The formation of amyloid ß (Aß) plaques, resulting from the inappropriate aggregation of the protein beta-amyloid, is a major pathology associated with Alzheimer's disease (AD). One potential therapy for Alzheimer's disease is to reduce cerebral Aß plaque deposition through stem cell therapies. We hypothesize that myeloablative therapy, using lethal irradiation, as well as non-myeloablative bone marrow transplantation, using non-lethal irradiation, will result in a reduction in Aß plaque accumulation in the cerebrum. To test the therapeutic potential of myeloablative and non-myeloablative bone marrow transplantation, we transplanted bone marrow into either lethally irradiated AD (APPswePSIdeltae9) mouse model recipients (myeloablative therapy) or non-lethally irradiated AD mouse model recipients (non-myeloablative therapy). The number of plaques present and the total plaque area are quantified using ImageJ software. Initial immunofluorescence quantification has shown that non-myeloablative bone marrow transplantation reduces total Aß plaque area in the cortex by 33% when compared to non-treatment controls. To further assess the therapeutic potential of both myeloablative and non-myeloablative bone marrow transplantation therapies, additional immunofluorescence, as well as immunohistochemistry, quantification of Aß plaque deposition will be performed. These preliminary results suggest non-myeloablative bone marrow transplantation is a potentially effective stem cell therapy in treating an Alzheimer's related pathology.

Ultra-high vacuum (UHV) techniques make it possible to observe interactions on clean, ordered surfaces without the complexity of realistic systems.  Final construction and testing of an improved UHV adsorption microcalorimeter capable of measuring the heat of adsorption of metals on single crystalline surfaces have recently been completed.  This calorimeter is the first of its kind to employ an electron beam evaporator to create a high, stable flux of metal atoms with low source radiation, which is then pulsed onto the thin single crystalline sample. Due to the properties of the electron beam evaporator, metals with high heats of sublimation such as Pd, Pt, and Au can be evaporated while maintaining the base pressures necessary for maintaining ideal surface conditions.  The new chamber is also equipped with a sample preparation chamber in which metal oxide surfaces can be grown on single crystalline samples.  Absolute calibration of the microcalorimeter was achieved by measuring the heat of formation of Cu multilayers on a Pt(111) surface, indicating that the theory behind our electron beam evaporator is correct, and will allow for the first direct measurements of the heats of adsorption of catalytically important metals such as Pt, Pd, and Au on any surface.

The reduction of CO₂ has become a global priority as the concerns of climate change and the adverse effects of atmospheric carbon dioxide on the environment continue to rise. One method of reducing CO₂ emissions is through conversion and utilization as a chemical feedstock. CO₂ is cheap, nontoxic, and can be recycled to produce valuable new products, making it an attractive feedstock. The increasing importance of CO₂ utilization processes requires a better understanding of the underlying mechanisms of its conversion. The industrial conversion of CO₂ is typically achieved using a heterogeneous catalyst, usually consisting of small transition metal particles supported on a high surface area metal oxide. Our project focuses on elucidating the mechanism of the reverse water-gas shift (RWGS) reaction on platinum, an extensively studied catalyst with a highly active surface. Our goals are (1) to quantitatively measure the RWGS rate under conditions of low H coverage and (2) to compare the measured rate to the rate of CO₂ dissociation (the rate-limiting step according to the surface redox mechanism) and to the theoretical rate calculated using a micro-kinetic model based on the associative mechanism. The information we gather from the investigation will clarify whether the RWGS reaction proceeds on platinum via the surface redox mechanism or the associative mechanism.

Mitochondrial dysfunction and oxidative stress have been proposed to contribute to organismal aging. In the nematode C. elegans, reduction of mitochondrial function through knockdown of genes encoding components of the electron transport chain (ETC) is sufficient to increase life span. The increased longevity is not solely the by-product of decreased oxidative damage generated by the ETC, but also involves induction of the mitochondrial unfolded protein response (UPR^mt), as evidenced by the observation that life span extension requires an intact UPR^mt. The cytoplasm, endoplasmic reticulum, and mitochondria have each evolved compartment-specific signal transduction pathways to alter nuclear gene expression in response to perturbations in protein homeostasis. However, little is known about the UPR^mt and the mechanism by which unfolded proteins are recognized in the mitochondria and signal changes in gene expression. Previous studies demonstrate that knockdown of ETC components and a subset of mitochondrial proteins induce the GFP reporters for mitochondrial chaperones hsp-6 and hsp-60. To identify novel genes involved in the UPR^mt, we are performing a forward genome-wide RNAi screen using the hsp-6::GFP reporter and measuring UPR^mt activity by fluorescent microscopy. Upon completion of the screen, we expect positive hits to include mitochondrial proteins, signaling molecules, and transcription factors that regulate the UPR^mt. Consistent with previous studies, gene knockdowns that have robustly induced the UPR^mt thus far in our screen are largely components of the ETC. In addition, the screen has yielded many novel hits including genes outside of the mitochondria and of unknown function. After the screen is complete, we will validate the RNAi clones that induce the UPR^mt and perform lifespan experiments to understand how the UPR^mt is involved in the aging process. Our screen will further understanding of how the mitochondria and nucleus communicate with one another in order to maintain mitochondrial proteostasis and illuminate how mitochondrial stress contributes to aging.

My research examines fairness and equity in the distribution of three wastewater treatment types across seven counties in the Puget Sound region. I begin my analysis with a thorough exploration into the concepts of fairness and equity, within the context of a variety of disciplines. Drawing on this analysis, I then look into the costs of these different systems, making sure to take into account all applicable considerations, including implementation, maintenance, and repair costs. Specifically, I investigate the costs of combined-sewer systems, separated sewer systems, and onsite septic systems at the household scale. Lastly, I use Geographical Information Systems and spatial analysis to compare the costs of these systems to their spatial distribution through the subject counties, and to the household median income within their respective census tracts. This methodology allows me to uncover any inequities in the way that the costs of these treatment types are distributed, and address a specific instance of fairness within urban planning that has yet to be investigated.

In the last decade, Seattle, like many other cities across the world, has tried to encourage bicycling by developing new bicycle infrastructures, cultures, and policies. In many cities, these efforts often start nearly from ‘scratch’. However, in The Netherlands, bicycling has been an important part of the transportation network for more than 100 years, with comprehensive infrastructure in place from policies developed during the 1960’s and 70’s. Our team, composed of two members, spent several months in Groningen, The Netherlands, on an exchange where we collected data on the bicycle infrastructure success that this region of the world is renowned for. Working with the Multimodal Project Development team at Seattle Department of Transportation (SDOT), we brought the lessons-learned and design of the Netherlands to our home, Seattle. We have evaluated the design of four critical Seattle intersections: 43rd Ave NE and University Way, 7th Ave NE and NE 40th St., 25th Ave NE and the Burke Gilman Trail, and 34th Ave N and N Fremont Ave. and compared them to successful infrastructure in Groningen. Through background research, interviews, and observation, we have assessed the comfort, safety, and directness of these selected intersections using quantitative and qualitative measures. Based on this data, we have suggested two alternatives for each intersection: one based on Dutch design which is novel to Seattle and very ambitious, and one of which is more practical and less expensive. The possible results of this study are far-reaching and significant. Whether our designs are adopted in some form by SDOT or not, our final designs have influenced SDOT employees. We are taking a step towards making our community a safer, healthier, and more enjoyable place for all street users.