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  • 1. Anderson, Richard PATHOPHYSIOLOGY OF THE eIF2A-KO MOUSE MODEL

    Doctor of Philosophy in Regulatory Biology, Cleveland State University, 2024, College of Arts and Sciences

    Eukaryotic initiation factor 2A (eIF2A) is a highly conserved 65 kDa eukaryotic protein that functions in minor initiation pathways, which affect the translation of only a subset of messenger ribonucleic acid (mRNAs), such as internal ribosome entry site (IRES)-containing mRNAs and/or mRNAs harboring upstream near cognate/non-AUG start codons. These non-canonical initiation events are important for regulation of protein synthesis during cellular development, differentiation and/or the integrated stress response. Selective eIF2A knockdown in cellular systems was shown to inhibit translation of such mRNAs, which rely on alternative initiation mechanisms for their translation. However, there existed a gap in our understanding of how eIF2A functions in mammalian systems in vivo (on the organismal level) and ex vivo (in cells). To address this question we have developed the eIF2A-total body knockout (KO) mouse model. Using this model, we presented evidence implicating eIF2A in the biology of aging and metabolic syndrome. We discovered that eIF2A-KO mice have reduced life span and that eIF2A plays an important role in maintenance of lipid homeostasis, the control of glucose tolerance and insulin resistance. We also showed the eIF2A KO affects male and female mice differently, suggesting that eIF2A may affect sex-specific pathways. The metabolic syndrome phenotype has three main etiological categories: obesity and disorders of adipose tissue (particularly increased size of adipocytes); glucose intolerance and insulin resistance; and a constellation of independent factors of hepatic, vascular, and immunologic origin and all of these features were observed in the eIF2A-KO mice. Increased adipocyte size is, in particular, well known to be positively correlated with impaired insulin sensitivity and glucose tolerance leading to metabolic syndrome. To specifically check whether the absence of eIF2A in adipose tissue is responsible for metabolic abnormalities observed in the tota (open full item for complete abstract)

    Committee: Anton Komar (Committee Chair); Barsanjit Mazumder (Committee Member); Roman Kondratov (Committee Member); William Baldwin III (Committee Member); Merlin Gnanapragasam (Committee Member); William Merrick (Committee Member) Subjects: Biology; Molecular Biology; Physiology
  • 2. Devine, Racheal Regulatory Features of the 5' Untranslated Leader Region of aroL in Escherichia coli K12 and the sRNA, ryhB, in Shewanella oneidensis MR-1

    Doctor of Philosophy, Miami University, 2018, Microbiology

    RNA is an important regulator of gene expression within bacterial, eukaryotic, and archaeal cells. This work focuses on two aspects of RNA regulation: the first half investigates the role of regulatory features within the 5' untranslated leader region (UTR) of the E. coli aroL mRNA and the second half focuses on an sRNA in S. oneidensis MR-1. The 5'UTR of mRNAs contain information necessary for ribosome recognition and subsequent translation initiation. Translation initiation is a prominent part of gene expression, as it is the rate-limiting step of translation. The 70S ternary initiation complex contains initiator tRNA and the mRNA's start codon positioned in the P-site of the 70S ribosome. The Shine-Dalgarno (SD) sequence within the 5'UTR of the mRNA is an important feature that helps facilitate the initial interaction between the mRNA and the 30S subunit. Translation of mRNAs lacking an SD has been reported and suggests that alternative mechanisms of mRNA-30S interactions exist. The aroL mRNA contains a short open reading frame within its 5'UTR. Ribosome binding and expression assays showed that this open reading frame gets translated, and its translation affects aroL translation downstream. The upstream open reading frame binds 30S subunits in the absence of a canonical SD sequence. In this work, we have shown that multiple signals in the mRNA (upstream and downstream of the AUG) contribute to 30S binding to and translation from the AUG start codon. In this work we have also characterized an sRNA, a ryhB homologue, in S. oneidensis MR-1. sRNAs contain regulatory features in their sequence and structure that help regulate translation of bacterial mRNAs in response to environmental cues. Similar to what has been reported in E. coli, the sRNA is regulated in response to iron limitation in S. oneidensis MR-1 and may have a regulatory role in iron metabolism.

