-cell immunotherapies to treat hematologic malignancies — blood cancers which include acute myeloid leukemia and myelodysplastic syndrome (MDS). These treatments rely on the identification of neoantigens (cancer-specific gene mutations) which are potentially highly cancer-specific and are promising as targets for new immunotherapies. My project will be in the identification of these neoantigens, under the supervision and mentorship of Dr. Melinda Biernacki, a research associate in Dr. Bleakley’s lab. My project will focus on generating in silico and preliminary in vitro data for candidate neoantigens in high-risk MDS.
The project will have two parts. First, the identification of candidate MDS neoantigens using human leukocyte antigen (HLA)-binding prediction algorithms to identify mutated amino acid sequences (peptides) that have a high probability of binding HLA molecules. Because T-cell antigens consist of a peptide-HLA molecule complex, this step will filter out mutant peptides that are unlikely to be recognized by T cells. Second, in vitro assays will determine which candidate neoantigens are immunogenic (can actually be recognized by the body’s T-cells). HLA-binding predictions do not reliably predict immunogenicity of candidate neoantigens, so in vitro testing is needed to assess T-cell recognition. The end product will be the identification of potential T-cell targets from mutations in various genes that are shared in subgroups of MDS patients that could be used to develop immunotherapies for MDS.

The growing use of opioids in the United States has become a dangerous epidemic. The people most susceptible to overdosing on opioids are those who relapse after extended drug abstinence, whether forced or by choice. This study investigates the effects of heroin addiction on KCNQ channels in the basal ganglia, which plays an integral role in addiction.  More specifically, our research is focused on relapse after a prolonged period of no drug use. If the population of KCNQ channels are affected by heroin use and addiction, then these channels are a possible site for treatment to target. The drug retigabine, a KCNQ channel opener, has shown promise in reducing self-administration after abstinence by affecting dopamine levels in the striatum, a neurological center often involved in addiction. Given that dopamine release is critical in establishing and affecting addiction, retigabine is a likely candidate to diminish relapse behaviors and, therefore, reduce the occurrence of relapse-related overdoses. This study measures the effect of a global administration of retigabine. Catheters were surgically into the animals’ jugular vein to allow for self-administration of heroin with limited researcher interference. Over the course of three weeks, we ran our animals inoperant boxes for periods of self-administration following various drug availability periods and ending with forced abstinence. After two weeks of forced abstinence, the animals with high and low responding on self-administration were separated into three different treatment groups: Retigabine, XE991 — a  drug that has the opposite effects of retigabine — and a control solution (all administered intraperitoneally). Our animals then underwent one hour of continuous access self-administration where they could relapse. Behaviors such as drug intake, drug seeking, drug taking, and motivation to administer were measured across all six groups.The results from this study will provide evidence on the efficacy of retigabine in reducing relapse behavior after abstinence.

The influenza virus is known for its rapid evolution, or the ability to fix many mutations over a short period of time. Some of these mutations lead to amino acid substitutions in regions of the virus targeted by the immune system. Such changes are often selected for because they confer a fitness advantage by allowing the virus to "escape" immune response. This pattern of repeated immune escape is a detriment to public health because it necessitates an annual update to the influenza vaccine. Therefore, identifying sites on the influenza virus which are targeted by the immune system could help predict which influenza strain will circulate in the future, inform vaccine design, and help understand basic evolutionary questions. Using molecular phylogenetic techniques, we can identify sites potentially targeted by the immune system by looking for "positive selection", a phenomenon which manifests as a higher than expected rate of evolution. To identify sites evolving faster than expected, we defined a null expectation of the evolutionary rate of influenza in the absence of immune pressure. This null model is defined using empirical measurements from a high-throughput functional assay known as deep mutational scanning. This null model differs from traditional phylogenetic models in that it describes the constraints on influenza on a site-specific basis and, as a result, has been shown to be a more accurate and powerful null model. I have implemented an empirical Bayes approach to identify sites which deviate from the null model by an unexpectedly high evolutionary rate, suggesting positive selection. Preliminary results show that my method outperforms other methods for identifying sites under positive selection. Next, I will apply these methods to the influenza virus surface protein, hemagglutinin, which is a major target of the immune system.

This research is aimed at improving the functionality and use of multi-robot control through several different aspects. One important aspect of this project is collision avoidance between multiple ASEA Brown Boveri (ABB) industrial robots. The active collision avoidance software is an efficient tool that detects potential collisions between multiple robots working in collaboration and the surrounding cell. The user can specify a safety net around each robot, which notifies the user if one or more robots are on a collision course. Each robot’s position is graphically displayed to the screen with respect to the user-defined world coordinate system, complete with logs of tool center point positions and time stamps, so collisions can be reproduced. This software is intended to be used in conjunction with automated scheduling as an external safety checker. Another important aspect of this research is the end effector, an attachment that is secured onto the end of the ABB robot and used to drill a series of holes in a given surface. The end effector has gone through numerous design improvements through which it became smaller and more cost efficient. The latest design incorporates the addition of a raspberry pi, a small single-board computer, which serves as a failure test. The pi is programmed to generate random failures which notifies the user to take the robot out of the running program. This system will eventually be used to detect real robot failures and alert the user of the malfunction. The end effector also has a separate attachment which is used to hold a camera in order to incorporate machine vision into the multi-robot system. Adding machine vision helps robot position calibration, along with detecting foreign objects other than the moving robots in the robot cell. This addition also improves security and liability of the system.

The transient receptor potential vanilloid 1 (TRPV1) ion channel is well known for its role in sensing numerous “noxious” stimuli. It responds to noxious heat, acid, capsaicin (the active compound that makes chili peppers “spicy”), and inflammatory signals, which can be perceived by the brain to be painful. When the TRPV1 channel senses a signal such as capsaicin, it goes from a closed, non-conducting state, to an open state that allows the passage of ions into the cell, generating an electrical signal. Since TRPV1 is activated by a variety of different stimuli one of our aims is to determine if the structural mechanisms that open the channel is the same or different for each stimulus, which could have important clinical implications. For example, failed clinical trials of some TRPV1 antagonists resulted in elevated body temperatures in patients, indicating that the body’s ability to regulate body temperature is impaired when TRPV1 is completely inhibited. Hence, if TRPV1 can be inhibited in most cases, but still respond to temperature, it will be a better target. We aim to combine cysteine-scanning mutagenesis with spectroscopic techniques to map the structural changes of TRPV1 activation in response to different stimuli. Since introduction of mutations can result in impaired channel function, each mutant needs to be functionally verified. My research will be to generate a broad library of single-cysteine TRPV1 mutants and verify their function using calcium imaging. Mutants that preserve TRPV1 function can then be used for further spectroscopic studies.

Omega-3 fatty acids provide numerous health related benefits, and are commercially available in the form of supplements. However, these fatty acids have the tendency to oxidize over time and can have potentially harmful effects on the human body. Additionally, neutrophil oxidation of fatty acids in vitro has been shown to be a marker for oxidative stress. Oils oxidized with a biologically relevant concentration of sodium hypochlorite were used to simulate the behavior of neutrophils in the human body and these results were analyzed and compared to control samples. In order to characterize the oxidation byproducts of common fatty acids, the oxidation products and control samples were treated with acidified methanol in toluene to perform a fatty acid methyl esterification (FAMEs). This facilitated the analysis by gas chromatography and mass spectrometry (GC-MS) and provided proof-of-concept for the fatty acid analysis method. This methodology was applied to 0.29 mmols of each sample of oil oxidized with .05 mMols of sodium hypochlorite to evaluate the products of this reaction to simulate the behavior of neutrophils in the human body. GC-MS data for the composition of the FAMEs and oxidation derivatives detected will be presented as well as their relative amounts.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition associated with deficits in social interaction and the presence of restricted patterns of behavior. ASD is clinically and phenotypically heterogeneous. The most recent update to the diagnostic definitions for mental disorders (DSM-5) provides additional flexibility for capturing the diverse array of phenotypes shown by diagnosed individuals. Despite categorized behavioral symptoms across core and comorbid dimensions of ASD, the neural mechanisms are unknown. Studies have shown atypical neuroanatomy and functional connectivity of the brains of individuals with ASD, suggesting a neural etiology. Here, we focus our attention on the superior temporal sulcus (STS), a region of the brain demonstrated to play a role in processing communication, social information, and theory of mind. Our research question evaluates whether neural activity in STS is affected by behavioral phenotype in children with ASD. We speculate that neural activity between individuals with ASD varies significantly more than typically developing (TD) children, who show more clustered, similar outcomes. Functional near infrared spectroscopy (fNIRS) distinguishes concentrations of oxygenated (HbO) and deoxygenated (HbR) hemoglobin in regions of cortical vasculature, signifying neurovascular coupling. This study uses HbO and HbR measured as subjects watch the events of a social scene on a monitor and analyzes ASD individuals’ deviance from average TD activity. Eye-tracking, clinical assessments, and parent questionnaires are considered to extrapolate possible correlations between ASD individuals’ variation in neural outcome and the behavioral phenotype expressed. We expect that individuals showing higher degree of neural variance from TD activity will show more severe autism behavioral phenotype. It is possible that in the search for neural mechanisms of ASD, considering behavioral factors signifying atypical variance could reveal significant differences. This exploratory analysis aims to examine the wide range of possible influential factors on neural heterogeneity within the social brain of individuals with ASD.

Manu National Park in southeastern Peru is an incredibly bio-diverse national reserve at the meeting point of the Tropical Andes and the Amazon lowland rain forest, and an important location for tropical ecology research. Cocha Cashu Biological Station is one of few research locations in the Neotropical rain forest in which mammal communities remain almost completely undisturbed by human impact, including hunting and road construction. As a result, mammal population densities and compositions accurately reflect their natural environmental state. Among these mammals are fifteen known species of primates, and as major seed dispersers they play a critical role in the stability of the ecosystem. The aim of this study was to learn more about the behaviors of eight primate species within the Cocha Cashu trail system, during September of the dry season, using quantitative and qualitative observational methods. We used the focal sampling methods to quantify the proportions of time spent on daily activities for each species, and created activity budgets from this data to compare time spent on each activity. We also collected data on troop size, social interactions, habitat, and location throughout the day in order to compare and contrast the different groups. We were correct in our prediction that most species spent the largest proportion of time moving and feeding, but varied in other activity categories such as curiosity and aggressiveness. We found that there was significant overlap in the habitats and resources used by different species, but there were notable differences in foraging behaviors, troop size, canopy level, and the time of day designated to different activities.

The Washington State Department of Transportation (WSDOT) implemented a fifteen-mile stretch of toll lanes between Bellevue and Lynnwood in 2015. The purpose of our research is to apply economic principles and data analysis to understand how commuters respond to toll fares and the effect of toll lanes on traffic trends on I-405. We obtained hourly individual transaction data in 2018 from WSDOT. The data shows when and where an individual vehicle entered and exited the tolls, the toll fare, billing type, and travel time between toll plazas. We visualized the demand for toll plazas using hourly and daily transactions and captured factors driving the demand. We incorporated these factors into a regression model, which accounts for the variation in the day of the week, time of day, toll plaza and toll fare. After estimating the model, we identified variables important to the demand of toll lanes and traffic congestion. Our findings provide insights into improving traffic efficiency on the toll lanes, especially the HOV (high-occupancy vehicle) lanes. Our research is applicable to other studies related to toll lanes design and traffic optimization.

Autism Spectrum Disorder (ASD) is neurodevelopmental disorder that impairs an individual’s social, communicational, and behavioral skills. Boys are 4.5 times more likely to be diagnosed with ASD compared to girls. A potential cause for differences in diagnostic rates may be that girls tend to be more socially focused, allowing them to better camouflage their autism symptoms. Puberty is a period in an adolescent’s life where teens experience significant changes in social experiences and expectations. While puberty often increases social motivation, it’s unclear if males and females improve in the same ways or at the same rates. The goal of this study is to investigate sex differences in the relation between autism behaviors and stages of pubertal development. Participants included 140 children (70 males, 70 females) between the ages of 8 and 17 with a diagnosis of autism. Participants or their parents completed the Pubertal Developmental Scale, which provides a score of the child’s physical progression through puberty. Parents of the children also completed the Social Responsiveness Scale (SRS-2) which scores their child’s social and autism-related impairments. Our analyses (1) Compare SRS scores between youth with ASD based on their pubertal groups (pre/early/mid/late/post). We expect an increase in social awareness, motivation, and cognition for children going through puberty or in post puberty relative to those who have not yet started puberty. (2) Examine sex differences in SRS subdomain scores within each pubertal group and in the pattern of differences between pubertal groups. We expect to find no sex differences before puberty, but lower SRS scores in girls during and after puberty. Investigating the relationship between puberty and social behaviors could help us develop better supports for youth with ASD that incorporate biological and physical changes that come with development and consider how that might impact the youth’s social environment.

