Physical Sciences and Mathematics Commons^™

Incorporating Solvation Thermodynamic Mapping In Computer-Aided Drug Design, Yeonji Ji

Dissertations, Theses, and Capstone Projects

Advancements in computational techniques have revolutionized structure-based drug design, substantially improving the efficiency and effectiveness of the drug discovery process by reducing time, costs, and labor requirements. These advancements include various methods, such as investigating small molecule ligands binding to proteins, exploring alternative protein conformations, and solvation mapping on the protein surfaces. Among these methods, understanding the correlation between protein-ligand binding and the role of solvation is important.

A fundamental concept in protein-ligand binding is shape and electrostatic complementarity, which is complicated by the inherent flexibility of proteins. In the absence of small molecule ligands, proteins are complementary to surface …

Microencapsulation Of Cosmos Caudatus Kunth Extract Using Sodium Alginate And In Vitro Antioxidant Activity Test, Safina Samara Nur Fadlila, Oktavia Eka Puspita, Zubaidah Ningsih, Anna Safitri

Makara Journal of Science

This study aims to encapsulate Cosmos caudatus K. leaf extract in sodium alginate crosslinked with calcium chloride (CaCl₂) as coating materials through freeze-drying. Antioxidant assays were performed to evaluate the applicability of the microcapsules as antidiabetic medicines. Their characteristics, antioxidant activity, and encapsulation efficiency (EE) were also examined. Results indicated that the concentration of sodium alginate and pH influenced the manufacturing process of the microcapsules. The highest EE was obtained at pH 6 and alginate concentration of 2% (w/v). The IC₅₀ for the antioxidant activity of the microcapsules was 139.96 ± 1.094 μg/mL. Scanning electron microscopy confirmed …

Potent And Selective Small Molecule Mcl-1 Inhibitor Demonstrates Anti-Myeloma Activity And Overcomes Chemotherapy Resistance, Omar Sami Faleh Al-Odat

Theses and Dissertations

Despite a record number of clinical studies investigating various anti-myeloma treatments, the 5-year survival rate for multiple myeloma (MM) patients in the US is only 55%, and nearly all patients relapse. Poor patient outcomes demonstrate that myeloma cells are "born to survive” which means they can adapt and evolve following treatment. Thus, new therapeutic approaches to combat survival mechanisms and target treatment resistance are required. Importantly, Mcl-1, anti-apoptotic protein, is required for the development of MM and treatment resistance. This study looks at the possibility of KS18, a selective Mcl-1 inhibitor, to treat MM and overcome resistance. Our investigation demonstrates …

Mathematical Modeling And Examination Into Existing And Emerging Parkinson’S Disease Treatments: Levodopa And Ketamine, Gabrielle Riddlemoser

Undergraduate Honors Theses

Parkinson’s disease (PD) is the second most common neurodegenerative disease across the world, affecting over 6 million people worldwide. This disorder is characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta (SNpc) due to the aggregation of α-synuclein within the brain. Patients with PD develop motor symptoms such as tremors, bradykinesia, and postural instability, as well as a host of non-motor symptoms such as behavioral changes, sleep difficulties, and fatigue. The reduction of dopamine within the brain is the primary cause of these symptoms. The main form of treatment for PD is levodopa, a precursor …

Synthesis Of Thermoresponsive Poly(N-Isopropyl Acrylamide) Based Core-Shell And Hollow Shell Nanogel With Tunable Core And Shell Thickness, Mohamad Hijazi, Molla R. Islam

Student Scholar Symposium Abstracts and Posters

Nanogels have emerged as a notably safer and more effective means for drug delivery, primarily due to their adjustable drug-loading capabilities. Hollow-core nanoparticles offer some unique properties that are desirable for drug delivery applications. Initially, silica core nanoparticles were synthesized using the Stöber process at different temperatures where Tetraethoxysilane (TEOS) undergoes hydrolysis in the presence of ethanol and then a condensation reaction to form silica nanoparticles. Scanning Electron Microscopy (SEM) and Optical Microscopy (OM) analysis revealed that the size of silica core particles varied with the synthesis temperature (300 nm at 30°C to 150 at 60°C). The core silica particles …

