ItemThe Masculine Other: Choreographing for the Asian Male Ballet Dancer(2017-03) Ha, Steven; Eliot, KarenClassical ballet tends to foreground images of women who are ethereal and lithe, and men who are chivalrous partners and virtuosic athletes. And yet male dancers are often subject to scrutiny in which their masculinity is questioned and their sexuality is assumed to be homosexual. In response, ballet choreographies often emphasize heterosexual relationships and incredible feats of athleticism in attempts to counter such rhetoric through hyper-masculinization. However, what of queer dancers or men who present non-normative gender identities? Or Asian men, who have been historically effeminized through Orientalist discourse? This paper endeavors to consider and develop choreographic strategies that have the potential to allow for alternative performances of masculinity in a classical ballet context, where highly specified gender roles and movement vocabularies designated for men and women have ossified into tradition. Drawing largely upon the work of Gilles Deleuze and Félix Guattari and their concepts of deterritorialization and reterritorialization, paired with Jane M. Bacon and Vida Midgelow’s Critical Articulations Process (CAP), I argue for a development of choreographic methods that can encompass a wider range of masculinities, allowing for a variety of artistic expressions and a restructuring of ballet pedagogy to encourage inclusivity. ItemDetermining total emissions and environmental drivers of methane flux in a Lake Erie estuarine marsh: The Old Woman Creek Wetland(2017-03) Rey-Sanchez, Camilo; Bohrer, GilEstuarine marshes can act as an important ecosystem for carbon storage and flux. We monitored CH4 and CO2 fluxes in Old Woman Creek, an estuarine wetland of Lake Erie, Ohio. The eddy covariance (EC) technique was used to measure fluxes of CH4 and CO2 continuously during the growing seasons of 2015 and 2016. Simultaneously, monthly sampling of gas exchange was conducted using accumulation chambers in four distinct land-cover types in the wetland: Open water, emergent vegetation (Typha spp.), floating vegetation (Nelumbo spp.) and mud flats. Chambers and EC measurements were combined to provide estimates of the continuous contributions of each land cover to the total methane emissions of the wetland. In addition, water and meteorological measurements were used to determine the most important environmental drivers of methane flux in the wetland. We found an average rate of emission from the Typha patch of 1.9 g CH4 m-2 d-1, which was much higher than rates reported in similar emergent vegetation types in other wetlands. Mud flats had the highest rates of CH4 emission, followed by Nelumbo, and Typha patches, and Open water. Mud flats contributed 6.8% of the total CH4 emissions of the wetland despite occupying only 1.5% of the wetland area, whereas open water contributed 16.1% despite occupying 47% of the wetland area. Water temperature, and wind speed were the strongest environmental drivers of CH4 flux to the atmosphere. Carbon fluxes were strongly correlated to methane fluxes. Fluctuating water levels above the wetland’s surface had a weak effect on overall CH4 emissions in the wetland. Providing an empirical model that predicts the influence of different environmental drivers on the emissions of methane in the wetland, can aid in the design of estuarine wetlands that retain nutrients and reduce coastal eutrophication while minimizing greenhouse gas emissions. ItemFrom Failures to Innovation – How Organizations Learn from Failures to Innovate(2017-03) Awate, Kiran; Makhija, MonaExperimentation and failures play pivotal role in innovation (Sitkin, 1992; March 1991). Failures not only provide crucial insights about causal relationships when complete understanding of the underlying novel mechanism is unavailable but also create options to choose from for further experimentation. Organizations learn from failures and alter their search based on the feedback (Weick, 1979; Sitkin, 1992; Argyris & Schön; 1978; Austin, Devin & Sullivan, 2012; Khanna Guler & Nerkar, 2015). Two streams of literature have examined issues related to innovation and learning from failures. First stream of literature has examined whether and how diverse knowledge elements can lead to new discoveries (Utterback, 1994; Galunic & Rodan, 1998; Hargadon and Douglas, 2001; Rivkin, 2000; Fleming 2001; Ahuja & Katila 2004). This literature argues that innovation occurs through combination and recombination of existing elements into novel artifacts. While predictions from this literature provide insights into the factors that may lead to innovation, this research does not provide systematic explanations about processes that precede innovation. Specifically, this research remains silent on how organizations learn from prior recombination attempts that failed. ItemBlack Men in No Man's Land: Race, Masculinity, and Citizenship in World War I Literature(2017-03) Wilder, Blake; Friedman, RyanNearly 400,000 African Americans served in the U.S. Army during the First World War. At the same time, white servicemen survived wartime injuries at an unprecedented rate. This paper explores how these trends reflect a cultural moment that disrupted Jim Crow narratives about race and masculinity. Through an investigation of scenes where black and white men confront each other on the battlefield, this paper reveals that wartime disruptions engendered new formations of race and masculinity as legible identities. I argue that new depictions of black men as assertive or heroic challenged the reductive stereotypes that were used to