Ammonia-oxidizing archaea and bacteria (AOA, AOB) are important contributors to soil ecosystem function, as they convert nitrogen (N) as ammonium (NH4+) into nitrate (NO3-), a more readily available form for plant uptake. This study examines the abundance of AOA and AOB in forest soils of the Pacific Northwest that have experienced wildfire 31, 7, and 5 years previously. Charcoal, a common residue of wildfire, may play a significant role in stimulating nitrification in soils, possibly by adsorbing monoterpenes that may inhibit mono-oxegynase activity in nitrifying organisms. The goal of this study was twofold. We first hypothesized that charcoal would increase the quantity and quality of AOB and/or AOA in wildfire-affected soils. To test this hypothesis, we extracted and compared DNA between burned and unburned sites using real-time quantitative polymerase chain reaction (RT-qPCR). We expect to find a greater abundance of AOA and AOB nucleotides in the burned sites indicated by qPCR, and a larger array of species indicated by DGGE analysis. Secondly, we will introduce monoterpenes (α-pinene) into soils with charcoal present, and soils void of charcoal to assess the interaction between the terpenes and charcoal surfaces. We hypothesize that the addition of terpene will readily adsorb onto charcoal surfaces. Therefore, burned soils will show reduced nitrification inhibition compared to soils without charcoal present and result in higher nitrification rates. These data will be matched with an assessment of the AOA and AOB from the burned and unburned soils, with and without the addition of charcoal in order to reach a better understanding of wildfire effects on forest soils.

Little is understood about how Supermassive black holes affect their host galaxies in terms of growth and shape. Using the Simulation Romulus25, we are able to study how galaxy properties correlate with black hole properties throughout time. The simulation is a cube with lengths of 25 Mpc on each side, which is about 75 million ly or 21000 Milky way galaxies. We look at how the properties of galaxies relate to the properties of their black holes. We present trends that distinguish star forming galaxies from quenched galaxies.

Retinitis Pigmentosa, a progressive neurodegenerative disease, is a significant contributor to loss of vision due to retinal degeneration. The retina is made up of light sensing cells called rods (for night vision) and cones (for day vision). In patients afflicted with this disease, there is a degeneration of rod photoreceptors over time, which leads to a decreased visual field and night blindness. At a certain point, the loss of rod cells leads to the breakdown and loss of cone cells, which are responsible for color vision. Mutations in the rod gene Rhodopsin have been linked to the development of this disease. By down regulating this defective gene, the degeneration of rods would likely be prevented. Subsequently, cone degeneration would also be prevented, limiting the loss of vision in afflicted individuals. The expression of Rhodopsin is controlled by a nuclear hormone-like receptor transcription factor called Nr2e3. In collaboration with another lab (Dr. Sheng Ding, UCSF), we have identified small drug-like molecules that can block Nr2e3, and we have called them CA88, CA95, and CA97. We predict these antagonists will lower the expression of rod genes. Wildtype mouse retinas were treated in culture with CA88, CA95, or CA97. The use of these small molecules resulted in the significant down regulation of a number of rod genes. These genes include Rhodopsin, NRL, NR2E3, and GNAT1.  Stained tissue sections further confirmed a decrease in Rhodopsin with treated retinas.  When retinal ex plants were done using mice with a P23H mutation in the Rhodopsin gene, treated retinas were found to have a significantly thicker photoreceptor layer than non-treated, indicating the ability for these compounds to prevent retinal degeneration. With a way to reliably down regulate problematic genes such as Rhodopsin, a potential avenue for treatment of humans affected by Retinitis Pigmentosa is opened.

The present study examines low-income Latina mothers' influence on their preschool aged children's self-regulation of caloric intake. There is limited research done on the minority population in regards to parenting styles associated with children's self-regulation of eating. The research conducted is part of a larger study and analyzes the children's self-regulation and parents pressuring their children to eat as contributors to childhood obesity in terms of several procedures. The total number of participants consisted of 187 low-income Head Start Latina mothers with the exception of 2 grandmothers and their preschool children. Mothers were recruited through Head Start, a federally funded preschool program for low-income families and their children. Four procedures are used in my study, which observe children in the eating in the absence of hunger task, caregiver reports of feeding practices, observed pressure to eat during meals, and anthropometrics. It is predicted that caregivers who pressure their children to eat at the first time point will have children who show low levels of self-regulation and higher BMI's 18 months later. These results will have implications for the development of programs to address childhood obesity.