Electrochemical Modulation Of Surface Plasmon Wave To Investigate Dna-Based Sensing Platforms And Detection Of Sars-Cov2., Anil Sharma

Electronic Theses and Dissertations

This study offers a thorough comparative analysis of optical and electrical signaling strategies for assessing the electrochemical properties of different redox-labeled DNA-based biosensing platforms. In addition, it illustrates the development of an optical interrogation technique with electrochemical modulation of surface plasmon waves (ECM-SPW) as a route for analyzing and implementing DNA-based hybridization sensors. For those quantitative analyses, we chose a model sensing platform composed of a methylene blue (MB)-modified single-stranded DNA (ssDNA) signaling probe and an unlabeled capture ssDNA probe that complements the signaling probe. Two types of signaling probes were employed in this work: one with MB attached to …

Predicting Ffar4 Agonists Using Structure-Based Machine Learning Approach Based On Molecular Fingerprints, Zaid Anis Sherwani, Syeda Sumayya Tariq, Mamona Mushtaq, Ali Raza Siddiqui, Mohammad Nur-E-Alam, Aftab Ahmed, Zaheer Ul-Haq

Pharmacy Faculty Articles and Research

Free Fatty Acid Receptor 4 (FFAR4), a G-protein-coupled receptor, is responsible for triggering intracellular signaling pathways that regulate various physiological processes. FFAR4 agonists are associated with enhancing insulin release and mitigating the atherogenic, obesogenic, pro-carcinogenic, and pro-diabetogenic effects, normally associated with the free fatty acids bound to FFAR4. In this research, molecular structure-based machine-learning techniques were employed to evaluate compounds as potential agonists for FFAR4. Molecular structures were encoded into bit arrays, serving as molecular fingerprints, which were subsequently analyzed using the Bayesian network algorithm to identify patterns for screening the data. The shortlisted hits obtained via machine learning protocols …

Evaluating The Effect Of Skipping Ticagrelor Doses And Need For Bolus Doses Upon Treatment Resumption Through Population Pk/Pd Simulation, Hiroyoshi Matsui, Le Thien Truc Pham, Eyob D. Adane

ONU Student Research Colloquium

Ticagrelor (Brilinta (R)) is the first reversibly binding oral P2Y12 receptor antagonist. It is used, mostly in combination with aspirin, in patients with acute coronary syndromes to reduce thrombosis. The manufacturer of ticagrelor recommends discontinuing it at least 5 days before any surgery when possible. While the effect of dose interruptions on the risk of thrombosis is not directly studied, it is important to understand the impact of skipping doses on ticagrelor's PK/PD profile for clinical-decision making. The objectives of the current study were to simulate the impact of therapy interruption on the PK/PD of ticagrelor and examine the need …

Apigenin Alleviates Autistic-Like Stereotyped Repetitive Behaviors And Mitigates Brain Oxidative Stress In Mice, Petrilla Jayaprakash, Dmytro Isaev, Keun-Hang Susan Yang, Rami Beiram, Murat Oz, Bassem Sadek

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Studying the involvement of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in neuropsychiatric brain disorders such as autism spectrum disorder (ASD) has gained a growing interest. The flavonoid apigenin (APG) has been confirmed in its pharmacological action as a positive allosteric modulator of α7-nAChRs. However, there is no research describing the pharmacological potential of APG in ASD. The aim of this study was to evaluate the effects of the subchronic systemic treatment of APG (10–30 mg/kg) on ASD-like repetitive and compulsive-like behaviors and oxidative stress status in the hippocampus and cerebellum in BTBR mice, utilizing the reference drug aripiprazole (ARP, 1 …

