SPUR Participants

Past Participants

SPUR 2020 was cancelled due to the COVID-19 pandemic.

Amanda Adams, The University of Tulsa (Prof. Lauren Barth-Cohen, Educational Psychology)

Aspects of Data Analysis in an Introductory Physics for the Life Sciences (IPLS) Laboratory Course

The Next Generation Science Standards (NGSS) for K-12 education propose an active, three-dimensional science education. Students utilize Scientific Practices, such as Analyzing and Interpreting Data, to scientifically investigate the world, which enables students to learn and apply Crosscutting Concepts, such as cause and effect, to achieve understanding of Disciplinary Core Ideas in areas such as the physical and life sciences. The physics education research community has designed Physics for the Life Sciences (IPLS) lecture and laboratory courses with the goal of connecting physics to biology. Though developed prior to the publication of the NGSS, these labs contain three-dimensional learning throughout, intending for students to develop their research skills, including Analyzing and Interpreting Data. As of yet, there is little understanding about how students engage in this practice in IPLS labs. Needed is a more detailed understanding of this practice, which in turn can support the development of research and assessment tools. Our team conducted qualitative analysis of students' lab reports, and audio/video recordings of pilot task-based interviews and of classes, to support the development of a preliminary theory of Analyzing and Interpreting Data that involves the following aspects: data collection, data cleaning, data manipulation, data interpretation, argumentation, mathematization, and utilizing representations. We then analyzed the first semester IPLS lab course at the University of Utah to specify where students engaged in each aspect of data analysis within each lab. These preliminary results supported the design of a task-based assessment to assess students' skills in these aspects. Our team is currently piloting the assessment, where it will be further refined and validated. This assessment, along with other sources of data, will provide insight into, and enable theorization of, how students engage in the process of data analysis in IPLS lab courses at the University of Utah.

Marcus Blackburn, University of Utah (Prof. Frank Sachse, Bioengineering)

Cellular Structures Involved in Heart Contraction Degrade With Age

Heart disease continues to be the leading cause of death in the United States and accounts for one in every four deaths in patients 65 and over. Heart failure is a specific heart disease where the heart weakens to the point that it cannot pump effectively, and affects approximately 7% of men and 5% of women over 60 the United States. Some of the major components that take part in the conversion of cardiomyocyte excitation to its contraction are transverse tubules (t-tubules), ryanodine receptors (RyR), and junctophilin-2 (JPH2). T-tubules and RyRs remodel in heart disease, leading to less effective contraction. However, there is not an explicit characterization between t-tubule, RyR, and JPH2 remodeling with age. Confocal image stacks of t-tubules, RyRs, and JPH2 were obtained from left ventricular myocardial tissue slices of two human donor hearts of ages 21 yr (young) and 69 yr (old). These 3-dimensional (3D) image stacks of the t-tubules, RyRs, and JPH2 were then processed and visualized to study the spatial distribution of the three structures relative to each other. The 3D reconstructions of the two samples were visualized. The t-systems in the young and old donors are similar; however, the RyR clusters are more numerous and closer to the t-tubules in the younger donor than in the older donor. The JPH2 clusters follow a similar pattern but are even less numerous in the older donor than in the younger donor. These preliminary results from the young and old donors suggest that as a heart ages there is an observable degree of remodeling between the three components and that the three components' relative distances to each other increase. More data is needed to further investigate the relationship between aging and cardiomyocyte structure remodeling.

Sophie Buysse, College of St. Benedict and St. John's University (Prof. Bill Anderegg, School of Biological Sciences)

Genetic Influence on Drought Tolerance in Quaking Aspen (Populus tremuloides)

Climate change poses a threat to quaking aspen (Populus tremuloides) in the southwestern U.S. as increases in temperature and decreases in precipitation are predicted to lead to more frequent, severe droughts. While some populations of quaking aspen tolerate drought, the extent of their tolerance has limitations which future environmental conditions may exceed. Quaking aspen are a clonal species, which provides an ideal system to study genetic contributions to drought-tolerance traits. By quantifying levels of drought tolerance from multiple trees within the same clone, the variability in how one clone responds to drought can be studied (i.e. phenotypic plasticity). By comparing drought-tolerance traits between nearby clones, genetic influences on drought tolerance can be detected. Phenotypic plasticity combined with genetic influences on drought-tolerance traits may allow certain clones to tolerate more severe drought than others. To investigate phenotypic plasticity and genetic influence on drought response in quaking aspen, we investigated the extent to which physiological drought-tolerance traits differ within ramets of a single clone and between clones across an elevation gradient in aspen forest stands in the San Juan National Forest in Colorado during a severe drought year (2018). The following drought-tolerance traits were measured: percent loss of stem hydraulic conductivity (PLC), leaf area-to-sapwood area ratio, specific leaf area, and water potential at leaf turgor loss point. These traits capture the level of drought stress on a tree (e.g. PLC) as well as ways for trees to physiologically respond to drought stress (e.g. decreasing leaf area-to-sapwood area). We observed variation in all drought-tolerance traits between ramets of the same clone. Variation was also observed between clones, though it could not be directly attributed to genetic influence. These results indicate that while genetic influence may be a factor in drought-tolerance traits, factors such as environmental conditions likely play a larger role.

Saffron Collins, University of Utah (Prof. Claudia Geist, Sociology)

Examining the Perceived Hypothetical Impact of Pregnancy

Through data from HER Salt Lake, an longitudinal data collection initiative with Planned Parenthood and the University of Utah's Division of Family Planning, we have been looking at the reasons that individuals give for not wanting a pregnancy at this time in their life. Dr. Geist is specifically interested in the financial aspects of the issue. Through coding and analysis, we hope to get a better look at the perceived impacts of a hypothetical pregnancy.

Kobe Cornelison, University of Utah (Prof. Trafton Drew, Psychology)

Independent Component Analysis of Electroencephalography

Independent Component Analysis (ICA) is a novel analytical tool that can be used to reduce noise in non-gaussian data sets to extract normally distributed data. In lab we developed a new analysis protocol employing ICA for the purpose of analyzing Electroencephalography (EEG) data containing major muscle artifacts. Using this pipeline, we are able to generate more precise Event-related Potentials (ERP). This method is particularly useful in regards to EEG since data can often contain movement-based artifacts as well as random noise that are irrelevant to waveforms. ICA uses an algorithm to reduce the amount of noise in the raw data set by organizing the source electrodes into components that are then presented in order of the amount of variance the component contributes. By removing components that account for the highest amount of variance in the data, ICA is able to reduce the number of movement-related artifacts and overall noise in the data set. This is useful during the analytical process because by reducing variance across the data set we are better able to isolate the EEG component in the data that is associated with the task when creating ERPs. By creating more precise ERP waveforms we are better able to isolate the relevant components of the waveform that are associated with a task increasing the accuracy of the analysis.

Logan Edvalson, Brigham Young University (Prof. Micah Drummond, Physical Therapy and Athletic Training)

Neuromuscular Electrical Stimulation and Protein Supplementation During Bed Rest in Older Adults Increases Muscle Macrophages but Is Not Related to Preserved Lean Mass

Periods of inactivity in older adults due to injury or disease have shown to have negative effects on muscle strength. Therapies that mitigate these effects would reduce recovery time and allow patients to return to their lives sooner. Macrophage polarization states play a significant role in the repair and maintenance of muscle; one being proinflammatory (M1) and the another anti-inflammatory/pro-fibrotic (M2). Previously we found that neuromuscular electrical stimulation when combined with protein supplementation (NMES+PRO) preserved thigh lean mass in healthy older adults. Therefore, we hypothesized that induction of muscle macrophages by NMES+PRO may be partly responsible for maintenance of lean tissue. We analyzed muscle sections (CON, N=10; NMES+PRO, N=8) for macrophages and fibrosis before and after bed rest in both a CON and NMES+PRO groups. Analysis was quantified either by counting the number of macrophages per unit area in ImageJ or finding the percentage of section that was dyed (marker of fibrosis) using Nikon's image analysis software. Surprisingly, we found that the change in M1 macrophage was significantly higher (p<0.05) in the NMES group (vs control) after bed rest while M2 macrophages were unchanged. Moreover, the percentage of fibrosis trended upwards in the NMES group after bed rest (p=0.06). Neither Thigh lean mass nor fibrosis correlated with muscle macrophages. We conclude that daily treatment with NMES+PRO during bed rest induced a muscle pro-inflammatory response and tended to increase connective tissue deposition which might be a reflection of overuse (treatment: 3x day for 4 consecutive days) but was not related to the preservation of thigh lean mass that was observed previously.

Braden Fallon, University of Utah (Prof. Melodie Weller, Dentistry)

Hormone-Mediated Regulation of Hepatitis Delta Antigen Expression in HEK 293 Cells

Persistent low-level infections of the Hepatitis Delta Virus (HDV) have been suggested to lead to the full development of primary Sjogren's syndrome (pSS). Primary Sjogren's syndrome is a chronic autoimmune disease characterized by decreased tear and/or saliva production, inflammation within salivary gland tissues and development of autoantibodies. Women are 9 times more likely to be diagnosed with pSS and are most often diagnosed during early-stage menopause where progesterone, estrogen and testosterone levels decrease. We hypothesize that differential hormone profiles associated with peri- or post-menopausal women may lead to increased HDV antigen expression and increased risk of pSS development. Therefore, a study was designed to identify whether changes in concentrations of these hormones affect the expression of the HDV antigen in an in-vitro system. HEK 293 cells expressing the small HDV antigen under control of a tetracycline-inducible promoter (HEK-293-SAG) were cultured in 96-well plates with media containing gradients of hormone concentrations within physiological constraints. Testosterone, progesterone, B-estradiol, and DHEA were selected as study hormones. HEK-293-SAG cells were incubated for 3 days +/- hormone exposure and +/- 0.1 ug/mL tetracycline to activate the tetracycline promoter. The cells were incubated under experimental conditions for 72 hours. At the termination of the study, RNA was isolated, and the antigen copy number was quantified via qPCR. An increased HDV transcript copy number indicates stimulation of antigen transcription while a decreased copy number indicates inhibition. Based on previous research, it is expected to observe an increase in HDV antigen transcripts with lower hormone concentrations. Further studies are warranted to validate the mechanism of hormone-mediated regulation of HDV antigen expression.

Billy Finlay, University of Utah (Prof. Brennan Payne, Psychology)

The role of left inferior frontal gyrus in memory for predictable and unpredictable words: An event-related transcranial magnetic stimulation study.

Humans comprehend language with remarkable speed. One way that the brain appears to accomplish this feat is by generating predictions about likely upcoming input. When input is predictable based on the prior context (e.g., "I take my coffee with cream and sugar"), word recognition is facilitated, whereas less-predictable words (e.g., with cream and honey) are processed with less ease. At the same time, there is little understanding of the fate of these words in long-term memory. Some studies suggest that predictable words are better remembered, whereas others suggest that prediction violations are encoded more saliently in memory. Although the use of context in predicting upcoming words has been thoroughly studied using EEG techniques, the underlying neural mechanisms involved in memory for (un)predictable words are less well understood. One area of the brain known for speech production and cognitive control, the left inferior frontal gyrus (LIFG), may be recruited to predict upcoming words. In this study, we applied a novel technique to examine the role of the LIFG in memory for predictable and unpredictable words: transcranial magnetic stimulation (TMS). TMS is a non-invasive neurostimulation technique that induces electric currents in the brain. In this study, participants read category cues (e.g., A type of tree) paired with target words that were either predictable (high typicality, e.g., oak), unpredictable (low typicality, e.g., ash), or incongruent (out of category, e.g., tin). Repetitive event-related TMS (5Hz) was used to induce cortical inhibition of the LIFG or its right-hemisphere homologue (RIFG, an active control site) during the category cue. Memory was assessed via a delayed cued-recall task. If LIFG is recruited in the prediction process, we expect cortical inhibition of LIFG during category processing to impact the subsequent recall of predictable and unpredictable words. Pilot results from our initial 10 participants will be presented and discussed. Findings have implications for our understanding of the neural mechanisms of language prediction.

Rejoice Fon, University of Utah (Prof. Russell Richardson, Geriatrics)

Long term effects of Hypertensive Disease of Pregnancy On Vascular function

Hypertensive disease of pregnancy (HDP, - preeclampsia and gestational hypertension), a relatively common pregnancy disorder, is an important cardiovascular disease (CVD) risk factor likely leading to the development of CVD and other diseases in both the mother and baby. In the United States, ≈160,000 pregnancies per year are affected by HDP, implying, ultimately, a substantial increment in the cost of healthcare for these women and their offspring and a consequent reduction in their quality of life. Utilizing pulse wave velocity, to define arterial stiffness, and flow-mediated dilation and passive limb movement, to define endothelial- dependent vascular function, the goal of the study is to determine whether women with a history of recurrent preeclampsia and/or gestational hypertension have an accelerated vascular aging phenotype to shed more light on the pathophysiology of CVD among women who have experienced these forms of HDP. The intent is study 20 exposed women, 10 unexposed women matched for age, and 10 unexposed older women (> 70 yrs). The Utah Population Database (UPDB) was used to identify a cohort of women with (exposed) or without (unexposed) a history of recurrent HDP who delivered their first pregnancy 10-15 years ago. To date 42 women have been identified as exposed women (i.e. including all the HDP), with 10 meeting the eligibility criteria of the study (i.e. experienced preeclampsia or gestational hypertension, but with minimal other comorbidities). Appropriate classification is crucial for this study. Of the 10 eligible women, 4 have responded positively to inclusion in the study and have been consented and the vascular health and function assessments have been scheduled. Recruitment, screening, and, ultimately vascular assessments continue, with the goal to determine if previous HDP causes accelerated vascular aging.

Caitlin Gallivan, University of Utah (Prof. Aylin Rodan, Internal Medicine)

VPS33B is Required in the Drosophila Tubule and Hindgut for Normal Excretion

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare and fatal genetic disease in which affected individuals rarely live past infancy. This disease is accompanied by several severe phenotypes including renal tubular dysfunction. It has been shown that ARC Syndrome patients possess genetic mutations in either the Vacuolar protein sorting-associated proteins 16B or 33B (VPS16B and VPS33B respectively), but how these genes affect renal tubular function is unknown. Our lab uses the fruit fly, Drosophila melanogaster, to study pathways relevant to mammalian kidney function in the Drosophila renal system. VPS16B and VPS33B are conserved in Drosophila, and we hypothesized that they are important for fly renal function. In order to test this hypothesis, we employed the “poop-drop assay” to evaluate excretion in Drosophila melanogaster in which we knocked down Drosophila Vps16B and Vps33B in different parts of the fly excretory system. Using the GAL4/UAS-RNAi system, we knocked down our genes of interest in either the Malpighian tubules or the hindgut, the two parts of the fly excretory system, and measured excretory (“poop”) drops per fly. We fed the flies either a normal diet or a diet supplemented with high salt (0.3 M NaCl). Here we report that there is no significant excretion phenotype when Vps16B is knocked down in the hindgut or in the tubules. However, Vps33B knockdown males express a reduced excretion phenotype with uro-GAL4, which is localized in the tubule, when fed high salt fly food. Furthermore, we observe a significant increase in excretion in Vps33B/c601 females exposed to normal fly food. The c601-GAL4 is expressed in the hindgut. Collectively, our data suggest that the VPS33B protein affects excretion and functions in both the tubule and hindgut, while VPS16B has not been proven to play a significant role in either tissue.

Angie Gamarra, University of Utah (Prof. Sarah Projansky, Film & Media Arts)

Comprehensive Analysis (History, Present, & Future) of Title IX's Role in Addressing Sexual Misconduct on University Campuses

This project looked at mainstream media coverage and feministic logics starting from 1972 - present to identify best practices based on careful analysis, precedent, and the day to day experiences of Title IX coordinators. We investigated and analyzed court arguments that use Title IX to protect against sexual misconduct as well as did a parallel search on Office of Civil Rights (OCR) documents to comprehend the parameters of Title IX's role in protecting against sexual violence on university campuses. Victim advocacy/appropriate aid and transparency in university policy is the core of this research. This research exposed us to current strategies universities use to address sexual misconduct but also made us more sensitive and aware of Title IX rules currently being in transition on many campuses nationwide. We found that this project has the potential to have a significant impact as we all grapple with the on-going changes in Title IX.

Davis Garner, Brigham Young University (Prof. David Belnap, School of Biological Sciences)

Investigating the Polymorphs of Polyomavirus Particles

The structure of the polyomavirus is primarily composed of the capsomere VP1. VP1 forms pentamers with a protruding tail from each monomer; pentamers bind together to form the viral capsid. Interestingly, VP1 pentamers will create polymorphic capsids that vary in shape and size when put in different environmental conditions. The conditions and structure of the pathogenic polyomavirus capsid have been thoroughly studied in previous research, which has revealed that the VP1 tails of adjacent pentamers interact to hold the capsid together. However, nonpathogenic capsid assemblies have received little attention and there is much knowledge to be gleaned from examining them. To do so, we are constructing high-resolution models of multiple VP1 capsids by expressing and purifying VP1, stimulating the formation of the capsids of interest, and then imaging the capsids via cryo-electron microscopy. All the images taken will be composited through software to create accurate and detailed models of the unique capsids. The models that we create will not only give great insight about the capsids of interest, but they will also elucidate interactions between VP1 tails that have never been understood before.