A barrier to quality healthcare in low-resource, rural areas is the lack of surgical care, and current anesthetic delivery devices either are expensive or require resources such as electricity. The Bioengineers Without Borders have proposed a low-cost, point-of-care anesthetic vaporizer, and seek a tool to assist in designing the device. To this end, a finite element model was constructed to predict the performance of a device in different operating conditions. We have imported the prototype’s geometry into finite element multiphysics software and added a domain representing the liquid anesthetic. Conservation equations and boundary conditions for mass, momentum, and heat transfer were applied to the domains of the device and numerically solved over clinically relevant time periods. Physical properties of the liquid halothane, stainless steel, and air were approximated using literature values of similar compounds. The model is currently being validated by comparing the vaporizer’s benchtop measurements of concentration and temperature to the computational model’s prediction. Computational results indicate that a vaporizer with no external heat transfer will experience a significant temperature and concentration drop, which in turn lowers the amount of anesthetic vaporized. When validated, the model will prove useful to engineers as proposed modification may be tested computationally before production, allowing for design refinement and less chance of device failure.

Macrophages play a large part in the immune response to Mycobaterium tuberculosis (M.tb) infection, and its response to infection is modulated by pattern recognition receptors. CD43 is a receptor glycoprotein on the macrophagal surface that has been shown to be associated with differential response severity of TB. The mechanism behind CD43 involvement in the macrophage response to M.tb is still unknown. Our hypothesis is that CD43 controls M.tb growth in human macrophages by mediating pro-inflammatory modulators. We knocked out the CD43 gene in the monocytic cell line THP-1 using the gene editing system lentiviral CRISPR Cas9. Using this cell line, we investigated how the knocked-out cells were affected when infected with M.tb compared to wild-types. We did this by measuring replication of a luminescent M.tb strain. Additionally, since M.tb capsule protein CPN 60.2 is a known ligand of CD43, we used CPN 60.2 to stimulate a tumor necrosis factor (TNF) cytokine response in both wild-type and knocked-out cells. We evaluated the TNF response using an ELISA assay. We found a statistically significant higher rate of replication in the CD43 knocked-out cells compared to wild type cells, indicating that CD43 plays a significant role in the macrophage’s pathway of killing M.tb. We also found significantly lower TNF secretion in CD43 knocked-out cells when compared to wild type cells after stimulation with CPN 60.2, which shows that cytokine response to M.tb is likely modulated by CD43 as well. Taken together, these results show that CD43 is a novel receptor on the macrophage surface that modulates the innate immune response to M.tb by controlling growth and pro-inflammatory cytokines such as TNF. The next steps in this project are to explore the exact mechanisms, such as M.tb macrophagal uptake and phagosome formation, that CD43 targets to control M.tb growth to develop targeted therapies for better TB treatment.

For my history thesis I am studying French intellectuals’ appropriation of World War II memory in debates over the Algerian war. My research involves close readings of the works of key French intellectuals, some of which were printed in major French periodicals like Le Monde, L’Express, and Les Temps modernes. I focus predominantly on the last Governor-General of Algeria Jacques Soustelle and philosopher Jean-Paul Sartre. In these intellectuals’ arguments, two opposing conceptions of national honor arise. Soustelle was a staunch supporter of French sovereignty in Algeria. He connected the war to France’s duty to combat totalitarian and tyrannical threats to democracy, embodied in his eyes in the FLN Algerian rebels. In contrast, Jean-Paul Sartre argued against the war and colonialism, disparaging France for resembling Germany during World War II and compromising its democratic values through the use of torture. Within the context of intellectual petitions and French military coup d’états, these opposing conceptions of honor polarized contemporary debates. These debates in turn contributed to an environment of political instability that brought about the fall of the Fourth French Republic in 1958 and pushed France to settle a cease-fire with the FLN in 1962. However, despite their differences, both Soustelle and Sartre’s conceptions of honor were rooted in the same democratic ideals of the French Resistance of World War II. My research thus also reveals the unique, powerful, yet also dangerous multiplicity of memory. Algerian war intellectual debates revealed that intellectuals could draw on the same collective memory of a previous conflict in order to support radically opposing contemporary arguments and agendas. This reminds us that contemporary conflicts and ensuing debates cannot be understood in a vacuum. Memory is a strong rhetorical tool, and in many ways must be considered central to political and historical scholarship.