    Committee: Mitch Balish (Advisor) Subjects: Microbiology; Molecular Biology
  • 3. Frank, Joseph Social Determinants of Recent Alcohol Use and Episodic Heavy Drinking among African American and Hispanic Young Adults

    PhD, University of Cincinnati, 2016, Education, Criminal Justice, and Human Services: Health Education

    Study One Abstract Introduction: The purpose of this study was to examine the social determinants of recent alcohol use (past 30 days) and episodic heavy drinking among African American young adults aged 18 to 25 years.Methods: A secondary data analysis of the 2012 National Survey on Drug Use and Health (NSDUH) was performed in this study. African American young adults (n = 2,573) completed the survey. Approval to conduct this study was granted by the university'sinstitutional review board. Results: Results indicated that 51.9% of African American young adults reported recent alcohol use and 27.3 % reported episodic heavy drinking. Those at highest risk for recent alcohol use were male, had less than a high school diploma, had a family income of less than $20,000, had worked in the past 12 months, lived in a large metropolitan area, had good/fair/poor self-reported health status, and had used alcohol, tobacco and marijuana before age 21. Discussion: These results should be considered when developing public health efforts to prevent alcohol abuse among African American young adults. Study Two Abstract Introduction: The purpose of this study was to examine the social determinants of recent alcohol use (past 30 days) and episodic heavy drinking among Hispanic young adults aged 18 to 25 years.Methods: A secondary data analysis of the 2012 NSDUH was performed in this study. Hispanic young adults (n = 3,452) completed the survey. Approval to conduct this study was granted by the university'sinstitutional review board. Results: Results indicated that 51.8% Hispanic young adults reported recent alcohol use and 35.0 % reported episodic heavy drinking. Those at highest risk for recent alcohol use were male, had some college or more, had a family income of $20,000 or more, had worked in the past 12 months, lived in a large metropolitan area, had excellent/very good self-reported health status, and had used alcohol, tobacco and marijuana before age 21. Discussio (open full item for complete abstract)

    Committee: Keith King Ph.D. (Committee Chair); Ashley Merianos Ph.D. (Committee Member); Rebecca Vidourek Ph.D. (Committee Member) Subjects: Health Education
  • 4. Day, James Isolation of Streptomyces lividans ribosomes and initiation factors and their characterization using in vitro mRNA binding assays

    Doctor of Philosophy, Miami University, 2004, Microbiology

    A primer extension inhibition (toeprint) assay was developed using ribosomes and ribosomal subunits from Streptomyces lividans. This assay allowed the study of ribosome binding to streptomycete leaderless and leadered mRNA. Purified 30S subunits were unable to form a ternary complex on aph or cat leaderless mRNAs, whereas 70S ribosomes could form ternary complexes on both of these mRNAs. 30S subunits formed ternary complexes on aph and malE leadered mRNA. The translation initiation factors (IF1, IF2, IF3) from S. lividans were isolated and included in toeprint and filter binding assays with leadered and leaderless mRNA. Generally, the IFs reduced the toeprint signal on leadered mRNA; however, incubation of IF1 and IF2 with high-salt washed 30S subunits promoted the formation of a ternary complex on aph leaderless mRNA. Our data suggest that, as reported for Escherichia coli, initiation complexes with leaderless mRNAs might use a novel pathway involving 70S ribosomes or 30S subunits bound by IF1 and IF2 but not IF3. Some mRNA-ribosome-initiator tRNA reactions that yielded weak or no toeprint signals still formed ternary complexes in filter binding assays, suggesting the occurrence of ternary complex interactions that are not stable in the toeprint assay. Further, the streptomycete 50S subunit was observed forming a ternary complex on aph and cat leaderless mRNAs; a model is presented for an alternate translation initiation pathway involving 50S subunits binding to leaderless mRNA in the streptomycetes. This is the first comprehensive look at the interactions of the molecular components involved in translation in the streptomycetes.