Tory Glomb, University of Utah (Prof. Julio Facelli, Biomedical Informatics)

Structural Profiling of MicroProteins: Aiding in the Classification and Identification

MicroProteins are small, single-domain proteins, usually less than 100 amino acids in length. Previous research has tried to classify the differences between a small proteins and a MicroProteins. However, there are varied interpretations as to how micro-proteins should be identified leading to a poor definition of exactly what constitutes a MicroProtein. The goal of this research is to find if there are structural features that are characteristic of MicroProteins. We selected 48 well characterized and suspected MicroProteins from the SWISS PROT repository, from which we extracted their amino acid sequences. These sequences were used as input to QUARK, in order to predict 3-D models of each protein. From the predicted tertiary structures, DSSP and bmi scripts were used to predict the secondary structures of these proteins. The secondary structures were used to determine the prevalence of turns, coils, and helix. We used BLAST, STRING, and RaptorX to get information on binding sites, structural properties, gene connections, and functions. Comparisons of structural disorder, the types of solute binding, turns, coils, and helix percentages, gene connections and functions were used to create the structural profiles of the MicroProteins. In future work we will use machine learning techniques to classify these features. This research was supported by a Supplement to the NLM Training grant T15 LM00712418, with additional support from the Utah Center for Clinical and Translational Science funded by NCATS award 1ULTR002538. Computer resources were provided by the University of Utah Center for High Performance Computing, which has been partially funded by the NIH Shared Instrumentation Grant 1S10OD02164401A1.

Stephen Harman, University of Utah (Prof. Samir Abdelrahman, Biomedical Informatics)

Temporal Risk Factor Analysis for Acute Kidney Injury

Acute kidney injury (AKI) is a condition frequently experienced by patients in intensive care units (ICUs) that is associated with increased morbidity and mortality. We defined AKI using the guidelines set by the Kidney Disease Improving Global Outcomes foundation’s urine output criteria. Using the MIMIC-III data set, a freely accessible critical care database (Johnson AEW, Pollard TJ, Shen L, Lehman L, Feng M, Ghassemi M, Moody B, Szolovits P, Celi LA, and Mark RG. Scientific Data (2016). DOI: 10.1038/sdata.2016.35) we extracted data from 53,432 adult patients admitted in an intensive care unit. From this data, we derived 26 time series of variables that could be considered as predictive features. We conducted a risk factor analysis to understand how the significance of these features change over time. For each of the first twelve hours in which a patient was admitted into the intensive care unit, we used Chi-squared and Kruskal-Wallis H tests to determine the significance of these features with respect to the patients’ stage of AKI within the next 6, 12, 24, 36, 48, and 72 hours. This research was supported by a Supplement to the NLM Training grant T15 LM00712418. Computer resources were provided by the University of Utah Center for High Performance Computing, which has been partially funded by the NIH Shared Instrumentation Grant 1S10OD02164401A1.

Elizabeth Hayes, University of Utah (Prof. Minna Roh-Johnson, Biochemistry)

Characterizing tumor cell dissemination through analyses of cell-matrix interactions

The leading cause for mortality in cancer patients is due to metastasis. Mechanistically identifying how the tumor cells disseminate in vivo, however, continues to evade healthcare professionals. Recently, focal adhesions have been shown to form in melanoma cells during migration in in vivo models. Focal adhesions are macromolecular structures formed on the leading edge of a cell that interact with the microenvironment and are known to be key regulators in cell migration. Bytargeting known proteins of focal adhesions, integrin and paxillin, we may be able to gain a better insight into the behavior and migratory patterns of tumor cells during dissemination within an organism. To do this, we fluorescently tagged integrin and paxillin through traditional cloning methods and transduced them into zebrafish melanoma cells to further visualize the focal adhesion-based dissemination behavior within transparent zebrafish. By characterizing the in vivo microenvironment of tumor cells, the clinical regulation of metastasis in cancer patients, and thus survival, may become a closer reality within healthcare.

Tim Hui, Boston College (Prof. Stavros Drakos, Internal Medicine)

MPC1 DEFICIENCY CAUSES HEART FAILURE AND EXACERBATES REPERFUSION INJURY IN A MOUSE MODEL OF ISCHEMIA-REPERFUSION

Coronary artery disease and its role in myocardial infarction (MI) has become the leading cause of death and disability globally. Treatment of MI has improved with advances in reperfusion. However, up to 50% of the damage that occurs after acute myocardial Infarction (AMI) is due to reperfusion injury. Unfortunately, there has been little success in reducing reperfusion injury. Our study utilized an Impella, a percutaneous ventricular assist device, to unload the left ventricle (LV) of a porcine heart while simultaneously reperfused the ischemia, resulting in more salvaged myocardium. Furthermore, a recent study of a porcine ischemia reperfusion (I/R) injury model has implicated a transporter protein, Mitochondrial Pyruvate Carrier (MPC), as being cardio-protective during I/R. The study reported isolated mouse hearts subjected to I/R indicated that inhibition of MPC using an inhibitor exacerbated myocardial infarction. While the exact mechanism of MPC in I/R injury is not well understood, we hypothesize that the reduced level of MPC in cardiac muscle will exacerbate the impact of IR injury in adult mice. To test this, cardiac specific and inducible MPC1 knockout mice were generated through cre-loxP-mediated-Recombination which allows the gene to be deleted when the mouse is 8 weeks old upon tamoxifen injection. The MPC1-/- mouse revealed signs of heart failure 10-12 weeks post-induction such as, an increase in left ventricular end diastolic diameter, decreased ejection fraction, and increased LV mass as compared to the wild type littermates. Preliminary data of I/R injury on these mice before development of heart failure symptoms indicated that the MPC1 deficiency exacerbated the MI in comparison to the control group. The MPC1 deficient mice were prone to mortality during the procedure hinting at a role of MPC1 in myocardial salvage during I/R. In the future, we will examine the metabolic profile and gene expression in these mice during I/R.

Grayson Hull, University of Utah (Prof. Owen Chan, Internal Medicine)

Novel Somatostatin Receptor Antagonist Improves Glucagon Secretion in Diabetic Rats

Hypoglycemia is the most serious acute complication for type 1 diabetic (T1D) patients trying to reach optimal glycemic goals. Key to this is loss of the ability to secrete glucagon in response to hypoglycemia, which occurs within 5 years after the onset of diabetes. Glucagon is the primary hormone that helps to raise blood glucose levels back to normal when they begin to fall. Finding pharmacotherapies that can restore glucagon secretion from the pancreatic α-cells is crucial to helping prevent or reduce the incidence of hypoglycemia in patients with T1D. The regulation of glucagon secretion is controlled by multiple factors, one of which is somatostatin (SST). SST is a hormone that is secreted by pancreatic δ-cells and it acts through SST type 2a receptors (SSTR2a) to suppress glucagon secretion. In T1D, SST levels are elevated and it may contribute to loss of the glucagon response to hypoglycemia. Therefore, antagonists of SSTR2a may be a promising therapy to help restore this response. Streptozotocin (STZ)-diabetic rats were used to evaluate the efficacy of ZT-01, which is a new SSTR2a antagonist. Surgery to cannulate the left carotid and right jugular was performed on the rats one week after induction of diabetes. The animals were then subjected to a hyperinsulinemic-euglycemic-hypoglycemic clamp one week after surgery. The control group received injections of vehicle and the treatment groups received varying dosages of ZT-01 one hour prior to inducing hypoglycemia to find the lowest effective drug dose that would enhance glucagon secretion during hypoglycemia. We evaluated four different doses ranging from 0.3mg/kg to 0.1ug/kg. The most promising dose was 0.3mg/kg which increased glucagon secretion by almost 8-fold compared to vehicle-treated STZ rats. Lower doses exhibited a dose-dependent decline in efficacy with 0.1ug/kg showing no effect. In conclusion, our pre-clinical findings indicate that ZT-01 shows great potential as a therapy to improve glucagon secretion in rats with T1D.

Shalini Kasera, University of Utah (Prof. Lisa Joss-Moore, Pediatrics)

IUGR and development alter hepatic PEMT levels in the rat

Intrauterine growth restriction (IUGR) is a phenomenon in which the fetus fails to achieve its genetic growth potential in-utero. IUGR dysregulates circulating docosahexaenoic acid (DHA), an ω-3 fatty acid essential for organogenesis and favorable neonatal outcomes. This can lead to metabolic issues, such as lipid accumulation in the liver. Our group showed, in a rat model, that IUGR induces sex-divergent outcomes, with increased liver lipid accumulation in juvenile males and successful clearing of excess liver lipid in juvenile females. We also showed that DHA supplementation reduces hepatic lipids in male juvenile IUGR rats. The phosphotidylethanolamine methyltransferase (PEMT) phospholipid methylation pathway governs the export of lipids from the liver in the form of very low density lipoproteins (VLDL). Higher hepatic lipid concentration is thus associated with lower PEMT activity. We hypothesize that IUGR reduces PEMT expression in male rats and alters the temporal expression of PEMT in the liver. We also hypothesize that DHA supplementation normalizes hepatic PEMT levels. To test our hypothesis, we measured mRNA and protein levels of liver PEMT in juvenile control and IUGR rats. In order to identify developmental timepoints critical for PEMT expression, we also measured PEMT mRNA throughout development in control rats. mRNA levels were measured using real-time RT PCR, relative to HPRT. In juvenile rats, IUGR increased PEMT mRNA and protein in the liver of female rats, but did not affect PEMT levels in liver of male rats. DHA supplementation normalized female hepatic PEMT mRNA levels. Assessment of liver PEMT mRNA levels from younger rats (day 0, 7, 14, and 21) showed that PEMT mRNA appears to peak at day 14. We conclude that IUGR induces altered hepatic PEMT expression in female rats, which is normalized with DHA. We speculate that increased PEMT in female IUGR liver leads to increased hepatic lipid clearance. Ongoing studies are evaluating the effect of IUGR on PEMT and hepatic lipids at earlier developmental timepoints.

Rachel Kon, University of Utah (Prof. Ram Gouripeddi, Biomedical Informatics)

Profiling Exhaled Breath Condensates in Exposomic Studies

It is well established that polluted air causes and exacerbates pulmonary disease such as chronic obstructive pulmonary disease (COPD), asthma, and sleep apnea. However, the biological mechanisms involved in these conditions is not well understood. The goal of this research is to identify biomarkers from exhaled breath condensate samples obtained from participants with these conditions, and trace biological pathways triggered by pollutants. These EBC samples which have been well preserved and catalogued are being analyzed using gas chromatography mass spectroscopy (GCMS) with solid phase microextraction (SPME) to identify various chemical signatures. Also, we collected air quality measurements for the time periods and geographic locations associated with these participants' residential locations and times of sample collection. The GCMS analysis results and environmental data are then integrated and assimilated to generate high-resolution spatio-temporal records of exposure and chemical signatures of biological mechanisms leveraging the Exposure Health Informatics Ecosystem (http://prisms.bmi.utah.edu/). We also will evaluate computational models of pollutant levels in this assimilation effort. Finally we will review any existing literature for those biomarkers that we find significant from our analysis for each of these respiratory conditions.

Evelyn Lauren, University of Utah (Prof. Man Hung, Orthopaedics)

Risk Modeling of Unmet Dental Needs using Machine Learning

Background: Oral health is a gateway to a person's overall health and well-being, however unmet dental care needs remain as a global public health concern. Previous studies have suggested that social determinants might be associated with unmet dental care needs, but there is a lack of study using large national data in this area. This study seeks to identify leading factors towards unmet dental care needs through the use of machine learning tree classifiers. Methods: Data were obtained from the household component of the 2016 Medical Expenditure Panel Survey. Sampling weights were applied to obtain demographic characteristics representative of the United States' population. Random Forest, ExtraTrees Classifier, Decision Tree Classifier, and Gradient Boosting Classifier were used to acquire the top predictors towards unmet dental care needs based on relative importance, and the results were compared with those examined using chi-square test and independent samples t-test. Results: The top predictors obtained were consistent across the different tree classifiers, except for Random Forest. Delayed in getting necessary medical care, family having problem paying medical bills, inability to get necessary medical care, family size, and total income were consistently rated as the top predictors of unmet dental care needs. All of the predictors are significant when chi-square test or independent samples t-test were applied. Conclusion: Social determinants are strongly related with unmet dental care needs. The use of machine learning tree classifiers provides the ability to process hundreds of variables at once and outputs the top variables based on order. Thus, it is possible to discover top predictors that were not previously found using traditional statistics. This study provides an opportunity for healthcare professionals and policy makers alike to identify populations in need of dental care more efficiently.

Chelsea Li, University of Utah (Prof. Julio Facelli, Biomedical Informatics)

Understanding the Relationship between Protein Structure and Pathogenicity for PRNP Variants Associated with Creutzfeldt-Jakob Disease (CJD) and Gerstmann-Sträussler-Scheinker (GSS) Disease

PRNP is a gene coding for the major prion protein that is composed of 253 amino acids. This protein has a role in neuronal development and synaptic plasticity along with myelin sheath maintenance and homeostasis. Various mutations of PRNP can lead to genetic prion diseases, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker (GSS) are two prion diseases that are the focus of this analysis. CJD patients develop rapid dementia with a short survival time, while GSS patients who may have similar symptoms have survival times that can last 3-10 years. To understand the role of mutations of these two clinically different neurodegenerative diseases protein structure prediction can be used to analyze how changes of the amino acid sequence affect structure. From Swiss Uniprot, the canonical sequence of PRNP was obtained. Using I-TASSER we predicted the 3D structures of PRNP for, both the canonical amino acid sequence and those obtained by single substitutions for each variant that have been reported to cause either CJD or GSS. The protein structures were compared to the wild-type structure and among themselves. Further investigation for this study will include using more tools to assess pathogenicity and deeper analysis and comparison between each of the variants along with seeing how the major prion protein interacts with other proteins to develop a potential pathway that it interacts. This research was supported by a Supplement to the NLM Training grant T15 LM00712418, with additional support from the Utah Center for Clinical and Translational Science funded by NCATS award 1ULTR002538. Computer resources were provided by the University of Utah Center for High Performance Computing, which has been partially funded by the NIH Shared Instrumentation Grant 1S10OD02164401A1.

Jordan Little, Clemson University (Prof. Karen Eilbeck, Biomedical Informatics)

Variant curation for newborn screening genomic panels.

In the US, NBS was established as a public health initiative in the 1960s, with the goal of identifying infants with life threatening but treatable disorders before the onset of symptoms. This allows treatment to begin before clinical symptoms (i.e. permanent brain damage, growth retardation, sepsis, or severe anemia) or death can occur in the newborn. The Utah Department of Health is implementing exome sequencing for infants flagged by the initial test. Interpretation of genomic results is non-trivial, especially in cases where there are rare or novel variants in combination with metabolic data. There exist many databases that have over the years attempted to catalogue genetic variants associated with the many metabolic and immune disorders on the exome panel. Also a national database: ClinVar has become the hub for variant annotation by reference labs, and is a starting place for in depth curation activities. The team at UDoH needs to have a comprehensive set of all reported variants for each disorder to use in their interpretation pipeline. This project set out with the goal of finding and parsing all historical genomic variants for 542 genes, from 7 databases and converting them all to the same coordinate system for comparison. We have collected 20,310 variants, reduced to 14,017 non-redundant variants and compared to ClinVar annotations with and with assertion criteria for the list of 37 SCID genes. 29 of the 30 SCID genes that were analyzed had at least one variant that overlapped between ClinVar and the curated niche databases We have found that ClinVar is still the standard for annotated variants. When compared to the other databases; if ClinVar had less variants the niche datasets were lacking any annotation, making them difficult to use in a clinical setting and challenging the validity of the submission.

John Lund, Brigham Young University (Prof. Jason Wiese, School of Computing)

Identifying Principles for Software to Support Daily Action Planning

A variety of software applications are designed with the intention to support people in their time management. Despite the availability of these tools, many people struggle to get things done in the time they have, suggesting a disconnect between them. Existing literature takes a tool-based focus, looking at digital calendars, to-do lists, email, or personal information management rather than a holistic investigation of time management. This work reports results from an interview and diary activity data from 19 graduate students investigating the tools (digital and paper) and strategies used to manage their time. It also explores how these students engage in a short-term planning task and respond to making concrete plans for the next day for multiple days. Participants relied on unique combinations of tools, habits, and their own memory to manage their time. However, there were structural similarities in their approaches, indicating opportunities for technology to better support time management. Based on principles informed by these similarities, we are developing a mobile application designed to support users in developing daily plans. The application departs from conventional to-do list applications by creating a text-editor-based experience to introduce greater flexibility while still maintaining powerful capabilities such as calendar integration, date formatting, and easy sharing.

