The development of new medications is critical for treating disease and extending life. Approximately 40-60% of drugs target a specific type of membrane protein termed G-Protein Coupled Receptors (GPCRs), which permit cells to communicate with each other (by binding neurotransmitters) and regulate body physiology. The Hague lab studies the molecular mechanism of drugs targeting these receptors. Specifically, they examine a small, yet important structural portion of the receptor - the PDZ binding motif - which acts a protein-protein interaction site. Interestingly, of the ~800 different GPCRs in the body, 30 have this PDZ binding motif, including those activated by the neurotransmitter 5-hydroxytryptamine (5-HT), which is commonly known as serotonin. Serotonin regulates many key CNS processes including mood, sleep, and appetite. Current 5-HT medications that are on the market are used to treat depression, generalized anxiety disorder, and social phobia. Two common antidepressants that affect serotonin GPCRs are Selective Serotonin Reuptake Inhibitors, or SSRIs, and Monoamine Oxidase Inhibitors, or MAOIs. My goal was to examine the necessity of the PDZ binding motif for 5-HT serotonin receptor function in human cells. To do this, HEK293 cells expressing the wild-type 5HT receptor (WT) or mutated 5-HT receptor missing the PDZ binding motif (ΔPDZ) were subjected to diagnostic assays including: microscopy, protein biochemical analysis, proteomics, and cellular signaling. In summary, the data suggest the PDZ-binding motif is not essential for 5-HT serotonin receptor function in HEK293 cells, although further experiments are necessary to solidify this conclusion.

The process of directing auditory attention was first analyzed by Colin Cherry in 1953 and classically dubbed “the cocktail party problem”, referring to how an individual is able to follow one conversation at a noisy gathering. In this project I will explore how eye-gaze position may direct auditory attention and thus affect detection thresholds of sounds in noise. Behavioral studies researching this issue have shown that it is easier to segregate a target sound when it comes from a different location than the masking noise, a phenomenon known as the masking level difference (MLD). This can be observed as the improvement in detection threshold of a tone in noise when they are separated versus when they are collocated. However, these past studies did not control for eye gaze. Recent electrophysiological studies have found that the inferior colliculus, a critical auditory midbrain nucleus, shows visual and oculomotor responses. The behavioral significance of these interactions to human listeners is not yet well understood, but suggests that the oculomotor system may be able to modulate auditory processing. My project focuses on eye-gaze and the MLD. I will test whether subjects have better detection thresholds when their eye-gaze is directed towards the location of the tone versus towards the location of the noise. The experiment is generally laid out in two blocks. During the first block of trials, the subject will have visual primers directing eye-gaze; in the second block, auditory primers that do not direct eye-gaze will be used. Control trials that give uninformative visual and auditory cues will also be tested. I have promising preliminary data shows that trials using informative auditory cues can improve thresholds over trials with uninformative auditory cues. However, the more noteworthy result this study looks for is the possibility of yet another improvement when eye-gaze is brought into play.

Our objective was to further explore the facial feedback hypothesis. This theory, that facial movements (efference) can influence one’s emotional experience, has historically been studied using either positive or negative stimuli. We used neutral stimuli to see if facial efference is affective in influencing emotion in the absence of stimuli that prompt an emotional response. Participants were randomly assigned to one of three conditions created by holding a chopstick – forced smile (chopstick between teeth), forced frown (chopstick between lips), or neutral (chopstick in nondominant hand). Participants were then shown 5 neutral images, each for 6 seconds, via PowerPoint. They then rated the images on 11-point Likert scales, from 0 (extreme sadness) to 10 (extreme happiness), indicating what emotion the image was expressing. Results showed no statistically significant difference between those whose facial expressions were manipulated into smiles and those who had neutral or frowning facial expressions. A deeper understanding of the relationship between facial expressions and emotions could alter the way in which we explore treatments for both mental and physical health conditions.

