University at Albany, State University of New York
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Development Of Small Ligands Targeting Pathogenic Rna Repeats In Neurodegenerative Diseases
Get PDFPathogenic microsatellite RNA expansions are toxic and can cause neuronal degeneration and dysfunction. Therapeutics that eliminate or neutralize these RNA repeats hold great promise for the treatment of many neurodegenerative diseases because they are uniformly fatal but there is no effective treatment available today. New compounds targeting these pathogenic RNA repeat sequences represent new hope to treat these diseases. The overall goal of my dissertation is to develop a high-throughput screening assay to identify small ligands as potential drug candidates against disease-associated RNA repeats and probe binding mechanisms to guide the design of optimized drug candidates, and eventually validate therapeutic functions of these lead compounds by biological studies. We used oligonucleotides to mimic cellular RNA repeats and developed an efficient fluorescence-based assay, in which the fluorescence is minimized by covalently incorporating a fluorescein into the RNA repeat sequences to improve the sensitivity and reduce false positive readings. Our studies using a previously identified CUG repeat-targeting ligand as the positive control showed that this assay was consistent with other classic binding characterization techniques such as ITC, indicating its feasibility for wide applications to measure the binding constants and kinetics in a simple and high-throughput fashion. We further expanded this assay into a hit-to-lead platform by adding a novel fluorescence thermal melting assay with traditional UV Tm and complementary CD melting assays. We have optimized our HTS fluorescent assay and expanded the library of cyclic peptidomimetics with various chemical functionalities based on a leading hit. These novel cyclic peptide compounds and other identified ligands may hold great promise as therapeutic agents for the treatment of myotonic dystrophy and other RNA repeat-related diseases
Von Neumann Algebras Of Thompson-Like Groups From Cloning Systems
Get PDFLet be a sequence of groups equipped with a so-called -ary cloning system, and denote by the resulting Thompson-like group, which ought to be regarded as a ``Thompson-esque\u27\u27 limit of the sequence . In this thesis, we record the progress made so far in our studies on the von Neumann algebras of Thompson-like groups arising from -ary cloning systems. For example, we study the inclusion of group von Neumann algebras, where is the smallest of the Higman-Thompson groups. We prove that if is equipped with a ``diverse -ary cloning system, then the inclusion satisfies the so-called weak asymptotic homomorphism property, which is equivalent to being a weakly mixing type \II_1 subfactor. As a consequence, is a singular type \II_1 subfactor in (i.e., the normalizer of in generates ) and the inclusion is irreducible, which allows us to upgrade factoriality to , i.e., will also be a type \II_1 factor. With a few other natural assumptions on the -ary cloning system, we also give sufficient conditions for when these Thompson-like groups coming from cloning systems yield type \II_1 McDuff factor von Neumann algebras and hence inner amenable groups. In particular we prove the surprising result that the pure braided Higman-Thompson group is inner amenable. Along the way, we also prove that the Higman-Thompson groups and are non-inner amenable, which is an improvement and extension of Haagerup and Olesen\u27s result that and are non-inner amenable. We prove all these and a variety of other results in this thesis
Coping With Stress In Caregiving Among Korean Immigrant Parents Of A Child With Adhd
Get PDFParents of children with ADHD were found to struggle with additional demands in caregiving. Immigrant populations reported acculturative stress as they encountered immigration stressors, including language barriers, cultural differences, lack of social support, discrimination, and so forth. Belonging to both social groups, Korean immigrant parents of children with ADHD are likely to face numerous stressors and undergo a great deal of stress. Nevertheless, little has been known about how they experience stress and coping. It is important to identify their experiences because the knowledge can be used to support their well-being and quality of life. To fill this gap, this study aims to investigate in-depth the experiences of coping with stress in caregiving among Korean immigrant parents of children with ADHD. A multiple case study was employed to identify both similarities and differences in their experiences. Purposive sampling was utilized to locate study participants. Recruitment took place at a family counseling center in New Jersey that serves Korean immigrant families. Seven weekly sessions of group psychoeducation and a free ADHD workshop were provided at the center to