Doctor of Philosophy, Case Western Reserve University, 2024, Genetics

Exportin-1 (XPO1) is an essential regulator of cellular nuclear export that traffics hundreds of cargo proteins from the nucleus into the cytoplasm. Nearly three decades of research led to a detailed understanding of the mechanisms underlying XPO1-mediated transport, and this knowledge generated many XPO1-targeting small molecule probes that validated the therapeutic potential of drugging nucleocytoplasmic trafficking. More recently, growing evidence has implicated XPO1 in other functions, including in the coordination of mitotic events, regulation of gene transcription, and formation of biomolecular condensates. These functions operate independently of nuclear export and implicate XPO1 as a broad regulator of many cellular functions. In this work, we demonstrate that many structural classes of electrophilic small molecules target XPO1 at cysteine 528 to suppress T cell activation. In contrast to known cytotoxic XPO1 modulators such as Leptomycin B and the FDA-approved Selinexor, we identify a new class of “Selective Inhibitors of Transcriptional Activation” (SITAs) that display potent inhibition of T cell function with minimal impacts on XPO1-mediated nuclear export, mitotic regulation, and cell viability. To assess how SITAs suppress T cell activation despite their muted effects on nuclear export, we provide evidence that XPO1 scaffolds transcription factors of the NF-κB, AP-1, and NFAT families during T cell activation. SITAs selectively disrupt XPO1 occupancy at euchromatic regions to indirectly abrogate the chromatin localization of NFAT, thereby suppressing T cell activation without affecting cell viability. Beyond the transcription factors that are critical for T cell function, we further demonstrate that the p300 histone acetyltransferase shares many chromatin occupancy sites with XPO1. Targeted modulation of XPO1 by SITAs or small molecule degraders indirectly suppresses p300 chromatin binding and activity, providing a potential mechanistic link between XPO (open full item for complete abstract)

Committee: Drew Adams (Advisor); George Dubyak (Committee Member); Anthony Wynshaw-Boris (Committee Member); Paul Tesar (Committee Chair) Subjects: Biology; Biomedical Research; Cellular Biology; Chemistry; Immunology; Molecular Biology; Organic Chemistry; Pharmacology

Doctor of Philosophy, The Ohio State University, 2023, Slavic, East European and Eurasian Studies

“How can teachers help students improve their second language (L2) speaking accuracy?” This is a question that most L2 educators ask themselves every day. Although L2 writing is a popular topic among Second Language Acquisition (SLA) researchers, the consideration that L2 writing has the potential to act as a scaffold for L2 speaking accuracy has often been overlooked. This research attempts to draw SLA researchers' attention to the untapped potential that L2 writing has on improving L2 speaking accuracy. This research provides empirical evidence that L2 writing have a great potential to improve accuracy of L2 oral discourse. Twenty-three Novice, twenty-one Intermediate, and twenty Advanced university students of Russian participated in the study. They completed a text reconstruction task by working with the original text to 'notice the gap' using both written and spoken modes of recall. Both written and spoken forms of recall provided sufficient opportunity for improving semantic accuracy and produced textual complexity, and for acquiring new vocabulary with all three levels of learners. However, only the Novice, Intermediate, and Advanced learners working with the texts in writing showed improvement in their speaking accuracy. These findings can be considered the first step in drawing scholars' attention to the benefits of utilizing L2 writing to improve L2 speaking accuracy that have often been overlooked. This research also bridges the gap in our understanding of written and spoken recall of texts written in L2. The relationship between written and spoken recall has primarily been analyzed with English-speaking monolinguals. It has been reported that written recall provides semantically more accurate responses than spoken recall due to the higher cognitive load and attention required to produce a text. The pilot study described in this dissertation examined the written and spoken text recall relationship in L2 learners of Russian, and analyzed how individual w (open full item for complete abstract)

Committee: Ludmila Isurin (Advisor); Mineharu Nakayama (Committee Member); Wynne Wong (Committee Member) Subjects: Foreign Language; Language; Linguistics; Slavic Studies

Doctor of Professional Studies (D.P.S.) in Instructional Design Leadership, Franklin University, 2021, International Institute for Innovative Instruction

