America has become a world leader in medical research because of the achievements in research and technology made by pioneering physicians in various specialist medical fields. In America, specialist physicians have come to dominate the physician population, more than in other developed nations. For government health insurance programs such as Medicare, specialist physicians already receive substantially higher reimbursements than primary care physicians, namely because of the higher costs of running their practice, in addition to complex and risky nature of their field of medicine. Medicare calculates reimbursements based on the costs, skills and liability of a physician's practice at the same rate throughout the country. However, Medicare provides for regional adjustments of these costs through the Geographic Practice Cost Index. I hypothesize that the geographic index amplifies the difference in how much specialist physicians make compared with their primary care counterparts. As the index increases in value, the compensation gap between the two groups widens, providing additional incentives for specialists to practice in areas where the geographic index is high. Using physician population statistics and the Geographic Practice Cost Index, I ask whether the income advantage of specialty physicians where the index is high leads to an undersupply of primary care physicians compared to other areas.

Does gubernatorial leadership matter? Declining revenues associated with the great recession encourage state governments to use their limited resources more efficiently. However, elected officials will often disagree about priorities, which can make enacting necessary reforms difficult. The goal of this research is to investigate whether state variations in gubernatorial powers impact the ability of governors to respond to important challenges, such as the effects of the great recession. I study fifty states from 1960 to 2012, and ask whether unified government versus divided government, the strength of the governor’s veto power and the strength of the governor’s budget powers is related to a state’s economic performance. Controlling for other factors, I expect to find that states where governors have more veto and budget power, and where the government is unified under same party also tend to have lower unemployment rates. By improving our understanding of the relationship between governors and state economic performance, this study may also shed light on how national reforms strengthening the executive powers might impact presidential economic performance.

In Africa, emergency humanitarian relief operations, in response to ongoing conflict and natural disasters, continue to struggle with violent, targeted attacks on humanitarian workers, aid supplies and refugees. While food aid plays an important role in addressing food shortages, previous studies suggest that food aid can contribute to the spread of civil conflicts under certain conditions. The purpose of this study is to examine the possibility that certain levels of food aid could exacerbate political violence against refugees in Africa because armed groups are likely to be motivated to prevent food aid distribution to an opponent refugee population, and to achieve material gain. To evaluate this claim, I analyze the relationship between three different types of food aid and delivery methods reported in the World Food Programme between 1988 and 1998, and data on affected refugee population by political violence against refugees in African countries. Food aid, defined as emergency food aid, programme food aid and project food aid, is delivered through direct transfer, local purchase and triangular purchase. In this study, the basic conditions of food aid consist of all commodities and all donor countries. There are fifty-three African countries that reported the amount of food aid they received, and twenty-six African countries that reported the number of refugees affected by political violence during the years of study. Based on the available data, I create several regression models that show the effects of each food aid and delivery method on rate of violence. I expect that emergency food aid and direct transfer have a strong positive correlation with violence involving refugees because they are directly delivered to targeted refugees who are at risk for insurgent attack.

Since gaining the right to vote, women’s influence in the political sphere has been on the rise. While voters have started to embrace women as political leaders, research done by Huddy and Terkildsen on gender stereotypes and their effects on candidates finds that female leaders are not given the same respect as male leaders when it comes to military and police issues. Their research also finds that the inverse is true; male leaders are not perceived to have the same competence as female leaders on social welfare issues such as health care and family support programs. I will investigate this question of gender issue ownership by examining the impact of gender on gubernatorial power in 50 states over ten years. I will compare the changes in state spending across policy areas. I hypothesize that, other things equal, a change in the gender of the governor will predict changes in program spending across policy areas. I expect that governors who are perceived to be more competent in a specific policy area will have a greater effect on the spending in that area and therefore that a change in gender of the governor will predict a change in spending.

One role of the state is to help foster economic growth. Financial incentives and regulations are thought to play important roles in industry location and investment decisions. Industries related to bioscience address important problems in society, from how to increase food production to how to defend against viruses. These industries are projected to see large levels of growth over the next 20 years. To explain differences in bioscience industry growth across states, I created a data series that analyzes the incentives available in each state against the impact of each of their bioscience industries. I then defined the quantitative and qualitative effects of these policies in order to show which provide the best areas for growth of bioscience firms and in-turn State economies. I expect to find that high levels of state incentives and reduced regulation directly lead to increased levels of employment, increased number of bioscience establishments, and an overall more impactful bioscience industry.

This project was aimed at helping UW Recycling identify inefficiencies in waste disposal and provide them with information that will assist in ascertaining their optimized waste diversion rate of 70% by 2020. Having a 70% diversion rate means that the UW would be sending 70% of its waste to recycling or compost facilities instead of a landfill. In turn, this means the University has less monetary investment in waste disposal practices while simultaneously making a beneficial and a substantial reduction in its environmental footprint. We hypothesized that individuals were not properly utilizing the trash, recycle and compost bins, and that upon evaluation of these bins we would find contamination that would allow us to identity inefficiencies. To test if waste was indeed being deposited incorrectly we chose to sort and examine trash, recycling, and compost from two locations over a five week period. During this time we documented the weights of pre-defined categories of waste and observed common trends in the waste stream. This revealed that compost was the main source of contamination in both the recycling and trash bins. The average trash and recycle bin compost contamination was 72% and 36%, respectively. However, the composition of the compost container showed that 93% of the materials in the bin were indeed compostable. These results align with our initial hypotheses. Furthermore, our study allowed us to identify possible causes for this behavior and to propose a series of measures to help mitigate it. We hope to expand this work with future efforts, including: educational outreach through trash sorts, implementing programs that engage the community and further divert waste, experimenting with new bin labeling systems, using Geographic Information System for mapping of campus compost bins for better tracking, and introducing more compost bins throughout campus buildings.