justify the oppressive practices of lynching and disenfranchisement. And I contend that the depictions of white men as wounded and in need of assistance offered new possibilities for how Americans might relate across the color line. Scenes of black and white soldiers meeting in no man’s land allow African American authors to reframe the battlefield as a space where Jim Crow racism is defeated through interracial cooperation. Although the eventual re-normalization of white masculinity has obscured those World War I disruptions that allowed white and black Americans to imagine new ways of being in the world, my project recovers a period when social turmoil allowed black men to be viewed in new, more positive ways. ItemHydrostatic Pressure Induces Glioblastoma Cell Death in Tumor Edema Model(2017-03) Calhoun, Mark; Winter, JessicaGlioblastoma is a highly lethal brain tumor that leaves patients with a median 14 month survival time. The gold standard for patients is surgery, followed by radiation and chemotherapy, yet patient outlook is dismal. Thus, there is a critical need for new drug targets in order to improve patient outcomes. Physical forces in the tumor microenvironment represent an innovative source of drug targets, and here we have chosen to focus on interstitial fluid pressure (IFP). IFP is the result of angiogenesis and new leaky blood vessels. In our in vitro model, we simulate this IFP and find that tumor cells experience the most cell death at an IFP within the range of a normal healthy adult. Further, this cell death is apoptotic and p-Akt and beta-1 integrin are implicated in this cell death mechanism. These data help to move the field of mechanobiology forward, and begin to pave the way towards the development of a new drug that works in conjunction with a physical force in the tumor microenvironment to destroy tumor cells. ItemIntercultural Competence and College Readiness: A Mixed Methods Study of First-Year Students at a Community College and a Traditional 4-Year University(2017-03) Houston, Leona; Anthony, AnikaThe workplace and colleges increasingly desire the skills of intercultural competence (ICC) but ICC is not part of most notions of college readiness. Behavioral research, employer demands, and many colleges have already identified intercultural competence as a skill that is in high demand; however, to date there is a lack of research that examines whether first-year college students perceive cultural competence as relevant to college and workplace readiness. The purpose of this mixed methods, explanatory, social justice, study was to investigate first-year college students’ perceptions of intercultural competence as a factor for college readiness and to understand the influences they perceived as having contributed to their development of intercultural competence. This study involved 67 first-year college students attending either a community college or a traditional 4-year university in a large, Midwestern U.S. city. For the first part of the study, I used the Intercultural Development Inventory (IDI; Hammer, 2012) to assess and then compare college students’ levels of intercultural competence. Subsequently, data from the surveys were used to recruit eight participants for semi-structured interviews to explore students’ perceptions of intercultural competence as a factor relevant to college and workplace readiness. Significant findings from the quantitative portion of the study are, first, that the mean level of intercultural competence overall (n = 67) was 83.48 which indicates that participants in this study were at the IDI Developmental Orientation of Polarization, or have an “us versus them” perspective where individuals from diverse backgrounds typically feel uncomfortable (Hammer, 2012); second, there was no statistically significant difference in IDI scores between City Community College (CCC; n = 24) and Traditional State University (TSU; n = 43) students; and third, there was a statistically significant difference (n = 67; p = .045) between participants’ perceptions of the level of cultural understanding valued by their high schools and the level of cultural understanding first-year college students perceived will be valued by their future workplaces. Interview data indicates participants perceived intercultural competence was treated as optional across their secondary and post-secondary academic settings. This is problematic because participants also perceived that ICC will be highly valued by their workplace. The findings from this research show first-year college students desire ICC skills, not just for the future workplace but also for their first years on a college campus. ItemImproving speech understanding in bionic hearing prostheses(2017-03) Carter, Brittney; Healy, Eric; Apoux, FredAn estimated 37.5 million Americans suffer from hearing impairment (NIDCD, 2015). For individuals with severe to profound hearing impairment, a bionic hearing prosthesis called a cochlear implant (CI) is a standard treatment option. The CI is a medical device that encodes sound as a series of electrical signals, which are transmitted directly to the auditory nerve via surgically-implanted electrodes. Despite decades of technological advancements, the most pervasive barrier to progress is poor speech understanding in background noise, especially in settings with many simultaneous talkers. The current CI simulation study evaluates the efficacy of a ‘dual-carrier’ CI processing strategy as a means to present simultaneous speech signals to a listener on two unique carrier rates. Results showed that (1) dual-carrier processing improves intelligibility of two simultaneous