Discussion board forums have become commonplace within online learning environments (OLEs). With student enrollment in online classes continuing to rise and the emergence of COVID-19, more students will be utilizing discussion forums within OLEs than ever before. Positive pedagogical support for the use of discussion forums abounds, but studies on the efficacy of discussions in online forums show mixed results. This study seeks to compare two types of discussion forums. One type, instructor-led scaffolding, was designed with pedagogy such as feedback, discussion prompts, and scaffolding implemented by the instructor. The second type, technology-enhanced scaffolding, was designed to foster autonomous motivation in students, while some feedback and scaffolding were implemented automatically by the technology-enhanced platform and offloaded onto discussion TAs provided for instructors by the platform. The study used the Interaction Analysis Model (IAM) to measure student knowledge construction levels and interpreted results to determine the impact of pedagogical design implementation on student knowledge construction in undergraduate online learning environments.

Committee: Meghan Raehll (Committee Chair); Matthew Barclay (Committee Member); Lewis Chongwony (Committee Member) Subjects: Adult Education; Artificial Intelligence; Design; Education; Educational Technology; Instructional Design

Doctor of Philosophy, The Ohio State University, 2021, Educational Studies

This dissertation study was set within a collaborative, discussion-based classroom intervention called Collaborative Social Reasoning (CSR). In this study, I aim to examine teacher scaffolding moves, or strategies used to support students' learning, in relationship with student equity in CSR discussions. Equity indicators analyzed include uptake, or use of a peer's idea in a subsequent turn of talk; relational invitations, a construct derived from the data and consisting of students inviting a peer to share; and conflicts for the floor, which occurred when one student prevented another from sharing their idea. This last factor indicates lower levels of equity, while the initial two indicate higher equity. Teacher scaffolding was analyzed with equity indicators at the turn-by-turn level using statistical discourse analysis and more holistically by examining the proportion of turns containing the variables of interest in repeated measures logistic regression analysis. The results showed that teacher scaffolding was negatively or not related to all equity indicators. This suggested that, in this context, teacher scaffolding was associated with reduced uptake and relational invitations, but also with reductions in conflicts for the floor. In turn, this suggests that teacher scaffolding improved participatory equity by reducing conflicts for the floor but was associated with reduced relational equity via uptake and relational invitations. The relationship with uptake was stronger and more consistent than the relationship with conflicts for the floor, suggesting that teachers' largest influence on equity is on relational, rather than participatory, equity.

Committee: Tzu-Jung Lin Ph.D. (Committee Chair); Lynley Anderman Ph.D. (Committee Co-Chair); Shayne Piasta Ph.D. (Committee Member) Subjects: Educational Psychology; Educational Theory; Elementary Education

Doctor of Philosophy, The Ohio State University, 2018, EDU Teaching and Learning

The purpose of this study was to examine the reflexive ways in which tensions between desired academic perspectives and life experiences, which are brought forth by learners when dealing with modeling contexts, are addressed by teachers so to advance learners' modeling capacity. In particular I examined the activities of one 11th grade pre-calculus teacher as she attempted to establish a classroom culture of mathematical modeling. Of interest was unpacking how learners were enculturated into a mathematical modeling practice, and ways that the teacher's enacted view of modeling advanced the development of both modeling capacity and curricular knowledge. The multiple lenses of ethnomathematics (D'Ambrosio, 1985) and in particular ethnomodeling (Orey & Rosa, 2010) coupled with linguistic discourse analysis (Bloome et al, 2010) were utilized to more precisely identify the local views of mathematical modeling that the participating teacher held. The analysis of data revealed 23 specific components indicative of the teachers' mathematical modeling practice. Results of this study indicated that the teacher's view of mathematical modeling was not as a vehicle for the learning of new mathematical concepts, nor was it that of a content in its own right, but rather a bridge between these two perspectives which served the opportunity to both advance modeling capacity and meet curricular demands.

