Chronic inflammation is a silent killer, contributing to death in patients with chronic kidney disease (CKD) and other chronic disorders, such as diabetes and obesity. Although the specific molecular pathways linking inflammation contribute to CKD pathogenesis still remain unclear, interleukin-6 (IL-6), the prototypic inflammatory biomarker and a potential mediator, is believed to be able to help us understand the mechanism that leads to CKD. We have been investigating the role of IL-6 family of genes using different animal models, such as the Unilateral Ureteral Obstruction (UUO), to induce interstitial fibrosis. The results from our studies have demonstrated that IL-6 and gp130 are profibrotic molecules. Therefore, our goal was to understand the mechanisms of IL-6 in myofibroblasts, the major contributors of collagen during fibrosis. For these studies, we used wild-type mice, IL6 (+/+), IL6 (-/-) and αSMA-Cre-IL-6(fl/fl), in the UUO model of interstitial fibrosis. We hypothesized that IL-6 regulates the crosslinking of collagen by regulating the lysyl-oxidase gene. Therefore, we assessed the Extracellular matrix expansion and collagen accumulation by measuring the changes in gene expression of Col-1, 3, and 4, IL-6, Lysyl-oxidase, Fli-1 and Hells at different time points during renal fibrogenesis. We consider that the change in collagen crosslinking is an important factor in the turnover rate of collagen and it changes its stability to be degraded/accumulated. The examination of the role of IL-6 could potentially provide a new therapeutic breakthrough for treatment and better detection/assessment of renal fibrosis.

Most adults have some degree of atherosclerosis. In a subset of these individuals, atherosclerosis progresses more rapidly. Increased activity of proteases (enzymes that digest proteins) in atherosclerotic plaques is a plausible cause both of atherosclerosis progression and of atherosclerotic plaque rupture. Plaque rupture is often a terminal event that results in blockage of arteries, heart attacks and strokes. Urokinase plasminogen activator (uPA, a protease that is present in plaques) functions by converting plasminogen (a zymogen, or enzyme precursor) into its active form, plasmin. The uPA/plasminogen pathway facilitates macrophage migration, enhances the release of inflammatory mediators, and activates other proteolytic enzymes, all of which may contribute to atherosclerosis progression and plaque rupture. We hypothesize that inhibition of uPA will decrease atherosclerosis progression and prevent plaque rupture. To begin to test our hypothesis, we use a mouse model of uPA-accelerated atherosclerosis (mice that are genetically predisposed to develop atherosclerosis and express high levels of uPA). We inject an antibody (mU1) that binds to and inhibits uPA, or a control antibody, and we measure atherosclerosis in aortic roots and pinned aortas. We anticipate finding less atherosclerosis in mice treated with mU1. We also expect to find fewer macrophages in atherosclerotic plaques of mice treated with mU1. If we find that inhibition of uPA decreases atherosclerosis progression and that it is also well tolerated by mice, we will later set up an experiment in older mice to determine whether anti-uPA treatment with mU1 will prevent plaque rupture. If uPA activity contributes to atherosclerosis progression, and if inhibiting uPA decreases atherosclerosis progression and prevents plaque rupture, drugs could be developed that inhibit uPA. These drugs could be used to treat humans who are at high risk for atherosclerosis progression and plaque rupture.

When a photon is absorbed by materials called semiconductor nanocrystals or quantum dots (QDs), the energy from the photon is also absorbed and can be used to excite the semiconductor nanocrystals. If the energy of the photon is at least twice the energy of the bandgap, or the energy between two specific states, at least two charge carriers can be created. Charge carriers are inherent in any material which can absorb energy and undergo a process of excitation to a higher energy state by the photon followed by relaxation to its normal energy state accompanied by a release of energy. Conversely, when the energy of the light does not exceed twice the band gap, only one excitation is observed. If a material exhibits the property of creating multiple charge carriers, often called Multiple Exciton Generation (MEG), it can be stated that this material will likely enhance a solar cell since energy from the light absorbed by the cell will result in multiple charge carriers created followed by multiple relaxations and the releasing of energy. MEG has been shown to exist in a variety of QDs. Here, we attempt to confirm the presence of MEG in germanium QDs. This was done by pumping 400 nm and 800 nm light with a pump-probe laser and collecting the absorbance spectra at different power levels. The spectra can be analyzed to demonstrate if MEG occurs by comparing the absorbance at these different power levels. The results have provided no conclusive evidence of MEG in germanium nanoparticles. This result allows for further research to be performed on what may impact MEG and what materials are ideal for MEG.