Highly controllable adhesives refers to adhesives that can be activated to attach strongly when needed but deactivated for easy and non-damaging detachment. There currently is a need to develop highly controllable adhesives that work optimally in wet environments, like those found inside the human body. Single fimH proteins, found at the tip of E. coli type 1 fimbria, form bonds with mannose that can be activated to bind strongly when pulled at high speeds, but are not activated under low speeds and as a result bind weakly. We hypothesize that thin-films composed of E. coli type 1 fimbriae can act as a nanoscale locking seatbelt, where they lock in at high speeds but not at low speeds, and that we can use mechanical force to control the adhesive behavior. Using atomic force microscopy (AFM) we tested the adhesive behavior between fimbriae thin-films and mannose covered surfaces. We observed that the force required to break the surfaces apart, as well as the number of activated bonds formed, increased the faster the surfaces were pulled away from each other. Also, by using the AFM to preload the bonds with high force, we observed that we could increase the number of activated bonds by a near 4 fold, as opposed to pulls with no preload. Inactivation after preload was also observed by allowing enough time for bonds to inactivate under no force, which decreased the bonds activated to only a 2 fold increase. These results show that these adhesive thin-films are capable of acting like a nanoscale locking seatbelt and can be controlled through mechanical force. An adhesive that can display these properties can have the potential to be incorporated into devices like pill endoscopy, giving an increased ability of controlled precise movement in fields like medical micro-robotics.

During the 1960s and 70s, jazz enters the curriculae of school music programs as a result of social protest in the wake of the Civil Rights and Black Power movements. In Seattle, this acceptance of jazz as an academic art form coincides with the downfall of its popularity in the once vibrant club scenes of Jackson Street and the Central District. While Seattle once boasted a jazz scene that nurtured the likes of Ray Charles, Quincy Jones, and Ernestine Anderson, by the 1960s, the tradition of jazz becomes confined within high school and college jazz ensembles. Thus, Seattle's jazz scene is distanced from its working class roots, and its accessibility limited to those students who could afford to study it. Yet, even within these programs, racial tensions persist, particularly in the development of the University of Washington jazz program within the School of Music. I will argue that the complicated racial politics and history of Seattle's high school and college level jazz programs through the 1960s, 70s, and 80s restricted the availability of formal jazz education in Seattle to the wealthy and privileged. While many students, educators, and musicians from this time period viewed jazz as free of racial tensions, citing integrated ensembles as evidence, this idealized perspective ignores the larger political and economic factors that have always affected equal access and opportunity to quality jazz education. I expect that if we examinine the complex history of jazz education in Seattle, we will gain a greater understanding of why we must strive to make music programs accessible for all students.

What Persian politicians dubbed as ‘the woman question’ in the early twentieth century towards the end of the Qajar Dynasty became, and still remains, a hotly debated topic in Iran that is undeniably intertwined with Iranian ideas of nationalism. The question asked what the new role of women should be in society and what should be done to accomplish it. My honors history thesis examines how both the Pahlavi monarchy (1925-1979) and the Islamic Republic of Iran (1979-present) used women to visualize the national state of wellbeing. This thesis is rooted in extensive research in primary sources conducted over five months; my main sources include oral interviews of local Iranian-Americans, Mohammad Reza Shah Pahlavi’s autobiography, Women and Her Rights in Islam by Ayatollah Motahari, Tehran’s most popular women’s magazine, Zan-e Ruz, private family photo collections, newspaper articles, and speeches by the main political figures of the time. I answer the questions: how did each of the respective governments use control of women’s clothing as a strategy to implement their contrasting nationalist ideologies, and what was their reasoning behind the specific compulsory dress codes? Through analysis of books and speeches by Mohammad Reza Shah and Ayatollahs Khomeini and Motahari [leading Shiite clerics of the creation of the Islamic Republic], I conclude that parallel to the cultural notion that women represent familial honor, both regimes viewed women as symbols of national honor, and thus sought to control their clothing and socialization. Through poetry, political cartoons, and advertisements found in Zan-e Ruz, I investigate the transitions between mandatory hijab to Western clothing in the 1930s and back to mandatory hijab after the Islamic Revolution in 1979. Using oral history methodology, I determine a paradox that shows that despite outward appearances, a new contrary culture developed in the private realm.