Committee: Azita Manouchehri (Advisor); Theodore Chao (Committee Co-Chair); James Fowler (Committee Member) Subjects: Mathematics Education

Doctor of Philosophy, University of Akron, 2016, Elementary Education

The purpose of this study is to examine the sibling relationship as it pertains to the development of early literacy skills. If siblings do, in fact, help to foster early literacy skills, then perhaps we can help preschool teachers to capitalize on this mentor-like relationship among siblings. Preschool teachers could use similar mentor models in their classrooms and help to educate parents about the powerful influence that siblings have on one another and how this influence can be used in positive ways. If parents lack the ability to learn about fostering the sibling relationship, then perhaps preschool teachers could directly influence their students to share literacy activities with their younger siblings. Guiding Questions: (1) What scaffolding activities do parents report when older sibling(s) support younger sibling(s) in the acquisition of early literacy skills? (2) What sibling interactions do parents report when older sibling(s) support younger sibling(s) in the acquisition of early literacy skills? (3) What patterns of behavior do parents report when the older sibling(s) support younger sibling(s) in the acquisition of early literacy skills?

Committee: Lisa Lenhart Dr. (Committee Chair); Xin Liang Dr. (Other); Al Daviso Dr. (Committee Member); Harold Foster Dr. (Committee Member); Ronald Otterstetter Dr. (Committee Member) Subjects: Education

Doctor of Philosophy, The Ohio State University, 2016, EDU Teaching and Learning

The notion of scaffolding is commonly referred to in educational research and practice, however there is little empirical evidence on its role in literacy learning, and even less so in the context of early writing. Additionally, of the empirical work on the topic, scaffolding is often used as synonymous with any form of guidance or support. Therefore, bringing the theoretical tenets of the scaffolding metaphor to bear, this study examined the nature of and relationship between teachers' scaffolding, in particular the teacher's instructional and domain contingency during writing, and first grade students' writing outcomes. Data sources were taken from an extant dataset and included 56 videos of 24 teachers working one-to-one with 25 first grade students during the writing portion of the Reading Recovery lesson, students' pre and post assessment data on three measures of writing, lesson records, and student writing samples. Problem-solving cycles in which the teacher and child interacted on a particular writing-related content were transcribed and coded in terms of instructional contingency, how the teacher adjusted her degree of control in response to the student, and domain contingency, which referred to the content focus of the interaction and the overall appropriateness of the teaching moves in the problem-solving cycle. Hierarchical and stepwise regression were used to determine whether the proportion of instructionally and domain contingency moves and cycles accounted for any variance in the students' writing outcome scores above and beyond entry score. Results of the hierarchical regression indicated that neither the proportion of instructionally contingent moves, nor the proportion of cycles rated as good teaching moves had a significant impact on exit Writing Vocabulary, Hearing and Recording Sounds in Words, or Early Writing Observational Rubric score, nor did the teacher's shift in degrees of control within opportunities for contingency. However, s (open full item for complete abstract)

Committee: Emily Rodgers Ph.D (Advisor); Jerome D'Agostino Ph.D (Committee Member); Ian Wilkinson Ph.D. (Committee Member) Subjects: Education; Literacy

Doctor of Philosophy, University of Akron, 2013, Secondary Education

The purpose of this study is to demonstrate how Q Methodology can be used as a needs assessment tool for a Biology graduate teaching assistant (GTA) instructional training program. GTAs are used as the instructors of an increasingly diverse population of undergraduate students. GTAs are a diverse population of students with varying amounts of pedagogical preparation, research abilities, and motivation to complete their graduate study. They are often expected to prepare and grade exams, write their own syllabi, design course curriculum, prepare and present lectures, monitor student progress, hold office hours, and assign final grades, all with minimal faculty supervision. Although not all GTAs will become professors, many will, and the teaching assistantship remains the major preparation for their roles as faculty members. Since the majority of science professors have been GTAs, this instructional training program is of critical importance. Approaches to developing instructional training programs for GTAs vary from departmental workshops to campus-wide instructional seminars. Program evaluation is an intrinsic part of assuring that such programs best serve GTA needs, and that GTAs can best fulfill their roles in their respective departments. Q Methodology offers a number of potential advantages over traditional survey techniques for assessing needs of GTAs throughout their graduate school career, allowing program supervisors to evaluate and modify the program relative to GTA needs. Q Methodology allows the researcher to identify and interpret various viewpoints the GTAs hold in regard to graduate school. This is not only important to the supervisors of GTA instructional programs, but to the GTAs. This Q Methodology study led to three GTA viewpoints (“The Emerging Teacher,” “The GTA Who Prefers Research,” and “The Anxious GTA”) that provide insight about GTA and programmatic needs. Q Methodology can provide predictor profiles, or “typologies” that are more usefu (open full item for complete abstract)