elicit research participation. Seven Korean immigrant parents of a child with ADHD who agreed to participate became study participants. This study used multiple data collection methods, including a brief background questionnaire, observations, focus group interviews, and individual interviews. Data analysis followed multiple case study principles including within and cross-case analyses. NVivo, qualitative data analysis software, was used to organize the database and assist with analysis. Findings suggested that while the parents each had a unique history of caregiving and immigration, there were similarities in their experiences, with active coping at their core. The experiences of stress and coping among Korean immigrant parents of a child with ADHD consisted of six common themes: 1) constantly struggling with simultaneous multiple stressors; 2) having a variety of intense stress responses; 3) undergoing negative impacts on personal well-being; 4) encountering both coping resources and obstacles at multiple levels; 5) exerting coping efforts at multiple levels; and 6) recognizing both positive changes and negative consequences at multiple levels. As time progressed, Korean immigrant parents of a child with ADHD moved forward with active coping, using positive changes as a new source of coping and reflecting on negative outcomes to modify their ineffective coping. Findings imply the ongoing and evolving nature of their coping process, suggesting the importance of existing strengths and positive changes in each system that sustain active coping. The knowledge should inform the development of culturally competent clinical services and government policies. Future studies can be extended to immigrant parents of children with ADHD who come from different socio-economic and cultural backgrounds
How Regional Innovation Networks Are Governed: Three Essays On The Roles Of Network Management In Network Effectiveness And Evolution
Get PDFAlthough a networked mode of governance has been often considered as an alternative or superior approach compared to hierarchy and market-based models, it has become clear that networks are also susceptible to failure without purposeful and deliberative management of interorganizational relationships. Constructing a longitudinal dataset of 16 regional innovation networks in South Korea, this dissertation examines how Regional Public Research Institutes (RPRIs) serve as network managers who initiate, facilitate, and mediate regional innovation systems. Drawing on a network research tradition rooted in the Dutch School of governance networks, this study examines how RPRIs leverage social structural resources, originating from their network embeddedness, to improve regional innovation outcomes and catalyze network formation over time. The first essay expands our understanding of network management by exploring the role of RPRIs from both intra- and inter-network perspectives. Their intra-regional ties enable them to reduce transactional costs of collaboration, and their inter-network ties serve as a pipeline through which novel information and perspectives flow. The second essay employs a collaboration paradox as a theoretical lens to investigate the combined effects of social capital and network management. Bridging and bonding forms of social capital result in unity-diversity tension, and network management serves as a key contingency to use these double-edged swords without being stabbed. The third essay examines the impact of public research institutes on network evolution compared to other influential actors, like universities and conglomerate firms. Evidence from a Stochastic-Actor Oriented Model shows that their varying influence on tie formation stems from whether they convey integrity-based or competency-based trust to their potential partners through their organizational and social structural resources
Searching For Regulators Of Catalase Activity Using Enzymatic Screens
Get PDFCatalase is found in a plethora of organisms and plays a crucial role in safeguarding cells against oxidative stress-induced damage to proteins, RNA, and DNA. Catalase catalyzed the decomposition of hydrogen peroxide (H2O2) into oxygen and water. Deficiencies in catalase have been linked to pathological conditions such as Diabetes, Alzheimer\u27s, and Cancer, underscoring its significance in cellular health. In bacteria like Escherichia coli, catalase is encoded by two genes, KatG and KatE, both subject to regulation through transcription, translation, and post-translational modification. Our study focused on assessing the catalase activity of mutants lacking stress response genes (e.g., lexA, soxR, soxS, marA, perR, ahpC, selD, and recA) and genes involved in translational regulation (e.g., trxB, topB, iscS, selA, selB, and selD), aiming to identify novel regulators of catalase gene expression and activity. Mutants for katE, lexA, and RecA genes show significant reductions in catalase activity, highlighting