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Bhattacharjee, AnukanaCharacterization of the DNA Binding Properties of CST (CTC1-STN1-TEN1) And Their Importance for CST Function in Telomeric as well as Genome-wide Replication
PhD, University of Cincinnati, 2017, Medicine: Molecular Genetics, Biochemistry, & Microbiology
Telomeres are the protective DNA-protein complexes at the ends of chromosomes. Mammalian telomeres are composed of double-stranded DNA with a repetitive sequence (TTAGGG) followed by a short single-stranded overhang. The DNA is bound by a series of proteins that prevent chromosome fusions and protect the DNA terminus from being sensed as damage. These telomere proteins also aid in telomere replication. Shelterin, the primary telomere protein complex, binds to both the double- and single-strand regions of the telomere. Shelterin is important for protecting telomeres from being sensed as damage. It also brings in telomerase for telomere extension. The other major telomere protein complex is CST (CTC1-STN1-TEN1). CST functions in telomere replication first by aiding passage of the replication machinery through the telomere duplex and then enabling fill-in synthesis of the telomeric C-strand following telomerase action. CST also has genome-wide roles in the resolution of replication stress. CST resembles Replication Protein A (RPA) in that it binds ssDNA and STN1 and TEN1 are structurally similar to RPA2 and RPA3. Here we address CST mechanism by using STN1 OB-fold mutant (STN1-OBM) to examine the relationship between DNA binding and CST function. In vivo, STN1-OBM affects resolution of endogenous replication stress and telomere duplex replication but telomeric C-strand fill-in and new origin firing after exogenous replication stress are unaffected. In vitro binding studies show that STN1 directly engages both short and long ssDNA, however STN1-OBM preferentially destabilizes binding to short substrates. CST is expected to engage DNA substrates of varied length and structure as it acts to resolve different replication problems. Since STN1-OBM will alter CST binding to only some of these substrates, the mutant should affect resolution of only a subset of replication problems, as was observed in the STN1-OBM cells. The in vitro studies also provide insight into CST binding mechanism. Like RPA, CST likely contacts DNA via multiple OB folds. However, the importance of STN1 for binding short substrates indicates differences in the architecture of CST and RPA DNA-protein complexes. Although the architecture of DNA binding differ for RPA and CST, their overall structural similarity motivated us to use RPA as a model to investigate DNA binding properties underlying CST function. RPA binds to ssDNA with high affinity, yet individual OB-folds can micro-dissociate from the DNA promoting sliding of RPA on the DNA, melting of dsDNA or secondary structures, recruitment of interaction partners. By using single molecule fluorescence assays, we show that CST cannot melt dsDNA but it can resolve secondary structures such as G4. The efficiency of G4 unfolding by CST, and its known abundance in G-rich regions genome-wide could explain its role in resolution of replication stress. Our work has also shown that CST can recognize ss-dsDNA junctions which start to explain the incremental nature of the telomeric C-strand fill-in reaction after G-strand extension by telomerase. Overall, our work provides insight into the mechanism by which CST might resolve replication issues at the telomere and genome wide.

Committee:

Carolyn Price, Ph.D. (Committee Chair); Iain Cartwright, Ph.D. (Committee Member); Rhett Kovall, Ph.D. (Committee Member); Anil Menon, Ph.D. (Committee Member); Satoshi Namekawa, Ph.D. (Committee Member)

Subjects:

Biogeochemistry

Keywords:

Telomere;Replication;CTC1 STN1 TEN1;DNA binding;OB fold

Terway, SaakshiPreserving the Intangible Heritage: Neemrana Kala Kendra – A Crafts and Tourism Complex
MARCH, University of Cincinnati, 2017, Design, Architecture, Art and Planning: Architecture
With rapid modernization and globalization, as the world is coming closer together, it gets even harder to preserve the unique history and culture of each region. By providing a `Kala Kendra’ for the artists and craftsmen of Neemrana Village, this project will look in depth at the problem of gradual erosion of the region’s intangible heritage. By analyzing the present-day challenges encountered by regional identity around the world, this project will look into the elements that form the heritage of Neemrana Village, as well as the persistent problems within the village that are causing the extinction of these elements. To preserve the culture of Neemrana, this thesis looks at the past attempts made around the world to address similar issues. Also, by evaluating the traditional and vernacular architecture of the village, as well as the arts and crafts of Neemrana, this project will use its essence to propose an adequate solution to preserve its heritage without causing hindrance to the village’s growth and development. Through blending methods of education and exhibition, a better typology will arise to more effectively serve the community of Neemrana Village. Such a project requires a revised understanding of the art and architecture and their maker’s process, and context. This new model will return art to the public to validate its importance as a process and not just the final product.

Committee:

Elizabeth Riorden|, M.Arch. (Committee Chair); Aarati Kanekar, Ph.D. (Committee Member)

Subjects:

Architecture

Keywords:

heritage;culture;artists;craftsmen;Neemrana Village;Kala Kendra

Romero, VeronicaComputational Measurement of Social Communication Dynamics in Children with Autism Spectrum Disorder
PhD, University of Cincinnati, 2017, Arts and Sciences: Psychology
Adolescents with Autism Spectrum Disorder (ASD) exhibit impairments in social interactions that last throughout their lives and at the core of these impairments are social communication deficits. An ever growing body of literature has shown that language and interpersonal motor coordination are intertwined and both very important to achieve successful social interactions. Understanding where this relationship breaks down in children with ASD has the potential to provide great insights into the social communication deficits observed in the disorder. The current project used a standard clinical assessment tool of social communication (ADOS-2) to explore and determine the time-evolving semantics present in verbal communications, how these measures were related to frequently-used qualitative measures and how the verbal and nonverbal components of communication were related to each other in children with and without ASD. More specifically, the project: (1) quantified verbal conversational dynamics through the use of Discursis and categorical recurrence quantification analysis; (2) quantified the nonverbal aspects of conversational exchanges (by looking at bodily movement dynamics) using pixel change time-series extraction and continuous recurrence quantification analysis; and finally (3) determined the relationship between verbal and nonverbal aspects exhibited during the conversational exchanges and traditional measures used to quantify ASD severity through the use of correlational methods. Experiment 1 consisted of children between the ages of 6 and 10 years, all previously diagnosed with ASD to test the differences (or lack thereof) of behaviors exhibited by the children in two kinds of conversations (free flow vs. structured) given that children with ASD are seen as having difficulties adjusting behavior to suit various contexts. Experiment 2 had older participants (between 10-15 years of age) as well as typically developing children who were recruited to complete the ADOS-2 and serve as an age-matched control group, so that the expected social behaviors could be compared to those exhibited by children previously diagnosed with ASD. Differences were found between some verbal behaviors exhibited by children with and without ASD. These differences were not only confined to the pragmatics of language, but also to semantic and lexical components. Nonverbal behaviors exhibited during conversations involving children with ASD differed from those involving typically developing child. More importantly, both verbal and nonverbal dynamical measures were related to the traditional measures used to diagnose ASD and measure symptom severity. As a result, the dynamical measures explored here have the potential to improve diagnostic and therapeutic interventions in the future. However, some of the results observed were inconclusive due to low power. A larger sample size and a greater variety of test administrators and age groups should be explored in the future.