The mammalian brain is composed of a wide variety of neurons, all of which signal through structurally and biochemically heterogeneous synapses. Understanding the proteomic makeup of these synapses is crucial for understanding brain function. However, biochemical isolation and characterization has proven difficult due to the morphological complexity of neurons. MS-based proteomics could be a useful tool for studying such diversity, but spatial information is lost because the analysis is performed post-lysis. In this study we proposed to overcome this limitation by using proximity biotin labeling of genetically specified neuronal subpopulations. I thus constructed APEX2-GFP fusion constructs with post-synaptic proteins which could be expressed in vivo using an adeno-associated virus (AAV). Four post-synaptic proteins were chosen: LRRTM1 and LRRTM2 to localize excitatory synapses, and NGLN2 and SLITRK3 to localize inhibitory synapses. A pAAV-CAG (AAV plasmid with CAG promoter) backbone was digested using NotI and AscI, and an APEX2-GFP fragment with NotI and AscI ends was generated via Phusion PCR. Following NotI/AscI double digests, the pAAV-CAG backbone and APEX2-GFP fragment were ligated together in order to make a pAAV-CAG-APEX2-GFP vector. The pAAV-CAG-APEX2-GFP vector was opened with a NotI digest, and gene fragments of the four post-synaptic proteins with Gibson overlaps were then generated via Phusion PCR. Gibson assembly was then used to assemble the pAAV-CAG-APEX2-GFP vector with the gene fragments, and pAAV-CAG-gene-APEX2-GFP vectors were generated for LRRTM1 and LRRTM2. The vectors were then expressed in HEK cells and monitored for GFP expression and biotinylation activity. The pAAV-CAG-APEX2-GFP vector showed bioluminescence and biotinylation activity, but the vectors with gene inserts did not. Although we successfully cloned two of the target constructs, current investigations are still under way in order to optimize them.

Have you ever had to motivate the team? What was the result? The English language Wikipedia is notable for its large number of articles. However, 288 other active language editions of Wikipedia have also developed through the intricate interactions of contributing editors. While the editor interactions in the English Wikipedia have been researched extensively, these other language editions remain understudied. To understand how editors currently come to consensus in article building in the French language, a team of researchers has leveraged an existing English framework that depicts how power and policies play a role in mass collaboration. Using this English language framework, we are using qualitative coding methods to build a unique model of the editor interactions on the French language Wikipedia. The results of this study will help contribute to a deeper understanding of how a framework in a different language edition of Wikipedia differs from the English. Our preliminary results show that policy plays a large role in justifying editor decisions for the edits they make on various articles. Furthermore, our research findings have expanded our knowledge of the issues surrounding replication of an English framework in a different language platform.

About 3.1 million adolescents are diagnosed yearly with depression. Adolescent onset of depression is associated with acute or chronic difficulties in physical, mental, and psychosocial functioning. However, over 60% of adolescents with depression do not receive mental health care, and, among those who do, treatment engagement is low. Behavioral Activation (BA) is an evidence-based psychosocial intervention for individuals with depression. While BA holds promise as an effective treatment, researchers have found that adolescents may be better reached and engaged through social and mobile technologies. In addition, BA requires frequent interaction from patients over time, which can be difficult and costly to administer in-person. There is an opportunity to improve the usability of and engagement with EBPIs via online technologies. Asynchronous Remote Communities (ARC) is a promising technology-based approach for engaging adolescents that leverages technology’s reach while providing support, social interactions, and motivation. ARCs are private online groups on which researchers can deliver weekly research tasks to participants and gather information about their perceptions in a format that is lightweight, accessible, usable, and low burden. We have used ARC to both discover design requirements and to design/build a platform for administering BA, which we have tested with clinicians and adolescents. We used ARC with 10 mental health clinicians specializing in treating teens with depression to discover their needs. Specifically, we worked with mental health clinicians to better understand their needs and to identify facilitators and barriers to adapting BA to ARC. We used the Slack online platform to create an accessible, anonymous environment where we posted 20-minute long design activities each week for 10 weeks to be completed asynchronously. We were then able to recruit teenagers to understand their needs. Based on the results, we are adapting BA to ARC settings and then testing out the feasibility.

Aging is driven by the time-dependent disruption of cellular processes.  Collectively these changes lower physiological resilience and increase the probabilitity of death.  As the population of elderly humans gets larger, studying pathways that mitigate age-dependent changes has taken on increasing importance.  The round worm Caenorhabditis elegans has proven to be a powerful model organism for studying the basic mechanisms of aging.  Here we have investigated a novel life-extending pathway acting in these animals that is triggered in response to mitochondrial electron transport chain disruption, a phenomemon that occurs naturally in humans with age.  The pathway is comprised of mitogen-activated protein kinase (MAPK) signaling cascade comprised of DLK-1, SEK-3, and PMK-3 and the downstream reporter gene tbb-6.  Our primary objective in this study has been to identify signaling factors triggered distal to PMK-3 activation that mediate life extension.  We have utilized several independant approaches including both targeted and unbiases genetic screens, as well as co-immunoprecipitation.  Among a family of 33 candidate bZIP transcription factors, we have identified six that are required for PMK-3 mediated life extension.  Using an ENU mutagenesis screen we have identified ten genetic mutations that trigger constitutive tbb-6 activation.  Sequencing tests suggest that these lines contain specifc allelic mutations that form on the X chromosome.   Finally we have generated transgenic strains containing tagged versions of PMK-3 and SEK-3.  We have succeeded in immunoprecipitating both proteins from whole worm lysates, in preparation for future mass spectral analyses.  Updated results from our studies will be presented.

The DNA damage checkpoint (DDC) is critical for survival as it responds to damage such as mutations or chromosomal rearrangement, and prohibits the cell cycle from proceeding through a failed replication. One of the many responses DDC activates is histone degradation. When wrapped around histone proteins, DNA is blocked from repair mechanisms. By reducing histone and nucleosome density, the cell increases DNA mobility and allows the DNA to be quickly repaired via homologous recombination. The cell does this by uncoupling histone transcription from the S-phase of the cell cycle, which is normally confined to this phase. When DDC is activated outside of S-phase, the cell can no longer produce histones to replace those it consumed and ensure proper chromatin packing after the DNA is repaired. According to published literature, uncoupling histone transcription from S-phase increases lifespan but should compromise the DNA damage response. However, it is largely unknown how this uncoupling affects the DNA damage response in different mutants. Our goal is to explore how this affects mutants with reduced DNA damage responses. Our mutants of interest are 1) rad52Δ, which reduces homologous recombination, and 2) lif1Δ, which reduces non-homologous end joining (NHEJ). Our protocol involves yeast (Saccharomyces cerevisiae) spotting and exposing yeast to different durations of high-intensity UV energy. We will compare colony sizes across different strains, dilution factors, and UV-exposure degrees. We expect to see strains with rad52 or lif1 deletion to have a lower growth rate compared to the wild type. Following this experiment, we will explore how altering histone transcription interacts with, and may enhance rad52 and lif1 in DNA repair. We hope to apply our findings to mammalian and human genes, and help to decrease the onset frequency of age-related diseases such as cancer due to genomic instability.

Fatty Acid Binding Proteins (FABPs) are intracellular proteins that facilitate the transport of fatty acids and other lipophilic substances into the cell for various biological functions. For example, FABP5 is important for binding endocannabinoid anandamide (AEA) which helps regulate cognition, learning, and memory. Compounds such as tetrahydrocannabinol (THC), the psychoactive component of cannabis, competitively inhibit FABP5 and prevent catabolism of AEA in the cytosol by fatty acid amide hydrolase (FAAH). Because many drugs (like ibuprofen and progesterone) are also lipophilic and poorly water-soluble, we predict that FABP5 has a role in their metabolism. The goal of this investigation is to better understand how FABP binding may affect drug metabolism by determining the binding affinities of different drugs to FABP5 using a fluorescence displacement assay. We first validated an assay for screening drugs and determining drug-FABP5 binding. Both ANS and NBD-Stearate, molecular probes that generate a fluorescence signal upon binding, were evaluated. FABP5 was titrated with increasing concentrations of each probe and the resulting changes in fluorescence plotted a hyperbolic curve used to calculate Kd (dissociation constant). In these trials, NBD-Stearate was found to have high background fluorescence and low sensitivity to changes in fluorescence upon alternative ligand binding, so ANS was selected for further method development. We found that factors such as mixing and time to equilibrate affected the Kd, possibly from non-specific binding. The binding affinities for ANS were 1.177 ± 1.005 μM (Morrison equation fit average), and 4.744 ± 1.387 μM (One Site Specific average). The preliminary data showed that fluorescence decreased by 48.28% with the addition of arachidonic acid (positive control) which confirmed ANS as a suitable assay. By adding increasing concentrations of various drugs to competitively inhibit the binding of ANS, a decrease in fluorescence will be measured and used to calculate Ki (inhibitor binding affinity).

Alzheimer’s is a progressive, age-associated, neurodegenerative disease characterized by memory loss, deterioration in thinking and reasoning skills and gradual loss of executive function. Two well-documented biochemical hallmarks associated with disease progression are the accumulation of extracellular beta-amyloid (Aβ) plaques and intracellular neurofibrillary tangles found in the brains of Alzheimer’s patients. One theory of the disease holds that aggregated proteins found in these two deposits inhibit protein degradation by the 26S proteasome, a large protein that is one of the central components of the ubiquitin-proteasome clearance system. This system, of which the proteasome is a key component, executes most of the controlled protein degradation in the cell. Importantly, impairments in proteasome function are associated with multiple neurodegenerative diseases. The overall goal of this project is to determine whether proteasome stimulators can delay toxicity associated with Aβ aggregation in a C. elegans Alzheimer’s disease model. C. elegans is a powerful model organism in biomedical research due to its ease of culturing, well-described genetics, gene homology and availability of transgenic tools. My project utilizes a C. elegans strain that expresses the full-length human amyloid beta peptide (Aβ_1-42) in body wall muscle cells. These animals become paralyzed when up-shifted to a restricted temperature due to aggregation of Aβ proteins in the muscle. To test the hypothesis that proteasome stimulators delay the progression of Alzheimer’s symptoms, I will treat animals with four drugs and measure the time of paralysis. Using a high-throughput drug screening system recently developed in our lab, I will treat animals with four proteasome stimulators or vehicle controls, in triplicate, and determine the onset of paralysis for each drug. These results will help shed light on the involvement of protein aggregation clearance in treating symptoms of Alzheimer’s in this model organism, and help inform future treatments for this and other neurodegenerative disorders.

Risk taking is strongly associated with many disordered behaviors. Many studies implicate the orbitofrontal cortex (OFC) in such behaviors, though its modulation yields inconsistent results. This could be due to possible contrasting effects of intratelencephalic (IT) and pyramidal tract (PT) neurons, which have distinct morphologies and projections. Despite this, specific functionality differences are unknown. Given that 5-HT2A and D1 receptors have predominant expression in IT neurons over PT neurons, and antagonism of these receptors decreases risk-seeking, it was hypothesized that inhibition of all IT neuron activity in the OFC would also result in risk aversion. IT neurons in rats were inhibited during a risky-decision making task (RDT). To modulate IT neurons, an inhibitory designer receptor exclusively activated by designer drugs (DREADD) was injected into lateral OFC bilaterally, conjugated to CRE and FLP drivers injected into contralateral nucleus accumbens. In the full RDT, animals were presented with two levers: The “safe” lever delivered one pellet reward per press, while the “risky” lever delivered four pellets, with descending probability of reward administration (100%, 50%, 25%, 12.5%). Two test sessions were conducted whereby animals received intraperitoneal injections of clozapine-N-oxide (CNO) or a vehicle (DMSO) 30 minutes prior to task onset. Animals receiving CNO the first time received vehicle the second time. To determine if IT neurons were involved in perseverative responding, animals underwent a reversal task. They were presented with an active lever -which administered a food pellet per press -, and an inactive lever. Five consecutive responses on the active lever switched the inactive lever to the “active” lever. Results showed no significant changes in decision-making or reversal learning upon receiving CNO or vehicle. IT neuron modulation may need to be more temporally specific; future studies will focus on monitoring IT activity during decision-making paradigms to further elucidate their contributions within OFC.