Pathologic enlargement of the esophagus, termed megaesophagus, results in a failure to complete peristalsis leading to vomiting, severe weight loss and potential death. Megaesophagus is characterized in a number of disease states including parasitic (Chaga’s disease), autoimmune (myasthenia gravis), and neuromuscular (muscular dystrophies), however, a detailed cellular and mechanistic understanding is lacking. To address this deficit, we performed a comprehensive examination of the onset, pathology and cellular composition of megaesophagus in the mouse model of Duchenne muscular dystrophy (DMD). DMD affects ~1/3500 male births and is a catastrophic and ultimately fatal muscle wasting disease resulting from a mutation in the gene encoding the integral skeletal muscle protein dystrophin. Although poorly defined in human DMD patients, megaesophagus is documented in canine and mouse models of DMD. Advancements in DMD therapies has increased patient lifespan and underscored a need to assess the impact of the disease in a range of organ systems, including the esophagus. We find that older dystrophic mice can develop severe megaesophagus, but that the timing of onset depends on the nature of dystrophin expression in muscle and non-muscle tissues and the genetic background of the mice. Further studies are in progress to delineate the precise dystrophin expression pattern in different cell types of the esophagus that contribute to pathology. Work presented here will be essential for future work aimed at identifying new therapeutic targets for DMD.

Mirror self-recognition (MSR), the test of whether or not an animal can identify their own reflection, is one of the highest markers of animal intelligence. To assess this capability, a mark test is conducted. Through this method, the only animals that have reliably displayed self-recognition are humans, magpies, dolphins, and four species of primates. A recent study on magpies showed that this avian species passed a mark test and was capable of MSR. Building on their research, we looked at MSR in parrots (Psittaciformes) of varying species to determine if they too were capable of self-recognition. Our test was done on an individual level. Our test subjects come from varied backgrounds with different life histories, and therefore mark test results within each species differ. In our experiment we exposed 24 parrots to reflective mirror surfaces, and analyzed how their behavior towards the mirror changed over time. After the birds grew accustomed to the mirror, we conducted a mark test. We anticipate that individual birds capable of self-recognition will pass this test because of their high brain-to-body ratio and social predispositions, which are signs of a high intelligence level. If our research shows that Psittaciformes are capable of MSR, they will become only the second avian order ever to pass this test and this would put them on the same intelligence level as mammals.

Bathsheba, the Queen of Sheba, and Jezebel are the three queens presented in the Bible who are known most widely today.  These three figures are not the only important female leaders mentioned in the Bible: there are stories of numerous other women who stood near the heart of political power.  I argue that the Bible presents four archetypes of women in power.  The first is the Israelite women in an Israelite king’s court.  This woman will rarely speak in the text and, when she does, it is only to show her obedience to God’s will.  The second archetype is the Israelite women in a foreign king’s court.  They serve an instrument of God’s will within the foreign courts that they inhabit.  Their presence near the foreign power brings blessings and wealth to the Israelites in their adopted kingdom, at the expense of its native subjects.  The third group is the foreign women in the court of an Israelite king.  These women are viewed as dangerous.  They are nearly always portrayed as acting contrary to the interests of the kingdom and they also frequently accused of drawing the king away from God in some sense.  The fourth and final group is the foreign women of a foreign king’s court.  They represent God’s power to act even outside the boundaries of Israel, often acting as witnesses to God’s punishment or the instrument through which God acts to carry out his plans for Israel.  A study of these women, through a careful reading of the Bible, will give us a better understanding of how the biblical authors conceived of female power – whether that of queens or other positions of political power.

Leigh syndrome is a clinically defined collection of diseases comprised of multiple genetic defects related to mitochondrial function. This syndrome results in early death in children typically due to respiratory failure as a consequence of progressive neuropathy, and currently no viable treatment options exist. Leigh syndrome can result from mutations in several different mitochondrial genes, one of which encodes the NDUFS4 subunit of complex I in the mitochondrial electron transport chain. As the NDUFS4 knockout mice phenocopy human patients with Leigh syndrome remarkably well, this model was utilized for the purpose of this study. Dietary restriction (DR) was identified as a possible treatment for mitochondrial deficiencies through a yeast genetic screen, which found that mitochondrial gene mutants generally received a robust lifespan benefit from DR. Thus, the primary focus of our research is to determine the efficacy of rapamycin (a DR mimetic) as an intervention in the NDUFS4 -/- mitochondrial disease mouse model. Rapamycin functions as a DR mimetic through its inhibition of the mechanistic target of rapamycin (mTOR) signaling pathway, which is responsible for modulating a variety of metabolic and cellular processes. Our model suggests that the increased NADH/NAD ratio resulting from a complex I deficiency in these knockout mice is sensed as energy abundance and results in systemic metabolic derailment. We propose that inhibiting mTOR signaling addresses this defect by altering intracellular energy sensing and modifying metabolic status. In order to test the efficacy of rapamycin treatment, NDUFS4 -/- mice were treated with daily injections of rapamycin or vehicle. Lifespan data for each treatment and additional assays for health related parameters were conducted to determine the response to the treatment regime. Investigating Leigh syndrome in this context will allow us to better understand the underlying mechanisms of pathogenesis, and directly test novel interventions aimed at attenuating this disease.