Methionyl-Trna Synthetase Synthetic And Proofreading Activities Are Determinants Of Antibiotic Persistence, Whitney N. Wood, Miguel Angel Rubio, Lorenzo Eugenio Leiva, Gregory J. Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial antibiotic persistence is a phenomenon where bacteria are exposed to an antibiotic and the majority of the population dies while a small subset enters a low metabolic, persistent, state and are able to survive. Once the antibiotic is removed the persistent population can resuscitate and continue growing. Several different molecular mechanisms and pathways have been implicated in this phenomenon. A common mechanism that may underly bacterial antibiotic persistence is perturbations in protein synthesis. To investigate this mechanism, we characterized four distinct metG mutants for their ability to increase antibiotic persistence. Two metG mutants encode changes near the catalytic site …

Mechanistic Investigation Of C—C Bond Activation Of Phosphaalkynes With Pt(0) Complexes, Roberto M. Escobar, Abdurrahman C. Ateşin, Christian Müller, William D. Jones, Tülay Ateşin

Research Symposium

Carbon–carbon (C–C) bond activation has gained increased attention as a direct method for the synthesis of pharmaceuticals. Due to the thermodynamic stability and kinetic inaccessibility of the C–C bonds, however, activation of C–C bonds by homogeneous transition-metal catalysts under mild homogeneous conditions is still a challenge. Most of the systems in which the activation occurs either have aromatization or relief of ring strain as the primary driving force. The activation of unstrained C–C bonds of phosphaalkynes does not have this advantage. This study employs Density Functional Theory (DFT) calculations to elucidate Pt(0)-mediated C–CP bond activation mechanisms in phosphaalkynes. Investigating the …

De Novo Drug Design Using Transformer-Based Machine Translation And Reinforcement Learning Of An Adaptive Monte Carlo Tree Search, Dony Ang, Cyril Rakovski, Hagop S. Atamian

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The discovery of novel therapeutic compounds through de novo drug design represents a critical challenge in the field of pharmaceutical research. Traditional drug discovery approaches are often resource intensive and time consuming, leading researchers to explore innovative methods that harness the power of deep learning and reinforcement learning techniques. Here, we introduce a novel drug design approach called drugAI that leverages the Encoder–Decoder Transformer architecture in tandem with Reinforcement Learning via a Monte Carlo Tree Search (RL-MCTS) to expedite the process of drug discovery while ensuring the production of valid small molecules with drug-like characteristics and strong binding affinities towards …

Use Of Artificial Intelligence In Drug Development, Louise C. Druedahl, Nicholson Price, Timo Minssen, Dipl Jur, Ameet Sarpatwari

Articles

Considerable focus has been placed on the health care applications of artificial intelligence (AI). Already, machine learning, a subset of AI that involves “the use of data and algorithms to imitate the way that humans learn” has been used to predict diseases, while AI-powered smartphone apps have been developed to promote mental health and weight loss. Owing in part to such successes, the market for AI in health care has been forecasted to increase more than 1000% between 2022 and 2029, from $13.8 billion to $164.1 billion. One area of substantial promise is drug development, which is poised to benefit …

Swosu Research And Scholarly Activity Fair 2024, Swosu Office Of Sponsored Programs

SWOSU Research and Scholarly Activity Fair Programs

On behalf of the members of the University Research and Scholarly Activity Committee (USRAC) and the Office of Sponsored Programs (OSP) at Southwestern Oklahoma State University (SWOSU) - Welcome to the Thirty-Second SWOSU Research and Scholarly Activity Fair! There are 61 poster presentations and 10 oral presentations involving over 100 student and faculty researchers, writers, presenters, artists, collaborators, and faculty sponsors encompassing activities from the SWOSU Departments of Biological Sciences, Chemistry & Physics, Engineering Technology, Kinesiology, Language & Literature, Mathematics, Music, Parks and Recreation Management, Pharmacy, Psychology, and Social Sciences.