Committee:

Michael Richardson, Ph.D. (Committee Chair); Amie Duncan (Committee Member); Paula Fitzpatrick, Ph.D. (Committee Member); Michael Riley, Ph.D. (Committee Member); Paula Silva, Ph.D. (Committee Member)

Subjects:

Psychology

Keywords:

Autism Spectrum Disorder;Social communication dynamics;Discursis;Recurrence quantification analysis;ADOS-2

Xie, JiajingAn Architectural Rendition of Shadow Puppetry: a Translation from Shadow Puppetry to Architecture Through Movement
MARCH, University of Cincinnati, 2017, Design, Architecture, Art and Planning: Architecture
Shadow puppetry is an ancient performing art. It uses silhouette figures that are manipulated to create the illusion of moving images in front of an illuminated screen. The characteristics of the movement in shadow puppetry include the rhythm of disappearing and reappearing; blurriness and darkness of shadows, which create dramatic effects. The analysis of movement in shadow puppetry provides an analogy from which design principles can be drawn. Through the exploration of the choreography of movement and circulation as well as a variety of translucent materials, the thesis offers an enriching experience of light, shadow, space and time. The design of a visitor resort for a bamboo park in a Chinese country, and a center for the exploration and performance of shadow puppetry, will be the vehicle for the exploration of the movement of shadows. The design uses specific devices analogous to shadow puppetry. Through the movement of shadows, the dramatic architectural promenade inspires a curiosity and leads the occupants to question their surroundings, just like watching a shadow puppetry show.

Committee:

Aarati Kanekar, Ph.D. (Committee Chair); Christoph Klemmt, A.A. Dipl. (Committee Member)

Subjects:

Architecture

Keywords:

shadow puppetry;movement;experience;space and time;light and shadow;architecture

Chávez Wulsin, AynaraGlucocorticoid Mechanisms of Epileptogenesis and Comorbid Emotional Dysregulation
PhD, University of Cincinnati, 2017, Medicine: Neuroscience/Medical Science Scholars Interdisciplinary
Dysregulation of the hypothalamo-pituitary-adrenocortical (HPA) axis is common in temporal lobe epilepsy. It is characterized by excess glucocorticoid signaling, a process that is similar to what is seen in a subset of patients with major depression. Although activation of the glucocorticoid receptor (GR) is essential for survival, exposure to excess glucocorticoids can lead to disruption of key neuronal circuits, particularly in the hippocampus. This disruption may compromise physiological and behavioral adaptations to stress. It is well documented that chronic exposure to excess corticosterone in rodents may be linked to the development of depressive and anxiety-like phenotypes. These effects can be blocked by treatment with GR antagonists. In addition to modulating behavior, glucocorticoids have been shown to exhibit pro-convulsant effects in several animal models of epilepsy. Thus hyperactivity of the HPA axis may be a common pathological mechanism that may help explain the high incidence of psychopathologies in epilepsy. The underlying mechanisms and long-term consequences of HPA axis hyperactivity in epilepsy are currently unknown. Exposure to elevated glucocorticoids may be particularly deleterious in epilepsy, as it may exacerbate hippocampal pathologies, increase brain excitability (pro-convulsant) and raise susceptibility for the development of depressive and anxiety-like phenotypes. These data support a role for GR in epileptogenesis. The studies presented in this dissertation aimed at testing our underlying hypothesis, that chronic hyper-activation of GR occurs early in the disease and contributes to the comorbid development of epilepsy and depression/anxiety-like phenotypes. In chapter 2, I used the pilocarpine induced status epilepticus (SE) mouse model of TLE to characterize changes in stress-regulatory circuitry and emotional behavior associated with TLE. These studies demonstrate that SE results in hypersecretion of baseline glucocorticoids. This elevation persists through the chronic period of epilepsy and is accompanied by increased glucocorticoid secretion in response to acute stress. Importantly, epilepsy generates profound impairments in the recruitment of forebrain circuits that are key in regulating stress inhibition and emotional reactivity. In chapter 3 I utilized the glucocorticoid antagonist RU486 to block glucocorticoid receptor signaling in the hours following SE. Glucocorticoid blockade successfully normalizes corticosterone secretion and reduces hippocampal pathologies associated with epileptogenesis, including reduction of mossy cell loss and decreased ectopic placement of post-SE generated cells. These findings support a role for GR in epileptogenesis. In chapter 4 we utilized a newly-develop glucocorticoid receptor modulator C108297 to test whether modulation rather than complete blockade has beneficial potential in epileptogenesis. Results from this study demonstrate a disease modifying effect of C108297 in the hippocampus and promising reduction in seizure severity. The studies conducted as a part of this dissertation research may prove critical for understanding mechanisms of epileptogensis, and suggest the potential of GR as a therapeutic target for the treatment of epilepsy and its comorbidities.

Committee:

Matia Solomon, Ph.D. (Committee Chair); Steve Danzer, Ph.D. (Committee Member); James Herman, Ph.D. (Committee Member); Louis Muglia, M.D. (Committee Member); Michael Privitera, M.D. (Committee Member)

Subjects:

Neurology

Keywords:

glucocorticoids;temporal lobe epilepsy;status epilepticus;C108297;Mifepristone;mice

Chaton, Catherine TMetal Binding Specificity and N-terminal Function of the Staphylococcal Biofilm Protein Aap
PhD, University of Cincinnati, 2017, Medicine: Molecular Genetics, Biochemistry, & Microbiology
Staphylococcus epidermidis, a typical human commensal bacterium, is a serious contributor to hospital-acquired infections (HAI) when accidently introduced to surgical sites and in the immunocompromised. The majority of S. epidermidis HAIs involve the formation of macrocellular structures called biofilms. These specialized surface-adherent colonies confer resistance to antibiotics and shield the bacteria from recognition by the host immune response. The accumulation-associated protein (Aap) is a multifunctional cell-wall protein which mediates intercellular adhesion through metal-dependent self-assembly. In addition, it contains elements for the recognition and attachment to host-cell surface features. The N-terminus of Aap begins with a sequence of short 16-residue `A-repeats’ which are followed by a globular lectin domain. The C-terminal half contains 5-17 tandem copies of B-repeat domains, which, once proteolytically processed from the N-terminal domains, are capable of forming anti-parallel, intertwined protein bridges. This assembly requires coordination to divalent cations through each B-repeat’s G5 domain. Previously solved crystal structures of a minimal B-repeat construct (Brpt1.5) have characterized a zinc-dependent dimer. This work describes novel research into the specificity and selectivity of the metal-coordination and N-terminal regulation of Aap by the A-repeats. Cu2+ has been found to be capable of inducing assembly using the same coordinating residues as Zn2+. Longer constructs of B-repeat (Brpt5.5) with an increased number of G5 domains require lower metal concentrations for assembly. The boundary between monomer to dimer transition also narrows, suggesting cooperativity between the G5 domains. By responding to increasing local concentrations of Zn2+ and Cu2+, divalent metals both implicated in host immunity, Aap can act as an environmental sensor. However, Aap is only capable of assembly once the A-repeats have been proteolytically processed from the tandem B superdomain. Interactions between the A-repeats and the unique sequence of the first G5 domain act to block B-repeat assembly until processing. The N-terminal residues of the A-repeats fold back in a hairpin structure, both regulating Aap assembly and positioning the globular lectin domain in an optimal orientation for host-cell attachment. While the specific targets have not yet been identified, initial structural analysis indicates it shares many characteristics with other lectin domains found in staphylococcal virulence factors. Better understanding of Aap’s N-terminal regulation and domain function reveals novel targets for the development of monoclonal antibody and small-molecule inhibitor based therapeutics.