A critical problem in the treatment of addiction is the tendency of addicted individuals to relapse to drugs-seeking with as many as 90% of addicts relapsing to use within one year. Exposure to stress is an important factor that precipitates relapse, though the exact mechanism is yet unknown. The Lateral Habenula (LHb) and the Rostromedial Tegmental Nucleus (RMTg), nuclei in the dorsal diencephalon, have recently become brain regions of interest in addiction research. Both regions have been shown to be important regulators of the midbrain dopaminergic systems, which are involved in relapse to cocaine seeking. However, very little is known about the precise role of these nuclei in stress-induced cocaine relapse. In our initial experiments, male, Long-Evans rats were handled for 3 days, and then injected with cocaine (10mg/kg) or exposed to intermittent footshock. Preliminary results demonstrate an increase in the expression of cFos, an early-detection transcription factor and marker for neuronal activity, in both the LHb and RMTg upon acute exposure to cocaine or foot shock. Studies are currently underway to determine the role of the LHb, and LHb projections to the RMTg on stress-induced cocaine reinstatement using the DREADD (Designer Receptors Exclusively Activated by Designer Drugs) technology in a rat self-administration reinstatement model.

Being the target of a positive stereotype (e.g., “women are nurturing”) can elicit many negative effects. The current study investigates the influence of positive stereotypes on women’s math performance and their identification with science, technology, engineering, and math (STEM) fields. In the present study, some women were the target of a positive stereotype before being asked to take a math test. Women who were positively stereotyped did not differ in their math performance compared to women who were not the target of a positive stereotype. However, positively stereotyped women felt that it was less important for them to do well in math than women who were not the target of a positive stereotype. These results suggest that positive stereotypes may lead women to identify less with STEM fields, an important predictor of success or retention in a field, and may be a factor in perpetuating gender disparities.

Ramsey Theory is an intricate field of pure mathematics, but it also has applications in computer science, where graphs are commonlu used as data structures. Every pair of "forbidden" graphs has a Ramsey number, which indicates when one of those graphs must occur. A Ramsey number for a pair of forbidden graphs is the smallest number of points R for which every edge-coloring of the complete graph on R points includes one of the forbidden graphs in its respective color. In this paper we use two original methods to find and prove new Ramsey number formulas for certain tadpole graphs based upon known Ramsey number formulas for arbitrary cycle graphs.  A tadpole graph Qn,t is formed by connecting one end of a path graph on t points (called the “tail”) to a cycle of size n (called the “head”). A pan graph Qn is defined as a tadpole graph with t=1. We first use an intuitive counting method to prove exact Ramsey number formulas for all “near-diagonal” pan graphs, i.e. those pairs of pan graphs where the maximum cycle size of the pair is no more than 5/2 times the minimum cycle size. Then, we demonstrate a number-theoretic method to find exact Ramsey numbers for arbitrarily far-from-diagonal tadpole pairs with arbitrarily long tails. However, the second method requires that the tadpoles meet number-theoretic constraints (rather than size constraints). For example, in the diagonal cases, n-1 must be relatively prime to n+t, where either n-1 has an odd order (mod n+t) or the additive inverse of n-1 has an even index relative to n-1 (mod n+t). These “scattered” on- and off-diagonal results provide upper bounds on the Ramsey numbers for other tadpole pairs that fail to meet the number-theoretic constraints.

One of the most universal problems faced by persons with transtibial amputations is volume fluctuation of their residual limb. Since the shape and size of a prosthetic socket stays the same, fluctuations in limb volume affect the fit of a socket. For example, if a prosthesis is too tight; pressure spots, skin irritation, and muscle atrophy can occur. Conversely, a loose prosthesis creates gait instability and compromises the comfort of a patient’s prosthetic. Prosthetic socks of different materials and thicknesses are worn to compensate for the changes in volume and manage the discomfort created by daily and monthly volume changes. Properly fitting a residual limb to a socket is further confounded since the industry standard measurement of sock thickness is Ply, a non-linear unit of measurement. Our research examines how absolute thickness and material properties of prosthetic socks change with regular use. We measured the thickness and compression response of new out-of-box socks at three distinct points while in a donned condition. Measurement locations corresponded to area traditionally related to high interface stresses. Thickness and compression response were measured by a custom instrument. Participants walked for two hours while wearing a new sock, after which thickness was measured again in all three locations. Afterwards, volunteers took the socks home, along with a activity monitor, for regular use and returned every two days for one week, and then weekly for a month to re-assess sock thickness and response. The compression response after two hours of walking was used to validate cyclic testing conducting on an Instron material testing machine. Thickness response over long periods of normal use was used to characterize sock fatigue. We hope our study will help practitioners create more accurate volume management recommendations for their patients with a new understanding of the sock stiffness and durability.

 From the fillers that give body to ordinary paper to the antacids that relieve indigestion, calcium carbonate suspensions play an important role in our day-to-day lives. It is often desirable to work with slurries that contain the highest possible fraction of solids. The goal of this research has been to investigate ways to improve the flow of high solids dispersions of calcium carbonate through the use of of rheology modifiers. These are chemicals which, when added in small amounts, allow the dense slurries to flow as easily and smoothly as possible. Improving flow characteristics of high solids dispersions has a huge potential for reducing the amount of energy needed for various processes, such as pumping, coating and de-watering. One very promising modifier has been found to be sodium polyacrylate . Both traditional and new products, like nano-sized calcium carbonate particles, have shown significant improvements using this modifier. In this research, the rheological properties such as the viscosity function and the yield stress are determined as functions of additive amount, volume fraction of solids, and pH of the aqueous dispersion medium. All of these have been shown to important parameters in achieving optimum performance.