Advancements In The Synthesis Of Polyoxygenated Oxepanes And Thiepanes For Applications To Natural Products, Aditya R. Pote, Shayne M. Weierbach, Mark W. Peczuh, Kyle M. Lambert

Chemistry & Biochemistry Faculty Publications

Oxepanes are central motifs and tenants of many biologically important molecules, and their synthetic construction often presents a challenge to chemists due to consequential entropic and enthalpic barriers that have limited the synthetic toolbox to access these seven-membered oxacycles. This review covers the breadth of synthetic methods to afford the oxepane/thiepane moiety, with a focus on polyoxygenated oxepanes and includes radical cyclizations, Lewis acid-mediated cyclizations, ring closing-metathesis, Nicholas-Ferrier rearrangement, homologations, and ring-expansion strategies. Implementation of these tactics towards sugar-based and non-sugar based (de novo) approaches is presented alongside their extensive application to the total synthesis of several complex polyoxygenated oxepane-containing …

Implementation Of Prognosticator Algorithm For Initiation Of Serious Illness Discussions And Improving The Rate Of Palliative And Hospice Referrals, Joy Isebor

Doctor of Nursing Practice (DNP) Scholarly Projects

Context: Early serious illness conversations related to end-of-life and goals of care with seriously ill patients have been associated with improving patients' outcomes and quality of care (Bernacki et al., 2015). However, initiating these serious illness discussions has been challenging in the home-based primary care setting.

Objectives: To train and support home-based primary care clinicians in integrating best practices in serious illness discussions and decision-making engagement among patients sixty-five and older with serious illnesses, optimize the alignment between patient goals and the medical care they receive, improving their quality of life and the rate of palliative care and hospice referrals. …

Outpatient Fall Prevention In Ambulatory Adults 65 Years Old And Over, Dorothy L. Osborne-White

Doctor of Nursing Practice (DNP) Scholarly Projects

Abstract

Background: In the United States (U.S.), falls are the leading cause of injury among adults 65 and over, resulting in 36 million falls yearly (Moreland et al., 2020). According to the Centers for Disease Control and Prevention (CDC, 2023), one in four older adults experiences a fall each year. Falls are the world's second most prominent cause of accidental deaths (World Health Organization [WHO], 2021). Falls are the leading cause of both fatal and non-fatal injuries among older adults (Moreland et al., 2020).

Methods: A quality improvement project that included a fall bundle was implemented in a primary clinic. …

Combined Risk Based Inspection And Fault Tree Analysis For Repetitive 3-Phase Line Piping Leakage At West Java Offshore Topside Facility, Dona Yuliati, Akhmad Herman Yuwono, Datu Rizal Asral, Donanta Dhaneswara

Journal of Materials Exploration and Findings

Hydrocarbon releases might result in serious consequences in various aspects. In addition to the contribution to environmental pollution, repetitive leakages need high repair costs. This study aim is to minimize potential repetitive leakage for other typical 3-phase piping systems. We conducted the risk assessment by adopting Risk Based Inspection (RBI) API 581 to identify risk level, calculating piping lifetime, recommended inspection plan and mitigations. The most relevant root causes can be obtained through quantitative Fault Tree Analysis (FTA). Observation and investigation was taken from eight 3-phase piping systems that experienced repetitive leakages. It has been found that the risk level …

Nitrogen Gas Quenching Pressure Effect On Bs S155 Alloy Steel In Vacuum Furnace, Agus Mulyadi Hasanudin, Eddy Sumarno Siradj

Journal of Materials Exploration and Findings

The production of metal and alloy products requires the use of heat treatment, when during the heat treatment process, quenching is a crucial step. The quenching medium can be anything from water, a salt bath, oil, air and gas. In a vacuum furnace, pressurized gas, most frequently nitrogen (N₂) gas, serves as one of the quenching mediums. One of the drawbacks of the quenching process is the distortion and dimensional change of the parts. This paper aims to investigate the influence of nitrogen gas quenching pressure on the distortion and dimensional change of aerospace actuator gear planet parts …

The Potential Of Stem Cell Therapy In Multiple Sclerosis Treatment: A Review, Sorina Amarculesei, Ava O'Meara Cushen, Cathy Brougham