While language delay and speech impairment in individuals with Autism Spectrum Disorders (ASD) have been widely investigated, few studies have analyzed the role that non-verbal forms of communication, such as gestures, may play in augmenting impaired speech in individuals with ASD. One system that has been heavily studied, which has the potential to enhance or inhibit communication, is the Mirror Neuron System (MNS). While the MNS could serve to augment speech, the dysfunction of this system could prove detrimental to those who already possess impaired language skills. If the MNS were to be equally affected by ASD, individuals with this disorder would be unable to compensate for impairments in verbal communication with non-verbal forms of interaction. Although reduced activity in MNS areas in ASD individuals has been identified, the implications of this dysfunction remain unclear. In order to identify if the dysfunction of the MNS impairs non-verbal forms of communication, we recorded 16 typically developing (TD) adolescents and 13 ASD adolescents as they played a game of charades. We utilized charades that were not associated with speech centers, but instead have been shown to rely heavily on an intact MNS and motor cortex to mimic the action. This allowed us to identify whether reduced activation of mirror neurons impacts neural centers that serve to augment language through nonverbal means. Using video footage, two blind coders scored the quality of gestures based upon a 0-8 point scale that was unique to each gesture. Our preliminary results suggest that adolescents with ASD do not have significantly lower scores of functional gesture quality compared to TD individuals. One possible implication of these data is that other regions of the brain may compensate for MNS dysfunction and, importantly, may serve as potential therapeutic targets for strategic interventions to minimize the language impairments associated ASD.

Neurons are specialized cells that receive and relay information throughout an organism, and the compartment that inputs the signal has multi-complex structures known as dendrites. The form of the dendrite is tightly regulated to neuron function; therefore, any abnormality that alters the structure of the dendritic arbor can lead to severe defects in neuronal function. However, the mechanisms of how dendrites develop and maintain their arborization are poorly understood. One mutant allele, Acsl (Acyl-CoA synthetase long-chain), leads to a complete loss of terminal dendrites, which carries a two amino acid change that renders the gene product non-functional. Interestingly, Acsl is also associated with human X-linked mental retardation (XMR). However, to date, little is known about the signaling pathway that may be involved in this unique function of Acsl in neurons. As such, we conducted a modifier screen, which serves to identify functional modulators with genetic interaction of Acsl in maintenance of terminal dendrites. Here we report our results of funcional signaling (and/or) regulatory genes from this screen. We also conducted comparative GC/MS of the lipid profiles in both whole larval body and brains to identify the specific lipid species being affected by acsl mutation. In return, this will reveal to us more about the function and signaling pathway of Acsl in maintenance of terminal dendrites. Results from this project will lead to a greater understanding of dendrite abnormalities in neuronal development and of neurodegenerative disorders.

The somatic mutation theory of aging states that aging is the result of accumulated DNA mutations in somatic cells, which lead to loss of physiological integrity through tissue and organ level dysfunction. In mouse model systems, decreases in lifespan through high mutation rates have been documented by creating mutator phenotypes in these organisms. Mutator phenotypes are marked by increased cellular mutation rates, and are known drivers of tumor development in human cancers. Mutator-driven adaptations occur in natural microbial populations. Mutators represent a unique opportunity to test the somatic mutation accumulation theory of aging due to their sustained high mutation rates. Nutritional status, particularly carbohydrate metabolism, influences lifespan in numerous organisms. In yeast, which preferentially ferments glucose to ethanol before switching to respiratory metabolism upon glucose depletion, the induction of respiratory metabolism is associated with increased lifespan. This study examines the effects of high mutation rate on yeast replicative lifespan and whether induction of respiratory metabolism is sufficient to change lifespan in organisms with increased mutation load. To do this, yeast defective for DNA replication proofreading, mismatch repair, and base-excision repair were grown under dietary restriction (reduced glucose) and in the presence of non-fermentable carbon sources. Then, mutation rates and replicative lifespan were assayed. Our results show that increased mutation rates correlate with decreased lifespan in strong mutators and that this decrease in lifespan can be partially suppressed through growth on limited glucose and non-fermentable media. These findings suggest that the metabolic state of the cell modulates the severity of mutator phenotypes, which has important implications for the role that mutators play in carcinogenesis.