Electrophoretic displays, such as the Kindle®, currently employ electrostatic effects in apolar media to create a paper-like display. In an electrophoretic display, images are comprised of black and white pixels generated by applying an electric field to reposition charged pigment particles. The optimization of this technology is limited due to the incomplete knowledge of the mechanism(s) by which particles acquire charge in these systems. My project explores the charging behavior of carbon black pigments dispersed in apolar media. Previous studies of mineral oxide particles have provided support for the theory of an acid-base charging mechanism for particles dispersed in apolar media with various charge stabilizing surfactants. My current work looks at the possible extension of the theory of an acid-base charging mechanism to carbon black pigments in apolar systems. I have investigated the charging behavior of four different carbon black pigments by measuring the electrophoretic mobility of each pigment dispersed in solutions of heptane, and a charge stabilizing surfactant at varying weight percentages. Three surfactants were used for charge stabilization: Aerosol OT, SPAN 80 and OLOA 11000. Aerosol OT is a neutral surfactant in water, whereas SPAN 80 is acidic and OLOA 11000 is basic. The surface characteristics of each carbon black pigment were studied by Inverse Gas Chromatography (IGC) and X-ray Photoelectron Spectroscopy (XPS). The preliminary findings of my investigation show the sign of the charge for the carbon black pigments to be dependent on the charge stabilizing surfactant used.

Serotonin (5-HT) is implicated in numerous emotional behaviors, including depression and anxiety. One form of serotonin receptors is the 5-HT_1B autoreceptor, which is involved in regulating 5-HT transmission and uptake. 5-HT_1B autoreceptors are located on serotonergic neurons and are pharmacologically indistinguishable from 5-HT_1B heteroreceptors located on non-serotonergic neurons. Distinguishing between activation of the two receptor types is important as they have different functions. A novel strategy to accomplish this is to use an engineered receptor to mimic the 5-HT_1B autoreceptor using a modified DREADD receptor (Designer Receptor Exclusively Activated by a Designer Drug). The DREADD-1B receptor will mimic the 5-HT_1B autoreceptor function with pharmacological specificity. The DREADD-1B receptor is G_i/o-coupled G-protein coupled receptor that is activated by the selective ligand clozapine-N-oxide. When G_i/o-coupled GPCRs are activated, decreases in intracellular adenylyl cyclase and, subsequently, cAMP levels are measured. It is expected that when the DREADD-1B receptor is activated, a decrease in cAMP levels will be observed. To verify this, I created a stable DREADD-1B cell line and will use transient transfections of a luciferase plasmid to measure cAMP levels via proportional luminescence using luciferin. Optimizing the conditions for receptor activation and observing sufficient decreases in cAMP levels will confirm the general functionality of the receptor. If there are large variations in the downstream biochemistry between the DREADD-1B receptor and the 5-HT_1B autoreceptor, using the DREADD-1B receptor as a surrogate for the 5-HT_1B autoreceptor could have profound effects on behavioral data obtained in other projects. Creating and characterizing the DREADD-1B receptor in an in vitro setting will provide valuable information and tools for future projects involving the 5-HT_1B autoreceptor and this novel tool.

The primary cilium is a sensory organelle found on most cells. In the brain, most or all neurons contain a single primary cilium, yet its function is not entirely understood. Ciliopathies are defined as a group of disorders physiologically characterized by malformation or dysfunction of primary cilia, which in turn result in a variety of symptoms including cognitive deficits, retinal blindness, situs inversus and polydactyly. The serotonin 6 receptor (5-HT6) is the only 5-HT receptor that localizes to neuronal primary cilia, and previous research has implemented the receptor in learning, memory, and drug addiction. Our experiment will investigate the link between neuronal primary cilia and 5-HT6 in an attempt to better understand the significance of this unique localization. Using an immortalized line of rat adrenal cells (PC12), we will express the 5-HT6 receptor using viral vectors, and then pharmacologically manipulate the activity of the receptors with either an agonist (WAY 399885) or an antagonist (SB 208466). We will first stain the cells using immunohistochemistry, then image using florescence microscopy, and lastly quantify the morphological change in primary cilia length. We expect to see a shortening of primary cilium in response to the introduction of an antagonist, and an increase in length with an agonist. Since the 5-HT6 receptor has been shown to be homologous between rats and humans, a practical application of this research could eventually result in a pharmaceutical solutions to some of the cognitive symptoms associated with ciliopathies like congenital cerebellar ataxia or Joubert syndrome.

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy (SMEI), is a rare genetic form of epilepsy, caused by a mutation in the neuronal voltage-gated sodium channel, NaV1.1, encoded by the SCN1A gene. This form of epilepsy is characterized by febrile seizures at infancy that often change with age into afebrile seizures, which include generalized tonic-clonic and myoclonic seizures. In most cases, DS is a debilitating disorder that renders patients with decreased cognitive function and impaired development. To study this disorder, a mouse model of DS, with heterozygous deletion of the SCN1A gene (Scn1a +/-), was developed, demonstrating a phenocopy of the DS condition, with similar seizure patterns and atypical behaviors. In vitro work in the model demonstrates selective loss of sodium current and excitability in hippocampal GABAergic interneurons. However, it remains unknown if similar changes in neocortical GABAergic interneuron excitability occur. We hypothesize that fast spiking neocortical interneurons are responsible for control of cortical excitability via GABAergic inhibition and that reduced excitability of fast spiking interneurons associated with heterozygous loss of NaV1.1 contributes to hyperexcitability and seizures. To explore this hypothesis, we will compare neocortical interneuron excitability measured from single action potential parameters and repetitive action potential firing patterns in unaffected wild type mice and the DS mouse model, using pre-existing single-cell recordings. Excitability will be determined from the peak amplitude, width at half height, threshold for single action potentials, and from total number of action potentials in induced neuronal spike trains. If this hypothesis is correct, we expect that there will be atypical action potentials and firing patterns showing reduced excitability. This experiment will provide more insight into DS epilepsy and better therapeutic targets for the disorder.