The study of the behavior of multiple agents, specifically human and machine, in a dynamic environment is challenging due to the unpredictable individual behaviors. Humans will naturally formulate beliefs about the machine’s behavior, which would directly affect their future decisions. Our research aims to develop a framework for the study of human-machine dynamic interactions. With the imperfect information humans and machines have about each other and their environment, a game-theoretic approach was done to study the natural model of their interactions. We derive theoretical models for steady-state (i.e. equilibrium) and transient (i.e. learning) behaviors of humans interacting with other agents (humans and machines). We also design experiments to validate our theory. A haptic testbench, in the shape of a robotic arm, is used as a dynamic simulation platform for studying the trajectories of the human/machine interaction, allowing us to study both theoretically and experimentally. The robotic arm has a position control system that supports a wide variety of human/machine experiments. The user is provided with visual and haptic feedback, which allows for experiments to be designed to study the sensorimotor learning processes. The robotic arm is built using direct-drive brushless motors, force sensors, an open-source ODrive motor controller, and an arm lever. The motor firmware is designed in C/C++, and integrated with a user-interface in Python. With the wide variety of potential applications, we hope our research will give insights into the different natures of human motion and be a fundamental platform for technological breakthroughs in the medical field.

Tuberculosis (TB) remains a major international health concern and one of the top 10 causes of death worldwide, according to the World Health Organization. Previous clinical work in our lab demonstrated that oral swab analysis (OSA) can successfully diagnose tuberculosis by detecting Mycobacterium tuberculosis DNA in the mouths of infected patients. In order to strengthen OSA against traditional but more invasive methods, such as sputum sampling, improvements to DNA extraction and swab type must be investigated. I am comparing different degrees of automation with MolBio’s Trueprep, the AudioLyse, and ThermoFisher’s KingFisher against our previously validated manual Qiagen extraction protocol—with the comparison lying in sensitivity and efficiency. In order to increase the versatility and sensitivity of OSA, I am also investigating boil preparations and dissolvable swabs. Boil preparation of swabs is a relatively simple extraction procedure, and early results have demonstrated its comparability against the Qiagen extraction. Meanwhile, dissolvable swabs have a hypothetical 100% yield of sample material. I have successfully dissolved calcium alginate swabs from Puritan in acidic sodium citrate solutions, and Luna swabs were dissolved in chaotropic agents. DNA yields are compared to non-dissolvable, previously validated swabs.

Molecular interactions that occur between surface components of pathogens, termed adhesins, and complementary receptors presented on host cells are critical for establishment of infection. The adhesion-receptor binding event may trigger diverse signaling cascades in the host cell that result in activation of innate host defenses or the subversion of cellular processes facilitating bacterial colonization or invasion. Hence, microbial adhesins are important targets for the development of antimicrobial therapeutics and vaccines. One of the interests of the Sokurenko Lab at UW is understanding the structure and function of the ubiquitous Escherichia coli adhesin, FimH, and its potential as a vaccine candidate against urinary tract infections. FimH is expressed on top of filamentous hair-like appendages called type 1 fimbriae that confer bacterial binding to glycoproteins with terminally exposed mannose. In the laboratory, we use a variety of assays to study FimH-mediated bacterial adhesion and test different mannose-containing compounds and glycoproteins for optimal inhibition of FimH-mediated interactions. We also elicited a great number of FimH-specific monoclonal antibodies that are tested for their potency to inhibit binding properties of the FimH, and to understand the structural mechanisms of antibody-mediated inhibition. By generating and analyzing various FimH mutants, we seek to elucidate how the function of FimH protein can be efficiently regulated. The ultimate goal of these experiments is to gain knowledge on the optimal structure (conformation) of the FimH protein that can be used as an antigen for efficient induction of protective antibodies during immunization.

LiveOcean is a computer model of the Pacific Northwest Coastal Ocean created by the UW Coastal Modeling Group. It forecasts chemical and biological properties of the ocean much the same way that atmospheric models forecast the weather. One of the many parameters that LiveOcean forecasts is phytoplankton, which form the basis of the marine food web. This study compares LiveOcean forecasts of phytoplankton populations with remote-sensed estimates of chlorophyll concentrations from satellites. The assumption is that satellite sensors, which base their chlorophyll estimates off of the color of reflected light from the ocean, represent something near the true concentration of phytoplankton. To validate this assumption, we obtained ship-based data from NOAA along a frequently sampled line near Newport, OR. Using these two sources for comparison, we were able to get an idea of how accurate the model was. Evaluating over 8-day and 32-day time periods, we started by looking at the continental shelf over the entire geographic range of the model. Then we broke it up into five zones from north to south. What we found was that the model and satellite showed the same general annual pattern of growth and decline, but they differ in many of the specifics. Most notably, the model fails to show the decrease in phytoplankton populations from north to south that satellite observations reveal and has been observed through oceanographic fieldwork. This project provides a basis for future revisions and improvements to the LiveOcean model.

A national organization named 2-1-1 provides assistance to populations with basic needs, mainly informing and answering questions, and researching resources covering 50 states. Not only is the demand for information growing, but also the complexity of calls is increasing. For example, a person may need information on shelters, medical issues, legal assistance, debt management and other services. Consequently, calls are taking longer, and with limited resources, wait times are increasing and even critical calls are sometimes abandoned. Assigning more staff to a call center is not realistic under limited budgets. Hence, an efficient call center system must be designed. Our research seeks to address the efficiency of the WA 2-1-1 call center system, in Washington State. We hypothesize that the application of call prioritization and skill-based routing can reduce the holding-call time, and eliminate call abandonment for those with urgent needs. We will identify classifications of calls, and evaluate how automation can be used to navigate or direct callers to a correct resource and expedite the whole process. Appropriate classification of calls and prioritization may not only decrease the waiting time but also help training operators with an appropriate skill set. We will apply the concept of operations research to forecast seasonal demand using available data within Washington State, and will estimate the number and allocation of resources the organization should provide. The anticipated result of the research is a call center design that will decrease the number of abandoned calls, provide an immediate response to an urgent call, decrease waiting time, and assign calls to available operators to exploit the limited resources. The WA 2-1-1 call center is important to provide assistance to efficiently serve populations in need. Increasing the efficiency of call centers with limited resources will enable WA 2-1-1 to reach more people in need.

Social determinants of health (SDOH) are non-medical factors that contribute to a person’s health and well-being. The Centers for Medicare/Medicaid Services recently released a standardized 26-question survey designed to capture SDOH in the following 13 domains: living situation, food insecurity, transportation, utility help, personal safety, financial strain, employment, family and community support, education, physical activity, substance use, mental health, and disabilities. However, there is limited study using this survey tool in a safety-net institution. Harborview Medical Center (HMC) is the public hospital serving King County, WA and provides care to a wide variety of patients. This project was a prospective, observational study which aimed to investigate implementation of this survey tool and to measure relevant SDOH and other medical factors in this setting. My role included administering the survey to patients admitted to the HMC Hospital Medicine service from October to December, 2018. I collected data related to the duration of the survey and any challenges patients encountered responding to the survey, as well as review of patient charts for demographic information, medical system utilization, and medical history. In total, only 24 of 90 patients (27%) completed the survey. Major challenges included patient lack of interest, language barrier, ability to consent, and competing time demands. These results have implications for the generalizability of this tool and whether it comprehensively identifies SDOH needs.

This project aims to better understand the effects of removing global topography on atmospheric and oceanic circulation in numerical climate model simulations. The Community Earth System Model (CESM) was run for a hundred years under three different scenarios: the removal of all mountain ranges, the removal of the Rockies, and the removal of the Tibetan and Mongolian Plateaus. When mountains are removed it results in changes to ocean and atmospheric circulation. This begins with warmer surface temperatures where the mountains were removed (without the elevation-induced cooling) and changes in both vertical and horizontal air motion in the vicinity of the mountains (as the topographic-induced circulations are disrupted). Consequently, rainfall is altered due to changes in temperature and air motion. Our research aims to better understand how mountain ranges affect rainfall, particularly in the tropics. and how this in turn affects local climatology in tropical regions.

Campylobacter jejuni is a Gram-negative spirochete bacteria that colonizes the guts of many bird species. They are pathogenic to humans and typically consumed with undercooked poultry or contaminated water. In this study, two species of crow, separated by 7,000 miles, have been examined for their ability to carry C. jejuni. Crow fecal samples were collected from Bothell, Washington (WA) and Kolkata, India (KK). All of the crow Campylobacter isolates were confirmed by qPCR and PCR methods to be C. jejuni. No other species are isolated. We compared these isolates by method of MLST (Multilocus Sequence Typing) and searched for known allelic profiles on the PubMLST database.Thirteen  isolates were analyzed for seven housekeeping genes : aspA, glnA, glyA, gltA, pgm, tkt, uncA. Using primers specified in the PubMLST database portions of the genes were amplified by PCR, verified by gel-electrophoresis and sent to Eurofin Genomics for sequencing. Once the sequence files were returned, they were aligned and assembled using Mega7 software. An allele number was obtained for each sequence for each sequence from PubMLST database. The allelic profile of the 7 genes for each isolate was used to obtain the Sequence type (ST) of the isolate. MLST of 15 crow isolates that represented different phylogenetic clusters based on fla-SVR sequencing, showed a majority of the WA isolates to belong to sequence types ST2678, ST9271, ST3322, ST5472. The Kolkata isolates were ST8288 and ST5472. All types were shown to occur in wild birds. One crow’s ST3174 from Kolkata has been shown to occur in human stool, while 4 isolates including Kolkata and Washington were of unknown ST’s. Although Kolkata and WA isolates belonged to different ST’s, majority were from wild birds that have rarely been isolated from humans.

Coevolution is a process where two or more species reciprocally affect each other's evolution over time. The traits of one species evolves in response to the other. This process can lead to the diversification of organisms with unique adaptive traits. Previous experiments tested whether coevolution occurred during the 2000 generations of evolution between the bacteria Desulfovibrio vulgaris and archaea Methanococcus maripaludis by pairing populations from 1000 generations with mutualist partners from their evolutionary past or future. Results suggested patterns of coevolution, but hypothesizing that those patterns occurred by accident, we tested whether or not patterns can occur that look like coevolution with microbes that could not possibly coevolve. We conducted a timeshifts control experiment using freezer stocks of D. vulgaris and M. maripaludis that evolved alone for 2000 generations and created pairings of the mutualists with five different generational pairings. They then were paired with an ancestral control group and a modern test group from the 1000th generation. Growth rates were calculated for each coculture. Graphs of the effects the 1000th generation of M. maripaludis and D. vulgaris had on coculture growth rate showed that M1000 had similar growth rates irrespective of its partners evolution while D1000 results were variable. An ANOVA test showed the mean log ratios statistically indistinguishable across all timepoints, indicating that the null hypothesis should be accepted. This result suggests that both partners have the same effects on fitness no matter how long they evolved. However, due to variations in results between D. vulgaris and M. maripaludis it is still unclear whether these populations have the ability to create patterns of coevolution due to their adaptation to their abiotic environment.

Joseph Mathia Svoboda, a European residing in Baghdad and working as a steamship officer, kept a detailed daily diary from 1861 to 1908, in which he recorded his trips on the Tigris, family events, and his medical and financial concerns, as well as each day’s weather. Working with the UW Svoboda Diaries Project, part of the Newbook Digital Texts Collective, I transcribe these diaries and help develop resources for their analysis and the promotion of digital humanities. Digital humanities work changes not only the literal, physical forms of texts but their literary forms as well, and digitizing a text such as a diary and opening it to public scholarship presents new questions about how we think about private writings. Literary scholarship on diaries addresses the unique psychological and philosophical aspects of keeping a diary and attempts to analyze its own position in relation to its object of study, as what is personal to a diarist is placed in plain view. Svoboda himself wrote in a largely impersonal, factual style, with little personal commentary, for instance, but scholars mine social and political sentiments from his choice of language or attention. In this project, I will consider the Svoboda diaries (focusing on three diaries written between 1897 and 1899) as textual objects and describe the transformations they have undergone since their writing, with a special focus on the transformation of the private nature of a diary. What do the diaries become as we study them? While digital humanities seeks faithfulness to the original contents of a text, drastic transformation of forms such as “making the private public” naturally opens those same contents to new uses, and understanding these changes is crucial to understanding the full extent of digital humanities scholarship.