    Committee: Gary Janssen (Advisor) Subjects:
  • 5. Brown, Petrice The Mammalian Process of Meiotic Synapsis

    Doctor of Philosophy, Case Western Reserve University, 2007, Genetics

    The synaptonemal complex (SC) provides the structural framework for synapsis and recombination of homologous chromosomes during meiotic prophase. The relationship between the SC and other prophase events differs among species but studies of model organisms clearly demonstrate that the completion of prophase is dependent on the formation of mature SCs. Although the SC is essential to meiosis, little is known about the details involved in the construction of the mammalian SC. Human testicular biopsy material provides an opportunity to study the meiotic process in the human male. The studies described in this thesis were designed to characterize synapsis and formation of the synaptonemal complex in spermatocytes of normal human males. Using current cytogenetic techniques, SCs were characterized at different stages of prophase to determine genome-wide synaptic patterns, patterns of individual chromosomes and variation within and among individuals. We initially focused on the correlation between synapsis and recombination, by evaluating the temporal relationship between SC formation and the emergence of double strand breaks. Subsequent studies investigated the possibility of co-localization of synaptic initiation sites with sites of recombination. Our results indicated that recombination is initiated before the formation of the SC, and that sites of synaptic initiation are not translated into sites of exchange. We then characterized the process of synapsis in detail by determining the location and number of synaptic initiation events on specific chromosomes. Initial analysis showed that in the human male, synapsis predominantly begins at the distal region. We identified synaptic patterns based on chromosome structure, wherein acrocentric chromosomes harbor one synaptic initiation event on the long arm while nonacrocentric chromosomes may sustain two initiation sites, one per chromosome arm. Subsequent analysis of the synaptic process determined that the SC progresses to (open full item for complete abstract)

    Committee: Terry Hassold (Advisor) Subjects:
  • 6. Sirimamilla, Pavana MECHANISTIC STUDY OF CRACK INITIATION AND PROPAGATION IN CROSSLINKED ULTRA HIGH MOLECULAR WEIGHT POLYETHYLENES (UHMWPE) SUBJECTED TO STATIC AND CYCLIC LOADING

    Doctor of Philosophy, Case Western Reserve University, 2013, EMC - Mechanical Engineering

    Many total joint replacement (TJR) designs incorporate a hard bearing material articulating against a soft bearing (polymeric) material. The bearing polymer, typically made of ultra high molecular weight polyethylene (UHMWPE) has been successfully used for the last four decades. However, these bearing materials can fail as a result of in vivo mechanical loads. Reports suggest that the fracture resistance of UHMWPE could be improved which can help the longevity of the components in vivo. Fatigue crack propagation behavior of two crosslinked UHMWPE formulations was investigated to estimate the mechanical governing factor for stable crack propagation. Frequency, waveform and R-ratio were varied between test conditions to determine the governing factor for fatigue crack propagation. It was found that the crack propagation velocity in crosslinked UHMWPE is driven by peak stress intensity (Kmax) in a loading cycle. The findings suggest that stable crack propagation can occur in a static mode rather than in a cyclic mode. Crack initiation from a notch under fatigue conditions is also investigated for remelted 100 kGy material and compared to crack initiation under constant loading conditions. Crack initiation times for fatigue loading conditions were found to be substantially lower compared to static loading conditions. The results suggest that the crosslinked UHMWPE material is resistant under static loading conditions compared to fatigue loading conditions. Fracture resistance of two crosslinked UHMWPE formulations was also investigated. Fracture research utilizing the traditional LEFM and EPFM approaches has not yielded a definite failure criterion for UHMWPE. Therefore, an advanced viscous fracture model has been applied to various notched compact tension specimen geometries to estimate the fracture resistance. Results suggest that the viscous fracture model can be applied to the crosslinked UHMWPE materials and a single value of critical energy (Jc) governs crack i (open full item for complete abstract)

    Committee: Clare Rimnac (Committee Chair); Davy Dwight (Committee Member); Joseph Mansour (Committee Member); John Lewandowski (Committee Member) Subjects: Engineering
  • 7. Tomer, Jacqulyn Bridging Care Gaps in the Cancer Control Continuum: A Focus on Cancer Screening and Time to Treatment Initiation

    PHD, Kent State University, 2025, College of Public Health

    As cancer incidence and mortality continue to rise in the US, concerns about inequitable access and utilization of cancer care services across the cancer care continuum have grown. Cancer screening compliance and timely cancer treatment initiation are critical factors in improving outcomes and reducing disparities. Despite advancements cancer research and prevention efforts, many patients are still being diagnosed with late-stage cancers and experiencing delays in cancer treatment initiation. This dissertation aims to explore these inequities by evaluating the impact of Cleveland Clinic Taussig Cancer Center's patient navigation program on breast and colorectal cancer screening rates as well as identifying patient characteristics associated with screening noncompliance and treatment delays. These findings will provide insights to help Taussig Cancer Center administrators and clinicians design targeted interventions to better support high-risk patient populations.