In order to communicate, patients with total loss of muscle control including eye movement can rely on brain computer interfaces (BCI) that utilize evoked related potentials (ERP) which are voltage deflection of the brain following stimulus presentation recorded using EEG. Typically, ERP spellers rely on visual input. However, due to the auditory system's acute ability to selectively attend an auditory stream in what's known as the "cocktail effect", new speller paradigms that aid listeners' ability to selectively attend may increase the maximum bitrate of communication. The focus of this project was to create a unique auditory ERP-based speller that allows users to successfully use tone, spatial location, and informational cues to aid in auditory streaming while still increasing the total amount of selections of auditory streams. The research project can be separated into two phases: 1) a proof of concept psychophysics experiment assessing users ability to discriminate different auditory cues used in an auditory BCI environment and 2) an application of psychophysics findings from the previous phase to an online analysis of bitrate using EEG recording which will be conducted in the summer of 2014. This presentation will focus on analyzing and applying the experimental findings from the first phase to explore how can we modify parameters of the experiment design to maximize the bitrate (i.e. either through maximizing the ERP response amplitude, improving accuracy, lowering trial time, etc.). This project offers future possibilities for auditory systems to help not only improve the ease of use and practicality for the community of individuals who rely on speller systems but in other areas for the BCI community as a whole.

The Federal Reserve wields enormous financial power through both policy and press. It is commonly understood in economics that the rational expectation of - and ensuing reaction to - an expected market phenomenon can be as impactful as the actual occurrence of the phenomenon itself. When the Federal Reserve helped form market-wide expectations of a “tapering” of their $85 billion per month quantitative easing program in September 2013 and then did not follow through, the overarching criticism from analysts was that the Federal Reserve “lost credibility” as a result of its apparent reneging. My goal is to quantify and measure the effect of such a change in credibility, should it exist, as its economic implications are immense in both theoretical and practical application. I aim to measure this change in credibility through changes in market volatility and inflationary expectations following a particular FOMC minutes release where the policy was considered to be "unexpected" as compared to historical time series data available. I expect recent data of unexpected decisions to show a trend of less "lost credibility" than previous data due to the differing and lesser known nature of the policy being exerted (quantitative easing as opposed to traditional monetary policy before the recession) and the inherent assumption of the temporariness of quantitative easing as recessionary policy. Should this prove to be the case, one could argue that quantitative easing has additional effectiveness as recessionary economic policy due to the Fed's ability to boost the economy with lesser inflationary horizons through expectation management as compared to the longer lasting inflationary horizons present in traditional monetary policy.

To escape Earth's atmosphere, traditional high powered rockets require significant amounts of fuel. Rocket fuel is very expensive and often consumes a majority of the budget allotted for a rocket. In the 1950's James Van Allen used weather balloons to lift rockets to high altitudes and take early video of solar activity. This rocket-balloon system, nicknamed the Rockoon, is a potentially cost-efficient way of conducting high altitude sounding experiments and putting low mass payloads in low earth orbit. By launching from high up in the atmosphere, the rocket uses less fuel because the distance to the desired altitude is shorter and the atmosphere is less dense, meaning less drag on the rocket. While Van Allen and others, such as JP Aerospace, have had successful Rockoon launches, they have all been sounding rockets (i.e. the rocket does not enter orbit but comes down after reaching apogee). The long-term goal of our research project is to use our Rockoon system to deliver a payload into a shallow orbit around the Earth. The Rockoon system uses two weather balloons to lift a two-stage high powered rocket and electronics package to a significant height. The rocket is remotely fired from the ground and recovered using GPS and radio frequency transmitters. In March of 2014, the two-stage rocket prototype was launched from an altitude of 5,000ft at Black Rock, NV. The rocket had a maximum velocity of Mach 2.2 and reached an apogee of ~45,000ft. The next phase of our research is to do an untethered launch at 100,000ft using a thermally insulated sounding rocket. By improving upon future iterations of the Rockoon, we can develop a system and instrumentation that can be used by a variety of professionals and amateurs as an affordable and faster method for delivering payloads to space.