speech signals compared to simulations of current CI technology and (2) dual-carrier processing enables listeners to monitor and switch attention between simultaneous speech signals at will. ItemMixed communities of mucoid and non-mucoid Pseudomonas aeruginosa exhibit enhanced resistance to host antimicrobials(2017-03) Malhotra, Sankalp; Wozniak, DanielPseudomonas aeruginosa (P.a.) is a bacterial pathogen that causes chronic lung infections in cystic fibrosis (CF) patients. The CF lung is hyperinflammatory due to an abundance of neutrophil-derived antimicrobials, including reactive oxygen species [e.g. hydrogen peroxide (H2O2)] and antimicrobial peptides (e.g. LL-37). P.a. colonizes the CF lung by acquiring adaptive mutations. Mutation of mucA results in a mucoid phenotype due to the overproduction of the polysaccharide alginate. Mucoid isolates often revert to a nonmucoid phenotype through second mutations. Mucoid and nonmucoid strains are often isolated from the same patient sample, suggesting a selective advantage for the co-existence of these variants in the CF lung. We hypothesized that mucoid/non-mucoid P.a. may be differentially susceptible to neutrophil products, exhibiting heightened resistance to host factors in consortia. While clinical mucoid P.a. isolate (FRD1) was 10-fold more resistant to LL-37 compared to non-mucoid variants, FRD1 was also more sensitive to H2O2 compared to a non-mucoid, algT revertant. Resistance to H2O2 was dependent on catalase (katA) expression, which was likely regulated by two transcription factors, AlgT and AlgR. Extracellular release of KatA was found to be dependent on the expression of lys, which encodes an endolysin in P.a. already implicated in eDNA release. Co-cultures of mucoid/non-mucoid strains (mimicking CF lung co-isolates) exhibited greater tolerance to both H2O2 and LL-37 than mono-culture. These data provide an important rationale to study the interaction of mucoid/non-mucoid P.a. variants as contributors to CF pathology. ItemHormonal Response to Prolonged Endurance Exercise in Elite Keto-Adapted Ultra-Endurance Athletes(2017-03) Hyde, Parker; Volek, JeffObjective: A burgeoning body of empirical and experimental evidence indicates that nutritional ketosis induced by carbohydrate restriction has clinical and physical performance applications. We recently reported that elite keto-adapted endurance athletes had greater than two-fold higher rates of fat oxidation, yet muscle glycogen at rest and after exercise was the same as a matched group of high-carbohydrate athletes. Given the importance of endocrine regulation of substrate mobilization and oxidation, the purpose of this study was to compare hormonal profiles to prolonged exercise in keto-adapted and high-carbohydrate athletes. Methods: Low Carbohydrate (n=10) and High Carbohydrate (n=10) ultra-endurance athletes, in the top 10% of race finishers, were enrolled for participation in this study. Participants completed body composition assessment via dual energy x-ray absorptiometry followed by a 180-min treadmill run at 64% VO2max. Venous blood sampling was obtained pre, during, and up to 2 hr post-exercise to assess testosterone, insulin-like growth factor 1, growth hormone, insulin like growth factor binding protein 1, glucagon, leptin and cortisol. Baseline hormone concentrations and body composition differences were assessed via independent t-tests. Biochemical responses to exercise and diet were assessed via a 2-way repeated measures analysis of variance. Results: No significant differences existed between groups in body composition. Resting plasma growth hormone concentrations in keto-adapted athletes were 3.5-fold higher (P<0.05). Glucagon concentrations were significantly higher in all but one timepoint for low carbohydrate athletes. A significant main effect of time, but not diet, was observed for testosterone, insulin-like growth factor 1, growth hormone, insulin like growth factor binding protein 1, and cortisol. Normalized testosterone and insulin like growth factor 1 demonstrated trends for higher concentrations in the low carbohydrate group post-exercise. Conclusion: The pronounced shift to lipid oxidation at rest and during submaximal exercise in keto-adapted athletes is accompanied by a differential endocrine response characterized by elevated growth hormone and glucagon and decreased leptin concentrations. ItemScreening Food Microbiota for Novel Antimicrobial Compounds suitable for Food Preservation(2017-03) Hussein, Walaa E.; Yousef, AhmedThe excessive use of antimicrobials has led to the decrease of their effectiveness against foodborne pathogens and spoilage bacteria. Therefore, innovations are needed for discovery of new potent antimicrobials to be used in food. In this study, twenty one samples of fermented food products were screened for beneficial microorganisms that show potent antimicrobial activity. Out of 1500 tested isolate, an Enterococcus durans OSY-EGY strain, isolated from an Egyptian cheese, was found to produce an antimicrobial compound at pH 4.6 and a concentration of 800 arbitrary units/ml. This compound is most active against Listeria sp., Lactobacillus sp., Pediococcus sp., and Lactococcus lactis. The antimicrobial compound retained its activity after storage at 4°C for 12 months, heating at 100°C for 80 minutes and 120°C for 25 minutes, treatment with alpha-chymotrypsin, trypsin, carboxypeptidase, aminopeptidase, papain enzymes and over a pH range from 1.5 to 13.5. The compound was purified by cationic exchange resin and C18silica cartridges with elution by dimethyl sulfoxide which indicated the compound’s cationic and amphipathic