Growing concern regarding brain injury in football has encouraged research on head impact exposure (HIE), incidence of concussion, and strategies to reduce injury risk. Reducing HIE in games has presented challenges due to the physical nature of the sport. However, limiting the amount of full-contact in practice may present a means for both decreasing HIE and minimizing concussion risk. In the past few years, guidelines limiting contact have been proposed, including decreasing the intensity of contact (limiting "two-a-days"), decreasing the number of full-contact practices, and eliminating practice drills associated with greater contact (such as the "Oklahama drill"). A few states have even modified their existing concussion legislation to include provisions limiting contact. The goal of our study is to review the literature regarding limitations on contact as a means for improving safety in football and to evaluate whether evidence supports this approach as a means for mitigating risk. We have identified studies assessing the impact of limitations on contact for either reducing HIE or concussive risk in football. We have then categorized the resulting studies by level of evidence, and summarized our findings. We concluded that reduced contact should result in a decrease in HIE and thereby a decrease in injury rate. 

As we look forward to a global increase in our aging population and rising burden of noncommunicable diseases worldwide, exploring future treatments for age-associated diseases such as cardiovascular diseases, neurodegenerative diseases, cancers, diabetes, and chronic respiratory disease are of increasing importance to public health. Some studies credit the increasing burden of age-associated disease, especially that in younger populations, to the abandoning of traditional cultural practices and their replacement by Westernized diet, lifestyle, and medicine. This study explores conserved pathways of aging in response to compounds and extracts recognized by indigenous and ancestral medicine from various cultures. Employing a novel image acquisition robot, lifespan and age-associated disease phenotypes of wild type C. elegans nematodes exposed to selected compounds and extracts are observed and compared to identify potential treatments for age-associated diseases. Through conversations with traditional healers, review of the literature, and exploration of historical texts 4 major medicinal plants of interest were identified. Bitter Melon (Momordica charantia), vijayasar (Pterocarpus marsupium), rooibos (Aspalathus linearis), and Alaskan blueberries (Vaccinium ovalifolium) are recognized in East Asian, Indian, South African, and Native American traditional medicine, respectively, as treatments for slowing aging and age-associated diseases. Our research investigates how these compounds affect the longevity of C. elegans, with a focus on identifying their interactions with conserved longevity pathways. Our results contribute independent data and analysis for underrepresented compounds in aging and longevity literature, inform future research on more complex organisms, and increase recognition of indigenous and ancestral knowledge in the field of aging and longevity research. In our evermore connected global society, recognizing and respecting knowledge from diverse and often marginalized cultures and sources is critical to progressing longevity research, promoting equity, and improving health in our communities.

The English language Wikipedia is notable for its large number of articles. The development of this online encyclopedia would not be possible without the intricate interactions of editors that help sustain the virtual collaborative platform. Editors have a role in creating and reshaping articles and therefore have a role in how Wikipedia evolves over time. Our study replicates a qualitative coding scheme created over 12 years ago that demonstrates that policy and power play a role in mass collaboration. The prior work shows that user interactions including collaboration, conflict, coercion, and consensus have influenced changes on Wikipedia articles. A team of researchers are currently working to replicate this qualitative coding scheme on English Wikipedia talk pages to understand how these different types of user interactions occur in current editor discussions around article construction. Our findings will help contribute to a deeper understanding of how power plays between users have changed since the initial study. Our preliminary results, show that editor debates often lead to questions around article scope and legitimacy of sources. Furthermore, while policies play a large role in article building, editors own opinions influence how editing occurs.

The Wrangel Island State Nature Reserve (WISNR) serves as a vital refuge for the Alaska-Chukotka (AC) population of polar bears (Ursus maritimus) during the ice-free season. In September 2017, a total of 181 polar bears were observed near a bowhead whale (Balaena mysticetus) carcass on the island. This gathering is the largest aggregation of polar bears ever recorded for the AC population. This study sorted, labeled, and processed photographs of the polar bear aggregation taken by a professional photographer from a boat a day before initial ground-based observations were made. Our objective was to use the photographs to evaluate characteristics of the polar bear aggregation including animal sex, age, reproductive composition (e.g., adult females that have first-year or second-year cubs), and body condition (i.e., fatness). To do this, we selected representative subsets of photos, categorized them by time and location, and labeled individual bears across multiple photographs. The resulting set of processed photographs was evaluated by multiple polar bear experts, and the results were statistically analyzed. Based on knowledge of polar bear social systems and an initial review of the photographs, we hypothesized that both feeding activity and the locations of bears in the vicinity of the carcass will be structured by sex, age, reproductive status, and time of day. This study provides a unique opportunity to collect information on a large number of polar bears and document behavioral interactions. The resulting information will help address key conservation challenges for the AC polar bear population, including the effects of sea-ice loss due to climate warming, increased industrial activity, and identifying a sustainable rate for subsistence harvest.

At the terminus of every robotic manipulator is an end-effector. Sensors mounted at the end-effector provide egocentric perception, enabling the robot to touch and see the world from a unique viewpoint. Our existing wireless perception module has been able to stream visual (RGBD) and force (haptic) data wirelessly to other devices and is integral to our autonomous feeding robot application. As our robot applications have grown in scope, the demand for more sensors with higher quality and greater frequency has increased too. This research focuses on identifying the bottleneck of the data transmission speed of multiple sensors and implementing task-driven data extraction and compression methods. The module compresses the sensor data with optimized processing methods, such as real-time object detection, face detection, and pressure prediction. Additionally, this project involves a hardware design portion which improves the previous design and aims to easily exchangeable mounting technique and sensors. This research uses the Nvidia Jetson TX2, which is able to complete more complex tasks in shorter computing power than the Intel Joule used in the last version. The new embedded board mainly uses Python to run deep learning instances and uses low-level packages and hardware encoders to interact with sensors and cameras. This project also compares processing speed with different deep learning frameworks on Jetson infrastructure and results in a faster and more accurate solution. The sensor module becomes a processing node in the robot network, freeing the robot to focus on task-level computation rather than lower-level perception calls.

This purpose of this project was to investigate the impact of a rocket penetrator for sample-return missions focused on Jupiter’s icy moon, Europa. In particular, primary analysis used the kinetic energy from the ejecta plume of the impact crater to halt the momentum of the primary payload to model the impact. To do so, steel alloy projectile impacts in a material with properties of ice (so as to simulate the surface of Europa) were simulated using ANSYS Autodyn computational dynamics software. ANSYS Autodyn makes use of both Lagrangian and Hamiltonian meshes, as well as smooth particle hydrodynamic mesh-less modeling with cross-coupling so as to best represent the impact of the projectile, the material deformation, and the projectile deformation. This analysis of elastic and plastic behavior, as well as bulk failure and separation, resulted in accurate depictions of deformation in both the projectile and target material, validating it as a model with the potential to simulate the impact of a Europa sample-return rocket penetrator. This analysis serves as a basis for future progress, and will soon be enhanced via further simulation in conjunction with ISAIL simulations so as to accurately depict the material deformation and ejecta plume. The data from these computer simulations can eventually be compared to physical experiments and field tests that are to be conducted under the University of Washington’s Kinematics and Impacts Laboratory (KILa).

Infectious diseases contribute to the death of over seventeen million people every year. Early detection of disease allows patients to seek care at earlier stages and improve health outcomes. Nucleic acid amplification tests (NAATs) are one strategy to detect pathogens present in low concentrations in biological samples. Unfortunately, current nucleic acid microfluidic diagnostic tests are expensive, require complex user steps, and take too long to be relevant at the point of care. The Yager Lab uses paper-based microfluidics to make low-cost, simple, and rapid NAATs suitable for the point of care. In order to control the flow rate of fluids, microfluidic devices often utilize chemicals, varied device geometries, and mechanical means as valving mechanisms. My research focuses on engineering a simple valving system for paper-based microfluidic NAATs which automatically delivers a biological sample into fibrous amplification pads after the sample is lysed. The valving system is comprised of a fatty acid wax plug and several layers of hydrophobic and hydrophilic paper-like materials within a laser-cut acrylic cartridge. When heated, the melted wax is absorbed by the hydrophobic layer and the fluid sample is able to flow into downstream pads for amplification of the pathogenic nucleic acids. Optimized through over 30 iterations, I designed a wax plug which could melt over a small heating region. The design had an average fluid release time of 47 seconds (standard deviation 8 seconds) and an average fluid delivery time of 15 seconds. For future designs, valve actuation time and fluid delivery time can be tuned by changing the length, shape, and volume of the wax channel. The development of this valving system will help aid the diagnostic community in the design of simpler and lower cost microfluidic systems, potentially expanding access to point-of-care NAATs and enabling widespread disease detection in low-resource settings.

Metacarpal and phalangeal fractures can be treated in a variety of surgical procedures ranging from k-wire fixation, plate/screw constructs, external fixation, or intramedullary fixation. All treatments must account for normal pressure loading, stability, and maintenance of normal tendon and ligament function. Intramedullary fixation has gathered interest as it has advantages in less surgical work, the cannulated screw being guided by a wire, shorter time of operation, no interference of soft tissue, and enough stability to immediately begin range of motion rehab. The crucial question is whether there is a change in pressures from joint contact and reaction forces of the proximal interphalangeal and metacarpophalangeal joint as a result of the articulating surface area due to this procedure. The methods of this study were comparing joint contact pressures in ten fresh-frozen cadaveric hands that I prepared before and after intramedullary fixation, and developing finite element models of the fingers. These have allowed more precise results of changes in joint contact pressures as well as testing of other conditions such as changes in joint pressure when the location of the hole in the joint is changed. Grasping forces were simulated by my attaching weights to flexor and extensor tendons while a pressure sensor inside the joint recorded forces. The anticipated result of this ongoing study is that placement of an intramedullary screw in the joint articular surface will increase contact pressures throughout regions of the joint that contact the articular defect. The significance of this study is that joint replacement research in cadavers has been shown to cause a change in contact pressures, however there is no literature detailing if this is true of the proximal interphalangeal and metacarpophalangeal joint. Once a CT-based finite element analysis model is validated by cadaver testing it will be usable for deeper research of finger surgery.

Many psychiatric disorders, including substance abuse, have been linked to risky decision-making, but the mechanisms underlying these pathologies remain unclear. Cortical intratelencephalic and pyramidal tract (PT) neurons have distinct projections, morphology, and firing properties, but their role in behavioral regulation remains unknown. PT neurons have been identified in the orbitofrontal cortex (OFC), which is known to be heavily involved in the cognitive process of decision making. Based on previous studies in our lab demonstrating that inactivation of PT neurons increases reward preference, we hypothesized that PT neuron inhibition would increase risky decision-making. To test this hypothesis, rats were trained on a risky-decision task (RDT) in which they were trained to lever press for a food pellet reward. In order to target PT neurons in the OFC, CAV2-CRE virus was bilaterally injected into the pontine reticular nucleus (PnC), and an inhibitory Designer Receptor Exclusively-Activated by Designer Drugs (DREADD; DIO-hM4Di) was injected bilaterally into the OFC; this strategy allows selective expression of DREADDs in PT neurons. In the RDT, two options were presented: a “risky” choice associated with descending probability of administration (100%, 50%, 25%, and 12.5%) for delivery of four food pellets, or a “safe” lever that always delivers one food pellet. To evaluate response flexibility, rats underwent a reversal task whereby five consecutive responses on the active lever switched the “active” lever to the previously inactive one. In both tasks, rats underwent two sessions: in the test session, animals received an injection clozapine-N-oxide (CNO) to activate DREADDs, and in the control session, animals received an injection of vehicle (DMSO). Interestingly, we found that inhibiting PT neurons did not significantly alter decision-making or reversal-learning. Future studies will monitor activity of PT neurons using in vivo calcium imaging to determine the contribution of this cell population to decision-making tasks.

Imidacloprid (IMI), a neonicotinoid insecticide, is being sought by shellfish growers to control burrowing shrimp (ghost shrimp, Neotropea californiensis) in Willapa Bay and Grays Harbor, Washington. The shrimp destabilize sediments resulting in poor survival and low yields of the commercially harvested Pacific oyster (Crassostrea gigas), threatening the local shellfish industry. A permit for the use of IMI has been denied by the State, Pacific County has declared an economic emergency, and the outcome of an appeal by the growers remains uncertain. We have undertaken studies to determine if un-iodized table salt may be an alternative to IMI, specifically targeting juvenile shrimp (recruits) inhabiting the upper 10-15 cm of the sediment. Studies in 2018 indicated that a 2-3-fold increase in salinity resulted in 100% mortality when juveniles were exposed in artificial seawater. In 2019, we exposed juveniles (3 replicates, 5 shrimp each) within 10 cm of native sediment to five different salt solutions to achieve sediment pore water salinities of 25 (ambient, control), 35, 50, 70, and 100 ppt. Salt solutions were prepared with native seawater, added on top of the sediment (depth = 2 cm), and allowed to percolate through the sediment column for 6 h (low tide). At 6 h, 2 cm of ambient seawater (25 ppt) were added to simulate tidal inundation and allowed to remain on the surface for 12 h (low-high + high low tide) with two subsequent drawdowns and tidal inundations at 25 ppt (total test duration = 48 h). The sediment was then sieved to remove the shrimp and determine mortality. Average survival of controls (25 ppt) was 73.3% whereas none of the shrimp exposed to elevated salinities survived. Additional tests are underway to examine different exposure scenarios. Results to date suggest table salt may be a viable and greener alternative to IMI.