    Committee: Lynette Phillips PhD (Committee Chair); Madhav Bhatta PhD (Committee Member); Vinay Cheruvu PhD (Committee Member); Mary Step PhD (Committee Member); Dana Hansen PhD (Other) Subjects: Epidemiology; Health Care; Oncology
  • 8. Ours, Benjamin Investigation of Increased Fatigue Strength by Laser-Heat-Treatment of AISI 1045 Steel

    Master of Science (MS), Ohio University, 2024, Mechanical Engineering (Engineering and Technology)

    This work investigated the influence of selective heat treatment through a Laser-Heat- Treatment (LHT) process on the bending fatigue performance of AISI 1045 steel. Staircase tests were performed on normalized and LHT (or ‘irradiated') specimens in resonance-based flexural bending for quantitative and qualitative comparison of fatigue behavior at endurance (106 cycles). Irradiated samples were subjected to a LHT process focused at localized sections of higher stress caused by changes in geometry before undergoing fatigue testing. The mean endurance limits between the two conditions did not have a statistically significant difference (p = 0.116), but different trends of crack initiation sites were seen between the two sample types. Post-mortem samples were analyzed to determine high-density crack initiation sites. Normalized samples showed a much higher crack location density in high stress regions near stress concentrations caused by geometry changes. When this same section of material was subjected to the LHT process, a sharp drop in crack initiation sites was seen.

    Committee: Timothy Cyders (Advisor) Subjects: Materials Science; Mechanical Engineering
  • 9. John, Benjamin The Homeric Psychology of Parmenidean Meditation

    Doctor of Philosophy, The Ohio State University, 2024, Greek and Latin

    This dissertation interprets the journey of the youth (kouros) in Parmenides' proem as an idealized mythological representation of a meditative practice by analyzing its deployment of Homeric psychological terminology. The first chapter puts forth an interpretation of Homeric psychology in light of what we now call the autonomic nervous system and suggests that thumos corresponds roughly to the “fight or flight” response of the sympathetic arm and psuche to the “rest and digest” response of the parasympathetic arm. At death, I argue, characters pass from the “hot” end of that spectrum to the “cold” end as the psuche exits the body. The second chapter uses this Homeric psychological scheme to argue that the journey of the kouros in Parmenides' proem depicts in mythological terms a process of heating and immortalizing the mind by increasing the thumos. This in turn allows him to meet and understand the unnamed goddess that greets him beyond the gates of Night and Day. I argue that this journey involves an ascent (anabasis) of the thumos towards the light of the sun rather than exclusively a descent to the underworld (katabasis), a common interpretation in recent years. The third chapter builds on the psychological and mythological interpretations developed in the first two chapters and examines one aspect of a meditative practice behind the proem. I argue that the kouros would heat and immortalize his mind by “inhaling” (αμπνυτο) more “wind” (πνοιη) to increase his thumos as an initial purification to prepare for the ascent. This proposal finds support in later Greek representations of meditative breathing practices that involve inhaling hot pneuma in the Chaldean Oracles and the “Mithras Liturgy” as well as comparison with similar ideas about “heat-generating ascetic practices” (tapas) in some Indian sources. I conclude that archaic Greek sages may have used inhalation-emphasized breathing practices to stimulate the sympathetic arm of the autonomic nervou (open full item for complete abstract)

    Committee: Thomas Hawkins (Advisor); Sarah Iles Johnston (Committee Co-Chair); Benjamin Folit-Weinberg (Committee Member); Hugh Urban (Committee Member) Subjects: Ancient Civilizations; Ancient History; Ancient Languages; Classical Studies; Comparative Literature; History; Language; Philosophy
  • 10. Wessel, Danielle Early Initiation of Pulmonary Rehabilitation and COPD Readmission Rates

    Doctor of Nursing Practice, Mount St. Joseph University , 2024, Department of Nursing

