Bone tissue healing is problematic for more than a fifth of fractures, bone defects, massive bone loss, and osteoporosis and requires regeneration or implantation of bone. The introduction of a therapeutic bone strategy in the body elicits the foreign body immune response which is characterized by the inflammatory cell recruitment and subsequent encapsulation of the foreign material by fibrotic tissue. The formation of the fibrotic tissue is generated by a process in which macrophages adhere to the foreign material and fuse to generate multi-nucleated cells called foreign body giant cells (FBGCs). FBGCs effectively separate the foreign material from surrounding tissue resulting in sustained inflammation and reduced efficiency. This response, known specifically as the chronic inflammatory response, represents a very challenging complication for biomaterial fabrication in tissue engineering applications. Very recently, preliminary evidence has indicated that an optimal pore size exists in porous scaffolds that upon implantation result in the regeneration of a variety of tissues. Simultaneously incident findings in vivo have indicated that differentiated macrophage may have greater plasticity than previously accredited, and may transdifferentiate into various cell types. These advances may aid clinical treatments for bone repair by facilitating bone growth and avoiding stem-cell therapy controversies. The aim of the project was to design a porous scaffold to promote efficient bone tissue regeneration by enabling macrophage transdifferentiation. The proposed biomaterial synthesizes new information on optimal scaffold pore size and macrophage plasticity in conjunction with a well-studied osteoinductive cue, to both control the human body immune response and facilitate bone growth. The approach thus far has entailed an in vitro analysis of macrophage morphology and structural fabrication of the biomaterial.

To be infected with human immunodeficiency virus (HIV) is to face a lifelong battle. Even with the combined force of multiple antiretroviral drugs to target different phases of the HIV life cycle, one cannot eliminate human immunodeficiency virus (HIV) from the body. This is due to persistence of virus reservoirs, compartments, or sanctuaries. Reservoirs are tissue sites characterized by collection of virus over time: viral populations show low divergence from the founder virus and high diversity between each other. Compartments are tissues with limited gene flow: they are pockets of virus with limited entry and exit. Sanctuaries are tissues that resist penetration of antiretroviral drugs: they can set up the conditions for reservoirs or compartments. To understand how and where these sites of persistent infection endure in the body even during antiretroviral therapy (ART), we are conducting a systematic characterization of possible sites in the infected host. We are studying viral populations present in biopsy-derived gut-associated lymphoid tissues (GALT) and other autopsy-derived tissues of patients who died while on antiretroviral therapy (ART). Viral populations are sampled from tissues using molecular lab techniques (including polymerase chain reaction and Sanger sequencing) and analyzed using phylogenetic trees and computational programs that measure diversity, divergence, and clustering. Our study addresses two main aims: (1) to find the tissue sites in the host critical in maintaining latent HIV infection during suppressive ART and (2) to find tissue sites critical in supporting continued viral replication and the emergence of pathogenic phenotypes during ART by characterizing sites as reservoirs, compartments, or drug sanctuaries. Hopefully our research will help to direct future methods of HIV treatment by allowing researchers and clinicians to better understand how and where virus persists in the body.

Colloidal zinc oxide nanocrystals (NCs) become charged with electrons upon reduction with decamethylcobaltocene. Understanding this redox chemistry can further develop research on quantum dot sensitized solar cells and other various applications of NCs. The goal of my project is to determine whether this electron transfer can be characterized by an equilibrium constant K_eq, and if so, to see which variables in the reaction affect the K_eq. Two models were tested: (1) in which the concentration of NCs would affect the K_eq, and another (2) in which it would not. Using data from optical titrations, I found that the K_eq is affected by NC concentration and is therefore better described by model (1). Similarly, other variables are currently being tested in order to refine a working model that can accurately describe the reaction of NCs with reductants. The contribution of a simple model for these charge transfer processes can be applied to various areas.