This project demonstrates a new synthetic approach to tetrapod-shaped colloidal nano structures using a combination of Mn doped CdSe quantum dot cores and CdS rods. These structures are achieved using a variation in quantum dot hot injection synthesis in which Mn is added before the injection of the anionic precursors. Once the initial synthesis is complete the products are characterized by UV/VIS absorption, photo-luminescence, EPR, and TEM imaging. Once characterized the doped quantum dots are re-immersed for arm growth to achieve the tetrapod shape. Mn doping provides a magnetic probe in the nano particle that would allow us to probe the carriers during temperature dependent luminescence. Semiconductor quantum dots are believed to be useful materials in solar energy cell applications because their band-gap can be manipulated by changing the size of the particles. However, one of the limiting factors in the efficiency of these dots is the fast recombination of the carriers in the material. Tetrapod nano structure semiconductors have demonstrated the ability to extend the lifetime of exitonic emission which enables greater separation of the carriers and may potentially increase the efficiency of future solar applications. Preliminary results show that Mn doped tetrapods can be synthesized using this method; however yields need to be maximized in order for future applications to come to fruition.

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.

Climate change is arguably the most important issue society faces in the next century. A principle driver of climate change is the emission of “greenhouse” gases to the atmosphere, which enhance warming by trapping heat. Methane in particular has a powerful warming potential relative to other greenhouse gases. One potential source of methane to the atmosphere is gas hydrates, solid crystalline structures of natural gas and water found in marine sediment. Gas hydrates are solid only under certain conditions of temperature and pressure; otherwise, the crystal structure releases gaseous methane in the water column. Gas hydrates pose a threat to the climate in two ways – by dissociation in unstable conditions and by passive “leakages” of methane from deep reservoirs that bypass the gas hydrate stability field. Both processes result in bubble plumes of methane gas in the water column, which may be reaching the atmosphere through gas exchange. Hydrate Ridge, offshore Oregon, represents a good model system to study for understanding gas hydrate dynamics, and it is a known site of passive fluxes of methane. This study uses novel sampling methods, such as ROV sampling for increased accuracy, to collect water samples at Hydrate Ridge which will be analyzed for methane content. Multibeam sonar data were also collected to image the spatial extent of the bubble plumes. The data will indicate the degree to which methane is penetrating into the water column and reaching the atmosphere. Hydrocasts from the research vessel R/V Thompson were taken at Southern Hydrate Ridge over two years, 2010 and 2011, for analysis in the lab with a gas chromatograph. The end goal of the project is to quantify the flux of methane into the mixed layer of the ocean, which exchanges methane with the atmosphere faster than it is consumed by microbial oxidation.

This research explores the function and dynamics of gold nanoparticles functionalized with azobenzene- modified DNA. When exposed to UV light, the azobenzene groups photoisomerize, melting the DNA and dissociating aggregated nanoparticles. This process is reversible with introduction to blue light, initiating the isomerization that allows the DNA to rehybridize and the particles to form aggregates once again. Our research focuses on the dynamics of this transition, determining the extent of trans-cis isomerization of the azobenzene DNA coupled to gold nanoparticles, a process which is monitored through pronounced changes in light absorption between the trans and cis conformations. This information creates a baseline for future photoswitching calculations, accounting for differences in behavior between free azobenzene DNA and such DNA in the presence of gold nanoparticles. We also use the kinetics of the light-induced dissociation and reassociation to provide information about the composition of the DNA, with respect to location of the azobenzene group embedded in the DNA strand. This information can assist with detection and location of base-pair mismatches within the coupled DNA.

The concept of dynamically causing physical distortion of molecular frameworks to influence reactivity offers an intriguing opportunity for synthetic polymer chemists and materials scientists. Strained rings have been shown to undergo chemical transformations under different stimuli but their mechanochemical behavior is a relatively newer field of study. We postulate that directing a reaction pathway mechanochemically may be a viable means to increasing the selectivity in the ring opening event. Before the mechanochemistry is investigated, the polymeric materials containing these ring systems must be designed and synthesized. The development of our strained ring system is multi-step synthesis starting from a commercially available small molecule. Once the strained ring small molecule is created, the final step of the synthesis is to incorporate it in the middle portion of a polymer. After the molecular framework has been built, its mechanochemical reactivity is studied via solution-based experiments using an ultrasound probe and processor (20 kHz) of variable power output (up to 750 watts). This approach will facilitate product characterization, mechanistic inquiries, and reactivity profiles. Collectively, the ambitious research objectives provide a fundamental basis of how mechanical forces may be used to guide and control reaction profiles.