SURE Journal: Science Undergraduate Research Experience Journal

Multiple Sclerosis is an autoimmune and neurodegenerative disease of the central nervous system. There are currently 2.8 million people living with Multiple Sclerosis worldwide, including 9000 people in Ireland, with a prevalence of 193 per 100,000 people. Symptoms of Multiple Sclerosis include sensory loss, fatigue, cognitive dysfunction, spasticity, depression, optic neuritis, gait ataxia, diplopia, and loss of bladder control. Currently, there is no standardised treatment or cure for Multiple Sclerosis with many strategies focusing on symptoms. Stem cells have emerged as promising approaches for Multiple Sclerosis therapeutics. Clinical trials primarily focus on mesenchymal stem cell-based therapies for Multiple Sclerosis. Furthermore, …

Significant Improvement Of Fidelity For Encoded Quantum Bell Pairs At Long And Short-Distance Communication Along With Generalized Circuit, Syed Emad Uddin Shubha, Md Saifur Rahman, M R C Mahdy

Student and Faculty Publications

Quantum entanglement is a unique criterion of the quantum realm and an essential tool to secure quantum communication. Ensuring high-fidelity entanglement has always been a challenging task owing to interaction with the hostile channel environment created due to quantum noise and decoherence. Though several methods have been proposed, correcting almost all arbitrary errors is still a gigantic task. As one of the main contributions of this work, a new model for 'large distance communication' has been proposed, which may correct all bit flip errors or other errors quite extensively if proper encoding and subspace measurements are used. To achieve this …

The Effect Of Heat Treatment And Chemical Treatment On Natural Fibre To The Durability Of Wood Plastic Composites – A Review, Nuratiqah Asyiqin Mohd Nasharudin, Nur Fatihah Sulaiman, Nurul Aziemah Mohammad, Wan Nor Raihan Wan Jaafar, Falah Abu Dr., Siti Norasmah Surip

Journal of Materials Exploration and Findings

The application of WPC is not only limited to indoor applications but has been extended to exterior applications where properties of WPC could compromise during service life. WPC was derived from wood fiber of various sizes to reinforce polymers. Wood fiber has the advantage of a cheaper price, being abundantly available, and ease of processing, however, the critical factor is its hydrophilic nature, where moisture absorption is likely to occur. Thus, treatments for reducing the hydrophilicity of wood fibers are applied. By treatment of wood fiber, the surface impurities were removed, leaving the roughened surface of fibers, thus providing a …

Computer-Aided Drug Design Of Bakuchiol-Inspired Lxrα Modulators Against Acute Lymphoblastic Leukemia, Dillon P. Cao

LSU Master's Theses

Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children, accounting for approximately 25% of pediatric malignancies. Although glucocorticoids are commonly used to treat ALL, prolonged use can lead to steroid resistance, rendering the drug regimen ineffective. Therefore, alternative treatment avenues are needed for high- risk pediatric patients that do not respond well to traditional regimens.

Liver X Receptor α (LXRα) is presented as a potential alternative drug target for pediatric patients that exhibit suboptimal response to glucocorticoids. Limitations of the current LXRα modulators such as indiscriminate isoform selectivity between LXRα and LXRβ and consequent adverse effects …

Artemisinin And Its Derivatives Reactions: Characterization Of The Reaction Products Using Lc/Tof Ms, Kogila Vijayan

Theses and Dissertations

Artemisinin (ART) is a sesquiterpene lactone and a popular malaria drug with potential anticancer properties. In this work, LC/TOF MS was used to investigate the reaction of ART with DNA bases and estradiol. ART-deoxyadenosine and ART-deoxycytidine interactions were studied in the presence of Fe (II) ions. ART-deoxyadenosine and ART-deoxycytidine reaction mixtures gave chromatographic signatures that remained unchanged at room temperature but grew after incubation at 37°C. The change in temperature from room temperature to 37°C was the main driver of adduct formation in these reactions. ART was found to react with Fe (II) ions as observed from several new chromatographic …