Kiana Luu, University of Utah (Prof. Dave Symons, Nutrition and Integrative Physiology)

Whole-body inducible disruption of dihydroceramide desaturase: Vascular implications

Type 2 diabetes mellitus (T2DM) precipitates cardiovascular complications (e.g., impaired vision and atherosclerosis). These complications are associated with vascular dysfunction, which is a generic term to describe arteries that do not dilate or constrict appropriately. Gaining a thorough understanding of the mechanisms responsible for vascular dysfunction is requisite for the design and development of new therapeutic strategies to treat cardiovascular complications associated with T2DM. Our laboratory has shown that when vascular accumulation of the sphingolipid ceramide is prevented in mice, arterial dysfunction and hypertension that otherwise develop in response to high-fat (HF) feeding does not occur. Here, we tested the hypothesis that inhibiting ceramide biosynthesis in mice wherein ceramide has already accumulated reverses arterial dysfunction. Eight-week-old male mice consumed HF chow for 12 weeks. At 20 weeks of age, tamoxifen was administered (3 mg/day for 5 consecutive days via IP injection) to induce knockout (KO) of dihydroceramide desaturase (DES1), an enzyme responsible for ceramide biosynthesis. These mice were compared to a control group wherein DES1 was intact. A week after the last tamoxifen dose, mice were characterized metabolically through glucose and insulin tolerance tests. Then, the endothelial cells from carotid arteries were obtained to determine the efficacy of knockdown, and femoral and cerebral arteries were used to assess endothelial and vascular smooth muscle function on an isobaric myograph. Non-receptor mediated vasocontraction to potassium chloride, endothelium-dependent vasodilation to acetylcholine, endothelium-independent vasodilation to sodium nitroprusside, and intraluminal flow-mediated vasodilation to pressure gradients from 6-30 mmHg were not different when responses were compared in cerebral and/or femoral arteries between DES1 KO mice and the control group. Whole-body inducible KO of DES1 does not reverse vascular dysfunction that develops in mice wherein ceramide has already accumulated.

Cara Mogan, Susquehanna University (Prof. My Helms, Internal Medicine)

The Role of Cystic Fibrosis Transmembrane Conductance Regulator in Cell Migration

Cystic Fibrosis (CF) is a genetic disorder that damages the lungs and digestive system due to disrupted salt and water transport across epithelium. Patients with CF are now living longer as a result of improved treatments that reduce the symptoms of thick mucus and blocked secretion of digestive enzymes. Unfortunately, as individuals with CF age, they are at increased risk of other diseases, such as colon cancer. Colon cancer is 4 to 8 times more likely to develop in patients with CF than the general population. The risk of colon cancer is 11 times higher for CF patients with a history of distal intestinal obstruction syndrome and increases to over 30 times higher for patients who have received a solid organ transplant. To determine if the elevated incidence of colon cancer in CF patients is due to defective cystic fibrosis transmembrane conductance regulator (CFTR) function, a scratch assay was performed on cultured human colon cells. The scratch was imaged every 24 hours for five days. Wound area and cell migration were measured in the presence of 5 mM Forskulin and 500 mM IBMX (a CFTR activator) or 5 mM CFTRi (a CFTR inhibitor). Control and CFTR inhibitor treated cells grew to fill in the wound area by day 3 with an average migration of 55.38 and 63.94 mm2/24 hours respectively. The CFTR activator treatment group did not completely grow into the space by this time with an average migration of 27.45 mm2/24 hours and about 70% of the wound area still open on the third day. The cystic fibrosis transmembrane conductance regulator plays an important role in the rate of cell migration and thus cancer progression.

Ryan Murdock, University of Utah (Prof. Taylor Sparks, Materials Science and Engineering)

Is chemical domain knowledge even necessary when machine learning materials properties?

The process of predicting material properties using machine learning often involves engineering a description of the materials being assessed, which is then used as input to various models for regression or classification. This description commonly comes in the form of a list of easily-measured characteristics of elements in the material. For instance, one might include the boiling point, atomic radius, and electronegativity of each element within a particular chemical formula. Creation of such composition-based feature vectors (CBFVs) can be time-intensive and requires significant domain knowledge. The advent of learned elemental embeddings and elemental encodings created with no explicit knowledge of chemistry challenges the practice of utilizing and creating CBFVs. Further, it raises questions concerning the necessity of domain knowledge for the practice of material informatics. This work assesses the efficacy of CBFVs and chemistry-free representations given different predicted properties and dataset sizes in order to compare these two approaches. We find that the simple one-hot encoding of elements performs competitively with other representations under some circumstances. For instance, preliminary results indicate that using one-hot encoding with a simple model and a large dataset may reduce the mean absolute error (MAE) of predicting shear modulus by 2.5% when compared to Mat2Vec, a learned embedding. Further, these preliminary results indicate a potential 9.5% decrease in MAE with one-hot on predicting formation energy when compared to Magpie, a CBFV.

Dylan Neff, University of Utah (Prof. Liz Conradt, Psychology)

The Intergenerational Effects of Maternal Anxiety During Pregnancy

Prenatal programming theory predicts that maternal stress during pregnancy increases the likelihood that infants will exhibit altered behaviors and emotions after birth (O’Connor et al., 2002), which may be adaptive for a stressful environment. Additional research (Glover, 2015) has shown that there is reason to suspect that maternal psychobiological factors can have wide-ranging effects on infant development. One way to measure those effects is to observe physiological arousal during stress. Electrodermal activity, a measure of the sympathetic nervous system, has also been widely used as an indicator of emotion arousal in adults and children. For this study, mothers completed a battery of questionnaires during their third trimester of pregnancy that included the State-Trait Anxiety Inventory. They returned to the lab with their infants seven months postpartum, and participated in the Still-Face Paradigm. During this task, mothers played with their infants for two minutes, then stopped interacting and maintained a flat affect for two minutes, then finally resumed normal play. This short period of parental unavailability allows researchers to observe infants' regulatory ability. Using data from this experiment, it was hypothesized that high levels of prenatal maternal anxiety would firstly be related to high infant baseline sympathetic system arousal, and secondly be related to high infant sympathetic reactivity to stress. Using linear regression, the author found that mothers with higher trait (general) anxiety during the third trimester of pregnancy had infants who were less reactive to the stressor(β = -.26, p < .05). Infant sex, household income, and maternal race and age were included in the regression as control variables. Baseline reactivity was not significantly related to maternal anxiety. While neither hypothesis was supported, the finding that prenatal maternal anxiety is significantly related to infants’ postnatal physiological reactivity lends support to the theory that in utero experiences may “program” infant stress response systems.

Andrea Palos-Jasso, University of Mount Olive (Prof. Sujee Jeyapalina)

Micro-Patterned Silicone Surfaces Limit Capsular Thickness Around Breast Prostheses

Breast prostheses are often accompanied by clinical complications such as bacterial infection (~2.4-16%) or capsular contracture (CC; ~7.6-40%) formation and result in pain and discomfort to the patients. The formation of CC has been attributed to bacterial colonization, either on the surface of the implant or within the surrounding capsule. Thus, it was realized that the use of antibacterial eluting implants or surfaces that deter bacterial adhesion could circumvent this adverse outcome. SharkletTM surfaces that mimic shark skin denticle patterns are known to deter bacterial adhesion and biofilm formation. Therefore, it was hypothesized that similar micropatterns would limit bacterial adhesion, and in turn, CC thickness around implants. In order to test this hypothesis, 10 mm diameter silicone implants with 3X3, 5X5, and 10X10 micropatterns, in addition to a non-patterned control implant, were fabricated. Efficacies of these designs to limit CC formation were tested in a rat model; where twelve Sprague Dawley rats were divided into 4 groups. During the implantation surgery, a longitudinal incision was made parallel to the spinal column, and a subdermal pocket was made on the opposite side of the spine by blunt dissection. A single implant (i.e., 10X10, 5X5, 3X3, or smooth control) was then inserted into this pocket, which was then inoculated with Staphylococcus aureus (3.0 x 104CFU). The incision line was closed, and animals were allowed to ambulate for 12 weeks. At necropsy, the implants and adjacent tissues were collected, fixed with 10% formaldehyde, embedded in PMMA, sectioned, polished to optical finish, and then histologically analyzed. The CC thickness data revealed that 3X3 and 5X5 groups had significantly thinner capsules (p<0.05) when compared to the smooth control group, which supported the tested hypothesis. It was therefore concluded that micropatterns could be used to prevent thicker CC formation around breast prostheses.

Alec Parent, University of Utah (Prof. Kathy Sward, Nursing)

Research Platform for Studies using Sensors

Purpose: This SPUR project focused on software to help researchers monitor sensors when they are used with study participants. Background: Software engineering was an integral part of the overarching study research aims. Sensor-based monitoring has been emerging as a tool for health-related research. Tiny sensors can continuously record aspects of a person's behavior, as well as their environment and social context. Sensors in consumer electronic devices and "wearables" like fitness trackers can provide important information for health researchers. Including sensor information in research is a complex task, however. The Study: The Utah PRISMS Informatics center was funded by NIH to create an infrastructure to support using sensors as part of pediatric asthma research. This project was part of one key component of that infrastructure. Research Activities: I learned about health related research, and about research that combines informatics, human-computer interaction, and software engineering. I was able to practice my programming skills and learn new aspects of software engineering.

Henry Ponce-Orellana, University of Utah (Prof. Jill Shea, Surgery)

Rat Adipose-Derived Stem Cell Behavior on Fluoridated Hydroxyapatite Bone Substitutes

Introduction: Bone grafts are used to aid bone repair and regeneration in various surgeries ranging from dental implants to limb salvaging operations. Our group has been conducting research bone substitutes composed of hydroxyapatite and two fluoridated variants. These materials are representative of the various fluoridated forms of hydroxyapatite, which is a mineral found in bone and teeth. We have previously shown that both keratinocytes and osteoblasts adhere to and osteoblasts differentiate on our varying biomaterial surfaces. The goal of this project is to analyze cell proliferation and differentiation of rat adipose-derived stem cells (ADSC) on pellets made from fluorohydroxyapatite (FHA; Ca10[PO4]6FOH), fluorapatite (FA; Ca10[PO4]6F2), and hydroxyapatite (HA; Ca5[PO4]3OH). Methods: The powder for the pellets (FHA/FA/HA) was synthesized and sintered at either 1150 or 1250 degrees Celsius, which directly impacts the crystalline structure of the pellets. For the course of this study, the pellets and a control titanium disk (Ti) were plated with rat ADSC (1,316 cell/cm^2) and incubated for 2- or 10-days. Cell proliferation was measured via an Alamar Blue assay, with all data reported relative to titanium control. Cell proliferation was compared between the different materials using an ANOVA followed by a Tukey’s post hoc test. Results/Conclusion: At two days post plating cell proliferation was statistically greater on the HA1150 pellets (156%±8%) compared all other surfaces (100± 10%; p<0.05). However at 10 days post plating the HA (142±25), FA (149±14), and FHA (141±17) sintered at 1250°C and FA (143±22) sintered at 1150°C had statistically greater cell proliferation compared to the titanium control (100±10%; p<0.05). While there was no difference between the FHA (121±2%) and HA (124±2%) 1150°C and titanium (p>0.05). Future work will evaluate number of cells adhered to the different surfaces, as well as protein (western blot) and gene expression markers (RT-PCR) linked to differentiation of cells to an osteoblasts lineage.

Madison Putich, University of Utah (Prof. Anandh Babu Pon Velayutham, Nutrition and Integrative Physiology)

Effect of dietary blueberry on vascular function in aged C57BL/6J mice

Aging is a major risk factor for cardiovascular diseases such as atherosclerosis, which are major causes of disability and mortality in the elderly. Endothelial dysfunction plays a major role in aging-associated vascular complications. Dietary change may be one of the novel strategies to ameliorate endothelial dysfunction and aging-associated complications. Our lab recently showed that dietary supplementation of blueberries improves vascular inflammation and dysfunction in diabetic mice. In our present study, we investigated the effect of dietary blueberries on vascular function in aged mice. Adult male mice (two months old) and old male mice (17 months old) were fed a control rodent diet (Y and O respectively). The subgroups of Y and O mice were fed a diet supplemented with 3.8% freeze-dried blueberries (Y+BB, O+BB respectively) for 15 weeks. Based on normalization to body surface area, this dose in mice is equivalent to ~1.5 servings of blueberries (~240 g) in humans. Mesenteric arteries were collected and used to assess vascular function using a wire myograph system. After arteries were precontracted to ~65% of maximal phenylephrine-induced contraction and tension was stable, responses to acetylcholine (ACh, 10-8-10-6 M) were evaluated to determine endothelium-dependent vasorelaxation. In our study, there is no difference existed between Y vs. O and O vs. O+BB indicating the vascular function was similar among the groups. Our ongoing studies are focused on identifying the effect of dietary blueberries on vascular inflammation in aged mice and the possible molecular mechanisms involved.

Karishma Shah, University of Utah (Prof. Martin Tristani-Firouzi, Pediatrics)

Disruption of NFATc1 Nuclear Translocation Caused by M527L Mutation

Atrial fibrillation is the most common sustained arrhythmia in clinical practice and causes patients increased risk of stroke and early cardiovascular death. A Utahn family has been identified where the phenotype of early-onset atrial fibrillation segregates with a missense M527L mutation in the NFATc1 protein, an important transcription factor to normal cardiac function. This project aims to identify whether the M527L mutation disrupts the ability of the NFATc1 protein to translocate to the nucleus upon Ca2+ activation. Adenoviral overexpression was used to produce an abundance of wildtype and mutant NFATc1 protein fused to GFP in HL-1 cells. These cells were then incubated for one hour with varying concentrations of isoproterenol to activate the signaling pathway before being fixed. Confocal microscopy was utilized to image these cells and quantify translocation differences between wildtype and mutant NFATc1. This study found significant differences in the trends between nuclear translocation between the wildtype and mutant NFATc1, with the mutant NFATc1 consistently experiencing less translocation upon Ca2+ activation. Reduced translocation could implicate reduced transcriptional activity of downstream gene programs that prevent atrial cells from functioning normally. These results continue to question the cell's ability to regulate NFATc1 nuclear importation and exportation in lieu of the M527L mutation. This abnormal functionality within an atrial model of cardiac cells could provide a starting explanation for the early-onset atrial fibrillation phenotypically identified in the aforementioned family as well as adding to the growing knowledge of gene control over cardiovascular disease.

Darshan Shimpi, University of Utah (Prof. Ed DiBella, Radiology & Imaging Sciences)

Comparing the Effects of Different Processing Pipelines on Producing Diffusion Metrics

Diffusion MRI is becoming increasingly popular due to its ability to non-invasively analyze and visualize areas of the brain, by tracking the motion of water molecules through tissue tracts. The technique has been used in the analysis of strokes, brain tumors, and white matter diseases, however, suffers from distortions which can alter the metrics utilized in clinical applications. Many post-processing methods, however, exist and are being increasingly utilized in pipeline sequences to generate results and data that are uncorrupted by distortion artifacts. With many pipelines being suggested and utilized, it is pertinent to find the most efficient pipelines and programs that can produce optimal image results. In our work we compare the popularized Human Connectome Project Pipeline, to a recently developed pipeline from the University of Wisconsin-Madison, to test for efficiency in creating diffusion metrics. Testing was done by comparing the reproducibility of each pipeline in generating usable results from incomplete data subsets. Image quality metrics were then used to assess the difference between subset and full data parameter maps. The Wisconsin pipeline illustrated a 3% increase in structural similarity between subset maps and complete maps, along with other improved image metrics when compared to the HCP pipeline. The pipeline also processed data quicker than the HCP pipeline, suggesting a slightly more efficient approach in generating diffusion metrics for research purposes.

Trent Stafford, College of William and Mary (Prof. Bobby Mohanty, Chemical Engineering)

Electrocatalytic, Black Titania Lysing of Cells for Biofilm Elimination, Water Purification and Biofuel Refining

My lab has created an electrocatalytic, black titania probe which, when current is run through it, fires hydroxyl radicals at cells it is directed towards, mechanically shredding them.  This technology can be used to destroy biofilms, or antibiotic-resistant, surgical infections that afflict over 100,000 people each year. The current required to eliminate biofilms is not great enough to harm patients treated by it.  This technology can also be used to eliminate pathogens in water.  Since the probes are very inexpensive, require little voltage to operate, and are easily shipped/assembled, they can help provide clean water to the 800 million people worldwide in resource-limited areas who lack it.  Lastly, this technology can destroy the cell walls of algae at a lower energy-cost than contemporary methods.  Since many algae develop large amounts of lipids which can be refined into fuel for engines, our methods mark a substantial step toward making algal biofuels a viable energy source.