Francisella noatunensis is an emerging fish pathogen that causes disease and mortality for several economically important fish including tilapia and Atlantic cod. The Francisella Pathogenicity Island (FPI) is a region of the genome known to govern virulence for the genus. PdpA is one of the genes found in the FPI that has been implicated in the ability of Francisella tularensis, the human pathogen, to replicate in infected phagocytes. A recent study by our laboratory using zebrafish as a model host indicated that pdpA is important for the ability of F. noatunensis to cause mortality in infected zebrafish—thus the functional role of the pdpA protein appears to be conserved for the genus. Our goal is to compare the innate immune response of zebrafish during infection with either wild type or pdpA knockout strains of F. noatunensis to determine if the host immune response is altered. To accomplish this, we are monitoring the expression of key proinflammatory genes (IL1B and TNFA) using quantitative RTPCR during acute Francisella infection in zebrafish. The results from this study will provide additional information about the potential use of the F. noatunensis pdpA knockouts as live vaccine candidates for fish.

Earmark spending has proven to be a popular political tool for members of Congress because it allows them to claim credit for a concrete economic benefit for their districts. I ask whether expectations of political benefits similarly influence large-scale stimulus spending allocations and, more importantly, whether these allocations have political benefits for the incumbent president. This research project examines the link between federal spending and shifts in election outcomes. It asks whether spending in the stimulus package of 2009 substantively influenced President Obama’s share of the popular vote in 2012. Other things equal, did competitive regions of the nation receive disproportionately more spending, and was that spending associated with increased vote shares for the incumbent president between 2008 and 2012? To answer these questions I examine government spending and popular vote shares in over 3,000 counties from 2008 to 2012. I also control for underlying social and economic issues by county, such as foreclosure and unemployment rates. Finally, I control for other political influences on stimulus spending, including whether certain counties had representatives in powerful congressional roles. Overall, this study will promote understanding of the political implications of large-scale federal spending. It will also shed light on the political dynamics of “swing counties” and whether stimulus spending is a useful political tool for winning these counties.

Asian Americans respond negatively to being the target of a positive stereotype (e.g., Asians are smart) even though these stereotypes are often attempts at praising their group. The current work focuses on how targets’ responses to positive stereotypes depend on the race of the stereotyper. Asian and Asian American participants imagined an interaction with a White classmate or an Asian classmate who stated a positive stereotype of their group or stated no stereotype. Results showed that participants responded more positively when the stereotyper was Asian compared to when the stereotype was White. Participants did not respond differently to White and Asian classmates who stated no stereotype, suggesting that it is positive stereotypes which lead to different responses based on who says them. These results show that group membership is an important consideration when thinking about stereotypes.

American students regularly get advised to “follow your passion” in choosing a career. However, people's passions are often shaped by what is considered appropriate for their gender. Could encouraging students to follow their passion inadvertently perpetuate gendered career choices? The present work examines how the cultural ideal to follow your passion may maintain gender imbalance in stereotypically masculine or feminine careers. In the current study, some participants were randomly assigned to write about what it means to “follow one’s passion” before writing about their career plans. We hypothesized that women who wrote about following their passions would report more feminine career plans compared to women who did not. Similarly, we predicted that men who wrote about following their passions would report more masculine career plans compared to men who did not. The American cultural ideal to “follow one’s passion” may help reinforce the gender makeup of career fields, contributing to the underrepresentation of women in certain fields like science.

The low educational attainment of students of Mexican origin in the United States is a growing concern. Research identifies parental involvement (PI) as an important asset to student success and defines it as parents’ active participation in their children’s education at home and at school. Little research addresses the ways Mexican parents help their children during their K-12 education and college-going process, however. To address this gap, this research attempts to understand Mexican parents’ involvement and other factors first year Mexican-American college students perceived as important in shaping their educational success. Semi-structured interviews were conducted with 17-college freshman that identified themselves as Mexican, first-generation, low-income, and migrant/seasonal farmworker background. Based on students’ responses, Mexican parents provide deliberate exposure to agriculture work in order to direct their children towards an educational path. They also provided emotional support and encouragement to their children. Findings indicate that Mexican parents are involved in their children’s education, but in a different form than described by the initial models and definitions of parental involvement. Based on these findings, a new model of parental involvement can be created – one that recognizes Mexican parents’ contributions and guides schools to better work with parents in their efforts to increase the proportion of Mexican origin students going to college.

The project I worked on was part of a larger project in which we examined the activity of O6-methylguanine-DNA methyltransferase activity, CpG promoter methylation, and progression-free survival following alkylating agent therapy in glioblastoma and anaplastic glioma brain tumors. For my part in the research I performed standard biochemical assays to quantify O6-methyalguanine-DNA methyltransferase (MGMT) in extracts of glioblastoma (GBM) and anaplastic glioma (AG) tumor samples from adult patients operated on with consent at the University of Washington Medical Center between 1991 and 2008. MGMT is a DNA repair protein that excises methyl adducts from the O6 position of guanine residues. Chemotherapy and other alkylating agents such as methylating triazene derivative temozolomide (TMZ) are responsible for methylating DNA, or damaging the DNA and thus destory the tumor cell. There has been poor prognosis for GBM due to the intrinsic resistance mechanisms in the MGMT that limit the efficacy of TMZ and other alkylators. GBM and other gliomas display a wide range of MGMT activity and thus the question for research was whether the amount of MGMT in tumors correlated with progression-free survival following alkylator-based chemotherapy. Overall the data strongly supported that MGMT activity in GBM and AG tissue mediates resistance to alkylator therapy.