M dwarf stars are classified by their small radii and relatively cool surface temperatures. Their internal structures are known to be almost entirely convective, and this extreme convection causes a tangling of the stars' magnetic field lines. Upon realignment of the magnetic field lines, an incredible amount of energy is released from the star in what is called a flare. This research project is an ongoing observation of the flare activity on the M dwarf stars GJ1243 and GJ1245. Two months of flare activity was observed using the flux measurements made by NASA's Kepler telescope. The frequency, duration and types of flares were recorded and analyzed with the aid of the computer program "Flares by Eye." It has been observed that most flares have short rise times and long decay times, the intensities of which seem to follow a power law. Continued research on this topic will help us learn more about the physics behind the ignition of these stellar explosions, how the flares decay, and how the stars become less active as they age.

Two strains of Botryococcus braunii algae were grown in three different sets of conditions to compare growth characteristics and lipid production. One species, UTEX LB 572, was a Race A Botryococcus braunii from the culture collection of the University of Texas in Austin. The second species, AC 762, was a Race B Botryococcus braunii from the culture collection of the University of Caen, France. UTEX 572 was found to produce two hydrocarbon chain lengths of C:16 and C:18 in a 2:3 ratio respectively. The AC 762 was found to produce hydrocarbons called botryococcenes of chain lengths between C:30 and C:36. The lipid chain lengths of both strains were evaluated by mass spectrometry. The UTEX 572 lipid content was quantified by analytical spectrometry after direct transesterification of the lipid content to biodiesel. The AC 762 lipid content was quantified by a photospectrometry technique developed by UC Berkeley researchers Eroglu and Melis (1985). Cells of both species were harvested during exponential growth phase from 400 mL of growth media and then freeze dried and analyzed gravimetrically. Nine flasks of each species were grown with 3000 lux average light intensity on a 12h:12h light:dark cycle at room temperature averaging 22° C. Three flasks of each species were grown with 1.5% CO2 in BG-11 media, three flasks of each species were grown in BG-11 media with air only and three control flasks were grown in respective carrier medias as those used in the algae collection of origin. Knowledge of the rates at which AC 762 and UTEX 572 produce hydrocarbons as well as the specific lengths and proportions of those hydrocarbons contributes to data needed for comparison of economic considerations in industrial applications.

All plants contribute to the productivity and biomass of an ecosystem. With generalized formulas we have gained an understanding of these fundamental processes, however, to understand the precise contribution of a particular plant species more accurate and specific equations are required. Through the dissection and fine-scale measurements of individual plants, allometric equations relating detailed plant structure to easily measurable quantities (i.e., stem diameter) can be developed. Because of their relative small stature and relatively small contribution to total ecosystem biomass, little is known about the exact biomass and productivity of shrubs. Yet, diverse angiosperm shrubs in western forests can have a disproportionately large impact on the ecosystem in terms of providing a food source for wildlife and fuel for low-intensity fires. Field measurements and samples were collected from 41 individual plants of Cornus sericea L. [Cornaceae] (red osier dogwood) in Yosemite National Park, California, USA. In the lab I processed the field data and calculated a number of allometric equations, including cambial surface area, wood mass, bark mass, and foliage mass in relation to basal diameter and diameter at breast height. This dataset will generate a foundation for future research helping scientists more accurately determine carbon stocks, carbon sequestration rates, fuel loads, and other changing trends. The collection of more comprehensive and scientifically accurate data will also help improve land management policies in an era of projected climate change.

Silicon microring resonator biosensors utilize nanoscale light confinement to detect biomolecules in a real-time and label-free manner with high sensitivity. Detecting the presence of antibodies that bind human tissue and blood antigens is crucial in transplant and transfusion medicine, as mismatched products can impact the clinical outcome of the recipient. The focus of the current research is to improve data analysis methods to perform serologic analysis of human plasma using a silicon photonic chip. Microring resonator chips were prepared by physisorption of streptavidin followed by functionalization with biotin-conjugated histo-blood group antigens. Testing was performed using undiluted human plasma to detect histo-blood group antibodies on the functionalized chip surface. A secondary enhancement step using an anti-immunoglobulin antibody enabled the quantification of the surface bound antibodies. Data analysis was performed using on-chip positive and negative controls, and kinetic analysis was accomplished using association models. The quantitative determination of antibody binding profiles with a model antibody system is discussed to show how these devices can ascertain kinetic behavior. Positive determination of plasma antibody content is shown, proving these devices can be used in this application at current clinical standards. These devices are suited for clinical translation and with proper quantitative models and testing they could surpass current clinical methods.