The Hille Zebrafish Lab studies embryonic development and is particularly interested in cell motility and adhesion. We use zebrafish as a model organism due to its small size and rapid development, as well as for having clear embryos that allow researchers to observe somites form. One way that cells can crawl is through extending filopodia with actin microfilaments. The cell is anchored to other cells with adherens junctions and can push off against these anchor points, then form new adherens junctions with cadherin and other proteins. This method of walking is used for cells to move between other cells and is highly visible in premesoderm cell walking and somite formation. Cells need to regulate both elongation and adhesion, and a protein called p120 catenin activates both cadherins (which are needed for adhesions junctions) and the proteins RAC1 and CDC42 that stimulate motility through actin microfilament elongation and filopodia formation. Our hypothesis is that p120 catenins with phosphorylated tyrosines bind to Cadherins. In our mutant p120 RNA sequences, we test the activity of phosphorylatable residues by mimicking post-translational modifications with residues that can not be phosphorylated. For example, aspartic acid can mimic phosphorylated serine. Our lab has made and injected mutated mRNA sequences for p120 catenin to test if the mutant protein is able to rescue morpholino knocked-down embryos. We predict that if the tested amino acid is necessary for binding to a motility protein, then we will see rescue in phosphorylation mimics and no rescue in dephosphorylation mimics. My project was to make a p120 mutant that is missing most of the predicted regulatory amino acids. The truncated p120 sequence is called 4A and is a splice variant of wild type p120 that starts at the fourth methionine, omitting the regulatory region containing many phosphorylatabe sites.

Prior research has found that physical activity (PA) does not significantly predict academic achievement (AA) among college students. Studies have shown that PA buffers the effect of stress, while other studies have suggested stress has a negative impact on AA. Thus, stress can be a mediator of the relationship between PA and AA, which is commonly overlooked in studies. This study examines the mediation of stress in the relationship between physical activity and academic performance in college students. Behaviors incompatible to PA, such as TV and game/computer usage were also considered in the meditational analysis. For achieving this goal, 377 college students were recruited and completed a demographic survey and the State and Local Youth Risk Behavior Survey. The participants were 22.4 years old on average, predominantly female (76%), and mostly Caucasian (52%). In results, PA was significantly correlated to game/computer usage (r=-0.11, p<0.05), but not with TV usage (r=-0.03, ns). No significant direct relationship was found between PA and AA, but the indirect effect of PA on AA via stress was significant (z=-1.95, p<0.05). Likewise, game/computer usage had a significant indirect relationship with AA through stress (z=1.96, p<0.05). This indirect relationship was only significant in women (z=2.36, p<0.05), but not men. No significant direct and indirect effects were found for TV usage and AA. In conclusion, PA may enhance AA through its health and stress-reducing benefits. This provides an alternative explanation to prior research that couldn’t find a direct link between PA and AA; many different behavioral/psychological factors and their interrelationships need to be considered while investigating AA among students. Schools should consider ways to increase students’ physical activity such as using behavioral prompts on campus and increasing options for affordable transportation, thus reducing perceived levels of stress to enhance students’ academic performances.

Control of the cell-cycle is a topic of fundamental importance in cell biology. We are using the unicellular eukaryotic green alga Chlamydomonas reinhardtii to better understand how DNA damage affects transition of these cells in and out of the mitotic cell cycle. We find that UV treatment of cultures of C. reinhardtii gametes (in Go) delays re-entry of these cells into the mitotic cell cycle upon addition of nitrogen to cultures of gametes, a standard treatment which releases these cells to re-enter mitosis. Using a C. reinhardtii mutant which is unable to carry out photorepair of UV-induced DNA damage, we are characterizing the degree to which the kinetics of re-entry into mitosis depends on this very important repair system; we are thus beginning the 'parsing out' of the relative importance of the various DNA repair systems in controlling the transition from Go, a non-dividing stage, to G1,  the start of DNA replication and cell division. This will potentially provide insight into other downstream effects of UV exposure, such as mutagenesis. Our work is of a very basic nature, but with application to understanding e.g. dynamics of natural populations of microalgae in a changing global environment.

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.

Utilizing the Type III Secretion System (T3SS), Shigella spp. uses a cascade of proteins to manipulate, penetrate, and colonize host eukaryotic cells. Inducing epithelial necrosis, Shigella spp. infection is responsible for moderate to severe diarrhea in millions of children and immunocompromised individuals — the majority from low and middle income countries. Previous translational research for Shigella spp. has been limited due to a lack of robust in vitro and in vivo models to screen therapeutic efficacy. Understanding infectivity of Shigella spp. heavily relies on imprecise estimations of intracellular Shigella spp., which ultimately impacts vaccine and antibiotic efforts. This project aims to address this problem by developing a novel red intracellular reporter to quantify successful invasion of Shigella flexneri. By using a series of polymerase chain reaction (PCR) and Gibson assemblies, we have constructed a plasmid with a RFP reporter to be expressed during successful invasion of Shigella spp. The IpaH9.8 MxiE promoter, which has been shown to be expressed upon cell entry, is integrated within the pUltra RFP plasmid and electroporated into a streptomycin-resistant S. flexneri strain. We will test the recombinant strain in vitro by activating ipaH9.8 in broth culture and inoculating a mammalian cell line (HCT-8). RFP expression will be monitored with a BioTek FLX-800 plate reader and visually imaged using a FX-EVOS microscope. The expected outcomes of this project will provide an accurate and efficient method of quantifying invasive S. flexneri. in vitro and in vivo, as well as quantifying pharmacodynamics and pharmacokinetics of new treatment therapies. The implications of this project are crucial to the advancement of shigellosis research and in furthering the efforts of the international community to abate the steadily increasing cases of drug resistant shigellosis cases observed worldwide.

p120 catenin is an adherens junction-associated protein responsible for stimulating both cell adhesion, through interactions with RhoA and E-cadherin, and cell motility through interactions with Vav-2 and Cdc-42/Rac-1. Recent research in vitro has identified selective phosphorylation as a regulation mechanism for which pathway p120 catenin undergoes, but the results have yet to be replicated in vivo. Here, I specifically focus on the effects of phosphorylation of the tyrosine at 228 (Y228) on dorsal axis extension in zebrafish embryos during embryogenesis. This was accomplished through co-injection of mutant mRNAs Y228E (glutamic acid) and Y228F (phenylalanine) alongside an anti-sense splice-site morpholino specific to p120 catenin δ1. When compared to uninjected embryos, embryos injected with Y228E and morpholino exhibited much poorer dorsal axis extension whereas embryos injected with Y228F and morpholino exhibited relatively normal dorsal axis extension. These findings suggest that phosphorylation of p120 catenin at Y228 promotes interaction with RhoA and E-cadherin, thus reducing interaction with Vav-2 and Cdc-42/Rac-1 and limiting cell motility, although the specific pathway is still unclear. I shall further validate these findings through co-precipitation of mutant p120 catenin and its binding partners by preforming immunoprecipitation (ReCLIP) of proteins obtained from developing injected zebrafish embryos. As loss of E-cadherin function is closely associated with cancer progression, the ability to facilitate E-cadherin function through phosphorylation of p120 catenin at Y228 suggests a novel method and area of study for combatting cancer.

While medical education currently teaches students effective patient-provider communication, it lacks specific training for effective interactions between healthcare providers and patients diagnosed with communication disorders (PCDs), such as dysarthria from Parkinson’s disease. Poor patient-provider communication involving PCDs results in negative patient outcomes. PCDs are at increased risk for medical errors, often report a loss of autonomy, and are less satisfied with their healthcare services compared to those without communication disorders. To address this potential gap in medical education, a training program focused on improving patient-provider communication involving PCDs was conducted with second-year nursing students at the University of Washington. Pre- and post-training simulated medical interactions between nursing students and standardized patients trained to portray dysarthia from Parkinson’s disease were video-recorded. The purpose of this study was to evaluate preliminary inter- and intra-rater reliability of a newly developed rating tool designed to evaluate specific aspects of nursing student communication demonstrated pre- and post-training during these interactions. One speech-language pathologist (SLP) and two SLP graduate students volunteered to each rate a randomized series of twenty, 10-minute video-recorded interactions between nursing students and standardized patients portraying dysarthria. After watching a brief orientation video on how to use the instrument, the participants rated twenty videos, blinded to whether each video was pre- or post-training. Additionally, they were given two final videos to re-rate in order to assess intra-rater reliability. Data collection is still underway. However, after four initial videos were rated by all three raters, preliminary inter-rater reliability calculations have suggested a high level of reliability (ICC = .93). If the instrument demonstrates a high level of inter- and intra-rater reliability, we can use the results of these ratings in future research to validate the instrument and determine the effectiveness of the training program on improving patient-provider communication during medical interactions.

Harborview Medical Center performed 3230 regional blocks as primary anesthetic or postoperative analgesia for outpatient surgical procedures in the period of 2016-2017. In order to obtain a better understanding regarding the success of nerve blocks among patients, existing data on patient satisfaction and postoperative pain management was reviewed. Nurses followed up with patients the day after their procedure via phone call. A six question regional block questionnaire was presented responses were recorded and entered into the Hospital’s Patient Call Manager database (PCM). The PCM data was extracted and reviewed for the period between: January 1, 2016 to December 31, 2017. The primary outcomes I assessed were patient satisfaction, time of block wearing off and willingness to receive a nerve block again. I reviewed and analyzed one hundred and fifty-four responses. Fifty-four percent of patients reported being “very satisfied” while five percent of patients reported being “somewhat dissatisfied” with their postoperative pain relief. About two thirds of patients indicated that they would choose to have a nerve block if they were to have the same procedure again. Approximately three-fourth of patients started taking prescribed oral pain medications by postoperative day one. Ninety-one patients had no sensory motor impairment at the time of telephone call. Eighty-seven patients were very satisfied with overall recovery. Postoperative follow up data related to regional blocks were available for only five percent of patients, this likely has multifactorial causes including: patient demographics, language barriers for phone calls and lack of tagging patient charts who had a regional anesthetic. The available data, does indicate an overall satisfaction with regional anesthesia. This study demonstrates nerve blocks are a manageable and successful alternative to general anesthesia or narcotics in the setting of outpatient extremity procedures, a valuable finding which could benefit patients unable to use general anesthesia or narcotics.

The American crow (Corvus brachyrhynchos) emits a variety of vocalizations, but the meaning of these calls is not well understood. To better understand crow vocal communication, we tested whether the playback of call sequences with accelerated, decelerated, or randomized pauses, or bouts of silence between calls, caused different behavioral responses in wild crows. Previous research has shown that the pattern of silence between call syllables may code important information in this species. We manufactured crow vocal sequences using Audacity audio editing software to produce variations of the same overall sequence with differing pause rates. We then played them to crows on diurnal foraging areas in Western Washington and measured the latency to move towards the playback speaker, closest approach, and the number of crows responding. After 20 trials we detected non-significant trends suggesting an effect of pause rate. We are currently increasing our sample size in an attempt to resolve these trends.

The #MeToo movement has sparked a national conversation about what constitutes sexual consent, and a series of debates have erupted over the actions of famous men like Brett Kavanaugh, Louis C.K., and Aziz Ansari. Popular hits like Robin Thicke’s song “Blurred Lines” have also come under fire for promoting sexual violence by celebrating confusion around sexual consent. At this moment, when norms and expectations around sexual interactions seem to be changing quickly, it is especially important that we have comprehensive and systematic data on how people define sexual consent and interpret ambiguous sexual experiences. Existing studies have shown characteristics of an individual matter when it comes how they conceptualize appropriateness. However, we still do not know to what extent these characteristics matter. This study addresses this gap by answering the question: How do people of varying groups define appropriate sexual behaviors and boundaries? A Q-Method study of over 200 people will reveal how individuals of different characteristics sort scenarios of various sexual interactions into categories ranging from “most appropriate” to “most inappropriate.” Q method is similar to a rank-order techinque and allows for representation or reconstruction of perspectives concerning any given topic of interest. In addition to providing insight about how different people make sense of sexual behaviors, this study shows how Q-sorts can provide a more detailed look at sexual norms than the survey and vignette studies currently used in the field.