High powered rocketry has a problem. Many individuals looking to deliver large payloads into the atmosphere have restrictive budgets. This project’s solution is a cluster rocket. These are rockets which use a group of smaller motors to deliver the same thrust as a larger motor. However, these smaller motors cannot deliver thrust for the same amount of time as the larger motors, resulting in a lower maximum altitude. A logical solution is a cluster rocket off another cluster rocket. In this study, an eleven motor cluster-on-cluster rocket is being designed with this in mind. This means that the rocket first fires seven motors simultaneously. After these motors have spent their fuel, the section containing them drops away and a second set of cluster motors fires. This more than doubles the maximum altitude of a single stage rocket. Because a rocket like this has never been launched at UW before, several experimental parts were designed for it. These include a flight computer a sixth the size of a traditional one, an internal cluster motor mount, and a transition capable of reinforcing a body tube internally. In order to complete this project, we utilized a wide variety of materials and construction techniques, from wet-lay carbon fiber to Kevlar to Popsicle sticks. We also put together one of the largest teams devoted to a single rocket, with members in the ME, AA, EE, IE, HCDE, and physics departments. This prototype was launched in March at Black Rock, NV and saw a reasonable amount of success. All motors ignited coming off the pad and the rocket maintained structural integrity until the recovery system on the first stage failed and it crashed. The second stage was recovered with no damage and will continue to be used as an example in the construction of internal clusters.

The Advanced Propulsion Lab from the Earth & Space Sciences Department has developed a Pulsed Plasma Thruster (PPT) which utilizes a propulsion system ideal for operating in a low pressure and high altitude environment. In order to test the PPT, a high-altitude flight will be carried out at the end of May 2014. The structure housing the thruster is a zeppelin-type aircraft composed of two lifting balloons, a primary zeppelin balloon, and a supporting frame. There are several constraints that need to be fulfilled by the aircraft. The zeppelin frame needs to be strong and durable enough to support the thruster, while still light enough to fulfill the weight compliance from the FAA. In addition, the zeppelin needs to be able to raise the payload above the jet stream to an altitude of approximately 70,000 feet and maintain that height once reached. To achieve this, the structure uses two 800-g high altitude latex balloons with 150 cubic feet of helium providing the lifting force. Once the optimal height is reached, the two balloons will be separated from the main structure through the uses of NiChrome wire and the primary balloon will take over, providing neutral buoyancy at the desired location in order to accurately measure the thrust of the PPT. The main core of zeppelin is currently being fabricated in house using mylar as the primary material for the balloon and carbon fiber rod for the supporting frame by our team. Current calculations estimate the size of the zeppelin to be 45 feet horizontally with a 4.5 feet radius. There are several issues the zeppelin is currently facing such as the fragility of the material used, the expansion of the helium at high altitude, the weight of the payload, and the sheer size of the aircraft. We are currently testing various materials and structural designs that will house the payload in order to develop a lightweight and aerodynamic aircraft that will address these issues. 

Understanding the relationship between student engagement and academic motivation is important when considering the experience of undergraduate students. We hypothesized that the more students engaged with the university, the more motivated they would be. Participants were invited via class appeals and Facebook posts to complete an online survey on SurveyMonkey. Eighty-three participants fully completed the National Survey for Student Engagement (NSSE), the Academic Motivation Scale (Wabash University, 2009), and demographic questions (major, gender, cumulative GPA, year in school, and graduation date). Regression analyses showed four subfactors of engagement to be significantly related to motivation. The first three subfactors fall under the NSSE’s theme “Academic Challenge,” while student-faculty interaction falls under the theme “Experiences with Faculty.” Thus, those who were engaged academically and with professors were more academically motivated. The findings may have implications for how universities engage and retain students, and the effectiveness of programs used to motivate students academically.

Although previous studies have found that commuting increases our salivary cortisol (stress) levels, little is known about how it affects salivary testosterone, the sex hormone associated with aggression. Even less is known about the impacts that different modes of transportation may have on these hormone levels. My project therefore aims to 1) identify how commuting influences both salivary cortisol and testosterone patterns and 2) compare the salivary cortisol and testosterone levels of commuters when they drive to when they take the bus to determine how different modes of transportation affect these hormone levels. I hypothesized that 1) commuting (in general) would have a noticeable impact on salivary testosterone and cortisol levels, 2) that testosterone levels would be highest shortly after commuting for both busing and driving, and 3) that salivary cortisol and testosterone levels would be higher when study participants drove than when they took the bus. Ten male and female participants selected two days to commute home via bus and two days to commute home via driving their own car or vehicle. Shortly before and after all four of these commutes, each participant completed mood surveys and stress scales and collected 2 mL of saliva specimen. Cortisol and testosterone were assayed in the specimens using enzyme immunoassays. Bus commute day hormone levels were compared to car commute day hormone levels. Findings from this research project could have implications for future research on stress and transportation which could encourage commuters to use one mode of transportation instead of another since long-term exposure to elevated stress levels has been shown to be bad for one’s health.