The Fourteenth Amendment attributes citizenship to all those born within the “jurisdiction” of the United States. However, the acquisitions of the Philippines and Puerto Rico by the United States challenges conceptions of citizenship, as both colonies’ inhabitants were neither entitled to citizenship nor were able to stake claims on American identity upon annexation. Through a legalize investigation centering on Supreme Court cases and legislations, I will show the manipulation of citizenship to politically disenfranchised colonies while promoting empire. The Insular Cases amplify the complexity of territorial citizenship, by stating that the Philippines and Puerto Rico are “foreign to the United States in a domestic sense”- a paradoxical relationship where the Philippines and Puerto Rico are prohibited from establishing independence, yet alienated within the United States. However, the Jones Act (1917) administers U.S. citizenship over Puerto Rico, inferring a preferential treatment towards Puerto Ricans over Filipinos. In actuality, transcripts of Congressional hearings and committee debates pontificate different tactics of U.S. policymakers to remedy resistance and independence movements within the Philippines and Puerto Rico. Economic incentives, evidence of Americanization, but most importantly, the racial conception between the two parties justifies the granting of citizenship for Puerto Ricans over Filipinos. The varying racialization coupled with the intimate connection between citizenship and American identity influenced not only politicians but national sentiment as to who is and is not an American. The examination of U.S. citizenship between Filipinos and Puerto Ricans ends with the enactment of the Tydings-McDuffie Act (1934), granting the Philippines independence and self-government after a period of time. In retrospect and comparison to contemporary issue, the idea of citizenship is subject to change and is closely linked to national identity. Nonetheless, the administration of citizenship defines and denies power and privilege among groups of people.

As consumers continue to face high energy bills and the efficient use of resources becomes vital to the sustainability of modern society, the need for a device to intelligently manage electricity consumption grows. The Energy Saving Butler, a computer system to be installed in homes and workplaces, seeks to meet this need by simultaneously minimizing the cost and unnecessary use of electricity--all without inconveniencing the users. The Butler is true to its name: acting behind the scenes and within the confines of the household's schedule, while working to allocate electricity efficiently and discreetly. Our team has conceptualized the features and functions that will drive the future technical design of this device. Based on data from the power company and data on appliance use, the Butler can delay or initiate tasks, such as laundry and dishwashing, so that they occur at times where power rates are at their lowest. Using a complex and dynamic priority level system, this control of power allocation is designed to work within the user’s schedule. If the user is having a dinner party one night, for example, the Butler will automatically suspend its own activities so as to not interfere with any social functions. If that user also finds his or herself driving home on a cold night, that user’s smart-phone can notify the Butler when it is within a 10-mile radius, so that the Butler can turn on the home’s heating. With these and a wide array of other practical features, we feel that the Energy Saving Butler will go a long way in saving consumers' money and working to stabilize the over-burdened power grid. It’s appealing to the consumer; it’s appealing to the utility companies; it’s a step in the right direction for a more sustainable society.

Colloidal semiconductor nanocrystals (NCs), often referred to as quantum dots, are a class of materials that exhibit size dependent photo physical properties. This class of materials has great potential for application in a variety of fields such as photovoltaics, light emitting diodes and spintronics. Doping NCs with transition metals provides additional tunability of the optical and physical properties has been synthesized. By tuning the energy gap of these NCs within thermal reach of the Mn2+ 4T1 excited state a highly temperature sensitive dual emission is acheived. The synthetic route to these dual emitting nanocrystals required the synthesis of a Mn2+:ZnSe core followed by the sequential growth of three shell layers. Doping Mn2+ into a Zn1-xCdxSe allow however, could prove to be a more efficient route to dual emitting nanocrystals with higher stability. Successful incorporation of Mn2+ into Zn1-xCdxSe alloys has resulted in dual emitting NCs.

In the past decade, there has been increasing interest in the potential of new thin-film solar technologies. Research in this field has focused largely on organic photovoltaics (OPVs) utilizing a bulk heterojunction (BHJ) design, consisting of blended films of conjugated polymer electron donors and fullerene electron acceptors.Use of semiconductor nanocrystals or “quantum dots” as a replacement acceptor material for the fullerene has been proposed as an alternative. In this research, charge transfer between lead sulfide nanocrystals and a conducting polymer, "poly(2,3-didecyl-quinoxaline-5,8-diyl-alt-N-octyldithieno[3,2-b:2′,3′-d]pyrrole) " or PDTPQx is investigated by time resolved spectroscopy. Previous work has found that incident light exciting the polymer results in transfer of an electron from the polymer to lead sulfide nanocrystals present in the blend. This electron transfer leaves a net positive charge on the polymer, which is accompanied by a characteristic spectroscopic signature. It is found in this research that selective excitation of the lead sulfide nanocrystals using an infrared laser also results in observable positive charge carriers on PDTPQx. This indicates that light absorption at the lead sulfide nanocrystals results in transfer of positive charges from the nanocrystals to the polymer. Confirmation of this additional charge transfer process has important implications for the potential this system in photovoltaics.

