SACM - United States of America
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Item Restricted Efficacy of MDM2 and Epigenetic Inhibitors for Neuroblastoma Treatment(Nova Southeastern University, 2024) Momenah, Tahani Mohammad; Rathinavelu, AppuNeuroblastoma (NB), a prevalent pediatric solid tumor originating from neural crest cells, remains a significant challenge in childhood cancer treatment, accounting for 15% of pediatric cancer-related deaths. This comprehensive study investigated the effects of two promising compounds, RG-7388 and CM-272, on neuroblastoma cells. RG-7388 is a potent MDM2 inhibitor, whereas CM-272 is a dual inhibitor targeting G9a and DNMT1. This study utilized two well-established neuroblastoma cell lines, SK-N-SH and IMR-32, to elucidate the molecular mechanisms underlying the anticancer properties of these compounds. Initial cytotoxicity studies were established for 24 hours. showed a decrease in the viability of SK-NSH and IMR-32 cells, in a time and concentration-dependent manner. Moreover, The experimental findings demonstrated that both RG-7388 and CM-272 effectively induced apoptosis in neuroblastoma cells, as evidenced by elevated levels of PARP and cleaved PARP with CM272 and activation of Caspase-3/7 confirmed through DEVD-amc substrate fluorescence analysis for both RG-7388 and CM-272. In addition, Immunofluorescence results revealed significant upregulation of p21 expression following both treatments. Western blot analysis confirmed distinct mechanisms of action: RG-7388 stabilized p53 by inhibiting MDM2, resulting in increased p53, MDM2, and p21 protein levels. At the same time, CM-272 showed no effect on p53 or MDM2 but significantly elevated p27 levels, suggesting its role in cell cycle regulation through epigenetic mechanisms via DNMT and G9a inhibition. RG-7388 and CM272 effectively downregulated anti-apoptotic proteins BCL-XL and XIAP, though neither affected autophagy markers Beclin-1, LC3-I, and LC3-II. qRT-PCR analysis revealed significant upregulation of CDKN1A (p21) mRNA and downregulation of PARP1 mRNA in treated cells, with CM-272 additionally reducing the expression of DNMT-associated genes. We conducted a gene expression analysis to elucidate further the molecular changes induced by these compounds. This comprehensive approach revealed significant alterations in the expression of cell cycle-related genes after CM- 272 treatment. These findings provide valuable insights into the distinct and complementary mechanisms by which RG-7388 and CM-272 exert their anticancer effects, advancing the understanding of targeted therapeutic strategies for high-risk neuroblastoma.16 0Item Restricted The Influence of Ultrasonic Vibrations on Convective Heat Transfer and Pressure Dynamics in Multi-Geometrical Heat Transfer Systems Using Water, Propylene Glycol, and Ionic Liquids(ARIZONA STATE UNIVERSITY, 2024) Alenezi, Abdulmajeed; Phelan, Patrick E.Thermal management in modern devices has become increasingly challenging due to the higher heat output from advanced electronics. Effective cooling solutions are essential to enhance performance, extend operational life, and reduce device failure rates. For every 10℃ increase in ambient temperature, device lifespan decreases by 50%, underscoring the need for innovative cooling methods. Micro/minichannel heat sinks have emerged as a promising solution due to their compact size and low thermal resistance. Various mechanisms have been studied to enhance thermal performance, including novel geometries, tailored fluid properties, and the use of ultrasonic waves. Ultrasonic waves have gained attention for their potential to improve heat transfer by disrupting boundary layers and enhancing fluid mixing. This thesis explores whether ultrasound can enhance thermal system performance and investigates the influence of key fluid properties, material selection, and varying parameters such as flow rate, heat input, and ultrasound power on heat transfer and pressure drop. Three experiments were conducted to evaluate the effects of ultrasonic vibrations on heat transfer and pressure drop across different systems. In the first experiment, ultrasonic vibrations enhanced heat transfer by 13.5% in a circular minichannel heat sink made of stainless steel, using water as the coolant. In the second experiment, using a rectangular minichannel heat sink with water and propylene glycol-water mixtures, ultrasound improved heat transfer, with the highest enhancement observed in deionized water, while the effectiveness decreased with higher propylene glycol concentrations. The third experiment, conducted in a horizontal copper tube, showed a 13.5% heat transfer improvement for water and 11.3% for an ionic liquid. Across all experiments, the effect of ultrasound diminished as flow rates increased, and higher viscosity fluids reduced its effectiveness. Additionally, ultrasound