their roles in maintaining cellular redox homeostasis. In the exponential phase, mutants for katE, soxS, marA, and perR genes exhibit altered catalase activity, suggesting their involvement in regulating catalase function during rapid growth. We have demonstrated that defects in transcription factors and RNA modification activity can diminish catalase activity, suggesting a complex regulatory network governing catalase levels and function. These findings support that regulation of the oxidative stress response pathways in E. coli utilizes activities that regulate translation. This research holds significance in uncovering new insights into the intricate mechanisms governing catalase regulation, which could have implications for understanding cellular physiology
Topographies Of Desire: On Becoming The Other In Urban Crime Fiction
Get PDFThis thesis incorporates psychoanalysis in an exploration of the dynamics of body, identity, motion, and desire throughout urban crime fiction. Starting at the very origins of the genre with Edgar Allan Poe’s “The Man of the Crowd” (1840), working its way to Patricia Highsmith’s Strangers on a Train (1950) and Megan Abbott’s contemporary Dare Me (2012), to finally culminating with the film Saltburn (2023). The examination of subjectless subjects within these texts reveal the ways in which homoeroticism coalesces against the sexualized modern landscape
Textual Assessment of Leaders Individual Differences: Exploring TALID
Get PDFThe Textual Assessment of Leader Individual Differences (TALID) is a growing archive of leader speech and a dataset of individual difference scores for more than 750 global leaders. TALID includes texts accumulated by Social Science Automation, Inc and Margaret G. Hermann during a variety of research projects conducted since 1997. Recent additions to TALID include documents for Joseph Biden and Donald Trump contributed by the Xiamen University Digital Presidents Project. The scores in the data set are all generated using automated coding schemes running on Profiler Plus (Levine & Young, 2014). Variables included in TALID are for Leadership Trait Analysis (LTA) (Hermann M. G., 1980), Operational Code Analysis (OCA) (Walker, Schafer, & Young, 1988), Motive Analysis (MA) (Winter, (1987)), Verbal Behavior Analysis (VBA) (Weintraub, 1989), and Conceptual Integrative Complexity (Suedfeld, Tetlock, & Siegfried, 1992). TALID is available at: https://www.albany.edu/cehc/research/laio. Scores are provided at both the document and leader level
How Does the Degree of Remote Work Impact Perceptions and Productivity for Undergrad Accounting Workers?
Get PDFA recent development in the field of accounting is the concept of working remotely and being able to be part of a company without ever setting foot inside its doors. This concept has been accelerated by the recent pandemic that prevented companies from surviving financially if they did not adapt to allow employees to work remotely. As companies have recently been opening their doors back up to employees working in person, there is increasing dialogue about whether or not remote work should be embraced as a tool for success or rejected as a potential distraction.
This study will explore literature on how the field of accounting has adapted since 2020 to fit the remote work of an accounting firm. The research will target senior and graduate level students to determine how they have responded to working remotely at internship and entry level accounting jobs. The intention is to discover their insights on remote accounting work through qualitative questions related to how they view their productivity while working remotely versus in person. Ideally, this will also gain the perceptions of students who have not worked remotely to see how the groups compare. The importance of this project is to document the perspectives of the next generation of accounting professionals to determine whether accounting should embrace new technology
Active Equity Funds that Incorporate Venture Capital
Get PDFIn this paper, the performance of active equity funds that incorporate venture capital (VC) as part of their investment strategy is measured to gain insight into the value of VC use. Previous evidence suggests that VC investing requires a specialized skill set. PSN Enterprise data from 2000 to 2022 are analyzed to determine whether a sample of 24 active equity funds with VC investments obtain higher returns than non-VC funds despite their lack of experience in originating VC investments. Funds with VC investments are matched to corresponding funds without VC investments that are from the same asset class, have similar assets under management (AUM), and use the same performance benchmark. The results indicate that funds incorporating VC underperform across all tests. The results support the notion that using VC investments is not an automatic means of achieving higher returns, and that the successful use of VC requires specialized expertise