Emma Thornton, Utah State University (Prof. David Viskochil, Pediatric Administration)

Guidelines of Care in Prader-Willi Syndrome Multi-disciplinary Clinics

Introduction/Background: Prader-Willi syndrome (PWS) is a complex, multi-system disorder affecting approximately 1/15,000-1/30,000 individuals. The complexity of the disorder along with the numerous medical needs of individuals with PWS entails the implementation of a multidisciplinary approach for the care of these individuals. We hypothesize that a set of guidelines, if used by most multispecialty clinics, would provide optimal care for individuals with PWS. The main research aim of our study is to assess the practical implementation of care for multispecialty PWS clinics, and document impeding challenges. We started this process by assessing the use of guidelines in multi-disciplinary clinics affiliated with Prader-Willi Syndrome Association-USA (PWSA-USA). Methods: We contacted PWSA-USA and received the contact list of clinics specializing in PWS, most recently updated in March of 2017. We asked those contacts for age-dependent guidelines of care, invited the contact to share the guidelines, and requested comments on the specific utility of the guidelines. Results: We found 9 multispecialty clinics with a care coordinator and email address to follow up with an email invitation to share information. After a ten-day response period, 5 of the contacts gave the requested information. We determined that each of the responding clinics use different guidelines: 3 utilize published guidelines (Duis et al, 2018; AAP Health Supervision for Children with Prader-Willi Syndrome, 2011; IPWSO Website, 2019), and 2 use independent specialty-specific guidelines. The guidelines range from 2011 to 2019 in publishing date. One of five clinics responded with comments on utility of the guidelines for care that they use. Conclusions: The multispecialty PWS clinics throughout the United States generally use independent guidelines to direct the care of individuals with PWS. We propose that regular discussion sessions surrounding specific standards of care at the PWS National Conference, and collaboration through online portals will facilitate a community of care.

Eylul Yel, University of Utah (Prof. Sarita Gaytán, Sociology)

Managing Authenticity in the Utah Craft Spirit Industry

The craft alcohol industry is booming throughout the country. The concept of "craft, " however, is interpreted differently by consumers as well as producers. Large brands and small companies alike promote their products as craft. This project explores how Utah craft spirit distillers distinguish themselves in an emerging market. Drawing on the content of website "About us" pages, social media posts, and structured interviews, initial findings suggest that for local distillers, "craft" is linked to notions of authenticity related to aspects of their personal backgrounds, the production process, the history of their company, and the places where they operate.

Jacob Young, University of Utah (Prof. Jared Rawlings, School of Music)

BULLYING, PEER GROUPS, AND MUSIC PARTICIPATION: THE SOCIALIZATION OF BULLYING BEHAVIOR IN ADOLESCENCE

School violence has emerged in the last ten years as a significant public health crisis that include behaviors ranging from bullying, hate-based language, sexual harassment, and physical assaults (Robers, Kemp, & Truman, 2013). A recent study found that almost one-third of students in grades 6-12 reported they had been victimized by peers, and 5% to 13% admitted to bullying others (Hymel & Swearer, 2015). Researchers in music education acknowledge peer victimization and bullying is also a serious concern for music students (Elpus & Carter, 2016; Silveira & Hudson, 2015; Rawlings, 2015, 2016). Elpus and Carter (2016) examined data from the 2005, 2007, 2009, 2011, and 2013 datasets of the School Crime Supplement to the National Crime Victimization Survey (NCVS) to determine the prevalence of reported school victimization through physical, verbal, and relational aggression among US performing arts students. Elpus and Carter found that male music and theater students are at a 69% greater risk than non-arts students when experiencing face-to-face bully victimization and male music and theatre students were confronted with a 63% greater risk of being cyber bullied than non-arts participants. Therefore, if school music students may be more likely to be targets of victimization and feel unsafe at school when compared to their non-music peers, then research is needed to determine the prevalence of these behaviors and document detailed instances of this phenomenon. To date, there has been no published research examining the the prosocial and anti-social behavior development of school-based music ensemble performers.

Cathleen Zhang, University of Utah (Prof. Akiko Kamimura, Sociology)

Exploring the Relationship Between Patient Satisfaction and Expectations among Free Clinic Patients

People have the right to fully participate in the planning and implementation of their healthcare. In health policy, patient feedback is often used to better the policies that hospitals, clinics, and other healthcare organizations use in improving or changing their health delivery methods. It is pertinent that providers know what patients expect for the care they receive so that they can address them in a timely and efficient manner, better meet the patient's, and increase patient satisfaction. Relatively few studies have looked into the expectations and satisfaction levels of free clinic patients who are low income and uninsured. Socioeconomic factors play a large role in what expectations-both idealistic and realistic-patients may have of their treatment, and thus their satisfaction with their treatment. This study evaluated the expectations that patients utilizing a free clinic had about their treatment, as well as their satisfaction with the health care services that this clinic provided. Paper-self-administered survey data were collected from patients 18 years of age or older, who use the Maliheh Free Clinic in Salt Lake City, Utah. The sample was from both Spanish speaking and non-Spanish speaking patients. In general, there was no difference for patient satisfaction among subjects. Non-U.S. born Spanish speaking patients were more satisfied with their treatment than U.S. born English speakers when it came to sub-factors such as consultation with a physician and receptionist attitude. Patients who had been at the clinic for two or more years, had higher education attainment, and lower levels of satisfaction with consultation and treatment tended to have higher expectations. Along with highlighting the needs of free clinic patients, the results of this proposed study will help improve the quality of care for underserved populations.

Ashley Allen, University of Utah (Prof. Elisabeth Conradt, Psychology)

Maternal Borderline Personality Disorder and Stress Responses During Pregnancy as Predictors of Newborn Neurobehavior

Borderline personality disorder (BPD) is characterized by difficulty with emotion regulation, impulsivity, and unpredictable relationships (American Psychiatric Association, 2013). Women with BPD tend to have difficulties regulating their stress responses and impacts of stress while in utero affects infants neurobehavioral functioning at birth and throughout their lifespan (Kuo & Linehan, 2009). The maternal brain undergoes psychophysiological changes during pregnancy in preparation for motherhood (Rosenblatt et al., 1994). These complex processes make BPD symptoms during pregnancy problematic for both maternal and child health outcomes. Although existing literature examines risks for offspring of women with BPD, the literature on physiological mechanisms impacting infant neurobehavioral outcomes are largely lacking. Examining maternal physiologic reactivity is important because research supporting Marsha Linehan’s (2009) biosocial developmental theory suggests maternal BPD and their associated physiological stress responding during pregnancy may shape infant neurobehavior while in utero, creating risk for neonatal impairments in attention, self-regulation, stress/abstinence, and arousal/ excitability (Crowell et al., 2009; Crandell, Patrick, & Hobson, 2003; White et al., 2011). Building on this research, the present study aims to extend previous findings in research examining infant neurobehavioral outcomes for women with BPD by examining the associations between BPD and physiological responses during baseline and to the trier social stress test (TSST) in pregnant women and by examining the associations between BPD and newborn neurobehavior. I hypothesized that higher maternal BPD symptomatology would be associated with heightened heart rate (HR) and reduced respiratory sinus arrhythmia (RSA) during baseline. I also hypothesized RSA to increase somewhat but not significantly during the recovery phases to reflect difficulty with emotion regulation. Lastly, I hypothesized higher maternal BPD symptomatology would be associated with impairments in newborn neurobehavior.

Jessica Bigley, Washington University in St. Louis (Prof. Anandh Babu Pon Velayutham, Nutrition & Integrative Physiology)

Effect of blueberry supplementation on vascular NADPH oxidases in db/db mice

Background: Cardiovascular disease is the leading cause of death in the United States. Diabetes greatly increases the risk of cardiovascular disease such as atherosclerosis. Recently we demonstrated that blueberry supplementation reduces vascular inflammation and improves vascular dysfunction in diabetic mice. NADPH oxidases (NOXs) are ROS generating enzymes that play a major role in vascular homeostasis and vascular pathology. An increased NOXs in vascular endothelium contributes to vascular inflammation and dysfunction in diabetes. We investigated the effect of blueberry supplementation on vascular NOX signaling in diabetic mice. Methods: Seven-week old male diabetic db/db mice were either fed standard chow (db/db) or chow supplemented with 3.8% freeze-dried blueberries (db/db+BB), which is equivalent to ~240 g in humans, for 10 weeks. A control group of non-diabetic mice were fed standard chow (db/+). Gene expression analysis of NOX1, NOX2 and NOX4 in the aortic vessels was determined by qPCR. Briefly, mRNA was isolated from aortic vessels using RNeasy plus mini kit, cDNA was synthesized using the reverse transcription kit, and qPCR analysis was completed with SYBR Green. The gene expression levels of NOXs were calculated by normalizing to the level of GAPDH. Results: In our study, vessels from db/db mice exhibited an increased expression of NOX2 and NOX4 without a change in NOX1 expression compared to db/+ mice. Blueberry supplementation decreased NOX4 expression in db/db+BB compared to db/db mice indicating the possible role of NOX signaling. Conclusion: Blueberry supplementation may benefit diabetic patients by preventing the vascular complications associated with diabetes.

Tyler Bodily, University of Utah (Prof. Edward DiBella, Radiology & Imaging Sciences)

Cardiac Perfusion with Continuous Multi-Slice MR Imaging

More individuals are suffering from cardiac diseases than ever before. We are in need of faster and more precise means of diagnosing patients who suffer from heart diseases. MR imaging is quickly becoming an effective means to analyze and diagnose patients for coronary artery disease. This research hopes to successfully produce and quantify cardiac perfusion (blood flow into the heart muscle) in patients who suffer from coronary artery disease using 2D csms (continuous multi-slice) MR imaging. Throughout MR imaging breath holds were not used and both rigid and deformable registration was used to correct cardiac and respiratory motion. Rather than using successive sat pulses after each beat continuous sat pulses over several heart beats were used. Data was processed and displayed using the fermi model and run through Matlab.

Billy Chien, Indiana University Bloomington (Prof. Stavros Drakos, Internal Medicine)

The Role of the Pentose Phosphate Pathway in LVAD-Induced Myocardial Recovery from Heart Failure

Heart failure is a crippling disease that has a high prevalence of 2-3% within the United States. A common therapeutic treatment for heart failure (HF) is mechanical unloading by Left Ventricular Assist Devices (LVADs). It has been reported that LVAD treatment leads to improvements in the cardiac function of a subset of HF patients (responders). Glucose via glycolysis serves as the major energy substrate in failing hearts, however studies show that upon LVAD unloading, glycolytic intermediates do not enter the TCA cycle as they normally would. We hypothesize that glucose is channeled into accessory cardio-protective/repair pathways such as the pentose phosphate pathway (PPP) to facilitate the myocardial recovery seen in responders to LVAD treatment. To investigate this hypothesis, we obtained myocardial tissue samples from HF patients at the times of LVAD implantation (pre-LVAD) and LVAD explantation or cardiac transplantation (post-LVAD); as well as, control samples (donors) from non-failing rejected hearts. The tissue samples were then analyzed using gas chromatography-mass spectrometry (GC-MS) to determine metabolite levels, RNA sequencing to determine transcription levels, and western-blot to determine the levels of enzymes involved in PPP. Although the metabolomics studies are still currently being processed, a preliminary dataset with a smaller sample size shows a trend towards increased PPP metabolites in post-LVAD responders. Western-blot analysis shows that glucose-6-phosphate dehydrogenase (G6PDH) and transketolase (TKT), major enzymes in the PPP, are significantly increased in post-LVAD responders. Furthermore, TKTL1 mRNA expression is upregulated in this group as well. These results suggest that more glucose is being shuttled into the PPP, which leads to increased cardiac recovery in responders. However, corresponding results from the full metabolomics study are needed to strengthen this claim. Additionally, future metabolic flux studies using stable isotope labeled 13C-glucose tracers are planned to track the precise pathways of glucose metabolism.

Randy Chou, Brown University (Prof. Stavros Drakos, Internal Medicine)

The One-Carbon Pathway and cardiac function recovery post LVAD treatment for heart failure patients

A substantial portion of the population suffers from chronic heart failure. Mechanical unloading by way of a left ventricular assist device has proved to be an effective interventive treatment. Following removal of the LVAD, most heart failure patients continue to show HF symptoms and worsening cardiac function(non-responders), however a subgroup showed substantial recovery (responders). Metabolic and energy balance perturbations during mechanical unloading have been implicated in these responses. Prior studies have revealed that LVAD-induced mechanical unloading causes an increase in glycolysis without increase in TCA cycle activity. A possible explanation is that the pyruvate, produced from glycolysis, is funneled into an alternative pathway. We hypothesize that the glycolytic intermediates are channeled into the cardioprotective and repair pathway one-carbon metabolism, resulting in the cardiac recovery response. To test this hypothesis, we performed metabolomics using GC-mass spectrometry and western blotting on human cardiac tissue obtained at the time of the LVAD implant (pre), LVAD explant (post), and control samples (donors) from non-failing hearts. The preliminary metabolomics indicate an upregulation of one-carbon metabolites, serine and glycine in the responders compared to non-responders post-LVAD. Furthermore, western blot of key one-carbon enzymes, PHGDH and SHMT1 shows responders with a higher concentration compared to non-responders. Since one-carbon metabolism is a major source of NADPH, levels of the antioxidant were examined using an assay kit. As expected, levels were higher in post-LVAD responders compared to non-responders. Although data from GC-MS with a larger sample size is currently in progress, these findings indicate an association of increased one-carbon metabolism to cardiac recovery in post-LVAD patients. By trying to understand the metabolic adaptations in the recovering heart, this study's ultimate goal is to intervene in patients with no signs of cardiac recovery after LVAD unloading to mimic the metabolic profile of respon

Eavan Donovan, Carleton College (Prof. Wesley Sundquist, Biochemistry)

The Roles of Human MIT Proteins in ESCRT Biology

Cell division allows cells to proliferate and pass on genetic information. In contrast, cell checkpoints halt the cell cycle until errors have been searched for. Just as air traffic control gives permission for flights to come and go, proteins that function in abscission checkpoints look for mitotic errors, and interact to promote cell separation. One class of machinery that functions in the abscission checkpoint is the Endosomal Sorting Complexes Required for Transport (ESCRT). ESCRT proteins facilitate more than fifteen known cellular membrane remodeling processes, including cytokinetic abscission, and viral budding. ESCRT-I and -II complexes function to mark specific membranes, while ESCRT-III factors form filaments that act to mediate membrane fission. Our understanding of these processes is incomplete, therefore our primary goal is to characterize new ESCRT-III interacting proteins. Structurally, each of the twelve known human ESCRT-III proteins has a conserved N-terminal helical core, and a diverged C-terminal tail that contains MIT Interacting Motifs (MIMs), which bind to proteins that contain Microtubule Interacting and Trafficking (MIT) domains. These MIM-MIT interactions recruit MIT proteins to sites of ESCRT activity. For example, the MIT domain of VPS4 localizes the enzyme to remodel ESCRT-III filaments. Humans express 22 proteins that contain MIT domains. To date our lab has cloned, purified and tested the ESCRT-III binding activities of MIT domains from 18 of these proteins and the final four human MIT proteins (FIDGETIN (3) and KATANAL2) are being tested. The MIT constructs are expressed in E. coli, purified using Ni2+ chromatography, cleaved, and purified using size exclusion chromatography. Fluorescence polarization experiments measure the binding of each MIT domain to the C-terminal MIM elements from all twelve different fluor-labeled ESCRT-III C-terminal tails. Subsequent structural analyses of productive MIT-MIM interactions will then be used to obtain a full picture of MIT-MIM motif with the goal of identifying novel biological activities.

Asmita Dulal, University of Utah (Prof. Sujee Jeyapalina, Surgery)

Osteoblast Cells Behavior on Fluoridated Hydroxyapatite

Hydroxyapatite (HA; Ca5(PO4)3(OH)) coating is known to modulate the surrounding tissues’ biological environment and improve the biocompatibility of orthopaedic implants. However, particulate debris from the HA coating reported to lead to an adverse tissue reactions. Biological apatites are not strictly stoichiometrically pure HA; they in fact contain carbonates, fluoride, chloride etc. Fluorohydroxyapatite (FHA) and Fluorapatite (FA) are a form of HA, in which, one or both hydroxyl ions have been replaced with fluoride ions, respectively. As FHA and FA are known to resist acid degradation much better than HA, it is predicted to have limited degradation in vivo. However, their potential as bone substitutes is less well studied and documented. Previous data generated from our group indicated improved cellular adhesions and differentiations of osteoblasts when they were sintered. This study is, therefore, aimed at investigating the in vitro osteogenic properties of sintered apatites for orthopedic application using qualitative polymerase chain reactions (qPCRs). For this study, apatite powders were compressed into 10 mm thin disks and sintered at 1050, 1150 and 1250oC for 2 hours. After which, sterilized apatite disks and titanium controls were seeded with a known number of 5.5x104 osteoblast cells and allowed to adhere and proliferate. At 48 and 72 hours post-seeding, cells that were attached to the disks were rinsed, and lysed with lysate buffer RLT for RNA extraction using the standard techniques, extracted RNAs were converted to cDNA. The validated primers for mineralization markers (alkaline phosphatase (Alp), secreted phosphoprotein 1 (SPP1), Runt-related transcription factor 2 (Runx), and osteopontin (OPN)) were then used to perform qPCR analyses in triplicates. Overall, when compared to the Ti surfaces, the result indicated overexpression levels of Runx, OPN, and SPP1 markers in osteoblasts that were seeded on apatite surfaces. However, protein assays need to be undertaken to confirm whether or not respective proteins were synthesized. Early results do support the potential of using FA sintered at 1250oC for orthopedic applications.

