Tuberculosis (TB), an infectious disease caused by the bacterium Mycobacterium tuberculosis (Mtb), kills nearly 2 million people a year and is a major cause of morbidity and mortality worldwide. The increasing prevalence of multi-drug resistant (MDR) strains that fail to respond to all currently available drugs underscores the critical need for new therapeutic strategies. DNA topoisomerases (topos) are a class of enzymes responsible for maintaining the correct topological state of DNA molecules by modulating the degree of supercoiling through the breakage and reforming of covalent phosphodiester bonds in the DNA backbone. With the precedent-setting success of several anticancer and antibacterial drugs that target topos, focus in TB research has increasingly turned to these enzymes as new potential targets for chemotherapy. In this study, we isolated Mtb topoisomerase type IA (MtbTOPA), a subclass that only acts on single-stranded DNA (ssDNA), as our target of interest. At least one type IA topo activity must be present in every organism for resolving topological obstacles that require ssDNA cleavage, and fortuitously, Mtb happens to only encode one type IA, further validating MtbTOPA as a high-value drug target. We have cloned, expressed, and isolated highly purified recombinant MtbTOPA protein for enzymatic studies and work is currently underway to solve its crystal structure to aid in target-based approaches to drug development. In efforts to develop a high-throughput screen (HTS) for identification of small molecule inhibitors of MtbTOPA, we have collaborated with the Global Alliance for TB Drug Development (GATB) and leading structural genomics centers to gain access to large compound libraries as well as to accelerate the drug discovery process. We adopted a HTS method based on fluorescence resonance energy-transfer (FRET) and requisite MtbTOPA mutants were designed. It is our hope that the HTS will identify several hits that can be developed into novel TB drugs.

This project explores a grassroots organic food movement in Chengdu, China through a case study of an organic co-op in Anlong Village in the outskirts of the city. Due to its small size and inadequacy of official organic certification standards, the Anlong farmers refer to their produce “ecological” vegetables, as opposed to “organic” vegetables. Since the farms converted to “ecological” production in 2006, small, but growing number of Chengdu urbanites has turned to Anlong farms for a source of healthy and fresh organic produce while other affluent urban consumers enjoy organic products at metropolitan supermarkets. Given that the produce of these farms in Anlong is not officially certified, and given the fact that the cost of the produce is still on par with certified organic produce, why are they gaining popularity among urban customers who could easily buy similar produce at a shopping center nearby? Based on analyses of semi-structured interviews I conducted with Anlong farmers and customers and field observation, I argue that the consumption of Anlong products carries significance that extends beyond actual processes of production to suggest a symbolic purity untainted by the government association. In China, due to a series of reports on counterfeit food labels and the limited success of government regulations on food industry, government certified labels hardly evince moral attributes of organic foods, but generate negative interpretations. Anlong’s produce absent an official label shuns such suspicion and validates honest values that the organic agriculture elicits. 

Although patients diagnosed with pulmonary hypertension (PHTN) are at a higher risk for postoperative complications, studies to date have not distinguished whether this applies equally to all PHTN patients, nor have they determined the severity of postoperative complications should they occur. Pre-operative screenings take place in the form of echocardiograms (ECHO), which are accurate but rather expensive. This study, one of the largest pulmonary hypertension studies to date, is headed by Dr. Gail Van Norman, director of the Pre-Anesthesia Clinic at the University of Washington Medical Center (UWMC). We look to explore the correlation between the severity of pre-existing pulmonary hypertension and post-operative complications. This study additionally explores the correlation between metabolic equivalences (METS) and PHTN, which could yield a new, more cost-effective method of screening for the disease.
As research interns on this project, we abstract data from the medical records of eligible patients at UWMC. We focus on patients who have undergone surgery with moderate to severe PHTN, and collect pre-op and post-op data using hospital affiliated databases. Patients with these specific conditions are believed to have <4 METS and are at an elevated risk for post-operative complications. Should these hypotheses be proven correct, the results of this study will benefit both patients and providers, reducing the cost of screening, as well as improving patient care by allowing doctors to better manage the disease in the peri- and postoperative settings, reducing both complication and mortality rates.
 

 For thousands of years, the Chengdu Plain in Sichuan, China has been characterized by the linpan settlement pattern, a system where the family compound is located amongst the lands they farm as well as thickets of bamboo and trees, creating a patchwork of farmland and human life across the Plain. A recent Chinese government program entitled “A New Socialist Countryside” threatens this unique pattern through nationwide reconsolidation of rural households into concentrated villages. This style of living undoubtedly places a new ecological strain on the Chengdu Plain, an effect believed to be more serious due to the concentration of environmental pollutants compared to the former dispersed pattern of waste flows. I sampled water in an area with both new and old settlement patterns, measuring the levels of nitrates, phosphates, ammonia and chemical oxygen demand. Through a comparative study of the results, initial findings point towards supporting the hypothesis that consolidated housing is more ecologically harmful than the linpan. The consolidation of the Chengdu Plain presents the exciting opportunity to capture and record the effects of modernization within rural farmland.