Development And Validation Of A Uplc-Ms/Ms Method To Investigate The Plasma Pharmacokinetics Of A KCa2.2/KCa2.3 Positive Allosteric Modulator In Mice, Mohammad Asikur Rahman, Devaraj Venkatapura Chandrashekar, Young-Woo Nam, Basir Syed, David Salehi, Hamidreza Montazeri Aliabadi, Miao Zhang, Reza Mehvar

Pharmacy Faculty Articles and Research

Rationale

There is currently no treatment for spinocerebellar ataxias (SCAs), which are a group of genetic disorders that often cause a lack of coordination, difficulty walking, slurred speech, tremors, and eventually death. Activation of K_Ca2.2/K_Ca2.3 channels reportedly exerts beneficial effects in SCAs. Here, we report the development and validation of an analytical method for quantitating a recently-developed positive allosteric modulator of K_Ca2.2/K_Ca2.3 channels (compound 2q) in mouse plasma.

Methods

Mouse plasma samples (10 μL) containing various concentrations of 2q were subjected to protein precipitation in the presence of a structurally similar internal …

Structure-Guided Mutagenesis Reveals The Catalytic Residue That Controls The Regiospecificity Of C6-Indole Prenyltransferases, Ahmed R. Aoun, Nagaraju Mupparapu, Diem N. Nguyen, Tae Ho Kim, Christopher M. Nguyen, Zhengfeiyue Pan, Sherif I. Elshahawi

Pharmacy Faculty Articles and Research

Indole is a significant structural moiety and functionalization of the C−H bond in indole-containing molecules expands their chemical space, and modifies their properties and/or activities. Indole prenyltransferases (IPTs) catalyze the direct regiospecific installation of prenyl moieties on indole-derived compounds. IPTs have shown relaxed substrate flexibility enabling them to be used as tools for indole functionalization. However, the mechanism by which certain IPTs target a specific carbon position is not fully understood. Herein, we use structure-guided site-directed mutagenesis, in vitro enzymatic reactions, kinetics and structural-elucidation of analogs to verify the key catalytic residues that control the regiospecificity of all characterized regiospecific …

A Machine Learning Approach For Predicting Clinical Trial Patient Enrollment In Drug Development Portfolio Demand Planning, Ahmed Shoieb

Masters Theses

One of the biggest challenges the clinical research industry currently faces is the accurate forecasting of patient enrollment (namely if and when a clinical trial will achieve full enrollment), as the stochastic behavior of enrollment can significantly contribute to delays in the development of new drugs, increases in duration and costs of clinical trials, and the over- or under- estimation of clinical supply. This study proposes a Machine Learning model using a Fully Convolutional Network (FCN) that is trained on a dataset of 100,000 patient enrollment data points including patient age, patient gender, patient disease, investigational product, study phase, blinded …

Virtual And In Vitro Screening Of Natural Products Identifies Indole And Benzene Derivatives As Inhibitors Of Sars-Cov-2 Main Protease (MPro), Dony Ang, Riley Kendall, Hagop S. Atamian

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The rapid spread of the coronavirus disease 2019 (COVID-19) resulted in serious health, social, and economic consequences. While the development of effective vaccines substantially reduced the severity of symptoms and the associated deaths, we still urgently need effective drugs to further reduce the number of casualties associated with SARS-CoV-2 infections. Machine learning methods both improved and sped up all the different stages of the drug discovery processes by performing complex analyses with enormous datasets. Natural products (NPs) have been used for treating diseases and infections for thousands of years and represent a valuable resource for drug discovery when combined with …

The Science Of Oral Carbapenems, Landon Olsen, Daniel J. Yang, Aiyi Chen, Thahn-Liem Vu, H. Stephen Lee

Annual Research Symposium

No abstract provided.

Sulopenem For The Treatment Of Complicated And Uncomplicated Bacterial Urinary Tract Infection (Uti), Aiyi Chen, Thanh-Liem Vu, Daniel J. Yang, Landon Olsen

Annual Research Symposium

No abstract provided.