During the Cambrian Period, 541 Ma to 485.4 Ma, the radiation of animals generated substantial diversity and produced most extant phyla. However, there remains a poor understanding of nutrient cycling during this exciting evolutionary interval. Furthermore, the point at which Earth’s oceans became fully oxygenated – and widely amenable to animal life – is unknown. It thus remains unclear whether oxygen exerted the primary control on the distribution of animals during their early evolution in the Cambrian. In order to elucidate the dynamic between oxygen and early animal ecosystems, we examined the Mt. Isa drill core from the Georgina Basin, Australia, which intersects the exceptionally well-preserved ~510 Ma Currant Bush Limestone. We used measurements of organic carbon (δ¹³C_org) and nitrogen (δ¹⁵N) isotope ratios as proxies for oxygen and nutrient cycling in ancient marine environments. The preliminary data suggest that at ~510 Ma, the Georgina Basin water column was predominantly anoxic. Nitrogen isotope ratios (δ¹⁵N from 0 to -1%) are indicative of anaerobic N₂-fixation-dominated ecosystems. Ratios of total organic carbon to total nitrogen (25 to 30) also suggest anaerobic organic matter remineralization, as smaller ratios would be expected in well-oxygenated waters. Both of these signals are consistent with low ocean oxygen levels. The organic carbon isotope ratios (δ¹³C_org) range from -30% to -31%, consistent with carbon fixation by oxygenic photosynthesis, suggesting that oxygen production was insufficient to fully oxygenate seawater. Future work will explore whether these signs of anoxia correlate with organic biomarker proxies for eukaryotes, indicating animal abundance, from work done by our collaborators at Australian National University. Together, these data will clarify the ecology of this mid-Cambrian animal ecosystem.

 A method of negative-pulse partial modulation for comprehensive two-dimensional gas chromatography (GC×GC) using a pulse flow is studied. The capability of a pulse flow valve modulator has been shown to enhance many aspects of GC performance such as chemical selectivity and reduced analysis time, allowing complex GC×GC analysis in a shorter time scale. In our study, we explored a particular configuration of a pulse flow valve that periodically (specified by modulation period, P_M) disrupts the carrier gas flow to achieve partial modulation. This disruption of flow creates a "plug" of higher concentration on top of the primary GC signal, which is further separated in a secondary column. The size of the plug determined by pulse width, P_W, has a direct relationship to chemical selectivity and sensitivity. For our experiment, we determined the ideal P_W to be around 8 ms. Therefore, a 20-component mixture was evaluated using P_W of 8 ms and P_M of 100 ms, producing an average peak width, ²W_b, of 12 ms and approximated ideal peak capacity, ²n_c, of 8 on the second dimension. All 20 compounds were separated in a 12 second separation window. This powerful partial modulation method was achieved by the unique concept of the flow disruption with short modulation period, demonstrating high peak capacity and improved selectivity between compounds and chemical sensitivity. Due to the significant increase in GC performance, this form of partial modulation using a pulse flow valve allows efficient and faster GC×GC analysis that can be implemented in a variety of GC×GC applications.

As the Earth’s population rises, it is increasingly important to find new ways to manage food demands and pollution. One strategy is to use endophytes, which are organisms—usually fungi or bacteria—that naturally live within a plant. These microbes can help the plant in various ways, from nutrient acquisition to increased resilience in stressful environments. There are multitudes of applications for these organisms, as they can be transferred from one plant to another, thereby transferring these helpful qualities. My first project aims to explore the possibility of using bacteria to protect plants from fungal diseases. This would reduce the need for manmade pesticides, which can have, a high cost, many detrimental environmental effects, and susceptibility to fungal resistance. The effectiveness of an array of bacterial strains on different fungal plant pathogens has already been determined. Now, the anti-fungal chemicals secreted by the bacteria must be identified. To do so, each fungus and bacterium will be plated together, and the area of inhibition will be collected. The chemicals secreted will be extracted with methylene chloride, and characterized via mass spectrometry. My second project involves studying phytoremediation, which is the use of plants to remove or modify pollutants in the environment. Arsenic is a fairly common and toxic pollutant. It has been observed that the effective endophytes used for this remediation produce a biofilm when in contact with arsenic. This biofilm production has not been quantified, and it is unclear if or how it affects the phytoremediation process. One possibility is that the bacteria sequester arsenic in the biofilm, potentially reducing the phytotoxic effects on the host plant. This second project will determine the production rate of biofilm and how that changes when exposed to arsenic.

Causal inference is a large and long-standing field that attempts to answer a very fundamental question: does X cause Y? This question arises in many fields such as healthcare, genomics, biology, and econometrics. The complex systems analyzed in these fields often have many interacting components mathematically represented as nodes and edges (connectivity) of a network. Network inference is the study of the time-dependent behavior of these nodes to reverse-engineer the network connectivity. The theory of causal inference has many contending definitions of causality such as state-of-the-art techniques Granger Causality (GC) and Convergent Cross Mapping (CCM). These algorithms are computationally tractable and easy to use but require strong mathematical assumptions. We simulate networks of harmonic and Kuramoto oscillators and attempt to reconstruct their ground-truth network structure using observations of oscillator displacements over time. Our analysis investigates the performance of inference methods on Erdos-Renyi and scale-free random graphs. We show that the GC and CCM inference methods systematically fail to determine network structure by returning overly sparse or dense connectivity results. These findings challenge the applications of such top-down inference approaches to physical and biological systems. Using a few basic assumptions, we demonstrate how networked systems of coupled oscillators can be successfully reconstructed if perturbations of the system are allowed. We propose a Perturbation Causal Inference (PCI) algorithm that uses systematic perturbations and tracks how perturbation cascades spread through the network. Using changepoint detection, correlation, and windowed variance statistics, we predict causal relationships between nodes in the graph. Our analysis shows that PCI works at scale and efficiently returns high accuracy reconstructions of large networks with varying coupling strengths and connectivity structures. We conclude by proposing future applications of perturbation inference methods into neuroscience and make a connection with Hebbian learning rules.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by elevated inflammatory mediators, bone resorption, and cartilage destruction. These changes are caused in part by fibroblasts, which invade cartilage and amplify inflammation by producing a variety of cytokines and chemokines. Previous research suggests that activation of the receptor tyrosine kinases platelet-derived growth factor receptors (PDGFRs) may play a major role in fibroblast expansion and invasion in RA. These receptors are homo- or heterodimers composed of α or β subunits, and can be stimulated by five different ligands. Although the signaling pathways activated by PDGFR-α and PDGFR-β are very similar, they have been shown to play different roles in disease models. We propose that PDGFR-α and PDGFR-β activation produce independent responses in joint (synovial) fibroblasts, depending on both receptor signaling and ligand availability, contributing to their different roles in disease. We found activation of both receptors stimulated fibroblast proliferation and recycling of Cad-11, a cell-to-cell adhesion molecule that plays an important role in the signaling that produces the inflammatory response. This was found by comparing receptor phosphorylation data from Western Blot, ELISA, and flow cytometry experiments. However, when silencing PDGFRs with a multi-tyrosine kinase inhibitor, only PDGFR-α was found to affect Cad-11, meaning Cad-11 likely works through PDGFR-α to regulate cell proliferation. In contrast, PDGFR-β activation has been shown to induce a more motile morphology change in immunofluorescence experiments with 3D cell cultures. qRT-PCR experiments have also provided evidence that the same cell lines stimulated with different ligands resulted in distinct genotypes. These results support our hypothesis that PDGFR-α and PDGFR-β may have unique functions in synovial fibroblasts that contribute to RA pathology.

 The Diabetes Community Care Ambassador (DCCA) Program represents a promising intervention for improving glycemic control in youth with type 1 diabetes (T1D) struggling with diabetes management. In this novel program, lay health workers called DCCAs supported youth with T1D with poor glycemic control (HbA1 >8.5%) and their caregivers through home visits, school visits, and phone support, and connected participants with legal support. Given the findings that youth with T1D in the DCCA Program demonstrated improved glycemic control, we carried out a follow up qualitative study to understand the salient components of the DCCA program that promoted improved diabetes self-management from the youth and caregiver participant perspectives. We conducted semi-structured exit interviews with a subset of DCCA Program participants (18 caregivers, 14 youth). Participants reported on how the DCCA was helpful in supporting the youth’s diabetes management and how DCCA support compared to care provided by the multidisciplinary diabetes care team. A qualitative content analysis was carried out and emergent themes were identified. We found that within the home environment, participants felt the DCCAs helped youth address underlying weaknesses in their diabetes management routine and provided accountability for self-care goals between visits with their diabetes provider. DCCAs also provided psychosocial support that youth and caregivers believed they did not sufficiently receive from their usual multidisciplinary diabetes care team. At school, caregivers, in particular, felt that DCCAs successfully advocated on behalf of the student’s interests to facilitate diabetes management at school and also provided diabetes education to school staff. Finally in the community setting, caregivers shared that DCCAs helped to connect them to legal and support resources and better navigate the healthcare system. Our study results highlight the value of using lay health workers in providing individualized assistance for youth with T1D in supporting diabetes management outside of the ambulatory care setting.

Microplastics are fragments of plastic smaller than five millimeters in length, often created by the breakdown of larger plastic materials. The ubiquitous presence of this form of debris in marine environments has led to detrimental effects when ingested by marine organisms including false sense of fullness, impaired reproduction, and stunted growth. Microplastics are heterogeneously distributed in water, animals, and sediment, making it necessary to compare and contrast conditions when considering any biological effects. Due to the variability of microplastics across space and time, different locations may have varying types and sizes of microplastics. This study examines the relationship between anthropogenic activity and microplastics in areas ranging from low to high population density in the Salish Sea. In July and August of 2018, samples of mussels, water, and sediment were collected from ten sites around the Salish Sea. The samples were chemically digested with hydrogen peroxide over a five-micrometer filter. Debris collected by the filters was photographed through a microscope and subsequently characterized. The images were processed using ImageJ for length, width, shape (fiber, fragment, film, or sphere), and color. We hypothesized sites have different microplastic compositions and there is a correlation between anthropogenic activity and microplastic abundance. The results of this study could aid in efforts to locate point sources of specific types of microplastics in the Salish Sea and determine priority locations for marine debris management.

With an increasing demand for more complex and efficient structures, the world is in need of more structural engineers. I have been developing educational tools to make structural engineering more intuitive, tactile, and approachable. Using K’Nex, a readily available construction toy system, I build structures accompanied by computer models to illustrate key structural engineering principles. These products will aid in the education and promotion of structural engineering and are targeted towards children and undergraduates students. This research involves the investigating of physical properties of K’Nex members in order to create accurate numerical (computer) models. Experiments include load tests to determine material properties, buckling stresses, and failure modes. Many of these tests are designed to be approachable and can be performed using everyday household objects. Numerical models are created in MATLAB and are used to predict behaviors under certain load combinations, as well as highlight shortcomings of simplified elastic theory. The results and methodology of this research are designed to focus on building an intuition and interest for structural engineering.

The North Creek Wetlands Restoration on the University of Washington Bothell campus is host to a communal crow roost, with upwards of 16000 crows in the autumn and winter and significantly fewer during the spring and early summer. Crows congregate in larger and larger groups, called pre-roost aggregations, as they approach their roost each night. The function of these aggregations is not yet clear. We set up a night vision video camera and four audio recorders to observe the social behavior of crows on a pre-roost aggregation on the roof of Discovery Hall, adjacent to the aforementioned communal roosting site. The average duration of stay at this pre-roost aggregation was 24 minutes. We assessed video footage using a mix of scan and ad libitum sampling with a focus on aggressive interactions. We defined aggressive interactions between crows as approaching, pecking, and tail and wing pulling. I compared the frequency of these interactions for crows in the breeding and non-breeding seasons. Preliminary analyses suggest a significant increase in tail pulling during breeding (2.9 +/- 0.8) as compared non-breeding periods (0.3 +/- 0.3), but no differences in approaching, pecking, and wing pulling between these life history stages. I am currently increasing my sample size to better discern any differences, and am beginning to investigate social dynamics in pre-roost aggregations using social network analyses.