In recent years, multi-cultural education has become commonplace in policy making and public discourse. While policy makers, educators, parents and community members surely make an earnest effort to seek out and implement standards and practices which fairly address multiple cultures, many children and young adults remain faced with intense challenges in the form of curriculum and social pressure. This study sought to better understand how students in a South Seattle refugee community negotiate identity and achievement while engaged in this American public education system. It also attempts to explore how and why certain aspects of social fabric are maintained and others dismissed in favor of mainstream American culture and the ways which these interact with this system. The common view of multi-cultural education is based on supplementing otherwise standardized curriculum and the creation of certain types of spaces. This process of supplementing pre-existing curriculum is problematic because it leads to the exclusion of increasing numbers of students from both the public education system and future socioeconomic advancement in the United States. While this system deeply affects the lives of children, young adults, parents and community, these issues remain underexplored. Therefore, this study engaged participants from South Seattle’s Yesler Terrace neighborhood to explore these concerns using ethnographic data collected based on a “mosaic approach”, including one-on-one and group participant led interviews, photo-voice, social mapping and participant observation. Using these methods, this study explored two sites within this neighborhood. The first is an after school tutoring program run by Catholic Community Services at the Yesler Terrace Community Center which pairs students one on one with tutors for help outside of the classroom. The second is a first grade classroom at a neighboring elementary school. This study has found that the complexities faced by young people in the United States education system are incredibly individualized experiences. One of the primary goals of this research is to emphasize the importance of these individual experiences over those understood through collective sets of data. It is hoped that this study may open doors for further exploring the lives of individuals in order to better serve them in the public education system. Simultaneously, this study focuses on the anthropological process and the relationships that arise from it, the various roles of anthropologists and the impacts of research.

The physiological mechanism of light-induced leaf expansion may begin with the capture of blue light by the photoreceptor phototropin. This process is responsible for growth of the plant which influences photosynthetic ability and overall productivity. Our goal was to determine whether phototropin has an affect on expansion and if so, what phototropin's role in growth is. In this study, we grew Arabidopsis thaliana WT (wild type), phot1, phot2, and phot1/2 mutants in pots in a growth chamber under continuous light. Each plant's fifth leaf was photographed every day and measured with ImageJ to obtain growth rates. This experiment was run three times. The results show that phot1 mutants do not significantly differ from WT, phot2 mutants had a similar growth rate to WT but continued growing at a fast rate for a day longer, and phot1/2 had a much slower growth rate than WT. A second experiment was done using the same growth conditions, but using only WT, phot2, and phot1/2. On the sixth day after its appearance, the fifth leaf was removed from each plant and floated in a 5 millimolar solution of KCl for 24 hours. These leaves were photographed before and after to obtain their growth rates and the results were consistent with the first experiment which used intact leaves. The second experiment demonstrates that there is a phot-mediated mechanism contained within the leaf which influences growth. Knowing the cellular mechanism regulating leaf growth rate may help to understand how environmental stresses such as drought reduce plant productivity. Our next step will be to determine the mechanism which is causing the difference between the rates. First, we will look at anatomy of the leaves to determine if cell expansion or division is most affected by phototropin.

This study attempts to examine China’s New Socialist Countryside Construction policy and its potential environmental and socio-political consequences. Aggressive urbanization threatens the traditional landscape and governance structures of Sichuan province’s Chengdu Plain. Current scholarship on this subject examines potential reconstruction models and population densities on villages throughout Sichuan. I examine Zhanqi Village as a case study, an experimental region which is currently undergoing transformation. This study explores how alternative development strategies can be deployed to maintain the cultural and historic landscape, while maintaining local planning goals. I employ current urban planning theories focusing on population density and anthropological theories of spatial relationships. Using data collected from consultations with experts and critical reading of existing scholarship I provide a historical overview of the physical landscape and discuss potential redevelopment schemes currently being considered by local authorities. Lastly, I conclude with a discussion on the challenges and obstacles that will arise as a result of these programs. I hope that my research will inform local authorities on the challenges of current development models and contribute to a broader discussion on sustainable countryside development in China.

Malaria is an infectious disease caused by various species of the Plasmodium parasite which affects an estimated 207 million individuals, resulting in approximately 627,000 deaths per year. While this disease is primarily prevalent in developing nations, over half of the world’s population is at risk for malaria. Among existing malaria drugs, primaquine is uniquely effective against late-stage Plasmodium gametocytes and liver hypnozoites; however, it is dangerous to patients who are G6PD deficient. G6PD deficiency is caused primarily by point mutations in the Glucose-6-Phosphate Dehydrogenase (G6PD) protein—an enzyme that catalyzes the formation of NAPDH (a reducing agent) in the Pentose Phosphate Pathway. This condition affects around 400,000 individuals worldwide, most of whom live in areas at risk for malaria. Screening for G6PD deficiency is not readily available in many of these at risk areas and thus complicates treatment of malaria with primaquine. Therefore, screening for compounds that stabilize mutant forms of G6PD may yield potential candidates that can be used in combination with primaquine for a new therapeutic regimen. In a screen of ~100,000 compounds, 71 compounds were found to have stabilizing effects on mutant G6PD R454H (Andalus). Screening was done with a standard biochemical assay that measured enzyme activity through the detection of reaction product, NADPH (detected by fluorescence). Additional biochemical assays and studies on these 71 hits will follow to assess the mechanism and extent to which these compounds increase mutant G6PD Andalus activity. Candidate compounds that make it through these follow up experiments will then be tested with other G6PD mutants in search of a stabilizer of multiple G6PD mutants.