Expression of glycans or carbohydrate antigens on mucosal surfaces is known to influence interactions between the host and bacteria. Variation in the expression of a single glycosyltransferase B4galnt2 is associated with significant shifts in the composition of the intestinal microbiota of mice (Staubach F, ISME, 2012). Glycosyltransferases are a class of enzymes that transport and assemble glycans. Preliminary studies of a mouse Salmonella model has found a significant association between Salmonellosis and expression of B4galnt2. In this project we will test the hypothesis that Salmonella spp. show preferential binding to the B4galnt2 β 1-4 GalNac sugar, which is commonly expressed by human intestinal epithelial cells (Mohlke et al., Cell 1999). We have adapted an in vitro method from Ruiz-Palacios et al. (JBC, 2003) to study this question, which utilizes Chinese hamster ovary (CHO) cell genetically engineered to express specific glycans to assay bacterial binding. Cells will be grown toconfluency in chamber slides then they are they are fixed and blocked. Clinical Salmonella enterica isolates will be grown in culture tubes overnight. Diluted bacteria will then be directly applied to the CHO Cells in the chamber slides and incubated together. After incubation the slides will be fixed and stained with a fluorescein isothiocyanate (FITC) conjugated anti Salmonella antibody. Stained slides are examined under a fluorescent microscope to quantify the number of bacteria bound to CHO-B4galnt2 cells vs. control CHO cells. Increased numbers of bacteria binding to the CHO-B4galnt2 cells compared to the control CHO cells would support a role for the B4galnt2 β 1-4 GalNac in host-Salmonella interactions. If no significant difference in binding is seen by this method, we will also test the hypothesis by doing introducing shear in a modified dot blot binding assay using mucus from B4galnt2 (+/+) and (-/-) mice to investigate Salmonella spp. differential adherence.

A replicative lifespan (RLS) screen in yeast (Saccharomyces cerevisiae) was recently performed in the Kaeberlein lab to determine how different mutants respond to caloric restriction (CR). The results of this screen indicated that many mutants lacking genes encoding proteins related to mitochondrial function were rescued to wild-type lifespan by CR. The beneficial effects of CR in both yeast and mammals are mediated by reduced signaling through the mechanistic target of rapamycin (mTOR) pathway and can be mimicked by the drug rapamycin, a specific inhibitor of mTOR. Based on the findings from the yeast screen, we decided to investigate the effects of rapamycin on mitochondrial disease in a mammal. Leigh syndrome is clinically defined as a collection of genetically heterogeneous human mitochondrial diseases. These diseases result from mutations in genes encoding mitochondrial proteins and are characterized by progressive neurological degeneration resulting in early childhood mortality. To test rapamycin as a therapeutic intervention for Leigh syndrome, we are using a mouse line carrying a heterozygous loss of the electron transport chain complex I subunit Ndufs4, a direct homolog of the human NDUFS4 gene whose mutation causes Leigh syndrome. Mice homozygous for loss of NDUFS4 provide a robust phenocopy of the human disease, including neurological degeneration and early life mortality. Our results so far show that rapamycin dramatically increases lifespan and rescues the Ndufs4-/- mice for several health-related parameters, such as general mobility, visual ability, and grip strength. We are working towards determining the mechanistic basis for these effects, and we hypothesize that they may result from a metabolic shift toward increase fat metabolism in the liver. Understanding how rapamycin rescues Leigh Syndrome mice has clear translational implications, as rapamycin derivatives are FDA approved and patients with Leigh syndrome and other human mitochondrial diseases currently have limited treatment options.

 Personalized medicine aims to improve patient outcome by tailoring cancer treatment to individuals based on the specific molecular makeup of tumors. This approach is showing particular promise in the treatment of gliomas, the most common type of primary brain cancer. The DNA repair protein O⁶-methylguanine-DNA methyltransferase (MGMT) removes O⁶-alkylguanine adducts from DNA produced by the therapeutic methylating agent temozolomide (TMZ). In glioblastoma multiforme (GBM) tumors, low levels or lack of MGMT activity is correlated with longer progression free survival (PFS) following TMZ treatment and other alkylating chemotherapy. However, in oligodendorgiomas and oligoastrocytomas the effect of MGMT activity on tumor resistance has not been established. Better clinical outcome is associated with 1p and 19q loss of heterozygosity (LOH), which occurs in an appreciable fraction of oligodendrogliomas. Other studies associate these deletions with CpG methylation of the MGMT promoter, an epigenetic indicator of low MGMT activity. However, there have been no studies linking MGMT activity to chromosomal deletion, and 1p/19q LOH is associated with better clinical outcome regardless of therapy, suggesting that other mechanisms may also be responsible for prolonged survival. To clarify the unknown role of MGMT in these tumors, we tested the hypothesis that 1p/19q LOH accompanies low MGMT activity by: [1] assaying MGMT activity by measuring the extent of transfer of tritium-labeled methyl groups at the O6 position of guanine to MGMT in substrate DNA extracts of deleted and non-deleted tumors; [2] assessing promoter CpG methylation status using methylation specific PCR; and [3] examining the correlation of MGMT activity to TMZ treatment response using a Cox regression analysis. This approach should help to clarify the relationship of MGMT activity and 1p/19q LOH.