Erin Feeley, University of Utah (Prof. Erin Castro, Educational Leadership & Policy)

Year One Program Evaluation for the University of Utah Prison Education Project

This study consists of a year one program evaluation for the University of Utah Prison Education Project (UPEP). UPEP is a college-in-prison program that was developed through years of dialogue and relationship building in the local community and was launched in Spring 2017 out of a Praxis Lab supported by the University of Utah Honors College. Following a rigorous admissions process during Summer 2017, the Project initiated programming in two correctional facilities at the Utah State Prison in Draper in Fall 2017. During the 2017-2018 academic year, UPEP facilitated two college-level non-credit-bearing courses per semester in each facility. During this period, UPEP supported additional extracurricular events and opportunities on Campus and in the Prison. The purpose of this study is to conduct a process evaluation of the programming and engagement offered during the first year of operation. The secondary purpose of this study is to identify and quantify some of the preliminary impacts UPEP has had on incarcerated students, non-incarcerated volunteers, and the greater campus community. This evaluation will consist of several surveys designed for distinct populations of program participants that utilize Likert scale, yes and no, and short response questions. The surveys have been developed through a conscious benchmarking effort across the field of higher education in prison as well as through several informal focus group discussions conducted on Campus and in the Prison. While the results of the survey are still forthcoming, the data is expected to have significance for the Project's decision-making and development during the 2018-2019 year and beyond. Additionally, the evaluation is expected to help the Project better articulate its value to the University of Utah, the Utah State Prison, the state of Utah, and the broader community. Ultimately, these data are critical for supporting the Project's quality, longevity, and growth, especially as it seeks funding to make the transition to for-credit programming.

Rebecca Higham, University of Utah (Prof. Akiko Kamimura, Sociology)

Stress Management Classes for Uninsured Free Clinic Patients in the United States

Stress has become a growing public health concern in the United States (US). Uninsured, low-income or minority patients utilizing a free clinic are exposed to stress disproportionately across various areas of life. Health promotion programs regarding stress management have the potential to benefit vulnerable, low income populations by reducing stress related health issues. The purpose of this study was to describe and evaluate the "stress-management" education class taught at a free clinic that provides healthcare to uninsured patients. Data for this study were collected by a pre-stress management class survey, field notes during the stress management class, and post-class survey at a free clinic for low-income, uninsured patients. The surveys and class took place in June 2018. Direct observations were based off the Theory of Planned Behavior (TPB). 55 stress management classes were offered with a total of 83 participants. Among the class participants, 71 filled out the survey. Free clinic patients experience cumulative negative situations. One strategy to cope with stress is to organize participant responsibilities. Main stressors among the participants included finances, family, emotions, work, health, social relationships, and a sense of not belonging. Providing resources regarding these stressors would be a feasible solution for patients at free clinics. Future projects should work to develop stress management class which responds to the results of this study.

Coby Hudac, University of Utah (Prof. Aylin Rodan, Internal Medicine)

Bestrophin-1 Chloride Channel in Drosophila Melanogaster

Bestrophin-1 is a swell-activated chloride ion channel that has been found in Drosophila melanogaster.  Flies with a loss of function mutation in the bestrophin-1 gene were shown to have increased sensitivity to a high salt diet compared to wild type, shown by an elevated rate of lethality for bestrophin-1 mutants vs wild type on high salt food. Additionally, wild type function could be restored in the bestrophin-1 mutants using a genomic rescue construct.  I have researched the water weight and excretion behavior of bestrophin-1 mutants on normal and high salt food to better understand the function and importance of bestrophin-1. I developed new assays to measure both water weight and excretion. Also, I have been conducting experiments on flies with rescued bestrophin-1 function in specific regions of the Malpighian (renal) tubule and gut to learn more about where bestrophin-1 is required for normal salt sensitivity and excretory behavior. I have observed a significant increase in excretion in bestrophin-1 mutants compared to wild type, as well as an elevated rate of lethality in response to water deprivation stress. No significant difference in water weight was observed, though similar experiments with increased feeding times are ongoing.  This research will be important to fully understand the physiological mechanisms by which Drosophila maintain ionic and osmotic balance.

Siddharth Iyer, University of Utah (Prof. Michael Deininger, Internal Medicine)

Autophagy realted causes to AML Cell death post SIRT5 KO

Acute Myelocytic Leukemia (AML) is a blood cancer with an overall 5-year survival rate of less than 30%. Common treatments for AML include various forms of chemotherapy, a treatment that puts a considerable stress on the patient's body and provides varying degree's of success. Recent literature suggests that the knockdown of the mammalian sirtuin, SIRT5, significantly hinders the proliferation of certain unique AML cell lines. The pathway involved in this process is as of yet unknown, and further analysis is required. An understanding of this pathway could pave the road to a novel medical alternative to chemotherapy. The purpose of my study was to examine and measure the physiological process known as autophagy in various AML cell lines and to determine its level of influence on the SIRT5 KO pathway. Autophagy is the process by which the cell creates an organelle within the cytoplasm known as an autophagosome, which then engulfs other organelles to be recycled into raw materials for cell proliferation. The effect of autophagy was measured using various analytical methods including: flow cytometry, fluorescence microscopy, western blot analysis, and MTS assays.

Anna Jacobsen, University of Utah (Prof. Sarah Franklin, Internal Medicine)

Clarifying the role of Smyd5 in heart disease

The increasing prevalence of heart disease in the United States means that researchers need to develop better treatments, which requires deeper understanding of heart disease and failure. One characteristic that arises on the path to heart failure is cardiac hypertrophy, the growth of cardiomyocytes in response to hemodynamic stress. While the thickened heart muscle alleviates the overload temporarily, this growth stiffens the muscle, leading to decreased overall function. Since hypertrophy hastens heart failure, it is important to comprehend the pathophysiology of cardiac hypertrophy on a cellular level. The Franklin lab studies the role of the Smyd protein family in heart disease. These proteins are histone methyltranferases, meaning they modify the proteins surrounding DNA, altering gene expression. This epigenetic transformation has significant implications for cell growth regulation. Experiments performed in the Franklin lab include inducing hypertrophy in animal and cellular models to measure the impact of overexpression and knockout of the Smyd proteins on the development of heart disease. My first objective this summer was to confirm the suitability of a cellular model of cardiomyocytes used by the lab, the H9c2 cell line. H9c2 cells are myoblasts, or muscle cell precursors, that can be differentiated into myocytes. I treated these cells with differentiation conditions, then tested expression of cardiac markers at different time points to track the progression of a cardiac muscle-like phenotype. My second objective was to test whether Smyd5 ameliorates hypertrophic growth in cultured cells. I performed knockdown of Smyd5 in 3T3 cells using siRNA to impede expression. My third objective was to infect H9c2 cells with a titration of Smyd5 adenovirus to ascertain the best multiplicity of infection. I treated infected cells with phenylephrine and imaged them to see morphological changes. These data combined establish a baseline for future experiments using H9c2 cells that will combine Smyd5 knockdown or overexpression with phenylephrine-induced hypertrophy.

Julia Larkin, University of Utah (Prof. Eric Poitras, Educational Psychology)

Voice-Activated Digital Assistant: An Application for Teacher Professional Development and Technology Integration

As the job of a teacher is demanding, digital classroom assistants help off-load duties. Funding the amount of necessary assistants can become a financially daunting task. Voice-activated digital assistants are becoming increasingly more prevalent in the classroom, allowing teachers and students to interact and receive information. In doing so, students may interact with an agent that serves as either a teacher or a peer. The objectives of this study were two-fold: (1) develop a semi-automated workflow to author conversational trialogues leveraging metadata embedded in open educational resources and, (2) create a prototype version of the agent for usability testing. The semi-automated workflow combines the use of unsupervised and supervised machine learning algorithms to analyze unstructured text crawled from the web. In particular, the approach is applied to analyze metadata defined through standardized schemas for the semantic web. As an example, we compare and contrast several modes of dialogue, showing how an agent can teach a subject matter (i.e., learning by transmission), but also may be taught a topic by a student (i.e., learning by teaching). We discuss the implications of the authoring framework for designing conversational agents as instructional aids for teachers in the classroom in an automated manner.

Youn Lee, University of Utah (Prof. Frank Sachse, Bioengineering)

Functional and Structural Remodeling in Heart Failure: A Potential Predictor of Cardiac Recovery in Patients with Left Ventricular Assist Devices

Left ventricular assist devices (LVADs) are often implanted in heart failure (HF) patients as a bridge to heart transplantation. Some patients respond to LVAD implantation with sustained cardiac recovery and these patients will not need a heart transplant. The aim of our study was to investigate functional and structural remodeling in HF at the cellular level and predict cardiac recovery after LVAD unloading. Left ventricular tissues from donors (n=7) and HF patients (n=8) were sectioned, labelled, and imaged via a Leica SP8 TCS confocal microscope. We labelled the cardiac tissue sections with wheat germ agglutinin (WGA), DAPI, RyR2 antibody, and JPH2 antibody for extracellular matrix, cell nuclei, ryanodine receptors, and junctophilins, respectively. After imaging, 3D image stacks were deconvolved using measured point spread functions, and we corrected the depth-dependent signal attenuation using MatLab R2018a (Mathworks, Inc). We found major remodeling in some, but not all HF patients. The t-system in those patients exhibited sheet-like remodeling. Protein distributions were altered in tissues from some HF patients versus donor tissues. In particular, we observed that JPH2 clusters were re-localized from t-tubules to outer cell membrane (sarcolemma). Also, RyR2 clusters were redistributed with increasing distance from sarcolemma. Our results showed that cell microstructure is remodeled in many HF patients undergoing LVAD unloading. Assuming that proper localization of JPH2 and RyR2 to the t-system is crucial for normal cardiomyocyte function, we suggest that only patients without remodeling can recover cardiac function. Thus, the remodeling can serve as a predictor of cardiac recovery. We also suggest that a better understanding of functional and structural remodeling will contribute to developing innovative therapies for HF. 

Levi Neely, Utah Valley University (Prof. Owen Chan, Internal Medicine)

Carvedilol Improves Hypoglycemia Awareness in Rats

Patients with diabetes often encounter hypoglycemia resulting from insulin treatment, which decreases the adrenergic response. This contributes to hypoglycemia unawareness and increases morbidity. We used Sprague-Dawley rats to assess whether the adrenergic blocker, carvedilol, can improve hypoglycemia awareness (HA). The rats were treated with repeated 2-deoxyglucose (2DG; 200mg/kg, SQ) injections to make them "hypoglycemia unaware" before being treated with carvedilol. In humans, hypoglycemia unawareness is evaluated using a questionnaire that rates the intensity of hypoglycemic symptoms experienced. However, a questionnaire is not feasible for rodents, thus hypoglycemia unawareness must be measured using hunger or food-seeking behavior. We measured food intake in response to insulin-induced hypoglycemia as a surrogate marker for HA. Compared to Controls, 2DG reduced food intake in response to hypoglycemia and treatment with carvedilol increased food intake in 2DG rats (P<0.01). We conclude that carvedilol may be a useful therapeutic strategy to improve HA in RH rats.

Samantha Nelson, McPherson College (Prof. Anandh Babu Pon Velayutham, Nutrition & Integrative Physiology)

Dietary supplemation of blueberry modifies NFκB signaling in the aortic vessels of diabetic mice

Background: Cardiovascular disease is the leading cause of death in diabetic patients. Individuals with diabetes are more susceptible to cardiovascular disease such as atherosclerosis. In our recent study, blueberry supplementation reduced vascular inflammation in diabetic mice and blueberry metabolites attenuated endothelial dysfunction in human aortic endothelial cells. Nuclear factor-κB (NFκB) plays a major role in vascular inflammation by up-regulating chemokines and adhesion molecules. Inhibitor κB kinase (IκKβ) activates the nuclear translocation of NFκB-p50/p65 by degrading the inhibitor IκBα.  In the nucleus, p50/p65 binds to the promoters of NFκB-dependent inflammatory genes and mediate vascular inflammation. In the present study, we studied the effect of blueberry supplementation on vascular IKKβ and IκBα in diabetic mice. Methods: Wild type db/+ and diabetic db/db mice (7-wk) consumed standard diet or diet supplemented with 3.8% freeze-dried blueberries for 10 wk. Gene expression analysis of IκKβ and IκBα in the aortic vessels was determined by qPCR. Briefly, RNeasy plus mini kit was used to isolate RNA from aortic vessel, Reverse Transcription kit was used to synthesize cDNA, and SYBR green was used to complete qPCR analysis. The gene expression levels were calculated by normalizing to the level of GAPDH. Results: Diabetes increased the expression of IκKβ in the aortic vessels of diabetic mice but did not change IκBα. Blueberry supplementation suppressed IκKβ in diabetic mice indicating the vascular effects of blueberry may be mediated through regulation of NFκB signaling.Conclusion: Blueberry consumption may be an adjunct therapy to reduce vascular complications in diabetes.

Nicole Orabona, The Pennsylvania State University (Prof. Michael Simpson, Metallurgical Engineering)

Electrochemical Analysis of MgCl2/KCl/NaCl Molten Salt Candidate Heat Transfer Fluid for Concentrating Solar Power

Solar energy is one of the leading candidates for alternative energy, however the intermittent nature of energy harvesting puts a strain on the electric grid. If energy storage could be integrated with solar energy collection, this problem could be solved. Concentrating solar power (CSP) plants collect thermal energy rather than converting it directly to electricity.  This presents the opportunity to store the collected energy and convert it to electricity as needed by the electric grid. The implementation of chloride salts provides higher thermal stability at higher temperatures than the existing thermal energy storage (TES) materials, such as oils and nitrate molten salts. Putting these chloride salts into the application of concentrating solar power (CSP) plants will result in an increased efficiency of storage due to the thermodynamic benefits of collecting energy at higher temperatures. However, the problem with this solution is the corrosivity of the chloride salts, which is caused by impurities such as oxide ions, and hydroxide ions. To measure these impurities, cyclic-voltammetry (CV) measurements were performed in molten MgCl2/KCl/NaCl (60/20/20 mol %). The CVs were obtained at 500 °C at varying scan rates of 100, 200, and 300 mV/s. Through these measurements, a consistent profile of the salt was obtained, as well as verification of the OH- and Mg2+ reduction peaks. Dissolution of Mg metal successfully reduced the OH- peak height. It also produced a large, broad oxidation peak that is possibly due to the presence of soluble Mg metal. This theory will be tested using titration techniques in order to determine changes in the concentration of O2/OH- in the salt. Further research is needed to investigate the oxidation peak associate with soluble Mg metal in the salt.

Julia Peek, University of Utah (Prof. Ilya Zharov, Chemistry)

Nanoparticle Catalysts for Suzuki Cross-coupling

Catalysis is used for accelerating chemical reactions, which can significantly reduce the reaction cost. The use of catalysts is abundant in pharmaceuticals, petroleum, and synthetic fuel industries. Although transition metal-based catalysts are the most abundant, they have specific limitations such as the high cost of metals and the difficulty involved in separation from product. Catalytic membrane reactors (CMR) are one popular type of catalytic reactor and are unique in that they combine the "reaction" and "separation" step. The separation occurs between unwanted byproducts or within the catalyst itself. I have synthesized Au and Pd silica supported nanoparticles in order to catalyze a Suzuki cross-coupling reaction. Before designing and characterizing a CMR made of Au or Pd coated silica nanoparticles I demonstrated that the Suzuki cross-coupling reaction will take place in bulk conditions with the metallic catalysts I have prepared. Each trial was given 24 hours to complete at room temperature or 60 C in the presence of nitrogen gas; they were then characterized by analyzing progress of reaction and presence of the product, biphenyl, by thin-layer chromatography (TLC). I found that both Au and Pd catalysts are active in the selected conditions and produced the best yield at room temperature, although Pd gives a better percent yield than Au (approximately 70% compared to a 15% yield, respectively). Either Au or Pd supported nanoparticles would be adequate catalysts to make a catalytic membrane; however, considering that palladium gives a higher conversion percentage, this will be the material that we will continue to work with to make and optimize a catalytic membrane.