Committee:

Andrew Herr, PhD (Committee Chair); George Deepe, PhD (Committee Member); Rhett Kovall, PhD (Committee Member); William Miller, PhD (Committee Member); George Stan, PhD (Committee Member)

Subjects:

Biophysics; Medicine

Keywords:

accumulation associated protein;Staphylococcus epidermidis;biofilm;hospital-acquired infection;macromolecular assembly;analytical ultracentrifugation

Bhave, Chittatosh CA Computational Study of the Heat Transfer Characteristics of Offset-Strip Fin Cores
MS, University of Cincinnati, 2017, Engineering and Applied Science: Mechanical Engineering
Enhanced extended surfaces such as offset-strip fins (OSF) are effective in increasing the area density as well as altering the convective flow behavior to provide higher heat transfer coefficient in compact heat exchangers. This is achieved by periodic disruption and reattachment of the new thin boundary layer on the fin plate of each offset-strip fin module. The heat transfer characteristics and the flow physics inside the OSF cores is revisited in this computational analysis for laminar air flows (Pr = 0.7) and their performance is compared with plain fins. A simplified model of thin fins is used to study the effect of fin geometric parameters, viz., offset-fin length l, fin separation s and fin thickness t. The parametric variation is restricted to the practical range of fin density (8 fpi to 22.6 fpi) and low blockage ratio to the flow (<20%) while systematically increasing the offset-fin length (1 < l/s < 35). The results show that the short offset-fin length provides higher heat transfer enhancement compared to the plain rectangular fins, while the fin thickness and fin separation show negligible improvement in heat transfer rate for a constant offset-fin length ratio (l/s). The offset-fin effect diminishes as Reynolds number decreases or the offset-fin length becomes very large, as the OSF performance asymptotically approaches towards that of a plain rectangular fin. The OSF cores are shown to reduce the heat transfer surface area by 30% - 50% while keeping a constant pressure drop as that for a plain rectangular fin. A practical case with short offset-fin length (~ 3mm) having a squarer cross-section fins (s/h > 0.5) with intermediate to low fin density (8 fpi to 12 fpi) provides smaller pressure drop gradients as well as larger heat transfer enhancement capacity for a constant heat duty application.

Committee:

Milind Jog, Ph.D. (Committee Chair); Je-Hyeong Bahk, Ph.D. (Committee Member); Raj Manglik, Ph.D. (Committee Member)

Subjects:

Mechanics

Keywords:

Heat Transfer;Offset-Strip Fin

Riffle, StephenMulticellular Tumor Spheroids as a Model to Study Tumor Cell Adaptations within a Hypoxic Environment
PhD, University of Cincinnati, 2017, Medicine: Molecular and Developmental Biology
Hypoxia is a common feature in solid tumors which facilitates the development of therapeutically resistant and aggressive tumor phenotypes. As oxygen levels decrease, cellular metabolism and energy production becomes impaired and the potential for catastrophic DNA damage increases. To prevent cell death, tumor cells undergo several adaptations which prevent depletion of nutrients, minimize DNA damage, and re-acquire blood flow. The mechanisms behind tumor cell survival during hypoxia are poorly understood. Tumor neovascularization is a critical step in facilitating continued tumor growth. Accordingly anti- angiogenic therapy has shown significant success in preventing progression free survival however increased tumor aggression and alternative neovascularization methods result in decreased overall patient survival. Vasculogenic mimicry is one such proposed method of alternative neovascularization wherein tumor cells transdifferentiate and form de novo vascular structures. Although there are indications that this process is driven by hypoxia and is linked to aggressive tumor phenotypes, there is little known about the signaling pathways inducing such an adaptation. Evidence from in vitro studies suggest that activation of DNA damage repair proteins in proliferating hypoxic cells is critical for sustained proliferation and cell viability thus implicating repair proteins as potential therapeutic targets. In vivo studies demonstrating a correlation between hypoxia and the formation of γ-H2AX further support this potential. The evaluation of such therapeutic targets is limited by the inability of in vitro monolayer culture models to recreate therapeutically relevant aspects of a 3D in vivo tumor. Multicellular tumor spheroids (MCTS) represent a 3D in vitro culture model in which tumor cell adaptations to the hypoxic tumor microenvironment are recreated. These include the accumulation of metabolic waste, appearance of nutrient gradients, and development of proliferative heterogeneity. MCTS have been used extensively to characterize radiation resistance in a hypoxic environment.We set out to describe the relationship between proliferation, hypoxia, DNA damage repair, and vasculogenic mimicry using the MCTS model. Using MCTS, we demonstrate for the first time the activation of DNA damage repair proteins in hypoxic proliferating cells residing within the MCTS core and further show the ability to study the efficacy of therapeutics targeting this cell population. Although metabolic adaptations and DNA damage repair protein activation are observed in this model, MCTS formed using the liquid overlay method do not experience vasculogenic mimicry. The results presented herein advances the field of tumor biology by validating the utility of MCTS as a model system in which clinically relevant features of a tumor can be recreated and studied. Furthermore our studies identify the Eyes Absent tyrosine phosphatase as a therapeutic target whose activity regulates DNA damage repair under both normoxic and hypoxic conditions and may be involved in vasculogenic mimicry.

Committee:

Rashmi Hegde, Ph.D. (Committee Chair); Zelia Correa, M.D. Ph.D. (Committee Member); Richard Lang, Ph.D. (Committee Member); Qing Richard Lu, Ph.D. (Committee Member); Kathryn Wikenheiser-Brokamp, M.D. Ph.D. (Committee Member)

Subjects:

Cellular Biology

Keywords:

Multicellular Tumor Spheroids;DNA damage repair;Eyes Absent;Hypoxia;Cancer;Ewing Sarcoma