nature. Polyacrylamide gel electrophoresis showed the purified compound as a single band and the matrix-assisted laser desorption ionization showed that the molecular mass of the compound is 5200 kDa. In conclusion, the investigated antimicrobial compound is showing unique physico-chemical characteristics and stability to proteolytic enzymes, heat, acidic and alkaline pH; these traits make it a good candidate as a food preservative. ItemGrowth in Child Executive Function and Maternal Depressive Symptoms: Maternal Sensitivity as a Mediator(2017-03) Ku, Seulki; Feng, XinThis study examined the mediating role of maternal sensitivity in the links between trajectories of maternal depressive symptoms and developmental trajectories of child executive function (EF). Participants were 1,364 children and their mothers from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development date set. Maternal depressive symptoms (from 6 months through grade 5) and sensitivity (from 36 months grade 5) decreased over time, while child EF (from grade 1 to 5) increased over time. Mediation effects were found: first, low levels of maternal depressive symptoms at 6 months predicted high levels of child EF at grade 1 through increased levels of maternal sensitivity at 36 months; and second, lower levels of maternal depressive symptoms at 6 months were associated with greater growth in child EF through higher levels of maternal sensitivity at 36 months. The results suggest that maternal depressive symptoms in early childhood are important for children’s EF growth in middle childhood, and furthermore, maternal sensitivity is suggested to serve a mechanism linking the associations between early maternal depressive symptoms and child executive function growth. ItemManaging Medicaid Misclassification: Using Simulation Techniques to Identify Administrative Leverage Points in Policy Implementation(2017-03) Frazier, Lisa; Desai, AnandA fundamental challenge for state Medicaid programs is the ongoing task of implementing beneficiary enrollment according to specified eligibility criteria. Errors in enrollment present themselves in the form of eligible individuals not taking up coverage (missed take-up), individuals continually moving on and off the program (churn), and ineligible individuals receiving coverage (fraud). In addition to posing problems for the coverage and continuity of care of vulnerable populations, enrollment errors create difficulties for state program planning, budgeting, and contract arrangements. Despite passage of the Affordable Care Act in 2010, state Medicaid programs remain varied in the structure of their eligibility categories and their processes for determination and enrollment of beneficiaries. There are multiple levels of prescribed action and discretion in these systems, and both short (month-to-month) and long (multiple year) time horizons are of interest. Previous studies model enrollment outcomes as a deterministic function of personal characteristics (e.g., race/ethnicity) and general economic indicators (e.g., unemployment rate). The policies and procedures defining design and administration of the program are rarely included in models estimating enrollment patterns, thus ignoring potentially important sources of enrollment dynamics. The purpose of this research is to understand the mechanism by which Medicaid eligibility criteria are transformed into enrollment outcomes among state program populations. Drawing on insights from systems science and implementation research, this study uses simulated experiments with program structure to describe and explain the dynamics of Medicaid eligibility determination and enrollment processes. Program-level state Medicaid enrollment patterns are modeled in terms of the dynamics among individual characteristics, program eligibility criteria, and administrative procedures within relevant social, economic, demographic, and political contexts. The effects of federal guidelines, along with exemplary cases of state eligibility rules and determination procedures, are analyzed through a set of system dynamics models of program-level enrollment patterns. This study tests the possible effects of a number of implementation strategies drawn from the Medicaid enrollment literature on eligibility determination and benefit enrollment errors. Interrelationships among defined eligibility categories and (re)determination procedures create enrollment implementation error in Medicaid systems even when household economic conditions and decision making are stable. Delays in (re)determination processes lead to accumulations of households in enrollment states not consistent with their eligibility. A nonlinear relationship between the demand for benefits and the administrative capacity to process applications leads to further accumulation of misclassified households. Enrollment errors, including missed take-up, churn, and fraud, are shown to arise form the structure and dynamics of the program system itself, rather than solely from individual circumstance or exogenous economic shock. These simulations allow policy makers and scholars to experiment with various implementation strategies with effectively zero social costs. Illuminating the core dynamics of the Medicaid enrollment mechanism aids in forecasting enrollment and spending levels, revealing administrative leverage points to improve system performance, and evaluating potential tradeoffs between costs and coverage over time. Additionally, the simulations can be tailored to specific economic, demographic, and program conditions, providing a picture of the possible range of outcomes associated with specific administrative