Titanium dioxide (TiO₂) displays a variety of interesting properties and has been intensely investigated for applications in environmental cleanup, photocatalysis, dye-sensitized solar cells, and semiconductor fabrication among others. However, the underlying mechanisms which govern TiO₂ chemistry are not well understood. Here, the tendency for reduced TiO₂ nanoparticles to donate stored electrons to other reagents is being characterized. The reduced ("charged") nanoparticles are made by UV irradiation which excites an electron from the valence band to the higher energy conduction band of the TiO₂ nanoparticles. In the absence of oxygen and other oxidants, the charged TiO₂ nanoparticles are stable and can be easily monitored by their absorption of visible light and blue color. We are exploring the chemical reactions of the charged particles. If the optical spectrum changes after the addition of other reagents, that is an indication that the nanoparticles are reducing the reagents. Removal of the electrons from the nanoparticles has been previously accomplished using aqueous Cu²⁺, but not Zn²⁺ or Mn²⁺. I am repeating this result and extending it to other metal ions such as Cr³⁺ in order to estimate the standard reduction potential of the charged particles. In addition, I am studying optically and via NMR whether dimethyl sulfoxide (DMSO) is reduced to dimethyl sulfide by charged TiO₂ nanoparticles. Because one-electron reduction of DMSO results in extremely unfavorable intermediates we are probing whether the reaction by charged TiO₂ occurs by the direct transfer of two electrons from the TiO₂ nanoparticles to the DMSO. These studies will provide valuable insight into the electronic chemistry of TiO₂ and will aid in the application of TiO₂ to other systems which require the transfer of multiple electrons.

Administration of Anti-Retroviral Therapy (ART) slows disease progression and reduces HIV-1 viremia to near undetectable levels. Poor adherence or withdrawal of therapy often results in rapid rebound of viremia with the potential for the establishment of drug resistant variants. HIV is known to establish latency in long-lived central memory T-cells (CM) and is often referred to as “the reservoir”. However, we now understand that there is both latent and actively replicating HIV-1 that comprises reservoir sites. Using sequence information and computational tools we can define reservoirs as cells or tissues harboring HIV-1 with genotypic features of reduced temporal structure, high diversity within the population, and low divergence from their most recent common ancestor (MRCA). This is because reservoirs are populated with virus seeded at both early and late periods of infection. If a reservoir is established in a site with reduced drug penetrance, “drug-sanctuaries”, continued viral replication and diversification could occur. This may result in the accumulation of drug resistant variants that lead to therapy failure. Here we hypothesize that tissue and cellular sites with phenotypes reflective of reservoirs may also be drug restricted providing a boundary for unrestricted viral replication. To test this hypothesis we sequenced single genome template derived amplicons (SGA) of env and pol regions of HIV-1. Presented is data from the autopsy of subject S104. S104 presented with multi-drug resistant genotypes in all tissues sampled. Bioinformatical analysis measuring viral genetic diversity within and divergence from the MRCA of the viral population of S104 demonstrated reservoir phenotypes in tissue virus isolated from lung. We continue to expand our characterization of reservoirs and compartments to clearly define sites that must be targeted to eradicate HIV-1 in the host.

My project explores the stereoscopic technique to express Mt. Rainier in 3D images for the first time.  By extending the camera distances to fabricate the vision of a giant, the mountain and its surrounding terrian is experienced disembodied, yet familiar. This effort represents a 3-year culmination of art-practice with the stereoscopic-3D video medium. Experiments with projection surfaces, short film, video-installation art, and computing have placed me as a leader in the field at the University. Stereo-3D's rise and fall in popularity and its function in popular culture is easily visible, but my research places it in the Fine Arts context in an attempt to embed 3D video in a tradition of visual poetics and technique.