Liu, ZhouyangHeterogeneous Catalytic Elemental Mercury Oxidation in Coal Combustion Flue Gas
PhD, University of Cincinnati, 2017, Engineering and Applied Science: Chemical Engineering
The new Mercury and Air Toxics Standards issued by US EPA require the reduction of mercury emissions from coal-fired power plants by 90% starting from 2016. Oxidizing elemental mercury using the HCl that exists in the flue gas or additional halogen and catalysts, followed by oxidized mercury capture in the wet Flue Gas Desulfurizer (FGD), is a viable option for mercury removal in coal-fired power plants. The aim of this study is to develop effective and reliable mercury oxidation catalysts, advance the mechanistic understandings of heterogeneous mercury oxidation, and obtain information on heterogeneous mercury oxidation kinetics. CuCl2 supported on ?-Al2O3 showed excellent Hg(0) oxidation performance and SO2 resistance at 140 °C. After extensive characterizations of the CuCl2/?-Al2O3 catalyst, the existence of multiple copper species was identified. It was found that CuCl2 forms inert copper aluminate on the surface of ?-Al2O3 at lower loadings. At higher loadings, CuCl2 exists in a highly dispersed amorphous form that is active for Hg(0) oxidation by working as a redox catalyst. The CuCl2/?-Al2O3 catalyst with high loadings has the potential to be used as a low temperature Hg(0) oxidation catalyst. RuO2 catalyst was found to be an excellent Hg(0) oxidation catalyst. When rutile TiO2 was used as the catalyst support, RuO2 formed well dispersed nano-layers due to the very similar crystal structures of RuO2 and rutile TiO2, giving higher Hg(0) oxidation activity over anatase TiO2 support. The RuO2/rutile TiO2 catalyst showed good Hg(0) oxidation performance under sub-bituminous and lignite coal simulated flue gas conditions with low concentration of HCl or HBr gas. It also showed excellent resistance to SO2. The RuO2/rutile TiO2 catalyst can be used at the tail end section of the SCR unit for Hg(0) oxidation. Linear combination fitting of the X-ray Absorption Near Edge Spectroscopy (XANES) was used to quantify oxidized mercury species over RuO2/TiO2 and SCR catalysts under different simulated flue gas conditions. In the absence of halogen gas, elemental mercury can react with sulfur that is contained in both the RuO2/TiO2 and SCR catalysts to form HgS and HgSO4. In the presence of HCl or HBr gas, HgCl2 or HgBr2 is the main oxidized mercury species. When both HCl and HBr gases are present, HgBr2 is the preferred oxidation product and no HgCl2 can be found. Other simulated flue gas components such as NO, NH3, SO2 and CO2 do not have significant effect on oxidized mercury speciation when halogen gas is present. Mechanistic and kinetic studies of the heterogeneous oxidation of Hg(0) by HCl gas over a RuO2/rutile TiO2 catalyst were conducted. The experimental evidence of HCl adsorption was obtained using in-situ Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS). Based on this result, a steady-state kinetic study was conducted to determine an intrinsic reaction kinetic expression for Hg(0) oxidation over the catalyst under HCl, NH3 and SO2 gases for the first time. The kinetic expression obtained could reasonably predict the Hg(0) oxidation performance under the competitive adsorption of NH3 and SO2 gases.

Committee:

Joo Youp Lee, Ph.D. (Committee Chair); Anastasios Angelopoulos, Ph.D. (Committee Member); William Connick, Ph.D. (Committee Member); Peter Panagiotis Smirniotis, Ph.D. (Committee Member)

Subjects:

Chemical Engineering

Keywords:

heterogeneous catalysis;mercury removal;kinetic;mechanism;characterization;ruthenium oxide

Ondja'a, BertinUniversity Social Responsibility: Achieving Human and Social Development in Cameroon
PhD, University of Cincinnati, 2017, Education, Criminal Justice, and Human Services: Educational Studies
As place-based institutions, higher education institutions (HEIs) have the intellectual capacity and resources, both private and public, to transform communities facing human and social development issues. As such, HEIs must revisit their role/contribution and recognize their social responsibility to remain relevant in today’s society. Indeed, social responsibility requires new community research and revitalization, job creation, teaching, and innovation. This study explores the role/contribution of Cameroonian HEIs in addressing human and social development issues through a qualitative case study of the University of Douala. More specifically, this study explored how the university advances development agendas through the use of interviews and a photovoice project, examining historical, social, and political events and practices that frame the role/contribution of HEIs in Cameroon. The findings suggest that HEIs are an important asset for the community and make significant educational, social, environmental, economic, and cultural contributions to the community. Specifically, the findings indicate the contribution of the University of Douala in the following areas: service, innovation, advocacy, leadership, and capacity building. Consequently, HEIs can help to advance human and social development. However, their contribution in these areas remains underutilized. Also, stakeholder engagement and lack of funding emerge as elements that downplay the contribution of the University of Douala in human and social development issues. Adaptive solutions for complex issues should consider the potential contribution of HEIs. This study concludes with recommendations and implications that aim to educate different stakeholders and practitioners on how HEIs can maximize their potential. En tant qu'institutions operant dans les territoires, les etablissements d'enseignement superieur possedent des capacites intellectuelles et materielles pouvant transformer les communautes confrontees aux problemes de developpement humain et social. En tant que tel, ils doivent regulierement actualiser leur engagement et mission envers la societe pour rester pertinent au regard d’un environnement instable et imprevisible. En tant que potentiel levier du developpement durable, ils doivent adopter la responsabilite sociale. En effet, la responsabilite sociale des universites (RSU) doit etre considerer comme etant un precurseur du reveil communautaire, creation d’emplois, developpement economique et durable, et innovation technologique. La presente etude explore l’apport des universites au developpement humain et social dans un contexte Camerounais. Une etude de cas qualitative realisee a l’Universite de Douala par le biais des entretiens et un projet photovoice et en tenant compte de l’environnement historique, social et politique dans lequel l’enseignement superieur s’est forge, cette etude demontre la capacite des universites a accompagner l’Etat dans ses multiples missions. Cependant, ces atouts restent largement sous-exploites. Dans le cas precis de l’Universite de Douala, le manque d’engouement des parties prenantes, l’organisation institutionnelle et l’absence de financement apparaissent comme etant des elements qui minimisent la contribution de l'Universite de Douala aux problemes de developpement humain et social dans son milieu. Projeter des solutions adaptees aux problemes complexes devrait tenir compte du potentielle des etablissements de l’enseignement superieur. Cette etude se termine par des prescriptions et des incidences qui visent a sensibiliser les agents de developpement sur la facon dont ces etablissements peuvent maximiser leur contribution au developpement humain et social.

Committee:

Constance Kendall Theado, Ph.D. (Committee Chair); Mary Brydon-Miller, Ph.D. (Committee Member); David Edelman, Ph.D. (Committee Member); Joseph Takougang, Ph.D. (Committee Member)

Subjects:

Higher Education

Keywords:

University Social Responsibility;Photovoice;Regional Development;University Engagement;Human and Social Development;Growth Pole

Nickum, Elisa AAnalysis of Regulated Drugs Using Chromatographic and Spectrophotometric Techniques Coupled with Spectroscopy An Orthogonal Approach to Protecting Public Health
PhD, University of Cincinnati, 2017, Arts and Sciences: Chemistry
A considerable number of dietary supplements suspected of containing phosphodiesterase-5 (PDE-5) inhibitors and substituted phenethylamines have been analyzed by the U.S. Food and Drug Administration. Often these samples are found to contain the active pharmaceutical ingredients (API) such as sildenafil or phentermine, and in many cases, products contain multiple PDE-5 inhibitors or substituted phenethylamines. In an analytical setting, it is important to confirm the presence of any API with two or more independent methods, and this requirement can often put undo strain on a laboratory. The development and use of methods that inherently contain two unique identification techniques is preferred, and the creation and validation of three of those methods is outlined here. First, direct deposit Fourier transform infrared detection and mass spectrometric detection (GC/FT-IR/MS) is used to identify PDE-5 inhibitors. Generally, GC/MS is not generally used for this category of drugs due to low volatility; PDE-5 inhibitors often co-elute and can produce non-specific electron ionization fragmentation patterns. In contrast, FT-IR has been proven to be more selective for identifying PDE-5 inhibitors, but is generally not as sensitive as spectrometric techniques. However, it has been shown that each technique can compensate for the other, which allows a wider range of usability. Using this combined technique can save time and resources while still delivering a high level of certainty in identification by providing results from two scientifically uncorrelated techniques. Multiple reference standards were utilized for method validation, including determination of linearity, dynamic range, and limit of detection. Second, a single HPLC-UV method has been developed for the determination of PDE-5 inhibitors and related analogs in pharmaceutical dosage forms and dietary supplement products. Using this protocol, 14 PDE-5 inhibitor compounds can be separated and determined in a single analysis. Multiple reference standards were utilized for method validation, including determination of linearity, dynamic range, injection precision, limits of detection and quantitation, accuracy and precision. It was also demonstrated that, in cases where a standard for a specific analog is not readily available, another reference standard can be used to approximate the level of analog present, based on similarities in their chemical structures and absorbance spectra. Third, an HPLC-UV method has been developed for the determination of substituted phenethylamines in pre-workout dietary supplements. The number of these products on the market has greatly increased in recent years, and the labeled ingredients did not seem to account for amazing energy and euphoria experienced by users. Using GC-MS analysis, methamphetamine-like compounds are often detected but can be difficult to identify; as standards are not always available for comparison. To characterize any new analog, it is necessary to separate it from the matrix using an acid-base extraction, followed by HPLC-UV fraction collection and characterization using HRAM-MS and nuclear magnetic resonance. Recently, these techniques were used to characterize N-ethyl-a-ethylphenethylamine in a powdered drink supplement. Using this HPLC-UV method, five substituted phenethylamines can be separated and determined in a single analysis. Multiple reference standards were utilized for method validation, including determination of linearity, dynamic range and injection precision.