contributed to an increase in pressure drop in all cases. Overall, these findings highlight the potential of ultrasonic vibrations as an effective technique for enhancing heat transfer. This thesis could provide a basis for future research into ultrasonic technology as a promising technique.10 0Item Restricted Molecular mechanisms regulating G protein signaling bias(University of Rochester, 2024) Alabdali, Rana; Orlandi, CesareG Protein Coupled Receptors (GPCRs) are the largest group of membrane receptors in mammals. They are seven transmembrane proteins that couple and transduce signals through heterotrimeric G proteins and β-arrestins which further regulate various downstream signaling pathways. In this context, biased signaling is defined as the ligand-dependent selectivity for certain signal pathways when compared to a reference ligand acting on the same receptor. The most classical example of biased signaling is the functional selectivity between G proteins and β- arrestin. However, signaling bias can also be generated in response to distinct activation of individual Gα proteins leading to different downstream effectors. Therefore, we hypothesize that agonist structure, accessory molecules, and post- transcriptional modifications are three major contributors of G protein signaling bias that in turn regulates unique intracellular effectors and responses. Using cell- based assays, I investigated the effect of agonist structure on serotonin 1A receptor (5-HT1AR) coupling profile using our optimized G protein nanoBRET assay. Also, I examined the effect of accessory lipid such as cholesterol on G protein coupling using 5-HT1AR as model in transfected HEK293 cells. Additionally, I explored the effect of the interaction with the accessory protein receptor component protein (RCP) on the G protein coupling profile of CGRP receptor. Finally, I studied how RNA edited isoforms of serotonin 2C receptor (5- HT2CR) could tune its G protein coupling profile. This would help in understanding how Gα protein preferential selection can potentially alter cellular responses.13 0Item Restricted The Emerging Link between Microbial Derived DPP-4 and Cognitive Health: The Gut-Microbiome Perspective(North Carolina State University, 2024) Aljumaah, Mashael Riyadh; Bruno-Barcena, Andrea Azcarate-Peril and JoseAs a pivotal microbial-host isozyme and counterpart to human dipeptidyl peptidase-4 (hDPP-4), microbial dipeptidyl peptidase-4 (mDPP-4) holds significant potential for understanding and treating metabolic and cognitive disorders across diverse demographic groups including aging populations. Chapter 1 introduces the research problem and evidence of gut microbiome involvement in cognitive aging, emphasizing how host-microbe interactions can regulate and maintain host homeostasis. Chapter 2 provides clinical evidence from a double- blind, placebo-controlled, randomized clinical trial by examining variations and their links to cognitive decline in aging populations. The study focused on middle-aged and older adults diagnosed with mild cognitive impairment (MCI) and compared their gut microbiome compositions to those of neurologically healthy individuals. A key aspect of our finding was the identification of specific microbial species, Prevotella ruminicola, Bacteroides thetaiotaomicron, and Bacteroides xylanisolvens, which showed a significant correlation with MCI at baseline; notably, both genera Prevotella and Bacteroides are among the main groups that carry mDPP-4 genes. The intervention with probiotic Lactobacillus rhamnosus GG (LGG) significantly reduced the absolute abundance of Prevotella sp. and correlated with improved cognitive scores in the MCI group. These findings suggest that targeted microbial interventions serve as effective strategies for enhancing cognitive function and slowing the progression of cognitive decline in compromised populations. Chapter 3 reviews the properties of hDPP-4 and introduces mDPP-4, underscoring the need for more research on its role in human health. We analyze mDPP-4's structure, compare it with human analogs, and discuss the potential impact of conventional hDPP-4 inhibitors on the gut microbiome, proposing the need for personalized microbiome interventions. In Chapter 4, we conduct an in-depth examination of mDPP-4, emphasizing its enzymatic functions, similarities, and differences with hDPP-4. We propose a novel classification for mDPP-4, which defines distinct classes and clades that differ significantly from hDPP-4. Finally, Chapter 5 highlights the main findings of this study and delineates future research directions in the field of mDPP-4 research. This body of work highlights the potential of mDPP-4 as a viable target for therapeutic development, extending to systemic conditions involving hDPP-4. It underscores the efficacy of personalized microbiome-targeted interventions, setting the stage for precision