Quantum dots are nanoparticles with several applications including cellular imaging and drug delivery. Because of quantum confinement, their ability to fluoresce under ultraviolet light is size dependent. However, quantum confinement not only plays a role in emissive properties, but is also a factor in the absorbance spectrum of quantum dots. As a result, there is not a simple relationship between the concentration of quantum dots and optical density. It is the goal of this project to craft a new approach in accurately measuring the concentration of quantum dots in solution. We have determined a correction factor relating response units as measured by surface plasmon resonance (SPR) to values of refractive index. With this, we further use SPR in conjunction with analytical ultracentrifugation (AUC) to determine the concentration dependence of the refractive index, dn/dc, for TOPO-PMAT quantum dots. The measurement of dn/dc for the quantum dots allows us to use an interferometric determination of their total fringe increment observed by AUC synthetic boundary to measure the concentration of quantum dots in solution. We have estimated a dn/dc for 565 TOPO-PMAT CdSe quantum dots. In addition, we have used AUC to show that total fringe increments scale with concentration. Furthermore, we have estimated mass extinction coefficients for all wavelengths at which absorbance is observed for these quantum dost. This allows for UV-vis determination of concentration. Our results indicate that our strategy holds promise for providing a new method for measuring the concentration of quantum dots in solution.

The unique geography and ice dynamics of the West Antarctic Ice Sheet (WAIS) are believed to make it susceptible to instability and rapid collapse. Predictions of WAIS stability in a warming world rely heavily on ice sheet model simulations; one drawback is that ground truth for these models comes from the last ice age, when the climate was colder. Geologic evidence of ice sheet behavior during warm interglacial periods is currently hidden beneath the Antarctic and Greenland ice sheets. We expect WAIS to have been thinner and less extensive under warmer conditions, and we ultimately plan to determine its past extent with cosmic ray exposure dating of subglacial bedrock. As a prelude to subglacial sampling, during January-February 2013 we collected samples from elevation transects of exposed granitic bedrock at three WAIS nunatak sites: the Pirrit Hills, Nash Hills, and Whitmore Mountains. We also conducted radar reconnaissance surveys to evaluate potential sites for future subglacial rock sampling, which will extend the transects beneath the ice sheet. We have separated out the quartz and potassium feldspar content of our samples for measurement of cosmogenic beryllium-10/aluminum-26, and chlorine-36 respectively. We are using the results of these analyses to determine the history of exposure and ice cover in the past 1-2 million years at each sampled elevation. Based on field observations, we expect our samples to show evidence of prolonged exposure, suggesting that presently subglacial surfaces were also exposed in the past. Ultimately our work will determine whether rock surfaces beneath the WAIS have ever been exposed to cosmic rays, providing clear evidence for or against a thinner ice sheet in the past. Such data will be useful in tuning ice sheet model conditions and establishing WAIS vulnerability to collapse, which is crucial to forecasting future sea level change.

Pulsed plasma thrusters are a modular electric propulsion technology with extensive flight heritage. Flight-ready PPTs are tailored to a specific mission based on the power and mass budget of a mission. The lower bound for both parameters is far less than competing electric propulsion (EP) technologies, such as Arcjets and Hall Thrusters, which makes them desirable as spacecraft size decreases. The variable components of PPTs are typically electrode geometry, capacitor size, spark plug geometry, and fuel feeding system, but rarely if ever does a space mission select an unusual fuel. Teflon is used almost exclusively, and PPT fuel research is effectively stagnant. This investigation has concluded that alternative fuels are indeed significant. The sulfur PPT (SPPT) is inspired by natural sulfur plasmas in the Jovian magnetosphere. Thrust stand tests over the course of six months have demonstrated clearly that the specific thrust (thrust per unit power) is three times higher than in a corresponding test using a Teflon PPT of the same electrode geometry. Both pure sulfur and a sulfur-epoxy binder have been considered, and show the same specific thrust within error of the experiment. Pure sulfur will outgas in space, and may not be suitable for long missions, but the sulfur-epoxy fuel could potentially solve this problem. Additionally, an insulated semi-conductive bismuth sulfide compound shows similar thrust characteristics to the Teflon fuel, albeit at a lower exhaust velocity. This investigation is ongoing, with a parallel application project performing the SPPT experiment on a high-altitude balloon airship. This mission will demonstrate systems control, test the SPPT in a non-laboratory environment, build flight heritage, and represent and important advancement in PPT applications.

During the last ice age the Missoula Floods – huge cataclysmic floods caused by failure of the glacier dam that impounded Lake Missoula, a massive ephemeral meltwater lake – spilled across eastern Washington in periods of a few days. Repeated floods transformed the Eastern Washington landscape, eroding coulees and re-working the resulting sediment into extensive sand, gravel, and boulder deposits. Although widely studied, debate persists over the number and timing of the floods. Flooding is known to have spanned a period of several thousand years; this is constrained by several areas of research including radiocarbon dates, dated volcanic ashes, and examination of the interbedding of Missoula Flood deposits with those of the 18,000 yr BP Bonneville Flood on the Snake River. To further constrain the chronology of flooding, we plan to measure the cosmic ray produced isotope Beryllium-10 in granitic quartz from boulder deposits near Ephrata, and at Priest Rapids on the Columbia River. Concentrations of Be-10, accumulated since the boulders were deposited, will allow us to determine their exposure ages. So far, we have collected several samples from the Ephrata boulder fan and from the Priest Rapids deposit. We have sampled high-standing, water-polished boulders to avoid the effects of past sediment cover and post-depositional erosion, both of which can lead to erroneous age estimates. We have crushed the samples and separated quartz in preparation for Be-10 analysis. After further purification, the quartz will be dissolved for extraction and isotopic analysis of Beryllium. We expect results of this work to better constrain the relative timing of the deposits at Ephrata and Priest Rapids, and the age of the floods that produced them, the last to pass through the Grand Coulee and Sentinel Gap, respectively.  