Committee:

Peng Zhang, Ph.D. (Committee Chair); Anna Gudmundsdottir, Ph.D. (Committee Member); Laura Sagle, Ph.D. (Committee Member)

Subjects:

Chemistry

Keywords:

PDE 5 Inhibitor;GC MS;FT IR;HPLC UV;GC FT IR MS;Phenethylamine

Locke, KellieUnknown Encounters: Surrealist Thought Examined for Provoking Self-Reflection in Architecture
MARCH, University of Cincinnati, 2017, Design, Architecture, Art and Planning: Architecture
The creation of architecture is often approached as a social act: many buildings are created for public consumption, and many architects believe the users’ experiences (and by association the architecture itself) are enriched through encountering public spaces and opportunities to interact with other users or with the public at large. Moments are identified within the design where potentially disparate paths will cross and the people on them will acknowledge and understand each other. This investigation argues that the same architectural tools used to engineer these moments of collision may also be employed differently to be productively disruptive of the user’s journey, creating moments of mental solitude. To that end, this thesis explores the architecture of self-reflection, solitude, and self-understanding. Rather than identifying ways to encourage interaction with others, this is an examination of how architecture might suggest that users look inward. To create architectural experiences of this nature, inhabitants’ visual and spacial perception are challenged through manipulation of form and space. In the perceptual vacuum that is created when the user’s idea of reality is denied, the inhabited space is, in a sense, Surreal. This investigation proposes that when we are unsure of the space we inhabit, and the Surreal dominates, we are given a moment to look inward. In this way, the spacial constructions informed by surrealist thought can promote meditation and reflection. Building on surrealist intentions, themes of the surreal may be applied to architecture to fulfill similar architectural intentions of this thesis: questioning the true nature of our environment to promote self-reflection. Through an iterative case study exercise, architectural form is manipulated using strategies informed by surrealist ideology to challenge the user’s perception of reality, providing an opportunity to reflect.

Committee:

Christoph Klemmt, A.A. Dipl. (Committee Chair); Aarati Kanekar, Ph.D. (Committee Member)

Subjects:

Architecture

Keywords:

surrealism;perception;meditation;reflection

Bdaiwi, AbdullahCategorizing Cortical Dysplasia Lesions for Surgical Outcome Using Network Functional Connectivity
MS, University of Cincinnati, 2017, Arts and Sciences: Physics
Lesion-symptom mapping is a powerful and broadly applicable approach that is used for linking neurological symptoms to specific brain regions. Traditionally, it involves identifying overlap in lesion location across patients with similar symptoms. This approach has limitations when symptoms do not localize to a single region or when lesions do not tend to overlap. In this thesis, we show that we can expand the traditional approach of lesion mapping to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves assessing the functional connectivity of each lesion volume with the rest of the typical healthy brain using a database of healthy pediatric brain imaging data (C-MIND), available at CCHMC. Our study included 24 subjects that had cortical dysplasia lesions and underwent surgery for seizures that did not respond to drug therapy. We tested our approach using healthy brain imaging data across all ages (2-18 years old) and using age & gender specific groupings of data. The analysis sought categorization of lesion connectivity based on five subject characteristics: gender, cortical dysplasia pathology, epilepsy syndrome, scalp EEG pattern and surgical outcome. Our primary analysis focused on surgical outcome. The results showed that there are some substantial connectivity differences in the outcome analysis. Lesions with stronger connectivity to default mode and attention/motor networks tended to result in poorer surgical outcomes. This result could be expanded with a larger set of data with the ultimate goal of allowing examination of lesions of cortical dysplasia patients and predicting their seizure outcomes.

Committee:

Mark Difrancesco, Ph.D. (Committee Chair); Darren Kadis (Committee Member); Rostislav Serota, Ph.D. (Committee Member); L. C. R. Wijewardhana, Ph.D. (Committee Member)

Subjects:

Physics

Huffman, AshleyDiscovery of Movement: An Exploration of Physical Activity through Architecture
MARCH, University of Cincinnati, 2017, Design, Architecture, Art and Planning: Architecture
Insufficient physical activity is a key factor in cardiovascular diseases, cancers, and diabetes. The increase in physical inactivity is a large contributor to the worldwide obesity epidemic. Social changes and economic growth increased the sedentary activities like watching television, using the computer, and playing video games. Promoting activities through daily living, walking, using the stairs, can increase the total energy expenditure that can help in maintaining energy balance or even losing weight. Architecture can be more than a space for people to occupy, it can become the foundation for which people move, thus exploring the role of how the built environment can help facilitate in a healthier lifestyle. Focusing on the impacts of public health, the built environment can help facilitate an active spaces that will encourage people to move. By incentivizing a series of towers that will allow people of all ages to passively engage in exercise without realizing it, through walking and climbing stairs, they reap the benefits of improving their overall health.

Committee:

Elizabeth Riorden, M.Arch. (Committee Chair); Udo Greinacher, M.Arch. (Committee Member)

Subjects:

Architecture

Keywords:

physical inactivity;obesity;health;stairs

Tobe, RachelThe Chimera
MARCH, University of Cincinnati, 2017, Design, Architecture, Art and Planning: Architecture
My goal is to design a home for user-directed change. Studies of kinetic architecture have tackled this in different ways, often not overlapping multiple methods for the sake of design simplicity. I intend to merge three usually separate scales of kinetic architecture (the scale of the whole building, the scale of the exterior skin, and the scale of the interior program) to create a completely new flexible housing option. This will provide the user with the ability to control their location, the interior of their home, and the connection they have to their site. With this new design type, I will offer informed predictions for the ramifications and impacts this design would have on its user and on whole communities.