medicine across a spectrum of metabolic and cognitive disorders through microbiome research.4 0Item Restricted PARENTS’ OPINIONS ON USING APPLIED BEHAVIOR ANALYSIS (ABA) TO INCREASE NEUROTYPICALLY DEVELOPING CHILDREN’S LEVEL OF PHYSICAL ACTIVITY(Oakland University, 2024) Faheem, Ahlam; Korneder, JessicaPhysical activity is important to reduce the risk of several diseases and in some cases death. Early childhood theorists stressed the importance of physical activity, lowering its cost, and rewarding physical movements. ABA interventions were an essential part of this paper because of its importance in altering the behavior and keeping the desired change even after the intervention. In general, parents and teachers’ motivations and engagement with children were the most effective way to increase physical activity in both ABA and ECE articles. Results of this research found that general knowledge of ABA is low and there is a need to increase ABA awareness and usage in the society before directing toward specific interventions. Finally, the cost of ABA interventions without insurance coverage is astronomical, yet all children have the right to receive behavioral treatments and live in an altered environment that ensure them the best overall development.8 0Item Restricted PARENTS’ OPINIONS ON USING APPLIED BEHAVIOR ANALYSIS (ABA) TO INCREASE NEUROTYPICALLY DEVELOPING CHILDREN’S LEVEL OF PHYSICAL ACTIVITY(Oakland University, 2024) Faheem, Ahlam; Korneder، JessicaPhysical activity is important to reduce the risk of several diseases and in some cases death. Early childhood theorists stressed the importance of physical activity, lowering its cost, and rewarding physical movements. ABA interventions were an essential part of this paper because of its importance in altering the behavior and keeping the desired change even after the intervention. In general, parents and teachers’ motivations and engagement with children were the most effective way to increase physical activity in both ABA and ECE articles. Results of this research found that general knowledge of ABA is low and there is a need to increase ABA awareness and usage in the society before directing toward specific interventions. Finally, the cost of ABA interventions without insurance coverage is astronomical, yet all children have the right to receive behavioral treatments and live in an altered environment that ensure them the best overall development.Item Restricted A Grammar of Alnamas Arabic(The University at Buffalo, 2024-12-17) Alamri, Mohammed; Good, JeffThis dissertation is a grammar of Alnamas Arabic, an endangered variety of Arabic spoken predominantly by an estimated 4,800 individuals from the older parent and grandparent generations in the Alnamas region of southwestern Saudi Arabia. The dialect is part of the southwestern Arabic dialect group and exhibits distinctive linguistic features that set it apart from other varieties of Arabic. This grammar is based on the author’s fieldwork, which included recording and analyzing speech from native speakers in Alnamas. Since Alnamas Arabic has remained largely unstudied, this research provides the first major documentation and description of the dialect, offering a comprehensive analysis of its phonology, morphology, and syntax.15 0Item Restricted In Between Sovereigns-The Political Economy of International Oil Concessions(University of Pittsburgh, 2024-11-13) Sulaimani, Mohammed; Murtazashvili, IliaThis dissertation develops a novel theory of oil nationalization based on insights from new institutionalism in political science and economics, arguing that high enforcement costs inherent in international oil concession agreements contribute significantly to oil nationalization. The 20th century, characterized by fragile international oil governance, saw numerous instances where international oil companies (IOCs) struggled to enforce contracts, leading to host state opportunistic behavior and ultimately nationalization. While existing scholarship offers valuable insights into the political, economic, and ideological drivers of oil nationalization, it often overlooks a crucial structural factor: the lack of third-party enforcement in international oil concession agreements. This research utilizes a case study methodology, focusing on the Aramco concession agreement with the Saudi Arabian government. Through an analysis of archival data, diplomatic correspondence and personal memoirs, the research reveals the substantial enforcement costs paid by both Aramco and the United States’ government in their efforts to maintain the concession agreement. These costs, manifesting as financial compromises, diplomatic maneuvering, and even covert operations, highlight the fragility of self-enforcing contracts in the absence of a formal third-party enforcement mechanism. The dissertation argues that nationalization emerges as a consequence of the