The tumor microenvironment (TME) dictates the outcome of many immuno-oncology therapies for solid tumors. To better understand the dynamic milieu of the TME, new multiplexed, spatially-resolved histologic techniques are being developed. A key limitation to evolving these techniques is identifying specific and selective antibodies that perform well in an immunohistochemistry (IHC) platform. The over-arching goal of this project is to develop a flexible, high-throughput platform to empirically test the IHC staining characteristics of antibodies in formalin-fixed paraffin-embedded (FFPE) tissues with improved throughput and lower test volumes. Essential elements in our platform design include: 1) flexibility to test a variety of biologic materials, which is dependent on the test antigen, 2) compatibility with manual and semi-automatic tissue microarray (TMA) builder, 3) easy use for pathologic assessment, and 4) future compatibility with fully-automated tissue staining instrumentation. Using computer-aided design software, and a stereolithography printer, we prototyped a guide template to build recipient TMA FFPE blocks. To screen for a variety of antigens in TMA "cores", we prepared cell lines, and acquired mouse tumor xenografts and human tissues. Standard IHC techniques were used to screen hybridoma supernatants generated from mouse immunizations. We have designed and tested six different multi-well slide-based IHC screening platforms. The current format consists of a six by four array of 2 mm cores. We have screened antibodies from two different mouse hybridoma campaigns. Thus far, we have identified candidate IHC antibodies for exogenous epitopes to identify chimeric antigen receptor T cells used to treat solid tumors, and a fusion protein hypothesized to be an oncogene in pediatric liver cancer. This project developed a single-slide antibody screening prototype for IHC. The device offers the flexibility to test multitude of tissues, and is built with design considerations for future automated tissue staining compatibility.

Research has shown that wildfire smoke exposure is associated with various respiratory health effects. To help protect the lungs, respirator masks that are labeled as N95 can be worn to filter out fine particulate matter produced from wildfire smoke. Previous studies show that video-based education is effective in increasing knowledge and intervention practices among viewers, and it was hypothesized that an N95 mask instructional video could help educate the lay-public. A video-content needs assessment was conducted using semi-structured key informant interviews. Eight experts knowledgeable in air quality, message communication, N95 respirators, and respiratory and cardiovascular health were interviewed for important content needs. Response themes were identified and used to inform the content and style of the video entitled, Smoke from Fires: N-95 Respirator Masks. A Knowledge, Attitude, and Practice (KAP) survey, using a 5-point likert scale, was created to assess the video’s knowledge transference, and effect on attitudes and commitment to practice use. The KAP survey was given to undergraduate students before and after viewing the video. The results from our key informant interviews included instruction on proper use, mask limitations, incorrect alternatives, and appropriate use of language, images, and tone. The KAP survey results indicate the video enhanced the participants’ knowledge of N95 masks with regards to proper fit, incorrect alternatives, and limitations. Additionally, attitudes of increased ease of use and mask effectiveness were demonstrated. Since this study investigated a video-based intervention, possible future research includes testing the effectiveness of different education methods on N95 mask fit, in addition to knowledge, attitudes, and commitment to practice.

Mycobacterium tuberculosis (Mtb) is a bacterium that can cause both latent Mtb infection (LTBI) and tuberculosis disease (TB). LTBI affects one quarter of the world’s population of those who are LTBI positive, 5-10% develop TB disease which left untreated can be fatal. Most individuals who are highly exposed to Mtb develop LTBI and show positive results for the tuberculin skin test (TST) or interferon-g release assay (IGRA). The Hawn lab has followed a cohort of Ugandans with heavy exposure to Mtb within the household but test negative by the TST and IGRA tests and define these individuals as Mtb 'resisters'. The presence of these Mtb ‘resister’ genes suggests a possible pathway for host directed therapies. Using transcriptomic profiling to compare the ex vivo Mtb response in LTBI and resister monocytes, several candidate resister genes were identified. We hypothesized that these candidate resister genes modulate antimicrobial functions through an effect on pro-inflammatory cytokine secretion which restricts Mtb growth. Individual ‘resister’ genes were inactivated by CRISPR/Cas9 gene editing in THP-1 cells and then differentiated into macrophage-like cells prior to various stimulations. Macrophage signaling pathways were stimulated with LPS (Toll-like Receptor 4 (TLR4)), PAM3 (TLR2/1) as well as with whole cell lysate from Mtb. I measured pro-inflammatory cytokine secretion in supernatants after 24h (IL-6, IL-1b, and TNF-a). We identified two genes, SETDB1 and NFIL3_03, that may differentially regulate pro-inflammatory cytokines compared to the control THP-1 cells. By uncovering the function of these genes, we hope to better understand how Mtb infections can result in variable immunopathogenesis.

We have built an air quality sensor to track smoke from wildfires at UW’s Manastash Ridge Observatory (MRO). The increasing number of wildfires over the last few years has raised concern that smoke may contaminate the telescope optics at MRO. Our goal is to measure the amount of smoke in the air at the site in real time. Our design consists of an Adafruit micro-controller connected to two dust sensors that connect to Wi-fi. We interviewed Edmund Seto, a professor at UW, since he has much more experience with building sensors. He suggested that we use multiple of the same device so that we could average the data or have a backup sensor if one were to stop working. Using Arduino code and Adafruit.io, we were able to code the micro-controller and connect the data to a Wifi-interface so we could watch the data come in. We are currently field testing the sensor in Seattle, but we expect to permanently install at the MRO this summer.

As climate change progresses, predictions of long lasting and severe droughts are projected to affect many communities. These communities are encouraged to utilize food resources that produce high yields for sustainability. Learning the key physiological differences between drought tolerant and sensitive plants may help communities like this adapt. A key difference between tolerant and sensitive plants is the efficiency of sugar mobilization. Drought sensitive plants tend to hinder mobilization of sugars while drought tolerant plants maintain this sugar flow. Here, our objective is to locate and understand where the mobilization of sugars is bottle-necked in the sensitive plants, and how that differs for tolerant plants. We hypothesize that more drought-tolerant plants display an increase in sugar mobilization resulting in higher fruit yield, faster rate of seed filling/fruit formation, and an overall greater rate of plant growth as compared to drought-sensitive plants. Our experimental protocol consists of eight different genetic lines ranging in sensitivity to drought. By reducing soil moisture content to 50%, we will induce drought and start measuring growth rates of the middle leaflet of the third trifoliate, pod elongation, seed length, and biomass of different plant tissues to determine the bottleneck of carbon and sugar movement in all lines. By contrasting this net movement of sugars across lines, we hope to observe differences indicating physiological mechanisms distinguishing tolerant from sensitive lines. Understanding these differences would help educate and improve communities who are affected by drought due to increasing climate change and overall help improve sustainability of crop production.

Hypoxic-ischemic encephalopathy (HIE) and inflammatory responses are commonly seen in premature infants which can lead to cognitive delay and behavioral problems. A novel rodent preterm brain injury model is being developed to simulate histological and behavioral changes seen in preterm brain injury. It was hypothesized that injured pups [(in-utero hypoxia-ischemia followed by post-natal inflammation with lipopolysaccharide (LPS) + hypoxia + hyperoxia] will have a significant late behavioral deficit compared to controls. The rodent model of preterm brain injury includes: intrauterine hypoxia at embryological day 18, with LPS administration on Postnatal (P) day 2 followed by hypoxia (8% oxygen) and hyperoxia (80% oxygen). In order to assess late behavioral effect of early neonatal injury, I conducted motor tests on rats. The motor testing included: gait analysis via CatWalk XT and Rotarod analysis. For the Rotarod analysis, I performed testing on both, the injured rats and controls, on P28 to test their locomotor ability. Gait analysis was performed on P35. The results will be tested for significant differences between the groups. Future research will be conducted by repeating this experiment to verify these results and clarify what aspects of late behavior are impacted most by this injury model.

Metal-organic frameworks (MOFs) represent an important new class of adsorbent materials, catalysts, and catalytic supports. As such, it is important to fundamentally understand its adsorption capacity and selectivity of simple gases. NU-1000 is a prototypic zirconium-based MOF which has shown to be thermally stable up to 250 C and has a number of interesting catalytic and adsorbent properties. It is composed of zirconium oxide nodes connected by pyrene linkers with COO- end groups. We determined the isosteric heats of adsorption (Qst) versus coverage of four gases (N2, CO, Ar, and CH4) on NU-1000 by measuring volume-pressure equilibrium isotherms at very low coverages (under 0.1 monolayer) and above 90K. We then compared our experimental measurements to density functional theory (DFT) calculations of adsorption enthalpies at 77 K for the zero-coverage adsorption of the same gases at seven different types of sites of the MOF lattice. These comparisons showed remarkable agreement between the measured and theoretical isosteric heats in trend as well as reasonable agreement in magnitude, indicating that the sites predicted by DFT calculations are populated sequentially in order of decreasing absolute enthalpyt. This study further increased our understanding of adsorption on this prototype MOF at very low coverages and reaffirmed the accuracy of theoretical calculations.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by clinically recognized deficits in social communication, repetitive behaviors, and restricted interests. While the etiological underpinnings of ASD have yet to be determined, biological indicators of the disorder (e.g. biomarkers) hold promise as valuable diagnostic methods. Neurological biomarker initiatives are particularly essential in their potential to pinpoint the neural activity that gives rise to the disorder’s hallmarks. Resting state electroencephalography (EEG) studies suggest altered default signaling associated with ASD, with particular deviations in the power of the alpha frequency band. However, previous work has produced contradictory findings regarding the directionality of these abnormal power patterns, which motivate the need to better understand the implications of certain methodological decisions. In this study, we acquired EEG recordings during resting state paradigms in individuals with ASD and a neurotypical control group. We hypothesized that individuals with ASD would display reduced alpha activity, in comparison. We suspect that activity will be reduced, both when analyzed by peak power and average power over the entire frequency band.

In paper manufacturing, the paper break is defined by when the paper being made on the paper-making machine ruptures while passing through the machine. Regarding the fact that paper break cost significantly for the paper manufacturing due to the resumption, the goal is to predict the rare event which is the unwanted paper break and find out the variable that causes this rare event using machine learning techniques. The data given by the stakeholder is a multivariate time series (MTS) data which contains sixty-one variables with 18398 records. There are four major models used in this research, which are logistic regression, LASSO, decision tree, and random forest model, examined in this report. Simultaneously, the testing tools like k-fold cross-validation, confusion model, ROC curve are used to improve the models. As a result, after comparing the results from these four models, random forest turns out to be the most suitable model to predict the multivariate time series data collected from the paper manufacturing. Our best model has 99.36% accuracy. The model prediction of the rare event can find out the variables that cause paper break as well predict the break before it happens. The prevention of the break could save cost and time. As a result, the efficiency could be improved.

Cysteine is an infrequently occurring but important amino acid critical to tertiary and quaternary structure. While peptide chains typically undergo post-translational modifications, cysteine is susceptible to further modification due to its reactive thiol group. The effects of these modifications are unclear, as they could either represent normal cell-cell communication or potentially harmful by-products. Common agents that affect the thiol group of cysteine are by-products from other biological processes, for example metabolic processes (which creates H₂O₂), natural toxicant defense (p450 or glutathione), and inflammation (HOCl). This experiment sought to discern the products that form when cysteine is exposed to biologically relevant concentrations of these oxidants. Liquid chromatography-mass spectrometry (LC-MS) was used to perform the analysis of the oxidation products. Cysteine was mixed with 5 mM bleach in vitro and pH buffered and the resulting solution was analyzed. Methods were developed by optimizing instrumental conditions—including molarity of solutions, voltage spray and flow rate, and acidity of the samples—in order to use LC-MS. Pending results will allow for the identification and quantity of the cysteine oxidation products.

Skin plays an important function as a highly innervated sensory organ. This sensory function is critical to organism survival, but the skin, and its axons, are easily damaged and need to be repaired to maintain homeostasis. Zebrafish are an excellent model to study tissue repair because they regenerate tissue efficiently and share conserved skin architecture with other vertebrates. A cell type shown in previous lab experiments to contribute to skin repair is a macrophage like cell, the Langerhans Cell. I hypothesize that if Langerhans Cells are not present within zebrafish epidermis then tissue repair will be incomplete or delayed. I investigated these cells using two different methods. First, I analyzed mutations that cause a loss of function in genes required for Langerhans Cell development. Second, I used the transgenic ablation technique to inducibly kill Langerhans Cells in the skin by addition of the antibiotic metronidazole. I imaged fluorescent Langerhans Cells in the zebrafish epidermis in both of these genetic scenarios to quantify the reduction in Langerhans Cells. Following the completion of these experiments, we expect to see that a lack of Langerhans Cells will induce slower or halted recovery from damage. In the loss of function method, I expect that various mutants will not have as many Langerhans Cells and that following induced ablation, Langerhans Cells will die out when the drug is introduced and slowly recover following metronidazole removal. The key implication of this is finding more about our own biology that can lead to faster healing. In theory, if Langerhans Cells have a major effect on this process then knowing more about our own skin can help us translate this understanding to our own healing process.