Committee:

Udo Greinacher, M.Arch. (Committee Chair); Aarati Kanekar, Ph.D. (Committee Member)

Subjects:

Architecture

Keywords:

Kinetic Architecture;Residential Architecture;Flexible Housing;Mobile Architecture;Flexible Interiors;Tiny House

Ariyabuddhiphongs, KrisSymmetry of Interpersonal Rhythmic Coordination: The Case of a Three-Person Drumming Task
PhD, University of Cincinnati, 2017, Arts and Sciences: Psychology
The mathematical theory of symmetry provides a framework to understand higher order structures of behavioral organization across various contexts; the same principle that explains the organization of quadruped gaits can also be applied to behavioral coordination in interpersonal contexts. The current studies examined how symmetries of perceptual coupling and social information influenced interpersonal coordination during a three-person drumming task. In Study 1, triads of participants performed a drumming task without explicit instructions to coordinate; each participant drummed to given metronome beats for 10 seconds and maintained his or her rhythm for the rest of the trial. Half of the 24 triads drummed at 60 bpm, and the other drummed at 45 bpm. Each triad performed the task under five auditory coupling conditions: the all-, rotation-, partial-, clamped-, and no-coupling conditions. During the task, participants could hear but not see each other’s drumming. The results showed that when coupling was present, the spontaneous coordination mode that emerged tended to be inphase. Regardless of drumming frequency, coordination in the all- and clamped-coupling conditions was more stable than in the partial-coupling conditions, indicating the effect of asymmetric coupling functions. In addition, period shifts were observed in the 45-bpm all-, rotation-, and clamped-coupling conditions. In Study 2, the minimal group paradigm was used to manipulate the symmetry of social identity among a triad. Fifteen triads were assigned to the heterogeneous condition, where two participants were in the minimal ingroup—the red group—and one in the minimal outgroup—the blue group. The other 14 triads were in the homogeneous condition (i.e., the control group) with all of them assigned to the red group. Beside the minimal group manipulation, there was no constraint on either visual or auditory information in Study 2. The participants first performed the drumming task without explicit instructions to coordinate (i.e., spontaneous coordination task) and, then, with explicit instructions to coordinate in a partial-inphase pattern (two participants inphase with each other and the third antiphase relate to the other two). The results showed that asymmetric minimal group identity had no effect on the spontaneous or explicit coordination. Plausible explanations for the null effects are discussed.

Committee:

Rachel Kallen, Ph.D. (Committee Chair); Michael Richardson, Ph.D. (Committee Member); Michael Riley, Ph.D. (Committee Member)

Subjects:

Psychology

Keywords:

rhythmic coordination;interpersonal coordination;symmetry;drumming;minimal group

Lindquist-Grantz, RobinYouth Participatory Action Research as a Strategy for Adolescent Suicide Prevention
PhD, University of Cincinnati, 2017, Education, Criminal Justice, and Human Services: Educational Studies
After years of decline, there has been a steady increase in the percentage of youth who report seriously considering suicide or making a suicide plan (Kann et al., 2016) and those who have died by suicide (CDC, 2016). As of 2014, suicide moved from being the third leading cause of death for youth ages 10 to 24 to being the second leading cause of death (CDC, 2014). Public strategies and funding to prevent suicide have increased; however, the effectiveness of existing strategies varies, especially in regard to youth help-seeking behaviors, problem-solving, and treatment engagement and utilization. Although youth are among the primary targets of suicide prevention strategies, they have largely been excluded from prevention efforts except as passive participants in programs and research studies. Youth Participatory Action Research (YPAR) is a collaborative approach to research that engages youth and academics as equal partners, and aims to build youth potential for being intentional agents of change for issues that directly affect them and their peers (Cammarota & Fine, 2008). The current study utilized YPAR within an integrated social ecological and positive youth development theoretical framework as an adolescent suicide prevention strategy in Cincinnati, Ohio. Multiple methods were used to determine the usability of YPAR as an innovative approach for building youth development, to explore youth experiences with YPAR for suicide prevention, and to understand youth capacity for conducting suicide prevention research. Findings revealed that confidence gained through YPAR processes contributed to important changes in individual youth development, which then fostered group development and positive perceptions of their capacity to work collectively to address adolescent suicide amongst themselves and with their peer group. The findings have important implications for understanding key processes within YPAR that lead to individual and group development, and where in the YPAR process these changes occur.

Committee:

Lisa Vaughn, Ph.D. (Committee Chair); Jacqueline Grupp-Phelan, M.D. (Committee Member); Farrah Jacquez, Ph.D. (Committee Member)

Subjects:

Public Health

Keywords:

adolescents;youth;suicide prevention;youth participatory action research;participatory research;positive youth development

Lanci, Michael PSongs for Joe Hill
DMA, University of Cincinnati, 2017, College-Conservatory of Music: Composition
Songs for Joe Hill is a collection of five protest songs based on the texts of late 19th century authors and poets who addressed issues of labor, social, and political rights within their work. This composition is dedicated to the Swedish immigrant, singer-song writer, and labor rights activist Joe Hill (1879- 1915), who was a member of the Industrial Workers Union of the World, which is still one of the largest union organizations in the world and can be accredited for helping fight for many of the labor rights we enjoy today. Although Joe Hill was an important influence in helping further the cause of the growing American labor movements of the early 20th century, it was not until the highly controversial trial that led to Joe Hill’s execution for the murder of John G. Morris and his son outside their Salt Lake City grocery store in 1914, that his beliefs were brought to the public’s attention. Speculation surrounding the evidence presented by the prosecution, and rumors of collusion between eyewitnesses and local mining companies that were strongly anti-union, led to the involvement of President Woodrow Wilson, the Swedish ambassador, and author Helen Keller in an unsuccessful bid for clemency. This helped further generate international media attention, turning Joe Hill into one of the more significant martyrs of the labor rights movement.

Committee:

Michael Fiday (Committee Chair); Mara Helmuth (Committee Member); Douglas Knehans (Committee Member)

Subjects:

Music

Keywords:

Music Composition;Songs;Protest;Labor;Social;Politics

DeLorenzo, Corrina JEvaluating the Use of Fecal Transthyretin as a Biomarker for Noninvasive Pregnancy Diagnosis in the Polar Bear (Ursus maritimus)
MS, University of Cincinnati, 2017, Arts and Sciences: Biological Sciences
Captive breeding of threatened and endangered wildlife is hindered by pseudopregnancy: animals that show signs of pregnancy but are not actually pregnant. Pseudopregnancy draws on limited resources with no chance of reproduction. Currently, there is no test to differentiate between pregnancy and pseudopregnancy in polar bears (Ursus maritimus). The objective of this study were to develop a more reliable method to distinguish pregnant from pseudopregnant and nonpregnant bears using transthyretin (TTR), a protein expressed in developing embryos. This study had three aims: 1) identify antibodies that crossreact with polar bear fecal TTR; 2) develop and validate an ELISA for measuring fecal TTR; and, 3) compare longitudinal fecal TTR concentration profiles among pregnant, pseudopregnant, and nonpregnant polar bears. Western blot assays were used to determine commercial antibody compatibility with polar bear fecal TTR. A sandwich ELISA was developed and validated to quantify fecal TTR concentrations. Total protein was extracted and TTR concentrations were quantified from samples collected from 15 bears to create longitudinal profiles for evaluation. Results also suggested a possible interaction between season and reproductive status on total protein concentrations. The TTR ELISA method was able to more reliably distinguish pregnant from pseudopregnant and nonpregnant bears using a threshold test. Future studies should investigate applying this test in a larger sample, and refinement of the threshold method to more clearly detect pregnancy using longitudinal data.