    Chronic Obstructive Pulmonary Disease (COPD) remains a significant public health challenge and a leading cause of hospital readmissions in the United States, imposing substantial financial and quality-of-life burdens. Global guidelines have advocated early initiation of pulmonary rehabilitation (PR) as an effective intervention to mitigate these readmissions. This Doctor of Nursing Practice (DNP) project aimed to evaluate the impact of early initiation of PR on the 30-day readmission rates for patients discharged with an acute exacerbation of COPD. A comprehensive evaluation was conducted on a cohort of 129 patients admitted with COPD across four months from October 2023 to January 2024. The project tracked 30-day readmission rates, PR referrals, and PR enrollment rates. These were compared against the same period from the previous year to gauge the effectiveness of the intervention. The initiative included inpatient PR consults, patient education, and scheduled PR intake evaluations post-discharge. Early findings indicate a decrease in the 30-day readmission rates, from an initial readmission rate of 14.71% in October 2023 to 12.82% in January 2024. The observed-over-expected readmission ratios demonstrated improvements, particularly notable in January 2024, with a ratio of 0.70. Additionally, there was a notable increase in PR referrals and significant improvement in staff knowledge about PR, indicating successful implementation of the initiative. The early initiation of PR post-discharge for patients with COPD may contribute to reducing 30-day readmission rates.

    Committee: Sandra Curtis (Advisor) Subjects: Health Care; Nursing; Rehabilitation
  • 11. Grove, Daisy Characterization of the inhibitory function of eIF2A in mRNA translation

    Doctor of Philosophy, The Ohio State University, 2024, Biochemistry Program, Ohio State

    Canonical eukaryotic messenger RNA (mRNA) translation primarily uses the heterotrimeric eukaryotic initiation factor 2 (eIF2) to deliver initiator transfer RNA (tRNA) to the 40S ribosomal subunit. Additionally, at least three other factors have been shown to deliver initiator tRNA, namely eIF2A, eIF2D, and the MCT-1•DENR complex, to the 40S ribosomal subunit. eIF2A, a monomer non-homologous to eIF2, was the first factor identified to deliver the initiator tRNA in eukaryotes. Further investigation into the mechanism of eIF2A dwindled once eIF2 was found to be the primary initiator tRNA carrier. The current model in the field posits that eIF2A delivers initiator tRNA to specific transcripts with near-cognate non-AUG start codons during normal conditions or cell stress. Biochemical analyses to verify the function of eIF2A were lacking due to the inability to achieve a high yield of soluble recombinant protein. Therefore, the exact function and mechanism of eIF2A in translation remains largely enigmatic. eIF2A depletion does not impact global translation levels in yeast, mouse, or human cells as shown by radiolabeled amino acid incorporation, polysome profiling, and ribosome profiling approaches. While eIF2A does not function in a major initiation pathway, this factor has been implicated in tumor progression and proper lipid metabolism in mice, indicating the importance of eIF2A in some biological processes. Multiple reports suggest that eIF2A is non-cytosolic, which is uncharacteristic of an initiation factor. During normal physiological conditions, eIF2A has specifically been reported to localize to the nucleus, endoplasmic reticulum, or mitochondria depending on the cell type. How and why eIF2A is kept away from the translation initiation machinery is unknown, but it may be a mechanism for cells to only use eIF2A in specific conditions. To gain insight into the function of eIF2A, we first developed a robust method to recombinantly express and purify eIF2A that yielde (open full item for complete abstract)

    Committee: Michael Kearse (Advisor); Karin Musier-Forsyth (Committee Member); Jane Jackman (Committee Member); Kurt Fredrick (Committee Member) Subjects: Biochemistry
  • 12. Pathirage, Chathuri Deshani Investigating the impact of host and viral factors on HIV-1 genomic RNA 5′ UTR structure and dynamics during reverse transcription initiation

    Doctor of Philosophy, The Ohio State University, 2023, Biochemistry Program, Ohio State