actions. ItemOptimizing microsatellite instability detection in cancer with MANTIS(Impact Journals, LLC, 2017-03) Bonneville, Russell; Roychowdhury, SameekPurpose Microsatellites are genomic loci that contain several repeats of short (1-6 base pair) nucleotide sequences. Microsatellite instability (MSI) is a genetic phenomenon in which uncorrected “slippage” of DNA fragments during DNA replication causes the repeat count to vary with cell division. MSI occurs frequently in several human cancers, most commonly colorectal, endometrial, and gastric adenocarcinoma. MSI results from defective DNA mismatch repair (MMR), which can occur either sporadically, or in patients with genetic predispositions. MSI is currently detected in these cancer types using two standard tests: immunohistochemistry (of four MMR proteins) and MSI-PCR (of five microsatellite loci). However, studies have provided increasing evidence of a potential role of MSI in several other cancer types, which may be missed with current standard diagnostic methods. The implementation of next generation sequencing (NGS) may facilitate ways to characterize the MSI status of multiple cancer types, and potentially identify MSI missed by current methods. We therefore sought to: 1) develop a new NGS-based method that utilizes matched tumor-normal data, 2) compare existing computational MSI detection methods, and 3) determine whether the number of loci evaluated has an impact on performance. Research Method We developed MANTIS, a novel computational method for research and clinical MSI detection in NGS data from matched tumor and normal samples. MANTIS was compared to the existing NGS-based algorithms mSINGS and MSISensor. For testing and validation, we applied all three tools to whole-exome sequencing data from 275 matched tumor and normal samples with known MSI status (from three cancer types) from The Cancer Genome Atlas. We then evaluated the tools’ performance in three additional cancer types, as well as their performance when utilizing variable numbers of target loci ranging from 10 to 2539. Findings All three computational methods were found to be accurate for detecting MSI, with MANTIS demonstrating the highest overall sensitivity (97.18%), specificity (99.68%) and accuracy (98.91%). MANTIS demonstrated superior performance to mSINGS and MSISensor in colorectal adenocarcinoma, gastric adenocarcinoma and pancreatic adenocarcinoma, and was noninferior in esophageal carcinoma and uterine carcinosarcoma. MSISensor performed slightly better in endometrial carcinoma. We additionally calculated the most predictive microsatellite loci for each tool with each cancer type. Each tool was then evaluated using its best 10 loci, 20, 30, 40, 50, 100, 250, 500, 1000, and the full set of 2539 microsatellite loci. We found that, in general, MSISensor performance increases with more loci considered, and mSINGS performance increases with fewer loci. However, MANTIS performance remains consistent across the range of loci numbers tested, even with only 10 loci, and across cancer types. We also identified loci that were preferentially more unstable across different cancer types. Implications This study may facilitate clinical NGS-based testing for multiple cancer types that are not routinely tested for MSI, and identification of MSI-positive tumors can provide eligibility for novel immunotherapy trials and treatments. Our results indicate that MANTIS may be useful in conjunction with a small targeted NGS panel, for identifying MSI in tumors that are sequenced for other purposes, and in a variety of cancer types. ItemOptimization of a Protocol for Visualizing Vascular and Cellular Pore Networks in Human Bone Using Multiphoton Confocal Microscopy(2017-03) Cole, Mary; Stout, SamuelBiological anthropologists measure changes in bone mass to make inferences about patterns of physical activity in the past. Bone is resorbed in response to low strain, and added in response to high strain. By measuring the typical amount and distribution of bone mass in a population, anthropologists can approximate how different bones were typically bent. They further infer physical behaviors that could have caused this bending pattern in the past population, commonly including subsistence, mobility, terrain, type of transportation, and tool use. About 70% of age-related bone loss in appendicular bones occurs in the cortical “wall” of bone. This is mostly due to the formation of vascular pores within the cortex, a factor not typically considered in analysis of bone mass. If anthropologists knew how mechanical strain changes affected the formation and structure of pore systems, they could use pore structures to infer trends in physical behavior too subtle to affect overall bone shape. Vascular pores also concentrate stress, such that microscopic damage initiates and spreads within pore systems, leading to bone fracture. Understanding how vascular pore systems enlarge could help clinical researchers to regulate pore-producing cellular processes in pathological bone loss such as osteoporosis. The relationship between mechanical strain and three-dimensional pore structure is poorly understood due to historical reliance on two-dimensional imaging methods. Pore numbers and sizes are distorted in two-dimensional cross-section by frequent splitting and merging of pore systems. Theoretically, vascular pores should be formed to help remove bone under low strains. Yet two-dimensional methods have produced many contradictory inferences about the relationship of pore number and orientation to mechanical demand. A separate cellular (lacunar-canalicular) pore network houses osteocyte cells, which