 The field of kinetic and interactive sculpture has been the focus of my research. Capturing the subtleties of movement in structures, experimenting with materials, and creating a slow, organic shifting of materials that functions as an open system in a modular kinetic sculpture which coexists with other elements in a space as an installation is the focus for my investigation of movement, fluidity, and flux as it relates to memory, shared experience and secrets. The central sculptural element in this installation uses modularity as a metaphor for this. Incorporating bones on the floor of the gallery along with a sound element tie together this experience as I explore the creation process of a whole and integrated installation. The next part of my research will incorporate the movement mechanisms more seamlessly as I will replace visible motors with nitinol muscle wire.

Around 650 health services professionals in the Washington State Department of Corrections provided care for over 24,000 inmates in the last year, and the number of people being housed in correctional facilities is on the rise. Discourse abounds regarding the necessity and adequacy of health care provided to this growing population in the US, yet the bulk of this discourse applies a biomedical lens. This exploratory study employs qualitative methods to examine the role of the health care provider in the prison environment in an effort to understand the factors within the correctional system that influence the provision of health care in prisons. Through participant observation, in-depth interviews, and cognitive mapping, this study aims to shed light on the interactions among the medical staff, correctional staff, and inmates. All research is conducted at a single Washington state prison. Interviews are conducted with around 10 health care professionals who volunteered to be interviewed; field notes are taken during the course of interviews and observations; and diagrams expressing inmates' perceptions of the process of receiving care are collected. For analysis, open coding is performed to identify significant themes in the data, and closed coding is performed to explore the themes more deeply and make connections among them. An understanding of how these major players in correctional health care perceive health care and perceive each other has the potential to help increase the effectiveness of care.

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

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

A century of fire suppression has led to higher tree densities, higher basal area, and increased abundance of shade-tolerant Abies concolor and Calocedrus decurrens in the lower montane forests of Yosemite National Park. Although fire was reintroduced to these systems over forty years ago, the effects of fire on forest structure and radial tree growth are still not well understood. This study compares live tree and snag basal area and density, seedling establishment, and radial growth patterns at four 0.1 ha plots in A. concolor-dominated stands of similar climatic water balance. Two sites had burned at different levels of low-severity fire in 2005, and two sites had not burned since the onset of fire suppression. On average, unburned plots had three times the tree density and 2.6 times more trees with DBH between 2.5 cm and 30.0 cm than burned plots. Burned plots had a mean seedling density 3.8 times greater than unburned plots. Low-severity fire also appeared to affect radial growth patterns as both burned plots showed decreased growth relative to the control plots for two years immediately post-fire. However, only burned plot 1, which burned at a higher severity than burned plot 2, showed increased growth relative to control plots 3 to 5 years post-fire. This study has implications pertaining to frequent fire forests of the West. 

Horseradish peroxidase (HRP) is part of a family of heme-containing metalloenzymes that reduce the O-O bond of peroxides while oxidizing a wide variety of substrates; in the case of HRP, hydrogen peroxide is reduced to water. In the presence of an oxidant and the absence of a substrate to oxidize, hydrogen peroxide coordinates to the iron cofactor of HRP, forming a ferric-hydroperoxide intermediate known as Compound 0, and subsequent O-O bond cleavage releases water and a very oxidizing ferryl-oxo porphyrin radical cation intermediate, known as Compound I. The goal of this project is to probe the potential reversibility of Compound I formation, a step traditionally thought to be irreversible. A key experiment will react HRP with unlabeled H₂O₂ in ¹⁸O-labeled water, and determine whether mixed-labeled H₂O₂ is formed. The presence of mixed-labeled H₂O₂ indicates that there is reversibility of the O-O bond cleavage that forms Compound I and its existence will be determined by addition of a water soluble phosphine that is too bulky to fit into the active site of HRP. In this case, the phosphine cannot be oxidized by Compound I, but can readily react with free hydrogen peroxide in solution to give the corresponding phosphine oxide. ³¹P-NMR will be used to determine whether the phosphine oxide is labeled because the NMR shifts of ¹⁶OPR3 and ¹⁸OPR3 are distinct. If this reaction proves to be reversible, this knowledge could then be used to describe other enzymes that catalyze oxidations with similar intermediates. This would not only be important to enzymatic systems, but possibly catalytic chemical processes.