G-protein coupled receptors (GPCRs) - characterized by seven transmembrane alpha helical domains - are the largest family of membrane proteins, constituting ~1% of the human genome. The α1D-adrenergic receptor (A1DAR) is a GPCR that regulates function of the cardiovascular, urinary, and central nervous systems. Dysfunction of this receptor can lead to various diseases including schizophrenia, benign prostate hypertrophy, hypertension, and PTSD. Prazosin, a non-specific α1-antagonist is the first line treatment for PTSD, however, chronic use has deleterious side effects including orthostatic hypotension and potentially fatal reflex tachycardia due to interactions with off-target related receptors. Thus, understanding how A1DARs are regulated will allow for the development of targeted therapeutics. To this end, the Hague Lab has previously discovered that A1DAR undergoes an endogenous cleavage of its extracellular N-terminal domain, affecting its membrane localization and response to agonist stimulation. Located within the N-terminal domain of A1DAR are two glycosylation sites at amino acids 65 and 82. Currently, how glycosylation of these sites regulates the cleavage event remains unknown. To characterize this phenomena, I used molecular cloning to mutate the glycosylation sites of A1DAR in the pSNAP vector for expression in Human Embryonic Kidney 293 (HEK293) cells. Near Infrared PAGE analysis revealed that glycosylation of both amino acids is required for cleavage and proper expression of A1DAR. Sucrose density gradient and dynamic mass redistribution further showed that glycosylation controls function and trafficking of A1DAR to the membrane. These results allow for the development of targeted medications specific to the N-terminal glycosylation sites of A1DAR, further reducing the potential side effects experienced by patients.

My research is a case study of coseismic landslides triggered by the M6.9 earthquake in Loma Prieta, California on 17 October 1989. Coseismic landslides bring deadly consequences, often resulting in more casualties and infrastructure damage than from the earthquake directly. In addition, coseismic landslides are understudied geomorphic features and are difficult to predict, resulting in a high safety hazard. My study area, located in the Forest of Nisene Marks State Park, California, a regional park in the Santa Cruz Mountains where the earthquake shaking was strongest, includes over a hundred coseismic landslides triggered from the 1989 earthquake. I am using geographic information systems (GIS) software to map and analyze the landslides on a high-resolution LiDAR Digital Elevation Model (DEM) and using data from the United States Geological Survey to create an inventory of the Loma Prieta coseismic landslides. This dataset will be compared against seismic shaking strength estimates and local lithology to look for spatial patterns in sliding. I am also using this dataset, an event of known age, to test a recently developed landslides Surface Roughness - Age model. I expect to find that the zones with greatest seismic shaking produced the most or biggest landslides, certain lithologies are prones to greatest failure, and that the 1989 coseismic landslides currently have approximately equal surface roughness. Learning how certain lithologies respond to seismic shaking will help predict future coseismic landslides, and evaluating the current surface roughness will help validate, or invalidate, the Surface Roughness - Age model.

How does one live an ethical and equitable life in the midst of a unequal world? Industrialization and globalization has created a hierarchy of wealth, giving the upper hand to the Global North while exploiting the Global South for cheap labor and lenient laws. As a result of this unequal reality that we live in, the Handcraft Movement was born in India. A modern adaptation of the Swadeshi Movement, a social crusade led by Mahatma Gandhi during the time of British colonization, the Handcraft Movement supports the self-sustaining nature of the handcrafting industry. It promotes the belief of staying, buying, and sourcing locally, ultimately redirecting the power to the people rather than to the large corporations. My interests lie in evaluating the social, economic, and political impacts this movement has had on this region but also on a global scale. To show the global effects, I lightly touched upon the parallel but differently located handcrafting industry found in the Pacific Northwest in order to better understand how value is ascribed due to locality rather than by sheer input. Gaining insight through interviews as well as with participant observation and photography, I have gained a more comprehensive perspective into the complexity behind how we as people ascribe value to materials in addition to seeing how this ascription has caused either failure or success in the handcraft industry. An ever evovling understanding, this project meerly scratches the surface of the significance of value and the subjectivity of this term. Acknowledging this complexity then allows for us as consumers and communities to better appreciate and more consciously participate in a globalized society.

Autism Spectrum Disorder (ASD) is a collection of neurodevelopmental disorders characterized by social-communicative and behavioral impairments that affects approximately 1 in 59 children in the US. Children with ASD, on average, exhibit increased rates of externalizing behaviors compared to their typically developing peers. Studies have shown that children with relatively low familial risk for ASD are more likely to develop ASD if they have a history of pregnancy complications and that presence of pregnancy or birth complication can exacerbate the severity of externalizing behaviors. In typical development, pregnancy complications are associated with a number of child psychiatric disorders and externalizing behaviors and males have increased levels of externalizing behaviors compared to females. In a sample of children with ASD, this study (1) investigated the relationship between pregnancy complications and externalizing behaviors and (2) compared sex differences in externalizing behaviors. The study involved 200 children with and without pregnancy complications, between the ages of 8 and 17 years. Pregnancy complications were provided by the parent during a medical history interview and refer to a wide range of complications including, among other things, health concerns for the mother or child, difficult birth, or coexisting pregnancy diagnosis such as gestational diabetes or preeclampsia. To assess for externalizing problems, parents of participants completed the Behavior Rating Inventory of Executive Functioning (BRIEF) questionnaire about their child. We predict that ASD children (1) with pregnancy complications (compared to those without complications) will demonstrate more externalizing behavior problems and (2) males with ASD will exhibit more externalizing behavior problems than females in the subscale mean scores. The results of this study provide insight to the connection between pregnancy complication and externalizing behaviors in children with ASD.

To keep peace with increasing world energy demands, scientific research has shifted to devising sustainable energy alternatives. Unlike widely used fossil fuels, solar energy is carbon-free and globally abundant, and therefore a promising energy supplement to aid global efforts in reducing anthropogenic carbon footprint. My project sought to employ light-harvesting colloidal semiconductor nanoparticles, namely quantum dots (QDs), to drive the energy-intensive depolymerization of lignocellulosic biomass and to store solar energy in chemical bonds. Accounting for 40% of biomass’ energy content, lignin is one of few naturally existing polymers composed of valuable functionalized aromatic species and is the target substrate for the decomposition reaction. Recently, iridium-based catalysts have been used to cleave β-O-4 linkages (predominant C-O lignin linkers), however, iridium’s high cost and poor long-term stability hinder its utility in extensive production and application. In contrast, prior work from my research team has demonstrated that QD photocatalysts boast lower synthetic costs, higher turnover frequencies (up to 15x faster), lower catalyst loading (333x less catalyst), and various traits desirable for industrial reproduction over iridium. Beyond QDs, my studies also looked at the synthesis of anisotropic nanoparticle photocatalysts such as nanorods and nanotetrapods. QDs are quantum confined, meaning photoexcited, oppositely-charged electrons and holes (electrons’ counter charges) recombine quickly in all dimensions, which endows them with size-tunable semiconductor functionalities. Nanorods and tetrapods are quantum confined in the width but not along the length dimension, which delays the recombination of paired electrons and holes (excitons). This elongated exciton lifetime allows more time for substrates to interact with our nanomaterials which facilitates photocatalysis. As pioneers in studying photoredox-active nanomaterials, we were motivated to decipher how nanomaterial design dictates photocatalytic performance, which not only furthers the search for most efficient photocatalysts but advances contemporary research on effectively using solar energy to derive solutions to presently-unfeasible, energy-demanding reactions.

Many people in today’s society do not devote enough time to enjoy the food they are eating, consuming their food with their attention devoted to phones or television screens, and in some instances even finishing their food without realizing how much they have eaten. This is especially prevalent in people who regularly eat alone, falsely believing that multitasking will increase their productivity. In this design research project, we investigate the problem of people’s lack of focus while eating with the goal of using our design insights to develop technological solutions to help people be intentional, mindful, and present when they eat. Our work is grounded in the premise that mindful eating provides health benefits and is a gentle and approachable way to introduce mindfulness into people’s lives. Our design process follows the established practice of exploration, divergent ideation, and then convergence, with an added reflection component. Specifically, we first explore the problem space by gaining a deep understanding of the relevant literature on mindfulness, multitasking, and the interactions between meals and technology, followed by conducting several user interviews about the problem. These interviews are with college students and other individuals who tend to eat alone in their homes. We then use divergent thinking to ideate many possible, diverse solutions, for example, a phone application, use of smart home technology, a standalone physical object. From there, we converge on a few candidate solutions and analyze the implications—positive and negative— of each. Design reflections consider not only the design outcomes but also our design process and key points in that design process. Our work contributes to a growing body of design research concerned with Slow Design, distraction, and mindfulness.

Electronic health records (EHRs) are often used by clinical and data researchers in numerous ways for various scientific investigations. When sharing patient information, certain precautions must be followed as to prevent the risk of a malicious actor being able to extract sensitive information. This study examines an experimental method of removing potentially identifiable information from free text medical notes by finding and removing phrases which are statistically uncommon. Furthermore, this study assesses if this method reduces risk of identification while also maintaining the utility of the data. The method involves analyzing a free-text dataset by first breaking all text up into fixed length phrases. The frequencies of these phrases are then tracked across the entire dataset on a per-patient, per-note, and dataset-wide basis. To benchmark the method, notes are de-identified using the method and privacy and utility are tested under different conditions. The results from using this method on real clinical notes are expected to produce text that will not only be more secure but will also retain information useful for applications such as machine learning, natural language processing, and data analysis. If this method proves to be successful, it could lead to institutions being able to share medical notes with researchers more easily. This in turn would eliminate a major obstacle which medical researchers face, as it would give them access to more data. Finally, when data are shared between institutions for research, the risk of identification can be represented as an objective and quantifiable metric.

Sea ice, frozen ocean water, in the Arctic is declining due to climate change. This is getting more attention, since sea ice can substantially affect wildlife, ecosystems, and human society. Sea ice extent, a measure of the surface area of the ocean covered by sea ice, is used to monitor the environment. A good sea ice extent model can benefit not only studies of the Arctic but also the global economy, as many ships use the Arctic area as part of their route. There are various sea ice extent models in the science community that give good estimates of sea ice extent. However, there are instances where their predictions do not match observations. My research explores bias correction methods that help predictions to match observations and compares the performance of sea ice models after bias correction. In this analysis, I consider the performance of a sea ice model produced by the Geophysical Fluid Dynamics Laboratory using boxplots and rank histograms. This work helps show the value of bias correction. I will compare the performence of the models to identify in what month and in what location models predict well. This information will support improved prediction of the Arctic going forward. 

There has been growing concern regarding rising carbon dioxide concentration in the atmosphere because CO₂ traps excessive heat and warms the planet through the greenhouse effect. One strategy to mitigate this problem is through the capture and conversion of CO₂ via hydrogenation to fuels and chemical feedstocks that are currently produced from fossil fuels. Given the complexity of these multi-electron, multi-proton transformations and the multitude of products that can result, catalysts are required to lower the energy barrier and direct the selectivity of CO₂ conversion reactions. One catalyst currently under development is a Ru(II) bis-(protic N-heterocyclic carbene) phosphine catalyst, which incorporates protic N-H wingtips adjacent to the metal center. The N-H wingtips are an interesting feature due to their ability to activate CO₂ through metal-ligand cooperation, their accessibility as a proton source near a metal active center, and the likelihood that they aid in splitting H₂ between the metal center and the nitrogen. Preliminary results have shown moderate turnover numbers (TONs) for both formate (130) and methanol (7), the latter of which is a rare transformation in a single catalyst system. In order to improve catalytic TONs and understand the role of protic N-H wingtips, a library of catalysts with varying ancillary ligands, including 2,2’-bipyridine, 4,4’-dimethoxy-2,2’-bipyridine (electron donating), 4,4’-dibromo-2,2’-bipyridine (electron withdrawing), and 1,2 bis(diphenylphosphino)ethane (sterics), is synthesized and screened under high pressure and temperature conditions using THF solvent and varying additives (e.g. Li₃PO, K₃PO₄, KPF₆) and additive concentration. It is expected that the ancillary ligands, bound trans to the bis-carbenes, will influence the proton donor ability of the N-H wingtips and catalytic turnover.