Committee:

Kenneth Petren, Ph.D. (Committee Chair); Joshua Benoit, Ph.D. (Committee Member); Daniel Buchholz, Ph.D. (Committee Member)

Subjects:

Biology

Keywords:

polar bear;pregnancy;pseudopregnancy;fecal proteins;transthyretin;ELISA

Ingale, Himanshu AFabrication and Characterization of a Wrinkled Polydimethylsiloxane Thin Film Bilayer System
MS, University of Cincinnati, 2017, Engineering and Applied Science: Mechanical Engineering
As technology is continuing towards smaller, thinner and lighter devices, thin polymer films have been in stringent demands as dielectric coatings, diffusion barriers and optical reflectors. In particular, instability phenomenon in thin films has received considerable attention due to the ease of such systems to generate self-organized, well-defined and complex topological features. Spontaneous formation of well-ordered surface wrinkles represents one of such instability driven self-organization of the thin films on soft substrate, examples of which are readily apparent in nature such as aging human skin, drying fruits. Such well-ordered surface wrinkling can be used in thin film solar cells, which would act as a textured surface, thus reducing the optical losses. In this thesis, a novel approach that is, well-ordered surface wrinkling formation using chemical oxidation of the surface and its effect on the efficiency of thin film solar cells has been studied. An automated setup for introducing strain in the soft substrate was designed and built in-house. An open source GRBL (Open source CNC controller) software was used to control and monitor the system for accurate measurements and strain of the substrate. The strained soft substrate that is Polydimethylsiloxane (PDMS) was then treated with chemical oxidizing agent (Piranha solution) in order to form thin stiff oxidized layer on PDMS substrate, resulting in bi-layer system. The morphology of the wrinkled surface was analyzed using profilometer and an Optical microscope. Further, the Young’s modulus of the oxidized layer was estimated using wrinkling mechanics mathematical model and was verified experimentally by carrying out Nano-indentation tests using Atomic Force Microscope (AFM). It was found that the deviations in Young’s modulus values of the oxidized layer using both mathematical model and Nano-indentation tests were within 11% variation to each other. Also, theoretical studies were carried out and found more than 10% increase in transmittance and short circuit current if a cadmium telluride (CdTe) solar cell is to be deposited on such substrate.

Committee:

Murali Sundaram, Ph.D. (Committee Chair); Jing Shi, Ph.D. (Committee Member); David Thompson, Ph.D. (Committee Member)

Subjects:

Engineering

Keywords:

Thin film solar cell;Surface wrinkling;Nano-indentation;Elastic moduli of thin films;Optical modeling of solar cell;Light trapping

Bruzina, Angela SBearcats in the Kitchen: A Food Lab-Based Cooking Intervention for Female Athletes
MS, University of Cincinnati, 2017, Allied Health Sciences: Nutrition
Purpose: The purpose of this study was to assess the acceptability and impact of a ten-week foods lab-based cooking intervention program on the energy and nutrient intake, body composition, and iron status indices in female collegiate athletes. Methods: Female Collegiate athletes were recruited for this study. Participants were excluded if they had severe food allergies, current or planned pregnancy, eating disorder diagnosis, or any metabolic disorder. Participants completed eight food lab-based intervention classes during their summer training period. The classes consisted of nutrition education focusing on healthy eating for optimizing sports performance, skill-based learning that incorporated basic kitchen skills with recipe preparation, and behavioral strategies including food monitoring and goal setting. Dietary intake, anthropometrics, and blood samples were analyzed pre- and post-intervention for changes as well as adequacy in meeting general sports nutrition recommendations for athletes. Dependent variables were anthropometric measures (weight, body fat percentage, fat mass, and fat free mass), iron status indicators (ferritin, hemoglobin (Hb), and hematocrit (Hct)), and dietary measures (energy, macronutrients, and iron). Shapiro-Wilk test of normalcy was run on all data and paired T-tests were used to examine the differences pre- to post-intervention for all outcome measures. Results: Eleven NCAA Division I Female Collegiate athletes, age (20.4 ± 1.2 years) participated in the intervention. At the end of the 10 weeks, lean mass increased significantly, 56.1 ± 4.6kg to 56.8 ± 4.6kg, respectively (p = 0.017). In terms of iron status, there were significant increases in Hct and Hb from pre- to post-intervention (p=0.01), while there was a downward trend in ferritin (p = 0.067). Thirty six percent of the participants did not meet the minimum 30g/kg energy recommendation for weight maintenance post-intervention. Further, not one athlete met the minimum carbohydrate recommendation of 5g/kg either pre- or post-intervention. In addition, three participants (n=3, 27%) did not meet the minimum 1.2g/kg protein recommendation post-intervention. The direction of change for all dietary measures was favorable, however, no significant differences were observed in energy, carbohydrate, protein, fat, or iron intake from pre- to post-intervention. Conclusion: A foods lab-based cooking intervention that incorporates nutrition education, cooking skills, and dietary goal setting may have benefits relative to nutritional intake, body composition, and iron status in female collegiate athletes. Larger, controlled studies are necessary to determine if Bearcats in the Kitchen could be a useful approach to improve the dietary intake of macronutrients and body composition in collegiate athletes across different sports.

Committee:

Abigail Peairs, Ph.D. (Committee Chair); Sarah Couch, Ph.D. (Committee Member)

Subjects:

Nutrition

Keywords:

Athlete Dietary Intake;Collegiate Athlete;Female Athlete;Cooking Intervention

Pandey, RaghavMicroRNA Mediated Proliferation of Adult Cardiomyocytes to Regenerate Ischemic Myocardium
PhD, University of Cincinnati, 2017, Medicine: Cancer and Cell Biology
Cardiovascular diseases have been the biggest killer in the United States for decades. Despite tremendous research and new innovations, these trends do not seem to be slowing down, with more than 1 in every 3 deaths related to cardiovascular disease in 2016. In the U.S. cardiovascular diseases affect close to 92.1 million people, causing 807,775 deaths each year. According to the American Heart Association statistics report update of 2016, 17.3 million deaths worldwide were attributed to cardiovascular diseases. Moreover, this number is estimated to rise to more than 23.6 million by the year 2030. In addition, U.S. healthcare cost associated with cardiovascular disease has been rising with a massive $316 billion of associated direct and indirect cost, which is estimated to rise to $918 billion by the year 2030. Moreover, as the average age of the U.S. population increases this trend will most likely stay the same, if not increase. Etiologically, lack of oxygen and blood to the heart tissue is one the major cause of this ischemic injury and scar formation. This happens through the buildup of plaque in the arteries which reduces the blood flow and when left untreated can shut down the blood supply to downstream tissue. Our current medical approaches to deal with ischemic injuries include blood thinners, stents, beta-blockers, and surgical cleaning of the plaque. Although, heart transplants are the most optimal treatment, unavailability of donor hearts still remains a major concern when dealing with this problem. While microRNAs were first discovered in early 1990s by Ambros in C. elegans it was not until mid-2000s that first cardiac microRNA was discovered and studied. Binding to the 3’UTR (untranslated region) and inhibiting expression of the gene is the canonical mode of action for microRNAs, however there have been reports of 5’UTR binding and other non-canonical modes of action. Recent work by Matkovich et al. 2013 even determined miRNAs regulating other cardiac miRNAs. In addition to their discovery, microRNAs were shown to be differentially regulated in diseased and non-diseased cases. In addition, work by Eulalio et al. 2012 was one of the first to show miRNAs inducing proliferation in cardiomyocytes and inducing regeneration of lost myocardium, post injury. In this work, we have furthered the understanding of miRNAs and cardiovascular disease (specifically myocardial infarction) by showing a significant proliferation in adult cardiomyocytes both ex-vivo and in-vivo, which reduces infarction size and improves heart function as early as one month post treatment. We also confirmed the effect across different species (mice, rats, and human) and showed that miR1825 can induce significant proliferation in all three species. Lastly, we project a very high translational potential for this work due to the nature of miRNAs as a therapeutic: readily available, longer shelf-life, and no prerequisite for an autologous donor.