As Seattle's light rail system expands, one branch is being designed to cross the I-90 floating bridge in order to connect downtown to Redmond. The challenges associated with designing a rail system over a floating bridge are significant. Traditional train rail systems are not built to accommodate the wide range of movements undergone by a floating bridge but Parsons Brinckerhoff have designed a new kind of rail called CESURA that will allow this new branch of Link light rail to exist. I have been helping to construct and test a full-scale replica of part of the CESURA system and my personal research has focused on the specific stiffnesses of the rubber fasteners which hold the rails to the rest of the system. These stiffnesses are very difficult to determine without a specialized test to isolate their properties. A hydraulic actuator was used to provide loads that would either rotate or linearly translate a rail that was secured by a single fastener. Various instruments were calibrated and placed throughout the system in order to monitor the fastener's behavior in response to different loadings. The newly discovered fastener properties will improve computer models of CESURA and allow Parsons Brinckerhoff to more accurately understand how the entire system behaves. Armed with this new knowledge Parsons Brinckerhoff will be better prepared for their next test in Pueblo, CO with an actual Link light rail train running over the full CESURA system.

In the 20th century, mathematicians attempted to reduce mathematics to a set of axioms. One of the properties that David Hilbert, a famous mathematician, postulated was decidability. This refers to an algorithm that can determine whether or not another algorithm in the same system is actually computable. In his 1939 paper, Alan Turing proves decidability cannot occur in formal mathematical systems. Turing used an unconventional way to prove his argument—the Turing Machine. The machine is a theoretical computational device. This abstract device has revolutionized the way we think of computing and computers among other fields. It consists of four parts: a head that reads symbols, an infinite tape that stores inputs and outputs, a state register that holds the current state (or state of mind if you prefer), and a table that describes how the machine transitions from state to state. Turing machines can compute anything that is computable. Computability equates to being able to describe how to obtain the solution of some function with an algorithm. This abstract idea is interdisciplinary; which makes it a great educational tool. We have built a working Turing machine out of LEGOS. To both extend and improve functionality, we have added various components. These components cross over to other fields of study making the project great for students of various education paths to reproduce in a team setting. Our hope is that others can use our work and further devolop it. Besides providing a concrete example of an abstract idea,  building the Turing machine allows us to reaffirm findings.  It is in the spirit of scientific descovery to reproduce work. This research project allows us to follow in the foot steps of intellectual giants.

Observations suggest that the intracluster medium in galaxy clusters is strongly influenced by supermassive black holes residing in cluster centers. We investigate the consequences a black hole can have on the thermodynamics of the gas in galaxy clusters by comparing the properties of a simulated galaxy cluster without black holes to X-ray observations of real clusters, which have black holes. For our data we used Python to manipulate a cosmological simulation made with ChaNGa, a code capable of simulating gravity, thermodynamics, and other things. Our cluster simulation includes gravity, hydrodynamics, gas cooling, star formation, and stellar feedback in a fully cosmological setting. However, this simulation lacks black hole formation, growth, and feedback, allowing us to pinpoint the effects of these processes on the cluster by comparing to observations. In our investigation, we found only minor differences in the density, temperature, and pressures of the gas between the observed and simulated galaxy clusters in the cluster outskirts. However, we found significant deviations between the simulation and observations near the cluster centers, where a large spike in star formation is present in the simulated cluster, not seen in the observations. Our results suggest that black hole formation and feedback in galaxy clusters most strongly affect the cluster in the central regions, where it can significantly decrease star formation by heating the gas.

Thirty-four million people worldwide currently live with HIV-1. Despite the availability of highly-active antiretroviral therapy (HAART) which may prolong the lifespan of HIV patients, HAART does not target the latent viral reservoir in infected cells, enabling viral rebound in the absence of treatment. Introducing genetically-engineered DNA cutting enzymes (endonucleases) into HIV-infected cells may disrupt the integrated provirus. The site-specific DNA cutting activity of these endonucleases operating in conjunction with cellular error-prone DNA repair mechanisms may result in sustained damage to the integrated viral genome and prevent the virus from replicating. We are investigating 3 classes of engineered endonucleases: homing endonucleases (HEs), zinc finger nucleases (ZFNs) and transcriptional activator-like effector nucleases (TALENS). While the large DNA-binding domains of these endonucleases allow for customization to a desired target sequence, delivering these enzymes to a cell (vectorization) poses a challenge. TALENS in particular require a DNA coding sequence beyond the capacity of many viral vectors. As such, a method of co-transduction must be pursued, whereby two halves of the endonuclease coding sequence are delivered by separate viral vectors and coordinately expressed in the HIV-infected cell. My project aims to determine the optimal multiplicity of infection (MOI) for co-transducing HIV-infected cells using adeno-associated virus (AAV) vectors. I have determined AAV-1 to be the optimal serotype of AAV for infecting SupT1 cells, a cell line used as a model for HIV-infected T-cells. I have constructed two sets of AAV-1 viral vectors to express either Green Fluorescent Protein (GFP) or a red fluorescent protein (mCherry) as surrogates for endonuclease genes and infected SupT1 cells with both sets of vectors at variable MOIs, using flow cytometry to determine the rate of co-transduction. Through this method, I have successfully co-transduced cells with two AAV-1 viral vectors. These results may have applications in future HIV research and clinical therapy.