Cortisol, the main glucocorticoid hormone in humans, and testosterone, an androgenic hormone, are secreted from the adrenal cortex and gonads respectively in response to physiological and social stimuli. Cortisol and testosterone both display diurnal patterns with peaks in the early morning and gradual declines throughout the day. These morning peaks have been suggested to play a role in preparing the body for the day. The hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes regulate stochastic, homeostatic processes, which respond to short and long-term caloric changes. Although studies have determined the effect of fasting on cortisol and testosterone, the effect of the time of feeding is currently unknown, particularly the effect of eating close to bedtime on subsequent morning hormone levels. We hypothesized that the morning awakening response of cortisol will be resistant to changes in the timing of feeding before bed and testosterone will be more responsive to these changes. To test for the effect of timing of eating the night before, twenty male and female participants, aged 20 – 35, followed a four-day regimen. This protocol included three cycles of controlled time of evening feeding and next day saliva collections upon waking up and 30 minutes after waking up. The first cycle required consumption of dinner four hours before sleeping, the second cycle required consumption of dinner one hour before sleeping, and the third cycle was a repeat of the first. Salivary cortisol and testosterone were measured with enzyme immunoassays. Morning cortisol levels following late night feeding are expected to display no difference from those following normal dinner times, while morning specimens following late night feeding specimens may show increased testosterone awakening responses. This research may provide insights into the timing of eating and homeostatic regulation in humans.

 In the last ten years, social media use and user base have exponentially increased in prevalence and interface with everyday social activities. In part this increase can be attributed to the advent of mobile web technology. Currently, the popular assumption that social media use causes higher levels of anxiety in users is trending throughout media platforms. A 2013 study by Ethan Kross, of University of Michigan, predicts Facebook usage may issue a decline in subjective well-being in young adults. Our study was designed to examine any association of anxiety levels between users and their most frequented social media platforms. Participants were recruited via various social media outlets, Facebook, Twitter, E-mail, Snapchat, Instagram, and SMS messaging and directed to an online self-administered anxiety survey. The study also requested participants to field several questions surveying their own social media usage and activity. For validity purposes, the order of the anxiety survey and social media usage questionnaire were alternated between participants whose biographical data remained anonymous. Nominal age and gender data were reported in planned descriptives. We used the Zung Anxiety Scale (S.A.S.) which quickly quantifies levels of anxiety making it ideal for collecting data for our study. We anticipate that our results will reflect no relative difference between anxiety levels of participants and which social media platform they indicate as their primary channel(s). Results from this study may direct methods or areas for future research on the topics of social media and technology use and anxiety or mood disorders.

One of the goals of modern longevity research is to find pharmacological means to increase lifespan and/or healthspan without deleterious physiological effects. Berberine is a yellow, bitter-tasting natural alkaloid with a long history in Eastern Asian medicinal use in treatments of a variety of age-associated diseases and infections. In human cell culture models, berberine treatment increases AMPK activity, resulting in delayed senescence through inhibition of the mTOR/S6 pathway. Here, we use the budding yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans to investigate the effects of berberine on healthspan and lifespan. For the yeast S. cerevisiae, growth rates of haploid and diploid yeast cells, as well as chronological (a measure of population viability through time) and replicative (a measure of mitotic potential) yeast aging paradigms were assayed in the presence of concentrations of berberine ranging from 0.1 - 100.0 ng/uL. For C. elegans, organismal lifespan as well as various healthspan measures are being analyzed. Currently, we have found that concentrations of berberine greater than 10 ng/uL in haploids are sufficient to inhibit cell growth and lower concentrations (0.1-10 ng/uL) result in increased yeast viability when shifted to respiratory metabolism, a means of extending lifespan in yeast. Our lifespan studies are ongoing. Our experiments will provide valuable insights into the role of this long-used medicinal substance on cell aging and health using two important longevity models.