Nearly half of the US population is living with a chronic disease. A chronic disease is a prolonged illness that cannot be spontaneously resolved and can rarely be cured completely. Chronically ill patients feel more resentful, isolated, and prone to depression, stress, and anxiety; known factors which diminish a patient’s health. Studies indicate that support groups help patients to alleviate stress, depression, and cope with their illnesses. Currently there are many online support groups that help connect fellow patients of a chronic disease with each other while medical tools like WebMD help connect patients to an expert (not necessarily the patient’s own doctor). Triage is a system we are designing to bring together these connection mediums and provide chronic disease patients with a communication hub where they can connect with fellow patients, their own doctors, and researchers. Patients can share with fellow patients their personal journeys through the chronic disease, become friends with them, form groups, and view top posts from other patients. Patient to doctor communication will entail quick questions to the patient’s doctor, and short messages to the doctor that could easily answered without an appointment. Patients can also interact with researchers of their particular chronic disease who are looking for participants for their studies, can participate in studies, and get updates about new research in the field. Multiple usability tests will be conducted involving doctors, patients and researchers to evaluate and improve the overall design of the Triage project.

My research uses ethnographic methods to examine personal histories and subsistence strategies of health workers in Sierra Leone. The project is designed to ‘study up’ (Nadar 1969), that is, to use ethnography as a tool to understand the macro- political, social, and economic context of people’s day-to-day experiences. I look to understand the impacts of Sierra Leone’s post-conflict economic restructurings on the quality of life, employment distribution, and clinical practices of healthcare providers. My project includes a preparatory stage at the University of Washington and, subsequently, six weeks field research in Sierra Leone. My work particularly considers Sierra Leone’s debt-relationship to International Financial Institutions (IFIs), such as the International Monetary Foundation (IMF) and World Bank. Loans issued by IFIs stipulate shifts in governmental spending and regulation that, in terms of healthcare services, translate to reduced funding for governmental healthcare services, the development of a private healthcare sector, and use of NGOs to funnel aid money into the nation. These shifts, inspired by neoliberal market fundamentalism, result in fewer jobs and lower wages for health workers, as well as a discordant healthcare system fractured between NGO, private, and government services. Globally, anthropologists have worked to document the collateral damage to health from neoliberal economics. However, there is a dearth of ethnographic work explicitly considering economic restructuring’s effects on health in Sierra Leone. Health workers are integral to health services and their stories incisively reflect the toll of neoliberal economic agendas on health. My research adds to the anthropological evidence that these agendas are systematically denying people health services and undermining health in developing countries.

This study used the Hamilton Search and Set Breaking tasks to assess working memory, cognitive flexibility and inhibition control of a variety of domestic dog breeds. This memory task has been tested on pigtail macaque monkeys, as well as, other species. The Hamilton Search task consisted of 4 containers which the dog was allowed to search to find a randomly placed food reward. The latency and search patterns were recorded to determine performance of the task. After 5 sessions of Hamilton Search testing, the dogs moved on to the Set Breaking protocol. Set Breaking consisted of placing the reward in the same container every trial until the dog reached criterion by searching the correct location first 5 times consecutively. The container that the food reward was placed in was determined by calculating the container which was visited the least often during the pervious Hamilton Search trials. The results from this study will be compared across species and within the species of domestic dogs. Enough dogs of very diverse breeds were tested to allow us to analyze for similarities and differences between breeds. The results showed that dogs approached this task much differently than the pigtailed macaque monkeys. Current data suggests that the dogs, not dependent on breed, are approaching this task in a very systematic manner starting a search pattern at one end and working towards the other end. With this approach, rechecking a container is very rare, demonstrating perfect memory, but in fact the dogs are using a systematic approach that is less flexible, but efficient alternative to the use of memory. Results of this study can be applied to help refine training techniques and to establish the validity of these tasks for studying canine spatial learning and memory.

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