    Human immunodeficiency virus type-1 (HIV-1) infects CD4+ T cells, causing defects in the immune system leading to acquired immunodeficiency syndrome (AIDS). HIV-1 virus hijacks the transcriptional and translational machinery of the host cell to produce viral RNA and proteins. Full-length viral RNA is selectively packaged into virions, along with a number of host and viral factors that aid in successful viral infection of a target cell. The 5´ UTR, one of the most structurally and functionally dense regions of the viral RNA genome, is known to regulate many processes of the lifecycle, including RNA splicing, selective RNA packaging and dimerization, translation initiation and reverse transcription initiation. Interactions of the 5´ UTR with different host and cellular factors, as well as the RNA structure and conformational dynamics, are important to perform the aforementioned functions. In this work, we sought to characterize the conformational changes and interactions of the 5´ UTR that are involved in reverse transcription initiation. Human tRNALys,3 serves as the primer for HIV-1 reverse transcription. The 3′-18 nt of tRNALys,3 anneal to a complementary sequence called the primer binding site (PBS) in the 5´ UTR. HIV-1 reverse transcriptase (RT) binds to the primer-template complex and extends the 3′ OH group of tRNA. The initiation step of reverse transcription is slow and distributive, marked with several pausing events. In addition to the 3′ end of tRNA, several other regions of the primer are complementary to sequences within the 5´ UTR. Some of the additional interactions that have been identified in the HIV-1 MAL isolate 5´ UTR lead to conformational changes in viral RNA that facilitate reverse transcription initiation. Here we characterized the RNA conformational landscape of both tRNALys,3 and full-length HIV-1 NL4-3 5´ UTR upon forming the primer-template complex and upon RT binding, using selective 2′-hydroxyl acylation analyzed by primer extension (S (open full item for complete abstract)

    Committee: Karin Musier-Forsyth (Advisor) Subjects: Biochemistry
  • 13. Rao, Anupama Elucidating the Role of Translation Initiation Factor, eif41c in Cardiac Development and Regeneration in Zebrafish

    Doctor of Philosophy, The Ohio State University, 2023, Molecular, Cellular and Developmental Biology

    Cardiovascular disease is the leading cause of death worldwide, partly because humans lack appreciable capacity to repair or replenish lost or damaged cardiac tissue. Unlike mammals, adult zebrafish have a remarkable ability to regenerate large portions of cardiac tissues lost following injury. Most studies on zebrafish heart regeneration have focused on determining transcriptional changes occurring during this process. However, comparison of protein levels verses mRNA abundance shows that mRNA expression accounts for just 40% of the protein product. Only a minority of proteins, changing in abundance during heart regeneration, correlate with the amount of mRNA suggesting an important role for post-transcriptional regulation. Here, we describe a new family of translation factors called Eif4e1c which are related to canonical Eif4e proteins that initiate the rate limiting step of mRNA translation by binding to the 5' mRNA cap. Zebrafish mutants for eif4e1c have fewer cardiomyocytes and have reduced proliferation of heart muscle after injury. Additionally, eif4e1c mutants show widespread translational dysregulation of mRNA and metabolic changes in their hearts. Eif4e1c is more conserved throughout evolution than the canonical Eif4e proteins with a core group of 23 amino acids retained from ray-finned fish to sharks across ~480 million years. Interestingly, the Eif4e1c family is lost in amphibians and is absent from all terrestrial species. To our knowledge this makes eif4e1c the only fish specific gene with described roles in heart regeneration. In sum, we show that eif4e1c is critical for development and regeneration of zebrafish hearts revealing context-dependent requirements by translation initiation regulators during heart regeneration.

    Committee: Joseph Goldman (Advisor); Amanda Bird (Committee Member); Jill Rafael-Fortney (Committee Member); Sharon Amacher (Committee Member) Subjects: Cellular Biology; Developmental Biology; Molecular Biology
  • 14. Sinha, Debatrayee A Genetic Study of Fission Yeast pkd2

    Doctor of Philosophy, University of Toledo, 2023, Biology (Cell-Molecular Biology)