failure to adequately address these escalating enforcement costs. Building upon these findings, the dissertation suggests future research avenues exploring other historical nationalization cases, such as the Anglo-Iranian Oil Company (AIOC) in 1951, as well as contemporary examples such as Chinese national oil companies operating abroad. By investigating these diverse cases through the lens of enforcement costs, this research contributes to a deeper understanding of the complex dynamics shaping international resource governance.13 0Item Restricted Disinformation Classification Using Transformer based Machine Learning(Howard University, 2024) alshaqi, Mohammed Al; Rawat, Danda BThe proliferation of false information via social media has become an increasingly pressing problem. Digital means of communication and social media platforms facilitate the rapid spread of disinformation, which calls for the development of advanced techniques for identifying incorrect information. This dissertation endeavors to devise effective multimodal techniques for identifying fraudulent news, considering the noteworthy influence that deceptive stories have on society. The study proposes and evaluates multiple approaches, starting with a transformer-based model that uses word embeddings for accurate text classification. This model significantly outperforms baseline methods such as hybrid CNN and RNN, achieving higher accuracy. The dissertation also introduces a novel BERT-powered multimodal approach to fake news detection, combining textual data with extracted text from images to improve accuracy. By lever aging the strengths of the BERT-base-uncased model for text processing and integrating it with image text extraction via OCR, this approach calculates a confidence score indicating the likeli hood of news being real or fake. Rigorous training and evaluation show significant improvements in performance compared to state-of-the-art methods. Furthermore, the study explores the complexities of multimodal fake news detection, integrat ing text, images, and videos into a unified framework. By employing BERT for textual analysis and CNN for visual data, the multimodal approach demonstrates superior performance over traditional models in handling multiple media formats. Comprehensive evaluations using datasets such as ISOT and MediaEval 2016 confirm the robustness and adaptability of these methods in combating the spread of fake news. This dissertation contributes valuable insights to fake news detection, highlighting the effec tiveness of transformer-based models, emotion-aware classifiers, and multimodal frameworks. The findings provide robust solutions for detecting misinformation across diverse platforms and data types, offering a path forward for future research in this critical area.30 0Item Restricted Evaluation of Surface and Mechanical Properties of Ceramic-Reinforced PEEK as a Denture Base Material(The State University of New York- University at Buffalo, 2023) Almogbel, Lolowh; Li, RuiPurpose: This in vitro study aimed to compare flexural strength, surface roughness, and biofilm formation of ceramic-reinforced polyetheretherketone (PEEK) with conventionally heat-compressed and milled polymethylmethacrylate (PMMA) denture base materials. Materials and methods: Thirty strips (6.4 mm × 10 mm × 3 mm) and 30 discs (10 mm × 1 mm) were fabricated from a heat-compressed PMMA, milled PMMA, and ceramic-reinforced PEEK, 10 each. One surface of each sample was polished to mimic the laboratory procedure for denture base materials. Strips were then subjected to a three-point bend test using a universal testing machine at a crosshead speed of 5.0 mm/min. An optical profilometer was used to assess the Ra value (mm) of the discs on polished and unpolished sides. Biofilm formation behavior was analyzed by measuring the colony-forming unit (CFU)/mL of Candida albicans on the unpolished surface of the discs. One-way ANOVA followed by Tukey multiple comparison tests were used to compare the flexural strength, Ra value, and biofilm formation of the studied materials (a = 0.05). Results: Ceramic-reinforced PEEK showed significantly higher flexural strength (178.2 ± 3.2 MPa) than milled PMMA (89.6 ± 0.8 MPa; p < 0.001) and heat-compressed PMMA (67.3 ± 5.3 MPa; p < 0.001). Ceramic-reinforced PEEK exhibited a significantly higher Ra value than the other groups on unpolished sides; however, the polishing process significantly reduced the Ra values of all studied groups (p < 0.05). There was no significant difference in C. albicans adhesion among the groups (p < 0.05). Conclusion: The flexural strength of tested materials was within acceptable limits for clinical use as a denture base material. Ceramic-reinforced PEEK had the highest surface roughness; however, its similarity in biofilm formation to other groups indicates its clinical acceptability as denture base material.15 0