Committee: Jennifer Milam Dr. (Advisor); Susan Ramlo Dr. (Advisor); Robert Joel Duff Dr. (Committee Member); Gary Holliday Dr. (Committee Member); John Nicholas Dr. (Committee Member) Subjects: Biology; Education; Teacher Education; Teaching

PhD, University of Cincinnati, 2005, Medicine : Molecular Genetics, Biochemistry, and Microbiology

Tankyrases are novel poly(ADP-ribose) polymerases that have SAM and ankyrin protein-interaction domains. They are found at telomeres, centrosomes, nuclear pores and the Golgi-apparatus, and participate in telomere length regulation and resolution of sister chromatid association. Their other function(s) are unknown and it has been difficult to envision a common role at such diverse cellular locations. We isolated the chicken tankyrase homologs and examined their interaction partners, subcellular location and domain functions to learn more about their mode of action. Cross-species sequence comparison indicated that tankyrase domain structure is highly conserved and supports division of the ankyrin domain into five subdomains, each separated by a highly conserved LLEAAR/K motif. GST-pull down experiments demonstrated that the ankyrin domains of both proteins interact with chicken TRF1. Analysis of total cellular and nuclear proteins showed that cells contain approximately twice as much tankyrase 1 as tankyrase 2. Although ~90% of each protein is cytoplasmic, both tankyrase 1 and 2 were also nuclear. This nuclear location, together with its ability to interact with TRF1, point to a telomeric function for tankyrase 2. This work shows that tankyrases polymerize through their SAM domain to assemble large protein complexes. In vitro polymerization is reversible but still allows interaction with ankyrin-domain binding proteins. Polymerization also occurs in vivo, with SAM-dependent association of overexpressed tankyrase leading to the formation of large tankyrase-containing vesicles, disruption of Golgi structure and inhibition of apical secretion. Finally, tankyrase polymers are dissociated efficiently by poly(ADP-ribosy)lation. This disassembly is prevented by mutation of the PARP domain. Our findings indicate that tankyase 1 promotes both assembly and disassembly of large protein complexes. Thus, tankyrases appear to be master scaffolding proteins that regulate the format (open full item for complete abstract)

Committee: Dr. Carolyn Price (Advisor) Subjects:

Doctor of Philosophy, The Ohio State University, 2011, EDU Teaching and Learning

The present study was conducted to answer questions regarding the amount and types of scaffolding early childhood teachers use in their classrooms, as well as changes that may occur in their use of such strategies throughout the school year. Additionally, the present research explored the relationship between children's vocabulary gain and teachers' use of scaffolding strategies. In order to address these aims, this study examined the scaffolding strategies employed by 37 early childhood teachers and the vocabulary skills of 173 children in their classrooms. Specifically, this research looked at videotaped observations of teachers' use of scaffolding at three time points throughout the school year and assessed these observations for amount and type of scaffolding use. Descriptive analyses provided information regarding amount and types of scaffolding that occurred in these classrooms, while growth curve analyses was conducted to characterize changes in teachers' use of scaffolding types across the school year. Finally, hierarchical linear models (HLM) were used to examine the relationship between teachers' use of scaffolding and children's vocabulary gains. Results indicated that teachers utilized scaffolding strategies at relatively low rates and that they utilized strategies that could be characterized as low support (i.e., those strategies that encourage children's higher-order understandings about the lesson and help them generalize their learning beyond the lesson itself) more frequently than high-support scaffolding strategies (i.e., those strategies that enable children to successfully participate in activities and move gradually toward independence over time). Growth curve analyses demonstrated that teachers' use of high-support strategies declined over the year, whereas the use of low-support strategies increased. Finally, HLM models revealed that teachers' use of low-support scaffolding strategies at the beginning of the year was associated with children's (open full item for complete abstract)