    Polycystins are conserved eukaryotic mechanosensitive ion channels. Loss-of-function mutations in human polycystins lead to a common genetic disorder known as autosomal dominant polycystic kidney disease (ADPKD). ADPKD patients develop numerous kidney cysts leading to renal failure. There is substantial literature on the channel activity of polycystins, but their function in growth and cytokinesis is less understood. To understand the cellular functions of polycystins, I utilized a unicellular eukaryotic model organism fission yeast (Schizosaccharomyces pombe). Previously, our group discovered that the plasma membrane-localized fission yeast polycystin homolog Pkd2p is an essential protein required for cytokinesis. The first part of this dissertation explores the function of Pkd2p by isolating and characterizing a novel temperature-sensitive mutant, pkd2-B42. This mutant showed severe defects in growth, turgor homeostasis, and cytokinesis. Pkd2-B42p localized less at the cell tips and division plane than the wild-type and was mostly retained in the endoplasmic reticulum. Strikingly, many mutant cells rapidly lost significant cellular volume (~5 min), followed by a gradual recovery, a process that we termed deflation. Unlike cell lysis, deflation did not result in the plasma membrane rupture and occurred independent of the cell cycle progression. The tip extension rate of this mutant was 80% lower than that of wild-type cells and turgor pressure of the pkd2 mutant was 50% lower. In the latter part of my dissertation, I conducted a genetic screen to identify pathways regulated by Pkd2p. I found that pkd2 mutant interacted with several other mutants of cytokinesis, or polarized cell growth, or calcium signaling. Most significantly, both pkd2-B42 and the depletion mutant pkd2-81KD partially rescued several mutants of the septation initiation network (SIN). SIN is related to the mammalian Hippo tumor suppressor. It is essential for yeast cytokinesis. Both of the pk (open full item for complete abstract)

    Committee: Qian Chen (Committee Chair); Deborah Chadee (Committee Member); Wissam Aboualaiwi (Committee Member); Matthew Wohlever (Committee Member); Song-Tao Liu (Committee Member) Subjects: Biology
  • 15. Nordin, David The Dissolution of the Dos Passos Hero and the Structure of "One Man's Initiation" and "Three Soldiers"

    Master of Arts (MA), Bowling Green State University, 1960, English

    Committee: Robert Bashore (Advisor) Subjects: American Literature
  • 16. Nordin, David The Dissolution of the Dos Passos Hero and the Structure of "One Man's Initiation" and "Three Soldiers"

    Master of Arts (MA), Bowling Green State University, 1960, English

    Committee: Robert Bashore (Advisor) Subjects: American Literature
  • 17. Rohrer, Thomas Applying the Inhibitory Cascade Model to Molar Series of Two Human Population Samples

    Master of Arts, The Ohio State University, 2022, Anthropology

    The Inhibitory Cascade Model (ICM) is a model of molar development positing that molar tooth germs influence one another's growth by a balance of activator and inhibitor molecules as they form in series. Previous research on mammals has generally validated the model, but conformation of human molars to ICM predictions has been questioned. Previous work on humans has also not assessed the extent to which population variation in molar proportions conforms to ICM predictions. Here, two different human population samples are assessed based on expectations of the ICM. Both are expected to exhibit a pattern of decreasing size across molar series, as has been shown to be the most frequent pattern in previous studies for humans. However, the two populations are predicted to differ in terms of molar size ratios given that one population sample (Seminole Nation) derives from an ancestry group that exhibits high frequencies of third molar agenesis, while the other (Gullah-Geechee) does not. If the ICM influences differences in third molar agenesis between peoples of Native American vs. African ancestry, then it is expected that molar sizes will decrease across the molar row to a greater extent in the Seminole than they do in the Gullah. Such a difference, though not definitively demonstrating a role for the ICM in third molar agenesis, would be consistent with the possibility that in the Seminole, there is greater inhibition of growth across the molar row than there is in the Gullah. Buccolingual (BL), mesiodistal (MD), and area (BL x MD) dimensions of the teeth were analyzed. Frequencies of size proportion relationships for molar areas were analyzed, with attention to patterns consistent with ICM expectations. Molar size ratios for the BL and MD dimensions as well as for areas were compared for the two population samples in simple and multiple linear regression models. Across the entire sample set, there is a clear pattern aligned with expectations of the ICM, with greatest (open full item for complete abstract)

    Committee: Debbie Guatelli-Steinberg Dr. (Advisor); John Hunter Dr. (Committee Member); Hubbe Mark Dr. (Committee Member); Barbara Piperata Dr. (Committee Member) Subjects: Physical Anthropology
  • 18. Floring, Grace Detonation Quenching and Re-initiation Behind an Obstacle Using a Global 4-Step Combustion Model

    Master of Sciences, Case Western Reserve University, 2022, EMC - Aerospace Engineering

    In this thesis a four-species, four-step combustion model is coupled to an adaptive mesh refinement (AMR)-enabled compressible flow solver to simulate detonation attenuation and subsequent re-initiation following interaction with a half-cylinder obstacle in a stoichiometric methane-oxygen mixture. Six distinct categories of detonation behavior are identified: detonation quenching, critical ignition without detonation re-initiation, critical detonation re-initiation (CDR), CDR without transverse detonation, critical transmission, and unattenuated detonation transmission. It has been concluded from these simulations that the transverse detonation wave plays an important role in the re-initiation events of a quenched detonation. Only rare cases, both experimentally and numerically, show re-initiation without transverse detonation. Some cases exhibit a pocket of unburned gas, but it is not a necessary feature for re-initiation to occur. This study demonstrates the abilities of a 4-step combustion model with its ability to capture the transverse detonation wave, which has not been captured by previous simple chemistry models.