Miles Robertson, Utah State University (Prof. David Belnap, Biology)

Creating Octahedral Particles

Polyomavirus capsids are polymorphic under different chemical conditions. The protein in play, VP1, is the primary building block of the capsid. Five VP1 proteins come together and form highly stable structures called pentamers. The number of pentamers associating together determines the curvature and symmetry of the viral capsid. Only one form is found in infectious virions, and the structure of this native icosahedral form has been studied. However, the detailed structure of the octahedral capsid is not well known. The goal of my research is to determine the detailed structure of the octahedral capsid by electron microscopy. Many particles are necessary for electron microscopy to be successful. Therefore, I have produced and isolated these octahedral particles to provide necessary data for solving the capsid structure. This capsid shape is created through a long process beginning with purification of the VP1 protein. A recombinant plasmid containing DNA for a protein tag linked to VP1 is inserted into E coli which then produces this protein upon induction. The cells are lysed and VP1 is purified by selection for the protein tag in a flow column, where VP1 is then cleaved from the tag. This purified protein then passes through three distinct chemical environments that give the conditions necessary to make the octahedral particles.

Meg Rosales, University of Utah (Prof. Man Hung, Orthopaedics)

Prediction of oral health outcomes in the era of precision medicine

Background: Across the globe, dental caries, also known as cavities, are a common oral health issue. Without proper treatment, they may result in loss of teeth and diminished quality of life. However, dental caries are also quite preventable. This study utilized multiple machine learning methods to create an automated tool that can predict and diagnose root caries and tested the accuracy of the various methods. Methods: Demographic, physical examination, and oral health data were taken from the 2015-2016 National Health and Nutrition Examination Survey (NHANES). Due to an imbalance in the number of cases of presence vs. absence of root caries, sampling with replacement was used to create a balanced dataset. The data were divided into randomized training and test sets with 80% as training and 20% as test data. Tests of significance determined the top 15 most relevant input variables. An automated tool for identifying cases of root caries was created by applying supervised machine learning algorithms in WEKA 3.8.2 and Python 3.7.0, to the data. Performance metrics, including accuracy, sensitivity, specificity, and AUC (area under the receiver operating curve) were calculated. Results: Of the classifiers, Support Vector Machines (SVM) performed best with a root caries detection accuracy of 97.1%, precision of 95.1%, sensitivity of 99.6%, and specificity of 94.3% and an AUC of 0.997. Age was the feature most strongly related to root caries. Conclusions: To date, this appears to be the first study using machine learning to construct a predictive model for root caries. This work will aid in the detection, prevention, and treatment of root caries and assist in the development of computer-assisted tools for personalized predictions.

Celine Slam, University of Utah (Prof. Deshpande, Physics & Astronomy)

Thermoelectric Measurements of a Metal-Organic Framework

Power plants extract only 30 to 40% of usable energy from fuel and lose the rest of energy in the form of unusable heat [1]. Recovering this wasted heat will dramatically change the consumption of limited energy sources, such as petroleum and coal, leading to a sustainable society. Thermoelectric materials, which reliably and renewably convert heat into electricity, are promising for recovering wasted heat, as they do not produce carbon emissions and do not require complicated mechanical systems. Electricity is generated at the interface of a thermoelectric material applying a temperature gradient across the substrate. For a thermoelectric to be efficient it must have a high figure of merit (ZT), expressed as , where S is the Seebeck coefficient, σ the electrical conductivity, and κ the thermal conductivity. To optimize ZT, the Seebeck coefficient and electrically conductivity must be increased, while the thermal conductivity lowered. Commercially available thermoelectric materials exhibit a high ZT of around 1.5, [2], however they are toxic and costly. Metal-organic frameworks (MOFs), a new candidate for thermoelectrics, are inexpensive and non-toxic. MOFs are a favorable material because of their intrinsic porosity, which lowers their thermal conductivity. In general, MOFs have poor ZT values because of their low electrical conductivity.  However, copper-benzenehexathiol (Cu-BHT) exhibits an unusually high electrical conductivity for MOFs. As such, we have measured electrical and thermal conductivity of Cu-BHT. We have found Cu-BHT’s periodic, one nanometer pore size, effectively scatters phonons, contributing to its intrinsic low thermal conductivity, while conducting electrons. In future work we will focus on optimizing the ZT of Cu-BHT, by chemical doping.

Laura Snelling, University of Utah (Prof. John Horel, Atmospheric Sciences)

Investigating the Weather Conditions Near Wildfires

Each year wildland fires across the United States impact recreational land use, urban structures, and the safety of wildland firefighters. Understanding the weather surrounding wildfires is vital to preventing dangers associated with them and can be useful in developing effective ways to combat wildfires. Currently fire weather forecasters provide detailed weather information to support wildland firefighting operations with research underway to improve those forecasts. The objective of this project is to improve understanding of fire weather conditions by collecting and analyzing weather data near wildfires and how weather conditions affect fire behavior. A particular focus has been to investigate two local fires in Utah: (1) the Trail Mountain Fire, which started after a prescribed burn in central Utah escaped containment due to unexpected high winds and (2) the Dollar Ridge Fire, which accounted for the loss of over 70 structures and 56,000 acres of burned land near Strawberry Reservoir. Another major goal of the project is to help advance web applications that can potentially be used to assist firefighting operations by displaying the geographic locations in which red flag conditions are occurring. Red flag conditions are the weather and fuel conditions that may increase the potential for a wildfire to start or for wildfires to experience significant growth. In order to update the web application, current fire weather operation plans developed by U.S. federal agencies were referenced. The varying red flag criteria across the U.S. were documented and compiled into an interactive QGIS map that could be transitioned into web applications that display current weather conditions and map areas that are experiencing red flag warning criteria.

Hayli Spence, American University (Prof. Dimitri Traenkner, Biology)

Exploring Computational Networks Across an Entire Brain at Single Cell Resolution

Currently, large scale monitoring of neuronal activity in mouse models depends on either live imaging techniques or activity snapshots based on immediate early gene expression. Both methods pose challenges: live imaging techniques utilize expensive and training-intensive multi-photon technology, whereas activity snapshots use poorly definable test intervals and generate high background levels. To overcome these limitations, we generated a mouse line for the expression of the neuronal activity reporter CaMPARI. One of the newer tools out there, CaMPARI is a green fluorescent protein that irreversibly photoconverts to red fluorescence in the presence of high intracellular calcium levels and photoconversion (PC) light. High intracellular calcium is found naturally in active neurons, while PC light can be delivered deep into the brain through single or multiple light guides by the experimenter when and where a snapshot of neuronal activity is required.

William Steiner, University of Utah (Prof. Micah Drummond, Physical Therapy & Athletic Training)

The Effects of Metformin on Recovery of Muscle Mass and Mitochondrial Function in Older Hindlimb Unloaded Mice

Intro: Aging results in impaired recovery of muscle mass and function after periods of disuse. Inadequate restoration of muscle loss can lead to weakness, decreased physical function, and mitochondrial (mito) dysfunction. Evidence suggests that the widely prescribed FDA approved insulin sensitizer metformin, may enhance recovery of muscle after disuse-induced atrophy. Purpose: To compare muscle mass and mito function between mice provided with metformin (MET) vs placebo (PLAC) after 7 days of rec from hindlimb unloading (HU). Methods: A cohort of young (3 mo, n=6) and old (24 mo, n=8) mice were subjected to 14 days of HU via tail suspension, followed by 7 day return to normal ambulation. Muscle weights were measured (absolute and relative to body weight) to determine aged-related impairments in rec. A follow-up study was performed on old only mice, where one group was provided with MET (n=5) (vs PLAC, n=5) in their drinking water for the entire 21 days (14d HU+7d rec). Muscle mass and mito function (red and white gastrocnemius separately) using the Oxygraph-2K (Oroboros Instruments, Austria) were measured. Molecular targets of MET (AMPKα & Acetyl-CoA carboxylase) were analyzed with western blotting. Results: Rec of gastroc muscle mass was impaired in both MET and PLAC aged mice as compared to young. Direct comparison between MET and PLAC groups demonstrated a trend towards improved rec of the gastroc muscle mass with MET treatment (absolute: P=0.0999, relative: P=0.1189). Mito respiration for all complexes (per mg dry muscle) were different between red and white gastroc however no differences were found in mito function nor cellular signaling with MET vs PLAC. Interestingly, absolute gastroc weight and white gastroc complex 1&2 coupled respiration was positively correlated (R2=0.0325, P=0.0419). Conclusion: MET may assist in rec of gastroc muscle mass in aged mice, however metformin may not influence mito function nor AMPKα and ACC signaling during 7d of rec from HU. Rec of muscle mass is associated with greater complex 1&2 respiration in the white gastroc.

Brennan Theler, University of Utah (Prof. Taylor Sparks, Materials Science & Engineering)

Utilization of Machine Learning to Build a Price Prediction Model for Raw Minerals Sourcing

Materials scientists build materials with an eye towards performance, but businesses interested in new materials must also have an eye on economic aspects of materials. Most new materials require a wide range of minerals, and businesses must ensure sufficient supply exists and account for price volatility. Machine learning is a tool commonly used to predict future outcomes, but have not been used in the materials science field for large-scale predictions. Using data from the United States Geological Survey and other sources, a large and comprehensive dataset describing the minerals market in several attributes from 1998-2015 was collected. This dataset was normalized and fed into a set of different machine learning regression algorithms to look for predictive ability on the chosen attributes (mineral price, oil price, inflation index, current price, and total production) on next year's mineral price. The models returned show predictive ability, with r-squared scores just under .7, but with a significant amount of error, partially stemming from the normalization method used, and partially from the highly interpolative nature of the data and model parameters. Work on improving normalization methods and increasing the model's predictive ability at extreme ends of the dataset are ongoing.

Claire Ticknor, University of Utah (Prof. Jay Agarwal, Surgery)

Constructing Neurotrophic Gradient-Generating Peripheral Nerve Conduits and Assays to Measure Functional Outcomes

Severe injury and trauma often results in peripheral nerve injuries. With current surgical practices such as the use of autografts, regeneration from nerve injuries is slow and incomplete resulting in loss of motor and sensory function. Previous studies indicate that the combination of a synthetic nerve conduit and neurotrophic factors aide in the regeneration process. It is also known that nerves will grow toward a chemotactic gradient. This study aims to demonstrate that a nerve conduit that implements a neurotrophic gradient can improve functional recovery following peripheral nerve damage. To do this, biodegradable gradient-producing nerve conduits are manufactured. The gradient device is composed of multiple pieces, all constructed from poly-L lactic acid (PLLA). There are two concentric tubes (an inner and outer conduit) enclosing a reservoir from which neurotrophic drugs will diffuse through holes that are cut with a laser into the inner conduit. Location and size of the diffusion holes is altered resulting in varying gradient patterns. Two, o-shaped endcaps are placed between the inner and outer conduits and are then sealed to prevent drug leakage. Drug diffusion from the device is initially tested using a fluorescent dye. After implantation of the devices across a nerve gap, a functional assay is employed to assess recovery following a peripheral nerve injury. After designing and manufacturing a horizontal ladder rung test, healthy mice are trained to walk over at a constant pace. After being injured, the mice are then run across the ladder again and differences in functional ability are identified from counting how often and to what extent their leg slips off a rung. Full functional recovery is ideal after a peripheral nerve injury and the gradient design conduit has the potential to expedite this optimal recovery.

Alexis Torres, New Mexico State University (Prof. Trafton Drew, Psychology)

Neural processing of repeated search targets depends upon stimuli: Real world stimuli engage semantic processing and recognition memory

As part of our daily routines, we spend a vast amount of time searching for objects in our environment. In an everyday context, we may search for car keys in the morning. In a more specialized context, a radiologist searches for a fracture in a medical image. To search for and locate a novel object, we must form and hold a mental representation of it in visual working memory until we locate the object. There are two neural correlates of mental activity that inform us about whether an item is being held in visual working memory (VWM) or long-term memory (LTM), the CDA and n2pc. CDA is an indicator of working memory load and n2pc is an indicator of attention allocation to an object or an object's target features. When we get ready to search for a novel object, the representation of that item is housed in VWM-producing a larger CDA and a smaller n2pc (Kappenman & Luck, 2012). When an object is repeatedly presented, the representation is transferred into LTM-producing a smaller CDA (Carlisle, et al., 2011). In contrast to simple laboratory stimuli, repeated real-world objects result in a larger n2pc, suggesting real-world objects are more readily transferred into LTM (Jones, et al., 2018). For this project, we will investigate whether real-world objects presented repeatedly, then reintroduced after an extended period, are treated as new (represented in WM) or old (represented in LTM). Specifically, we are interested in whether the CDA is smaller and the n2pc larger for repeated real-world objects that are reintroduced after long periods of time. We expect that individuals will be faster and more accurate at locating real-world objects that have been shown repeatedly as compared to items that have only been shown once or are brand new.

Daniela Vidal, The University of Texas Rio Grande Valley (Prof. Russell Richardson, Geriatrics)

The role of enzyme and substrate dependence in NO-mediated vascular dysfunction with aging

The process of aging affects the vasculature, resulting in remodeling and dysfunction in both the macro- and microvascular systems. A marker of vascular health is the production and, ultimately, the bioavailability of nitric oxide (NO), which is recognized to be anti-atherogenic. NO synthesis predominantly depends upon the extracellular levels of L-arginine and the efficacy of endothelial nitric oxide synthase (eNOS), while reactive oxygen species can negatively impact both eNOS activity and NO directly leading to a decrease in NO bioavailability and vascular endothelial dysfunction. Tetrahydrobiopterin (Bh4), a cofactor which recouples eNOS, and chronic L-Citrulline (L-Cit), which increases plasma L-arginine, both by independent mechanisms, may increase NO bioavailability. Therefore, this study sought to evaluate the role of eNOS activity and/or L-arginine concentration in the NO-mediated vascular dysfunction associated with advancing age. Eight old subjects (73 ± 6 yr; ht: 168 ± 12 cm; wt: 84 ± 33 kg) received Bh4 acutely and underwent a 1 week supplementation of L-Citrulline (8 g per day). Vascular function was assessed by brachial artery flow mediated dilation (FMD: %) and passive leg movement (PLM: blood flow ΔPeak and AUC) with or without Bh4, both before and after L-Citrulline supplementation (Ctrl; Bh4; L-Cit; L-Cit + Bh4). PLM ΔPeak increased ≈35% and ≈27% in the Bh4 and L-Cit + Bh4 conditions, respectively (p< 0.05). PLM AUC increased ≈114% (p< 0.05) in the L-Cit + Bh4 condition. There were no significant intervention-induced changes in FMD. With advancing age, vascular function, as assessed by PLM, which may be more NO mediated than FMD, appears to be more limited by eNOS function than NO substrate. However, these findings also suggest that the combination of increased eNOS coupling and eNOS substrate most consistently enhances vascular function in the elderly, as assessed by the total (AUC) PLM response.

Karissa Wang, University of Utah (Prof. Martin Tristani-Firouzi, Pediatrics)

Correction of mutation in atrial fibrillation susceptibility gene NFATc1 using CRISPR-Cas9 systems

NFATc1 is a gene that has been linked to Atrial Fibrillation (AF). The Tristani Lab has identified a mutation in NFATc1 which has been found in only patients with early-onset AF. This project employs the use of CRISPR-Cas9 gene-editing systems to try to correct the mutation in NFATc1 and examine whether this grants normal function to stem cells differentiated into cardiomyocytes.

Sage Yeager, University of Utah (Prof. Anushka Abeysekara, Physics & Astronomy)

Using a Machine Learning Based Algorithm to Improve the Sensitivity of the HAWC Gamma-Ray Observatory

The High Altitude Water Cherenkov (HAWC) observatory is a detector sensitive to gamma-rays (photons) with energies between 100 GeV and 100 TeV. Both gamma and cosmic-rays stream through the universe from their origins outside our solar system, and eventually enter the Earth's atmosphere where they interact with air molecules. The result is a precipitation of charged particles known as an Extensive Air Shower (EAS). Sitting at an altitude of 4.1 km, HAWC detects thousands of EAS footprints per second. HAWC then uses characteristics of each footprint to reconstruct the properties of the original ray; these include species (gamma or cosmic), energy, angle of incidence, e.t.c. The primary purpose of HAWC is to detect gamma-rays. Therefore, EAS generated by hadronic cosmic-rays are significant sources of background. Currently, HAWC analysis packages use subtle differences between computer simulated gamma and cosmic-ray shower footprints to identify gamma-rays in the real data. The particles constituent to a gamma-ray shower are a subset of those present in a cosmic-ray shower; in most cases it is challenging to determine the original species responsible for each shower. An efficient algorithm with the ability to separate gamma-ray generated showers from cosmic-ray generated showers could drastically improve the sensitivity of HAWC. My research has explored the potential of using Python in conjunction with SciKit Learn's AdaBoostClassifier and DecisionTreeClassifier to develop a more efficient tool to select gamma-rays. In this symposium, I will present the new machine learning based algorithm and its performances compared with those of the algorithm currently in use by HAWC.