Committee:

Rafeeq Habeebahmed, Ph.D. (Committee Chair); Joshua Benoit, Ph.D. (Committee Member); Chunying Du, Ph.D. (Committee Member); Sohaib Khan, Ph.D. (Committee Member); Jerry Lingrel, Ph.D. (Committee Member); Jack Rubinstein, M.D. (Committee Member)

Subjects:

Biology

Keywords:

Cardiomyocytes;Cardiac regeneration;microRNAs;Heart disease;Cardiovascular;Cardiovascular diseases

Chintapalli, SrikarCommunication Protocols on the PIC24EP and Arduino - A Tutorial for Undergraduate Students
MS, University of Cincinnati, 2017, Engineering and Applied Science: Computer Engineering
With embedded systems technology growing rapidly, communication between MCUs, SOCs, FPGAs, and their peripherals has become extremely crucial to the building of successful applications. The ability for designers to connect and network modules from different manufacturers is what allows the embedded computing world to continue to thrive and overcome roadblocks, driving us further and further towards pervasive and ubiquitous computing. This ability has long been afforded by standardized communication protocols developed and incorporated into the devices we use on a day-to-day basis. This thesis aims to explain to an undergraduate audience and to implement the major communication protocols that are used to exchange data between microcontrollers and their peripheral modules. With a thorough understanding of these concepts, students should be able to interface and program their microcontroller units to successfully build projects, giving them hands on experience in embedded design. This is an important skill to have in a field in which configuring the electronics and hardware to work correctly is equally as integral as writing code for the desired application. The protocols that are discussed are the three main serial communication protocols: I2C (inter-integrated circuit), SPI (serial peripheral interface), and TTL UART (universal asynchronous receiver transmitter). BLE (Bluetooth low energy) is also explored to try and help students add cheap wireless functionality to their designs. In order to successfully put forth and apply the concepts, this thesis uses the Arduino Uno R3 (Atmel ATmega328 microcontroller) and the mikromedia for PIC24EP (PIC24EP512GU810 microcontroller) boards. On the Arduino, we use high level functions afforded by library support to go through the steps of implementing and using the UART, SPI, and I2C serial communication protocols. For the PIC, we write our own functions to write the protocols from scratch using registers in the hardware communication modules provided on board. To test these out, we use the BME280 and MCP9808 sensors that can be interfaced with I2C or SPI. In addition, we also go through the steps of using the Bluefruit LE shield by Adafruit to integrate multiple modules adding Bluetooth connectivity to the embedded controller. Based on the tutorial nature of this thesis, students should be able to implement these protocols and interface their own controllers to sensors and modules regardless of manufacturer or library support (given the operating voltages are compatible). At the end of this thesis, there will be a set of exercises to test procedural knowledge and to enable students to assess how well they retained the information.

Committee:

Carla Purdy, Ph.D. (Committee Chair); Rui Dai, Ph.D. (Committee Member); Wen-Ben Jone, Ph.D. (Committee Member)

Subjects:

Computer Engineering

Keywords:

embedded systems

Hernan, Colleen JUsing an Antecedent Intervention and Interdependent Group Contingency to Decrease the Inappropriate Use of Mobile Devices in High School Classrooms
PhD, University of Cincinnati, 2017, Education, Criminal Justice, and Human Services: School Psychology
Academic engagement has been shown to decline as students progress through elementary and middle school, reaching the lowest levels in high school. Increasing student engagement has been an explicit goal of many school and district improvement efforts, especially at the high school level. As the capabilities of portable technology continue to advance and become more accessible, educators are becoming more concerned about the impact of the inappropriate use of mobile devices on learning. An alternating treatments design was used to compare the effectiveness of an antecedent (Clear Box) intervention and an interdependent group contingency (Clear Box + GBG) intervention to typical classroom management techniques (Control) in increasing the academic engagement of students by reducing their use of mobile devices during instruction. This study was implemented in the high school setting with students exhibiting low levels of academic engagement and high levels of inappropriate use of mobile devices. Visual analysis was used to analyze the target behaviors, including academic engagement and inappropriate presence of mobile devices. The results indicate an increase in academic engagement and a decrease in the inappropriate presence of mobile devices in both classrooms with the implementation of the Clear Box + GBG. In addition, teacher and student social validity data were also examined, suggesting the intervention was viewed favorably by both the teachers and children involved in the study. Discussion focuses on contributions to the current literature, implications for practice, and suggestions for future areas of research.

Committee:

|Julie Morrison (Committee Co-Chair); Tai Collins (Committee Member); Stephen| Kroeger (Committee Member)

Subjects:

Education

Keywords:

mobile devices;academic engagement;antecedent interventions;group contingencies;good behavior game;cell phones

Harrison, LauraCorners of the Sky
DMA, University of Cincinnati, 2017, College-Conservatory of Music: Composition
Corners of the Sky was written for pianist Kristofer Rucinski and conductor Jon Norywota, as part of the New Concerto Project. This project was developed by composer Rachel Walker and myself to help promote orchestral works, specifically those written by young female composers. The title is an adaptation of a title of a poem by Frederico Garcia Lorca, In a Corner of the Sky. This piece is a single-movement work for piano soloist and orchestra, with a form that is constructed in four distinct sections: A-B-A’-C. These sections are contrasting in character, as well as being distinguished by different treatment of the harmonic material. The first section is fully chromatic, using a twelve-tone chord at the beginning, and an ostinato that also uses all twelve pitches. Although section B also uses chromatic harmony, it is more focused on intervallic relationships, specifically tritones and minor seconds, and later, perfect fifths. Section C is the least harmonically dense section of the piece. Although it uses eleven pitches in total over the course of the section, they are spread out in the piano part over a flowing pentatonic ostinato, while the rest of the orchestra presents a sustained pentatonic chord. The construction of this work is based on five motivic ideas. The first is a plodding, insistent ostinato, first presented in the piano at the beginning of the work, and then passed through the orchestra until it builds up to a tutti climax. The second idea, a brooding, angular melody is also first presented by the piano. Fragments of this melody appear recontextualized throughout the piece in various sections of the orchestra. The third idea develops over the course of the piece. It is a chromatic descent, which first appears as only two notes, but gradually adds notes until it becomes a full chromatic scale passed through the woodwind section and descending portamenti played by the strings. The repeated notes that constitute the fourth motivic idea is presented as a rhythmic ostinato, and are sometimes combined with other motivic ideas. The final motivic idea is sharp, accented notes that appear first in the woodwinds as interruptions, and is later taken up by other sections of the orchestra. This idea is often combined with the repeated notes and the chromatic gestures.

Committee:

Douglas Knehans, D.M.A. (Committee Chair); Michael Fiday, Ph.D. (Committee Member); Mara (Margaret) Helmuth, D.M.A. (Committee Member)

Subjects:

Music

Keywords:

Composition;Piano Concerto;Classical Music

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