    Committee: Brian Maxwell (Advisor); Bryan Schmidt (Committee Member); Ya-Ting Liao (Committee Member); Paul Barnhart (Committee Member) Subjects: Aerospace Engineering
  • 19. Soni, Divyang A Model for Prediction of Failure Initiation and Load Resistance Behavior in Finite Element Analyses of Connections with Welds and Bolts in Combination

    MS, University of Cincinnati, 2021, Engineering and Applied Science: Civil Engineering

    Situations such as repair and strengthening of existing structures sometimes make it unavoidable to use connections with both welds and bolts. These combined connections behave differently from only bolted or welded connections and it is known that adding the strengths of individual components of a combined connection does not equal its ultimate strength [Manuel and Kulak (2000)]. This can be attributed to differences in ductility and load resistance mechanisms of welds and bolts. The AISC specifications give some instructions on designing combined connections, which specify lower limits on strengths of welds and bolts in a combined connection, but this process of design does not take into account the bearing force in the bolts, leading to a very uneconomical design. The use of finite element analyses can be helpful in simulating combined connections under a variety of loads. The results can be helpful in examining the mode of failure and the contribution of bolts and welds in load-resistance at different stages of loading. Although previous research [Jiansuo et al. (2014); Shi et al. (2011a)] has delved in this area, the knowledge of failure initiation in combined connections remains very limited and questions about intricate details of modeling finite element analyses of combined connections remain unanswered. The objectives of this thesis were to prepare the foundations for modeling combined connections for finite element analysis and to use that knowledge to study the behavior of combined connections under a tensile load. For this it was essential to understand the details of the different modeling options available in ABAQUS along with the theoretical fundamentals of finite elements. It was also essential that the developed modeling approach be verified by comparing the results to experimental data available on this topic.

    Committee: Gian Andrea Rassati Ph.D. (Committee Chair); Thomas Burns Ph.D. (Committee Member); James Swanson Ph.D. (Committee Member) Subjects: Civil Engineering
  • 20. Kochendorfer, Logan Interpersonal Competencies and the Quality of Emerging Adults' Experiences in Friendship

    PHD, Kent State University, 2021, College of Arts and Sciences / Department of Psychological Sciences

    Friendships are among the most important interpersonal relationships in emerging adulthood. Indeed, high-quality friendships have been linked to increased happiness (Demir et al., 2015) and better adjustment (Barry et al., 2016). The mechanisms that might predict these high-quality friendship experiences are not yet well-established, however. Buhrmester et al. (1988) proposed five domains of interpersonal competence (conflict management; emotional support provision; initiation; self-assertion; self-disclosure); more recent literature has identified forgiveness and gratitude as possible additional interpersonal competencies that might influence close peer relationships (see Algoe, 2012; Worthington et al., 2017). The current study examines the measurement of these seven proposed interpersonal competencies and whether they are related to emerging adults' friendship quality experiences using both in-lab (global) measures and nightly report (daily) measures. Results provide preliminary evidence suggesting that measures of Buhrmester et al.'s (1988) interpersonal competency domains, and the two additional domains of forgiveness and gratitude, are reliable, valid, and are somewhat distinct. Additionally, each of the domains of interpersonal competence was found to be relevant for the quality of emerging adults' friendship experiences, though the relevance of each domain appears to vary depending on whether one is interested in predicting positive or negative friendship experiences, and whether one examines these experiences through global reports or reports of daily experiences.

    Committee: Kathryn Kerns (Advisor); Judith Gere (Committee Co-Chair); Angela Neal-Barnett (Committee Member); Nichole Egbert (Committee Member); Molly Merryman (Committee Member) Subjects: Psychology