Committee: Laura Justice PhD (Advisor); Ann OConnell EdD (Committee Member); Stephen Petrill PhD (Committee Member) Subjects: Early Childhood Education; Education; Language; Literacy; Reading Instruction; Teacher Education

Master of Science (MS), Ohio University, 1997, Mechanical Engineering (Engineering)

This Thesis evaluates the kinematics, statics, and dexterity of planar active scaffolding structures. These active structures are types of kinematically-redundant truss-based manipulators. The structures are combined and incorporated into a human-lift called the active scaffolding system. The active scaffolding system is advantageous in many work environments because it is compact and provides 3-dimensional motion. There are many steps necessary for proper design and implementation of the active scaffolding system, they are as follows: kinematic design, dynamic design, control system design, structural design, optimization, and experimental hardware. This Thesis lays the ground work necessary to achieve these design goals.

Committee: Robert Williams, II (Advisor) Subjects: Engineering, Mechanical

PHD, Kent State University, 2008, College of Education, Health, and Human Services / Department of Adult, Counseling, Health and Vocational Education

There is general acknowledgment on the positive effects of scaffolding on student learning. Yet, does the teacher have to mediate the scaffolding or can it be as effective if mediated by technology?This study addresses the need for library media specialists to teach students in the most effective and efficient manner in a limited time frame. The results of a quasi-experiment research design examines different deliveries of scaffolding: (a) a teacher mediated scaffold lesson that demanded 60 minutes of the librarian's undivided attention; (b) a technology mediated scaffold lesson that demanded 20 minutes of the librarian's undivided attention; and (c) a nonscaffolded group that required 5 minutes of the librarian's undivided attention. Participants included 73 (35 female and 38 male) 10th- grade health students from a predominately White suburban high school. All three groups covered the same material, worked collaboratively, and the end project requiring citations remained the same. Lessons addressed the need for students to evaluate resources on the Internet. Websites used for student research were scored for quality using a rubric. The three groups were involved in five research projects spaced 2 weeks apart. The lessons were implemented after their first project to obtain a baseline. The website evaluation scores from all research projects were assessed for quality to see if task achievement and longevity was achieved. Results showed the two groups that received some form of scaffolding instruction did not differ significantly from each other but each differed significantly on their web evaluation achievement and longevity scores from the nonscaffolded group. Gender, grade point average, race, and education program did not have an effect on scores.

Committee: Albert Ingram PhD (Committee Co-Chair); Cindy Kovalik PhD (Committee Co-Chair); Carolyn Sue Brodie PhD (Committee Member) Subjects: Educational Psychology

Doctor of Philosophy, The Ohio State University, 2013, EDU Physical Activity and Educational Services

This study examined the effectiveness of a sound box intervention that incorporated scaffolding procedures on preschoolers' phoneme segmentation skills. The participants consisted of four African-American preschool students attending a Head Start center and who had difficulty acquiring phonemic awareness skills as measured by the DIBELS and Get it Got Go! assessments. An intervention was employed which utilized a sound box and scaffolding procedures to improve preschool participants' performance on a phoneme segmentation task. Briefly, a sound box is a drawn rectangle with divided sections according to the number of phonemes in a word. Participants were required to slide tokens in respective divided sections as they articulated/segmented each sound in a word. Verbal as well as visual supports associated with the sound box technique were gradually faded in a systematic way (i.e., scaffolding) to assist children in segmenting phonemes without the use of those supports. A multiple probe design across four participants was used to measure the effects of the intervention. All participants improved in trend and level during intervention phases in contrast to their performance in the baseline phase. Participants were able to segment phonemes when verbal and visual supports were gradually removed, and generalized segmenting phonemes in words that were directly taught during intervention phases to words that were not directly taught during intervention phases. Implications for practitioners and future directions are discussed.

Committee: Laurice Joseph Ph.D. (Advisor); Antoinette Miranda Ph.D. (Committee Member); Laurice Joseph Ph.D. (Committee Member) Subjects: Education