The acid-catalyzed dehydration of 4-methylcyclohexanol yields a mixture of several isomeric methylcyclohexene products. The major product of this elimination reaction, 4-methylcyclohexene, is produced through the E2 mechanism. However, mechanisms for the formation of the minor methylcyclohexene products are not predicted by the traditional textbook explanations of carbocation rearrangements. 1-methylcyclohexene is thought to be produced by means of an E1 mechanism in which rearrangement of a carbocation intermediate takes place. This experiment was designed to classify the hydride shifts by observing the products of this reaction using 1,2-²H-4-methylcyclohexanol. The deuterated starting materials for this reaction were prepared in our lab. Gas chromatography-mass spectroscopy and nuclear magnetic resonance analysis were used in the characterization of the products and for the classification of the pair of 1,2 hydryde shifts in tendem and of the single 1,3 di-axial hydride shift, leading to the formation of the 1-methylcyclohexene product. This is useful to know when trying to predict the products of reactions in which intermolecular rearrangements occur during carbocation intermediates.

The mechanism to direct auditory attention consciously is not well understood. For hearing impaired people, it is very hard to direct attention efficiently between conversations with background noise. My project investigated the differences between maintaining and switching attention prompted by visual cues. In the behavioral task, two streams were presented simultaneously, one with high pitch and the other, low. Each stream consisted two triplets of spoken letters and the two triplets were separated by a silent gap that varied in duration. In the beginning of each trial, subjects were prompted by two spoken letters which stream (high or low) to pay attention to initially. Simultaneously, a visual cue directed subjects to either stay or switch between two streams during the silent gap period. Subjects were asked to respond when they heard the second ‘E’ from one of two streams that they attended to as quickly and accurately as possible. Preliminary results suggest that subjects needed more time to respond when they had to switch between streams. As expected, there were no differences between subjects attending to the high or low pitch stream. We also hypothesized that the shorter the gap period, the longer the response time will be—I hope to test this hypothesis through more in-depth data analysis. The result from this project will be analyzed together with neural data obtained using magnetoencephalography where subjects will be performing a similar task. The findings of this project will provide insight into the underlying mechanism of switching of auditory attention—a task that hearing impaired people find difficult to perform in a noisy environment, even with the help of hearing aids or other augmentative devices.

This project will investigate the hypothesis that in utero exposure to clinically relevant doses of diagnostic ultrasound increases the risk for the manifestation of symptoms of autism. It is hypothesized that autism is caused by a triple hit of risk factors: a genetic susceptibility, a developmental time window of vulnerability, and an environmental factor. Diagnostic ultrasound is a candidate environmental factor within this “Triple Hit Hypothesis” for autism. To take the first steps toward testing our hypothesis, we propose to assay for ultrasound-associated changes in behavior and neuroanatomy of three mouse strains that have been well characterized in terms of social behavior. One strain is known for normal social behavior and the other two are known to exhibit autistic-like behaviors. Specifically, standard diagnostic ultrasound will be applied to mice at a key developmental time point during pregnancy to half of a group of mothers, and the other half will undergo the same procedure, but the ultrasound will not be turned on (sham application). At three weeks of age, the social, repetitive, and other relevant behaviors of the pups will be assayed using a battery of tests that includes a social approach test, a juvenile play test, open field observation, and several other methods. We will then analyze the data for significant differences in magnitude or occurrence of these behaviors within the three strains of mice based on their ultrasound exposure group. If the magnitude and/or occurrence of these behaviors are greater in the ultrasound-exposed group compared to the sham group in at least one of these strains, then our hypothesis will be supported and further experiments will be critical.