trigger bone formation or resorption in response to mechanical strain changes or microdamage. Cellular pores should theoretically predominate in regions under high strain, where the cells are needed to detect damage. Yet two-dimensional methods can only count the number of these tiny lacunae and have not produced consistent associations with mechanical demand. We sought to optimize a three-dimensional imaging protocol for visualizing vascular and cellular pore networks in human bone. Confocal laser scanning microscopy (CLSM) is an emerging method for three-dimensional imaging of bone tissue, with higher resolution than more traditional micro-CT. Multiphoton CLSM uses two photons of infrared light to excite a fluorescent stain in a bone structure at a precise >1 µm diameter location and depth. Successive depths are stacked into a three-dimensional image. Current methods of staining human bone porosity for CLSM imaging use decalcification that can introduce histological defects, or require perfusion of a stain during life, or stain non-pore features. Ciani et al. (2009) developed a staining protocol for rats and mice, using fluorescein isothiocyanate isomer I (FITC) at 1% in 100% ethanol to exclusively stain vascular and cellular pores. However, rats and mice lack the large vascular pore systems seen in humans. We tested this protocol for visualizing vascular and cellular pore networks in human bone. Ten cross-sections approximately 500 to 600 µm in thickness were cut from the midshaft of a fresh cadaveric human rib. Each cross-section was placed in a 15 mL volume of freshly prepared 4% formaldehyde and fixed for 24 hours at room temperature under gentle rotation. Cross-sections were dehydrated in ascending grade ethanol (75%, 95%, and 100% for 5 minutes each). FITC was diluted in 100% ethanol at concentrations of 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.2%, and 0.1%. Each 10 mL solution was gently rotated for one hour and then filtered. Each cross-section was placed in a different concentration of solution for four hours under gentle rotation. Each cross-section was then rinsed in 15 mL of 100% ethanol under gentle rotation for 30 minutes, and then air dried. Small regions (508.93 µm x 508.93 µm) were imaged using an Olympus FV1000 MPE Multiphoton Laser Scanning Confocal microscope with N.A. 1.05, 25x water immersion objective, 800 nm laser excitation wavelength, resolution 1024 x 1024 pixels, step size 0.63 µm, and 2x Kalman averaging. Stain concentrations above 0.5% FITC could clearly resolve vascular and cellular pore structures approximately 100 µm deep into the sample (1% = 150.81 µm, 0.9% = 104.26 µm, 0.8% = 122.32 µm, 0.7% = 129.97 µm, 0.6% = 142.65 µm). As stain concentration fell below 0.5%, depth of penetration dropped off sharply (0.5% = 76.86 µm, 0.4% = 66.15 µm, 0.3% = 76.23 µm, 0.2% = 59.04 µm, 0.1% = 59.85 µm). As concentration decreased from 1% FITC, pore structures also became more variable in brightness at a given depth in the sample. The high voltage and offset values required to visualize the smaller cellular pores sacrificed resolution at the boundaries of the vascular pores, which were much brighter due to greater stain absorption. ItemThe Buzz behind "the Buzz" Matters: Energetic and Tense Arousal as Separate Predictors for Word of Mouth(2017-03) Teeny, Jacob; Deng, Xiaoyan; Unnava, RaoConsumer research on what motivates people to engage in word of mouth (WOM) is one of the fastest growing areas of focus because of WOM’s remarkable impact on a company’s success (Berger, 2014). In the present research, we examine a fundamental antecedent to WOM: the physiological arousal elicited by the consumer purchase/experience. Although previous research has also examined this relationship, it has failed to make the critical distinction between two types of arousal, energetic and tense. Across four studies, this research provides evidence of the discriminant predictive value of these arousals as well as the separate motivations that each one elicits. That is, this research provides convergent evidence that the amount of energetic (tense) arousal elicited by a positive (negative) consumer experience predicts the a consumer’s willingness to engage in positive (negative) word of mouth, a behavior that is motivated to increase (decrease) one’s extant energetic (tense) arousal. ItemBiobehavioral Intervention Improves Dietary Patterns and Biomarkers of Carotenoid and Fatty Acid Intakes in Overweight Cancer Survivors(2017-03) Hill, Emily B.; Spees, Colleen K.Cancer survivors are at risk for suboptimal nutrition due to therapy, inadequate dietary patterns, and susceptibility to unproven dietary advice. Effective biobehavioral interventions aimed at increasing adherence to evidence-based survivorship recommendations are key in reducing cancer recurrence, comorbidities, and all-cause mortality. Data from a six-month phase II non-randomized trial were analyzed to determine pre- to post- changes in: (1) dietary patterns; (2) skin and plasma carotenoids; and (3) red blood cell fatty acid (RBC FA) composition. Overweight cancer survivors (N=29) were provided weekly produce harvesting, semi-monthly group education, remote motivational interviewing, and access to a secure web portal. Data were collected at baseline and post-intervention. Dietary patterns were assessed via 30-day food frequency questionnaires (FFQs) and Healthy Eating Index 2010 (HEI-2010) scores. Skin carotenoids were measured by resonance Raman spectroscopy, plasma carotenoids by high performance liquid chromatography, and RBC FAs by gas chromatography. Increases were documented in HEI-2010 total diet (p=0.006), total fruit (p=0.003), and fatty acids (p=0.007) scores. HEI-2010 scores for total vegetables also trended positively (p=0.054). As assessed by FFQ, survivors increased total dietary intakes of carotenoids by 66% (p<0.001) including increased individual intakes of all five carotenoids analyzed. Mean total dietary fat intakes decreased by 12.37 g (p=0.010), with survivors also decreasing intakes of saturated, unsaturated, and trans fats. Plasma concentrations of total carotenoids increased by 35% (p<0.001), as did as did plasma alpha-carotene, beta-carotene, and lycopene (p<0.001, p<0.001, p=0.017, respectively). Total skin carotenoids increased (p=0.015) and were highly correlated with total plasma carotenoids (r=0.728, p<0.001). Despite changes in dietary intakes of FAs, RBC FA composition was largely unchanged. However, relative abundance of omega-3 FAs decreased by 6% as compared to baseline (p=0.001). Promising results warrant larger randomized controlled trials to establish efficacy. ItemCharacterization of Structural and Mechanical Properties of Fat Crystallized Under High Pressure(ACS Publications, 2017-03) Zulkurnain, Musfirah; Balasubramaniam, V.M. Bala; Maleky, FarnazPressure is a thermodynamic parameter that can accelerate lipid crystallization. However, there is still limited understanding on how pressure can be used to modify lipid crystalline network and ultimately its functionality for food texture applications. The objective of this study was to characterize structural and mechanical properties of a fat model crystallized under different high pressure processing conditions. A fat model consists of fully hydrogenated soybean fat and soybean oil (3:7 ratio) was crystallized under pressures (100-600 MPa) at maximum temperature under pressure of 80 ºC using a laboratory scale high pressure unit. The samples were melted, allowed to reach pre-determined initial temperature, pressurized to 80 ºC at the targeted pressure and cooled under isobaric condition at 30 ºC for 10 min. The crystallized samples were characterized using X-ray diffraction, small angle X-ray scattering, polarized light microscopy, and rheometer. Three groups of crystal morphologies were observed. At low pressure levels, a mixture of large and small microstructures (Group I) crystallized during isobaric cooling led to in low storage modulus, G’ (0.74 x 103 - 1.16 x 103 Pa). Above 300 MPa, high density of small microstructures (Group II) crystallized during adiabatic compression substantially increased G’ (1.74 x 103 - 1.84 x 103 Pa). The presence of smaller nanostructures of β crystal was documented in all samples crystallized under high pressure from the melt compared to a mixture of metastable β’ and β crystals in control samples and crystallized at atmospheric condition prior to pressurization. In conclusion, high pressure treatments improve texture properties of fat by modifying structural properties of the fat crystal network as affected by nucleation rate. ItemWhat’s Your Potential? The Influence of Joint Kinematics on a Muscle’s Ability to Contribute to the Sit-to-Stand Transfer(2017-03) Schloemer, Sarah; Siston, RobertInduced Acceleration Analysis (IAA) estimates how muscles facilitate movement by supporting the center of mass (COM) against the force of gravity and contributing to the progression of the COM in the direction of movement. Prior IAA studies provide a baseline of how muscles facilitate activities of daily living; however, the underlying elements of IAA describing the mechanisms by which muscle forces contribute to movement are complex and not fully understood. While muscle force greatly impacts IAA, kinematics influence these forces, as well as muscle moment arms and contributions to movement. This kinematic component of IAA is important, as it has been suggested that for patients to utilize strength gains from rehabilitation, kinematic retraining may be necessary to reprogram the motor pattern. However, existing methods for estimating muscle contributions to movement require extensive time and experimental resources, making patient specific-IAA impractical in a clinical setting. Therefore, the purpose of this study is to develop an efficient method for determining how changes to lower extremity joint kinematics affect the potential of individual muscles to contribute to support during the sit-to-stand (STS) transfer. A 4 link 2-dimensional sagittal plane model with 4 rotational joints was used to assess the effect of changes to kinematics on the function of 23 lower extremity muscles during each task. Kinematics were varied at each joint throughout ranges that are commonly observed during the momentum transfer phase of the STS. For each kinematic position, a muscle’s potential to contribute to support was estimated. Our new method predicted that positioning the feet more posteriorly (under the COM) during the STS increases the potential of the gluteus maximus, biceps femoris long head, vasti, and gastrocnemius to contribute to support. Additionally, a more anteriorly tilted pelvis increased the potential of the quadriceps muscles, but decreased the potential of posterior muscles. These results were verified by muscle potentials calculated using traditional experimental and simulation methods. This research represents the first effort to systematically evaluate how changes in joint kinematics affect muscle contributions to acceleration. The methods presented in this study demonstrate a mechanism for determining the cause of abnormal movement and for identifying potential rehabilitation techniques that leverage both kinematics and muscle strength to improve mobility. ItemComputational