Cognitive impairment in the form of dementia is a hallmark of Alzheimer’s disease (AD), an aging-related neurodegenerative disorder that is characterized by increasing deficits in memory and cognition. To allow for targeted, early intervention, it is necessary to develop reliable prognostic tools that can identify individuals at risk of developing AD. Studies suggest that several neuroimaging markers may be predictive of cognitive decline; these include atrophy of medial temporal lobe structures, reduced cerebral blood flow to the hippocampus, reduced functional connectivity between memory-related structures, and lower density of cholinergic cells within the nucleus basalis. In this study, we modeled the relationship between episodic memory test scores from Wechsler’s Adult Intelligence Scale using both established and novel neuroimaging markers while controlling for age, sex and education. Standard neuropsychological battery test scores and structural, diffusion and resting-state functional MRI data were collected from 54 participants (n = 29 women) aged 65 and above (mean = 78.6 years) recruited from Group Health Research Institute’s Adult Changes in Thought study. We found left hippocampal and left entorhinal cortex (LEC) volumes to be significantly smaller in cognitively impaired subjects as compared to healthy controls (p <0.05), and episodic memory scores were most positively correlated with LEC volumes (r = 0.45, p < 0.05) as compared to other MRI measures. Stepwise regression analysis also showed that LEC volume explained a significant portion of variance in memory scores (R² = 0.31, F = 6.88, p <0.05). In comparison to structural MRI markers, functional connectivity measures did not add predictive value, suggesting that physiological measures play a more mediating role in the relationship between cortical structure and performance. Overall, volumetric MRI measures served as better predictors of cognitive performance than other examined MRI measures, and the inclusion of these measures in future AD risk assessments may help to predict cognitive decline with greater sensitivity.

Antibodies play a critical role in our health system, adding specificity to diagnostics and therapeutics with their strong binding capabilities. Unfortunately, the binding cannot be controlled over time, introducing contamination of the target and preventing further testing with the bound sample. We propose an alternative to antibodies: a switchable binding protein. This protein has affinity for its binding target which can be modulated by environmental change without directly altering the binding site, otherwise known as allosteric regulation. This presents the potential to later change the binding target to a medically relevant antigen. A binding protein FimH, found on the end of bacteria pili, was used as the scaffold for the design because its binding depends on a significant structural change. I predict that if this protein is locked in place with a cross-linker or covalent bond, which experiences a large structural change under a simple external stimulus, FimH binding could be precisely triggered. Inserting a disulfide bond or a photoswitchable linker are two methods I am investigating with their binding triggers being dithiothreitol (DTT) and ultra-violet (UV) light, respectively. The photoswitchable linker design is ideal because it would induce reversible binding, allowing for reuse of our protein. Using past structural knowledge, multiple mutation designs are being created and their binding tested under external stimulus. The design requires mutation placed far from the binding site in order to create this allosteric switch. Initial results indicate the design with a disulfide bond between residues 112 and 189 does switch binding affinity, triggered to unbind, when DTT is added. This research also has the potential to contribute a novel approach to regulating large proteins and add specificity in diagnostics by concentrating the target.

