The overall objective of this research project is to develop a high-yield site-specific bioconjugation method for use in developing new cancer therapy agents using the reaction of benzaldehydes with oxyamines. Bioconjugation is the term to describe the development of new pharmaceuticals. It often involves coupling one biomolecule (e.g. monoclonal antibody) with another chemical species (e.g. drug, toxin, radionuclide-binding molecule). The first aim of the project is to synthesize four water-soluble discrete-sized polyethylene glycol (dPEG)-benzaldehyde derivatives, and then determine their relative reaction rates with a water-soluble oxyamine compound. The fastest reacting compound is determined by high performance liquid chromatography (HPLC) analyses and studied further. The second aim in the research project is to conjugate the two most reactive dPEG-benzaldehydes to a monoclonal antibody. The final aim is to assess the bioconjugation reaction of a biotin-oxyamine derivative with the two benzaldehyde-modified antibodies. The biotin-oxyamine conjugation yields will be determined using an avidin-binding (HABA) assay that uses UV quantification.

Statistically, Asian Americans have significantly lower traffic accidents than any other minority group in the United States. However, there exists a stereotype that Asian Americans are a bigger risk on the road than any other ethnicity. This study explored the perspectives of Asian Americans, specifically Korean American women living in the city of Bellevue. Despite having enough English speaking skills to live comfortably in America, they had either a difficult time understanding roadway signs and posts, or if they did, it was not intuitive at first glance or within the time span necessary to make a decision on the road. The major problem that these Asian Americans felt was that in their homeland, many traffic decisions were made based on their instincts due to minimal roadway signs, or enforcement was so minimal that conforming to these traffic laws were not a priority to them. They reported that this mentality was reinforced more so because even when traffic laws were ignored, accident rates were low. This suggests that Asian Americans, though involved in less traffic accidents, make decisions less-rapidly, are confused on the road, or less readily conforming to traffic regulations. This study helps uncover a largely untapped field of study involving traffic safety within minority groups, and will further contribute to future research in similar topics.

While sexual co-mingling of the races in the Americas began as early as the first cases of colonization, miscegenation remained an unspoken taboo in America until roughly the mid-century, when many cases of mixed-race couples began increasing in visibility in local communities, popular culture, and the courts. These couples found themselves thrust into the spotlight as either martyrs for the cause, fuel for the propaganda against mixed unions, or examples for popular interest pieces in magazines and newspapers. The role of news outlets in bringing public awareness to the presence of interracial relationships, for good or for bad, was crucial. This project explores newspaper articles over a 20 year period (late 1950s through the early 1970s) from three American Black newspapers: New York Amsterdam News, Pittsburg Courier, and Atlanta Daily World, and analyzes them from several perspectives, considering regional differences, date of the article (before or after the Loving v. Virginia decision), and subject matter of the article. Findings revealed several themes: emphasis on the white, female opinion, shifting generational divides, and the role of celebrity and celebrity mixed unions in public interracial marriage awareness. This project displays my discoveries in how the black community felt about interracial marriages during this period, as well as how the black media sought to influence public opinion regarding the topic.

Aging is a process that causes decline in normal biological function, eventually leading to disease and death. Aging is influenced by a number of factors, including stress-response pathways such as the hypoxic response. Over-expression of the hypoxic response pathway regulator, Hypoxia-inducible factor (HIF-1), increases lifespan in the nematode Caenorhabditis Elegans. Under atmospheric oxygen, HIF-1 is targeted for degradation by the Von Hippel Lindau (VHL-1) tumor suppressor protein, whose deletion increases nematode lifespan through increased HIF-1 activity. Since knocking out VHL-1 in mammals is known to cause disease, it is important to better understand the hypoxic pathway in nematodes to develop targeted therapies for age-related diseases in humans. The goal of this research is to determine the tissues and genes downstream of HIF-1 that modulate aging in C. elegans. To determine tissue specificity, we have developed vectors designed to reintroduce VHL-1 into VHL-1 knockout worms under the control of tissue specific promoters. Lifespan and other age-related parameters will be measured in these transgenic animals and compared to that of control groups. To further test tissue specificity, we are also developing vectors to overexpress a mutated non-degradable form of HIF-1 in specific tissues in wild-type worms, essentially the reverse of the reintroduction of VHL-1. To test for genes downstream of HIF-1 important for longevity, we have performed a screen and identified several genes that are important for HIF-1-induced lifespan extension. Our experiments will examine whether C. elegans lifespan is increased by the over-expression of these proteins, which would then suggest further characterization and a search for conserved proteins. Together, the results from these experiments will provide important information on how we might utilize the hypoxic response pathway to improve human health.

There is a high need for transitional housing in areas affected by natural disasters, particularly transitional housing that is permanent, high performing, economical, and sustainable. Current solutions, predominantly large tents, do not provide a satisfactory living state for the tens of thousands of people displaced by these natural disasters. Alternate housing options have been developed and implemented, but the response of these alternatives under seismic loading has not been sufficiently studied. A promising alternative is the use of strategically stacked earthbags in combination with frictional material between the bags, strapping, and render for aesthetic purposes. The placement and configuration of these materials impacts the flexural and shear response of the entire housing system. Through modeling force versus deflection of various models, we can predict the response of the earthbag structure. Using strategic bag placements and placement of restraining components, the goal is to quantify the response of the structure. We anticipate that weaving strapping throughout the bags will provide more resistance to buckling and failure in the configurations discussed throughout this paper. By quantifying the relationship of materials and response, we can design an economical and viable transitional housing solution to respond more predictably under earthquake loading. The design of this structure can provide an economical, accessible, and easily constructible housing alternative.