Analysis of Solid Tumor Oxygenation Facilitated by Polymerized Human Hemoglobins(2017-03) Belcher, Donald; Palmer, AndreIn the U.S., over 60% of patients diagnosed with stage III and IV solid tumors will undergo chemo- and/or radio-therapy during the course of their treatment. A major constraint in chemo-and radio-therapeutic cancer treatment is inadequate oxygenation of solid tumors. Hypoxic conditions in the tumor microenvironment induce quiescence in cancer cells, which reduces the effectiveness of cancer therapies. Consequently, alleviating hypoxia in solid tumors is considered a promising target for improving the efficacy of anti-cancer therapeutics. Polymerized human hemoglobin (PolyhHb) can be transfused to increase solid tumor oxygenation and improve the efficacy of anti-cancer therapeutics. In this study, we analyzed the biophysical properties of synthesized PolyhHbs with low and high oxygen (O2) affinity. Transfusion of PolyhHbs may alter microvascular hemodynamics, which could improve O2 transport into the tumor. We hypothesize that in silico models of the tumor microenvironment may be used to guide the dosage and type of PolyhHb as a function of tumor O2 consumption and O2 tension. yield low and high affinity PolyhHbs respectively, we first polymerized tense (T) and relaxed (R) state PolyhHb via glutaraldehyde as described previously. The diameter, cooperativity, O2 tension at 50% saturation (p50), and rapid offloading kinetics were each analyzed. The resulting biophysical parameters were used to populate a finite element multiphysics arteriole model in COMSOL. Here, blood fluid flow was modeled with the Quemeda constitutive law and the radius of the red blood cell rich core was approximated from experimental data. Starling flow was modeled with Brinkman’s equation for flow through the blood vessel wall and tissue space. The O2 equilibrium for all hemoglobin species was handled with the Hill Equation. In the simulation, we modeled PolyhHb delivery as an exchange transfusion. The inlet partial pressure of dissolved O2 (pO2,in) was varied from normal conditions (90 mm Hg) to hypoxic conditions (1 mm Hg). In addition, diameter of the arteriole, maximum rate of O2 consumption, and thickness of the tissue space were each varied. The fluid velocity profiles, apparent viscosity, wall shear stress, O2 distributions, O2 flux, and model sensitivity were each analyzed. We found that increasing the percent exchange transfusion of PolyhHb may decrease the apparent viscosity of blood in the arteriole. In addition, we found that PolyhHb transfusion decreased the wall shear stress at large diameters (> 20 μm) but increases wall shear stress for small diameters (< 10 μm). Both T- and R-state PolyhHb exchange transfusion may lead to elevated O2 delivery at low pO2,in. In addition, R-state PolyhHb exchange transfusion may be more effective than T-state PolyhHb at similar exchange volumes. The pO2 pressure drop per unit length signifies that while the O2 flux across the vessel wall is similar at high pO2,in, there is significantly more O2 lost at high pO2s but more O2 retained at low pO2s. At low pO2,in the radius of the arteriole had the greatest effect on O2 delivery. At high pO2,in the maximum rate of O2 consumption had the greatest effect on O2 delivery. Interestingly, R-state PolyhHb is much less sensitive to arteriole radius than T-state PolyhHb under hypoxic conditions ( < 10 mm Hg). Decreases in the apparent viscosity resulting from PolyhHb exchange transfusion may result in significant changes in flow distributions throughout the tumor microcirculatory network. The difference in wall shear stress implies that PolyhHb may have a more significant effect on capillary beds. The increased O2 flux and decreased pO2 drop per unit length indicates that both PolyhHbs are suited to deliver O2 under hypoxic conditions. However, the hypoxic volumes estimated here are inconsistent with the literature. This indicates that the assumptions in the Krogh tissue cylinder model may not adequately describe the tumor microenvironment. The system was more sensitive to changes in the tumor microenvironment than to the PolyhHb which indicates that a more descriptive model should be developed to match results from previous studies. ItemIdentification of NRAS isoform 2 over-expression as a novel mechanism facilitating BRAF inhibitor resistance in malignant melanoma(2017-03) Duggan, Megan; Carson, William, IIIActivating mutations in BRAF are found in 50% of melanomas and although treatment with BRAF inhibitors (BRAFi) is effective, resistance often develops. We now show that recently discovered NRAS isoform-2 is up-regulated in the setting of BRAF inhibitor resistance in melanoma, in both cell lines and patient tumor tissues. When isoform-2 was over-expressed in BRAF mutant melanoma cell lines, melanoma cell proliferation and in vivo tumor growth were significantly increased in the presence of BRAFi treatment. shRNA-mediated knockdown of isoform-2 in BRAFi resistant cells restored sensitivity to BRAFi compared to controls. Signaling analysis indicated decreased mitogen-activated protein kinase (MAPK) pathway signaling and increased phosphoinositol-3-kinase (PI3K) pathway signaling in isoform- 2 overexpressing cells compared to isoform-1 overexpressing cells. Immunoprecipitation of isoform-2 validated a binding affinity of this isoform to both PI3K and BRAF/RAF1. The addition of an AKT inhibitor to BRAFi treatment resulted in a partial restoration of BRAFi sensitivity in cells expressing high levels of isoform-2. NRAS isoform-2 may contribute to resistance to BRAFi by facilitating PI3K pathway activation.