Bacterial endocarditis is an infection on the inner lining of the heart. When studying bacterial adhesion, researchers often ignore that blood is pumped through the heart in a pulsatile manner. Because of this, all studies have been done with constant flow. We hypothesize that pulsatile flow conditions play a critical role in this disease. We studied how Streptococcus gordonii, a strain of bacteria that is known to cause bacterial endocarditis, bound in constant and pulsatile flow. The rate of adhesion in both constant and pulsatile flow was measured at different shear stresses. When suspended in buffer, the bacteria bound at the same rate in both flow conditions. The overall trend showed the rate of bacterial adhesion was highest at 10 dyne/cm². At the shear stresses predicted to be present within the heart, 20 – 80 dyne/cm², only about 10% of bacteria bound as compared to the peak value. In a solution with 50% buffer and 50% red blood cells (RBCs), the percentage commonly found in the blood, there was a dramatic change in the trend of bacterial adhesion in constant flow. Instead of having a peak value, the rate of adhesion increased with the level of shear stress, allowing for a much higher rate of binding in the 20 – 80 dyne/cm² range. We were unable to repeat this experiment using pulsatile flow due to limitations in our flow device but this could mean a dramatic change in the trend observed in pulsatile flow as well. We have created a new device to further investigate our hypothesis and better simulate the conditions found in the heart.

A Mycobacterium bovis-based Bacillus Calmette-Guerin (BCG) vaccine is protective against childhood TB meningitis but insufficient for controlling the disease. The development of efficacious vaccines requires mechanistic understanding of host immune response to MTb and the BCG vaccine. We have previously identified that single nucleotide polymorphisms in the gene HSP90B1 are associated with development of TB disease in South African children. HSP90B1 is a molecular chaperone for integrins and most Toll-like receptors (TLRs). TLRs recognize pathogen-associated molecular patterns (PAMPs), and are critical for the innate immune response to infection. In a mouse model, HSP90B1-deficient macrophages were unresponsive to ligands that target TLR2, 4, 5, 7, and 9. Our lab has generated an HSP90B1 gene knockout using CRISPR/Cas9 technology in a human monocyte cell line, and I have confirmed successful mutagenesis via a restriction fragment length polymorphism analysis. Our preliminary data indicates that exposure to TLR ligands PAM2, PAM3 and LPS, in addition to MTb whole cell lysate is correlated with a reduction in Tumor Necrosis Factor (TNF-α) secretion in the knockout cells compared to controls. We hypothesize that HSP90B1 is a critical modulator of the MTb-induced TLR signaling pathway, which drives the production of inflammatory cytokines and plays a key role in the immune response to MTb. My objective is to characterize the effects of HSP90B1 on the TLR signaling pathway by stimulating cells with TLR ligands such as flagellin for TLR5, imiquimod for TLR7, and performing cytokine quantification via enzyme-linked immunosorbent assays (ELISA). Moreover, I will conduct Griess assays to evaluate effects of HSP90B1 upon nitric oxide production, which is an important defense molecule in enhancing efferocytosis, the process of up taking apoptotic cells. These studies will improve our understanding of host immune responses to MTb and potentially lead to development of more efficacious TB vaccines.

Shear-enhanced adhesion is a mechanism in which binding is enhanced at high flow rates. Some species of bacteria within the genus Streptococcus demonstrate shear-enhanced adhesion under high flow conditions, which are present throughout the human body. The purpose of our research is to understand and compare the effect of constant and pulsatile flow in Streptococcus gordonii, a strain of bacteria that causes infections by binding to human platelets. Our research focuses primarily on cases of infective endocarditis, a life-threatening infection of heart valves caused by various strains of bacteria. Rates of incidence in a general population has been estimated between 2 and 6 cases per 100,000 person-years. In our model system, we utilized a flow chamber to mimic pulsatile flow conditions in heart valves, which oscillate between a low and high flow, with a maximum shear stress of 3 Pa. We took videos of S. gordonii, which uses a serine rich-repeat adhesin to bind to platelets, and determined the number of bacteria that bonded to the surface under constant low, peak, average, high, and pulsatile shear stresses. We analyzed the videos to determine the conditions that enhance adhesion and compared our results under pulsatile flow to constant flow for the same range of shear stresses. Our results indicated that pulsatile conditions promote low amounts of adhesion above 1-2 Pa, demonstrating that pulsatile flow does not explain how Streptococci bind to heart valves at 2-8 Pa. These results disproved our hypothesis that pulsatile flow enhances adhesion at 2-8 Pa. Further research may look to testing the mechanism behind which Streptococci bind to heart valves in bacterial lesions exposed up to 8 Pa in the circulatory system. By understanding the adhesive properties of S. gordonii, our research may contribute to the development of anti-adhesive therapies to treat bacterial endocarditis.