Jake Becker, Salt Lake Community College (Prof. Christie Toth, Writing & Rhetoric Studies)

Urban Writing Ecologies: Mapping Inter-Instituional Writing Transfer

As of 2014, 7.3 million students were enrolled for credit in the nation’s 1,108 community colleges. That is roughly 45% of all U.S. postsecondary students, and 41% of first-time, first-year college students (AACC). Approximately 80% of incoming community college students say they plan to earn a bachelor’s degree. Yet only 25% actually transfer to a four-year institution within five years, and just 17% earn a bachelor’s degree within six years of transferring (Jenkins and Fink). In light of these figures, our research is locally situated on student transfer between Salt Lake Community College (SLCC) and the University of Utah (UofU), specifically how students adapt writing knowledge across institutional settings. Currently, there has been very little research on how students transfer writing knowledge between postsecondary institutions (Gere et al.). Drawing upon ecological theories of writing, the goal of this research is to increase the pedagogical approaches for fostering successful student writing transitions, while simultaneously bolstering successful student transfer between SLCC and the U of U. To accomplish this, we have curated two pilot courses within the Department of Writing & Rhetoric Studies, with the goal of developing resources for incoming transfer students. Our research provides new insight on the value of prior knowledge for understanding and navigating new writing contexts, while also showcasing key meta-concepts that facilitate successful writing transfer.

Matt Conley, Brigham Young University (Prof. Jared Rutter, Biochemistry)

Stress Responsive Degradation of mRNA Encoding Mitochondrial Proteins.

The degradation of cytosolic mRNA is crucial to the regulation of gene expression and can be induced by numerous cellular perturbations including glucose deprivation, etc. Although many stressors are known, cytoplasmic mRNA degradation has never been studied in the context of organellar stress. Recent studies have demonstrated that mitochondrial protein import stress activates a cytosolic response that leads to the degradation of proteins bound for the mitochondria. However, in the context of a similar stress, there remains nothing known regarding the fate of cytoplasmic mRNA encoding mitochondrial proteins. Thus, we sought to study mitochondrial stress induced mRNA degradation. In order to assay the induction of mRNA degradation, we engineered several Saccharomyces cerevisiae strains, in which GFP was fused to proteins involved in mRNA decapping and degradation. The accumulation of these proteins in subcellular structures termed p-bodies is commonly used to assay active mRNA degradation. We hypothesized that the accumulation of p-bodies would increase in response to mitochondrial stress. In order to induce stress, we chose two methods. First, we treated the cells with small molecules that uncouple the mitochondrial membrane and disable mitochondrial protein import. Second, we used FASII mutant strains, thereby creating a genetic model of mitochondrial stress. In order to assess p-body accumulation, we have employed fluorescent microscopy. Furthermore, we will perform RNA-seq assay and measure the levels of mRNA encoding a subset of mitochondrial proteins and compare the results to the level of said mRNA levels when mitochondrial stress is induced.

Kelly Corbray, University of Utah (Prof. Christie Toth, Writing & Rhetoric Studies)

Urban Writing Ecologies: Mapping Inter-Instituional Writing Transfer 

As of 2014, 7.3 million students were enrolled for credit in the nation’s 1,108 community colleges. That is roughly 45% of all U.S. postsecondary students, and 41% of first-time, first-year college students (AACC). Approximately 80% of incoming community college students say they plan to earn a bachelor’s degree. Yet only 25% actually transfer to a four-year institution within five years, and just 17% earn a bachelor’s degree within six years of transferring (Jenkins and Fink). In light of these figures, our research is locally situated on student transfer between Salt Lake Community College (SLCC) and the University of Utah (UofU), specifically how students adapt writing knowledge across institutional settings. Currently, there has been very little research on how students transfer writing knowledge between postsecondary institutions (Gere et al.). Drawing upon ecological theories of writing, the goal of this research is to increase the pedagogical approaches for fostering successful student writing transitions, while simultaneously bolstering successful student transfer between SLCC and the U of U. To accomplish this, we have curated two pilot courses within the Department of Writing & Rhetoric Studies, with the goal of developing resources for incoming transfer students. Our research provides new insight on the value of prior knowledge for understanding and navigating new writing contexts, while also showcasing key meta-concepts that facilitate successful writing transfer.

Ali Dibble, University of Utah (Prof. Taylor Sparks, Materials Science & Engineering)

Evaluating Performance of Sustainable Materials and Design in Feminine Hygiene Pads

Disposable feminine hygiene products are typically made with synthetic materials and chemical additives, which create a tremendous amount of waste that takes nearly a century to degrade under landfill settings. Several companies sell products to mitigate these environmental concerns, but these products are either not completely biodegradable or are bulky and uncomfortable to the user due to a large quantity of cellulose fiber added for absorbency. This project aims to assess the differences in absorbent capabilities between industry products and proposed biodegradable alternatives to determine if a biodegradable product can be created without sacrificing absorbency or user comfort. It is found that biodegradable hydrogels are 4 times less absorbent than industry-processed hydrogels. Boiled cotton is not a sufficient processing method as it only absorbs 45% the amount of fluid as chlorine-bleached cotton, though sustainable H2O2-bleached cotton absorbs 113% the amount of fluid as industry cotton. Preliminary fiber alignment patterns are also investigated to maximize fluid flow through the product and compensate for inferior material performance.

Chance Fox, Brigham Young University (Prof. Jeffrey Anderson, Radiology)

Why so Atypical: Typicality of the Default Mode Network as a Measure of Social Function in Autism Spectrum Disorder

The extreme heterogeneity in both symptoms and severity of autism spectrum disorder (ASD) has proven an obstacle to establishing coherent neurophysiological criteria for improving diagnosis and treatment options. Brain MRI measurements in autism have been similarly heterogeneous, and specific differences have not been found to be reliable clinical predictors of severity or prognosis. Functional connectivity MRI evaluates synchronized brain activity to measure relationships between brain regions, estimating a "wiring diagram" for the brain. We hypothesized that the similarity of functional connectivity to mean values across a typically developing population (typicality) might be a useful biomarker for autism that is less sensitive to autism heterogeneity. We used two analyses, {1} a principal component (PC) analysis and {2} a dynamical simulation of brain network activity, to compare typicality of functional connectivity to social function. We calculated principal components of connectivity between 25 million pairs of brain regions and compared principal components from each individual's connectivity in a large (n=487 autism, n=646 control subjects) cohort of autism and control individuals to average values from the Human Connectome Project (n=820 typically developing subjects). We found that nine out of the first ten PCs represented in control subjects were significantly more similar to typically developing population averages than ASD subjects were. For one of these components, which represented the brain's default mode network that processes attention to one's internal thoughts, the atypicality of this component for each autism subject compared to population means correlated with the degree of social dysfunction they exhibited (p=0.0000093). A simulation of brain network convergence to the default mode network revealed that an atypical convergence pattern is also indicative of increased social dysfunction (p=.0012). These findings suggest that typicality is a potential measure of social function in ASD, and possibly other neuropsychiatric disorders.

Fadi Haroun, University of South Dakota (Prof. Alana Welm, Oncological Sciences)

Understanding the Mechanism of Tumor Remission in Response to a Novel Immunotherapy Treatment for Breast Cancer

Cytotoxic T Lymphocytes (CTL) have an important role in eliminating cancer cells. The immune system has mechanisms to deactivate these cells to prevent excessive inflammation. This deactivation is mainly done through receptors on the surface of the CTL called checkpoint molecules. However, these molecules are often exploited by cancer cells to avoid eradication by the immune system. Based on this, checkpoint blockade has been studied as a method of achieving immune activation to promote CTL function in fighting cancer cells. Checkpoint blockade has been shown to be effective in many clinical trials, where patients who responded to the treatment had durable responses. However, many patients did not respond to this treatment. Therefore, combination of checkpoint blockade with other treatments has emerged as a possible method to potentiate an immune response in more patients. Ron is a receptor tyrosine kinase known to suppress the immune response through several mechanisms such as the attenuation of inflammatory response by promoting M2 macrophage state, and the downregulation of IL-12, among other mechanisms. In addition, Ron is linked to the immune checkpoint axis since Ron activation can upregulate PD-L1 and CD80 checkpoint molecules. Therefore, we combined a checkpoint blocking antibody (anti-CTLA4) with a Ron tyrosine kinase inhibitor to block the suppression of the immune system on two different levels in a mouse model of breast cancer. The combination showed significantly higher response rates compared to the monotreatment. This project was aimed at understanding the mechanism by which this novel treatment improved response rates. Since tumor infiltration by CTLs is an important component of the cancer immunity cycle, we specifically investigated whether our novel treatment caused more tumor infiltration, by immune staining and analysis of endpoint tumor samples. Our combination treatment showed significant increase in tumor infiltration compared to vehicle-treated mice, but there was no significant difference from the monotreatment.

Sydney Lambert, Vassar College (Prof. Alex Shcheglovitov, Neurobiology)

The Regulation of Shank3 in the Absence and Presence of Different Deletions

Phelan McDermid Syndrome (PMDS) is a rare genetic disorder linked to autism that comes with a suite of phenotypes, including decreased muscle tone, developmental delays, and intellectual disabilities. PMDS occurs when the terminal end of chromosome 22 is deleted. This terminal deletion disrupts the function of the gene Shank3. Shank3 is a complex gene that codes for a scaffolding protein in the postsynaptic density. The Shank3 protein coordinates synaptic function and is mainly found in the brain. Its location poses an ethical barrier that prevents direct study. To get around the dilemmas of obtaining live brain tissue, we utilized induced pluripotent stem cells (iPSCs) to grow genetically identical neurons starting from less invasive, less critical tissue. After establishing these lines of neurons from patients with no Shank3 deletion, we employed a CRISPR/Cas9 system to introduce two specific deletions that we wanted to study: one complete heterozygous deletion and one partial homozygous deletion (Table 1). We suspected that the regulation of Shank3 would be changed in the presence of deletions. To test this, we designed promoter-specific sets of primers to target each of the sites that can produce unique isoforms. We then ran PCR and gel electrophoresis to identify the resulting isoform lengths. Preliminary results showed possible deletion-dependent regulation of Shank3. Understanding the regulation of Shank3 in the presence of different deletions will contribute to the overall knowledge of how genetic mutations create a plethora of observed phenotypes.

Billy Jeon, Rice University (Prof. Luke Timmins, Bioengineering)

Design and Construction of a Computer-Controlled Biaxial Testing Device for Vascular Tissue

Cardiovascular disease continues to be the leading cause of death in the world, and there is a clear need for research in this area. Exploring the biomechanics of the cardiovascular system, particularly arterial tissue, plays a key role in better understanding the pathogenesis of diseases, which would ultimately lead to better diagnosis and treatment options. Herein, we present the design and development of a computer-controlled, electromechanical biaxial testing device which can simultaneously apply pressure cycles (inflate) and axially stretch (extend) excised arteries. The device consists of four major parts: motion control (via 3-axis stages, motorized actuators, and modular posts), pressure control (via syringe pump and pressure transducer), imaging (monochrome CCD), and computer automation (via programming in LabVIEW). These components allow for the cyclic pressurization at multiple axial stretches, providing pressure/diameter and load/length curves. We tested our device with excised porcine carotid arteries. Data demonstrate a non-linearly elastic behavior under loading, which is commonly observed for soft biologic tissues. Through these experiments, we can better characterize the mechanical behavior of arterial tissue and understand how tissue responds to physiologic and pathologic loading conditions.

Raquel Maynez, University of Utah (Prof. Mike Shapiro, Biology)

MOLECULAR EFFECTS OF A CODING MUTATION IN A PIGMENTATION PATTERNING GENE

Color patterns in birds and other vertebrates are incredibly diverse and can impact fitness by affecting mate choice, crypsis, and survival. However, the genetic and developmental basis of this diversity is not well understood. In order to investigate pigmentation patterning variation, our lab studies the domestic pigeon. Domestic pigeons are immensely diverse in many traits, including pigmentation patterns. All pigeons have one of four major wing pigmentation patterns: T-check, checker, bar, or barless. Barless is the most recessive phenotype, characterized by a lack of the ancestral bars on the wing and an increased incidence of vision defects. Previously, the Shapiro lab found that variation in a gene that encodes a secreted protein is associated with the major wing pigmentation patterns. All barless birds are fixed for a start codon mutation that truncates the protein by 13 amino acids, shortening the signal peptide sequence. We are currently assessing whether this mutation effects secretion of the protein. In order to do this, we have begun constructing a mutant, wild type, and no signal sequence version of the gene with fluorescent tags, the latter two serving as controls for comparison to the mutant. We will then transform each construct into HeLa cells and visualize cellular localization of the tagged proteins using microscopy. We will also separate the supernatant (extracellular fluid) and cells of a liquid culture and use western blots to evaluate whether the protein was secreted into the supernatant or remained in the cells for all three constructs. I hypothesize that the mutant will have reduced secretion because of the shortened signal sequence. By collecting and examining our findings, we will gain insight into the molecular basis of pigmentation patterns found in pigeons and potentially gain insight into similar phenotypes found in wild bird species.

Johanna Mora, University of Texas Rio Grande Valley (Prof. Daniel Leung, Infectious Disease)

Optimizing Growth Conditions for Clonal Expansion of Mucosal-Associated Invariant T (MAIT) Cells

Mucosal-associated invariant T (MAIT) are innate-like T-cells that recognize microbial riboflavin metabolites presented by the highly conserved MR1 (MHC class-I Related) molecule. In humans, MAIT cells account for up to 10% of the peripheral blood T cells, and are enriched in the intestine and liver. The clonality, function, and activity of MAITs cells are not well understood. In preliminary experiments, we have found significant functional heterogeneity across different clonotypes. Current methods for expansion of MAIT clones are not well established, and the optimal conditions for cloning MAIT cells are not known. Here, we examine different conditions to determine which are optimal for expansion of MAIT cells. We compared various concentrations and presence of cytokines IL-2, CD3/CD28, and TGF-b. Results are pending at time of this abstract. Determining optimal growth conditions for expanding individual MAIT clones will be essential for better understanding their biology. Our lab is interested in using these techniques to clone MAITs from healthy and infected (HIV and cholera) donors to evaluate their plasticity and functional characteristics.

Vinny Morrow, Waynesburg University (Prof. Micah Drummond, Physical Therapy)

Skeletal Muscle Insulin Sensitivity and Cell Stress Signaling during Reduced Activity and Recovery in Older Adults

The Drummond laboratory has previously shown that signaling through the innate immune system contributes to the inflammatory response, ceramide biosynthesis, and metabolic disruptions such as impaired glucose uptake and insulin resistance. These physiological changes are allied with short term skeletal muscle inactivity in hindlimb unloading mice and healthy older adults on bed rest. These models are intended to be representative of short term periods of physical inactivity in older adults resulting from injury or disease that progresses to atrophy, sarcopenia, dynapenia, and eventually, functional dependency. Although insulin insensitivity and muscle atrophy are common in strict bed rest, often hospitalization does not entail strict bed rest and instead hospitalization and recovery in the following weeks can be characterized by reduced physical activity through a reduction in total daily steps. Therefore, we collected muscle biopsies from healthy older adults before (pre) after 2 weeks of step reduction (RA: <75% of normal activity) and 2 subsequent weeks of recovery (REC: return to baseline activity levels). Muscle samples were lysed and run through SDS-PAGE and transferred to a PVDF membrane for assessment of proteins expression related to insulin sensitivity, cell stress and ceramide biosynthesis pathways This will give insight if the insulin insensitivity and muscle atrophy following a period of step reduction are associated with the TLR-4/MyD88 signaling pathway.

Arthy Narayanan, BMS College of Engineering (Prof. Al Light, Anesthesiology)

Detection of Gene Variants in Chronic Fatigue Syndrome Patients

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM) are chronic conditions often present in the same patient, characterized by severe physical fatigue, widespread muscle and joint pain, mental fog and post-exertional worsening of symptoms. Patients with ME/CFS and FM experience difficulty in performing daily activities and in some cases are wheelchair-bound. In a pilot sample, the majority of ME/CFS patients had elevated autoantibodies to autonomic receptors and also showed variants (mutations) in genes linked to cellular energy (mitochondria). This study aims to identify some of the gene variants that may contribute to ME/CFS and FM by comparing the genetic sequences of these patients with that of the controls. Our hypothesis is that ME/CFS is both an autoimmune disorder and an energy deficiency disorder, so we have focused on both immune and mitochondrial/energy genes. Blood samples were drawn from ME/CFS patients and controls and the leukocytes were separated from it. The mRNA of these leukocytes, which represents the transcriptome of the cells, was extracted and then sequenced using the RNA-Seq method. The mutations in the genes were ranked as low, moderate or high impact on the function of the gene. In this initial sample of 44 of the planned 340 participants, we identified 3 automunity/immune function variants (LILRA6, RFTN1 and MARCH8) and several different multigene patterns for mitochondrial variants with moderate and high impact that occurred with greater frequency in the ME/CFS patients vs. controls. When the data from all 340 participants is complete, it will help identify biomarkers to make diagnosis easier and may also provide targets for developing new treatments for ME/CFS and FM.