Organisms have evolved specific mechanisms to respond to molecular and environmental stress. These stress-response pathways are evolutionarily conserved and can modify lifespan in model organisms, making them popular targets of aging research. Using the nematode Caenorhabditis elegans (C. elegans), we have found the loss of important genes in stress-response pathways can cause a phenomenon called a vulval integrity defect (Vid). Worms with Vid show a small protrusion near their vulva that can eventually lead to rupture of the gonad and premature death. While many labs have noted this phenotype, it is unknown if Vid is a natural part of C. elegans aging or if other genetic and environmental factors induce this phenotype, leading to confusion as to whether worms with Vid should be censored in aging experiments. The goal of our project is to determine the mechanism of Vid and whether it is part of normal worm aging. To further define the mechanism of Vid, we are using three experimental approaches: (1) using mutant worm strains, we are testing the genetic pathways important for causing and preventing Vid, (2) because Vid is temperature dependent, with frequency increasing inversely with temperature, we are testing at what point in their lifespan worms can still be rescued from Vid, (3) beginning with the gonad and vulval muscle, we are looking for cellular death and/or structural weaknesses that could be the direct mechanism behind Vid. Our initial work has identified several genes and genetic pathways important for Vid, including the hypoxic response pathway, the oxidative stress response pathway, and the protein assembly pathway. Our current work is close to identifying when worms are most susceptible to Vid and has begun to describe the physical mechanism of Vid. We intend to combine the results from these experiments to develop a model for Vid.

Aging research seeks to determine the processes that cause degeneration and disease in aged organisms, and to discover ways to prevent and/or slow their progression. Previous studies have shown that aging can be slowed in several model organisms through various means; however much is still not understood. In the model organism Caenorhabditis elegans, previous work shows that decreasing oxygen levels (hypoxia) significantly increases lifespan. The hypoxia-induced lifespan increase is observed when worms are exposed to hypoxia either from a late larval stage for life or if they are deprived of oxygen for just one day at the same larval stage. The low oxygen environment activates the hypoxic response pathway, mediated by the hypoxia-inducible factor (HIF-1). Previous data show that an increase of the HIF-1 protein, via genetic mutation or alterations in atmospheric oxygen, is sufficient to extend lifespan. However, much about this pathway remains unknown, including the mechanism for increased longevity, the difference between genetic and environmental manipulations of HIF-1, and the downstream proteins involved. My project examines the genetic components responsible for extending lifespan in hypoxia. To test this, we measured whether hypoxia increases the lifespans of worm strains with deletions or transgenic overexpression of known aging genes. Our results suggest that disruption of most of the non-HIF-1-related pathways have no effect on hypoxia-induced lifespan extension. However, the data show that the forkhead transcription factor, DAF-16, is required for hypoxia to increase lifespan, and subsequent work has shown that hypoxia causes DAF-16 to enter the nucleus. Interestingly, results indicate that hypoxia decreases lifespan when the oxidative stress response factor, SKN-1, is overexpressed, suggesting that SKN-1 is somehow toxic to worms in low oxygen. Collectively, the results show that hypoxic treatment increases lifespan in worms, but that the hypoxic pathway is intertwined with other stress responsive pathways.

Photoactivation of compounds such as chlorophyll derivatives results in the excitation of oxygen into a highly reactive singlet state which causes cellular damage and death. This property is used as a cancer therapy, specifically in photodynamic therapy (PDT.) Although PDT has been proven to be effective at eradicating cancer, it has not been widely adopted due to poor penetration of light into body tissues. To avoid this limitation, photosensitizing molecules that absorb light at longer wavelengths are being synthesized to allow deeper tissue penetration. It is possible that the modification of a chlorophyll derivative called chlorin e6 (Ce6) via cycloaddition reactions, such as the Diels-Alder reaction, will lead to a molecule with a wavelength absorption long enough (750-800 nm) to obtain good tissue penetration. Such a molecule will eventually be attached to a cancer-targeting antibody to increase its tumor concentration, which will boost treatment effectiveness and minimize healthy tissue damage. Among the methods employed in the organic syntheses being studied are high-performance liquid chromatography (HPLC), ultraviolet-visible spectroscopy (UV/Vis), nuclear magnetic resonance (NMR), and mass spectroscopy (MS.) The cycloaddition reactions of a Ce6 derivative with a synthesized molecule are currently under investigation. If successful, PDT with this compound can be applied to treat a wider variety of cancers in a targeted and systematic way, while avoiding the nasty side effects of chemotherapy.

Multi-Legged terrestrial biological systems demonstrate complex forms of locomotion by utilizing different gait patterns. These complex forms of locomotion provide a path for promising advancements in the development of biomimetic systems. In previous research, we analyzed various multi-legged terrestrial systems and several variables that effect the selection of the gait pattern became apparent. It was found that the number of legs, stability of the system, and velocity of the system all had a significant effect on the gait patterns selected and the gait patterns that are available for use in the system. This research focuses on constructing biomimetic walking systems, using LEGO Mindstorms NXT robotic kit, which implement the carious characteristics of animal locomotion to determine the effect of these variables on the gait patterns. The current systems under analysis consist of six legs controlled by interactive servo motors and an NXT micro-computer which allow the system to move with several distinct gait patterns. From the biomimetic system, it is shown that some gait patterns are inefficient under certain conditions and this may lead to determination of when a gait pattern change is necessary in both the biological and biomimetic systems. Application of this research include pattern selection in mechanical systems and design influence on biomimetic systmes.