MicroRNAs are a group of highly conserved non-coding RNAs that play critical roles in regulating networks of genes. MicroRNAs bind to target mRNAs and can inhibit translation and/or facilitate degradation. One of these miRNAs, microRNA-21, plays an important role in kidney disease as it has been shown to increase in animal models of disease. Recent studies have shown that microRNA-21 promotes interstitial kidney disease with fibrosis by silencing metabolic pathways and by promoting reactive oxygen species formation. Mice with microRNA-21 deletion show a decrease in kidney fibrosis.

Our hypothesis is that cells isolated from microRNA-21 knock out mice will have decreased expression of cytokines associated with fibrosis. I will look at the expression of reactive oxygen species by live imaging of cells where microRNA-21 has been blocked. Then I will use quantitative polymerase chain reaction and Western blots to analyze protein levels for known molecules associated with fibrosis and inflammation. We expect to see that cells treated with anti-microRNA-21 have a reduction in reactive oxygen species, leading to less fibrosis and inflammation. Blocking microRNA-21 is a potential new therapy to combat kidney disease.

The Yi people lives in the south west of China, leading a life of the combination of growing and grazing which has lasted for hundreds of years. They have a rather distinctive culture characters with their own writing system, religion, customs, and clothes. Jieshy and Vala are two kinds of capes that play an important role in Yi people’s daily life. They are made of wool and have several similarities in outlooks but are functioned differently, especially in social lives and celebrations.However, as modern life is eventually influencing the life of the Yi people, Jieshy and Vala are less worn in daily life. In order to know the status of these two traditional clothes in Yi people’s modern life, we did several field researches in three Yi counties in Sichuan Province, China, during the summer of 2013. Our research focused on the productions and the application of these two kinds of clothes in modern life, and the Yi people’s attitudes toward them. Through our observations and interviews with local people and scholars, we know that nowadays, Jieshy and Vala are still used in funerals and traditional weddings and have almost been considered as a symbol of the group. But there is indeed a trend of reduction in the use of these two kinds of traditional clothes. The goal of our project is to present how modernization shapes the tradition and how people react to the changes.

Although patients diagnosed with pulmonary hypertension (PHTN) are at a higher risk for postoperative complications, studies to date have not distinguished whether this applies equally to all PHTN patients, nor have they determined the severity of postoperative complications should they occur. Pre-operative screenings take place in the form of echocardiograms (ECHO), which are accurate but rather expensive. This study, one of the largest pulmonary hypertension studies to date, is headed by Dr. Gail van Norman, director of the Pre-Anesthesia Clinic at the University of Washington Medical Center (UWMC). We look to explore the correlation between the severity of pre-existing pulmonary hypertension and post-operative complications. This study additionally explores the correlation between metabolic equivalences (METS) and PHTN, which could yield a new, more cost-effective method of screening for the disease. As research interns on this project, we abstract data from the medical records of eligible patients at UWMC. We focus on patients who have undergone surgery with moderate to severe PHTN, and collect pre-op and post-op data using hospital affiliated databases. Patients with these specific conditions are believed to have <4 METS and are at an elevated risk for post-operative complications. Should these hypotheses be proven correct, the results of this study will benefit both patients and providers, reducing the cost of screening, as well as improving patient care by allowing doctors to better manage the disease in the peri- and postoperative settings, reducing both complication and mortality rates.

Intra-articular calcaneal (heel bone) fractures are common tarsal injuries that can require months for recovery. There are a few different treatment options available for these fractures including nonsurgical immobilization treatments, open reduction and internal fixation (ORIF) and percutaneous fixation. Classification of fractures can be a useful tool for medical professionals for communication and treatment planning. The existing calcaneal fracture classification systems used in clinical settings are subjective and not reliable tools for determining the best treatment for patients especially for highly fragmented (comminuted) calcanei. Calcaneal fracture treatments have high complication rates which compounds the need for a better treatment planning tool. The project goal is to develop a new calcaneal fracture classification system that utilizes CT image data to objectively calculate fracture severity metrics of the calcaneus, namely free bone surface area and the volume of surrounding soft tissue swelling. These metrics will be included on a calcaneal fracture report in addition to a model of the fractured calcaneus with fracture lines indicated. The software is developed using the Visualization ToolKit (VTK)  and the calcaneal model generated based on Simpleware ScanIP segmentation of the CT images. In the future, the software can be used to develop an index for the best treatment option for each fracture classification giving medical professionals a tool for aiding in treatment planning and a means of communicating fracture severity.