Populus trichocarpa, or Black Cottonwood, form a mutualistic relationship with diazotrophic bacteria, in which nitrogen is provided to the host plant in exchange for protection and energy. Understanding this form of symbiosis is essential in determining how biologically available nitrogen is cycled throughout our planet’s biomes. A well-known diazotrophic mutualism is found between leguminous species and Rhizobia or Frankia bacteria, where colonies are established inside root nodules of the host plant. Black Cottonwoods differ from legumes in that they form an endosymbiosis with nitrogen-fixing bacteria recruited from the environment, where the bacteria form colonies throughout the plant tissue. To determine the endophyte source, bacterial samples were obtained from sand, river water, and seed collected at the Three Forks Park in Washington to determine where in the environment Black Cottonwoods are coming into contact with these endophytes, and which species are found at each source. Nitrogen-fixing species were selected for by culturing bacteria using nitrogen free media, and were then subjected to PCR for amplification of the nitrogenase gene for confirmation. Species identification was performed by amplifying the 16sRNA, followed by sequencing and local alignment matching. Of the 29 samples collected from the Three Forks site, 27 were found to carry the nitrogenase gene, and species identification underway. Black Cottonwoods, in addition to other poplar species, have been found to be very useful industrially as biofuels and in the bioremediation of environmental pollutants. Nitrogen-fixation provides a major benefit for using poplars, where the use of fertilizers is reduced. It is thought that there is a common evolutionary link between more plant species and diazotrophic bacteria than is currently known, and understanding which species exist outside of the plant hosts may lead to the reduction of nitrogen-based fertilizer in other industrially useful plants.

In eukaryotic organisms, ubiquitin is a small protein modifier that is attached to proteins and targets them for proteasomal degradation. In an analogous fashion, in Mycobacterium tuberculosis (Mtb), the prokaryotic ubiquitin-like protein (Pup) is conjugated to lysine side-chains of substrate proteins and targets them for degradation by the Mtb 20S proteasome. This pathway has been shown to be essential for Mtb infection in mice, and is a potential target for theraputic reseach. The enzyme PafA is responsible for attaching Pup to its substrates and has previously been shown to be essential for lethal infections by Mtb in mice. We have developed a fluorescent activity-based probe to monitor PafA activity in vitro by conjugating Fluorescein isothiocyanate (FITC) to free lysine, a known substrate of PafA. FITC-Lys demonstrates a high degree of specificity for PafA, even in the presence of cell lysates. This probe was employed to visualize PafA activity by in-gel fluorescence. It has allowed us to identify a minimal sequence of Pup, the C-terminal 26 amino acids, that is recognized by PafA. Alanine mutants of the 25th and 26th C-terminal residues demonstrate that leucines at these positions are critical for PafA interaction.

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.

It is a common dilemma for undergraduate students to feel like their class material is inapplicable to the real world. This project aims to enhance traditional homework assignments with problems based on current scientific literature. The current class of interest is Physical Chemistry for Biochemists I at the University of Washington, taught by Dr. Munira Khalil. I developed homework questions using journal articles that focused on concepts of thermodynamics important in biochemistry. The questions test the students’ comprehension of the article and their ability to solve quantitative problems based on research presented in the article. These questions were integrated with traditional assignments already given in this course. Dr. Khalil’s class in Fall 2011 served as a test run for the literature focused homework assignments. At the end of this course, students evaluate the homework through an online survey. These evaluations were used to adjust the homework assignments for the same course in Winter 2012. Information from both quarters of surveys gave insight into how learning about research influenced a student’s interest and performance in the class.

Over the past ten years we have analyzed a variety of plants that produce volatile oils grown in our Chemical Garden on The Evergreen State College campus. These plants lend themselves well to extraction by steam or ethereal solvents and are easily analyzed through Gas-Chromatography Mass Spectrometry (GC/MS). The plants we have focused on are garlic, St. John's Wort, hops, mints, and lavender. This poster reports on our progress towards isolating and identifying individual constituents of Devil's Club (Oplopanax horridus), a local plant with a long history of use as a medicine. We have been curious as to the best time of year to harvest the plant, as there is some debate in the herbalism community on this point. The Devil's Club was distilled at different times of the year and analyzed using GC/MS. The non volatile constituents were extracted using a number of different solvents and analyzed using Thin Layer Chromatography (TLC). This research will provide information on the effects of harvest time on constituent levels, as well as providing knowledge of the chemical make up of this plant.

Model membranes are important tools for investigating physical properties of lipid bilayers. Unfortunately, current techniques for producing giant unilamellar vesicles (GUVs) with biologically and physically relevant properties (namely: inclusion of charged lipids, encapsulation of high salt buffer, and compositional asymmetry between the inner and outer leaflets) are difficult, unreliable, and/or low throughput. We examine a method called cDICE, developed by Abkarian et al., that has the potential to address all of these issues. Our results here for charged lipids in high salt buffers are promising, whereas asymmetry has proven difficult to measure.