Valeria Ortiz Torres, University of Puerto Rico, Mayaguez Campus (Prof. Matthew VanBrocklin, Surgery)

Development and testing of an immune receptor identification system to discover novel receptors for immune signaler, B7H3

Recently, therapies involving immune reactivation have held great promise for melanoma patients. Many of these immunotherapies include immune checkpoint inhibitors or blocking antibodies which reactivate the immune system by removing the malfunctioning brakes on T-cell function. For example, CTLA4 and PD1-targeting antibodies used together in Phase III clinical trials have resulted in tumor diminishing responses in up to 60% of patients. Although responses for combined blockade with CTLA4 and PD1 antibodies have been successful, there are up to 40% of patients which do not respond and additional means for immune activation need to be explored. Our goal in this summer research project has been to develop tools and begin testing the immune nature of the B7H3 signaling molecule and identify its receptors. Importantly, we seek to discover receptors for B7H3 involved in immune suppressive signals which may be targeted for immunotherapy blockade. B7H3 is in the same family as PD-L1 (aka. B7H1) which is the signaling ligand of the PD1 checkpoint receptor and thus is a likely target for successful immune checkpoint blockade. We have been testing eighteen different genes and their protein products in HEK293FT cells to identify binding interactions with B7H3. In this first phase of the overall project we have cloned the genes to be tested into expression vectors, performed E.coli transformations, made large-scale preps (maxi preps) of each DNA plasmid, transfected HEK293FT cells, and given B7H3 treatment and performed flow cytometry to measure binding and assess potential receptors identified.

Hannah Peterson, Belmont University (Prof. Christopher Reilly, Pharmacology & Toxicology)

Elucidation of Amino Acids Regulating the Species-Selective Activation of TRPM8 by Coal Fly Ash Particles

Transient receptor protein melastatin-8 (TRPM8) is an ion channel expressed by neurons and epithelial cells in the lungs. TRPM8 is activated by cold temperatures and soluble agonists that produce a "cooling" effect. Human TRPM8 is also activated by particulate matter, specifically coal fly ash (CFA), a calcium-rich material produced from burning coal. Exposure to CFA has been associated with adverse health effects on the respiratory system. When treated with CFA, human bronchial epithelial cells showed an induction of pro-inflammatory cytokines while instillation of CFA into mouse lungs showed minimal pro-inflammatory effects. Additionally, mouse Trpm8 was not activated by CFA. The goal of this project was to determine amino acids within the TRPM8 protein responsible for species-selective activation by CFA. Within the pore loop region of the TRPM8 protein, three residues (921,927, and 932) differed between human and mouse TRPM8. Site-directed mutagenesis was used to introduce corresponding amino acid changes.The mutant TRPM8 plasmid DNA was then transfected into human HEK-293 cells overexpressing the calcium-sensitive reporter gene GCaMP6s.Calcium flux assays were used to determine the activity of the mutant TRPM8 proteins relative to the respective wild type forms. The hG921S human to mouse mutation had little effect on human TRPM8 activity, but the corresponding mS921G mouse to human mutation increased activity compared to the wild-type mouse TRPM8; however, the response was only ~50% that of human TRPM8. The hA927S did not change responses of human TRPM8, but the mS927A exhibited responses comparable to wild-type human TRPM8.Finally, the hT932S and mS932T mutants were both inactive, similar to wild-type mouse TRPM8.These results reveal specific residues on the pore loop region of TRPM8 that regulate its activation by CFA. These findings improve our understanding of how TRPM8 is activated by particulate materials which will facilitate studies into its contribution to lung pathologies by providing the opportunity to develop new genetically modified mouse models.

Jose Porras, University of Texas Rio Grande Valley (Prof. Jason Shepherd, Neurobiology)

GENERATING SYNAPTIC REPORTERS FOR UNDERSTANDING MEMORY STORAGE

Understanding how memories are stored is essential to understanding Alzheimer's Disease as well as normal cognition. In the early 20th century, Richard Semon proposed the engram hypothesis, that connections between neurons were made as a result of stimulation. Recent studies support this hypothesis. However, when the encoding of various events occurs within two hours, these circuits can show overlap, suggesting the engram is not limited to whole cells. We hypothesize that the most basic form of the engram is one distinct set of synapses. To test this, we are developing SLAyR (synaptically localized activity reporter), a genetic tool designed to only label active synapses. We are doing this by modifying FingR (fibronectin intrabody generated with mRNA display), a probe that binds to PSD95, a scaffolding protein found in excitatory synapses. The modifications we plan to make, if successful, will limit binding to only PSD95 in active synapses. This can be achieved by adding a few selected components cloned from Arc (activity regulated cytoskeletal protein). These include an activity dependent enhancer and Arc's UTR (untranslated region). The activity dependent enhancer will regulate transcription of SLAyR to only active neurons while the 3'UTR will guide the mRNA to active synapses. Further activity will then promote the translation of this mRNA, which will bind to PSD95 in these active synapses where the protein was synthesized. I am assisting in this project by cloning versions of SLAyR with different enhancers and a smaller Dendritic Targeting Element in lieu of using the whole UTR. We are then testing these constructs in cultured neurons to verify that they are showing activity dependent expression and labeling only active synapses. Once the active synapses are targeted, we can elucidate changes in protein and cytoskeletal organization that are associated with memory. SLAyR will be an invaluable tool to guide us closer to understanding the molecular mechanism of memory storage, helping us develop better ways to treat conditions like Alzheimer's Disease.

Mu Pye, University of Utah (Prof. Akiko Kamimura, Sociology)

Patient Satisfaction and Perspectives of Continuity of Care among Free Clinic Patients in the USA

Free clinics are important resources for those who un- or under insured individual in the United states. The purpose of this study was to explore continuity of care and patient satisfaction from the perspectives of free clinic patients. Since the majority of free clinic providers are volunteers and may not be with a free clinic long-term, continuity of care should not be just seeing the same doctor over time, but also seeing well-coordinated providers. Because free clinics serve a wide variety of underserved populations, cultural competence training in medical education may not wholly t the socioeconomic and/or cultural realities of free clinic patients. And the result of continuity of care was not always perceived positively. There were potential miscommunications between providers or receptionists and patients. Patients may not be well informed of the available resources at the clinic. More in-person communication would be beneficial to distribute the information about available resources for free clinic patients. Communication among patients and receptionists, providers, and interpreters seemed to be a prevalent recurring topic across groups. The communication of health programs and appointment reminders are the areas to be improved. Training in communications with patients or cultural competence in medical education may need to consider a wide variety of patient backgrounds.

Michael Ruesch, Brigham Young University (Prof. Randy Jensen, Neurosurgery)

Knockout of hypoxia induced factor 1α in meningioma and glioma cell lines via short hairpin RNA interference and the CRISPR-Cas9 system

Introduction: Hypoxia, a decrease in oxygen perfusion from homeostatic levels, is common in a variety of primary brain tumors including meningiomas and gliomas. It has been found to correlate with more aggressive tumor growth, development of both meningiomas and gliomas, regulation of tumor microenvironment, as well as diffusion restriction and necrosis. Hypoxia-Inducible Factors (HIFs), specifically HIF-1α, are upregulated under hypoxic conditions and after radiation treatment, leading to a greater radioresistance in tumors. Previous work in our lab utilized a HIF-1α shRNA knockdown in a glioma primary cell model, which has been unsuccessfully produced in primary meningioma cells. Methods: A lentiviral-based clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 construct was used to generate a HIF-1α knockout in a primary human meningioma cell line (GAR). Viral particles were generated in Hek 293T cells. Verification of the transfection was performed using green fluorescence protein (GFP) analysis, morphological analysis of cells, and evaluation of cell proliferation dynamics. An adenovirus-mediated HIF-1α targeting shRNA was also developed and compared. Results: We have generated successful plasmid and concentrated viral particle as verified by GFP expression in Hek 293T cells and infected GAR cells. Generation of a HIF-1α targeting shRNA adenovirus was verified by immunofluorescence analysis of virus producing Hek 293T cells and PCR analysis of generated plasmids. Quantitative analysis of HIF-1α levels was determined via a HIF-1α based ELISA to determine knockout efficiency. Discussion: We successfully created a lentivirus-CRISPR/Cas9 and adenovirus-shRNA knockout model for HIF-1α. Further work will include in vitro characterization of infected cells and in vivo treatment of meningioma and glioma animal models. The impact of radiation on HIF-1α knockout cells will be evaluated. These results will aid in the understanding of HIF-1α on meningioma and glioma dynamics, as well as the impact of radiotherapy.

Abby Scott, Westminster College (Prof. Eric Schmidt, Medicinal Chemistry)

Optimizing Cyclization of Peptides for Use on Drug Analogs

Conotoxins, peptides found in cone snail venom, have a variety of potential pharmaceutical applications, such as a treatment for cocaine and nicotine addiction. Some difficulties with using peptides as pharmaceuticals are their large size and instability when linear. PatG and TruD, enzymes found in symbionts of the ascidian Lissoclinum patella, can be used to cyclize peptides. The purpose of this project was to optimize the cyclization of conotoxin peptide fragments for use as drug analogs. This was accomplished by assessing the cyclization activity of TruD, PatG, and a S783C PatG mutant in different combinations on 4 test substrates. Liquid Chromatography Mass Spectrometry (LCMS) was used to assess the resulting peptide structures in each of the assays.

Konrad Serbinowski, University of Utah (Prof. Taylor Sparks, Materials Science & Engineering)

Discovery and Synthesis of Superhard Materials

Superhard materials are materials which have a Vickers's hardness measurement exceeding 40 gigapascals. Currently the most well-know superhard material is diamond, but like most other superhard materials, diamond requires high temperature and pressure to synthesize which leads to high production costs. A promising solution to this is the synthesis of superhard materials which do not require high pressure for synthesis. Most of these materials are heavy transition metal borides and carbides which do not need to form as many short covalent bonds due to the layers of heavy transition metals which have d-valence electrons. Through the use of machine learning we are able to identify the best superhard materials which have low production cost and then cross check with HHI values and other economic factors in order to ensure the possibility of production on a larger scale.

Joseph Sheikh, University of Utah (Prof. Sophie Caron, Biology)

Mapping Gustatory Sensing Neural Circuits in Drosophila

A key question that remains unanswered in the field of neuroscience is how the brain combines different types of sensory information and generates a meaningful representation of the outside world. The Caron laboratory investigates how the Drosophila melanogaster brain, in particular the mushroom body, integrates sensory information. The first step in understand multimodal integration is understanding neural circuits, therefore the research conducted was to determine whether either the GR64f+ sweet sensing neurons, GR66a+ bitter sensing neurons, or ppk28+ water sensing neurons connect to gustatory projection neuron (gPN1). It was hypothesized that these connections exist due to anatomical evidence from previous research. In order to verify connections between the two neurons, GFP Reconstitution Across Synaptic Partners (GRASP) and fluorescent protein tdTomato were used to mark the neurons, then imaged using confocal microscopy. The results of this experiment have revealed a potential connection between GR64f+ and ppk28+ with gPN1; however, further data is needed to make a conclusion.

Kai Sin, University of Utah (Prof. Akiko Kamimura, Sociology)

Patient Satisfaction and Perspectives of Continuity of Care among Free Clinic Patients in the USA

Free clinics are important resources for those who un- or under insured individual in the United states. The purpose of this study was to explore continuity of care and patient satisfaction from the perspectives of free clinic patients. Since the majority of free clinic providers are volunteers and may not be with a free clinic long-term, continuity of care should not be just seeing the same doctor over time, but also seeing well-coordinated providers. Because free clinics serve a wide variety of underserved populations, cultural competence training in medical education may not wholly t the socioeconomic and/or cultural realities of free clinic patients. And the result of continuity of care was not always perceived positively. There were potential miscommunications between providers or receptionists and patients. Patients may not be well informed of the available resources at the clinic. More in-person communication would be beneficial to distribute the information about available resources for free clinic patients. Communication among patients and receptionists, providers, and interpreters seemed to be a prevalent recurring topic across groups. The communication of health programs and appointment reminders are the areas to be improved. Training in communications with patients or cultural competence in medical education may need to consider a wide variety of patient backgrounds.

Shane Tory, University of Utah (Prof. Taylor Sparks, Materials Science & Engineering)

A New Sodium Ion Conductor: Processing and Transport Relationships

Sodium based electrochemical cells are gaining interest in industry due to the high availability and abundance of sodium. A sodium ion conducting electrolyte is one essential component of an electrochemical cell. Sodium zirconium gallate (Na0.7Ga4.7Zr0.3O8) belongs to the beta gallate rutile structure type and was recently discovered. Preliminary measurements show it to be a one-dimensional sodium ion conductor. In a similar process, synthesis of Na-β''-alumina + 3 mol.%Y2O3-stabilized zirconia (YSZ) by a vapor phase process lead to a textured microstructure with accompanying anisotropic transport. Here, we report on the synthesis of Na0.7Ga4.7Zr0.3O8 + YSZ composites by a vapor phase process and observe no evidence of crystallographic texturing or anisotropy in ionic transport. In addition, the kinetics of vapor phase transformation in Na0.7Ga4.7Zr0.3O8 + YSZ composites were studied. The results showed a similar trend to the kinetic of previously studied Na-β''-alumina + YSZ composites suggesting a similar oxygen transport rate limiting mechanism of transformation.

Tyler Vail, Brigham Young University (Prof. KC Brennan, Neurology)

2-photon Microscopy Analysis of Neuronal Ca2+ Activity During Cortical Spreading Depression After Traumatic Brain Injury

Traumatic Brain Injury (TBI) is frequent among civilian and military personnel. TBI can result from car crashes, sports, violence, or blast injuries. Despite its relevance, the long-term effects of TBI are not fully understood. Spreading depolarization (SD) is a wave of excitation that passes through the brain that occurs at the time of and following TBI which may exhibit long term effects on brain tissue and cortical networks. The goal of our research is to investigate cellular changes after a traumatic brain injury. Controlled Cortical Impact (CCI) is a well-documented technique that can be used to replicate the injuries similar to TBI. We used CCI combined with two-photon microscopy to observe calcium levels during SD to detect changes on a cellular level. These changes suggest that TBI may be more serious than we thought because of increased damage due to spreading depolarizations.

Lacey Woods, Southern Utah University (Prof. Peter West, Pharmacology & Toxicology)

The Effects of Spontaneously Recurrent Seizures on Dentate Gyrus-Mediated Cognitive Function and Synaptic Plasticity in the Intra Amygdala Kayanate Model of Temporal Lobe Epilepsy

Seizures associated with epilepsy often result in cognitive comorbidities, such as memory loss, that still remain medically untreated. Mouse models have been useful in developing drugs to stop seizures in epileptic patients but not to treat the cognitive comorbidities that significantly affect the patient’s quality of life. Commonly used electrically-induced acute seizure models, such as the corneal kindled mouse model of focal seizures, have been shown to have impaired dentate gyrus (DG) mediated spatial pattern processing, learning, memory, and attenuated DG synaptic plasticity (Remigio et al., 2017). However, in the effort to develop treatments of cognitive comorbidities in epilepsy, more advanced models are needed that experience genuine spontaneous recurrent seizures (SRSs) and cognitive dysfunction. Therefore, the aim of this experiment is to evaluate the effects of SRSs on dentate gyrus-mediated cognitive function and synaptic plasticity in a novel model of temporal lobe epilepsy: the intra-amygdala kainate mouse (IAK) (Almeida Silva et al., 2016; Mouri et al., 2008). After a latent period of approximately 3-5 days, a cohort of the IAK mice was shown to experience approximately 1-2 spontaneous seizures per day (n=10). When tested in a task reliant on spatial pattern processing in the dentate gyrus (the metric task), these IAK mice were shown to have significant learning and memory impairments compared to the SHAM surgical and control mice. Finally, in a measure of experience-dependent synaptic plasticity commonly accepted as a model of learning and memory at the level of the synapse (Long-Term Potentiation, LTP), LTP at the perforant path – dentate granule cell synapse in the IAK group was significantly attenuated relative to both the control and SHAM surgical mice. These results strongly suggest that SRSs significantly impact cognitive function both in vivo and in vitro at the level of the dentate gyrus. Therefore, IAK mice may be useful as a tool to evaluate novel treatments for cognitive dysfunction associated with SRSs in patients with epilepsy.